Clinical Endocrinology News

SAN DIEGO – When Dawn Lemanne, MD, MPH, meets with cancer patients and their families, the question invariably comes up: “What should I eat?”

“The answer always is, ‘It depends,’” Dr. Lemanne, an oncologist who founded Oregon Integrative Oncology in Ashland, said at Natural Supplements: An Evidence-Based Update, presented by Scripps Center for Integrative Medicine. “The answers are not the same for each of these patients.”

According to Dr. Lemanne, targeted nutrition is evolving as a key component of cancer care. One of the goals of this approach is to decrease mTOR signaling. Normally, mTOR signaling promotes cell proliferation and metabolism; aberrant mTOR signaling can contribute to cancer initiation and progression.

“When mTOR speaks it says, ‘grow,’” said Dr. Lemanne, who is also an assistant professor of clinical medicine at the Andrew Weil Center for Integrative Medicine at the University of Arizona in Tucson. This message is meant to be heard by normal tissues, to stimulate normal tissue proliferation, such as in growing children or when a wound needs to be healed.

“However, cancer cells can hear and respond to mTOR’s message,” she said. “Normal cells may listen to mTOR’s ‘grow’ message or not, depending on the task they perform. Once we reach adulthood, we all likely have some precancerous or cancerous cells around, but they’re usually dormant. That’s why once you’re an adult, however, you don’t want too much mTOR signaling, because that might stimulate growth of things you definitely don’t want to grow.”

Having excessive levels of the growth hormone insulin-like growth factor-1 (IGF-1) also appears to play a role in cancer risk. Researchers studying members of a South American clan with Laron dwarfism – an inherited IGF-1 deficiency – found that besides being very short, affected members of this family rarely develop cancer (Cells. 2019;8[6]:596). “They also don’t get diabetes,” Dr. Lemanne said. “What we see in those with Laron dwarfism is that mTOR signaling is missing.”

She went on to note that studying type 2 diabetes gives physicians “a clue as to what dietary measures we might offer our patients in terms of decreasing their risk of dying from cancer or getting cancer.” The most common types of cancer are indeed more common in patients with type 2 diabetes. In addition, once someone with type 2 diabetes is diagnosed with cancer, their prognosis is poorer, compared with a cancer patient without diabetes.

“Metformin is often prescribed to patients with type 2 diabetes because it helps keep blood sugar low,” she said. “What’s fascinating is that diabetics on metformin develop cancer less frequently than diabetics not taking this drug. And also interesting, those diabetics who do develop cancer seem to do better if they’re on metformin before and after diagnosis.”

On the other hand, exogenous insulin therapy given to people with type 2 diabetes doubles the risk of cancer. Consistent with this is the two-decades-old finding that an elevated fasting insulin level also is associated with a poor breast cancer prognosis (J Clin Oncol. 2002 Jan 1;20[1]:42-51). “It’s really important to understand that, in a person destined to become a type 2 diabetic, the level of fasting insulin rises long before fasting glucose becomes abnormally high,” Dr. Lemanne explained. “A normal fasting glucose doesn’t let you off the hook in terms of checking your patient for insulin resistance.

“We will miss diagnosing many patients with dangerous insulin resistance and prediabetes if we don’t check the fasting glucose and the fasting insulin levels together. If the fasting insulin level is high, it’s important to limit carbohydrate intake enough to bring it down permanently, even when the fasting glucose is normal, or the patient is likely at increased risk for developing cancer.”

Two large, prospective randomized trials have examined breast cancer and diet: the Women’s Intervention Study (WINS) and the Women’s Health Eating and Living Study (WHEL). Patients in both trials had early stage breast cancer and were put on low-fat diets. In the end, there was a weak to negligible connection between breast cancer survival and dietary fat restriction. “That kind of shook up the oncology world,” Dr. Lemanne said, “because before these two studies, everyone ‘knew’ that dietary fat was related to breast cancer risk. These studies showed that wasn’t the case at all.”

According to Dr. Lemanne, unexpectedly, moderate carbohydrate restriction has been associated with lower risk of breast cancer recurrence in patients with postmenopausal hormone-receptor expressing breast cancer. Researchers at the University of California, San Diego, conducted a subanalysis of 265 postmenopausal patients with estrogen receptor positive breast cancer from the WHEL cohort (Cancer Epidemiol Biomarkers Prev. 2014 23[7]:1273-9). The recurrence risk was halved in those who cut their carbohydrate intake after diagnosis. The amount of decrease was modest, only 27 grams per day – the equivalent of one banana. “That is on par with a lot of our drugs, and maybe a little bit better,” she said. The effect was strongest if the breast tumor expressed IGF-1 receptor. Dr. Lemanne pointed out that decreasing dietary carbohydrate load was not the only treatment. These patients also had appropriate conventional cancer treatments, including surgery, radiation, and chemotherapy. “If we cut just some of the daily carb load in these patients, they might have a better cancer prognosis,” she said.

Overweight or obese patients with colon cancer also may benefit from moderate carbohydrate restriction. The CALGB 89803 study assessed 1,011 subjects with stage III colon cancer. It found that the subjects in the highest quintile of daily glycemic load and total carbohydrate intake had an increased risk of cancer recurrence and mortality (hazard ratio, 2.26; J Nat Cancer Inst. 2012;104[22]:1702-11). “This is pretty strong evidence that glycemic load and total carbohydrate intake play a role in colon cancer recurrence, but there’s a caveat here,” she said. “The effect was seen only in patients who were overweight or obese.” There was no association between carbohydrate intake and colon cancer recurrence in the absence of overweight or obesity.

Based on existing evidence, she said, clinicians could recommend restricting carb intake to 100 grams per day for patients with postmenopausal hormone-receptor expressing breast cancer and for overweight or obese patients with colon cancer.

“That’s pretty modest; that’s 400 calories of carbohydrates per day,” Dr. Lemanne said. “I tell patients that they can have fruit, starchy vegetables, and even very small amounts of healthy whole grains, although I’m not a fan of grains due to the heavy carbohydrate load. All those things are OK. We’re not talking about jelly beans and white sugar.

“I also have them measure their fasting glucose each day, because different people have different blood glucose responses to the same food.” The goals she aims for with many of her patients are a fasting morning glucose between 79 and 83 mg/dL consistently, an HbA1c of 5.4 or less, and a BMI of 24.9 kg/m² or less. “This set of goals, however, has to be individualized,” she said.

The ketogenic diet is another form of carb restriction, “but it’s much more drastic,” Dr. Lemanne said. “Most people require a carbohydrate load below 30 grams a day to enter a state of ketosis. But ketosis lowers the blood sugar and dampens the mTOR signaling.”

Evidence is emerging to support the use of a ketogenic diet as an adjunct to radiation therapy and as part of a complete course of treatment for glioblastoma multiforme and cancer cachexia. As an adjunct to radiation, a ketogenic diet decreases insulin and IGF-1 signaling. “This causes normal cells to enter dormancy, decreasing oxidative damage in normal cells,” Dr. Lemanne said. “There is also suppression of tumor angiogenesis, and thus poor DNA repair of radiation damage in tumor cells (Cancer Metastasis Rev. 2014;33[1]:217-29). Being in ketosis widens the therapeutic window. There are many animal studies which show that the ketogenic diet is helpful in cancer, mainly when combined with other anticancer treatments, such as radiation. Unfortunately, the evidence in humans is very anecdotal.”

One study found that if you feed mice with cancer ketogenic chow versus standard chow, they have a modestly improved survival (a mean of 43 days vs. 33 days; PLoS ONE. 2012;7[5]:e36197). However, when radiation was added to the keto diet, there was a dramatic improvement in survival (P less than 0.001). In fact, 75% survived to 250 days. “That’s pretty spectacular,” Dr. Lemanne said.

A ketogenic diet is standard therapy for several nonmalignant conditions, including glucose transporter 1 deficiency syndrome, pyruvate dehydrogenase deficiency syndrome, and refractory infantile epilepsy. The three major ketone bodies involved in human nutrition are acetoacetate, beta hydroxybutyrate, and acetone. Dr. Lemanne said beta hydroxybutyrate decreases inflammation and inhibits hexadecynoic acids (which induces apoptosis in cancer cells). Beta hydroxybutyrate also increases sirtuins, innate immunity, and seizure threshold; modulates circadian rhythm; and decreases insulin levels, she said.

In one case report from the scientific literature, a 38-year-old male with glioblastoma multiforme was placed on a hypocaloric ketogenic diet (Front Nutr. 2018 Mar 29;5:20). The patient had surgery, radiation, chemotherapy, and hyperbaric oxygen, and was given high doses of green tea extract in an attempt to antagonize glutamine metabolism. Two years after the beginning of his treatment, he was alive and had maintained a good level of tumor regression.

“We’ll see how he does,” said Dr. Lemanne, who was not involved in the report. “In my experience, I have a patient right now with a diagnosis of glioblastoma multiforme. She’s getting a keto diet in combo with intensive chemo, radiation, and surgery. She’s also had some hyperbaric oxygen and IV ozone therapy and is taking repurposed drugs. She has exceeded her expected survival, but she continues to have disease and symptoms. We are by no means out of the woods with this patient. But the keto diet has been quite feasible for her, because she has a lot of family and outside support.”

A ketogenic diet also may benefit patients with cancer cachexia, which is a loss of lean tissue. “Cancer cachexia is not completely understood,” Dr. Lemanne said. “What we know is that it is caused by inflammation created by the tumor itself, and this, in turn results in severe insulin resistance. Therefore, giving more calories as carbohydrate makes the cancer cachexia situation worse. Animal models of cancer cachexia have shown that the ketogenic diet normalizes metabolism and prevents lean tissue loss. Human studies are underway; we’ll see how they turn out.”

She closed her presentation by noting that in copious amounts of animal studies, fasting has been linked to improvements in chemotherapy efficacy and decreased side effects. In one study carried out at the University of Southern California in Los Angeles, volunteers fasted up to 140 hours before chemotherapy and an additional 156 hours afterward (Aging. 2009;1[12]:988-1007). The researchers found that the fasting was well-tolerated.

“The patients had some mild light-headedness, but there were no adverse effects on tumor volume or serum tumor markers,” Dr. Lemanne said. A more recent study of patients on cisplatin found that acaloric fasting led to decreased DNA damage in white blood cells, decreased IFG-1, and better white blood cell counts (BMC Cancer. 2016 Jun 10;16:360). “The benefits are immediate, and the optimal fasting time appears to be 48 hours,” Dr. Lemanne said.

One of her patients is a 64-year-old man on adjuvant cisplatin-based chemotherapy for cholangiocarcinoma. He fasts 24 hours before and 24 hours after each infusion, and has experienced no emesis or nausea. “His immune suppression and anemia are much milder than we expected, and he has not required any treatment for chemotherapy-related side effects,” Dr. Lemanne said. “That’s a big monetary value.”

Fasting 13 hours overnight has been associated with fewer breast cancer-related problems in patients already diagnosed with the disease. Chronic caloric restriction, just cutting calories by 25%-40% daily, has been shown to delay all diseases of aging, including cancer, and is associated with increased longevity in many species. “Chronic caloric restriction is difficult, however, because it results in chronic hunger and weight loss,” she said. “Occasional fasting is superior to chronic caloric restriction because it maintains normal weight, preserves lean muscle mass, enhances tumor sensitivity to chemotherapy and radiotherapy, and diminishes the side effects of chemotherapy.”

Dr. Lemanne reported having no financial disclosures.

dbrunk@mdedge.com

SAN DIEGO – When Dawn Lemanne, MD, MPH, meets with cancer patients and their families, the question invariably comes up: “What should I eat?”

“The answer always is, ‘It depends,’” Dr. Lemanne, an oncologist who founded Oregon Integrative Oncology in Ashland, said at Natural Supplements: An Evidence-Based Update, presented by Scripps Center for Integrative Medicine. “The answers are not the same for each of these patients.”

According to Dr. Lemanne, targeted nutrition is evolving as a key component of cancer care. One of the goals of this approach is to decrease mTOR signaling. Normally, mTOR signaling promotes cell proliferation and metabolism; aberrant mTOR signaling can contribute to cancer initiation and progression.

“When mTOR speaks it says, ‘grow,’” said Dr. Lemanne, who is also an assistant professor of clinical medicine at the Andrew Weil Center for Integrative Medicine at the University of Arizona in Tucson. This message is meant to be heard by normal tissues, to stimulate normal tissue proliferation, such as in growing children or when a wound needs to be healed.

“However, cancer cells can hear and respond to mTOR’s message,” she said. “Normal cells may listen to mTOR’s ‘grow’ message or not, depending on the task they perform. Once we reach adulthood, we all likely have some precancerous or cancerous cells around, but they’re usually dormant. That’s why once you’re an adult, however, you don’t want too much mTOR signaling, because that might stimulate growth of things you definitely don’t want to grow.”

Having excessive levels of the growth hormone insulin-like growth factor-1 (IGF-1) also appears to play a role in cancer risk. Researchers studying members of a South American clan with Laron dwarfism – an inherited IGF-1 deficiency – found that besides being very short, affected members of this family rarely develop cancer (Cells. 2019;8[6]:596). “They also don’t get diabetes,” Dr. Lemanne said. “What we see in those with Laron dwarfism is that mTOR signaling is missing.”

She went on to note that studying type 2 diabetes gives physicians “a clue as to what dietary measures we might offer our patients in terms of decreasing their risk of dying from cancer or getting cancer.” The most common types of cancer are indeed more common in patients with type 2 diabetes. In addition, once someone with type 2 diabetes is diagnosed with cancer, their prognosis is poorer, compared with a cancer patient without diabetes.

“Metformin is often prescribed to patients with type 2 diabetes because it helps keep blood sugar low,” she said. “What’s fascinating is that diabetics on metformin develop cancer less frequently than diabetics not taking this drug. And also interesting, those diabetics who do develop cancer seem to do better if they’re on metformin before and after diagnosis.”

On the other hand, exogenous insulin therapy given to people with type 2 diabetes doubles the risk of cancer. Consistent with this is the two-decades-old finding that an elevated fasting insulin level also is associated with a poor breast cancer prognosis (J Clin Oncol. 2002 Jan 1;20[1]:42-51). “It’s really important to understand that, in a person destined to become a type 2 diabetic, the level of fasting insulin rises long before fasting glucose becomes abnormally high,” Dr. Lemanne explained. “A normal fasting glucose doesn’t let you off the hook in terms of checking your patient for insulin resistance.

“We will miss diagnosing many patients with dangerous insulin resistance and prediabetes if we don’t check the fasting glucose and the fasting insulin levels together. If the fasting insulin level is high, it’s important to limit carbohydrate intake enough to bring it down permanently, even when the fasting glucose is normal, or the patient is likely at increased risk for developing cancer.”

Two large, prospective randomized trials have examined breast cancer and diet: the Women’s Intervention Study (WINS) and the Women’s Health Eating and Living Study (WHEL). Patients in both trials had early stage breast cancer and were put on low-fat diets. In the end, there was a weak to negligible connection between breast cancer survival and dietary fat restriction. “That kind of shook up the oncology world,” Dr. Lemanne said, “because before these two studies, everyone ‘knew’ that dietary fat was related to breast cancer risk. These studies showed that wasn’t the case at all.”

According to Dr. Lemanne, unexpectedly, moderate carbohydrate restriction has been associated with lower risk of breast cancer recurrence in patients with postmenopausal hormone-receptor expressing breast cancer. Researchers at the University of California, San Diego, conducted a subanalysis of 265 postmenopausal patients with estrogen receptor positive breast cancer from the WHEL cohort (Cancer Epidemiol Biomarkers Prev. 2014 23[7]:1273-9). The recurrence risk was halved in those who cut their carbohydrate intake after diagnosis. The amount of decrease was modest, only 27 grams per day – the equivalent of one banana. “That is on par with a lot of our drugs, and maybe a little bit better,” she said. The effect was strongest if the breast tumor expressed IGF-1 receptor. Dr. Lemanne pointed out that decreasing dietary carbohydrate load was not the only treatment. These patients also had appropriate conventional cancer treatments, including surgery, radiation, and chemotherapy. “If we cut just some of the daily carb load in these patients, they might have a better cancer prognosis,” she said.

Overweight or obese patients with colon cancer also may benefit from moderate carbohydrate restriction. The CALGB 89803 study assessed 1,011 subjects with stage III colon cancer. It found that the subjects in the highest quintile of daily glycemic load and total carbohydrate intake had an increased risk of cancer recurrence and mortality (hazard ratio, 2.26; J Nat Cancer Inst. 2012;104[22]:1702-11). “This is pretty strong evidence that glycemic load and total carbohydrate intake play a role in colon cancer recurrence, but there’s a caveat here,” she said. “The effect was seen only in patients who were overweight or obese.” There was no association between carbohydrate intake and colon cancer recurrence in the absence of overweight or obesity.

Based on existing evidence, she said, clinicians could recommend restricting carb intake to 100 grams per day for patients with postmenopausal hormone-receptor expressing breast cancer and for overweight or obese patients with colon cancer.

“That’s pretty modest; that’s 400 calories of carbohydrates per day,” Dr. Lemanne said. “I tell patients that they can have fruit, starchy vegetables, and even very small amounts of healthy whole grains, although I’m not a fan of grains due to the heavy carbohydrate load. All those things are OK. We’re not talking about jelly beans and white sugar.

“I also have them measure their fasting glucose each day, because different people have different blood glucose responses to the same food.” The goals she aims for with many of her patients are a fasting morning glucose between 79 and 83 mg/dL consistently, an HbA1c of 5.4 or less, and a BMI of 24.9 kg/m² or less. “This set of goals, however, has to be individualized,” she said.

The ketogenic diet is another form of carb restriction, “but it’s much more drastic,” Dr. Lemanne said. “Most people require a carbohydrate load below 30 grams a day to enter a state of ketosis. But ketosis lowers the blood sugar and dampens the mTOR signaling.”

Evidence is emerging to support the use of a ketogenic diet as an adjunct to radiation therapy and as part of a complete course of treatment for glioblastoma multiforme and cancer cachexia. As an adjunct to radiation, a ketogenic diet decreases insulin and IGF-1 signaling. “This causes normal cells to enter dormancy, decreasing oxidative damage in normal cells,” Dr. Lemanne said. “There is also suppression of tumor angiogenesis, and thus poor DNA repair of radiation damage in tumor cells (Cancer Metastasis Rev. 2014;33[1]:217-29). Being in ketosis widens the therapeutic window. There are many animal studies which show that the ketogenic diet is helpful in cancer, mainly when combined with other anticancer treatments, such as radiation. Unfortunately, the evidence in humans is very anecdotal.”

One study found that if you feed mice with cancer ketogenic chow versus standard chow, they have a modestly improved survival (a mean of 43 days vs. 33 days; PLoS ONE. 2012;7[5]:e36197). However, when radiation was added to the keto diet, there was a dramatic improvement in survival (P less than 0.001). In fact, 75% survived to 250 days. “That’s pretty spectacular,” Dr. Lemanne said.

A ketogenic diet is standard therapy for several nonmalignant conditions, including glucose transporter 1 deficiency syndrome, pyruvate dehydrogenase deficiency syndrome, and refractory infantile epilepsy. The three major ketone bodies involved in human nutrition are acetoacetate, beta hydroxybutyrate, and acetone. Dr. Lemanne said beta hydroxybutyrate decreases inflammation and inhibits hexadecynoic acids (which induces apoptosis in cancer cells). Beta hydroxybutyrate also increases sirtuins, innate immunity, and seizure threshold; modulates circadian rhythm; and decreases insulin levels, she said.

In one case report from the scientific literature, a 38-year-old male with glioblastoma multiforme was placed on a hypocaloric ketogenic diet (Front Nutr. 2018 Mar 29;5:20). The patient had surgery, radiation, chemotherapy, and hyperbaric oxygen, and was given high doses of green tea extract in an attempt to antagonize glutamine metabolism. Two years after the beginning of his treatment, he was alive and had maintained a good level of tumor regression.

“We’ll see how he does,” said Dr. Lemanne, who was not involved in the report. “In my experience, I have a patient right now with a diagnosis of glioblastoma multiforme. She’s getting a keto diet in combo with intensive chemo, radiation, and surgery. She’s also had some hyperbaric oxygen and IV ozone therapy and is taking repurposed drugs. She has exceeded her expected survival, but she continues to have disease and symptoms. We are by no means out of the woods with this patient. But the keto diet has been quite feasible for her, because she has a lot of family and outside support.”

A ketogenic diet also may benefit patients with cancer cachexia, which is a loss of lean tissue. “Cancer cachexia is not completely understood,” Dr. Lemanne said. “What we know is that it is caused by inflammation created by the tumor itself, and this, in turn results in severe insulin resistance. Therefore, giving more calories as carbohydrate makes the cancer cachexia situation worse. Animal models of cancer cachexia have shown that the ketogenic diet normalizes metabolism and prevents lean tissue loss. Human studies are underway; we’ll see how they turn out.”

She closed her presentation by noting that in copious amounts of animal studies, fasting has been linked to improvements in chemotherapy efficacy and decreased side effects. In one study carried out at the University of Southern California in Los Angeles, volunteers fasted up to 140 hours before chemotherapy and an additional 156 hours afterward (Aging. 2009;1[12]:988-1007). The researchers found that the fasting was well-tolerated.

“The patients had some mild light-headedness, but there were no adverse effects on tumor volume or serum tumor markers,” Dr. Lemanne said. A more recent study of patients on cisplatin found that acaloric fasting led to decreased DNA damage in white blood cells, decreased IFG-1, and better white blood cell counts (BMC Cancer. 2016 Jun 10;16:360). “The benefits are immediate, and the optimal fasting time appears to be 48 hours,” Dr. Lemanne said.

One of her patients is a 64-year-old man on adjuvant cisplatin-based chemotherapy for cholangiocarcinoma. He fasts 24 hours before and 24 hours after each infusion, and has experienced no emesis or nausea. “His immune suppression and anemia are much milder than we expected, and he has not required any treatment for chemotherapy-related side effects,” Dr. Lemanne said. “That’s a big monetary value.”

Fasting 13 hours overnight has been associated with fewer breast cancer-related problems in patients already diagnosed with the disease. Chronic caloric restriction, just cutting calories by 25%-40% daily, has been shown to delay all diseases of aging, including cancer, and is associated with increased longevity in many species. “Chronic caloric restriction is difficult, however, because it results in chronic hunger and weight loss,” she said. “Occasional fasting is superior to chronic caloric restriction because it maintains normal weight, preserves lean muscle mass, enhances tumor sensitivity to chemotherapy and radiotherapy, and diminishes the side effects of chemotherapy.”

Dr. Lemanne reported having no financial disclosures.

dbrunk@mdedge.com

SAN DIEGO – When Dawn Lemanne, MD, MPH, meets with cancer patients and their families, the question invariably comes up: “What should I eat?”

“The answer always is, ‘It depends,’” Dr. Lemanne, an oncologist who founded Oregon Integrative Oncology in Ashland, said at Natural Supplements: An Evidence-Based Update, presented by Scripps Center for Integrative Medicine. “The answers are not the same for each of these patients.”

According to Dr. Lemanne, targeted nutrition is evolving as a key component of cancer care. One of the goals of this approach is to decrease mTOR signaling. Normally, mTOR signaling promotes cell proliferation and metabolism; aberrant mTOR signaling can contribute to cancer initiation and progression.

“When mTOR speaks it says, ‘grow,’” said Dr. Lemanne, who is also an assistant professor of clinical medicine at the Andrew Weil Center for Integrative Medicine at the University of Arizona in Tucson. This message is meant to be heard by normal tissues, to stimulate normal tissue proliferation, such as in growing children or when a wound needs to be healed.

“However, cancer cells can hear and respond to mTOR’s message,” she said. “Normal cells may listen to mTOR’s ‘grow’ message or not, depending on the task they perform. Once we reach adulthood, we all likely have some precancerous or cancerous cells around, but they’re usually dormant. That’s why once you’re an adult, however, you don’t want too much mTOR signaling, because that might stimulate growth of things you definitely don’t want to grow.”

Having excessive levels of the growth hormone insulin-like growth factor-1 (IGF-1) also appears to play a role in cancer risk. Researchers studying members of a South American clan with Laron dwarfism – an inherited IGF-1 deficiency – found that besides being very short, affected members of this family rarely develop cancer (Cells. 2019;8[6]:596). “They also don’t get diabetes,” Dr. Lemanne said. “What we see in those with Laron dwarfism is that mTOR signaling is missing.”

She went on to note that studying type 2 diabetes gives physicians “a clue as to what dietary measures we might offer our patients in terms of decreasing their risk of dying from cancer or getting cancer.” The most common types of cancer are indeed more common in patients with type 2 diabetes. In addition, once someone with type 2 diabetes is diagnosed with cancer, their prognosis is poorer, compared with a cancer patient without diabetes.

“Metformin is often prescribed to patients with type 2 diabetes because it helps keep blood sugar low,” she said. “What’s fascinating is that diabetics on metformin develop cancer less frequently than diabetics not taking this drug. And also interesting, those diabetics who do develop cancer seem to do better if they’re on metformin before and after diagnosis.”

On the other hand, exogenous insulin therapy given to people with type 2 diabetes doubles the risk of cancer. Consistent with this is the two-decades-old finding that an elevated fasting insulin level also is associated with a poor breast cancer prognosis (J Clin Oncol. 2002 Jan 1;20[1]:42-51). “It’s really important to understand that, in a person destined to become a type 2 diabetic, the level of fasting insulin rises long before fasting glucose becomes abnormally high,” Dr. Lemanne explained. “A normal fasting glucose doesn’t let you off the hook in terms of checking your patient for insulin resistance.

“We will miss diagnosing many patients with dangerous insulin resistance and prediabetes if we don’t check the fasting glucose and the fasting insulin levels together. If the fasting insulin level is high, it’s important to limit carbohydrate intake enough to bring it down permanently, even when the fasting glucose is normal, or the patient is likely at increased risk for developing cancer.”

Two large, prospective randomized trials have examined breast cancer and diet: the Women’s Intervention Study (WINS) and the Women’s Health Eating and Living Study (WHEL). Patients in both trials had early stage breast cancer and were put on low-fat diets. In the end, there was a weak to negligible connection between breast cancer survival and dietary fat restriction. “That kind of shook up the oncology world,” Dr. Lemanne said, “because before these two studies, everyone ‘knew’ that dietary fat was related to breast cancer risk. These studies showed that wasn’t the case at all.”

According to Dr. Lemanne, unexpectedly, moderate carbohydrate restriction has been associated with lower risk of breast cancer recurrence in patients with postmenopausal hormone-receptor expressing breast cancer. Researchers at the University of California, San Diego, conducted a subanalysis of 265 postmenopausal patients with estrogen receptor positive breast cancer from the WHEL cohort (Cancer Epidemiol Biomarkers Prev. 2014 23[7]:1273-9). The recurrence risk was halved in those who cut their carbohydrate intake after diagnosis. The amount of decrease was modest, only 27 grams per day – the equivalent of one banana. “That is on par with a lot of our drugs, and maybe a little bit better,” she said. The effect was strongest if the breast tumor expressed IGF-1 receptor. Dr. Lemanne pointed out that decreasing dietary carbohydrate load was not the only treatment. These patients also had appropriate conventional cancer treatments, including surgery, radiation, and chemotherapy. “If we cut just some of the daily carb load in these patients, they might have a better cancer prognosis,” she said.

Overweight or obese patients with colon cancer also may benefit from moderate carbohydrate restriction. The CALGB 89803 study assessed 1,011 subjects with stage III colon cancer. It found that the subjects in the highest quintile of daily glycemic load and total carbohydrate intake had an increased risk of cancer recurrence and mortality (hazard ratio, 2.26; J Nat Cancer Inst. 2012;104[22]:1702-11). “This is pretty strong evidence that glycemic load and total carbohydrate intake play a role in colon cancer recurrence, but there’s a caveat here,” she said. “The effect was seen only in patients who were overweight or obese.” There was no association between carbohydrate intake and colon cancer recurrence in the absence of overweight or obesity.

Based on existing evidence, she said, clinicians could recommend restricting carb intake to 100 grams per day for patients with postmenopausal hormone-receptor expressing breast cancer and for overweight or obese patients with colon cancer.

“That’s pretty modest; that’s 400 calories of carbohydrates per day,” Dr. Lemanne said. “I tell patients that they can have fruit, starchy vegetables, and even very small amounts of healthy whole grains, although I’m not a fan of grains due to the heavy carbohydrate load. All those things are OK. We’re not talking about jelly beans and white sugar.

“I also have them measure their fasting glucose each day, because different people have different blood glucose responses to the same food.” The goals she aims for with many of her patients are a fasting morning glucose between 79 and 83 mg/dL consistently, an HbA1c of 5.4 or less, and a BMI of 24.9 kg/m² or less. “This set of goals, however, has to be individualized,” she said.

The ketogenic diet is another form of carb restriction, “but it’s much more drastic,” Dr. Lemanne said. “Most people require a carbohydrate load below 30 grams a day to enter a state of ketosis. But ketosis lowers the blood sugar and dampens the mTOR signaling.”

Evidence is emerging to support the use of a ketogenic diet as an adjunct to radiation therapy and as part of a complete course of treatment for glioblastoma multiforme and cancer cachexia. As an adjunct to radiation, a ketogenic diet decreases insulin and IGF-1 signaling. “This causes normal cells to enter dormancy, decreasing oxidative damage in normal cells,” Dr. Lemanne said. “There is also suppression of tumor angiogenesis, and thus poor DNA repair of radiation damage in tumor cells (Cancer Metastasis Rev. 2014;33[1]:217-29). Being in ketosis widens the therapeutic window. There are many animal studies which show that the ketogenic diet is helpful in cancer, mainly when combined with other anticancer treatments, such as radiation. Unfortunately, the evidence in humans is very anecdotal.”

One study found that if you feed mice with cancer ketogenic chow versus standard chow, they have a modestly improved survival (a mean of 43 days vs. 33 days; PLoS ONE. 2012;7[5]:e36197). However, when radiation was added to the keto diet, there was a dramatic improvement in survival (P less than 0.001). In fact, 75% survived to 250 days. “That’s pretty spectacular,” Dr. Lemanne said.

A ketogenic diet is standard therapy for several nonmalignant conditions, including glucose transporter 1 deficiency syndrome, pyruvate dehydrogenase deficiency syndrome, and refractory infantile epilepsy. The three major ketone bodies involved in human nutrition are acetoacetate, beta hydroxybutyrate, and acetone. Dr. Lemanne said beta hydroxybutyrate decreases inflammation and inhibits hexadecynoic acids (which induces apoptosis in cancer cells). Beta hydroxybutyrate also increases sirtuins, innate immunity, and seizure threshold; modulates circadian rhythm; and decreases insulin levels, she said.

In one case report from the scientific literature, a 38-year-old male with glioblastoma multiforme was placed on a hypocaloric ketogenic diet (Front Nutr. 2018 Mar 29;5:20). The patient had surgery, radiation, chemotherapy, and hyperbaric oxygen, and was given high doses of green tea extract in an attempt to antagonize glutamine metabolism. Two years after the beginning of his treatment, he was alive and had maintained a good level of tumor regression.

“We’ll see how he does,” said Dr. Lemanne, who was not involved in the report. “In my experience, I have a patient right now with a diagnosis of glioblastoma multiforme. She’s getting a keto diet in combo with intensive chemo, radiation, and surgery. She’s also had some hyperbaric oxygen and IV ozone therapy and is taking repurposed drugs. She has exceeded her expected survival, but she continues to have disease and symptoms. We are by no means out of the woods with this patient. But the keto diet has been quite feasible for her, because she has a lot of family and outside support.”

A ketogenic diet also may benefit patients with cancer cachexia, which is a loss of lean tissue. “Cancer cachexia is not completely understood,” Dr. Lemanne said. “What we know is that it is caused by inflammation created by the tumor itself, and this, in turn results in severe insulin resistance. Therefore, giving more calories as carbohydrate makes the cancer cachexia situation worse. Animal models of cancer cachexia have shown that the ketogenic diet normalizes metabolism and prevents lean tissue loss. Human studies are underway; we’ll see how they turn out.”

She closed her presentation by noting that in copious amounts of animal studies, fasting has been linked to improvements in chemotherapy efficacy and decreased side effects. In one study carried out at the University of Southern California in Los Angeles, volunteers fasted up to 140 hours before chemotherapy and an additional 156 hours afterward (Aging. 2009;1[12]:988-1007). The researchers found that the fasting was well-tolerated.

“The patients had some mild light-headedness, but there were no adverse effects on tumor volume or serum tumor markers,” Dr. Lemanne said. A more recent study of patients on cisplatin found that acaloric fasting led to decreased DNA damage in white blood cells, decreased IFG-1, and better white blood cell counts (BMC Cancer. 2016 Jun 10;16:360). “The benefits are immediate, and the optimal fasting time appears to be 48 hours,” Dr. Lemanne said.

One of her patients is a 64-year-old man on adjuvant cisplatin-based chemotherapy for cholangiocarcinoma. He fasts 24 hours before and 24 hours after each infusion, and has experienced no emesis or nausea. “His immune suppression and anemia are much milder than we expected, and he has not required any treatment for chemotherapy-related side effects,” Dr. Lemanne said. “That’s a big monetary value.”

Fasting 13 hours overnight has been associated with fewer breast cancer-related problems in patients already diagnosed with the disease. Chronic caloric restriction, just cutting calories by 25%-40% daily, has been shown to delay all diseases of aging, including cancer, and is associated with increased longevity in many species. “Chronic caloric restriction is difficult, however, because it results in chronic hunger and weight loss,” she said. “Occasional fasting is superior to chronic caloric restriction because it maintains normal weight, preserves lean muscle mass, enhances tumor sensitivity to chemotherapy and radiotherapy, and diminishes the side effects of chemotherapy.”

Dr. Lemanne reported having no financial disclosures.

dbrunk@mdedge.com

GRAPEVINE, TEX.* – Pregnant women with type 2 diabetes or prediabetes had significantly less gestational weight gain if they had metformin exposure at any point in their pregnancies, with no differences in infant birth weight or postnatal infant hypoglycemia, according to research presented at the meeting sponsored by the Society for Maternal-Fetal Medicine.

Kari Oakes/MDedge News

In a retrospective single-center review of 284 women without metformin exposure and 227 with metformin exposure in pregnancy, metformin exposure at any point in pregnancy was associated with a significantly greater chance of appropriate – rather than excessive – weight gain.

The relationship held true for the 169 women who had metformin in their first trimester of pregnancy. Here, 69% of women had appropriate weight gain using Institute of Medicine and American College of Obstetricians and Gynecologists standards, compared with 54% of the 282 women who had no metformin exposure (adjusted odds ratio 1.92, P = .003). A further 22% of women receiving metformin in their first trimester of pregnancy lost weight, compared with 9% of women without metformin exposure (aOR 2.11, P = .019). There was no significant difference between the two groups in infant birth weight.

Separately, study author Jacquelyn Adams, MD, and her colleagues analyzed outcomes for the full cohort of 227 women who received metformin at any point in their pregnancy, comparing them again to the 282 women who had not received metformin. Most women (85%) were on 2 g of metformin at the time of delivery. These results again showed a greater likelihood of appropriate weight gain in the metformin group (69%; aOR 1.85; P = .002). Maternal weight loss was seen in 20% of this group (aOR 1.98, P = .018). Infant birth weights were not significantly different between these two groups.

“We found that women who had been on metformin at any point in their pregnancy had more appropriate weight gain and less excessive weight gain,” said Dr. Adams, a maternal-fetal medicine fellow at the University of Wisconsin–Madison. “Actually, some women on metformin had even had a little bit of weight loss, with no difference in their baby’s birth weight. So that’s really exciting, because our starting prepregnancy body mass index was 33-36 [kg/m²], which is considered obese,” she said in an interview.

This is an important finding, said Dr. Adams, because previous work has shown that less weight gain in pregnancy is associated with lower risk for hypertension and preeclampsia, and lower rates of fetal macrosomia.

What about infant outcomes? Dr. Adams said that there were many concerns about metformin: “Would it affect baby outcome? Were those babies more likely to be hypoglycemic? Were they more likely to be growth restricted? Were they more likely to have issues in the NICU? And the answer was really, ‘No.’ ”

“So we can both help these women have appropriate weight gain and not have any negative effects on these babies,” she added.

Specifically, Dr. Adams and her coinvestigators found no significant differences between the groups in gestational age at birth, likelihood of neonatal ICU admission, Apgar scores, neonatal hypoglycemia, respiratory distress syndrome, or fetal death. Fetal growth restriction and anomalies occurred at a low and similar rate between the groups.

Dr. Adams said that she was not surprised to see that metformin was associated with less weight gain in pregnancy, but she was surprised at how highly significant the differences were with metformin use. “Metformin is first-line for diabetes in nonpregnant individuals because it’s associated with things like weight loss, and because of ease of use and lack of hypoglycemia – so I was really hoping to see this kind of result.”

Women receiving metformin were a mean 34 years old, while those who didn’t get metformin were 32 years old, a significant difference. Prepregnancy body mass index also was higher in those receiving metformin, and they were more likely to have a type 2 diabetes diagnosis. A similar proportion of both groups – about two-thirds – were white, and about 20% were Hispanic.

The lower weight gain seen in metformin-takers also might smooth the way post partum, said Dr. Adams. “My perception is that, when these women leave us, they might not have any primary care follow-up; they might not have anybody following their diabetes; and metformin is a very viable way to help them in their life outside of pregnancy.

“Not to mention that all the weight you gain in pregnancy, you do eventually have to lose post partum,” she added, “so having less pregnancy weight gain kind of sets them up for success in their postpregnancy life as well.”

Asked whether these results inform the ongoing question of whether insulin or metformin is the most appropriate first-line treatment for gestational diabetes, Dr. Adams first noted that “there’s a lot of crossover,” pointing out that over 60% of the participants in her study eventually also required insulin.

“It’s a question I would love to address in a head-to-head trial,” she said, adding that questions about metformin’s effects on the placenta and the potential for later deleterious effects require more study.

In her practice, Dr. Adams said that patients generally are discharged with a metformin prescription, and then meet with a diabetes educator 1 week after delivery to assess blood glucose levels and adjust medical management. Following that, a warm hand-off to a primary care practice who can continue management and education is optimal, she said.

In terms of next steps, “We would really love to look at metformin in the postpartum period,” said Dr. Adams. Ideally, future work could look for outcomes that extend beyond the 6- to 8-week postpartum follow-up visit. For example, she said, there are indications that women with insulin insensitivity might benefit from metformin while breastfeeding; it’s also possible that metformin might reduce the risk of postpartum preeclampsia.

Dr. Adams reported that she had no conflicts of interest and no outside sources of funding.

koakes@mdedge.com

SOURCE: Adams J et al. SMFM 2020, Abstract 335.

*This story was updated 2/10/2020.

GRAPEVINE, TEX.* – Pregnant women with type 2 diabetes or prediabetes had significantly less gestational weight gain if they had metformin exposure at any point in their pregnancies, with no differences in infant birth weight or postnatal infant hypoglycemia, according to research presented at the meeting sponsored by the Society for Maternal-Fetal Medicine.

Kari Oakes/MDedge News

In a retrospective single-center review of 284 women without metformin exposure and 227 with metformin exposure in pregnancy, metformin exposure at any point in pregnancy was associated with a significantly greater chance of appropriate – rather than excessive – weight gain.

The relationship held true for the 169 women who had metformin in their first trimester of pregnancy. Here, 69% of women had appropriate weight gain using Institute of Medicine and American College of Obstetricians and Gynecologists standards, compared with 54% of the 282 women who had no metformin exposure (adjusted odds ratio 1.92, P = .003). A further 22% of women receiving metformin in their first trimester of pregnancy lost weight, compared with 9% of women without metformin exposure (aOR 2.11, P = .019). There was no significant difference between the two groups in infant birth weight.

Separately, study author Jacquelyn Adams, MD, and her colleagues analyzed outcomes for the full cohort of 227 women who received metformin at any point in their pregnancy, comparing them again to the 282 women who had not received metformin. Most women (85%) were on 2 g of metformin at the time of delivery. These results again showed a greater likelihood of appropriate weight gain in the metformin group (69%; aOR 1.85; P = .002). Maternal weight loss was seen in 20% of this group (aOR 1.98, P = .018). Infant birth weights were not significantly different between these two groups.

“We found that women who had been on metformin at any point in their pregnancy had more appropriate weight gain and less excessive weight gain,” said Dr. Adams, a maternal-fetal medicine fellow at the University of Wisconsin–Madison. “Actually, some women on metformin had even had a little bit of weight loss, with no difference in their baby’s birth weight. So that’s really exciting, because our starting prepregnancy body mass index was 33-36 [kg/m²], which is considered obese,” she said in an interview.

This is an important finding, said Dr. Adams, because previous work has shown that less weight gain in pregnancy is associated with lower risk for hypertension and preeclampsia, and lower rates of fetal macrosomia.

What about infant outcomes? Dr. Adams said that there were many concerns about metformin: “Would it affect baby outcome? Were those babies more likely to be hypoglycemic? Were they more likely to be growth restricted? Were they more likely to have issues in the NICU? And the answer was really, ‘No.’ ”

“So we can both help these women have appropriate weight gain and not have any negative effects on these babies,” she added.

Specifically, Dr. Adams and her coinvestigators found no significant differences between the groups in gestational age at birth, likelihood of neonatal ICU admission, Apgar scores, neonatal hypoglycemia, respiratory distress syndrome, or fetal death. Fetal growth restriction and anomalies occurred at a low and similar rate between the groups.

Dr. Adams said that she was not surprised to see that metformin was associated with less weight gain in pregnancy, but she was surprised at how highly significant the differences were with metformin use. “Metformin is first-line for diabetes in nonpregnant individuals because it’s associated with things like weight loss, and because of ease of use and lack of hypoglycemia – so I was really hoping to see this kind of result.”

Women receiving metformin were a mean 34 years old, while those who didn’t get metformin were 32 years old, a significant difference. Prepregnancy body mass index also was higher in those receiving metformin, and they were more likely to have a type 2 diabetes diagnosis. A similar proportion of both groups – about two-thirds – were white, and about 20% were Hispanic.

The lower weight gain seen in metformin-takers also might smooth the way post partum, said Dr. Adams. “My perception is that, when these women leave us, they might not have any primary care follow-up; they might not have anybody following their diabetes; and metformin is a very viable way to help them in their life outside of pregnancy.

“Not to mention that all the weight you gain in pregnancy, you do eventually have to lose post partum,” she added, “so having less pregnancy weight gain kind of sets them up for success in their postpregnancy life as well.”

Asked whether these results inform the ongoing question of whether insulin or metformin is the most appropriate first-line treatment for gestational diabetes, Dr. Adams first noted that “there’s a lot of crossover,” pointing out that over 60% of the participants in her study eventually also required insulin.

“It’s a question I would love to address in a head-to-head trial,” she said, adding that questions about metformin’s effects on the placenta and the potential for later deleterious effects require more study.

In her practice, Dr. Adams said that patients generally are discharged with a metformin prescription, and then meet with a diabetes educator 1 week after delivery to assess blood glucose levels and adjust medical management. Following that, a warm hand-off to a primary care practice who can continue management and education is optimal, she said.

In terms of next steps, “We would really love to look at metformin in the postpartum period,” said Dr. Adams. Ideally, future work could look for outcomes that extend beyond the 6- to 8-week postpartum follow-up visit. For example, she said, there are indications that women with insulin insensitivity might benefit from metformin while breastfeeding; it’s also possible that metformin might reduce the risk of postpartum preeclampsia.

Dr. Adams reported that she had no conflicts of interest and no outside sources of funding.

koakes@mdedge.com

SOURCE: Adams J et al. SMFM 2020, Abstract 335.

*This story was updated 2/10/2020.

GRAPEVINE, TEX.* – Pregnant women with type 2 diabetes or prediabetes had significantly less gestational weight gain if they had metformin exposure at any point in their pregnancies, with no differences in infant birth weight or postnatal infant hypoglycemia, according to research presented at the meeting sponsored by the Society for Maternal-Fetal Medicine.

Kari Oakes/MDedge News

In a retrospective single-center review of 284 women without metformin exposure and 227 with metformin exposure in pregnancy, metformin exposure at any point in pregnancy was associated with a significantly greater chance of appropriate – rather than excessive – weight gain.

The relationship held true for the 169 women who had metformin in their first trimester of pregnancy. Here, 69% of women had appropriate weight gain using Institute of Medicine and American College of Obstetricians and Gynecologists standards, compared with 54% of the 282 women who had no metformin exposure (adjusted odds ratio 1.92, P = .003). A further 22% of women receiving metformin in their first trimester of pregnancy lost weight, compared with 9% of women without metformin exposure (aOR 2.11, P = .019). There was no significant difference between the two groups in infant birth weight.

Separately, study author Jacquelyn Adams, MD, and her colleagues analyzed outcomes for the full cohort of 227 women who received metformin at any point in their pregnancy, comparing them again to the 282 women who had not received metformin. Most women (85%) were on 2 g of metformin at the time of delivery. These results again showed a greater likelihood of appropriate weight gain in the metformin group (69%; aOR 1.85; P = .002). Maternal weight loss was seen in 20% of this group (aOR 1.98, P = .018). Infant birth weights were not significantly different between these two groups.

“We found that women who had been on metformin at any point in their pregnancy had more appropriate weight gain and less excessive weight gain,” said Dr. Adams, a maternal-fetal medicine fellow at the University of Wisconsin–Madison. “Actually, some women on metformin had even had a little bit of weight loss, with no difference in their baby’s birth weight. So that’s really exciting, because our starting prepregnancy body mass index was 33-36 [kg/m²], which is considered obese,” she said in an interview.

This is an important finding, said Dr. Adams, because previous work has shown that less weight gain in pregnancy is associated with lower risk for hypertension and preeclampsia, and lower rates of fetal macrosomia.

What about infant outcomes? Dr. Adams said that there were many concerns about metformin: “Would it affect baby outcome? Were those babies more likely to be hypoglycemic? Were they more likely to be growth restricted? Were they more likely to have issues in the NICU? And the answer was really, ‘No.’ ”

“So we can both help these women have appropriate weight gain and not have any negative effects on these babies,” she added.

Specifically, Dr. Adams and her coinvestigators found no significant differences between the groups in gestational age at birth, likelihood of neonatal ICU admission, Apgar scores, neonatal hypoglycemia, respiratory distress syndrome, or fetal death. Fetal growth restriction and anomalies occurred at a low and similar rate between the groups.

Dr. Adams said that she was not surprised to see that metformin was associated with less weight gain in pregnancy, but she was surprised at how highly significant the differences were with metformin use. “Metformin is first-line for diabetes in nonpregnant individuals because it’s associated with things like weight loss, and because of ease of use and lack of hypoglycemia – so I was really hoping to see this kind of result.”

Women receiving metformin were a mean 34 years old, while those who didn’t get metformin were 32 years old, a significant difference. Prepregnancy body mass index also was higher in those receiving metformin, and they were more likely to have a type 2 diabetes diagnosis. A similar proportion of both groups – about two-thirds – were white, and about 20% were Hispanic.

The lower weight gain seen in metformin-takers also might smooth the way post partum, said Dr. Adams. “My perception is that, when these women leave us, they might not have any primary care follow-up; they might not have anybody following their diabetes; and metformin is a very viable way to help them in their life outside of pregnancy.

“Not to mention that all the weight you gain in pregnancy, you do eventually have to lose post partum,” she added, “so having less pregnancy weight gain kind of sets them up for success in their postpregnancy life as well.”

Asked whether these results inform the ongoing question of whether insulin or metformin is the most appropriate first-line treatment for gestational diabetes, Dr. Adams first noted that “there’s a lot of crossover,” pointing out that over 60% of the participants in her study eventually also required insulin.

“It’s a question I would love to address in a head-to-head trial,” she said, adding that questions about metformin’s effects on the placenta and the potential for later deleterious effects require more study.

In her practice, Dr. Adams said that patients generally are discharged with a metformin prescription, and then meet with a diabetes educator 1 week after delivery to assess blood glucose levels and adjust medical management. Following that, a warm hand-off to a primary care practice who can continue management and education is optimal, she said.

In terms of next steps, “We would really love to look at metformin in the postpartum period,” said Dr. Adams. Ideally, future work could look for outcomes that extend beyond the 6- to 8-week postpartum follow-up visit. For example, she said, there are indications that women with insulin insensitivity might benefit from metformin while breastfeeding; it’s also possible that metformin might reduce the risk of postpartum preeclampsia.

Dr. Adams reported that she had no conflicts of interest and no outside sources of funding.

koakes@mdedge.com

SOURCE: Adams J et al. SMFM 2020, Abstract 335.

*This story was updated 2/10/2020.

New UK guidelines for the treatment of hyperthyroidism, including Graves’ disease, place heavier emphasis on the use of radioactive iodine as the frontline treatment for patients unlikely to remain remission-free on the medications, as opposed to the alternative of antithyroid medications as a first choice.
 

“Our evidence reviews indicated that radioactive iodine is the most clinically and cost-effective treatment for hyperthyroidism,” senior author Kristien Boelaert, MD, PhD, who led the guideline committee, said in an interview.

“Recommending the use of radioactive iodine as first-line treatment for adults with Graves’ disease is a change to current practice and should reduce the variation between centers as to when radioactive iodine is considered appropriate,” the guidelines further state.

The new recommendations on hyperthyroidism are part of broader guidelines on thyroid disease by the UK National Institute for Health and Care Excellence (NICE), which concludes that radioactive iodine results in cure in as many as 90% of hyperthyroidism cases.

The recommendations were published in a guideline summary in BMJ by research fellow Melina Vasileiou of the National Guideline Centre, Royal College of Physicians, London, and colleagues.

Current guidelines in the United Kingdom and Europe typically call for radioactive iodine to be reserved for use as a definitive treatment only after relapse following antithyroid medication treatment. The latest European Thyroid Association guidelines were published in 2018.

Elsewhere guidelines vary, with many, including those by the American Thyroid Association (ATA) – the most recent published in 2016 – generally calling for treatment with either antithyroid medications, radioactive iodine, or total thyroidectomy, in the absence of any contraindications to each treatment option.

“The U.S. tends to use more radioactive iodine, while Europe, Latin America, and Japan lean more toward (perhaps longer) use of antithyroid medications,” Angela Leung, MD, associate clinical professor of medicine in the division of endocrinology, diabetes, and metabolism, department of medicine, University of California, Los Angeles, said in an interview.

“Preferences of deciding which treatment option, which may involve more than one option if antithyroid medications are used initially, depend on a variety of factors related to patient desire, comorbidities, and availability of the therapy,” she explained.

Concerns including worsening thyroid eye disease, cardiovascular disease, and development of secondary cancers have caused some hesitation in the use of frontline radioiodine therapy.

And one notably controversial article, published last year, suggested a link between radioactive iodine therapy and an increased risk of cancer mortality. However, as reported by Medscape Medical News, the article spurred debate, with the Society for Endocrinology and British Thyroid Association issuing a joint statement urging caution in interpretation of the findings.

Evidence supporting first-line radioactive iodine

Patients treated with radioactive iodine take a single tablet that contains iodine and a low dose of radiation, which is absorbed by the thyroid. After taking the treatment patients are advised to avoid prolonged close contact with children and pregnant women for a few days or weeks and to avoid getting pregnant or fathering a child for several months. The treatment is likely to lead to an underactive thyroid gland that will require ongoing treatment with thyroid hormone replacement.

In providing evidence in favor of the benefits of radioactive iodine over the risks, the new NICE guidelines cite five randomized controlled trials of people with hyperthyroid disease, which, though defined as “low quality” evidence, collectively indicate that long-term outcomes were improved with radioactive iodine treatment compared with antithyroid drugs – despite the former having a higher risk of thyroid eye disease (also known as Graves’ ophthalmopathy).

In addition, eight nonrandomized studies show no evidence of a clinically important increase in cancer diagnoses or deaths between people treated with radioactive iodine or surgery, or between people treated with radioactive iodine and healthy controls, the guideline committee notes.

“The strongest arguments (in favor of radioactive iodine as a first-line therapy) were the likelihood of inducing remission of Graves’ disease with radioactive iodine, the finding that radioiodine is a safe treatment (confirmed in the safety review undertaken by NICE), and the reduction in the need for patients to remain on antithyroid drugs, which may have significant side effects and treatment which usually requires repeated hospital visits or follow-up under a hospital service,” said Dr. Boelaert.

The new guideline does recommend that antithyroid medication is acceptable as the first-line treatment among patients considered likely to achieve remission.

Dr. Leung explains that the percentage of patients with Graves’ disease who can achieve remission with antithyroid drugs ranges from 30% to 50%. She noted some evidence does suggest the long-term use of the drugs may be acceptable.

“There are some data that ... report the relative safety of long-term use of antithyroid drugs (beyond 24 months) for both Graves’ disease and autonomous thyroid nodules,” Dr. Leung elaborated.

Pregnancy concerns and cost-effectiveness of radioactive iodine

Radioactive iodine therapy is meanwhile not suitable if malignancy is suspected, if the patient is pregnant or trying to become pregnant, or if the patient has active thyroid eye disease, the experts agree.

Dr. Leung noted that although “it is generally advised to not treat Graves’ disease with radioiodine if there is concurrent thyroid eye disease, steroids are a proven effective therapy to decrease this risk in select patients.”

And among pregnant patients, “antithyroid medications should be minimally used in the lowest possible doses,” Dr. Leung said, although she added that, despite their potential risks, the drugs “represent a viable option” for this patient population.

“Also, many would actually advocate for total thyroidectomy in women who are thinking of pregnancy in the near future,” she noted.

Another factor of relevance in the guideline recommendations – cost – also favors radioactive iodine, the committee noted.

“Economic evidence showed that radioactive iodine was the most cost-effective intervention,” the committee pointed out.

Trabs advised for determination of hyperthyroidism cause

The new U.K. guidelines further underscore the importance of establishing the underlying cause of hyperthyroidism to ensure appropriate treatment, and the preferred method for doing so is the measurement of thyroid-stimulating hormone receptor antibodies (TRAbs).

“It is important to identify the underlying cause of thyrotoxicosis through measurement of TRAbs, or radioisotope scanning, in order to distinguish hyperthyroidism from transient causes of thyrotoxicosis such as transient thyroiditis, which only requires supportive treatment,” explained Dr. Boelaert, consultant endocrinologist and director of the National Institute for Health Research Integrated Academic Training Program at the Institute of Applied Health Research, University of Birmingham (England).

“In addition, this will help distinguish Graves’ disease from toxic nodular hyperthyroidism, which is important as antithyroid drugs are not effective in inducing a cure in the latter,” she explained.

Meanwhile, the new guidelines further note that although use of diagnostic ultrasound is informative when palpation suggests thyroid nodules, it is of limited diagnostic value for Graves’ disease.

“The recommendation (suggests that) thyroid ultrasonography should only be offered if there is a palpable thyroid nodule,” Dr. Boelaert noted.

She concluded: “There has been uncertainty in the U.K. about the best treatment for hyperthyroidism despite radioactive iodine being the most common first-line treatment for this condition in the United States. We are very pleased to have been able to work with NICE to provide clear new guidance which we hope will improve outcomes for patients with this condition.”

The National Guideline Centre was commissioned and funded by NICE to develop the guideline. No authors received specific funding to write the summary. Dr. Boelaert has reported no relevant financial relationships. Disclosures for the other authors are listed in the article.
 

This article first appeared on Medscape.com.

New UK guidelines for the treatment of hyperthyroidism, including Graves’ disease, place heavier emphasis on the use of radioactive iodine as the frontline treatment for patients unlikely to remain remission-free on the medications, as opposed to the alternative of antithyroid medications as a first choice.
 

“Our evidence reviews indicated that radioactive iodine is the most clinically and cost-effective treatment for hyperthyroidism,” senior author Kristien Boelaert, MD, PhD, who led the guideline committee, said in an interview.

“Recommending the use of radioactive iodine as first-line treatment for adults with Graves’ disease is a change to current practice and should reduce the variation between centers as to when radioactive iodine is considered appropriate,” the guidelines further state.

The new recommendations on hyperthyroidism are part of broader guidelines on thyroid disease by the UK National Institute for Health and Care Excellence (NICE), which concludes that radioactive iodine results in cure in as many as 90% of hyperthyroidism cases.

The recommendations were published in a guideline summary in BMJ by research fellow Melina Vasileiou of the National Guideline Centre, Royal College of Physicians, London, and colleagues.

Current guidelines in the United Kingdom and Europe typically call for radioactive iodine to be reserved for use as a definitive treatment only after relapse following antithyroid medication treatment. The latest European Thyroid Association guidelines were published in 2018.

Elsewhere guidelines vary, with many, including those by the American Thyroid Association (ATA) – the most recent published in 2016 – generally calling for treatment with either antithyroid medications, radioactive iodine, or total thyroidectomy, in the absence of any contraindications to each treatment option.

“The U.S. tends to use more radioactive iodine, while Europe, Latin America, and Japan lean more toward (perhaps longer) use of antithyroid medications,” Angela Leung, MD, associate clinical professor of medicine in the division of endocrinology, diabetes, and metabolism, department of medicine, University of California, Los Angeles, said in an interview.

“Preferences of deciding which treatment option, which may involve more than one option if antithyroid medications are used initially, depend on a variety of factors related to patient desire, comorbidities, and availability of the therapy,” she explained.

Concerns including worsening thyroid eye disease, cardiovascular disease, and development of secondary cancers have caused some hesitation in the use of frontline radioiodine therapy.

And one notably controversial article, published last year, suggested a link between radioactive iodine therapy and an increased risk of cancer mortality. However, as reported by Medscape Medical News, the article spurred debate, with the Society for Endocrinology and British Thyroid Association issuing a joint statement urging caution in interpretation of the findings.

Evidence supporting first-line radioactive iodine

Patients treated with radioactive iodine take a single tablet that contains iodine and a low dose of radiation, which is absorbed by the thyroid. After taking the treatment patients are advised to avoid prolonged close contact with children and pregnant women for a few days or weeks and to avoid getting pregnant or fathering a child for several months. The treatment is likely to lead to an underactive thyroid gland that will require ongoing treatment with thyroid hormone replacement.

In providing evidence in favor of the benefits of radioactive iodine over the risks, the new NICE guidelines cite five randomized controlled trials of people with hyperthyroid disease, which, though defined as “low quality” evidence, collectively indicate that long-term outcomes were improved with radioactive iodine treatment compared with antithyroid drugs – despite the former having a higher risk of thyroid eye disease (also known as Graves’ ophthalmopathy).

In addition, eight nonrandomized studies show no evidence of a clinically important increase in cancer diagnoses or deaths between people treated with radioactive iodine or surgery, or between people treated with radioactive iodine and healthy controls, the guideline committee notes.

“The strongest arguments (in favor of radioactive iodine as a first-line therapy) were the likelihood of inducing remission of Graves’ disease with radioactive iodine, the finding that radioiodine is a safe treatment (confirmed in the safety review undertaken by NICE), and the reduction in the need for patients to remain on antithyroid drugs, which may have significant side effects and treatment which usually requires repeated hospital visits or follow-up under a hospital service,” said Dr. Boelaert.

The new guideline does recommend that antithyroid medication is acceptable as the first-line treatment among patients considered likely to achieve remission.

Dr. Leung explains that the percentage of patients with Graves’ disease who can achieve remission with antithyroid drugs ranges from 30% to 50%. She noted some evidence does suggest the long-term use of the drugs may be acceptable.

“There are some data that ... report the relative safety of long-term use of antithyroid drugs (beyond 24 months) for both Graves’ disease and autonomous thyroid nodules,” Dr. Leung elaborated.

Pregnancy concerns and cost-effectiveness of radioactive iodine

Radioactive iodine therapy is meanwhile not suitable if malignancy is suspected, if the patient is pregnant or trying to become pregnant, or if the patient has active thyroid eye disease, the experts agree.

Dr. Leung noted that although “it is generally advised to not treat Graves’ disease with radioiodine if there is concurrent thyroid eye disease, steroids are a proven effective therapy to decrease this risk in select patients.”

And among pregnant patients, “antithyroid medications should be minimally used in the lowest possible doses,” Dr. Leung said, although she added that, despite their potential risks, the drugs “represent a viable option” for this patient population.

“Also, many would actually advocate for total thyroidectomy in women who are thinking of pregnancy in the near future,” she noted.

Another factor of relevance in the guideline recommendations – cost – also favors radioactive iodine, the committee noted.

“Economic evidence showed that radioactive iodine was the most cost-effective intervention,” the committee pointed out.

Trabs advised for determination of hyperthyroidism cause

The new U.K. guidelines further underscore the importance of establishing the underlying cause of hyperthyroidism to ensure appropriate treatment, and the preferred method for doing so is the measurement of thyroid-stimulating hormone receptor antibodies (TRAbs).

“It is important to identify the underlying cause of thyrotoxicosis through measurement of TRAbs, or radioisotope scanning, in order to distinguish hyperthyroidism from transient causes of thyrotoxicosis such as transient thyroiditis, which only requires supportive treatment,” explained Dr. Boelaert, consultant endocrinologist and director of the National Institute for Health Research Integrated Academic Training Program at the Institute of Applied Health Research, University of Birmingham (England).

“In addition, this will help distinguish Graves’ disease from toxic nodular hyperthyroidism, which is important as antithyroid drugs are not effective in inducing a cure in the latter,” she explained.

Meanwhile, the new guidelines further note that although use of diagnostic ultrasound is informative when palpation suggests thyroid nodules, it is of limited diagnostic value for Graves’ disease.

“The recommendation (suggests that) thyroid ultrasonography should only be offered if there is a palpable thyroid nodule,” Dr. Boelaert noted.

She concluded: “There has been uncertainty in the U.K. about the best treatment for hyperthyroidism despite radioactive iodine being the most common first-line treatment for this condition in the United States. We are very pleased to have been able to work with NICE to provide clear new guidance which we hope will improve outcomes for patients with this condition.”

The National Guideline Centre was commissioned and funded by NICE to develop the guideline. No authors received specific funding to write the summary. Dr. Boelaert has reported no relevant financial relationships. Disclosures for the other authors are listed in the article.
 

This article first appeared on Medscape.com.

New UK guidelines for the treatment of hyperthyroidism, including Graves’ disease, place heavier emphasis on the use of radioactive iodine as the frontline treatment for patients unlikely to remain remission-free on the medications, as opposed to the alternative of antithyroid medications as a first choice.
 

“Our evidence reviews indicated that radioactive iodine is the most clinically and cost-effective treatment for hyperthyroidism,” senior author Kristien Boelaert, MD, PhD, who led the guideline committee, said in an interview.

“Recommending the use of radioactive iodine as first-line treatment for adults with Graves’ disease is a change to current practice and should reduce the variation between centers as to when radioactive iodine is considered appropriate,” the guidelines further state.

The new recommendations on hyperthyroidism are part of broader guidelines on thyroid disease by the UK National Institute for Health and Care Excellence (NICE), which concludes that radioactive iodine results in cure in as many as 90% of hyperthyroidism cases.

The recommendations were published in a guideline summary in BMJ by research fellow Melina Vasileiou of the National Guideline Centre, Royal College of Physicians, London, and colleagues.

Current guidelines in the United Kingdom and Europe typically call for radioactive iodine to be reserved for use as a definitive treatment only after relapse following antithyroid medication treatment. The latest European Thyroid Association guidelines were published in 2018.

Elsewhere guidelines vary, with many, including those by the American Thyroid Association (ATA) – the most recent published in 2016 – generally calling for treatment with either antithyroid medications, radioactive iodine, or total thyroidectomy, in the absence of any contraindications to each treatment option.

“The U.S. tends to use more radioactive iodine, while Europe, Latin America, and Japan lean more toward (perhaps longer) use of antithyroid medications,” Angela Leung, MD, associate clinical professor of medicine in the division of endocrinology, diabetes, and metabolism, department of medicine, University of California, Los Angeles, said in an interview.

“Preferences of deciding which treatment option, which may involve more than one option if antithyroid medications are used initially, depend on a variety of factors related to patient desire, comorbidities, and availability of the therapy,” she explained.

Concerns including worsening thyroid eye disease, cardiovascular disease, and development of secondary cancers have caused some hesitation in the use of frontline radioiodine therapy.

And one notably controversial article, published last year, suggested a link between radioactive iodine therapy and an increased risk of cancer mortality. However, as reported by Medscape Medical News, the article spurred debate, with the Society for Endocrinology and British Thyroid Association issuing a joint statement urging caution in interpretation of the findings.

Evidence supporting first-line radioactive iodine

Patients treated with radioactive iodine take a single tablet that contains iodine and a low dose of radiation, which is absorbed by the thyroid. After taking the treatment patients are advised to avoid prolonged close contact with children and pregnant women for a few days or weeks and to avoid getting pregnant or fathering a child for several months. The treatment is likely to lead to an underactive thyroid gland that will require ongoing treatment with thyroid hormone replacement.

In providing evidence in favor of the benefits of radioactive iodine over the risks, the new NICE guidelines cite five randomized controlled trials of people with hyperthyroid disease, which, though defined as “low quality” evidence, collectively indicate that long-term outcomes were improved with radioactive iodine treatment compared with antithyroid drugs – despite the former having a higher risk of thyroid eye disease (also known as Graves’ ophthalmopathy).

In addition, eight nonrandomized studies show no evidence of a clinically important increase in cancer diagnoses or deaths between people treated with radioactive iodine or surgery, or between people treated with radioactive iodine and healthy controls, the guideline committee notes.

“The strongest arguments (in favor of radioactive iodine as a first-line therapy) were the likelihood of inducing remission of Graves’ disease with radioactive iodine, the finding that radioiodine is a safe treatment (confirmed in the safety review undertaken by NICE), and the reduction in the need for patients to remain on antithyroid drugs, which may have significant side effects and treatment which usually requires repeated hospital visits or follow-up under a hospital service,” said Dr. Boelaert.

The new guideline does recommend that antithyroid medication is acceptable as the first-line treatment among patients considered likely to achieve remission.

Dr. Leung explains that the percentage of patients with Graves’ disease who can achieve remission with antithyroid drugs ranges from 30% to 50%. She noted some evidence does suggest the long-term use of the drugs may be acceptable.

“There are some data that ... report the relative safety of long-term use of antithyroid drugs (beyond 24 months) for both Graves’ disease and autonomous thyroid nodules,” Dr. Leung elaborated.

Pregnancy concerns and cost-effectiveness of radioactive iodine

Radioactive iodine therapy is meanwhile not suitable if malignancy is suspected, if the patient is pregnant or trying to become pregnant, or if the patient has active thyroid eye disease, the experts agree.

Dr. Leung noted that although “it is generally advised to not treat Graves’ disease with radioiodine if there is concurrent thyroid eye disease, steroids are a proven effective therapy to decrease this risk in select patients.”

And among pregnant patients, “antithyroid medications should be minimally used in the lowest possible doses,” Dr. Leung said, although she added that, despite their potential risks, the drugs “represent a viable option” for this patient population.

“Also, many would actually advocate for total thyroidectomy in women who are thinking of pregnancy in the near future,” she noted.

Another factor of relevance in the guideline recommendations – cost – also favors radioactive iodine, the committee noted.

“Economic evidence showed that radioactive iodine was the most cost-effective intervention,” the committee pointed out.

Trabs advised for determination of hyperthyroidism cause

The new U.K. guidelines further underscore the importance of establishing the underlying cause of hyperthyroidism to ensure appropriate treatment, and the preferred method for doing so is the measurement of thyroid-stimulating hormone receptor antibodies (TRAbs).

“It is important to identify the underlying cause of thyrotoxicosis through measurement of TRAbs, or radioisotope scanning, in order to distinguish hyperthyroidism from transient causes of thyrotoxicosis such as transient thyroiditis, which only requires supportive treatment,” explained Dr. Boelaert, consultant endocrinologist and director of the National Institute for Health Research Integrated Academic Training Program at the Institute of Applied Health Research, University of Birmingham (England).

“In addition, this will help distinguish Graves’ disease from toxic nodular hyperthyroidism, which is important as antithyroid drugs are not effective in inducing a cure in the latter,” she explained.

Meanwhile, the new guidelines further note that although use of diagnostic ultrasound is informative when palpation suggests thyroid nodules, it is of limited diagnostic value for Graves’ disease.

“The recommendation (suggests that) thyroid ultrasonography should only be offered if there is a palpable thyroid nodule,” Dr. Boelaert noted.

She concluded: “There has been uncertainty in the U.K. about the best treatment for hyperthyroidism despite radioactive iodine being the most common first-line treatment for this condition in the United States. We are very pleased to have been able to work with NICE to provide clear new guidance which we hope will improve outcomes for patients with this condition.”

The National Guideline Centre was commissioned and funded by NICE to develop the guideline. No authors received specific funding to write the summary. Dr. Boelaert has reported no relevant financial relationships. Disclosures for the other authors are listed in the article.
 

This article first appeared on Medscape.com.

The Food and Drug Administration says it has no plans to recall any metformin products, used for the treatment of type 2 diabetes, after tests it conducted did not show any evidence of contamination with N-nitrosodimethylamine (NDMA) at levels that would cause concern.

The FDA began testing samples of metformin for the carcinogen NDMA at the end of 2019. Contamination with this substance has led to recalls of hypertension and heartburn medications within the past 2 years.

That announcement came on the heels of a recall of three versions of metformin in Singapore and the European Medicines Agency’s request that manufacturers test for NDMA.

This week, the FDA posted laboratory results in which NDMA levels in some metformin products ranged from “not detectable to low.”

“To date, no sample of metformin that FDA has tested exceeds the acceptable daily intake for NDMA. FDA has not recommended metformin recalls in the U.S.,” the agency indicates.

More than 30 million people in the United States have diabetes; 90%-95% of cases are of type 2. Metformin is the fourth most prescribed drug in the United States.

“Patients should continue taking metformin to keep their diabetes under control,” the FDA emphasized. “It could be dangerous for patients with this serious condition to stop taking their metformin without first talking to their health care professionals.”

The agency plans to post the methods used in laboratory testing of metformin in the near future. The FDA is collaborating with international regulators to share testing results for metformin, along with testing results for other drugs.

The U.S. agency says it will continue to monitor NDMA in metformin, along with other drug products, and will provide timely updates of new developments, including product recalls.

For more information about NDMA, visit the FDA’s nitrosamines webpage.

The FDA also encourages health care professionals and patients to report adverse reactions or quality problems with any human drugs to the agency’s MedWatch Adverse Event Reporting program.

This article first appeared on Medscape.com.

The Food and Drug Administration says it has no plans to recall any metformin products, used for the treatment of type 2 diabetes, after tests it conducted did not show any evidence of contamination with N-nitrosodimethylamine (NDMA) at levels that would cause concern.

The FDA began testing samples of metformin for the carcinogen NDMA at the end of 2019. Contamination with this substance has led to recalls of hypertension and heartburn medications within the past 2 years.

That announcement came on the heels of a recall of three versions of metformin in Singapore and the European Medicines Agency’s request that manufacturers test for NDMA.

This week, the FDA posted laboratory results in which NDMA levels in some metformin products ranged from “not detectable to low.”

“To date, no sample of metformin that FDA has tested exceeds the acceptable daily intake for NDMA. FDA has not recommended metformin recalls in the U.S.,” the agency indicates.

More than 30 million people in the United States have diabetes; 90%-95% of cases are of type 2. Metformin is the fourth most prescribed drug in the United States.

“Patients should continue taking metformin to keep their diabetes under control,” the FDA emphasized. “It could be dangerous for patients with this serious condition to stop taking their metformin without first talking to their health care professionals.”

The agency plans to post the methods used in laboratory testing of metformin in the near future. The FDA is collaborating with international regulators to share testing results for metformin, along with testing results for other drugs.

The U.S. agency says it will continue to monitor NDMA in metformin, along with other drug products, and will provide timely updates of new developments, including product recalls.

For more information about NDMA, visit the FDA’s nitrosamines webpage.

The FDA also encourages health care professionals and patients to report adverse reactions or quality problems with any human drugs to the agency’s MedWatch Adverse Event Reporting program.

This article first appeared on Medscape.com.

The Food and Drug Administration says it has no plans to recall any metformin products, used for the treatment of type 2 diabetes, after tests it conducted did not show any evidence of contamination with N-nitrosodimethylamine (NDMA) at levels that would cause concern.

The FDA began testing samples of metformin for the carcinogen NDMA at the end of 2019. Contamination with this substance has led to recalls of hypertension and heartburn medications within the past 2 years.

That announcement came on the heels of a recall of three versions of metformin in Singapore and the European Medicines Agency’s request that manufacturers test for NDMA.

This week, the FDA posted laboratory results in which NDMA levels in some metformin products ranged from “not detectable to low.”

“To date, no sample of metformin that FDA has tested exceeds the acceptable daily intake for NDMA. FDA has not recommended metformin recalls in the U.S.,” the agency indicates.

More than 30 million people in the United States have diabetes; 90%-95% of cases are of type 2. Metformin is the fourth most prescribed drug in the United States.

“Patients should continue taking metformin to keep their diabetes under control,” the FDA emphasized. “It could be dangerous for patients with this serious condition to stop taking their metformin without first talking to their health care professionals.”

The agency plans to post the methods used in laboratory testing of metformin in the near future. The FDA is collaborating with international regulators to share testing results for metformin, along with testing results for other drugs.

The U.S. agency says it will continue to monitor NDMA in metformin, along with other drug products, and will provide timely updates of new developments, including product recalls.

For more information about NDMA, visit the FDA’s nitrosamines webpage.

The FDA also encourages health care professionals and patients to report adverse reactions or quality problems with any human drugs to the agency’s MedWatch Adverse Event Reporting program.

This article first appeared on Medscape.com.

The time has come for good men and women to unite and rise up against a common foe. For too long nurses and doctors have labored under the tyranny of a dictator who claimed to help them provide high-quality care for their patients while at the same time cutting their paperwork to nil. But like most autocrats he failed to engage his subjects in a meaningful dialogue as each new version of his promised improvements rolled off the drawing board. When the caregivers were slow to adopt these new nonsystems he offered them financial incentives and issued threats to their survival. Although they were warned that there might be uncomfortable adjustment periods, the caregivers were promised that the steep learning curves would level out and their professional lives would again be valued and productive.

Of course, the dictator is not a single person but a motley and disorganized conglomerate of user- and patient-unfriendly electronic health record nonsystems. Ask almost any nurse or physician for her feelings about computer-based medical record systems, and you will hear tales of long hours, disengagement, and frustration. Caregivers are unhappy at all levels, and patients have grown tired of their nurses and physicians spending most of their time looking at computer screens.

You certainly have heard this all before. But you are hearing it in hospital hallways and grocery store checkout lines as a low rumble of discontent emerging from separate individuals, not as a well-articulated and widely distributed voice of physicians as a group. To some extent this relative silence is because there is no such group, at least not in same mold as a labor union. The term “labor union” may make you uncomfortable. But given the current climate in medicine, unionizing may be the best and only way to effect change.

But organizing to effect change in the workplace isn’t part of the physician genome. In the 1960s, a group of house officers in Boston engaged in a heal-in to successfully improve their salaries and working conditions. But over the ensuing half century physicians have remained tragically silent in the face of a changing workplace landscape in which they have gone from being independent owner operators in control of their destinies to becoming employees feeling powerless to improve their working conditions. This perceived impotence has escalated in the face of the challenge posed by the introduction of dysfunctional EHRs.

Ironically, a solution is at almost every physician’s elbow. In a recent New York Times opinion piece Theresa Brown and Stephen Bergman acknowledge that physicians don’t seem prepared to mount a meaningful response to the challenge to the failed promise of EHRs (“Doctors, Nurses and the Paperwork Crisis That Could Unite Them,” Dec. 31, 2019). They point out that, over the last half century, physicians have remained isolated on the sidelines, finding just enough voice to grumble. Nurses have in a variety of situations organized to effect change in their working conditions – in some cases by forming labor unions.

The authors of this op-ed piece, a physician and a nurse, make a strong argument that the time has come for nurses and doctors shake off the shackles of their stereotypic roles and join in creating a loud, forceful, and effective voice to demand a working environment in which the computer functions as an asset and no longer as the terrible burden it has become. Neither group has the power to do it alone, but together they may be able to turn the tide. For physicians it will probably mean venturing several steps outside of their comfort zone. But working shoulder to shoulder with nurses may provide the courage to speak out.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at pdnews@mdedge.com.

The time has come for good men and women to unite and rise up against a common foe. For too long nurses and doctors have labored under the tyranny of a dictator who claimed to help them provide high-quality care for their patients while at the same time cutting their paperwork to nil. But like most autocrats he failed to engage his subjects in a meaningful dialogue as each new version of his promised improvements rolled off the drawing board. When the caregivers were slow to adopt these new nonsystems he offered them financial incentives and issued threats to their survival. Although they were warned that there might be uncomfortable adjustment periods, the caregivers were promised that the steep learning curves would level out and their professional lives would again be valued and productive.

Of course, the dictator is not a single person but a motley and disorganized conglomerate of user- and patient-unfriendly electronic health record nonsystems. Ask almost any nurse or physician for her feelings about computer-based medical record systems, and you will hear tales of long hours, disengagement, and frustration. Caregivers are unhappy at all levels, and patients have grown tired of their nurses and physicians spending most of their time looking at computer screens.

You certainly have heard this all before. But you are hearing it in hospital hallways and grocery store checkout lines as a low rumble of discontent emerging from separate individuals, not as a well-articulated and widely distributed voice of physicians as a group. To some extent this relative silence is because there is no such group, at least not in same mold as a labor union. The term “labor union” may make you uncomfortable. But given the current climate in medicine, unionizing may be the best and only way to effect change.

But organizing to effect change in the workplace isn’t part of the physician genome. In the 1960s, a group of house officers in Boston engaged in a heal-in to successfully improve their salaries and working conditions. But over the ensuing half century physicians have remained tragically silent in the face of a changing workplace landscape in which they have gone from being independent owner operators in control of their destinies to becoming employees feeling powerless to improve their working conditions. This perceived impotence has escalated in the face of the challenge posed by the introduction of dysfunctional EHRs.

Ironically, a solution is at almost every physician’s elbow. In a recent New York Times opinion piece Theresa Brown and Stephen Bergman acknowledge that physicians don’t seem prepared to mount a meaningful response to the challenge to the failed promise of EHRs (“Doctors, Nurses and the Paperwork Crisis That Could Unite Them,” Dec. 31, 2019). They point out that, over the last half century, physicians have remained isolated on the sidelines, finding just enough voice to grumble. Nurses have in a variety of situations organized to effect change in their working conditions – in some cases by forming labor unions.

The authors of this op-ed piece, a physician and a nurse, make a strong argument that the time has come for nurses and doctors shake off the shackles of their stereotypic roles and join in creating a loud, forceful, and effective voice to demand a working environment in which the computer functions as an asset and no longer as the terrible burden it has become. Neither group has the power to do it alone, but together they may be able to turn the tide. For physicians it will probably mean venturing several steps outside of their comfort zone. But working shoulder to shoulder with nurses may provide the courage to speak out.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at pdnews@mdedge.com.

The time has come for good men and women to unite and rise up against a common foe. For too long nurses and doctors have labored under the tyranny of a dictator who claimed to help them provide high-quality care for their patients while at the same time cutting their paperwork to nil. But like most autocrats he failed to engage his subjects in a meaningful dialogue as each new version of his promised improvements rolled off the drawing board. When the caregivers were slow to adopt these new nonsystems he offered them financial incentives and issued threats to their survival. Although they were warned that there might be uncomfortable adjustment periods, the caregivers were promised that the steep learning curves would level out and their professional lives would again be valued and productive.

Of course, the dictator is not a single person but a motley and disorganized conglomerate of user- and patient-unfriendly electronic health record nonsystems. Ask almost any nurse or physician for her feelings about computer-based medical record systems, and you will hear tales of long hours, disengagement, and frustration. Caregivers are unhappy at all levels, and patients have grown tired of their nurses and physicians spending most of their time looking at computer screens.

You certainly have heard this all before. But you are hearing it in hospital hallways and grocery store checkout lines as a low rumble of discontent emerging from separate individuals, not as a well-articulated and widely distributed voice of physicians as a group. To some extent this relative silence is because there is no such group, at least not in same mold as a labor union. The term “labor union” may make you uncomfortable. But given the current climate in medicine, unionizing may be the best and only way to effect change.

But organizing to effect change in the workplace isn’t part of the physician genome. In the 1960s, a group of house officers in Boston engaged in a heal-in to successfully improve their salaries and working conditions. But over the ensuing half century physicians have remained tragically silent in the face of a changing workplace landscape in which they have gone from being independent owner operators in control of their destinies to becoming employees feeling powerless to improve their working conditions. This perceived impotence has escalated in the face of the challenge posed by the introduction of dysfunctional EHRs.

Ironically, a solution is at almost every physician’s elbow. In a recent New York Times opinion piece Theresa Brown and Stephen Bergman acknowledge that physicians don’t seem prepared to mount a meaningful response to the challenge to the failed promise of EHRs (“Doctors, Nurses and the Paperwork Crisis That Could Unite Them,” Dec. 31, 2019). They point out that, over the last half century, physicians have remained isolated on the sidelines, finding just enough voice to grumble. Nurses have in a variety of situations organized to effect change in their working conditions – in some cases by forming labor unions.

The authors of this op-ed piece, a physician and a nurse, make a strong argument that the time has come for nurses and doctors shake off the shackles of their stereotypic roles and join in creating a loud, forceful, and effective voice to demand a working environment in which the computer functions as an asset and no longer as the terrible burden it has become. Neither group has the power to do it alone, but together they may be able to turn the tide. For physicians it will probably mean venturing several steps outside of their comfort zone. But working shoulder to shoulder with nurses may provide the courage to speak out.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at pdnews@mdedge.com.

SNOWMASS, COLO. – Physical activity is potent medicine, and it doesn’t take all that much of it to derive the maximum cardiovascular benefit: namely, the equivalent of a brisk hour-long walk 5 days/week or jogging at a 10-minute-per-mile pace for half an hour twice weekly, Robert A. Vogel, MD, asserted at the annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.

Bruce Jancin/MDedge News

“I’m not telling you to run marathons. A message for your patients is, ‘You don’t have to do a lot, but you have to do something,’ ” said Dr. Vogel, a cardiologist at the University of Colorado at Denver, Aurora, with a longstanding interest in preventive cardiology.

He presented selected highlights from the massive evidence base underlying the recommendations put forth in the current comprehensive U.S. Department of Health & Human Services Physical Activity Guidelines for Americans.

One particularly compelling chunk of evidence comes from a Taiwanese government–funded prospective cohort study of more than 416,000 individuals followed for an average of 8 years. A key finding: 15 minutes of moderate-intensity physical activity daily was associated with a 14% reduction in the relative risk of all-cause mortality and a 19% reduction in death caused by cardiovascular disease, compared with that of inactive individuals. Moreover, each additional 15 minutes of daily moderate exercise further reduced mortality by 4%. These benefits extended across the full age spectrum of both sexes and applied to patients with cardiovascular disease (Lancet. 2011 Oct 1;378[9798]:1244-53).

“That’s a very impressive result for modest physical activity,” the cardiologist commented.

Data on more than 50,000 adult participants in the Aerobics Center Longitudinal Study based at the Cooper Clinic in Dallas show that vigorous exercise in the form of running at 6 mph for half an hour twice weekly, or a total of 10 metabolic equivalent of task hours (MET-HR) per week, was associated with a roughly 40% reduction in cardiovascular disease mortality. Importantly, 20, 40, or 50 MET-HR/week of vigorous exercise conferred no further survival benefit (J Am Coll Cardiol. 2014 Aug 5;64[5]:472-81). The same group showed that the sweet spot for moderate physical activity in terms of reduced cardiovascular mortality was brisk walking for an hour daily 5 days/week, for a total of 20 MET-HR, which was also associated with roughly a 40% risk reduction compared to inactivity. At that point the benefit plateaued, with no further mortality reduction noted with additional MET-HR of moderate exercise.

“For more than that, we have no evidence of additional cardiovascular benefit. It’s not going to get you to the Tokyo Olympics, but that’s what we need to be doing,” Dr. Vogel observed.

In another report from the Aerobics Center Longitudinal Study, investigators found that moderate-level cardiorespiratory fitness as defined by METs was associated with a 44% reduction in the risk of sudden cardiac death in men and women after adjustment for potential confounders, while high-level cardiorespiratory fitness was associated with a closely similar 48% reduction in risk. This applied to individuals who were hypertensive, overweight, and/or had poor health status, as well as to others (Mayo Clin Proc. 2016 Jul;91[7]:849-57).


 

All activity counts

Exercise physiologists speak of NEPA – nonexercise physical activity – such as taking out the garbage. Swedish investigators followed more than 4,200 individuals for an average of 12.5 years and found that high NEPA activity was independently associated with a 30% reduction in all-cause mortality and a 27% lower risk of a first cardiovascular disease event, compared with low NEPA. High NEPA in regular exercisers was associated with a lower rate of metabolic syndrome than in low-NEPA regular exercisers (Br J Sports Med. 2014 Feb;48[3]:233-8).

Don’t just sit there – stand!

The current federal physical activity guidelines place a new emphasis on the detrimental effects of sitting. A report on more than 221,000 participants in the Australian 45 and Up Study, with close to 1 million person-years of follow-up, demonstrated a linear inverse relationship between standing time per day and all-cause mortality. In a multivariate analysis adjusted for potential confounders, individuals who stood for 2-5 hours per day had a 10% lower risk of all-cause mortality than did those who stood for less than 2 hours. Standing for 5-8 hours was associated with a 15% relative risk reduction. And standing for more than 8 hours daily was linked to a 24% reduction in risk (Prev Med. 2014 Dec;69:187-91).

And it’s not just total daily sitting time that’s a risk factor. Prolonged, uninterrupted sedentary time was also associated with a dose-dependent increase in all-cause mortality in a prospective cohort study of nearly 8,000 U.S. adults (Ann Intern Med. 2017 Oct 3;167[7]:465-75).

“If you can’t walk around, talk to your patients standing up. That activity of getting out of your chair is lifesaving,” the cardiologist advised.
 

Get strong

Muscle-strengthening activity on at least 2 days/week is recommended in the federal guidelines because it’s independently associated with decreased all-cause mortality, even in individuals getting sufficient aerobic exercise, as shown in a large national study with 15-years’ follow-up (Prev Med. 2016 Jun;87:121-127).

“As we get older, we tend to forget about muscle. I work with the National Football League. These folks are pretty strong, but we never see diabetes in these very big players, who are often well over 300 lb. They’ve got a lot of muscle. If you want to prevent diabetes, be strong. It’s a very important factor,” Dr. Vogel said.
 

For the time constrained

Jogging is more time-efficient than brisk walking as a way to attain the maximum cardiovascular benefit of exercise. And the so-called “Weekend Warrior” study of nearly 64,000 U.K. adults showed that it’s okay to cram the full week’s worth of exercise into one or two sessions and be done with it. Compared with the inactive study participants, the weekend warriors had a 40% reduction in cardiovascular disease mortality, while individuals who split their physical activity up into three or more sessions per week had a nearly identical 41% relative risk reduction (JAMA Intern Med. 2017 Mar 1;177[3]:335-42).

Interval training is a standard way for athletes in training to improve their endurance by alternating short, intense exercise with brief recovery periods. It’s also a time saver: In one classic bicycling study, physically active men were randomized to standardized 2-week programs of sprint interval training or high-volume endurance training on the bike. The training time required to pass a rigorous cycling time trial test was 90% lower in the interval training group (J Physiol. 2006 Sep 15;575(Pt 3):901-11).

The same principle is applicable to the nonathlete interested in physical activity for heart health.

“When I run a couple of miles, I walk for 5 minutes, then maybe run for three-quarters of a mile, then walk again, then run. In interval training you get your heart rate up, and you drop it down. It’s a very good form of exercise. As a vascular biologist I know that if you put endothelial cells in a Petri dish and spin them real fast continuously, you will not get as good an improvement in endothelial function as if you spin the dish, stop it, spin it, stop it,” Dr. Vogel said.
 

High-volume exercise is safe, even with high coronary calcium

A clinically significant coronary artery calcification score of 100 Agatston units or more is no reason not to exercise. A Cooper Clinic report on nearly 22,000 middle-aged men without baseline cardiovascular disease who were followed for a mean of 10.4 years concluded that those in the highest-volume exercise group, many of whom were marathon runners and engaged in the equivalent of running for at least 5-6 hours/week at a pace of 10 minutes per mile, were 11% more likely to have an elevated baseline coronary artery calcification score than those who exercised less. But these highest-volume exercisers with elevated coronary calcium – their mean level was 807 Agatston units – had risks of all-cause and cardiovascular mortality that weren’t significantly different from those of men with elevated coronary calcium who exercised more moderately (JAMA Cardiol. 2019 Feb 1;4[2]:174-81).

Cardiac rehab

Dr. Vogel had harsh words for his physician colleagues with respect to the widespread underprescribing of cardiac rehabilitation programs.

“You guys are doing a crappy job with exercise in our most vulnerable patients: those who’ve had cardiovascular events,” he charged. “Cardiac rehabilitation is a Class I recommendation in our guidelines. And yet utilization in the United States is just 10%-20%. No other Class I recommendation is in that ballpark.”

A meta-analysis of 34 randomized trials totaling more than 6,000 post-MI patients concluded that those randomized to exercise-based cardiac rehabilitation had a 47% reduction in the risk of reinfarction, 36% lower cardiac mortality, and a 26% reduction in all-cause mortality (Am Heart J. 2011 Oct;162[4]:571-584.e2).

“The data show that cardiac rehabilitation is as effective as anything else we do in cardiovascular medicine. I understand that patients live far away, they don’t like to exercise – I’ve heard every excuse. But I am charging you with the responsibility of meeting a Class I recommendation that gets patients to live longer,” he declared.

Medicare now covers an enhanced, 72-session program called Intensive Cardiac Rehabilitation that teaches comprehensive lifestyle change and provides reasonable reimbursement. “It’s a good thing for our patients,” Dr. Vogel commented.
 

Yoga

For patients who are reluctant to pound the pavement, yoga may provide an alternative form of physical activity with tangible cardiovascular benefits. Dr. Vogel pointed to the Yoga-CaRe trial presented at the 2018 scientific sessions of the American Heart Association. Yoga-CaRe randomized 3,959 post-MI patients at 29 centers in India to a program of 13 supervised in-hospital yoga classes followed by yoga at home, or to a control group with three educational sessions. The rate of major adverse cardiovascular events over 42 months of follow-up was cut in half, compared with controls, in the 27% of participants who attended at least 10 of the 13 yoga classes. Their quality of life scores were higher, too.

Dr. Vogel reported serving as a paid consultant to the National Football League and the Pritikin Longevity Center. He is on the speaker’s bureau for Sanofi and Regeneron.

bjancin@mdedge.com

SNOWMASS, COLO. – Physical activity is potent medicine, and it doesn’t take all that much of it to derive the maximum cardiovascular benefit: namely, the equivalent of a brisk hour-long walk 5 days/week or jogging at a 10-minute-per-mile pace for half an hour twice weekly, Robert A. Vogel, MD, asserted at the annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.

Bruce Jancin/MDedge News

“I’m not telling you to run marathons. A message for your patients is, ‘You don’t have to do a lot, but you have to do something,’ ” said Dr. Vogel, a cardiologist at the University of Colorado at Denver, Aurora, with a longstanding interest in preventive cardiology.

He presented selected highlights from the massive evidence base underlying the recommendations put forth in the current comprehensive U.S. Department of Health & Human Services Physical Activity Guidelines for Americans.

One particularly compelling chunk of evidence comes from a Taiwanese government–funded prospective cohort study of more than 416,000 individuals followed for an average of 8 years. A key finding: 15 minutes of moderate-intensity physical activity daily was associated with a 14% reduction in the relative risk of all-cause mortality and a 19% reduction in death caused by cardiovascular disease, compared with that of inactive individuals. Moreover, each additional 15 minutes of daily moderate exercise further reduced mortality by 4%. These benefits extended across the full age spectrum of both sexes and applied to patients with cardiovascular disease (Lancet. 2011 Oct 1;378[9798]:1244-53).

“That’s a very impressive result for modest physical activity,” the cardiologist commented.

Data on more than 50,000 adult participants in the Aerobics Center Longitudinal Study based at the Cooper Clinic in Dallas show that vigorous exercise in the form of running at 6 mph for half an hour twice weekly, or a total of 10 metabolic equivalent of task hours (MET-HR) per week, was associated with a roughly 40% reduction in cardiovascular disease mortality. Importantly, 20, 40, or 50 MET-HR/week of vigorous exercise conferred no further survival benefit (J Am Coll Cardiol. 2014 Aug 5;64[5]:472-81). The same group showed that the sweet spot for moderate physical activity in terms of reduced cardiovascular mortality was brisk walking for an hour daily 5 days/week, for a total of 20 MET-HR, which was also associated with roughly a 40% risk reduction compared to inactivity. At that point the benefit plateaued, with no further mortality reduction noted with additional MET-HR of moderate exercise.

“For more than that, we have no evidence of additional cardiovascular benefit. It’s not going to get you to the Tokyo Olympics, but that’s what we need to be doing,” Dr. Vogel observed.

In another report from the Aerobics Center Longitudinal Study, investigators found that moderate-level cardiorespiratory fitness as defined by METs was associated with a 44% reduction in the risk of sudden cardiac death in men and women after adjustment for potential confounders, while high-level cardiorespiratory fitness was associated with a closely similar 48% reduction in risk. This applied to individuals who were hypertensive, overweight, and/or had poor health status, as well as to others (Mayo Clin Proc. 2016 Jul;91[7]:849-57).


 

All activity counts

Exercise physiologists speak of NEPA – nonexercise physical activity – such as taking out the garbage. Swedish investigators followed more than 4,200 individuals for an average of 12.5 years and found that high NEPA activity was independently associated with a 30% reduction in all-cause mortality and a 27% lower risk of a first cardiovascular disease event, compared with low NEPA. High NEPA in regular exercisers was associated with a lower rate of metabolic syndrome than in low-NEPA regular exercisers (Br J Sports Med. 2014 Feb;48[3]:233-8).

Don’t just sit there – stand!

The current federal physical activity guidelines place a new emphasis on the detrimental effects of sitting. A report on more than 221,000 participants in the Australian 45 and Up Study, with close to 1 million person-years of follow-up, demonstrated a linear inverse relationship between standing time per day and all-cause mortality. In a multivariate analysis adjusted for potential confounders, individuals who stood for 2-5 hours per day had a 10% lower risk of all-cause mortality than did those who stood for less than 2 hours. Standing for 5-8 hours was associated with a 15% relative risk reduction. And standing for more than 8 hours daily was linked to a 24% reduction in risk (Prev Med. 2014 Dec;69:187-91).

And it’s not just total daily sitting time that’s a risk factor. Prolonged, uninterrupted sedentary time was also associated with a dose-dependent increase in all-cause mortality in a prospective cohort study of nearly 8,000 U.S. adults (Ann Intern Med. 2017 Oct 3;167[7]:465-75).

“If you can’t walk around, talk to your patients standing up. That activity of getting out of your chair is lifesaving,” the cardiologist advised.
 

Get strong

Muscle-strengthening activity on at least 2 days/week is recommended in the federal guidelines because it’s independently associated with decreased all-cause mortality, even in individuals getting sufficient aerobic exercise, as shown in a large national study with 15-years’ follow-up (Prev Med. 2016 Jun;87:121-127).

“As we get older, we tend to forget about muscle. I work with the National Football League. These folks are pretty strong, but we never see diabetes in these very big players, who are often well over 300 lb. They’ve got a lot of muscle. If you want to prevent diabetes, be strong. It’s a very important factor,” Dr. Vogel said.
 

For the time constrained

Jogging is more time-efficient than brisk walking as a way to attain the maximum cardiovascular benefit of exercise. And the so-called “Weekend Warrior” study of nearly 64,000 U.K. adults showed that it’s okay to cram the full week’s worth of exercise into one or two sessions and be done with it. Compared with the inactive study participants, the weekend warriors had a 40% reduction in cardiovascular disease mortality, while individuals who split their physical activity up into three or more sessions per week had a nearly identical 41% relative risk reduction (JAMA Intern Med. 2017 Mar 1;177[3]:335-42).

Interval training is a standard way for athletes in training to improve their endurance by alternating short, intense exercise with brief recovery periods. It’s also a time saver: In one classic bicycling study, physically active men were randomized to standardized 2-week programs of sprint interval training or high-volume endurance training on the bike. The training time required to pass a rigorous cycling time trial test was 90% lower in the interval training group (J Physiol. 2006 Sep 15;575(Pt 3):901-11).

The same principle is applicable to the nonathlete interested in physical activity for heart health.

“When I run a couple of miles, I walk for 5 minutes, then maybe run for three-quarters of a mile, then walk again, then run. In interval training you get your heart rate up, and you drop it down. It’s a very good form of exercise. As a vascular biologist I know that if you put endothelial cells in a Petri dish and spin them real fast continuously, you will not get as good an improvement in endothelial function as if you spin the dish, stop it, spin it, stop it,” Dr. Vogel said.
 

High-volume exercise is safe, even with high coronary calcium

A clinically significant coronary artery calcification score of 100 Agatston units or more is no reason not to exercise. A Cooper Clinic report on nearly 22,000 middle-aged men without baseline cardiovascular disease who were followed for a mean of 10.4 years concluded that those in the highest-volume exercise group, many of whom were marathon runners and engaged in the equivalent of running for at least 5-6 hours/week at a pace of 10 minutes per mile, were 11% more likely to have an elevated baseline coronary artery calcification score than those who exercised less. But these highest-volume exercisers with elevated coronary calcium – their mean level was 807 Agatston units – had risks of all-cause and cardiovascular mortality that weren’t significantly different from those of men with elevated coronary calcium who exercised more moderately (JAMA Cardiol. 2019 Feb 1;4[2]:174-81).

Cardiac rehab

Dr. Vogel had harsh words for his physician colleagues with respect to the widespread underprescribing of cardiac rehabilitation programs.

“You guys are doing a crappy job with exercise in our most vulnerable patients: those who’ve had cardiovascular events,” he charged. “Cardiac rehabilitation is a Class I recommendation in our guidelines. And yet utilization in the United States is just 10%-20%. No other Class I recommendation is in that ballpark.”

A meta-analysis of 34 randomized trials totaling more than 6,000 post-MI patients concluded that those randomized to exercise-based cardiac rehabilitation had a 47% reduction in the risk of reinfarction, 36% lower cardiac mortality, and a 26% reduction in all-cause mortality (Am Heart J. 2011 Oct;162[4]:571-584.e2).

“The data show that cardiac rehabilitation is as effective as anything else we do in cardiovascular medicine. I understand that patients live far away, they don’t like to exercise – I’ve heard every excuse. But I am charging you with the responsibility of meeting a Class I recommendation that gets patients to live longer,” he declared.

Medicare now covers an enhanced, 72-session program called Intensive Cardiac Rehabilitation that teaches comprehensive lifestyle change and provides reasonable reimbursement. “It’s a good thing for our patients,” Dr. Vogel commented.
 

Yoga

For patients who are reluctant to pound the pavement, yoga may provide an alternative form of physical activity with tangible cardiovascular benefits. Dr. Vogel pointed to the Yoga-CaRe trial presented at the 2018 scientific sessions of the American Heart Association. Yoga-CaRe randomized 3,959 post-MI patients at 29 centers in India to a program of 13 supervised in-hospital yoga classes followed by yoga at home, or to a control group with three educational sessions. The rate of major adverse cardiovascular events over 42 months of follow-up was cut in half, compared with controls, in the 27% of participants who attended at least 10 of the 13 yoga classes. Their quality of life scores were higher, too.

Dr. Vogel reported serving as a paid consultant to the National Football League and the Pritikin Longevity Center. He is on the speaker’s bureau for Sanofi and Regeneron.

bjancin@mdedge.com

SNOWMASS, COLO. – Physical activity is potent medicine, and it doesn’t take all that much of it to derive the maximum cardiovascular benefit: namely, the equivalent of a brisk hour-long walk 5 days/week or jogging at a 10-minute-per-mile pace for half an hour twice weekly, Robert A. Vogel, MD, asserted at the annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.

Bruce Jancin/MDedge News

“I’m not telling you to run marathons. A message for your patients is, ‘You don’t have to do a lot, but you have to do something,’ ” said Dr. Vogel, a cardiologist at the University of Colorado at Denver, Aurora, with a longstanding interest in preventive cardiology.

He presented selected highlights from the massive evidence base underlying the recommendations put forth in the current comprehensive U.S. Department of Health & Human Services Physical Activity Guidelines for Americans.

One particularly compelling chunk of evidence comes from a Taiwanese government–funded prospective cohort study of more than 416,000 individuals followed for an average of 8 years. A key finding: 15 minutes of moderate-intensity physical activity daily was associated with a 14% reduction in the relative risk of all-cause mortality and a 19% reduction in death caused by cardiovascular disease, compared with that of inactive individuals. Moreover, each additional 15 minutes of daily moderate exercise further reduced mortality by 4%. These benefits extended across the full age spectrum of both sexes and applied to patients with cardiovascular disease (Lancet. 2011 Oct 1;378[9798]:1244-53).

“That’s a very impressive result for modest physical activity,” the cardiologist commented.

Data on more than 50,000 adult participants in the Aerobics Center Longitudinal Study based at the Cooper Clinic in Dallas show that vigorous exercise in the form of running at 6 mph for half an hour twice weekly, or a total of 10 metabolic equivalent of task hours (MET-HR) per week, was associated with a roughly 40% reduction in cardiovascular disease mortality. Importantly, 20, 40, or 50 MET-HR/week of vigorous exercise conferred no further survival benefit (J Am Coll Cardiol. 2014 Aug 5;64[5]:472-81). The same group showed that the sweet spot for moderate physical activity in terms of reduced cardiovascular mortality was brisk walking for an hour daily 5 days/week, for a total of 20 MET-HR, which was also associated with roughly a 40% risk reduction compared to inactivity. At that point the benefit plateaued, with no further mortality reduction noted with additional MET-HR of moderate exercise.

“For more than that, we have no evidence of additional cardiovascular benefit. It’s not going to get you to the Tokyo Olympics, but that’s what we need to be doing,” Dr. Vogel observed.

In another report from the Aerobics Center Longitudinal Study, investigators found that moderate-level cardiorespiratory fitness as defined by METs was associated with a 44% reduction in the risk of sudden cardiac death in men and women after adjustment for potential confounders, while high-level cardiorespiratory fitness was associated with a closely similar 48% reduction in risk. This applied to individuals who were hypertensive, overweight, and/or had poor health status, as well as to others (Mayo Clin Proc. 2016 Jul;91[7]:849-57).


 

All activity counts

Exercise physiologists speak of NEPA – nonexercise physical activity – such as taking out the garbage. Swedish investigators followed more than 4,200 individuals for an average of 12.5 years and found that high NEPA activity was independently associated with a 30% reduction in all-cause mortality and a 27% lower risk of a first cardiovascular disease event, compared with low NEPA. High NEPA in regular exercisers was associated with a lower rate of metabolic syndrome than in low-NEPA regular exercisers (Br J Sports Med. 2014 Feb;48[3]:233-8).

Don’t just sit there – stand!

The current federal physical activity guidelines place a new emphasis on the detrimental effects of sitting. A report on more than 221,000 participants in the Australian 45 and Up Study, with close to 1 million person-years of follow-up, demonstrated a linear inverse relationship between standing time per day and all-cause mortality. In a multivariate analysis adjusted for potential confounders, individuals who stood for 2-5 hours per day had a 10% lower risk of all-cause mortality than did those who stood for less than 2 hours. Standing for 5-8 hours was associated with a 15% relative risk reduction. And standing for more than 8 hours daily was linked to a 24% reduction in risk (Prev Med. 2014 Dec;69:187-91).

And it’s not just total daily sitting time that’s a risk factor. Prolonged, uninterrupted sedentary time was also associated with a dose-dependent increase in all-cause mortality in a prospective cohort study of nearly 8,000 U.S. adults (Ann Intern Med. 2017 Oct 3;167[7]:465-75).

“If you can’t walk around, talk to your patients standing up. That activity of getting out of your chair is lifesaving,” the cardiologist advised.
 

Get strong

Muscle-strengthening activity on at least 2 days/week is recommended in the federal guidelines because it’s independently associated with decreased all-cause mortality, even in individuals getting sufficient aerobic exercise, as shown in a large national study with 15-years’ follow-up (Prev Med. 2016 Jun;87:121-127).

“As we get older, we tend to forget about muscle. I work with the National Football League. These folks are pretty strong, but we never see diabetes in these very big players, who are often well over 300 lb. They’ve got a lot of muscle. If you want to prevent diabetes, be strong. It’s a very important factor,” Dr. Vogel said.
 

For the time constrained

Jogging is more time-efficient than brisk walking as a way to attain the maximum cardiovascular benefit of exercise. And the so-called “Weekend Warrior” study of nearly 64,000 U.K. adults showed that it’s okay to cram the full week’s worth of exercise into one or two sessions and be done with it. Compared with the inactive study participants, the weekend warriors had a 40% reduction in cardiovascular disease mortality, while individuals who split their physical activity up into three or more sessions per week had a nearly identical 41% relative risk reduction (JAMA Intern Med. 2017 Mar 1;177[3]:335-42).

Interval training is a standard way for athletes in training to improve their endurance by alternating short, intense exercise with brief recovery periods. It’s also a time saver: In one classic bicycling study, physically active men were randomized to standardized 2-week programs of sprint interval training or high-volume endurance training on the bike. The training time required to pass a rigorous cycling time trial test was 90% lower in the interval training group (J Physiol. 2006 Sep 15;575(Pt 3):901-11).

The same principle is applicable to the nonathlete interested in physical activity for heart health.

“When I run a couple of miles, I walk for 5 minutes, then maybe run for three-quarters of a mile, then walk again, then run. In interval training you get your heart rate up, and you drop it down. It’s a very good form of exercise. As a vascular biologist I know that if you put endothelial cells in a Petri dish and spin them real fast continuously, you will not get as good an improvement in endothelial function as if you spin the dish, stop it, spin it, stop it,” Dr. Vogel said.
 

High-volume exercise is safe, even with high coronary calcium

A clinically significant coronary artery calcification score of 100 Agatston units or more is no reason not to exercise. A Cooper Clinic report on nearly 22,000 middle-aged men without baseline cardiovascular disease who were followed for a mean of 10.4 years concluded that those in the highest-volume exercise group, many of whom were marathon runners and engaged in the equivalent of running for at least 5-6 hours/week at a pace of 10 minutes per mile, were 11% more likely to have an elevated baseline coronary artery calcification score than those who exercised less. But these highest-volume exercisers with elevated coronary calcium – their mean level was 807 Agatston units – had risks of all-cause and cardiovascular mortality that weren’t significantly different from those of men with elevated coronary calcium who exercised more moderately (JAMA Cardiol. 2019 Feb 1;4[2]:174-81).

Cardiac rehab

Dr. Vogel had harsh words for his physician colleagues with respect to the widespread underprescribing of cardiac rehabilitation programs.

“You guys are doing a crappy job with exercise in our most vulnerable patients: those who’ve had cardiovascular events,” he charged. “Cardiac rehabilitation is a Class I recommendation in our guidelines. And yet utilization in the United States is just 10%-20%. No other Class I recommendation is in that ballpark.”

A meta-analysis of 34 randomized trials totaling more than 6,000 post-MI patients concluded that those randomized to exercise-based cardiac rehabilitation had a 47% reduction in the risk of reinfarction, 36% lower cardiac mortality, and a 26% reduction in all-cause mortality (Am Heart J. 2011 Oct;162[4]:571-584.e2).

“The data show that cardiac rehabilitation is as effective as anything else we do in cardiovascular medicine. I understand that patients live far away, they don’t like to exercise – I’ve heard every excuse. But I am charging you with the responsibility of meeting a Class I recommendation that gets patients to live longer,” he declared.

Medicare now covers an enhanced, 72-session program called Intensive Cardiac Rehabilitation that teaches comprehensive lifestyle change and provides reasonable reimbursement. “It’s a good thing for our patients,” Dr. Vogel commented.
 

Yoga

For patients who are reluctant to pound the pavement, yoga may provide an alternative form of physical activity with tangible cardiovascular benefits. Dr. Vogel pointed to the Yoga-CaRe trial presented at the 2018 scientific sessions of the American Heart Association. Yoga-CaRe randomized 3,959 post-MI patients at 29 centers in India to a program of 13 supervised in-hospital yoga classes followed by yoga at home, or to a control group with three educational sessions. The rate of major adverse cardiovascular events over 42 months of follow-up was cut in half, compared with controls, in the 27% of participants who attended at least 10 of the 13 yoga classes. Their quality of life scores were higher, too.

Dr. Vogel reported serving as a paid consultant to the National Football League and the Pritikin Longevity Center. He is on the speaker’s bureau for Sanofi and Regeneron.

bjancin@mdedge.com

President Donald J. Trump took on multiple health care issues in his State of the Union address, imploring Congress to avoid the “socialism” of Medicare-for-all, to pass legislation banning late-term abortions, and to protect insurance coverage for preexisting conditions while joining together to reduce rising drug prices.

Mr. Trump said his administration has already been “taking on the big pharmaceutical companies,” claiming that, in 2019, “for the first time in 51 years, the cost of prescription drugs actually went down.”

That statement was called “misleading” by the New York Times because such efforts have excluded some high-cost drugs, and prices had risen by the end of the year, the publication noted in a fact-check of the president’s speech.

A survey issued in December 2019 found that the United States pays the highest prices in the world for pharmaceuticals, as reported by Medscape Medical News.

But the president did throw down a gauntlet for Congress. “Working together, the Congress can reduce drug prices substantially from current levels,” he said, stating that he had been “speaking to Sen. Chuck Grassley of Iowa and others in the Congress in order to get something on drug pricing done, and done properly.

“Get a bill to my desk, and I will sign it into law without delay,” Mr. Trump said.

A group of House Democrats then stood up in the chamber and loudly chanted, “HR3, HR3,” referring to the Lower Drug Costs Now Act, which the House passed in December 2019.

The bill would give the Department of Health & Human Services the power to negotiate directly with drug companies on up to 250 drugs per year, in particular, the highest-costing and most-utilized drugs.

The Senate has not taken up the legislation, but Sen. Grassley (R) and Sen. Ron Wyden (D-Ore.) introduced a similar bill, the Prescription Drug Pricing Reduction Act. It has been approved by the Senate Finance Committee but has not been moved to the Senate floor.

“I appreciate President Trump recognizing the work we’re doing to lower prescription drug prices,” Sen. Grassley said in a statement after the State of the Union. “Iowans and Americans across the country are demanding reforms that lower sky-high drug costs. A recent poll showed 70% of Americans want Congress to make lowering drug prices its top priority.”

Rep. Greg Walden (R-Ore.), the ranking Republican on the House Energy and Commerce Committee, said he believed Trump was committed to lowering drug costs. “I’ve never seen a president lean in further than President Donald Trump on lowering health care costs,” said Rep. Walden in a statement after the speech.

Trump touted his price transparency rule, which he said would go into effect next January, as a key way to cut health care costs.

Preexisting conditions

The president said that since he’d taken office, insurance had become more affordable and that the quality of health care had improved. He also said that he was making what he called an “iron-clad pledge” to American families.

“We will always protect patients with preexisting conditions – that is a guarantee,” Mr. Trump said.

In a press conference before the speech, Speaker of the House Nancy Pelosi (D-Calif.) took issue with that pledge. “The president swears that he supports protections for people with preexisting conditions, but right now, he is fighting in federal court to eliminate these lifesaving protections and every last protection and benefit of the Affordable Care Act,” she said.

During the speech, Rep. G. K. Butterfield (D-N.C.) tweeted “#FactCheck: Claiming to protect Americans with preexisting conditions, Trump and his administration have repeatedly sought to undermine protections offered by the ACA through executive orders and the courts. He is seeking to strike down the law and its protections entirely.”

Larry Levitt, executive vice president for health policy at the Kaiser Family Foundation, pointed out in a tweet that insurance plans that Trump touted as “affordable alternatives” are in fact missing those protections.

“Ironically, the cheaper health insurance plans that President Trump has expanded are short-term plans that don’t cover preexisting conditions,” Mr. Levitt said.

Socialist takeover

Mr. Trump condemned the Medicare-for-all proposals that have been introduced in Congress and that are being backed in whole or in part by all of the Democratic candidates for president.

“As we work to improve Americans’ health care, there are those who want to take away your health care, take away your doctor, and abolish private insurance entirely,” said Mr. Trump.

He said that 132 members of Congress “have endorsed legislation to impose a socialist takeover of our health care system, wiping out the private health insurance plans of 180 million Americans.”

Added Mr. Trump: “We will never let socialism destroy American health care!”

Medicare-for-all has waxed and waned in popularity among voters, with generally more Democrats than Republicans favoring a single-payer system, with or without a public option.

Preliminary exit polls in Iowa that were conducted during Monday’s caucus found that 57% of Iowa Democratic caucus-goers supported a single-payer plan; 38% opposed such a plan, according to the Washington Post.
 

Opioids, the coronavirus, and abortion

In some of his final remarks on health care, Mr. Trump cited progress in the opioid crisis, noting that, in 2019, drug overdose deaths declined for the first time in 30 years.

He said that his administration was coordinating with the Chinese government regarding the coronavirus outbreak and noted the launch of initiatives to improve care for people with kidney disease, Alzheimer’s, and mental health problems.

Mr. Trump repeated his 2019 State of the Union claim that the government would help end AIDS in America by the end of the decade.

The president also announced that he was asking Congress for “an additional $50 million” to fund neonatal research. He followed that up with a plea about abortion.

“I am calling upon the members of Congress here tonight to pass legislation finally banning the late-term abortion of babies,” he said.

Insulin costs?

In the days before the speech, some news outlets had reported that Mr. Trump and the HHS were working on a plan to lower insulin prices for Medicare beneficiaries, and there were suggestions it would come up in the speech.

At least 13 members of Congress invited people advocating for lower insulin costs as their guests for the State of the Union, Stat reported. Rep. Pelosi invited twins from San Francisco with type 1 diabetes as her guests.

But Mr. Trump never mentioned insulin in his speech.

This article first appeared on Medscape.com.

President Donald J. Trump took on multiple health care issues in his State of the Union address, imploring Congress to avoid the “socialism” of Medicare-for-all, to pass legislation banning late-term abortions, and to protect insurance coverage for preexisting conditions while joining together to reduce rising drug prices.

Mr. Trump said his administration has already been “taking on the big pharmaceutical companies,” claiming that, in 2019, “for the first time in 51 years, the cost of prescription drugs actually went down.”

That statement was called “misleading” by the New York Times because such efforts have excluded some high-cost drugs, and prices had risen by the end of the year, the publication noted in a fact-check of the president’s speech.

A survey issued in December 2019 found that the United States pays the highest prices in the world for pharmaceuticals, as reported by Medscape Medical News.

But the president did throw down a gauntlet for Congress. “Working together, the Congress can reduce drug prices substantially from current levels,” he said, stating that he had been “speaking to Sen. Chuck Grassley of Iowa and others in the Congress in order to get something on drug pricing done, and done properly.

“Get a bill to my desk, and I will sign it into law without delay,” Mr. Trump said.

A group of House Democrats then stood up in the chamber and loudly chanted, “HR3, HR3,” referring to the Lower Drug Costs Now Act, which the House passed in December 2019.

The bill would give the Department of Health & Human Services the power to negotiate directly with drug companies on up to 250 drugs per year, in particular, the highest-costing and most-utilized drugs.

The Senate has not taken up the legislation, but Sen. Grassley (R) and Sen. Ron Wyden (D-Ore.) introduced a similar bill, the Prescription Drug Pricing Reduction Act. It has been approved by the Senate Finance Committee but has not been moved to the Senate floor.

“I appreciate President Trump recognizing the work we’re doing to lower prescription drug prices,” Sen. Grassley said in a statement after the State of the Union. “Iowans and Americans across the country are demanding reforms that lower sky-high drug costs. A recent poll showed 70% of Americans want Congress to make lowering drug prices its top priority.”

Rep. Greg Walden (R-Ore.), the ranking Republican on the House Energy and Commerce Committee, said he believed Trump was committed to lowering drug costs. “I’ve never seen a president lean in further than President Donald Trump on lowering health care costs,” said Rep. Walden in a statement after the speech.

Trump touted his price transparency rule, which he said would go into effect next January, as a key way to cut health care costs.

Preexisting conditions

The president said that since he’d taken office, insurance had become more affordable and that the quality of health care had improved. He also said that he was making what he called an “iron-clad pledge” to American families.

“We will always protect patients with preexisting conditions – that is a guarantee,” Mr. Trump said.

In a press conference before the speech, Speaker of the House Nancy Pelosi (D-Calif.) took issue with that pledge. “The president swears that he supports protections for people with preexisting conditions, but right now, he is fighting in federal court to eliminate these lifesaving protections and every last protection and benefit of the Affordable Care Act,” she said.

During the speech, Rep. G. K. Butterfield (D-N.C.) tweeted “#FactCheck: Claiming to protect Americans with preexisting conditions, Trump and his administration have repeatedly sought to undermine protections offered by the ACA through executive orders and the courts. He is seeking to strike down the law and its protections entirely.”

Larry Levitt, executive vice president for health policy at the Kaiser Family Foundation, pointed out in a tweet that insurance plans that Trump touted as “affordable alternatives” are in fact missing those protections.

“Ironically, the cheaper health insurance plans that President Trump has expanded are short-term plans that don’t cover preexisting conditions,” Mr. Levitt said.

Socialist takeover

Mr. Trump condemned the Medicare-for-all proposals that have been introduced in Congress and that are being backed in whole or in part by all of the Democratic candidates for president.

“As we work to improve Americans’ health care, there are those who want to take away your health care, take away your doctor, and abolish private insurance entirely,” said Mr. Trump.

He said that 132 members of Congress “have endorsed legislation to impose a socialist takeover of our health care system, wiping out the private health insurance plans of 180 million Americans.”

Added Mr. Trump: “We will never let socialism destroy American health care!”

Medicare-for-all has waxed and waned in popularity among voters, with generally more Democrats than Republicans favoring a single-payer system, with or without a public option.

Preliminary exit polls in Iowa that were conducted during Monday’s caucus found that 57% of Iowa Democratic caucus-goers supported a single-payer plan; 38% opposed such a plan, according to the Washington Post.
 

Opioids, the coronavirus, and abortion

In some of his final remarks on health care, Mr. Trump cited progress in the opioid crisis, noting that, in 2019, drug overdose deaths declined for the first time in 30 years.

He said that his administration was coordinating with the Chinese government regarding the coronavirus outbreak and noted the launch of initiatives to improve care for people with kidney disease, Alzheimer’s, and mental health problems.

Mr. Trump repeated his 2019 State of the Union claim that the government would help end AIDS in America by the end of the decade.

The president also announced that he was asking Congress for “an additional $50 million” to fund neonatal research. He followed that up with a plea about abortion.

“I am calling upon the members of Congress here tonight to pass legislation finally banning the late-term abortion of babies,” he said.

Insulin costs?

In the days before the speech, some news outlets had reported that Mr. Trump and the HHS were working on a plan to lower insulin prices for Medicare beneficiaries, and there were suggestions it would come up in the speech.

At least 13 members of Congress invited people advocating for lower insulin costs as their guests for the State of the Union, Stat reported. Rep. Pelosi invited twins from San Francisco with type 1 diabetes as her guests.

But Mr. Trump never mentioned insulin in his speech.

This article first appeared on Medscape.com.

President Donald J. Trump took on multiple health care issues in his State of the Union address, imploring Congress to avoid the “socialism” of Medicare-for-all, to pass legislation banning late-term abortions, and to protect insurance coverage for preexisting conditions while joining together to reduce rising drug prices.

Mr. Trump said his administration has already been “taking on the big pharmaceutical companies,” claiming that, in 2019, “for the first time in 51 years, the cost of prescription drugs actually went down.”

That statement was called “misleading” by the New York Times because such efforts have excluded some high-cost drugs, and prices had risen by the end of the year, the publication noted in a fact-check of the president’s speech.

A survey issued in December 2019 found that the United States pays the highest prices in the world for pharmaceuticals, as reported by Medscape Medical News.

But the president did throw down a gauntlet for Congress. “Working together, the Congress can reduce drug prices substantially from current levels,” he said, stating that he had been “speaking to Sen. Chuck Grassley of Iowa and others in the Congress in order to get something on drug pricing done, and done properly.

“Get a bill to my desk, and I will sign it into law without delay,” Mr. Trump said.

A group of House Democrats then stood up in the chamber and loudly chanted, “HR3, HR3,” referring to the Lower Drug Costs Now Act, which the House passed in December 2019.

The bill would give the Department of Health & Human Services the power to negotiate directly with drug companies on up to 250 drugs per year, in particular, the highest-costing and most-utilized drugs.

The Senate has not taken up the legislation, but Sen. Grassley (R) and Sen. Ron Wyden (D-Ore.) introduced a similar bill, the Prescription Drug Pricing Reduction Act. It has been approved by the Senate Finance Committee but has not been moved to the Senate floor.

“I appreciate President Trump recognizing the work we’re doing to lower prescription drug prices,” Sen. Grassley said in a statement after the State of the Union. “Iowans and Americans across the country are demanding reforms that lower sky-high drug costs. A recent poll showed 70% of Americans want Congress to make lowering drug prices its top priority.”

Rep. Greg Walden (R-Ore.), the ranking Republican on the House Energy and Commerce Committee, said he believed Trump was committed to lowering drug costs. “I’ve never seen a president lean in further than President Donald Trump on lowering health care costs,” said Rep. Walden in a statement after the speech.

Trump touted his price transparency rule, which he said would go into effect next January, as a key way to cut health care costs.

Preexisting conditions

The president said that since he’d taken office, insurance had become more affordable and that the quality of health care had improved. He also said that he was making what he called an “iron-clad pledge” to American families.

“We will always protect patients with preexisting conditions – that is a guarantee,” Mr. Trump said.

In a press conference before the speech, Speaker of the House Nancy Pelosi (D-Calif.) took issue with that pledge. “The president swears that he supports protections for people with preexisting conditions, but right now, he is fighting in federal court to eliminate these lifesaving protections and every last protection and benefit of the Affordable Care Act,” she said.

During the speech, Rep. G. K. Butterfield (D-N.C.) tweeted “#FactCheck: Claiming to protect Americans with preexisting conditions, Trump and his administration have repeatedly sought to undermine protections offered by the ACA through executive orders and the courts. He is seeking to strike down the law and its protections entirely.”

Larry Levitt, executive vice president for health policy at the Kaiser Family Foundation, pointed out in a tweet that insurance plans that Trump touted as “affordable alternatives” are in fact missing those protections.

“Ironically, the cheaper health insurance plans that President Trump has expanded are short-term plans that don’t cover preexisting conditions,” Mr. Levitt said.

Socialist takeover

Mr. Trump condemned the Medicare-for-all proposals that have been introduced in Congress and that are being backed in whole or in part by all of the Democratic candidates for president.

“As we work to improve Americans’ health care, there are those who want to take away your health care, take away your doctor, and abolish private insurance entirely,” said Mr. Trump.

He said that 132 members of Congress “have endorsed legislation to impose a socialist takeover of our health care system, wiping out the private health insurance plans of 180 million Americans.”

Added Mr. Trump: “We will never let socialism destroy American health care!”

Medicare-for-all has waxed and waned in popularity among voters, with generally more Democrats than Republicans favoring a single-payer system, with or without a public option.

Preliminary exit polls in Iowa that were conducted during Monday’s caucus found that 57% of Iowa Democratic caucus-goers supported a single-payer plan; 38% opposed such a plan, according to the Washington Post.
 

Opioids, the coronavirus, and abortion

In some of his final remarks on health care, Mr. Trump cited progress in the opioid crisis, noting that, in 2019, drug overdose deaths declined for the first time in 30 years.

He said that his administration was coordinating with the Chinese government regarding the coronavirus outbreak and noted the launch of initiatives to improve care for people with kidney disease, Alzheimer’s, and mental health problems.

Mr. Trump repeated his 2019 State of the Union claim that the government would help end AIDS in America by the end of the decade.

The president also announced that he was asking Congress for “an additional $50 million” to fund neonatal research. He followed that up with a plea about abortion.

“I am calling upon the members of Congress here tonight to pass legislation finally banning the late-term abortion of babies,” he said.

Insulin costs?

In the days before the speech, some news outlets had reported that Mr. Trump and the HHS were working on a plan to lower insulin prices for Medicare beneficiaries, and there were suggestions it would come up in the speech.

At least 13 members of Congress invited people advocating for lower insulin costs as their guests for the State of the Union, Stat reported. Rep. Pelosi invited twins from San Francisco with type 1 diabetes as her guests.

But Mr. Trump never mentioned insulin in his speech.

This article first appeared on Medscape.com.

SNOWMASS, COLO. – The redefinition of hypertension as 130/80 mm Hg or higher introduced in the current American College of Cardiology/American Heart Association hypertension management guidelines has generated considerable controversy. Often overlooked, however, has been another major innovation included in the 2017 guidelines: the rise in the status of out-of-office 24-hour ambulatory blood pressure monitoring and home blood pressure self-measurement to a class I, level of evidence A recommendation, Andrew M. Kates, MD, observed at the annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.

Bruce Jancin/MDedge News

It’s a guideline he strongly endorses.

“We do a lot of this. It can be a challenge to get 24-hour ambulatory blood pressure monitoring covered by payers, so I’m a much bigger fan of home blood pressure monitoring with appropriate instruction of patients. It empowers them to take some control,” said Dr. Kates, professor of medicine and director of the cardiology fellowship program at Washington University, St. Louis.

He explained that one of the four key questions the guideline committee was tasked with answering at the outset of deliberations was this: What’s the evidence base for self-directed out-of-office blood pressure monitoring? Based on the panel’s systematic review of the literature, this practice wound up receiving the strongest possible class Ia recommendation, specifically for confirming the diagnosis of hypertension and for titration of antihypertensive medications. Moreover, the guidelines also endorsed home blood pressure monitoring for the detection of white-coat hypertension, this time as a Class IIa recommendation, as well as for identification of patients with masked hypertension, with class IIb status (Circulation. 2018 Oct 23;138[17]:e484-594).

The 2017 ACC/AHA guidelines include a detailed checklist for obtaining accurate measurements of office blood pressure. The suggestions include having the patient sit relaxed in a chair with both feet on the floor for at least 5 minutes before taking the measurement, no coffee or exercise for 30 minutes beforehand, empty the bladder, no talking, no clothing over the arm, and other recommendations. Many busy clinicians roll their eyes at the impracticality of doing all this on a routine basis.

“I don’t want to take an audience survey, but I’ll say that even in our office we are not successful in doing this. Patients run up the stairs to the office after dealing with traffic and the parking garage, they’re late for their appointment, in winter they’re wearing a sweater and don’t want to take it off. These are things we don’t do well, and they’re low-hanging fruit where we could do better,” Dr. Kates commented.

The challenges inherent in performing by-the-book office blood pressure measurement reinforce the importance of home self-monitoring of blood pressure in what is hopefully a more stress-free environment.

“We can give patients specific guidance about checking their blood pressure an hour after taking their medications, sitting for 5 minutes, and checking the pressures on a bare arm and not with the sleeve rolled up,” he noted.

The guidelines recommend using home blood pressure monitoring or ambulatory monitoring to detect white-coat hypertension in patients with an office blood pressure of 130/80 mm Hg or more, but less than 160/100 mm Hg, after a 3-month trial of lifestyle modification. If the home blood pressure is less than 130/80 mm Hg, that’s evidence of white-coat hypertension, for which the recommended treatment consists of continued lifestyle modification plus periodic monitoring of out-of-office blood pressures in order to promptly detect progression to hypertension. If, however, the out-of-office blood pressure is not less than 130/80 mm Hg, that’s hypertension, and the guidelines recommend starting dual-agent antihypertensive drug therapy while continuing lifestyle modification.

A confusing array of definitions of hypertension are now in use by various medical societies. While the 2017 ACC/AHA hypertension guidelines define hypertension as office blood pressure of 130/80 mm Hg or more, the 2018 European Society of Cardiology/European Society of Hypertension guidelines use a threshold of 140/90 mm Hg or more. Joint American Academy of Family Physicians/American College of Physicians guidelines recommend a treatment target of less than 150 mm Hg in hypertensive patients aged 60 years or older. And at the other end of the spectrum, the SPRINT trial showed a significant cardiovascular benefit for intensive treatment of hypertension to a target systolic blood pressure below 120 mm Hg, rather than less than 140 mm Hg (N Engl J Med. 2015 Nov 26;373[22]:2103-16).

Dr. Kates believes the debate over the “right” treatment target misses the central point, which is that hypertension is staggeringly undertreated. Indeed, the Centers for Disease Control and Prevention estimates only one in four adults with hypertension have their disease under control. That’s a disconcerting statistic given that hypertension accounts for more cardiovascular deaths than any other modifiable cardiovascular risk factor.

“There’s been some concern raised that maybe too much weight has been put on the SPRINT trial in making the ACC/AHA recommendations, but I think it’s helpful to understand that we vastly undertreat patients with hypertension. So I think that, rather than being so concerned that we’re going to be treating people to too low a target or we’re being overly aggressive, it should give us some pause to think about the fact that we’re ordinarily not being aggressive enough with many of our patients as it is,” the cardiologist said.

Dr. Kates reported having no financial conflicts regarding his presentation.

bjancin@mdedge.com

SNOWMASS, COLO. – The redefinition of hypertension as 130/80 mm Hg or higher introduced in the current American College of Cardiology/American Heart Association hypertension management guidelines has generated considerable controversy. Often overlooked, however, has been another major innovation included in the 2017 guidelines: the rise in the status of out-of-office 24-hour ambulatory blood pressure monitoring and home blood pressure self-measurement to a class I, level of evidence A recommendation, Andrew M. Kates, MD, observed at the annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.

Bruce Jancin/MDedge News

It’s a guideline he strongly endorses.

“We do a lot of this. It can be a challenge to get 24-hour ambulatory blood pressure monitoring covered by payers, so I’m a much bigger fan of home blood pressure monitoring with appropriate instruction of patients. It empowers them to take some control,” said Dr. Kates, professor of medicine and director of the cardiology fellowship program at Washington University, St. Louis.

He explained that one of the four key questions the guideline committee was tasked with answering at the outset of deliberations was this: What’s the evidence base for self-directed out-of-office blood pressure monitoring? Based on the panel’s systematic review of the literature, this practice wound up receiving the strongest possible class Ia recommendation, specifically for confirming the diagnosis of hypertension and for titration of antihypertensive medications. Moreover, the guidelines also endorsed home blood pressure monitoring for the detection of white-coat hypertension, this time as a Class IIa recommendation, as well as for identification of patients with masked hypertension, with class IIb status (Circulation. 2018 Oct 23;138[17]:e484-594).

The 2017 ACC/AHA guidelines include a detailed checklist for obtaining accurate measurements of office blood pressure. The suggestions include having the patient sit relaxed in a chair with both feet on the floor for at least 5 minutes before taking the measurement, no coffee or exercise for 30 minutes beforehand, empty the bladder, no talking, no clothing over the arm, and other recommendations. Many busy clinicians roll their eyes at the impracticality of doing all this on a routine basis.

“I don’t want to take an audience survey, but I’ll say that even in our office we are not successful in doing this. Patients run up the stairs to the office after dealing with traffic and the parking garage, they’re late for their appointment, in winter they’re wearing a sweater and don’t want to take it off. These are things we don’t do well, and they’re low-hanging fruit where we could do better,” Dr. Kates commented.

The challenges inherent in performing by-the-book office blood pressure measurement reinforce the importance of home self-monitoring of blood pressure in what is hopefully a more stress-free environment.

“We can give patients specific guidance about checking their blood pressure an hour after taking their medications, sitting for 5 minutes, and checking the pressures on a bare arm and not with the sleeve rolled up,” he noted.

The guidelines recommend using home blood pressure monitoring or ambulatory monitoring to detect white-coat hypertension in patients with an office blood pressure of 130/80 mm Hg or more, but less than 160/100 mm Hg, after a 3-month trial of lifestyle modification. If the home blood pressure is less than 130/80 mm Hg, that’s evidence of white-coat hypertension, for which the recommended treatment consists of continued lifestyle modification plus periodic monitoring of out-of-office blood pressures in order to promptly detect progression to hypertension. If, however, the out-of-office blood pressure is not less than 130/80 mm Hg, that’s hypertension, and the guidelines recommend starting dual-agent antihypertensive drug therapy while continuing lifestyle modification.

A confusing array of definitions of hypertension are now in use by various medical societies. While the 2017 ACC/AHA hypertension guidelines define hypertension as office blood pressure of 130/80 mm Hg or more, the 2018 European Society of Cardiology/European Society of Hypertension guidelines use a threshold of 140/90 mm Hg or more. Joint American Academy of Family Physicians/American College of Physicians guidelines recommend a treatment target of less than 150 mm Hg in hypertensive patients aged 60 years or older. And at the other end of the spectrum, the SPRINT trial showed a significant cardiovascular benefit for intensive treatment of hypertension to a target systolic blood pressure below 120 mm Hg, rather than less than 140 mm Hg (N Engl J Med. 2015 Nov 26;373[22]:2103-16).

Dr. Kates believes the debate over the “right” treatment target misses the central point, which is that hypertension is staggeringly undertreated. Indeed, the Centers for Disease Control and Prevention estimates only one in four adults with hypertension have their disease under control. That’s a disconcerting statistic given that hypertension accounts for more cardiovascular deaths than any other modifiable cardiovascular risk factor.

“There’s been some concern raised that maybe too much weight has been put on the SPRINT trial in making the ACC/AHA recommendations, but I think it’s helpful to understand that we vastly undertreat patients with hypertension. So I think that, rather than being so concerned that we’re going to be treating people to too low a target or we’re being overly aggressive, it should give us some pause to think about the fact that we’re ordinarily not being aggressive enough with many of our patients as it is,” the cardiologist said.

Dr. Kates reported having no financial conflicts regarding his presentation.

bjancin@mdedge.com

SNOWMASS, COLO. – The redefinition of hypertension as 130/80 mm Hg or higher introduced in the current American College of Cardiology/American Heart Association hypertension management guidelines has generated considerable controversy. Often overlooked, however, has been another major innovation included in the 2017 guidelines: the rise in the status of out-of-office 24-hour ambulatory blood pressure monitoring and home blood pressure self-measurement to a class I, level of evidence A recommendation, Andrew M. Kates, MD, observed at the annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.

Bruce Jancin/MDedge News

It’s a guideline he strongly endorses.

“We do a lot of this. It can be a challenge to get 24-hour ambulatory blood pressure monitoring covered by payers, so I’m a much bigger fan of home blood pressure monitoring with appropriate instruction of patients. It empowers them to take some control,” said Dr. Kates, professor of medicine and director of the cardiology fellowship program at Washington University, St. Louis.

He explained that one of the four key questions the guideline committee was tasked with answering at the outset of deliberations was this: What’s the evidence base for self-directed out-of-office blood pressure monitoring? Based on the panel’s systematic review of the literature, this practice wound up receiving the strongest possible class Ia recommendation, specifically for confirming the diagnosis of hypertension and for titration of antihypertensive medications. Moreover, the guidelines also endorsed home blood pressure monitoring for the detection of white-coat hypertension, this time as a Class IIa recommendation, as well as for identification of patients with masked hypertension, with class IIb status (Circulation. 2018 Oct 23;138[17]:e484-594).

The 2017 ACC/AHA guidelines include a detailed checklist for obtaining accurate measurements of office blood pressure. The suggestions include having the patient sit relaxed in a chair with both feet on the floor for at least 5 minutes before taking the measurement, no coffee or exercise for 30 minutes beforehand, empty the bladder, no talking, no clothing over the arm, and other recommendations. Many busy clinicians roll their eyes at the impracticality of doing all this on a routine basis.

“I don’t want to take an audience survey, but I’ll say that even in our office we are not successful in doing this. Patients run up the stairs to the office after dealing with traffic and the parking garage, they’re late for their appointment, in winter they’re wearing a sweater and don’t want to take it off. These are things we don’t do well, and they’re low-hanging fruit where we could do better,” Dr. Kates commented.

The challenges inherent in performing by-the-book office blood pressure measurement reinforce the importance of home self-monitoring of blood pressure in what is hopefully a more stress-free environment.

“We can give patients specific guidance about checking their blood pressure an hour after taking their medications, sitting for 5 minutes, and checking the pressures on a bare arm and not with the sleeve rolled up,” he noted.

The guidelines recommend using home blood pressure monitoring or ambulatory monitoring to detect white-coat hypertension in patients with an office blood pressure of 130/80 mm Hg or more, but less than 160/100 mm Hg, after a 3-month trial of lifestyle modification. If the home blood pressure is less than 130/80 mm Hg, that’s evidence of white-coat hypertension, for which the recommended treatment consists of continued lifestyle modification plus periodic monitoring of out-of-office blood pressures in order to promptly detect progression to hypertension. If, however, the out-of-office blood pressure is not less than 130/80 mm Hg, that’s hypertension, and the guidelines recommend starting dual-agent antihypertensive drug therapy while continuing lifestyle modification.

A confusing array of definitions of hypertension are now in use by various medical societies. While the 2017 ACC/AHA hypertension guidelines define hypertension as office blood pressure of 130/80 mm Hg or more, the 2018 European Society of Cardiology/European Society of Hypertension guidelines use a threshold of 140/90 mm Hg or more. Joint American Academy of Family Physicians/American College of Physicians guidelines recommend a treatment target of less than 150 mm Hg in hypertensive patients aged 60 years or older. And at the other end of the spectrum, the SPRINT trial showed a significant cardiovascular benefit for intensive treatment of hypertension to a target systolic blood pressure below 120 mm Hg, rather than less than 140 mm Hg (N Engl J Med. 2015 Nov 26;373[22]:2103-16).

Dr. Kates believes the debate over the “right” treatment target misses the central point, which is that hypertension is staggeringly undertreated. Indeed, the Centers for Disease Control and Prevention estimates only one in four adults with hypertension have their disease under control. That’s a disconcerting statistic given that hypertension accounts for more cardiovascular deaths than any other modifiable cardiovascular risk factor.

“There’s been some concern raised that maybe too much weight has been put on the SPRINT trial in making the ACC/AHA recommendations, but I think it’s helpful to understand that we vastly undertreat patients with hypertension. So I think that, rather than being so concerned that we’re going to be treating people to too low a target or we’re being overly aggressive, it should give us some pause to think about the fact that we’re ordinarily not being aggressive enough with many of our patients as it is,” the cardiologist said.

Dr. Kates reported having no financial conflicts regarding his presentation.

bjancin@mdedge.com

When people learn they have enough cardiovascular disease risk to start treatment with a statin or antihypertensive drug, the impact on their healthy-lifestyle choices seems to often be a wash, based on findings from more than 40,000 Finland residents followed for at least 4 years after starting their primary-prevention regimen.

American Heart Association

“Patients’ awareness of their risk factors alone seems not to be effective in improving health behaviors,” wrote Maarit J. Korhonen, PhD, and associates in a report published in the Journal of the American Heart Association.

“Initiation of antihypertensive or statin therapy appears to be associated with lifestyle changes, some positive and others negative,” wrote Dr. Korhonen, a pharmacoepidemiologist at the University of Turku (Finland), and associates. This was the first reported study to assess a large-scale and prospectively followed cohort to look for associations between the use of medicines that prevent cardiovascular disease (CVD) and lifestyle changes. Most previous studies of these associations “have been cross sectional and provide no information on potential lifestyle changes during the time window around the initiation of medication use,” they added.

The new study specifically found that, on average, people who began treatment with at least one CVD-prevention medication for the first time were more likely to gain weight and more likely to become less active during the years following their treatment onset. But at the same time, these patients were also more likely to either quit or cut down on their smoking and alcohol consumption, the researchers found.

Their analysis used data from 41,225 people enrolled in the Finnish Public Sector Study, which prospectively began collecting data on a large number of Finland residents in the 1990s. They specifically focused on 81,772 completed questionnaires – collected at 4-year intervals – from people who completed at least two consecutive rounds of the survey during 2000-2013, and who were also at least 40 years old and free of prevalent CVD at the time of their first survey. The participants averaged nearly 53 years of age at their first survey, and 84% were women.

The researchers subdivided the survey responses into 8,837 (11%) people who began a statin, antihypertensive drug, or both during their participation; 26,914 (33%) already on a statin or antihypertensive drug when they completed their first questionnaire; and 46,021 response sets (56%) from people who never began treatment with either drug class. People who initiated a relevant drug began a median of 1.7 years following completion of their first survey, and a median of 2.4 years before their next survey. During follow-up, about 2% of all participants became newly diagnosed with some form of CVD.

The results showed that, after full adjustment for possible confounders, the mean increase in body mass index was larger among those who initiated a CVD-prevention drug, compared with those who did not. Among participants who were obese at entry, those who started a CVD drug had a statistically significant 37% increased rate of remaining obese, compared with those not starting these drugs. Among those who were not obese at baseline, those who began a CVD prevention drug had a statistically significant 82%% higher rate of becoming obese, compared with those not on a CVD-prevention drug. In addition, average daily energy expenditure, a measure of physical activity, showed a statistically significant decline among those who started a CVD drug, compared with those who did not. In contrast, CVD drug initiators had an average 1.85 gram/week decline in alcohol intake, compared with noninitiators, and those who were current smokers at the first survey and then started a CVD drug had a 26% relative drop in their smoking prevalence, compared with those who did not start a CVD drug, both statistically significant differences.

The findings suggest that “patients’ awareness of their risk factors alone seems not to be effective in improving health behaviors,” the authors concluded. “This means that expansion of pharmacologic interventions toward populations at low CVD risk may not necessarily lead to expected benefits at the population level.”

The study received no commercial funding. Dr. Korhonen had no disclosures.

mzoler@mdedge.com

SOURCE: Korhonen MJ et al. J Am Heart Assoc. 2020 Feb 5. doi: 10.1161/JAHA.119.014.168.

When people learn they have enough cardiovascular disease risk to start treatment with a statin or antihypertensive drug, the impact on their healthy-lifestyle choices seems to often be a wash, based on findings from more than 40,000 Finland residents followed for at least 4 years after starting their primary-prevention regimen.

American Heart Association

“Patients’ awareness of their risk factors alone seems not to be effective in improving health behaviors,” wrote Maarit J. Korhonen, PhD, and associates in a report published in the Journal of the American Heart Association.

“Initiation of antihypertensive or statin therapy appears to be associated with lifestyle changes, some positive and others negative,” wrote Dr. Korhonen, a pharmacoepidemiologist at the University of Turku (Finland), and associates. This was the first reported study to assess a large-scale and prospectively followed cohort to look for associations between the use of medicines that prevent cardiovascular disease (CVD) and lifestyle changes. Most previous studies of these associations “have been cross sectional and provide no information on potential lifestyle changes during the time window around the initiation of medication use,” they added.

The new study specifically found that, on average, people who began treatment with at least one CVD-prevention medication for the first time were more likely to gain weight and more likely to become less active during the years following their treatment onset. But at the same time, these patients were also more likely to either quit or cut down on their smoking and alcohol consumption, the researchers found.

Their analysis used data from 41,225 people enrolled in the Finnish Public Sector Study, which prospectively began collecting data on a large number of Finland residents in the 1990s. They specifically focused on 81,772 completed questionnaires – collected at 4-year intervals – from people who completed at least two consecutive rounds of the survey during 2000-2013, and who were also at least 40 years old and free of prevalent CVD at the time of their first survey. The participants averaged nearly 53 years of age at their first survey, and 84% were women.

The researchers subdivided the survey responses into 8,837 (11%) people who began a statin, antihypertensive drug, or both during their participation; 26,914 (33%) already on a statin or antihypertensive drug when they completed their first questionnaire; and 46,021 response sets (56%) from people who never began treatment with either drug class. People who initiated a relevant drug began a median of 1.7 years following completion of their first survey, and a median of 2.4 years before their next survey. During follow-up, about 2% of all participants became newly diagnosed with some form of CVD.

The results showed that, after full adjustment for possible confounders, the mean increase in body mass index was larger among those who initiated a CVD-prevention drug, compared with those who did not. Among participants who were obese at entry, those who started a CVD drug had a statistically significant 37% increased rate of remaining obese, compared with those not starting these drugs. Among those who were not obese at baseline, those who began a CVD prevention drug had a statistically significant 82%% higher rate of becoming obese, compared with those not on a CVD-prevention drug. In addition, average daily energy expenditure, a measure of physical activity, showed a statistically significant decline among those who started a CVD drug, compared with those who did not. In contrast, CVD drug initiators had an average 1.85 gram/week decline in alcohol intake, compared with noninitiators, and those who were current smokers at the first survey and then started a CVD drug had a 26% relative drop in their smoking prevalence, compared with those who did not start a CVD drug, both statistically significant differences.

The findings suggest that “patients’ awareness of their risk factors alone seems not to be effective in improving health behaviors,” the authors concluded. “This means that expansion of pharmacologic interventions toward populations at low CVD risk may not necessarily lead to expected benefits at the population level.”

The study received no commercial funding. Dr. Korhonen had no disclosures.

mzoler@mdedge.com

SOURCE: Korhonen MJ et al. J Am Heart Assoc. 2020 Feb 5. doi: 10.1161/JAHA.119.014.168.

When people learn they have enough cardiovascular disease risk to start treatment with a statin or antihypertensive drug, the impact on their healthy-lifestyle choices seems to often be a wash, based on findings from more than 40,000 Finland residents followed for at least 4 years after starting their primary-prevention regimen.

American Heart Association

“Patients’ awareness of their risk factors alone seems not to be effective in improving health behaviors,” wrote Maarit J. Korhonen, PhD, and associates in a report published in the Journal of the American Heart Association.

“Initiation of antihypertensive or statin therapy appears to be associated with lifestyle changes, some positive and others negative,” wrote Dr. Korhonen, a pharmacoepidemiologist at the University of Turku (Finland), and associates. This was the first reported study to assess a large-scale and prospectively followed cohort to look for associations between the use of medicines that prevent cardiovascular disease (CVD) and lifestyle changes. Most previous studies of these associations “have been cross sectional and provide no information on potential lifestyle changes during the time window around the initiation of medication use,” they added.

The new study specifically found that, on average, people who began treatment with at least one CVD-prevention medication for the first time were more likely to gain weight and more likely to become less active during the years following their treatment onset. But at the same time, these patients were also more likely to either quit or cut down on their smoking and alcohol consumption, the researchers found.

Their analysis used data from 41,225 people enrolled in the Finnish Public Sector Study, which prospectively began collecting data on a large number of Finland residents in the 1990s. They specifically focused on 81,772 completed questionnaires – collected at 4-year intervals – from people who completed at least two consecutive rounds of the survey during 2000-2013, and who were also at least 40 years old and free of prevalent CVD at the time of their first survey. The participants averaged nearly 53 years of age at their first survey, and 84% were women.

The researchers subdivided the survey responses into 8,837 (11%) people who began a statin, antihypertensive drug, or both during their participation; 26,914 (33%) already on a statin or antihypertensive drug when they completed their first questionnaire; and 46,021 response sets (56%) from people who never began treatment with either drug class. People who initiated a relevant drug began a median of 1.7 years following completion of their first survey, and a median of 2.4 years before their next survey. During follow-up, about 2% of all participants became newly diagnosed with some form of CVD.

The results showed that, after full adjustment for possible confounders, the mean increase in body mass index was larger among those who initiated a CVD-prevention drug, compared with those who did not. Among participants who were obese at entry, those who started a CVD drug had a statistically significant 37% increased rate of remaining obese, compared with those not starting these drugs. Among those who were not obese at baseline, those who began a CVD prevention drug had a statistically significant 82%% higher rate of becoming obese, compared with those not on a CVD-prevention drug. In addition, average daily energy expenditure, a measure of physical activity, showed a statistically significant decline among those who started a CVD drug, compared with those who did not. In contrast, CVD drug initiators had an average 1.85 gram/week decline in alcohol intake, compared with noninitiators, and those who were current smokers at the first survey and then started a CVD drug had a 26% relative drop in their smoking prevalence, compared with those who did not start a CVD drug, both statistically significant differences.

The findings suggest that “patients’ awareness of their risk factors alone seems not to be effective in improving health behaviors,” the authors concluded. “This means that expansion of pharmacologic interventions toward populations at low CVD risk may not necessarily lead to expected benefits at the population level.”

The study received no commercial funding. Dr. Korhonen had no disclosures.

mzoler@mdedge.com

SOURCE: Korhonen MJ et al. J Am Heart Assoc. 2020 Feb 5. doi: 10.1161/JAHA.119.014.168.

LOS ANGELES – The way Christos S. Mantzoros, MD, DSc, PhD, sees it, nonalcoholic steatohepatitis (NASH) is an epidemic of the 21st century that can trigger a cascade of reactions.

Doug Brunk/MDedge News

“If more than 5.8% of fat is in the liver, we call it nonalcoholic fatty liver disease [NAFLD],” Dr. Mantzoros, professor of medicine at Harvard Medical School, Boston, and Boston University, explained at the World Congress on Insulin Resistance, Diabetes, and Cardiovascular Disease. “If inflammation develops to remove the fat, we call it NASH. If this progresses to decompensated reaction and fibrosis and cirrhosis, then we call it nonalcoholic steatohepatitis with fibrosis. That can lead to liver cirrhosis, hepatocellular carcinoma, and liver failure.”

The underlying problem stems from the rise in obesity prevalence, according to Dr. Mantzoros, who is also chief of endocrinology at the Boston Veterans Affairs Healthcare System. For 75%-80% of individuals with metabolically unhealthy obesity, the storage space in their adipose tissue is exceeded. “Fat is deposited into muscle, causing insulin resistance, and into the liver,” he explained. “If it’s more than 5.8%, it causes NAFLD. Most of us don’t realize that most of the patients with diabetes we have in our clinics also have nonalcoholic fatty liver disease. That’s because we don’t have an easy diagnostic tool or an easy treatment. It’s an unmet clinical need.” (There are currently no drugs approved for the treatment of NASH or NAFLD. Current recommended first-line treatment is weight loss through diet and exercise and control of diabetes, if it is present.)

“Assuming the rate of increase in cost due to NAFLD parallels the growth in obesity, the 10-year projection for direct cost is $1.005 trillion,” said Dr. Mantzoros, who is also editor in chief of the journal Metabolism. “Obesity, NAFLD, and insulin resistance are each independently associated with a twofold risk for diabetes. If all three are present, there is a 14-fold risk for diabetes. Insulin resistance promotes an increase in free fatty acid traffic to the liver, which can trigger hepatic lipotoxicity. Hyperinsulinemia enhances free fatty acid uptake and activates de novo lipogenesis. Hyperglycemia can also activate de novo lipogenesis.”

About 85 million Americans have NAFLD, he continued. Most (80%) are cases of steatosis, but 20% have NASH. Of those, 20% develop advanced fibrosis, which leads to liver failure and transplantation or death. A study of data from the National Health and Nutrition Examination Survey found that diabetes was the strongest predictor of advanced fibrosis in patients with NAFLD (odds ratio, 18.20), followed by a body mass index of 30 kg/m² or greater (OR, 9.10), hypertension (OR, 1.20), and age (OR, 1.08; Ailment Pharmacol Ther. 2017;46:974-80). “Most of the patients who come to our clinics with diabetes have nonalcoholic fatty liver disease – 75%-80% in our clinics, and about 10% have advanced fibrosis,” Dr. Mantzoros said. “Most of them go undiagnosed.”

Patients with type 2 diabetes and NAFLD progress faster to fibrosis and end-stage liver disease, compared with those who do not have diabetes. One study of 108 patients with biopsy-proven NALFD showed that 84% of those with fibrosis progression had type 2 diabetes (J Hepatol. 2015;62:1148-55). Other findings have shown that patients with type 2 diabetes are at increased risk of chronic NAFLD and hepatocellular carcinoma (Gastroenterol. 2001;126:460-8). “We are doing more liver transplantations because of NAFLD and NASH than because of hepatitis C,” Dr. Mantzoros said. “What we need to keep in mind is that, although liver morbidity and mortality is important, this is a component of the cardiometabolic syndrome. So, people have all the risk factors for cardiovascular disease. Because CVD is much more common, people with NAFLD suffer from and die from CVD. The more advanced the NAFLD, the higher the risk of death from cardiovascular disease.”

Multiple risk factors can help identify patients with advanced fibrosis because of NASH, he continued, including having features of the metabolic syndrome, being over 50 years of age, being Hispanic, having high levels of ALT/AST, low platelets, and having low albumin. “These are frequent tests that we can find in the EMR,” Dr. Mantzoros said. “The problem with ALT is that, in many stages of the disease, ALT goes up. But after a certain stage of the disease, when most of the liver is controlled by fibrosis and cirrhosis, most of the hepatocytes are dead and don’t secrete ALT, so ALT in end-stage renal disease goes up.”

Recent guidelines recognize the association between diabetes, NAFLD, and NASH, and call for increased vigilance and screening tests. According to guidelines from the American Association for the Study of Liver Diseases, the Fibrosis-4 Index or the NAFLD Fibrosis Score are clinically useful tools for identifying NAFLD in patients with higher likelihood of having bridging fibrosis or cirrhosis (Hepatology. 2018;67[1]:328-57). Vibration-controlled transient elastography or MRI are clinically useful tools for identifying advanced fibrosis in patients with NAFLD, whereas clinical decision aids, such as Fibrosis-4, NAFLD Fibrosis Score, or vibration-controlled transient elastography, can be used to identify patients at low or high risk for advanced fibrosis.

“If we have a patient with suspected NAFLD, we need to rule out alcohol use, we need to confirm NAFLD, and we need to risk stratify, and classify as low, intermediate, or high risk,” Dr. Mantzoros said. Most of his patients who meet criteria for high-risk NASH do not elect to undergo a liver biopsy. “I don’t blame them for that,” he said. “There is a 0.1 per 1,000 mortality risk, even in the best hands. If 80 million people who have fatty liver were to undergo a liver biopsy, we would have 16,000 deaths every year just because of that. We would not tolerate that.”

Recently, Dr. Mantzoros and colleagues published a proof-of-concept study that proposes novel models using lipids, hormones, and glycans that can diagnose the presence of NASH, NAFLD, or healthy status with high accuracy (Metabolism. 2019 Nov 8. doi: 10.1016/j.metabol.2019.154005). “We are now working with companies to validate it and expand it, not only as a diagnostic marker, but as a prognostic marker, and to try to commercialize it in the future,” he said.

Current pharmacotherapies are limited to patients with biopsy-confirmed NASH and fibrosis. Pioglitazone is a first-line, off-label pharmacologic treatment, while vitamin E may be used in patients with biopsy-confirmed NASH without diabetes. Metformin, glucagonlike peptide–1 receptor agonists, and sodium-glucose transporter 2 inhibitors are either not recommended or have insufficient evidence to recommend their use. More than 60 phase 2 trials are planned or ongoing, Dr. Mantzoros added, with phase trials underway for cenicriviroc, elafibranor, obeticholic acid, and selonsertib.

The role of lifestyle management is also important. “The Mediterranean diet has the best evidence, along with exercise, to improve early stages of NAFLD,” he said. “Weight loss is very important. If the patient loses 10% of their weight or more, there is NASH resolution 90% of the time. With less weight loss, we have less resolution. The problem is that only 10% of patients or less can sustain a more than 90% weight loss over a year.”

Dr. Mantzoros reported being a shareholder of Coherus BioSciences and Pangea Therapeutics, having served as an adviser to Coherus, Novo Nordisk, and Genfit and having received research grants through his institution from Coherus, Eisai, and Novo Nordisk.

dbrunk@mdedge.com

LOS ANGELES – The way Christos S. Mantzoros, MD, DSc, PhD, sees it, nonalcoholic steatohepatitis (NASH) is an epidemic of the 21st century that can trigger a cascade of reactions.

Doug Brunk/MDedge News

“If more than 5.8% of fat is in the liver, we call it nonalcoholic fatty liver disease [NAFLD],” Dr. Mantzoros, professor of medicine at Harvard Medical School, Boston, and Boston University, explained at the World Congress on Insulin Resistance, Diabetes, and Cardiovascular Disease. “If inflammation develops to remove the fat, we call it NASH. If this progresses to decompensated reaction and fibrosis and cirrhosis, then we call it nonalcoholic steatohepatitis with fibrosis. That can lead to liver cirrhosis, hepatocellular carcinoma, and liver failure.”

The underlying problem stems from the rise in obesity prevalence, according to Dr. Mantzoros, who is also chief of endocrinology at the Boston Veterans Affairs Healthcare System. For 75%-80% of individuals with metabolically unhealthy obesity, the storage space in their adipose tissue is exceeded. “Fat is deposited into muscle, causing insulin resistance, and into the liver,” he explained. “If it’s more than 5.8%, it causes NAFLD. Most of us don’t realize that most of the patients with diabetes we have in our clinics also have nonalcoholic fatty liver disease. That’s because we don’t have an easy diagnostic tool or an easy treatment. It’s an unmet clinical need.” (There are currently no drugs approved for the treatment of NASH or NAFLD. Current recommended first-line treatment is weight loss through diet and exercise and control of diabetes, if it is present.)

“Assuming the rate of increase in cost due to NAFLD parallels the growth in obesity, the 10-year projection for direct cost is $1.005 trillion,” said Dr. Mantzoros, who is also editor in chief of the journal Metabolism. “Obesity, NAFLD, and insulin resistance are each independently associated with a twofold risk for diabetes. If all three are present, there is a 14-fold risk for diabetes. Insulin resistance promotes an increase in free fatty acid traffic to the liver, which can trigger hepatic lipotoxicity. Hyperinsulinemia enhances free fatty acid uptake and activates de novo lipogenesis. Hyperglycemia can also activate de novo lipogenesis.”

About 85 million Americans have NAFLD, he continued. Most (80%) are cases of steatosis, but 20% have NASH. Of those, 20% develop advanced fibrosis, which leads to liver failure and transplantation or death. A study of data from the National Health and Nutrition Examination Survey found that diabetes was the strongest predictor of advanced fibrosis in patients with NAFLD (odds ratio, 18.20), followed by a body mass index of 30 kg/m² or greater (OR, 9.10), hypertension (OR, 1.20), and age (OR, 1.08; Ailment Pharmacol Ther. 2017;46:974-80). “Most of the patients who come to our clinics with diabetes have nonalcoholic fatty liver disease – 75%-80% in our clinics, and about 10% have advanced fibrosis,” Dr. Mantzoros said. “Most of them go undiagnosed.”

Patients with type 2 diabetes and NAFLD progress faster to fibrosis and end-stage liver disease, compared with those who do not have diabetes. One study of 108 patients with biopsy-proven NALFD showed that 84% of those with fibrosis progression had type 2 diabetes (J Hepatol. 2015;62:1148-55). Other findings have shown that patients with type 2 diabetes are at increased risk of chronic NAFLD and hepatocellular carcinoma (Gastroenterol. 2001;126:460-8). “We are doing more liver transplantations because of NAFLD and NASH than because of hepatitis C,” Dr. Mantzoros said. “What we need to keep in mind is that, although liver morbidity and mortality is important, this is a component of the cardiometabolic syndrome. So, people have all the risk factors for cardiovascular disease. Because CVD is much more common, people with NAFLD suffer from and die from CVD. The more advanced the NAFLD, the higher the risk of death from cardiovascular disease.”

Multiple risk factors can help identify patients with advanced fibrosis because of NASH, he continued, including having features of the metabolic syndrome, being over 50 years of age, being Hispanic, having high levels of ALT/AST, low platelets, and having low albumin. “These are frequent tests that we can find in the EMR,” Dr. Mantzoros said. “The problem with ALT is that, in many stages of the disease, ALT goes up. But after a certain stage of the disease, when most of the liver is controlled by fibrosis and cirrhosis, most of the hepatocytes are dead and don’t secrete ALT, so ALT in end-stage renal disease goes up.”

Recent guidelines recognize the association between diabetes, NAFLD, and NASH, and call for increased vigilance and screening tests. According to guidelines from the American Association for the Study of Liver Diseases, the Fibrosis-4 Index or the NAFLD Fibrosis Score are clinically useful tools for identifying NAFLD in patients with higher likelihood of having bridging fibrosis or cirrhosis (Hepatology. 2018;67[1]:328-57). Vibration-controlled transient elastography or MRI are clinically useful tools for identifying advanced fibrosis in patients with NAFLD, whereas clinical decision aids, such as Fibrosis-4, NAFLD Fibrosis Score, or vibration-controlled transient elastography, can be used to identify patients at low or high risk for advanced fibrosis.

“If we have a patient with suspected NAFLD, we need to rule out alcohol use, we need to confirm NAFLD, and we need to risk stratify, and classify as low, intermediate, or high risk,” Dr. Mantzoros said. Most of his patients who meet criteria for high-risk NASH do not elect to undergo a liver biopsy. “I don’t blame them for that,” he said. “There is a 0.1 per 1,000 mortality risk, even in the best hands. If 80 million people who have fatty liver were to undergo a liver biopsy, we would have 16,000 deaths every year just because of that. We would not tolerate that.”

Recently, Dr. Mantzoros and colleagues published a proof-of-concept study that proposes novel models using lipids, hormones, and glycans that can diagnose the presence of NASH, NAFLD, or healthy status with high accuracy (Metabolism. 2019 Nov 8. doi: 10.1016/j.metabol.2019.154005). “We are now working with companies to validate it and expand it, not only as a diagnostic marker, but as a prognostic marker, and to try to commercialize it in the future,” he said.

Current pharmacotherapies are limited to patients with biopsy-confirmed NASH and fibrosis. Pioglitazone is a first-line, off-label pharmacologic treatment, while vitamin E may be used in patients with biopsy-confirmed NASH without diabetes. Metformin, glucagonlike peptide–1 receptor agonists, and sodium-glucose transporter 2 inhibitors are either not recommended or have insufficient evidence to recommend their use. More than 60 phase 2 trials are planned or ongoing, Dr. Mantzoros added, with phase trials underway for cenicriviroc, elafibranor, obeticholic acid, and selonsertib.

The role of lifestyle management is also important. “The Mediterranean diet has the best evidence, along with exercise, to improve early stages of NAFLD,” he said. “Weight loss is very important. If the patient loses 10% of their weight or more, there is NASH resolution 90% of the time. With less weight loss, we have less resolution. The problem is that only 10% of patients or less can sustain a more than 90% weight loss over a year.”

Dr. Mantzoros reported being a shareholder of Coherus BioSciences and Pangea Therapeutics, having served as an adviser to Coherus, Novo Nordisk, and Genfit and having received research grants through his institution from Coherus, Eisai, and Novo Nordisk.

dbrunk@mdedge.com

LOS ANGELES – The way Christos S. Mantzoros, MD, DSc, PhD, sees it, nonalcoholic steatohepatitis (NASH) is an epidemic of the 21st century that can trigger a cascade of reactions.

Doug Brunk/MDedge News

“If more than 5.8% of fat is in the liver, we call it nonalcoholic fatty liver disease [NAFLD],” Dr. Mantzoros, professor of medicine at Harvard Medical School, Boston, and Boston University, explained at the World Congress on Insulin Resistance, Diabetes, and Cardiovascular Disease. “If inflammation develops to remove the fat, we call it NASH. If this progresses to decompensated reaction and fibrosis and cirrhosis, then we call it nonalcoholic steatohepatitis with fibrosis. That can lead to liver cirrhosis, hepatocellular carcinoma, and liver failure.”

The underlying problem stems from the rise in obesity prevalence, according to Dr. Mantzoros, who is also chief of endocrinology at the Boston Veterans Affairs Healthcare System. For 75%-80% of individuals with metabolically unhealthy obesity, the storage space in their adipose tissue is exceeded. “Fat is deposited into muscle, causing insulin resistance, and into the liver,” he explained. “If it’s more than 5.8%, it causes NAFLD. Most of us don’t realize that most of the patients with diabetes we have in our clinics also have nonalcoholic fatty liver disease. That’s because we don’t have an easy diagnostic tool or an easy treatment. It’s an unmet clinical need.” (There are currently no drugs approved for the treatment of NASH or NAFLD. Current recommended first-line treatment is weight loss through diet and exercise and control of diabetes, if it is present.)

“Assuming the rate of increase in cost due to NAFLD parallels the growth in obesity, the 10-year projection for direct cost is $1.005 trillion,” said Dr. Mantzoros, who is also editor in chief of the journal Metabolism. “Obesity, NAFLD, and insulin resistance are each independently associated with a twofold risk for diabetes. If all three are present, there is a 14-fold risk for diabetes. Insulin resistance promotes an increase in free fatty acid traffic to the liver, which can trigger hepatic lipotoxicity. Hyperinsulinemia enhances free fatty acid uptake and activates de novo lipogenesis. Hyperglycemia can also activate de novo lipogenesis.”

About 85 million Americans have NAFLD, he continued. Most (80%) are cases of steatosis, but 20% have NASH. Of those, 20% develop advanced fibrosis, which leads to liver failure and transplantation or death. A study of data from the National Health and Nutrition Examination Survey found that diabetes was the strongest predictor of advanced fibrosis in patients with NAFLD (odds ratio, 18.20), followed by a body mass index of 30 kg/m² or greater (OR, 9.10), hypertension (OR, 1.20), and age (OR, 1.08; Ailment Pharmacol Ther. 2017;46:974-80). “Most of the patients who come to our clinics with diabetes have nonalcoholic fatty liver disease – 75%-80% in our clinics, and about 10% have advanced fibrosis,” Dr. Mantzoros said. “Most of them go undiagnosed.”

Patients with type 2 diabetes and NAFLD progress faster to fibrosis and end-stage liver disease, compared with those who do not have diabetes. One study of 108 patients with biopsy-proven NALFD showed that 84% of those with fibrosis progression had type 2 diabetes (J Hepatol. 2015;62:1148-55). Other findings have shown that patients with type 2 diabetes are at increased risk of chronic NAFLD and hepatocellular carcinoma (Gastroenterol. 2001;126:460-8). “We are doing more liver transplantations because of NAFLD and NASH than because of hepatitis C,” Dr. Mantzoros said. “What we need to keep in mind is that, although liver morbidity and mortality is important, this is a component of the cardiometabolic syndrome. So, people have all the risk factors for cardiovascular disease. Because CVD is much more common, people with NAFLD suffer from and die from CVD. The more advanced the NAFLD, the higher the risk of death from cardiovascular disease.”

Multiple risk factors can help identify patients with advanced fibrosis because of NASH, he continued, including having features of the metabolic syndrome, being over 50 years of age, being Hispanic, having high levels of ALT/AST, low platelets, and having low albumin. “These are frequent tests that we can find in the EMR,” Dr. Mantzoros said. “The problem with ALT is that, in many stages of the disease, ALT goes up. But after a certain stage of the disease, when most of the liver is controlled by fibrosis and cirrhosis, most of the hepatocytes are dead and don’t secrete ALT, so ALT in end-stage renal disease goes up.”

Recent guidelines recognize the association between diabetes, NAFLD, and NASH, and call for increased vigilance and screening tests. According to guidelines from the American Association for the Study of Liver Diseases, the Fibrosis-4 Index or the NAFLD Fibrosis Score are clinically useful tools for identifying NAFLD in patients with higher likelihood of having bridging fibrosis or cirrhosis (Hepatology. 2018;67[1]:328-57). Vibration-controlled transient elastography or MRI are clinically useful tools for identifying advanced fibrosis in patients with NAFLD, whereas clinical decision aids, such as Fibrosis-4, NAFLD Fibrosis Score, or vibration-controlled transient elastography, can be used to identify patients at low or high risk for advanced fibrosis.

“If we have a patient with suspected NAFLD, we need to rule out alcohol use, we need to confirm NAFLD, and we need to risk stratify, and classify as low, intermediate, or high risk,” Dr. Mantzoros said. Most of his patients who meet criteria for high-risk NASH do not elect to undergo a liver biopsy. “I don’t blame them for that,” he said. “There is a 0.1 per 1,000 mortality risk, even in the best hands. If 80 million people who have fatty liver were to undergo a liver biopsy, we would have 16,000 deaths every year just because of that. We would not tolerate that.”

Recently, Dr. Mantzoros and colleagues published a proof-of-concept study that proposes novel models using lipids, hormones, and glycans that can diagnose the presence of NASH, NAFLD, or healthy status with high accuracy (Metabolism. 2019 Nov 8. doi: 10.1016/j.metabol.2019.154005). “We are now working with companies to validate it and expand it, not only as a diagnostic marker, but as a prognostic marker, and to try to commercialize it in the future,” he said.

Current pharmacotherapies are limited to patients with biopsy-confirmed NASH and fibrosis. Pioglitazone is a first-line, off-label pharmacologic treatment, while vitamin E may be used in patients with biopsy-confirmed NASH without diabetes. Metformin, glucagonlike peptide–1 receptor agonists, and sodium-glucose transporter 2 inhibitors are either not recommended or have insufficient evidence to recommend their use. More than 60 phase 2 trials are planned or ongoing, Dr. Mantzoros added, with phase trials underway for cenicriviroc, elafibranor, obeticholic acid, and selonsertib.

The role of lifestyle management is also important. “The Mediterranean diet has the best evidence, along with exercise, to improve early stages of NAFLD,” he said. “Weight loss is very important. If the patient loses 10% of their weight or more, there is NASH resolution 90% of the time. With less weight loss, we have less resolution. The problem is that only 10% of patients or less can sustain a more than 90% weight loss over a year.”

Dr. Mantzoros reported being a shareholder of Coherus BioSciences and Pangea Therapeutics, having served as an adviser to Coherus, Novo Nordisk, and Genfit and having received research grants through his institution from Coherus, Eisai, and Novo Nordisk.

dbrunk@mdedge.com