Endocrinology

Using artificial intelligence to analyze large amounts of information from social media platforms generated some novel insights into public perceptions about statins, results of a new study show.

The study, which used AI to analyze discussions about statins on the social media platform Reddit, corroborated previously documented reasons for statin hesitancy, including adverse effect profiles and general disenfranchisement with health care.

But it also found novel points of discourse, including linking statins to COVID-19 outcomes and the role of cholesterol, statins, and the ketogenic diet.

“We used AI to tell us what is being discussed about statins on social media and to quantify the information in topics that people think are important,” senior study author Fatima Rodriguez, MD, MPH, Stanford (Calif.) University School of Medicine, said in an interview.

“Some of the themes were surprising to us. While we expected discussion on side effects, we were surprised to see so much discussion refuting the idea that increased levels of LDL were detrimental. There were also a large amount of posts on statin use being correlated to COVID outcomes. Our findings show how widespread this misinformation is,” she said.

“As a preventative cardiologist, I spend a lot of my time trying to get patients to take statins, but patients often rely on social media for information, and this can contain a lot of misinformation. People tend to be more honest on online forums than they are in the doctor’s office, so they are probably asking the questions and having discussions on subjects they really care about. So, understanding what is being discussed on social media is very valuable information for us as clinicians.”

The study was published online in JAMA Network Open.

The researchers analyzed all statin-related discussions on Reddit that were dated between Jan. 1, 2009, and July 12, 2022. Statin- and cholesterol-focused communities were identified to create a list of statin-related discussions. An AI pipeline was developed to cluster these discussions into specific topics and overarching thematic groups.

A total of 10,233 unique statin-related discussions and 5,188 unique authors were identified. A total of 100 discussion topics were identified and classified into six overarching thematic groups: (1) ketogenic diets, diabetes, supplements, and statins; (2) statin adverse effects; (3) statin hesitancy; (4) clinical trial appraisals; (5) pharmaceutical industry bias and statins; and (6) red yeast rice and statins.

Several examples of statin-related misinformation were identified, including distrust of the hypothesis that LDL-C has a causal association with heart disease. Discussions included quotes such as, “I think LDL is pretty much irrelevant. Your HDL and triglycerides are far more important.”

Other topics suggested that certain natural supplements would be an acceptable alternative to statins. Quotes included: “Red yeast rice is a statin basically, by the way,” and “statins are basically mycotoxins and deplete you of fat-soluble nutrients, like coQ10, vit D, K, A and E, and in all likelihood through these depletions worsen cardiovascular health.”

The researchers also looked at temporal trends and found that these sorts of discussions have increased over time.

One of the common themes identified was using the ketogenic diet phenomenon as an argument against increased cholesterol levels being bad for health.

Dr. Rodriguez elaborated: “People think the ketogenic diet is healthy as they lose weight on it. And as it can be associated with a small increase in LDL cholesterol, there was a lot of opinion that this meant increasing LDL was a good thing.”

The researchers also conducted a sentiment analysis, which designated topics as positive, negative, or neutral with regard to statins.  

“We found that almost no topic was positive. Everything was either neutral or negative. This is pretty consistent with what we are seeing around hesitancy in clinical practice, but you would think that maybe a few people may have a positive view on statins,” Dr. Rodriguez commented.

“One of the problems with statins and lowering cholesterol is that it takes a long time to see a benefit, but this misinformation will result in some people not taking their medication,” she added.

Dr. Rodriguez noted that in this study AI is augmenting, not replacing, what clinicians and researchers do. “But it is a valuable tool to scan a large volume of information, and we have shown here it can generate new insights that we may not have thought of. It’s important to know what’s out there so we can try and combat it.” 

She pointed out that patients don’t read the medical literature showing the benefits of statins but rather rely on social media for their information. 

“We need to understand all sorts of patient engagement and use the same tools to combat this misinformation. We have a responsibility to try and stop dangerous and false information from being propagated,” she commented.

“These drugs are clearly not dangerous when used in line with clinical guidelines, and they have been proven to have multiple benefits again and again, but we don’t see those kinds of discussions in the community at all. We as clinicians need to use social media and AI to give out the right information. This could start to combat all the misinformation out there.”

A version of this article first appeared on Medscape.com.

Using artificial intelligence to analyze large amounts of information from social media platforms generated some novel insights into public perceptions about statins, results of a new study show.

The study, which used AI to analyze discussions about statins on the social media platform Reddit, corroborated previously documented reasons for statin hesitancy, including adverse effect profiles and general disenfranchisement with health care.

But it also found novel points of discourse, including linking statins to COVID-19 outcomes and the role of cholesterol, statins, and the ketogenic diet.

“We used AI to tell us what is being discussed about statins on social media and to quantify the information in topics that people think are important,” senior study author Fatima Rodriguez, MD, MPH, Stanford (Calif.) University School of Medicine, said in an interview.

“Some of the themes were surprising to us. While we expected discussion on side effects, we were surprised to see so much discussion refuting the idea that increased levels of LDL were detrimental. There were also a large amount of posts on statin use being correlated to COVID outcomes. Our findings show how widespread this misinformation is,” she said.

“As a preventative cardiologist, I spend a lot of my time trying to get patients to take statins, but patients often rely on social media for information, and this can contain a lot of misinformation. People tend to be more honest on online forums than they are in the doctor’s office, so they are probably asking the questions and having discussions on subjects they really care about. So, understanding what is being discussed on social media is very valuable information for us as clinicians.”

The study was published online in JAMA Network Open.

The researchers analyzed all statin-related discussions on Reddit that were dated between Jan. 1, 2009, and July 12, 2022. Statin- and cholesterol-focused communities were identified to create a list of statin-related discussions. An AI pipeline was developed to cluster these discussions into specific topics and overarching thematic groups.

A total of 10,233 unique statin-related discussions and 5,188 unique authors were identified. A total of 100 discussion topics were identified and classified into six overarching thematic groups: (1) ketogenic diets, diabetes, supplements, and statins; (2) statin adverse effects; (3) statin hesitancy; (4) clinical trial appraisals; (5) pharmaceutical industry bias and statins; and (6) red yeast rice and statins.

Several examples of statin-related misinformation were identified, including distrust of the hypothesis that LDL-C has a causal association with heart disease. Discussions included quotes such as, “I think LDL is pretty much irrelevant. Your HDL and triglycerides are far more important.”

Other topics suggested that certain natural supplements would be an acceptable alternative to statins. Quotes included: “Red yeast rice is a statin basically, by the way,” and “statins are basically mycotoxins and deplete you of fat-soluble nutrients, like coQ10, vit D, K, A and E, and in all likelihood through these depletions worsen cardiovascular health.”

The researchers also looked at temporal trends and found that these sorts of discussions have increased over time.

One of the common themes identified was using the ketogenic diet phenomenon as an argument against increased cholesterol levels being bad for health.

Dr. Rodriguez elaborated: “People think the ketogenic diet is healthy as they lose weight on it. And as it can be associated with a small increase in LDL cholesterol, there was a lot of opinion that this meant increasing LDL was a good thing.”

The researchers also conducted a sentiment analysis, which designated topics as positive, negative, or neutral with regard to statins.  

“We found that almost no topic was positive. Everything was either neutral or negative. This is pretty consistent with what we are seeing around hesitancy in clinical practice, but you would think that maybe a few people may have a positive view on statins,” Dr. Rodriguez commented.

“One of the problems with statins and lowering cholesterol is that it takes a long time to see a benefit, but this misinformation will result in some people not taking their medication,” she added.

Dr. Rodriguez noted that in this study AI is augmenting, not replacing, what clinicians and researchers do. “But it is a valuable tool to scan a large volume of information, and we have shown here it can generate new insights that we may not have thought of. It’s important to know what’s out there so we can try and combat it.” 

She pointed out that patients don’t read the medical literature showing the benefits of statins but rather rely on social media for their information. 

“We need to understand all sorts of patient engagement and use the same tools to combat this misinformation. We have a responsibility to try and stop dangerous and false information from being propagated,” she commented.

“These drugs are clearly not dangerous when used in line with clinical guidelines, and they have been proven to have multiple benefits again and again, but we don’t see those kinds of discussions in the community at all. We as clinicians need to use social media and AI to give out the right information. This could start to combat all the misinformation out there.”

A version of this article first appeared on Medscape.com.

Using artificial intelligence to analyze large amounts of information from social media platforms generated some novel insights into public perceptions about statins, results of a new study show.

The study, which used AI to analyze discussions about statins on the social media platform Reddit, corroborated previously documented reasons for statin hesitancy, including adverse effect profiles and general disenfranchisement with health care.

But it also found novel points of discourse, including linking statins to COVID-19 outcomes and the role of cholesterol, statins, and the ketogenic diet.

“We used AI to tell us what is being discussed about statins on social media and to quantify the information in topics that people think are important,” senior study author Fatima Rodriguez, MD, MPH, Stanford (Calif.) University School of Medicine, said in an interview.

“Some of the themes were surprising to us. While we expected discussion on side effects, we were surprised to see so much discussion refuting the idea that increased levels of LDL were detrimental. There were also a large amount of posts on statin use being correlated to COVID outcomes. Our findings show how widespread this misinformation is,” she said.

“As a preventative cardiologist, I spend a lot of my time trying to get patients to take statins, but patients often rely on social media for information, and this can contain a lot of misinformation. People tend to be more honest on online forums than they are in the doctor’s office, so they are probably asking the questions and having discussions on subjects they really care about. So, understanding what is being discussed on social media is very valuable information for us as clinicians.”

The study was published online in JAMA Network Open.

The researchers analyzed all statin-related discussions on Reddit that were dated between Jan. 1, 2009, and July 12, 2022. Statin- and cholesterol-focused communities were identified to create a list of statin-related discussions. An AI pipeline was developed to cluster these discussions into specific topics and overarching thematic groups.

A total of 10,233 unique statin-related discussions and 5,188 unique authors were identified. A total of 100 discussion topics were identified and classified into six overarching thematic groups: (1) ketogenic diets, diabetes, supplements, and statins; (2) statin adverse effects; (3) statin hesitancy; (4) clinical trial appraisals; (5) pharmaceutical industry bias and statins; and (6) red yeast rice and statins.

Several examples of statin-related misinformation were identified, including distrust of the hypothesis that LDL-C has a causal association with heart disease. Discussions included quotes such as, “I think LDL is pretty much irrelevant. Your HDL and triglycerides are far more important.”

Other topics suggested that certain natural supplements would be an acceptable alternative to statins. Quotes included: “Red yeast rice is a statin basically, by the way,” and “statins are basically mycotoxins and deplete you of fat-soluble nutrients, like coQ10, vit D, K, A and E, and in all likelihood through these depletions worsen cardiovascular health.”

The researchers also looked at temporal trends and found that these sorts of discussions have increased over time.

One of the common themes identified was using the ketogenic diet phenomenon as an argument against increased cholesterol levels being bad for health.

Dr. Rodriguez elaborated: “People think the ketogenic diet is healthy as they lose weight on it. And as it can be associated with a small increase in LDL cholesterol, there was a lot of opinion that this meant increasing LDL was a good thing.”

The researchers also conducted a sentiment analysis, which designated topics as positive, negative, or neutral with regard to statins.  

“We found that almost no topic was positive. Everything was either neutral or negative. This is pretty consistent with what we are seeing around hesitancy in clinical practice, but you would think that maybe a few people may have a positive view on statins,” Dr. Rodriguez commented.

“One of the problems with statins and lowering cholesterol is that it takes a long time to see a benefit, but this misinformation will result in some people not taking their medication,” she added.

Dr. Rodriguez noted that in this study AI is augmenting, not replacing, what clinicians and researchers do. “But it is a valuable tool to scan a large volume of information, and we have shown here it can generate new insights that we may not have thought of. It’s important to know what’s out there so we can try and combat it.” 

She pointed out that patients don’t read the medical literature showing the benefits of statins but rather rely on social media for their information. 

“We need to understand all sorts of patient engagement and use the same tools to combat this misinformation. We have a responsibility to try and stop dangerous and false information from being propagated,” she commented.

“These drugs are clearly not dangerous when used in line with clinical guidelines, and they have been proven to have multiple benefits again and again, but we don’t see those kinds of discussions in the community at all. We as clinicians need to use social media and AI to give out the right information. This could start to combat all the misinformation out there.”

A version of this article first appeared on Medscape.com.

SAN DIEGO – Primary care providers can draw from a wide range of diets to give patients evidence-based advice on how to lose weight, prevent diabetes, and achieve other health goals, according to a speaker at the annual meeting of the American College of Physicians.

“Evidence from studies can help clinicians and their patients develop a successful dietary management plan and achieve optimal health,” said internist Michelle Hauser, MD, clinical associate professor at Stanford (Calif.) University. She also discussed evidence-based techniques to support patients in maintaining dietary modifications.
 

Predominantly plant‐based diets

Popular predominantly plant‐based diets include a Mediterranean diet, healthy vegetarian diet, predominantly whole-food plant‐based (WFPB) diet, and a dietary approach to stop hypertension (DASH).

The DASH diet was originally designed to help patients manage their blood pressure, but evidence suggests that it also can help adults with obesity lose weight. In contrast to the DASH diet, the Mediterranean diet is not low-fat and not very restrictive. Yet the evidence suggests that the Mediterranean diet is not only helpful for losing weight but also can reduce the risk of various chronic diseases, including obesity, type 2 diabetes, cardiovascular disease (CVD), and cancer, Dr. Hauser said. In addition, data suggest that the Mediterranean diet may reduce the risk of all-cause mortality and lower the levels of cholesterol.

“I like to highlight all these protective effects to my patients, because even if their goal is to lose weight, knowing that hard work pays off in additional ways can keep them motivated,” Dr. Hauser stated.

A healthy vegetarian diet and a WFPB diet are similar, and both are helpful in weight loss and management of total cholesterol and LDL‐C levels. Furthermore, healthy vegetarian and WFPB diets may reduce the risk of type 2 diabetes, CVD, and some cancers. Cohort study data suggest that progressively more vegetarian diets are associated with lower BMIs.

“My interpretation of these data is that predominantly plant-based diets rich in whole foods are healthful and can be done in a way that is sustainable for most,” said Dr. Hauser. However, this generally requires a lot of support at the outset to address gaps in knowledge, skills, and other potential barriers.

For example, she referred one obese patient at risk of diabetes and cardiovascular disease to a registered dietitian to develop a dietary plan. The patient also attended a behavioral medicine weight management program to learn strategies such as using smaller plates, and his family attended a healthy cooking class together to improve meal planning and cooking skills.
 

Time‐restricted feeding

There are numerous variations of time-restricted feeding, commonly referred to as intermittent fasting, but the principles are similar – limiting food intake to a specific window of time each day or week.

Although some studies have shown that time-restricted feeding may help patients reduce adiposity and improve lipid markers, most studies comparing time-restricted feeding to a calorie-restricted diet have shown little to no difference in weight-related outcomes, Dr. Hauser said.

These data suggest that time-restricted feeding may help patients with weight loss only if time restriction helps them reduce calorie intake. She also warned that time-restrictive feeding might cause late-night cravings and might not be helpful in individuals prone to food cravings.
 

Low‐carbohydrate and ketogenic diets

Losing muscle mass can prevent some people from dieting, but evidence suggests that a high-fat, very low-carbohydrate diet – also called a ketogenic diet – may help patients reduce weight and fat mass while preserving fat‐free mass, Dr. Hauser said.

The evidence regarding the usefulness of a low-carbohydrate (non-keto) diet is less clear because most studies compared it to a low-fat diet, and these two diets might lead to a similar extent of weight loss.
 

Rating the level of scientific evidence behind different diet options

Nutrition studies do no provide the same level of evidence as drug studies, said Dr. Hauser, because it is easier to conduct a randomized controlled trial of a drug versus placebo. Diets have many more variables, and it also takes much longer to observe most outcomes of a dietary change.

In addition, clinical trials of dietary interventions are typically short and focus on disease markers such as serum lipids and hemoglobin A1c levels. To obtain reliable information on the usefulness of a diet, researchers need to collect detailed health and lifestyle information from hundreds of thousands of people over several decades, which is not always feasible. “This is why meta-analyses of pooled dietary study data are more likely to yield dependable findings,” she noted.
 

Getting to know patients is essential to help them maintain diet modifications

When developing a diet plan for a patient, it is important to consider the sustainability of a dietary pattern. “The benefits of any healthy dietary change will only last as long as they can be maintained,” said Dr. Hauser. “Counseling someone on choosing an appropriate long-term dietary pattern requires getting to know them – taste preferences, food traditions, barriers, facilitators, food access, and time and cost restrictions.”

In an interview after the session, David Bittleman, MD, an internist at Veterans Affairs San Diego Health Care System, agreed that getting to know patients is essential for successfully advising them on diet.

“I always start developing a diet plan by trying to find out what [a patient’s] diet is like and what their goals are. I need to know what they are already doing in order to make suggestions about what they can do to make their diet healthier,” he said.

When asked about her approach to supporting patients in the long term, Dr. Hauser said that she recommends sequential, gradual changes. Dr. Hauser added that she suggests her patients prioritize implementing dietary changes that they are confident they can maintain.

Dr. Hauser and Dr. Bittleman report no relevant financial relationships.

SAN DIEGO – Primary care providers can draw from a wide range of diets to give patients evidence-based advice on how to lose weight, prevent diabetes, and achieve other health goals, according to a speaker at the annual meeting of the American College of Physicians.

“Evidence from studies can help clinicians and their patients develop a successful dietary management plan and achieve optimal health,” said internist Michelle Hauser, MD, clinical associate professor at Stanford (Calif.) University. She also discussed evidence-based techniques to support patients in maintaining dietary modifications.
 

Predominantly plant‐based diets

Popular predominantly plant‐based diets include a Mediterranean diet, healthy vegetarian diet, predominantly whole-food plant‐based (WFPB) diet, and a dietary approach to stop hypertension (DASH).

The DASH diet was originally designed to help patients manage their blood pressure, but evidence suggests that it also can help adults with obesity lose weight. In contrast to the DASH diet, the Mediterranean diet is not low-fat and not very restrictive. Yet the evidence suggests that the Mediterranean diet is not only helpful for losing weight but also can reduce the risk of various chronic diseases, including obesity, type 2 diabetes, cardiovascular disease (CVD), and cancer, Dr. Hauser said. In addition, data suggest that the Mediterranean diet may reduce the risk of all-cause mortality and lower the levels of cholesterol.

“I like to highlight all these protective effects to my patients, because even if their goal is to lose weight, knowing that hard work pays off in additional ways can keep them motivated,” Dr. Hauser stated.

A healthy vegetarian diet and a WFPB diet are similar, and both are helpful in weight loss and management of total cholesterol and LDL‐C levels. Furthermore, healthy vegetarian and WFPB diets may reduce the risk of type 2 diabetes, CVD, and some cancers. Cohort study data suggest that progressively more vegetarian diets are associated with lower BMIs.

“My interpretation of these data is that predominantly plant-based diets rich in whole foods are healthful and can be done in a way that is sustainable for most,” said Dr. Hauser. However, this generally requires a lot of support at the outset to address gaps in knowledge, skills, and other potential barriers.

For example, she referred one obese patient at risk of diabetes and cardiovascular disease to a registered dietitian to develop a dietary plan. The patient also attended a behavioral medicine weight management program to learn strategies such as using smaller plates, and his family attended a healthy cooking class together to improve meal planning and cooking skills.
 

Time‐restricted feeding

There are numerous variations of time-restricted feeding, commonly referred to as intermittent fasting, but the principles are similar – limiting food intake to a specific window of time each day or week.

Although some studies have shown that time-restricted feeding may help patients reduce adiposity and improve lipid markers, most studies comparing time-restricted feeding to a calorie-restricted diet have shown little to no difference in weight-related outcomes, Dr. Hauser said.

These data suggest that time-restricted feeding may help patients with weight loss only if time restriction helps them reduce calorie intake. She also warned that time-restrictive feeding might cause late-night cravings and might not be helpful in individuals prone to food cravings.
 

Low‐carbohydrate and ketogenic diets

Losing muscle mass can prevent some people from dieting, but evidence suggests that a high-fat, very low-carbohydrate diet – also called a ketogenic diet – may help patients reduce weight and fat mass while preserving fat‐free mass, Dr. Hauser said.

The evidence regarding the usefulness of a low-carbohydrate (non-keto) diet is less clear because most studies compared it to a low-fat diet, and these two diets might lead to a similar extent of weight loss.
 

Rating the level of scientific evidence behind different diet options

Nutrition studies do no provide the same level of evidence as drug studies, said Dr. Hauser, because it is easier to conduct a randomized controlled trial of a drug versus placebo. Diets have many more variables, and it also takes much longer to observe most outcomes of a dietary change.

In addition, clinical trials of dietary interventions are typically short and focus on disease markers such as serum lipids and hemoglobin A1c levels. To obtain reliable information on the usefulness of a diet, researchers need to collect detailed health and lifestyle information from hundreds of thousands of people over several decades, which is not always feasible. “This is why meta-analyses of pooled dietary study data are more likely to yield dependable findings,” she noted.
 

Getting to know patients is essential to help them maintain diet modifications

When developing a diet plan for a patient, it is important to consider the sustainability of a dietary pattern. “The benefits of any healthy dietary change will only last as long as they can be maintained,” said Dr. Hauser. “Counseling someone on choosing an appropriate long-term dietary pattern requires getting to know them – taste preferences, food traditions, barriers, facilitators, food access, and time and cost restrictions.”

In an interview after the session, David Bittleman, MD, an internist at Veterans Affairs San Diego Health Care System, agreed that getting to know patients is essential for successfully advising them on diet.

“I always start developing a diet plan by trying to find out what [a patient’s] diet is like and what their goals are. I need to know what they are already doing in order to make suggestions about what they can do to make their diet healthier,” he said.

When asked about her approach to supporting patients in the long term, Dr. Hauser said that she recommends sequential, gradual changes. Dr. Hauser added that she suggests her patients prioritize implementing dietary changes that they are confident they can maintain.

Dr. Hauser and Dr. Bittleman report no relevant financial relationships.

SAN DIEGO – Primary care providers can draw from a wide range of diets to give patients evidence-based advice on how to lose weight, prevent diabetes, and achieve other health goals, according to a speaker at the annual meeting of the American College of Physicians.

“Evidence from studies can help clinicians and their patients develop a successful dietary management plan and achieve optimal health,” said internist Michelle Hauser, MD, clinical associate professor at Stanford (Calif.) University. She also discussed evidence-based techniques to support patients in maintaining dietary modifications.
 

Predominantly plant‐based diets

Popular predominantly plant‐based diets include a Mediterranean diet, healthy vegetarian diet, predominantly whole-food plant‐based (WFPB) diet, and a dietary approach to stop hypertension (DASH).

The DASH diet was originally designed to help patients manage their blood pressure, but evidence suggests that it also can help adults with obesity lose weight. In contrast to the DASH diet, the Mediterranean diet is not low-fat and not very restrictive. Yet the evidence suggests that the Mediterranean diet is not only helpful for losing weight but also can reduce the risk of various chronic diseases, including obesity, type 2 diabetes, cardiovascular disease (CVD), and cancer, Dr. Hauser said. In addition, data suggest that the Mediterranean diet may reduce the risk of all-cause mortality and lower the levels of cholesterol.

“I like to highlight all these protective effects to my patients, because even if their goal is to lose weight, knowing that hard work pays off in additional ways can keep them motivated,” Dr. Hauser stated.

A healthy vegetarian diet and a WFPB diet are similar, and both are helpful in weight loss and management of total cholesterol and LDL‐C levels. Furthermore, healthy vegetarian and WFPB diets may reduce the risk of type 2 diabetes, CVD, and some cancers. Cohort study data suggest that progressively more vegetarian diets are associated with lower BMIs.

“My interpretation of these data is that predominantly plant-based diets rich in whole foods are healthful and can be done in a way that is sustainable for most,” said Dr. Hauser. However, this generally requires a lot of support at the outset to address gaps in knowledge, skills, and other potential barriers.

For example, she referred one obese patient at risk of diabetes and cardiovascular disease to a registered dietitian to develop a dietary plan. The patient also attended a behavioral medicine weight management program to learn strategies such as using smaller plates, and his family attended a healthy cooking class together to improve meal planning and cooking skills.
 

Time‐restricted feeding

There are numerous variations of time-restricted feeding, commonly referred to as intermittent fasting, but the principles are similar – limiting food intake to a specific window of time each day or week.

Although some studies have shown that time-restricted feeding may help patients reduce adiposity and improve lipid markers, most studies comparing time-restricted feeding to a calorie-restricted diet have shown little to no difference in weight-related outcomes, Dr. Hauser said.

These data suggest that time-restricted feeding may help patients with weight loss only if time restriction helps them reduce calorie intake. She also warned that time-restrictive feeding might cause late-night cravings and might not be helpful in individuals prone to food cravings.
 

Low‐carbohydrate and ketogenic diets

Losing muscle mass can prevent some people from dieting, but evidence suggests that a high-fat, very low-carbohydrate diet – also called a ketogenic diet – may help patients reduce weight and fat mass while preserving fat‐free mass, Dr. Hauser said.

The evidence regarding the usefulness of a low-carbohydrate (non-keto) diet is less clear because most studies compared it to a low-fat diet, and these two diets might lead to a similar extent of weight loss.
 

Rating the level of scientific evidence behind different diet options

Nutrition studies do no provide the same level of evidence as drug studies, said Dr. Hauser, because it is easier to conduct a randomized controlled trial of a drug versus placebo. Diets have many more variables, and it also takes much longer to observe most outcomes of a dietary change.

In addition, clinical trials of dietary interventions are typically short and focus on disease markers such as serum lipids and hemoglobin A1c levels. To obtain reliable information on the usefulness of a diet, researchers need to collect detailed health and lifestyle information from hundreds of thousands of people over several decades, which is not always feasible. “This is why meta-analyses of pooled dietary study data are more likely to yield dependable findings,” she noted.
 

Getting to know patients is essential to help them maintain diet modifications

When developing a diet plan for a patient, it is important to consider the sustainability of a dietary pattern. “The benefits of any healthy dietary change will only last as long as they can be maintained,” said Dr. Hauser. “Counseling someone on choosing an appropriate long-term dietary pattern requires getting to know them – taste preferences, food traditions, barriers, facilitators, food access, and time and cost restrictions.”

In an interview after the session, David Bittleman, MD, an internist at Veterans Affairs San Diego Health Care System, agreed that getting to know patients is essential for successfully advising them on diet.

“I always start developing a diet plan by trying to find out what [a patient’s] diet is like and what their goals are. I need to know what they are already doing in order to make suggestions about what they can do to make their diet healthier,” he said.

When asked about her approach to supporting patients in the long term, Dr. Hauser said that she recommends sequential, gradual changes. Dr. Hauser added that she suggests her patients prioritize implementing dietary changes that they are confident they can maintain.

Dr. Hauser and Dr. Bittleman report no relevant financial relationships.

SAN DIEGO – For patients with obesity, surgery, lifestyle changes, and pharmacologic interventions are all treatment options, but antiobesity medications provide a better risk-to-benefit ratio, according to a presenter at the annual meeting of the American College of Physicians.

Lifestyle changes result in the least weight loss and may be safest, while surgery provides the most weight loss and has the greatest risk. Antiobesity medications, especially the newer ones used in combination with lifestyle changes, can provide significant and sustained weight loss with manageable side effects, said Daniel Bessesen, MD, a professor in the endocrinology, diabetes, and metabolism at University of Colorado at Denver, Aurora.

New and more effective antiobesity medications have given internists more potential options to discuss with their patients, Dr. Bessesen said. He reviewed the pros and cons of the different options.

Medications are indicated for patients with a body mass index greater than 30, including those with a weight-related comorbidity, Dr. Bessesen said. The average weight loss is 5%-15% over 3-6 months but may vary greatly. Insurance often does not cover the medication costs.
 

Older FDA-approved antiobesity medications

Phentermine is the most widely prescribed antiobesity medication, partly because it is the only option most people can afford out of pocket. Dr. Bessesen presented recent data showing that long-term use of phentermine was associated with greater weight loss and that patients continuously taking phentermine for 24 months lost 7.5% of their weight.

Phentermine suppresses appetite by increasing norepinephrine production. Dr. Bessesen warned that internists should be careful when prescribing it to patients with mental conditions, because it acts as a stimulant. Early studies raised concerns about the risk of cardiovascular disease (CVD) in patients taking phentermine. However, analysis of data from over 13,000 individuals showed no evidence of a relationship between phentermine exposure and CVD events.

“These data provide some reassurance that it could be used in patients with CVD risk,” he noted. Phentermine can also be combined with topiramate extended release, a combination that provides greater efficacy (up to 10% weight loss) with fewer side effects. However, this combination is less effective in patients with diabetes than in those without.

Additional treatment options included orlistat and naltrexone sustained release/bupropion SR. Orlistat is a good treatment alternative for patients with constipation and is the safest option among older anti-obesity medications, whereas naltrexone SR/bupropion SR may be useful in patients with food cravings. However, there is more variability in the individual-level benefit from these agents compared to phentermine and phentermine/topiramate ER, Dr. Bessesen said.
 

Newer anti‐obesity medications

Liraglutide, an agent used for the management of type 2 diabetes, has recently been approved for weight loss. Liraglutide causes moderate weight loss, and it may reduce the risk of CVD. However, there are tolerability issues, such as nausea and other risks, and Dr. Bessesen advises internists to “start at low doses and increase slowly.”

Semaglutide is the newest and most effective antiobesity drug approved by the Food and Drug Administration, providing sustained weight loss of 8% for up to 48 weeks after starting treatment. Although its efficacy is lower in patients with diabetes, Dr. Bessesen noted that “this is common for antiobesity agents, and clinicians should not refrain from prescribing it in this population.”

Setmelanotide is another new medication approved for chronic weight management in patients with monogenic obesity. This medication can be considered for patients with early-onset severe obesity with abnormal feeding behavior.

Commenting on barriers to access to new antiobesity medications, Dr. Bessesen said that “the high cost of these medications is a substantial problem, but as more companies become involved and products are on the market for a longer period of time, I am hopeful that prices will come down.”
 

Emerging antiobesity medications

Dr. Bessesen presented recent phase 3 data showing that treatment with tirzepatide provided sustained chronic loss and improved cardiometabolic measures with no diet. Tirzepatide, which targets receptors for glucagonlike peptide–1 and glucose-dependent insulinotropic polypeptide, is used for the management of type 2 diabetes and is expected to be reviewed soon by the FDA for its use in weight management.

A semaglutide/cagrilintide combination may also provide a new treatment option for patients with obesity. In a phase 1b trial, semaglutide/cagrilintide treatment resulted in up to 17% weight loss in patients with obesity who were otherwise healthy; however, phase 2 and 3 data are needed to confirm its efficacy.
 

A ‘holistic approach’

When deciding whether to prescribe antiobesity medications, Dr. Bessesen noted that medications are better than exercise alone. Factors to consider when deciding whether to prescribe drugs, as well as which ones, include costs, local regulatory guidelines, requirement for long-term use, and patient comorbidities.

He also stated that lifestyle changes, such as adopting healthy nutrition and exercising regularly, are also important and can enhance weight loss when combined with medications.

Richele Corrado, DO, MPH, agreed that lifestyle management in combination with medications may provide greater weight loss than each of these interventions alone.

“If you look at the data, exercise doesn’t help you lose much weight,” said Dr. Corrado, a staff internist and obesity medicine specialist at Walter Reed National Military Medical Center in Bethesda, Md., who spoke at the same session. She added that she has many patients who struggle to lose weight despite having a healthy lifestyle. “It’s important to discuss with these patients about medications and surgery.”

Dr. Bessesen noted that management of mental health and emotional well-being should also be an integral part of obesity management. “Treatment for obesity may be more successful when underlying psychological conditions such as depression, childhood sexual trauma, or anxiety are addressed and treated,” he said.

Dr. Bessesen was involved in the study of the efficacy of semaglutide/cagrilintide. He does not have any financial conflicts with the companies that make other mentioned medications. He has received research grants or contracts from Novo Nordisk, honoraria from Novo Nordisk, and consultantship from Eli Lilly. Dr. Corrado reported no relevant financial conflicts.

SAN DIEGO – For patients with obesity, surgery, lifestyle changes, and pharmacologic interventions are all treatment options, but antiobesity medications provide a better risk-to-benefit ratio, according to a presenter at the annual meeting of the American College of Physicians.

Lifestyle changes result in the least weight loss and may be safest, while surgery provides the most weight loss and has the greatest risk. Antiobesity medications, especially the newer ones used in combination with lifestyle changes, can provide significant and sustained weight loss with manageable side effects, said Daniel Bessesen, MD, a professor in the endocrinology, diabetes, and metabolism at University of Colorado at Denver, Aurora.

New and more effective antiobesity medications have given internists more potential options to discuss with their patients, Dr. Bessesen said. He reviewed the pros and cons of the different options.

Medications are indicated for patients with a body mass index greater than 30, including those with a weight-related comorbidity, Dr. Bessesen said. The average weight loss is 5%-15% over 3-6 months but may vary greatly. Insurance often does not cover the medication costs.
 

Older FDA-approved antiobesity medications

Phentermine is the most widely prescribed antiobesity medication, partly because it is the only option most people can afford out of pocket. Dr. Bessesen presented recent data showing that long-term use of phentermine was associated with greater weight loss and that patients continuously taking phentermine for 24 months lost 7.5% of their weight.

Phentermine suppresses appetite by increasing norepinephrine production. Dr. Bessesen warned that internists should be careful when prescribing it to patients with mental conditions, because it acts as a stimulant. Early studies raised concerns about the risk of cardiovascular disease (CVD) in patients taking phentermine. However, analysis of data from over 13,000 individuals showed no evidence of a relationship between phentermine exposure and CVD events.

“These data provide some reassurance that it could be used in patients with CVD risk,” he noted. Phentermine can also be combined with topiramate extended release, a combination that provides greater efficacy (up to 10% weight loss) with fewer side effects. However, this combination is less effective in patients with diabetes than in those without.

Additional treatment options included orlistat and naltrexone sustained release/bupropion SR. Orlistat is a good treatment alternative for patients with constipation and is the safest option among older anti-obesity medications, whereas naltrexone SR/bupropion SR may be useful in patients with food cravings. However, there is more variability in the individual-level benefit from these agents compared to phentermine and phentermine/topiramate ER, Dr. Bessesen said.
 

Newer anti‐obesity medications

Liraglutide, an agent used for the management of type 2 diabetes, has recently been approved for weight loss. Liraglutide causes moderate weight loss, and it may reduce the risk of CVD. However, there are tolerability issues, such as nausea and other risks, and Dr. Bessesen advises internists to “start at low doses and increase slowly.”

Semaglutide is the newest and most effective antiobesity drug approved by the Food and Drug Administration, providing sustained weight loss of 8% for up to 48 weeks after starting treatment. Although its efficacy is lower in patients with diabetes, Dr. Bessesen noted that “this is common for antiobesity agents, and clinicians should not refrain from prescribing it in this population.”

Setmelanotide is another new medication approved for chronic weight management in patients with monogenic obesity. This medication can be considered for patients with early-onset severe obesity with abnormal feeding behavior.

Commenting on barriers to access to new antiobesity medications, Dr. Bessesen said that “the high cost of these medications is a substantial problem, but as more companies become involved and products are on the market for a longer period of time, I am hopeful that prices will come down.”
 

Emerging antiobesity medications

Dr. Bessesen presented recent phase 3 data showing that treatment with tirzepatide provided sustained chronic loss and improved cardiometabolic measures with no diet. Tirzepatide, which targets receptors for glucagonlike peptide–1 and glucose-dependent insulinotropic polypeptide, is used for the management of type 2 diabetes and is expected to be reviewed soon by the FDA for its use in weight management.

A semaglutide/cagrilintide combination may also provide a new treatment option for patients with obesity. In a phase 1b trial, semaglutide/cagrilintide treatment resulted in up to 17% weight loss in patients with obesity who were otherwise healthy; however, phase 2 and 3 data are needed to confirm its efficacy.
 

A ‘holistic approach’

When deciding whether to prescribe antiobesity medications, Dr. Bessesen noted that medications are better than exercise alone. Factors to consider when deciding whether to prescribe drugs, as well as which ones, include costs, local regulatory guidelines, requirement for long-term use, and patient comorbidities.

He also stated that lifestyle changes, such as adopting healthy nutrition and exercising regularly, are also important and can enhance weight loss when combined with medications.

Richele Corrado, DO, MPH, agreed that lifestyle management in combination with medications may provide greater weight loss than each of these interventions alone.

“If you look at the data, exercise doesn’t help you lose much weight,” said Dr. Corrado, a staff internist and obesity medicine specialist at Walter Reed National Military Medical Center in Bethesda, Md., who spoke at the same session. She added that she has many patients who struggle to lose weight despite having a healthy lifestyle. “It’s important to discuss with these patients about medications and surgery.”

Dr. Bessesen noted that management of mental health and emotional well-being should also be an integral part of obesity management. “Treatment for obesity may be more successful when underlying psychological conditions such as depression, childhood sexual trauma, or anxiety are addressed and treated,” he said.

Dr. Bessesen was involved in the study of the efficacy of semaglutide/cagrilintide. He does not have any financial conflicts with the companies that make other mentioned medications. He has received research grants or contracts from Novo Nordisk, honoraria from Novo Nordisk, and consultantship from Eli Lilly. Dr. Corrado reported no relevant financial conflicts.

SAN DIEGO – For patients with obesity, surgery, lifestyle changes, and pharmacologic interventions are all treatment options, but antiobesity medications provide a better risk-to-benefit ratio, according to a presenter at the annual meeting of the American College of Physicians.

Lifestyle changes result in the least weight loss and may be safest, while surgery provides the most weight loss and has the greatest risk. Antiobesity medications, especially the newer ones used in combination with lifestyle changes, can provide significant and sustained weight loss with manageable side effects, said Daniel Bessesen, MD, a professor in the endocrinology, diabetes, and metabolism at University of Colorado at Denver, Aurora.

New and more effective antiobesity medications have given internists more potential options to discuss with their patients, Dr. Bessesen said. He reviewed the pros and cons of the different options.

Medications are indicated for patients with a body mass index greater than 30, including those with a weight-related comorbidity, Dr. Bessesen said. The average weight loss is 5%-15% over 3-6 months but may vary greatly. Insurance often does not cover the medication costs.
 

Older FDA-approved antiobesity medications

Phentermine is the most widely prescribed antiobesity medication, partly because it is the only option most people can afford out of pocket. Dr. Bessesen presented recent data showing that long-term use of phentermine was associated with greater weight loss and that patients continuously taking phentermine for 24 months lost 7.5% of their weight.

Phentermine suppresses appetite by increasing norepinephrine production. Dr. Bessesen warned that internists should be careful when prescribing it to patients with mental conditions, because it acts as a stimulant. Early studies raised concerns about the risk of cardiovascular disease (CVD) in patients taking phentermine. However, analysis of data from over 13,000 individuals showed no evidence of a relationship between phentermine exposure and CVD events.

“These data provide some reassurance that it could be used in patients with CVD risk,” he noted. Phentermine can also be combined with topiramate extended release, a combination that provides greater efficacy (up to 10% weight loss) with fewer side effects. However, this combination is less effective in patients with diabetes than in those without.

Additional treatment options included orlistat and naltrexone sustained release/bupropion SR. Orlistat is a good treatment alternative for patients with constipation and is the safest option among older anti-obesity medications, whereas naltrexone SR/bupropion SR may be useful in patients with food cravings. However, there is more variability in the individual-level benefit from these agents compared to phentermine and phentermine/topiramate ER, Dr. Bessesen said.
 

Newer anti‐obesity medications

Liraglutide, an agent used for the management of type 2 diabetes, has recently been approved for weight loss. Liraglutide causes moderate weight loss, and it may reduce the risk of CVD. However, there are tolerability issues, such as nausea and other risks, and Dr. Bessesen advises internists to “start at low doses and increase slowly.”

Semaglutide is the newest and most effective antiobesity drug approved by the Food and Drug Administration, providing sustained weight loss of 8% for up to 48 weeks after starting treatment. Although its efficacy is lower in patients with diabetes, Dr. Bessesen noted that “this is common for antiobesity agents, and clinicians should not refrain from prescribing it in this population.”

Setmelanotide is another new medication approved for chronic weight management in patients with monogenic obesity. This medication can be considered for patients with early-onset severe obesity with abnormal feeding behavior.

Commenting on barriers to access to new antiobesity medications, Dr. Bessesen said that “the high cost of these medications is a substantial problem, but as more companies become involved and products are on the market for a longer period of time, I am hopeful that prices will come down.”
 

Emerging antiobesity medications

Dr. Bessesen presented recent phase 3 data showing that treatment with tirzepatide provided sustained chronic loss and improved cardiometabolic measures with no diet. Tirzepatide, which targets receptors for glucagonlike peptide–1 and glucose-dependent insulinotropic polypeptide, is used for the management of type 2 diabetes and is expected to be reviewed soon by the FDA for its use in weight management.

A semaglutide/cagrilintide combination may also provide a new treatment option for patients with obesity. In a phase 1b trial, semaglutide/cagrilintide treatment resulted in up to 17% weight loss in patients with obesity who were otherwise healthy; however, phase 2 and 3 data are needed to confirm its efficacy.
 

A ‘holistic approach’

When deciding whether to prescribe antiobesity medications, Dr. Bessesen noted that medications are better than exercise alone. Factors to consider when deciding whether to prescribe drugs, as well as which ones, include costs, local regulatory guidelines, requirement for long-term use, and patient comorbidities.

He also stated that lifestyle changes, such as adopting healthy nutrition and exercising regularly, are also important and can enhance weight loss when combined with medications.

Richele Corrado, DO, MPH, agreed that lifestyle management in combination with medications may provide greater weight loss than each of these interventions alone.

“If you look at the data, exercise doesn’t help you lose much weight,” said Dr. Corrado, a staff internist and obesity medicine specialist at Walter Reed National Military Medical Center in Bethesda, Md., who spoke at the same session. She added that she has many patients who struggle to lose weight despite having a healthy lifestyle. “It’s important to discuss with these patients about medications and surgery.”

Dr. Bessesen noted that management of mental health and emotional well-being should also be an integral part of obesity management. “Treatment for obesity may be more successful when underlying psychological conditions such as depression, childhood sexual trauma, or anxiety are addressed and treated,” he said.

Dr. Bessesen was involved in the study of the efficacy of semaglutide/cagrilintide. He does not have any financial conflicts with the companies that make other mentioned medications. He has received research grants or contracts from Novo Nordisk, honoraria from Novo Nordisk, and consultantship from Eli Lilly. Dr. Corrado reported no relevant financial conflicts.

Seasonal variation in one of the hormones used to monitor thyroid function could in turn lead to false diagnoses of subclinical hypothyroidism and unnecessary prescriptions of levothyroxine, according to Yale clinical chemist Joe M. El-Khoury, PhD.

A Japanese study of more than 7,000 healthy individuals showed that thyrotropin-stimulating hormone (TSH) varies widely throughout the seasons, he said, peaking in the northern hemisphere’s winter months (January to February) with its low in the summer months (June to August). That paper was published last year in the Journal of the Endocrine Society.

Sebastian Kaulitzki/Fotolia

But free thyroxine (FT4) levels in the Japanese population remained relatively stable, he wrote in a letter recently published in Clinical Chemistry.

“If you end up with a mildly elevated TSH result and a normal FT4, try getting retested 2-3 months later to make sure this is not a seasonal artifact or transient increase before prescribing/taking levothyroxine unnecessarily,” advised Dr. El-Khoury, director of Yale University’s Clinical Chemistry Laboratory, New Haven, Conn.

“Because the [population-based, laboratory] reference ranges don’t account for seasonal variation, we’re flagging a significant number of people as high TSH when they’re normal, and physicians are prescribing levothyroxine inappropriately to healthy people who don’t need it,” he told this news organization, adding that overtreatment can be harmful, particularly for elderly people.

This seasonal variation in TSH could account for between a third to a half of the 90% of all levothyroxine prescriptions that were found to be unnecessary, according to a U.S. study in 2021, Dr. El-Khoury added.

In a comment, Trisha Cubb, MD, said that Dr. El-Khoury’s letter “raises a good point, that we really need to look at our reference ranges, especially when more and more studies are showing that so many thyroid hormone prescriptions may not be necessary.”

Dr. Cubb, thyroid section director and assistant professor of clinical medicine at Weill Cornell Medical College/Houston Methodist Academic Institute, Texas, also agrees with Dr. El-Khoury’s suggestion to repeat lab results in some instances.

“I think repeating results, especially in our patients with subclinical disease, is important,” she noted.

And she pointed out that seasonal variation isn’t the only relevant variable. “We also know that multiple clinical factors like pregnancy status, coexisting comorbidities, or age can all influence what we as clinicians consider an acceptable TSH range in an individual patient.” And other medications, such as steroids, or supplements like biotin, “can all affect thyroid lab values,” she noted.

“Ensuring that minor abnormalities aren’t transient is important prior to initiating medical therapy. With any medical therapy there are possible side effects, along with time, cost, [and] monitoring, all of which can be associated with thyroid hormone replacement.”
 

TSH reference ranges should be adapted for subpopulations

Dr. El-Khoury explained that to get an idea of how big the seasonal differences in TSH observed in the Japanese study were, “the upper end of the population they tracked goes from 5.2 [mIU/L] in January to 3.4 [mIU/L] in August. So you have almost a 2-unit change in concentration that can happen in the reference population. But laboratory reference ranges, or ‘normal ranges,’ are usually fixed and don’t change by season.”

The higher the TSH, the more likely a person is to have hypothyroidism. Major recent studies have found no benefit of levothyroxine treatment with TSH levels below 7.0-10.0 mIU/L, he said.

“So, I suggest that the limit should be 7.0 [mIU/L] to be safe, but it could be as high as 10 [mIU/L]. In any case, let’s shift the mindset to clinical outcome–based treatment cutoffs,” he said, noting that this approach is currently used for decisions on cholesterol-lowering therapy or vitamin D supplementation, for example.

Regarding this suggestion of using a TSH cutoff of 7 mIU/L to diagnose subclinical hypothyroidism, Dr. Cubb said: “It really depends on the specific population. In an elderly patient, a higher TSH may be of less clinical concern when compared to a female who is actively trying to get pregnant.

“Overall, I think we do need to better understand what appropriate TSH ranges are in specific subpopulations, and then with time, make this more understandable and available for general medicine as well as subspecialty providers to be able to utilize,” she noted.

Regarding the particular Japanese findings cited by Dr. El-Khoury, Dr. Cubb observed that this was a very specific study population, “so we would need more data showing that this is more generalizable.”

And she noted that there’s also diurnal variation in TSH. “In the [Japanese] paper, patients had their thyroid labs drawn between 8:00 a.m. and 9:00 a.m. in a fasting state. Oftentimes in the U.S., thyroid labs are not drawn at specific times or [during] fasting. I think this is one of many factors that should be considered.”
 

Acknowledging seasonal variation would be a start

But overall, Dr. Cubb said that both the Japanese study and Dr. El-Khoury’s letter highlight “how season, in and of itself, which is not something we usually think about, can affect thyroid lab results. I believe as more data come out, more generalizable data, that’s how evidence-based guidelines are generated over time.”

According to Dr. El-Khoury, fixing the laboratory reference range issues would likely require a joint effort of professional medical societies, reference laboratories, and assay manufacturers. But with seasonal variation, that might be a difficult task.

“The problem is, in laboratory medicine, we don’t have rules for an analyte that changes by season to do anything different. My goal is to get people to at least acknowledge this is a problem and do something,” he concluded.

Dr. El-Khoury and Dr. Cubb have reported no relevant financial relationships.
 

A version of this article first appeared on Medscape.com.

Seasonal variation in one of the hormones used to monitor thyroid function could in turn lead to false diagnoses of subclinical hypothyroidism and unnecessary prescriptions of levothyroxine, according to Yale clinical chemist Joe M. El-Khoury, PhD.

A Japanese study of more than 7,000 healthy individuals showed that thyrotropin-stimulating hormone (TSH) varies widely throughout the seasons, he said, peaking in the northern hemisphere’s winter months (January to February) with its low in the summer months (June to August). That paper was published last year in the Journal of the Endocrine Society.

Sebastian Kaulitzki/Fotolia

But free thyroxine (FT4) levels in the Japanese population remained relatively stable, he wrote in a letter recently published in Clinical Chemistry.

“If you end up with a mildly elevated TSH result and a normal FT4, try getting retested 2-3 months later to make sure this is not a seasonal artifact or transient increase before prescribing/taking levothyroxine unnecessarily,” advised Dr. El-Khoury, director of Yale University’s Clinical Chemistry Laboratory, New Haven, Conn.

“Because the [population-based, laboratory] reference ranges don’t account for seasonal variation, we’re flagging a significant number of people as high TSH when they’re normal, and physicians are prescribing levothyroxine inappropriately to healthy people who don’t need it,” he told this news organization, adding that overtreatment can be harmful, particularly for elderly people.

This seasonal variation in TSH could account for between a third to a half of the 90% of all levothyroxine prescriptions that were found to be unnecessary, according to a U.S. study in 2021, Dr. El-Khoury added.

In a comment, Trisha Cubb, MD, said that Dr. El-Khoury’s letter “raises a good point, that we really need to look at our reference ranges, especially when more and more studies are showing that so many thyroid hormone prescriptions may not be necessary.”

Dr. Cubb, thyroid section director and assistant professor of clinical medicine at Weill Cornell Medical College/Houston Methodist Academic Institute, Texas, also agrees with Dr. El-Khoury’s suggestion to repeat lab results in some instances.

“I think repeating results, especially in our patients with subclinical disease, is important,” she noted.

And she pointed out that seasonal variation isn’t the only relevant variable. “We also know that multiple clinical factors like pregnancy status, coexisting comorbidities, or age can all influence what we as clinicians consider an acceptable TSH range in an individual patient.” And other medications, such as steroids, or supplements like biotin, “can all affect thyroid lab values,” she noted.

“Ensuring that minor abnormalities aren’t transient is important prior to initiating medical therapy. With any medical therapy there are possible side effects, along with time, cost, [and] monitoring, all of which can be associated with thyroid hormone replacement.”
 

TSH reference ranges should be adapted for subpopulations

Dr. El-Khoury explained that to get an idea of how big the seasonal differences in TSH observed in the Japanese study were, “the upper end of the population they tracked goes from 5.2 [mIU/L] in January to 3.4 [mIU/L] in August. So you have almost a 2-unit change in concentration that can happen in the reference population. But laboratory reference ranges, or ‘normal ranges,’ are usually fixed and don’t change by season.”

The higher the TSH, the more likely a person is to have hypothyroidism. Major recent studies have found no benefit of levothyroxine treatment with TSH levels below 7.0-10.0 mIU/L, he said.

“So, I suggest that the limit should be 7.0 [mIU/L] to be safe, but it could be as high as 10 [mIU/L]. In any case, let’s shift the mindset to clinical outcome–based treatment cutoffs,” he said, noting that this approach is currently used for decisions on cholesterol-lowering therapy or vitamin D supplementation, for example.

Regarding this suggestion of using a TSH cutoff of 7 mIU/L to diagnose subclinical hypothyroidism, Dr. Cubb said: “It really depends on the specific population. In an elderly patient, a higher TSH may be of less clinical concern when compared to a female who is actively trying to get pregnant.

“Overall, I think we do need to better understand what appropriate TSH ranges are in specific subpopulations, and then with time, make this more understandable and available for general medicine as well as subspecialty providers to be able to utilize,” she noted.

Regarding the particular Japanese findings cited by Dr. El-Khoury, Dr. Cubb observed that this was a very specific study population, “so we would need more data showing that this is more generalizable.”

And she noted that there’s also diurnal variation in TSH. “In the [Japanese] paper, patients had their thyroid labs drawn between 8:00 a.m. and 9:00 a.m. in a fasting state. Oftentimes in the U.S., thyroid labs are not drawn at specific times or [during] fasting. I think this is one of many factors that should be considered.”
 

Acknowledging seasonal variation would be a start

But overall, Dr. Cubb said that both the Japanese study and Dr. El-Khoury’s letter highlight “how season, in and of itself, which is not something we usually think about, can affect thyroid lab results. I believe as more data come out, more generalizable data, that’s how evidence-based guidelines are generated over time.”

According to Dr. El-Khoury, fixing the laboratory reference range issues would likely require a joint effort of professional medical societies, reference laboratories, and assay manufacturers. But with seasonal variation, that might be a difficult task.

“The problem is, in laboratory medicine, we don’t have rules for an analyte that changes by season to do anything different. My goal is to get people to at least acknowledge this is a problem and do something,” he concluded.

Dr. El-Khoury and Dr. Cubb have reported no relevant financial relationships.
 

A version of this article first appeared on Medscape.com.

Seasonal variation in one of the hormones used to monitor thyroid function could in turn lead to false diagnoses of subclinical hypothyroidism and unnecessary prescriptions of levothyroxine, according to Yale clinical chemist Joe M. El-Khoury, PhD.

A Japanese study of more than 7,000 healthy individuals showed that thyrotropin-stimulating hormone (TSH) varies widely throughout the seasons, he said, peaking in the northern hemisphere’s winter months (January to February) with its low in the summer months (June to August). That paper was published last year in the Journal of the Endocrine Society.

Sebastian Kaulitzki/Fotolia

But free thyroxine (FT4) levels in the Japanese population remained relatively stable, he wrote in a letter recently published in Clinical Chemistry.

“If you end up with a mildly elevated TSH result and a normal FT4, try getting retested 2-3 months later to make sure this is not a seasonal artifact or transient increase before prescribing/taking levothyroxine unnecessarily,” advised Dr. El-Khoury, director of Yale University’s Clinical Chemistry Laboratory, New Haven, Conn.

“Because the [population-based, laboratory] reference ranges don’t account for seasonal variation, we’re flagging a significant number of people as high TSH when they’re normal, and physicians are prescribing levothyroxine inappropriately to healthy people who don’t need it,” he told this news organization, adding that overtreatment can be harmful, particularly for elderly people.

This seasonal variation in TSH could account for between a third to a half of the 90% of all levothyroxine prescriptions that were found to be unnecessary, according to a U.S. study in 2021, Dr. El-Khoury added.

In a comment, Trisha Cubb, MD, said that Dr. El-Khoury’s letter “raises a good point, that we really need to look at our reference ranges, especially when more and more studies are showing that so many thyroid hormone prescriptions may not be necessary.”

Dr. Cubb, thyroid section director and assistant professor of clinical medicine at Weill Cornell Medical College/Houston Methodist Academic Institute, Texas, also agrees with Dr. El-Khoury’s suggestion to repeat lab results in some instances.

“I think repeating results, especially in our patients with subclinical disease, is important,” she noted.

And she pointed out that seasonal variation isn’t the only relevant variable. “We also know that multiple clinical factors like pregnancy status, coexisting comorbidities, or age can all influence what we as clinicians consider an acceptable TSH range in an individual patient.” And other medications, such as steroids, or supplements like biotin, “can all affect thyroid lab values,” she noted.

“Ensuring that minor abnormalities aren’t transient is important prior to initiating medical therapy. With any medical therapy there are possible side effects, along with time, cost, [and] monitoring, all of which can be associated with thyroid hormone replacement.”
 

TSH reference ranges should be adapted for subpopulations

Dr. El-Khoury explained that to get an idea of how big the seasonal differences in TSH observed in the Japanese study were, “the upper end of the population they tracked goes from 5.2 [mIU/L] in January to 3.4 [mIU/L] in August. So you have almost a 2-unit change in concentration that can happen in the reference population. But laboratory reference ranges, or ‘normal ranges,’ are usually fixed and don’t change by season.”

The higher the TSH, the more likely a person is to have hypothyroidism. Major recent studies have found no benefit of levothyroxine treatment with TSH levels below 7.0-10.0 mIU/L, he said.

“So, I suggest that the limit should be 7.0 [mIU/L] to be safe, but it could be as high as 10 [mIU/L]. In any case, let’s shift the mindset to clinical outcome–based treatment cutoffs,” he said, noting that this approach is currently used for decisions on cholesterol-lowering therapy or vitamin D supplementation, for example.

Regarding this suggestion of using a TSH cutoff of 7 mIU/L to diagnose subclinical hypothyroidism, Dr. Cubb said: “It really depends on the specific population. In an elderly patient, a higher TSH may be of less clinical concern when compared to a female who is actively trying to get pregnant.

“Overall, I think we do need to better understand what appropriate TSH ranges are in specific subpopulations, and then with time, make this more understandable and available for general medicine as well as subspecialty providers to be able to utilize,” she noted.

Regarding the particular Japanese findings cited by Dr. El-Khoury, Dr. Cubb observed that this was a very specific study population, “so we would need more data showing that this is more generalizable.”

And she noted that there’s also diurnal variation in TSH. “In the [Japanese] paper, patients had their thyroid labs drawn between 8:00 a.m. and 9:00 a.m. in a fasting state. Oftentimes in the U.S., thyroid labs are not drawn at specific times or [during] fasting. I think this is one of many factors that should be considered.”
 

Acknowledging seasonal variation would be a start

But overall, Dr. Cubb said that both the Japanese study and Dr. El-Khoury’s letter highlight “how season, in and of itself, which is not something we usually think about, can affect thyroid lab results. I believe as more data come out, more generalizable data, that’s how evidence-based guidelines are generated over time.”

According to Dr. El-Khoury, fixing the laboratory reference range issues would likely require a joint effort of professional medical societies, reference laboratories, and assay manufacturers. But with seasonal variation, that might be a difficult task.

“The problem is, in laboratory medicine, we don’t have rules for an analyte that changes by season to do anything different. My goal is to get people to at least acknowledge this is a problem and do something,” he concluded.

Dr. El-Khoury and Dr. Cubb have reported no relevant financial relationships.
 

A version of this article first appeared on Medscape.com.

Early parathyroidectomy within 1 year of diagnosis of primary hyperparathyroidism (PHPT) did not reduce the risk of a sustained decline in kidney function, measured by a decline in estimated glomerular filtration rate (eGFR) of at least 50%, compared with observation (no surgery) in adults aged 60 and older.

Early parathyroidectomy was, however, associated with a reduced adjusted risk of this decline in kidney function in patients with newly diagnosed PHPT who were younger than age 60.

The findings, based on data from close to 43,000 veterans, were published online in Annals of Internal Medicine.

“The important takeaway from our study is that for older adults [age 60 or older] with primary hyperparathyroidism, preservation of kidney function should not be a primary consideration when making decisions about whether to undergo parathyroidectomy,” lead author Carolyn D. Seib, MD, told this news organization.

“It is important that physicians also discuss with their patients the potential long-term benefits of parathyroidectomy related to a reduced risk of fractures, kidney stones, and cardiovascular disease, and improved quality of life, in addition to the need for lifelong surveillance if surgery is declined, weighing these against an individual patient’s risk of surgery,” said Dr. Seib, a surgeon at Palo Alto (Calif.) VA Medical Center.

“However, in patients younger than 60, early parathyroidectomy may prevent progression to chronic kidney disease (CKD) and should be more strongly considered,” she noted.

Parathyroidectomy, she observed, is a low-risk outpatient surgery for most adults.

“Potential complications of surgery include temporary or permanent hoarseness, hypoparathyroidism (low postoperative parathyroid function), bleeding requiring return to the operating room, and complications related to general anesthesia, all of which are rare,” said Dr. Seib.

“Surgery by a high-volume surgeon is associated with a reduced risk of complications, so patients should seek out an experienced parathyroid surgeon,” she emphasized.  

Moreover, parathyroidectomy is the only treatment for primary hyperparathyroidism.
 

Does parathyroidectomy slow loss of kidney function?

Multidisciplinary guidelines recommend parathyroidectomy, at least in part to mitigate the risk for, and effects related to, the progression of CKD in patients with PHPT and an eGFR below 60 mL/min per 1.73 m², the researchers wrote.

However, whether parathyroidectomy slows the loss of kidney function in adults with PHPT is not clear.

Guidelines also state that “observation for PHPT disease progression can be considered when patients have no obvious end organ damage (i.e., eGFR > 60 mL/min per 1.73 m², normal bone mineral density, and no history of kidney stones or fractures),” Dr. Seib noted.  

To address the evidence gap, the researchers emulated a randomized target trial using observational data.

In this type of study, Dr. Seib explained, “although patients aren’t randomly assigned to a treatment, complex statistical methods are used to adjust for baseline confounders in an attempt to emulate random treatment assignment and account for bias that may affect the timing of when patients receive treatment.”

Using national Veterans Health Administration data, researchers identified 43,697 veterans with a new biochemical diagnosis of PHPT, defined as elevated parathyroid hormone (> 65 ng/mL) within 6 months of an elevated serum calcium level (> 32.55 mmol/L or >10.2 mg/dL), from 2000 to 2019.

Of these patients, 3,804 underwent parathyroidectomy within 1 year of diagnosis of PHPT, and 39,893 did not, and instead, a watchful waiting approach was adopted.

To be included in the analysis, patients had to have an eGFR above 30 mL/min per 1.73 m² for 12 months before PHPT diagnosis to exclude secondary or tertiary hyperparathyroidism.

The primary outcome was a sustained decline in eGFR of at least 50% from baseline.

In the overall cohort, patients had a mean pretreatment eGFR of 71.8 mL/min per 1.73 m². The mean age of patients was 67, 88% were men, and 68% were White.

After a median follow-up of 4.9 years, 6.7% of the patients had a decline in eGFR of at least 50%.

The cumulative incidence of this decline in eGFR was 5.1% at 5 years and 10.8% at 10 years in patients who had had early parathyroidectomy compared with 5.1% and 12.0%, respectively, in patients who did not undergo surgery.

In the overall population, the risk of at least a 50% decline in eGFR was similar in the early parathyroidectomy group versus the observation group (adjusted hazard ratio [HR], 0.98, 95% confidence interval [CI], 0.82-1.16).

However, diving deeper showed that parathyroidectomy was associated with a reduced risk of the primary outcome among patients younger than 60 years (adjusted HR, 0.75, 95% CI, 0.59-0.93) but not among those aged 60 or older (adjusted HR, 1.08, 95% CI, 0.87-1.34).

“When participating in shared decision-making for older adults [age 60 and older] with PHPT, clinicians should not consider parathyroidectomy for potential benefits of preservation of kidney function,” the researchers reiterated.

“For younger patients, clinicians should discuss the potential benefit of parathyroidectomy to reduce the risk for CKD and associated complications in adults with PHPT,” they concluded.

The study was funded by the National Institute on Aging. The authors reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Early parathyroidectomy within 1 year of diagnosis of primary hyperparathyroidism (PHPT) did not reduce the risk of a sustained decline in kidney function, measured by a decline in estimated glomerular filtration rate (eGFR) of at least 50%, compared with observation (no surgery) in adults aged 60 and older.

Early parathyroidectomy was, however, associated with a reduced adjusted risk of this decline in kidney function in patients with newly diagnosed PHPT who were younger than age 60.

The findings, based on data from close to 43,000 veterans, were published online in Annals of Internal Medicine.

“The important takeaway from our study is that for older adults [age 60 or older] with primary hyperparathyroidism, preservation of kidney function should not be a primary consideration when making decisions about whether to undergo parathyroidectomy,” lead author Carolyn D. Seib, MD, told this news organization.

“It is important that physicians also discuss with their patients the potential long-term benefits of parathyroidectomy related to a reduced risk of fractures, kidney stones, and cardiovascular disease, and improved quality of life, in addition to the need for lifelong surveillance if surgery is declined, weighing these against an individual patient’s risk of surgery,” said Dr. Seib, a surgeon at Palo Alto (Calif.) VA Medical Center.

“However, in patients younger than 60, early parathyroidectomy may prevent progression to chronic kidney disease (CKD) and should be more strongly considered,” she noted.

Parathyroidectomy, she observed, is a low-risk outpatient surgery for most adults.

“Potential complications of surgery include temporary or permanent hoarseness, hypoparathyroidism (low postoperative parathyroid function), bleeding requiring return to the operating room, and complications related to general anesthesia, all of which are rare,” said Dr. Seib.

“Surgery by a high-volume surgeon is associated with a reduced risk of complications, so patients should seek out an experienced parathyroid surgeon,” she emphasized.  

Moreover, parathyroidectomy is the only treatment for primary hyperparathyroidism.
 

Does parathyroidectomy slow loss of kidney function?

Multidisciplinary guidelines recommend parathyroidectomy, at least in part to mitigate the risk for, and effects related to, the progression of CKD in patients with PHPT and an eGFR below 60 mL/min per 1.73 m², the researchers wrote.

However, whether parathyroidectomy slows the loss of kidney function in adults with PHPT is not clear.

Guidelines also state that “observation for PHPT disease progression can be considered when patients have no obvious end organ damage (i.e., eGFR > 60 mL/min per 1.73 m², normal bone mineral density, and no history of kidney stones or fractures),” Dr. Seib noted.  

To address the evidence gap, the researchers emulated a randomized target trial using observational data.

In this type of study, Dr. Seib explained, “although patients aren’t randomly assigned to a treatment, complex statistical methods are used to adjust for baseline confounders in an attempt to emulate random treatment assignment and account for bias that may affect the timing of when patients receive treatment.”

Using national Veterans Health Administration data, researchers identified 43,697 veterans with a new biochemical diagnosis of PHPT, defined as elevated parathyroid hormone (> 65 ng/mL) within 6 months of an elevated serum calcium level (> 32.55 mmol/L or >10.2 mg/dL), from 2000 to 2019.

Of these patients, 3,804 underwent parathyroidectomy within 1 year of diagnosis of PHPT, and 39,893 did not, and instead, a watchful waiting approach was adopted.

To be included in the analysis, patients had to have an eGFR above 30 mL/min per 1.73 m² for 12 months before PHPT diagnosis to exclude secondary or tertiary hyperparathyroidism.

The primary outcome was a sustained decline in eGFR of at least 50% from baseline.

In the overall cohort, patients had a mean pretreatment eGFR of 71.8 mL/min per 1.73 m². The mean age of patients was 67, 88% were men, and 68% were White.

After a median follow-up of 4.9 years, 6.7% of the patients had a decline in eGFR of at least 50%.

The cumulative incidence of this decline in eGFR was 5.1% at 5 years and 10.8% at 10 years in patients who had had early parathyroidectomy compared with 5.1% and 12.0%, respectively, in patients who did not undergo surgery.

In the overall population, the risk of at least a 50% decline in eGFR was similar in the early parathyroidectomy group versus the observation group (adjusted hazard ratio [HR], 0.98, 95% confidence interval [CI], 0.82-1.16).

However, diving deeper showed that parathyroidectomy was associated with a reduced risk of the primary outcome among patients younger than 60 years (adjusted HR, 0.75, 95% CI, 0.59-0.93) but not among those aged 60 or older (adjusted HR, 1.08, 95% CI, 0.87-1.34).

“When participating in shared decision-making for older adults [age 60 and older] with PHPT, clinicians should not consider parathyroidectomy for potential benefits of preservation of kidney function,” the researchers reiterated.

“For younger patients, clinicians should discuss the potential benefit of parathyroidectomy to reduce the risk for CKD and associated complications in adults with PHPT,” they concluded.

The study was funded by the National Institute on Aging. The authors reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Early parathyroidectomy within 1 year of diagnosis of primary hyperparathyroidism (PHPT) did not reduce the risk of a sustained decline in kidney function, measured by a decline in estimated glomerular filtration rate (eGFR) of at least 50%, compared with observation (no surgery) in adults aged 60 and older.

Early parathyroidectomy was, however, associated with a reduced adjusted risk of this decline in kidney function in patients with newly diagnosed PHPT who were younger than age 60.

The findings, based on data from close to 43,000 veterans, were published online in Annals of Internal Medicine.

“The important takeaway from our study is that for older adults [age 60 or older] with primary hyperparathyroidism, preservation of kidney function should not be a primary consideration when making decisions about whether to undergo parathyroidectomy,” lead author Carolyn D. Seib, MD, told this news organization.

“It is important that physicians also discuss with their patients the potential long-term benefits of parathyroidectomy related to a reduced risk of fractures, kidney stones, and cardiovascular disease, and improved quality of life, in addition to the need for lifelong surveillance if surgery is declined, weighing these against an individual patient’s risk of surgery,” said Dr. Seib, a surgeon at Palo Alto (Calif.) VA Medical Center.

“However, in patients younger than 60, early parathyroidectomy may prevent progression to chronic kidney disease (CKD) and should be more strongly considered,” she noted.

Parathyroidectomy, she observed, is a low-risk outpatient surgery for most adults.

“Potential complications of surgery include temporary or permanent hoarseness, hypoparathyroidism (low postoperative parathyroid function), bleeding requiring return to the operating room, and complications related to general anesthesia, all of which are rare,” said Dr. Seib.

“Surgery by a high-volume surgeon is associated with a reduced risk of complications, so patients should seek out an experienced parathyroid surgeon,” she emphasized.  

Moreover, parathyroidectomy is the only treatment for primary hyperparathyroidism.
 

Does parathyroidectomy slow loss of kidney function?

Multidisciplinary guidelines recommend parathyroidectomy, at least in part to mitigate the risk for, and effects related to, the progression of CKD in patients with PHPT and an eGFR below 60 mL/min per 1.73 m², the researchers wrote.

However, whether parathyroidectomy slows the loss of kidney function in adults with PHPT is not clear.

Guidelines also state that “observation for PHPT disease progression can be considered when patients have no obvious end organ damage (i.e., eGFR > 60 mL/min per 1.73 m², normal bone mineral density, and no history of kidney stones or fractures),” Dr. Seib noted.  

To address the evidence gap, the researchers emulated a randomized target trial using observational data.

In this type of study, Dr. Seib explained, “although patients aren’t randomly assigned to a treatment, complex statistical methods are used to adjust for baseline confounders in an attempt to emulate random treatment assignment and account for bias that may affect the timing of when patients receive treatment.”

Using national Veterans Health Administration data, researchers identified 43,697 veterans with a new biochemical diagnosis of PHPT, defined as elevated parathyroid hormone (> 65 ng/mL) within 6 months of an elevated serum calcium level (> 32.55 mmol/L or >10.2 mg/dL), from 2000 to 2019.

Of these patients, 3,804 underwent parathyroidectomy within 1 year of diagnosis of PHPT, and 39,893 did not, and instead, a watchful waiting approach was adopted.

To be included in the analysis, patients had to have an eGFR above 30 mL/min per 1.73 m² for 12 months before PHPT diagnosis to exclude secondary or tertiary hyperparathyroidism.

The primary outcome was a sustained decline in eGFR of at least 50% from baseline.

In the overall cohort, patients had a mean pretreatment eGFR of 71.8 mL/min per 1.73 m². The mean age of patients was 67, 88% were men, and 68% were White.

After a median follow-up of 4.9 years, 6.7% of the patients had a decline in eGFR of at least 50%.

The cumulative incidence of this decline in eGFR was 5.1% at 5 years and 10.8% at 10 years in patients who had had early parathyroidectomy compared with 5.1% and 12.0%, respectively, in patients who did not undergo surgery.

In the overall population, the risk of at least a 50% decline in eGFR was similar in the early parathyroidectomy group versus the observation group (adjusted hazard ratio [HR], 0.98, 95% confidence interval [CI], 0.82-1.16).

However, diving deeper showed that parathyroidectomy was associated with a reduced risk of the primary outcome among patients younger than 60 years (adjusted HR, 0.75, 95% CI, 0.59-0.93) but not among those aged 60 or older (adjusted HR, 1.08, 95% CI, 0.87-1.34).

“When participating in shared decision-making for older adults [age 60 and older] with PHPT, clinicians should not consider parathyroidectomy for potential benefits of preservation of kidney function,” the researchers reiterated.

“For younger patients, clinicians should discuss the potential benefit of parathyroidectomy to reduce the risk for CKD and associated complications in adults with PHPT,” they concluded.

The study was funded by the National Institute on Aging. The authors reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

With more than 306 million views, #hormonebalance and #hormonebalancing are among the latest hacks to take over the social media platform TikTok, on which users post short videos. Influencers offer advice such as eating raw carrots for “happy hormones,” eating protein followed by fat for breakfast to regulate blood glucose, or taking vitamin B2 supplements for thyroid health.

Have you ever wondered if you were asleep during the lecture on “hormone balancing” in medical school? No, you weren’t. It was never a class for good reason, and you didn’t fail to read any such breakthrough studies in The New England Journal of Medicine either.

Although the sound bites no doubt garner attention among TikTok users, “hormone balancing” is a fictional term that is practically meaningless.

There are over 50 different hormones produced by humans and animals, regulating sleep, growth, metabolism and reproduction, among many other biological processes, so there is certainly no one-size-fits-all solution to ensure these are all working in perfect harmony.

When someone mentions “hormone balancing,” my mind wanders to the last time I took my car to have my tires rotated and balanced. If only it were as simple to balance hormones in real life. The best we can hope for is to get a specific hormone within the ideal physiologic range for that person’s age.

The term “hormone” can mean many things to different people. When a woman comes in with a hormone question, for example, it is often related to estrogen, followed by thyroid hormones. A wealth of misinformation exists in popular literature regarding these hormones alone.

Estrogen can be replaced, but not everyone needs it replaced. It depends on variables including age, underlying medical conditions, the time of day a test was drawn, and concomitant medications. Having low levels of a given hormone does not necessarily call for replacement either.

Insulin is another example of a hormone that can never completely be replaced in people with diabetes in a way that exactly mimics the normal physiologic release.

There are many lesser-known hormones that are measurable and replaceable but are also more difficult to reset to original manufacturer specifications.

A Google search for “hormone balancing” often sends you to “naturopaths” or “integrative medicine” practitioners, who often propose similar solutions to the TikTok influencers. Users are told that their hormones are out of whack and that restoring this “balance” can be achieved by purchasing whatever “natural products” or concoction they are selling.

These TikTok videos and online “experts” are the home-brewed versions of the strip-mall hormone specialists. TikTok videos claiming to help “balance hormones” typically don’t name a specific hormone either, or the end organs that each would have an impact on. Rather, they lump all hormones into a monolithic entity, implying that there is a single solution for all health problems. And personal testimonials extolling the benefits of a TikTok intervention don’t constitute proof of efficacy no matter how many “likes” they get. These influencers assume that viewers can “sense” their hormones are out of tune and no lab tests can convince them otherwise.

In these inflationary times, the cost of seeking medical care from conventional channels is increasingly prohibitive. It’s easy to understand the appeal of getting free advice from TikTok or some other Internet site. At best, following the advice will not have much impact; at worst, it could be harmful.
 

Don’t try this at home

There are some things that should never be tried at home, and do-it-yourself hormone replacement or remediation both fall under this umbrella.

Generally, the body does a good job of balancing its own hormones. Most patients don’t need to be worried if they’re in good health. If they’re in doubt, they should seek advice from a doctor, ideally an endocrinologist, but an ob.gyn. or general practitioner are also good options.

One of the first questions to ask a patient is “Which hormone are you worried about?” or “What health issue is it specifically that is bothering you?” Narrowing the focus to a single thing, if possible, will lead to a more efficient evaluation.

Often, patients arrive with multiple concerns written on little pieces of paper. These ubiquitous pieces of paper are the red flag for the flood of questions to follow.

Ordering the appropriate tests for the conditions they are concerned about can help put their minds at ease. If there are any specific deficiencies, or excesses in any hormones, then appropriate solutions can be discussed.

TikTok hormone-balancing solutions are simply the 21st-century version of the snake oil sold on late-night cable TV in the 1990s.

Needless to say, you should gently encourage your patients to stay away from these non–FDA-approved products, without making them feel stupid. Off-label use of hormones when these are not indicated is also to be avoided, unless a medical practitioner feels it is warranted.

Dr. de la Rosa is an endocrinologist in Englewood, Fla. He disclosed no conflicts of interest.

A version of this article first appeared on Medscape.com.

With more than 306 million views, #hormonebalance and #hormonebalancing are among the latest hacks to take over the social media platform TikTok, on which users post short videos. Influencers offer advice such as eating raw carrots for “happy hormones,” eating protein followed by fat for breakfast to regulate blood glucose, or taking vitamin B2 supplements for thyroid health.

Have you ever wondered if you were asleep during the lecture on “hormone balancing” in medical school? No, you weren’t. It was never a class for good reason, and you didn’t fail to read any such breakthrough studies in The New England Journal of Medicine either.

Although the sound bites no doubt garner attention among TikTok users, “hormone balancing” is a fictional term that is practically meaningless.

There are over 50 different hormones produced by humans and animals, regulating sleep, growth, metabolism and reproduction, among many other biological processes, so there is certainly no one-size-fits-all solution to ensure these are all working in perfect harmony.

When someone mentions “hormone balancing,” my mind wanders to the last time I took my car to have my tires rotated and balanced. If only it were as simple to balance hormones in real life. The best we can hope for is to get a specific hormone within the ideal physiologic range for that person’s age.

The term “hormone” can mean many things to different people. When a woman comes in with a hormone question, for example, it is often related to estrogen, followed by thyroid hormones. A wealth of misinformation exists in popular literature regarding these hormones alone.

Estrogen can be replaced, but not everyone needs it replaced. It depends on variables including age, underlying medical conditions, the time of day a test was drawn, and concomitant medications. Having low levels of a given hormone does not necessarily call for replacement either.

Insulin is another example of a hormone that can never completely be replaced in people with diabetes in a way that exactly mimics the normal physiologic release.

There are many lesser-known hormones that are measurable and replaceable but are also more difficult to reset to original manufacturer specifications.

A Google search for “hormone balancing” often sends you to “naturopaths” or “integrative medicine” practitioners, who often propose similar solutions to the TikTok influencers. Users are told that their hormones are out of whack and that restoring this “balance” can be achieved by purchasing whatever “natural products” or concoction they are selling.

These TikTok videos and online “experts” are the home-brewed versions of the strip-mall hormone specialists. TikTok videos claiming to help “balance hormones” typically don’t name a specific hormone either, or the end organs that each would have an impact on. Rather, they lump all hormones into a monolithic entity, implying that there is a single solution for all health problems. And personal testimonials extolling the benefits of a TikTok intervention don’t constitute proof of efficacy no matter how many “likes” they get. These influencers assume that viewers can “sense” their hormones are out of tune and no lab tests can convince them otherwise.

In these inflationary times, the cost of seeking medical care from conventional channels is increasingly prohibitive. It’s easy to understand the appeal of getting free advice from TikTok or some other Internet site. At best, following the advice will not have much impact; at worst, it could be harmful.
 

Don’t try this at home

There are some things that should never be tried at home, and do-it-yourself hormone replacement or remediation both fall under this umbrella.

Generally, the body does a good job of balancing its own hormones. Most patients don’t need to be worried if they’re in good health. If they’re in doubt, they should seek advice from a doctor, ideally an endocrinologist, but an ob.gyn. or general practitioner are also good options.

One of the first questions to ask a patient is “Which hormone are you worried about?” or “What health issue is it specifically that is bothering you?” Narrowing the focus to a single thing, if possible, will lead to a more efficient evaluation.

Often, patients arrive with multiple concerns written on little pieces of paper. These ubiquitous pieces of paper are the red flag for the flood of questions to follow.

Ordering the appropriate tests for the conditions they are concerned about can help put their minds at ease. If there are any specific deficiencies, or excesses in any hormones, then appropriate solutions can be discussed.

TikTok hormone-balancing solutions are simply the 21st-century version of the snake oil sold on late-night cable TV in the 1990s.

Needless to say, you should gently encourage your patients to stay away from these non–FDA-approved products, without making them feel stupid. Off-label use of hormones when these are not indicated is also to be avoided, unless a medical practitioner feels it is warranted.

Dr. de la Rosa is an endocrinologist in Englewood, Fla. He disclosed no conflicts of interest.

A version of this article first appeared on Medscape.com.

With more than 306 million views, #hormonebalance and #hormonebalancing are among the latest hacks to take over the social media platform TikTok, on which users post short videos. Influencers offer advice such as eating raw carrots for “happy hormones,” eating protein followed by fat for breakfast to regulate blood glucose, or taking vitamin B2 supplements for thyroid health.

Have you ever wondered if you were asleep during the lecture on “hormone balancing” in medical school? No, you weren’t. It was never a class for good reason, and you didn’t fail to read any such breakthrough studies in The New England Journal of Medicine either.

Although the sound bites no doubt garner attention among TikTok users, “hormone balancing” is a fictional term that is practically meaningless.

There are over 50 different hormones produced by humans and animals, regulating sleep, growth, metabolism and reproduction, among many other biological processes, so there is certainly no one-size-fits-all solution to ensure these are all working in perfect harmony.

When someone mentions “hormone balancing,” my mind wanders to the last time I took my car to have my tires rotated and balanced. If only it were as simple to balance hormones in real life. The best we can hope for is to get a specific hormone within the ideal physiologic range for that person’s age.

The term “hormone” can mean many things to different people. When a woman comes in with a hormone question, for example, it is often related to estrogen, followed by thyroid hormones. A wealth of misinformation exists in popular literature regarding these hormones alone.

Estrogen can be replaced, but not everyone needs it replaced. It depends on variables including age, underlying medical conditions, the time of day a test was drawn, and concomitant medications. Having low levels of a given hormone does not necessarily call for replacement either.

Insulin is another example of a hormone that can never completely be replaced in people with diabetes in a way that exactly mimics the normal physiologic release.

There are many lesser-known hormones that are measurable and replaceable but are also more difficult to reset to original manufacturer specifications.

A Google search for “hormone balancing” often sends you to “naturopaths” or “integrative medicine” practitioners, who often propose similar solutions to the TikTok influencers. Users are told that their hormones are out of whack and that restoring this “balance” can be achieved by purchasing whatever “natural products” or concoction they are selling.

These TikTok videos and online “experts” are the home-brewed versions of the strip-mall hormone specialists. TikTok videos claiming to help “balance hormones” typically don’t name a specific hormone either, or the end organs that each would have an impact on. Rather, they lump all hormones into a monolithic entity, implying that there is a single solution for all health problems. And personal testimonials extolling the benefits of a TikTok intervention don’t constitute proof of efficacy no matter how many “likes” they get. These influencers assume that viewers can “sense” their hormones are out of tune and no lab tests can convince them otherwise.

In these inflationary times, the cost of seeking medical care from conventional channels is increasingly prohibitive. It’s easy to understand the appeal of getting free advice from TikTok or some other Internet site. At best, following the advice will not have much impact; at worst, it could be harmful.
 

Don’t try this at home

There are some things that should never be tried at home, and do-it-yourself hormone replacement or remediation both fall under this umbrella.

Generally, the body does a good job of balancing its own hormones. Most patients don’t need to be worried if they’re in good health. If they’re in doubt, they should seek advice from a doctor, ideally an endocrinologist, but an ob.gyn. or general practitioner are also good options.

One of the first questions to ask a patient is “Which hormone are you worried about?” or “What health issue is it specifically that is bothering you?” Narrowing the focus to a single thing, if possible, will lead to a more efficient evaluation.

Often, patients arrive with multiple concerns written on little pieces of paper. These ubiquitous pieces of paper are the red flag for the flood of questions to follow.

Ordering the appropriate tests for the conditions they are concerned about can help put their minds at ease. If there are any specific deficiencies, or excesses in any hormones, then appropriate solutions can be discussed.

TikTok hormone-balancing solutions are simply the 21st-century version of the snake oil sold on late-night cable TV in the 1990s.

Needless to say, you should gently encourage your patients to stay away from these non–FDA-approved products, without making them feel stupid. Off-label use of hormones when these are not indicated is also to be avoided, unless a medical practitioner feels it is warranted.

Dr. de la Rosa is an endocrinologist in Englewood, Fla. He disclosed no conflicts of interest.

A version of this article first appeared on Medscape.com.

People who are physically active and on statins may have one less potential concern about the drugs. Despite their reputation for causing muscle injury, a study suggests statins won’t worsen the toll that sustained, moderately intensive exercise already takes on patients’ muscles.

Statin therapy in this prospective, controlled study wasn’t seen to aggravate normal muscle fatigue or pain from sustained exercise or adversely affect enzymes or other biomarkers associated with muscle injury.

The findings come from 100 individuals, of whom about two-thirds were on statins, participating in a public, 4-day, long-distance walking event held annually in the Netherlands. Results were published in the Journal of the American College of Cardiology with Neeltje A.E. Allard, MD, Radboud University Medical Center, Nijmegen, the Netherlands, as lead author.

For all of statins’ common use in adults with cardiovascular (CV) risk factors, the drugs are often blamed for causing excessive muscle pain or injury as a side effect. Yet there is a predominance of evidence to the contrary based on meta-analyses and clinical trials, suggesting that the drugs are taking the rap for many entirely unrelated muscle symptoms.

The new findings, from people ranging widely in fitness levels, suggest that “exercise of moderate intensity is feasible and safe” in statin users, that the drugs won’t exacerbate normal muscle symptoms from exercise, Dr. Allard told this news organization.

And that exercise doesn’t have to be on an unusual scale. Regular exercise in statin users can simply be consistent with broader guidelines, say 30 minutes of walking per day, she noted.

The study has such broad applicability, Dr. Allard said, because participants represented the spectrum of the thousands who signed up for the walking event, who varied in age, level of physical fitness, and number of CV risk factors. They included CV patients, the physically fit, “recreational walkers who didn’t really exercise regularly,” and “habitual nonexercisers.”

It enrolled three groups of participants in the Four Days Marches in Nijmegen, which in a typical year attracts tens of thousands of participants who walk up to 30 km, 40 km, or 50 km per day for 4 consecutive days.

They included 35 statin users who walked the event despite muscle symptoms, 34 on statins but without such symptoms, and 31 non–statin-using controls. Their mean ages ranged from 65 to 68 years.

Statin users were overwhelmingly on simvastatin or atorvastatin. The average statin therapy durations were 60 months and 96 months for those with and without symptoms, respectively.

Assessments were performed several days before the event, at baseline, and after the end of walking on days 1, 2, and 3.

Scores for muscle pain on the Brief Pain Inventory were higher at baseline for the symptomatic-on-statins group (P < .001) compared with the other two groups, and went up (P < .001) similarly across the three groups during each of the 3 days, the report notes. Fatigue scores on the Brief Fatigue Inventory followed the same pattern.

All biomarkers of muscle injury or stress were at comparable levels at baseline in the three groups and went up similarly (P < .001) with no significant differences at the end of day 3. Biomarkers included lactate dehydrogenase, creatine kinase, myoglobin, cardiac troponin I, and N-terminal pro-brain natriuretic peptide.

Statin-related reductions in levels of coenzyme Q 10 (CoQ10) have been thought to exacerbate muscle injury, the authors note. But levels of CoQ10 weren’t significantly different across the three groups at any point in the study, and they did not show any significant associations with measures of muscle injury, symptoms, or fatigue.

Patients with statin-associated muscle symptoms (SAMS) often limit physical activity because of muscle pain or weakness, but also “concerns that exercise will exacerbate muscle injury,” an accompanying editorial notes. “Therefore, exercise, a foundation of improving and maintaining cardiometabolic health, is often avoided or limited.”

But the current study, writes Robert S. Rosenson, MD, of Mount Sinai Heart, New York, indeed suggests that “many patients who develop SAMS may engage in a moderately intensive walking program without concern for worsened muscle biomarkers or performance.”

The exercise didn’t seem to improve muscle function in symptomatic statin users, compared with the other groups over the study’s very short follow-up, Dr. Rosenson observes. But “it remains uncertain from this study whether sustained exercise in SAMS patients will effectuate improved metabolic biomarkers or exercise capacity in the long term.”

Dr. Allard is supported by a grant from the Radboud Institute for Health Sciences; the other authors have disclosed no relevant financial relationships. Dr. Rosenson disclosed receiving research funding to his institution from Amgen, Arrowhead, Lilly, Novartis, and Regeneron; consulting fees from Amgen, Arrowhead, Lilly, Lipigon, Novartis, CRISPR Therapeutics, Precision BioSciences, Verve, Ultragenyx Pharmaceutical, and Regeneron; speaking fees from Amgen, Kowa, and Regeneron; and royalties from Wolters Kluwer (UpToDate); and that he holds stock in MediMergent.

A version of this article first appeared on Medscape.com.

People who are physically active and on statins may have one less potential concern about the drugs. Despite their reputation for causing muscle injury, a study suggests statins won’t worsen the toll that sustained, moderately intensive exercise already takes on patients’ muscles.

Statin therapy in this prospective, controlled study wasn’t seen to aggravate normal muscle fatigue or pain from sustained exercise or adversely affect enzymes or other biomarkers associated with muscle injury.

The findings come from 100 individuals, of whom about two-thirds were on statins, participating in a public, 4-day, long-distance walking event held annually in the Netherlands. Results were published in the Journal of the American College of Cardiology with Neeltje A.E. Allard, MD, Radboud University Medical Center, Nijmegen, the Netherlands, as lead author.

For all of statins’ common use in adults with cardiovascular (CV) risk factors, the drugs are often blamed for causing excessive muscle pain or injury as a side effect. Yet there is a predominance of evidence to the contrary based on meta-analyses and clinical trials, suggesting that the drugs are taking the rap for many entirely unrelated muscle symptoms.

The new findings, from people ranging widely in fitness levels, suggest that “exercise of moderate intensity is feasible and safe” in statin users, that the drugs won’t exacerbate normal muscle symptoms from exercise, Dr. Allard told this news organization.

And that exercise doesn’t have to be on an unusual scale. Regular exercise in statin users can simply be consistent with broader guidelines, say 30 minutes of walking per day, she noted.

The study has such broad applicability, Dr. Allard said, because participants represented the spectrum of the thousands who signed up for the walking event, who varied in age, level of physical fitness, and number of CV risk factors. They included CV patients, the physically fit, “recreational walkers who didn’t really exercise regularly,” and “habitual nonexercisers.”

It enrolled three groups of participants in the Four Days Marches in Nijmegen, which in a typical year attracts tens of thousands of participants who walk up to 30 km, 40 km, or 50 km per day for 4 consecutive days.

They included 35 statin users who walked the event despite muscle symptoms, 34 on statins but without such symptoms, and 31 non–statin-using controls. Their mean ages ranged from 65 to 68 years.

Statin users were overwhelmingly on simvastatin or atorvastatin. The average statin therapy durations were 60 months and 96 months for those with and without symptoms, respectively.

Assessments were performed several days before the event, at baseline, and after the end of walking on days 1, 2, and 3.

Scores for muscle pain on the Brief Pain Inventory were higher at baseline for the symptomatic-on-statins group (P < .001) compared with the other two groups, and went up (P < .001) similarly across the three groups during each of the 3 days, the report notes. Fatigue scores on the Brief Fatigue Inventory followed the same pattern.

All biomarkers of muscle injury or stress were at comparable levels at baseline in the three groups and went up similarly (P < .001) with no significant differences at the end of day 3. Biomarkers included lactate dehydrogenase, creatine kinase, myoglobin, cardiac troponin I, and N-terminal pro-brain natriuretic peptide.

Statin-related reductions in levels of coenzyme Q 10 (CoQ10) have been thought to exacerbate muscle injury, the authors note. But levels of CoQ10 weren’t significantly different across the three groups at any point in the study, and they did not show any significant associations with measures of muscle injury, symptoms, or fatigue.

Patients with statin-associated muscle symptoms (SAMS) often limit physical activity because of muscle pain or weakness, but also “concerns that exercise will exacerbate muscle injury,” an accompanying editorial notes. “Therefore, exercise, a foundation of improving and maintaining cardiometabolic health, is often avoided or limited.”

But the current study, writes Robert S. Rosenson, MD, of Mount Sinai Heart, New York, indeed suggests that “many patients who develop SAMS may engage in a moderately intensive walking program without concern for worsened muscle biomarkers or performance.”

The exercise didn’t seem to improve muscle function in symptomatic statin users, compared with the other groups over the study’s very short follow-up, Dr. Rosenson observes. But “it remains uncertain from this study whether sustained exercise in SAMS patients will effectuate improved metabolic biomarkers or exercise capacity in the long term.”

Dr. Allard is supported by a grant from the Radboud Institute for Health Sciences; the other authors have disclosed no relevant financial relationships. Dr. Rosenson disclosed receiving research funding to his institution from Amgen, Arrowhead, Lilly, Novartis, and Regeneron; consulting fees from Amgen, Arrowhead, Lilly, Lipigon, Novartis, CRISPR Therapeutics, Precision BioSciences, Verve, Ultragenyx Pharmaceutical, and Regeneron; speaking fees from Amgen, Kowa, and Regeneron; and royalties from Wolters Kluwer (UpToDate); and that he holds stock in MediMergent.

A version of this article first appeared on Medscape.com.

People who are physically active and on statins may have one less potential concern about the drugs. Despite their reputation for causing muscle injury, a study suggests statins won’t worsen the toll that sustained, moderately intensive exercise already takes on patients’ muscles.

Statin therapy in this prospective, controlled study wasn’t seen to aggravate normal muscle fatigue or pain from sustained exercise or adversely affect enzymes or other biomarkers associated with muscle injury.

The findings come from 100 individuals, of whom about two-thirds were on statins, participating in a public, 4-day, long-distance walking event held annually in the Netherlands. Results were published in the Journal of the American College of Cardiology with Neeltje A.E. Allard, MD, Radboud University Medical Center, Nijmegen, the Netherlands, as lead author.

For all of statins’ common use in adults with cardiovascular (CV) risk factors, the drugs are often blamed for causing excessive muscle pain or injury as a side effect. Yet there is a predominance of evidence to the contrary based on meta-analyses and clinical trials, suggesting that the drugs are taking the rap for many entirely unrelated muscle symptoms.

The new findings, from people ranging widely in fitness levels, suggest that “exercise of moderate intensity is feasible and safe” in statin users, that the drugs won’t exacerbate normal muscle symptoms from exercise, Dr. Allard told this news organization.

And that exercise doesn’t have to be on an unusual scale. Regular exercise in statin users can simply be consistent with broader guidelines, say 30 minutes of walking per day, she noted.

The study has such broad applicability, Dr. Allard said, because participants represented the spectrum of the thousands who signed up for the walking event, who varied in age, level of physical fitness, and number of CV risk factors. They included CV patients, the physically fit, “recreational walkers who didn’t really exercise regularly,” and “habitual nonexercisers.”

It enrolled three groups of participants in the Four Days Marches in Nijmegen, which in a typical year attracts tens of thousands of participants who walk up to 30 km, 40 km, or 50 km per day for 4 consecutive days.

They included 35 statin users who walked the event despite muscle symptoms, 34 on statins but without such symptoms, and 31 non–statin-using controls. Their mean ages ranged from 65 to 68 years.

Statin users were overwhelmingly on simvastatin or atorvastatin. The average statin therapy durations were 60 months and 96 months for those with and without symptoms, respectively.

Assessments were performed several days before the event, at baseline, and after the end of walking on days 1, 2, and 3.

Scores for muscle pain on the Brief Pain Inventory were higher at baseline for the symptomatic-on-statins group (P < .001) compared with the other two groups, and went up (P < .001) similarly across the three groups during each of the 3 days, the report notes. Fatigue scores on the Brief Fatigue Inventory followed the same pattern.

All biomarkers of muscle injury or stress were at comparable levels at baseline in the three groups and went up similarly (P < .001) with no significant differences at the end of day 3. Biomarkers included lactate dehydrogenase, creatine kinase, myoglobin, cardiac troponin I, and N-terminal pro-brain natriuretic peptide.

Statin-related reductions in levels of coenzyme Q 10 (CoQ10) have been thought to exacerbate muscle injury, the authors note. But levels of CoQ10 weren’t significantly different across the three groups at any point in the study, and they did not show any significant associations with measures of muscle injury, symptoms, or fatigue.

Patients with statin-associated muscle symptoms (SAMS) often limit physical activity because of muscle pain or weakness, but also “concerns that exercise will exacerbate muscle injury,” an accompanying editorial notes. “Therefore, exercise, a foundation of improving and maintaining cardiometabolic health, is often avoided or limited.”

But the current study, writes Robert S. Rosenson, MD, of Mount Sinai Heart, New York, indeed suggests that “many patients who develop SAMS may engage in a moderately intensive walking program without concern for worsened muscle biomarkers or performance.”

The exercise didn’t seem to improve muscle function in symptomatic statin users, compared with the other groups over the study’s very short follow-up, Dr. Rosenson observes. But “it remains uncertain from this study whether sustained exercise in SAMS patients will effectuate improved metabolic biomarkers or exercise capacity in the long term.”

Dr. Allard is supported by a grant from the Radboud Institute for Health Sciences; the other authors have disclosed no relevant financial relationships. Dr. Rosenson disclosed receiving research funding to his institution from Amgen, Arrowhead, Lilly, Novartis, and Regeneron; consulting fees from Amgen, Arrowhead, Lilly, Lipigon, Novartis, CRISPR Therapeutics, Precision BioSciences, Verve, Ultragenyx Pharmaceutical, and Regeneron; speaking fees from Amgen, Kowa, and Regeneron; and royalties from Wolters Kluwer (UpToDate); and that he holds stock in MediMergent.

A version of this article first appeared on Medscape.com.

A high salt intake is an important risk factor for atherosclerosis, even in the absence of hypertension, a large study from Sweden concludes.

jirkaejc/Getty Images

The study, including more than 10,000 individuals between the ages of 50 and 64 years from the Swedish Cardiopulmonary bioImage Study, showed a significant link between dietary salt intake and the risk for atherosclerotic lesions in the coronary and carotid arteries, even in participants with normal blood pressure and without known cardiovascular disease.

The finding suggests that salt could be a damaging factor in its own right before the development of hypertension, the authors write. The results were published online in European Heart Journal Open.

It has been known for a long time that salt is linked to hypertension, but the role that salt plays in atherosclerosis has not been examined, first author Jonas Wuopio, MD, Karolinska Institutet, Huddinge, and Clinical Research Center, Falun, Uppsala University, both in Sweden, told this news organization.

“Hardly anyone looks at changes in the arteries’ calcification, the atherosclerotic plaques and the association with salt intake,” Dr. Wuopio said. “We had this exclusive data from our cohort, so we wanted to use it to close this knowledge gap.”

The analysis included 10,788 adults aged 50-64 years, (average age, 58 years; 52% women) who underwent a coronary computed tomography angiography (CCTA) scan. The estimated 24-hour sodium excretion was used to measure sodium intake.

CCTA was used to obtain 3-D images of the coronary arteries to measure the degree of coronary artery calcium as well as detect stenosis in the coronary arteries. Participants also had an ultrasound of the carotid arteries.

After adjusting for age, sex, and study site (the study was done at Uppsala and Malmö, Sweden), the researchers found that rising salt consumption was linked with increasing atherosclerosis in a linear fashion in both the coronary and carotid arteries.

Each 1,000 mg rise in sodium excretion was associated with a 9% increased occurrence of carotid plaque (odds ratio, 1.09; P < .001; confidence interval, 1.06-1.12), a higher coronary artery calcium score (OR, 1.16; P < .001; CI, 1.12-1.19), and a 17% increased occurrence of coronary artery stenosis (OR, 1.17; P < .001; CI, 1.13-1.20).

The association was abolished, though, after adjusting for blood pressure, they note. Their “interpretation is that the increase in blood pressure from sodium intake, even below the level that currently defines arterial hypertension, is an important factor that mediates the interplay between salt intake and the atherosclerotic process,” they write. “As we observed an association in individuals with normal blood pressure, one possible explanation for these findings is that the detrimental pathological processes begin already prior to the development of hypertension,” they note, although they caution that no causal relationships can be gleaned from this cross-sectional study.

They also reported no sign of a “J-curve”; participants with the lowest levels of sodium excretion had the lowest occurrence of both coronary and carotid atherosclerosis, which contradicts findings in some studies that found very low sodium linked to increased cardiovascular disease–related events.

“There have been some controversies among researchers regarding very low intake, where some say very low salt intake can increase the risk of cardiovascular disease, but we could not find this in this study,” Dr. Wuopio said.

“Our study is confirming that excess salt is not a good thing, but the fact that it is linked to atherosclerosis, even in the absence of hypertension, was a bit of a surprise,” he said.

“I will be telling my patients to follow the advice given by the World Health Organization and other medical societies, to limit your intake of salt to approximately 1 teaspoon, even if your blood pressure is normal.”


 

Time to scrutinize salt’s role in atherosclerosis

In an accompanying editorial, Maciej Banach, MD, Medical University of Lodz, and Stanislaw Surma, MD, Faculty of Medical Sciences in Katowice, both in Poland, write that excessive dietary salt intake is a well-documented cardiovascular risk factor, and that the association is explained in most studies by increased blood pressure.

“We should look more extensively on the role of dietary salt, as it affects many pathological mechanisms, by which, especially with the coexistence of other risk factors, atherosclerosis may progress very fast,” they write.

“The results of the study shed new light on the direct relationship between excessive dietary salt intake and the risk of ASCVD [atherosclerotic cardiovascular disease], indicating that salt intake might be a risk factor for atherosclerosis even prior to the development of hypertension,” they conclude.
 

Confirmatory and novel

“Nobody questions the fact that high blood pressure is a powerful risk factor for atherosclerotic disease, but not all studies have suggested that, at least at significantly higher levels of sodium intake, that high salt intake tracks with risk for atherosclerotic disease,” Alon Gitig, MD, assistant professor and director of cardiology, Mount Sinai Doctors-Westchester, Yonkers, New York, told this news organization.

Most of the studies of salt intake in the diet are based on patient self-reports via food frequency questionnaires, which can give a general idea of salt intake, but are often not totally accurate, Dr. Gitig said.

“Here, they measured sodium in the urine and estimated the 24-hour salt intake from that, which is slightly novel,” he said.

Everybody knows that high blood pressure is associated with future cardiovascular disease risk, but what many don’t realize is that that risk starts to increase slightly but significantly above a blood pressure that is already in the range of 115 mm Hg/75 mm Hg, he said.

“The lower you can get your blood pressure down, to around 115-120, the lower your risk for cardiovascular disease,” Dr. Gitig said.

It is possible for most people to lower blood pressure through attention to diet, restricting sodium, performing cardio and weight training exercises, and maintaining a healthy weight, he said.

An example of a cardiovascular health diet is the Dietary Approaches to Stop Hypertension (DASH) diet.

“The DASH diet, consisting of 9 servings of fruits and vegetables a day with few refined carbs, flour and sugar, has been shown in a randomized trial to dramatically reduce blood pressure. There are two reasons for that. One is that the fruits and vegetables have many phytonutrients that are good for arteries. The other is that a large proportion of U.S. adults have insulin resistance, which leads to high blood pressure.  

“The more fruits and vegetables and healthy animal products, and less sugar and flour, the more you are going to improve your insulin resistance, so you can bring your blood pressure down that way,” Dr. Gitig said.

The study was funded by the Swedish Heart-Lung Foundation, the Knut and Alice Wallenberg Foundation, the Swedish Research Council and Vinnova (Sweden’s Innovation agency), the University of Gothenburg and Sahlgrenska University Hospital, the Karolinska Institutet and Stockholm County Council, the Linköping University and University Hospital, the Lund University and Skane University Hospital, the Umea University and University Hospital, and the Uppsala University and University Hospital. Dr. Wuopio and Dr. Gitig report no relevant financial relationships. Dr. Banach reports financial relationships with Adamed, Amgen, Daichii Sankyo, Esperion, KrKa, NewAmsterdam, Polpharma, Novartis, Pfizer, Sanofi, Teva, Viatris, and CMDO at Longevity Group (LU). Dr. Surma reports a financial relationship with Sanofi and Novartis.

A version of this article first appeared on Medscape.com.

A high salt intake is an important risk factor for atherosclerosis, even in the absence of hypertension, a large study from Sweden concludes.

jirkaejc/Getty Images

The study, including more than 10,000 individuals between the ages of 50 and 64 years from the Swedish Cardiopulmonary bioImage Study, showed a significant link between dietary salt intake and the risk for atherosclerotic lesions in the coronary and carotid arteries, even in participants with normal blood pressure and without known cardiovascular disease.

The finding suggests that salt could be a damaging factor in its own right before the development of hypertension, the authors write. The results were published online in European Heart Journal Open.

It has been known for a long time that salt is linked to hypertension, but the role that salt plays in atherosclerosis has not been examined, first author Jonas Wuopio, MD, Karolinska Institutet, Huddinge, and Clinical Research Center, Falun, Uppsala University, both in Sweden, told this news organization.

“Hardly anyone looks at changes in the arteries’ calcification, the atherosclerotic plaques and the association with salt intake,” Dr. Wuopio said. “We had this exclusive data from our cohort, so we wanted to use it to close this knowledge gap.”

The analysis included 10,788 adults aged 50-64 years, (average age, 58 years; 52% women) who underwent a coronary computed tomography angiography (CCTA) scan. The estimated 24-hour sodium excretion was used to measure sodium intake.

CCTA was used to obtain 3-D images of the coronary arteries to measure the degree of coronary artery calcium as well as detect stenosis in the coronary arteries. Participants also had an ultrasound of the carotid arteries.

After adjusting for age, sex, and study site (the study was done at Uppsala and Malmö, Sweden), the researchers found that rising salt consumption was linked with increasing atherosclerosis in a linear fashion in both the coronary and carotid arteries.

Each 1,000 mg rise in sodium excretion was associated with a 9% increased occurrence of carotid plaque (odds ratio, 1.09; P < .001; confidence interval, 1.06-1.12), a higher coronary artery calcium score (OR, 1.16; P < .001; CI, 1.12-1.19), and a 17% increased occurrence of coronary artery stenosis (OR, 1.17; P < .001; CI, 1.13-1.20).

The association was abolished, though, after adjusting for blood pressure, they note. Their “interpretation is that the increase in blood pressure from sodium intake, even below the level that currently defines arterial hypertension, is an important factor that mediates the interplay between salt intake and the atherosclerotic process,” they write. “As we observed an association in individuals with normal blood pressure, one possible explanation for these findings is that the detrimental pathological processes begin already prior to the development of hypertension,” they note, although they caution that no causal relationships can be gleaned from this cross-sectional study.

They also reported no sign of a “J-curve”; participants with the lowest levels of sodium excretion had the lowest occurrence of both coronary and carotid atherosclerosis, which contradicts findings in some studies that found very low sodium linked to increased cardiovascular disease–related events.

“There have been some controversies among researchers regarding very low intake, where some say very low salt intake can increase the risk of cardiovascular disease, but we could not find this in this study,” Dr. Wuopio said.

“Our study is confirming that excess salt is not a good thing, but the fact that it is linked to atherosclerosis, even in the absence of hypertension, was a bit of a surprise,” he said.

“I will be telling my patients to follow the advice given by the World Health Organization and other medical societies, to limit your intake of salt to approximately 1 teaspoon, even if your blood pressure is normal.”


 

Time to scrutinize salt’s role in atherosclerosis

In an accompanying editorial, Maciej Banach, MD, Medical University of Lodz, and Stanislaw Surma, MD, Faculty of Medical Sciences in Katowice, both in Poland, write that excessive dietary salt intake is a well-documented cardiovascular risk factor, and that the association is explained in most studies by increased blood pressure.

“We should look more extensively on the role of dietary salt, as it affects many pathological mechanisms, by which, especially with the coexistence of other risk factors, atherosclerosis may progress very fast,” they write.

“The results of the study shed new light on the direct relationship between excessive dietary salt intake and the risk of ASCVD [atherosclerotic cardiovascular disease], indicating that salt intake might be a risk factor for atherosclerosis even prior to the development of hypertension,” they conclude.
 

Confirmatory and novel

“Nobody questions the fact that high blood pressure is a powerful risk factor for atherosclerotic disease, but not all studies have suggested that, at least at significantly higher levels of sodium intake, that high salt intake tracks with risk for atherosclerotic disease,” Alon Gitig, MD, assistant professor and director of cardiology, Mount Sinai Doctors-Westchester, Yonkers, New York, told this news organization.

Most of the studies of salt intake in the diet are based on patient self-reports via food frequency questionnaires, which can give a general idea of salt intake, but are often not totally accurate, Dr. Gitig said.

“Here, they measured sodium in the urine and estimated the 24-hour salt intake from that, which is slightly novel,” he said.

Everybody knows that high blood pressure is associated with future cardiovascular disease risk, but what many don’t realize is that that risk starts to increase slightly but significantly above a blood pressure that is already in the range of 115 mm Hg/75 mm Hg, he said.

“The lower you can get your blood pressure down, to around 115-120, the lower your risk for cardiovascular disease,” Dr. Gitig said.

It is possible for most people to lower blood pressure through attention to diet, restricting sodium, performing cardio and weight training exercises, and maintaining a healthy weight, he said.

An example of a cardiovascular health diet is the Dietary Approaches to Stop Hypertension (DASH) diet.

“The DASH diet, consisting of 9 servings of fruits and vegetables a day with few refined carbs, flour and sugar, has been shown in a randomized trial to dramatically reduce blood pressure. There are two reasons for that. One is that the fruits and vegetables have many phytonutrients that are good for arteries. The other is that a large proportion of U.S. adults have insulin resistance, which leads to high blood pressure.  

“The more fruits and vegetables and healthy animal products, and less sugar and flour, the more you are going to improve your insulin resistance, so you can bring your blood pressure down that way,” Dr. Gitig said.

The study was funded by the Swedish Heart-Lung Foundation, the Knut and Alice Wallenberg Foundation, the Swedish Research Council and Vinnova (Sweden’s Innovation agency), the University of Gothenburg and Sahlgrenska University Hospital, the Karolinska Institutet and Stockholm County Council, the Linköping University and University Hospital, the Lund University and Skane University Hospital, the Umea University and University Hospital, and the Uppsala University and University Hospital. Dr. Wuopio and Dr. Gitig report no relevant financial relationships. Dr. Banach reports financial relationships with Adamed, Amgen, Daichii Sankyo, Esperion, KrKa, NewAmsterdam, Polpharma, Novartis, Pfizer, Sanofi, Teva, Viatris, and CMDO at Longevity Group (LU). Dr. Surma reports a financial relationship with Sanofi and Novartis.

A version of this article first appeared on Medscape.com.

A high salt intake is an important risk factor for atherosclerosis, even in the absence of hypertension, a large study from Sweden concludes.

jirkaejc/Getty Images

The study, including more than 10,000 individuals between the ages of 50 and 64 years from the Swedish Cardiopulmonary bioImage Study, showed a significant link between dietary salt intake and the risk for atherosclerotic lesions in the coronary and carotid arteries, even in participants with normal blood pressure and without known cardiovascular disease.

The finding suggests that salt could be a damaging factor in its own right before the development of hypertension, the authors write. The results were published online in European Heart Journal Open.

It has been known for a long time that salt is linked to hypertension, but the role that salt plays in atherosclerosis has not been examined, first author Jonas Wuopio, MD, Karolinska Institutet, Huddinge, and Clinical Research Center, Falun, Uppsala University, both in Sweden, told this news organization.

“Hardly anyone looks at changes in the arteries’ calcification, the atherosclerotic plaques and the association with salt intake,” Dr. Wuopio said. “We had this exclusive data from our cohort, so we wanted to use it to close this knowledge gap.”

The analysis included 10,788 adults aged 50-64 years, (average age, 58 years; 52% women) who underwent a coronary computed tomography angiography (CCTA) scan. The estimated 24-hour sodium excretion was used to measure sodium intake.

CCTA was used to obtain 3-D images of the coronary arteries to measure the degree of coronary artery calcium as well as detect stenosis in the coronary arteries. Participants also had an ultrasound of the carotid arteries.

After adjusting for age, sex, and study site (the study was done at Uppsala and Malmö, Sweden), the researchers found that rising salt consumption was linked with increasing atherosclerosis in a linear fashion in both the coronary and carotid arteries.

Each 1,000 mg rise in sodium excretion was associated with a 9% increased occurrence of carotid plaque (odds ratio, 1.09; P < .001; confidence interval, 1.06-1.12), a higher coronary artery calcium score (OR, 1.16; P < .001; CI, 1.12-1.19), and a 17% increased occurrence of coronary artery stenosis (OR, 1.17; P < .001; CI, 1.13-1.20).

The association was abolished, though, after adjusting for blood pressure, they note. Their “interpretation is that the increase in blood pressure from sodium intake, even below the level that currently defines arterial hypertension, is an important factor that mediates the interplay between salt intake and the atherosclerotic process,” they write. “As we observed an association in individuals with normal blood pressure, one possible explanation for these findings is that the detrimental pathological processes begin already prior to the development of hypertension,” they note, although they caution that no causal relationships can be gleaned from this cross-sectional study.

They also reported no sign of a “J-curve”; participants with the lowest levels of sodium excretion had the lowest occurrence of both coronary and carotid atherosclerosis, which contradicts findings in some studies that found very low sodium linked to increased cardiovascular disease–related events.

“There have been some controversies among researchers regarding very low intake, where some say very low salt intake can increase the risk of cardiovascular disease, but we could not find this in this study,” Dr. Wuopio said.

“Our study is confirming that excess salt is not a good thing, but the fact that it is linked to atherosclerosis, even in the absence of hypertension, was a bit of a surprise,” he said.

“I will be telling my patients to follow the advice given by the World Health Organization and other medical societies, to limit your intake of salt to approximately 1 teaspoon, even if your blood pressure is normal.”


 

Time to scrutinize salt’s role in atherosclerosis

In an accompanying editorial, Maciej Banach, MD, Medical University of Lodz, and Stanislaw Surma, MD, Faculty of Medical Sciences in Katowice, both in Poland, write that excessive dietary salt intake is a well-documented cardiovascular risk factor, and that the association is explained in most studies by increased blood pressure.

“We should look more extensively on the role of dietary salt, as it affects many pathological mechanisms, by which, especially with the coexistence of other risk factors, atherosclerosis may progress very fast,” they write.

“The results of the study shed new light on the direct relationship between excessive dietary salt intake and the risk of ASCVD [atherosclerotic cardiovascular disease], indicating that salt intake might be a risk factor for atherosclerosis even prior to the development of hypertension,” they conclude.
 

Confirmatory and novel

“Nobody questions the fact that high blood pressure is a powerful risk factor for atherosclerotic disease, but not all studies have suggested that, at least at significantly higher levels of sodium intake, that high salt intake tracks with risk for atherosclerotic disease,” Alon Gitig, MD, assistant professor and director of cardiology, Mount Sinai Doctors-Westchester, Yonkers, New York, told this news organization.

Most of the studies of salt intake in the diet are based on patient self-reports via food frequency questionnaires, which can give a general idea of salt intake, but are often not totally accurate, Dr. Gitig said.

“Here, they measured sodium in the urine and estimated the 24-hour salt intake from that, which is slightly novel,” he said.

Everybody knows that high blood pressure is associated with future cardiovascular disease risk, but what many don’t realize is that that risk starts to increase slightly but significantly above a blood pressure that is already in the range of 115 mm Hg/75 mm Hg, he said.

“The lower you can get your blood pressure down, to around 115-120, the lower your risk for cardiovascular disease,” Dr. Gitig said.

It is possible for most people to lower blood pressure through attention to diet, restricting sodium, performing cardio and weight training exercises, and maintaining a healthy weight, he said.

An example of a cardiovascular health diet is the Dietary Approaches to Stop Hypertension (DASH) diet.

“The DASH diet, consisting of 9 servings of fruits and vegetables a day with few refined carbs, flour and sugar, has been shown in a randomized trial to dramatically reduce blood pressure. There are two reasons for that. One is that the fruits and vegetables have many phytonutrients that are good for arteries. The other is that a large proportion of U.S. adults have insulin resistance, which leads to high blood pressure.  

“The more fruits and vegetables and healthy animal products, and less sugar and flour, the more you are going to improve your insulin resistance, so you can bring your blood pressure down that way,” Dr. Gitig said.

The study was funded by the Swedish Heart-Lung Foundation, the Knut and Alice Wallenberg Foundation, the Swedish Research Council and Vinnova (Sweden’s Innovation agency), the University of Gothenburg and Sahlgrenska University Hospital, the Karolinska Institutet and Stockholm County Council, the Linköping University and University Hospital, the Lund University and Skane University Hospital, the Umea University and University Hospital, and the Uppsala University and University Hospital. Dr. Wuopio and Dr. Gitig report no relevant financial relationships. Dr. Banach reports financial relationships with Adamed, Amgen, Daichii Sankyo, Esperion, KrKa, NewAmsterdam, Polpharma, Novartis, Pfizer, Sanofi, Teva, Viatris, and CMDO at Longevity Group (LU). Dr. Surma reports a financial relationship with Sanofi and Novartis.

A version of this article first appeared on Medscape.com.

A new study provides the first comprehensive safety profile of sodium-glucose cotransporter 2 (SGLT2) inhibitors in U.S. patients with chronic kidney disease (CKD) and type 2 diabetes receiving routine care and suggests that the benefits outweigh the risks.

Starting therapy with an SGLT2 inhibitor versus a glucagon-like peptide-1 (GLP-1) receptor agonist was associated with more lower limb amputations, nonvertebral fractures, and genital infections, but these risks need to be balanced against cardiovascular and renoprotective benefits, according to the researchers.

The analysis showed that there would be 2.1 more lower limb amputations, 2.5 more nonvertebral fractures, and 41 more genital infections per 1,000 patients per year among those receiving SGLT2 inhibitors versus an equal number of patients receiving GLP-1 agonists, lead author Edouard Fu, PhD, explained to this news organization in an email.

“On the other hand, we know from the evidence from randomized controlled trials that taking an SGLT2 inhibitor compared with placebo lowers the risk of developing kidney failure,” said Dr. Fu, who is a research fellow in the division of pharmacoepidemiology and pharmacoeconomics at Brigham and Women’s Hospital, Boston.

“For instance,” he continued, “in the DAPA-CKD clinical trial, dapagliflozin versus placebo led to 29 fewer events per 1,000 patients per year of the composite outcome (50% decline in estimated glomerular filtration rate [eGFR], kidney failure, cardiovascular or kidney death).”

In the CREDENCE trial, canagliflozin versus placebo led to 18 fewer events per 1,000 person-years for the composite outcome of doubling of serum creatinine, kidney failure, and cardiovascular or kidney death.

And in the EMPA-KIDNEY study, empagliflozin versus placebo led to 21 fewer events per 1,000 person-years for the composite outcome of progression of kidney disease or cardiovascular death.

“Thus, benefits would still outweigh the risks,” Dr. Fu emphasized.
 

‘Quantifies absolute rate of events among routine care patients’

“The importance of our paper,” he summarized, “is that it quantifies the absolute rate of events among routine care patients and may be used to inform shared decision-making.”

The analysis also found that the risks of diabetic ketoacidosis (DKA), hypovolemia, hypoglycemia, and severe urinary tract infection (UTI) were similar with SGLT2 inhibitors versus GLP-1 agonists, but the risk of developing acute kidney injury (AKI) was lower with an SGLT2 inhibitor.

“Our study can help inform patient-physician decision-making regarding risks and benefits before prescribing SGLT2 inhibitors in this population” of patients with CKD and diabetes treated in clinical practice, the researchers conclude, “but needs to be interpreted in light of its limitations, including residual confounding, short follow-up time, and the use of diagnosis codes to identify patients with CKD.”

The study was recently published in the Clinical Journal of the American Society of Nephrology.
 

Slow uptake, safety concerns

SGLT2 inhibitors are recommended as first-line therapy in patients with type 2 diabetes and CKD who have an eGFR equal to or greater than 20 mL/min per 1.73 m², and thus are at high risk for cardiovascular disease and kidney disease progression, Dr. Fu and colleagues write.

However, studies report that as few as 6% of patients with CKD and type 2 diabetes are currently prescribed SGLT2 inhibitors in the United States.

This slow uptake of SGLT2 inhibitors among patients with CKD may be partly due to concerns about DKA, fractures, amputations, and urogenital infections observed in clinical trials.

However, such trials are generally underpowered to assess rare adverse events, use monitoring protocols to lower the risk of adverse events, and include a highly selected patient population, and so safety in routine clinical practice is often unclear.

To examine this, the researchers identified health insurance claims data from 96,128 individuals (from Optum, IBM MarketScan, and Medicare databases) who were 18 years or older (65 years or older for Medicare) and had type 2 diabetes and at least one inpatient or two outpatient diagnostic codes for stage 3 or 4 CKD.

Of these patients, 32,192 had a newly filled prescription for an SGLT2 inhibitor (empagliflozin, dapagliflozin, canagliflozin, or ertugliflozin) and 63,936 had a newly filled prescription for a GLP-1 agonist (liraglutide, dulaglutide, semaglutide, exenatide, albiglutide, or lixisenatide) between April 2013, when the first SGLT2 inhibitor was available in the United States, and 2021.

The researchers matched 28,847 individuals who were initiated on an SGLT2 inhibitor with an equal number who were initiated on a GLP-1 agonist, based on propensity scores, adjusting for more than 120 baseline characteristics.

Safety outcomes were based on previously identified potential safety signals.

Patients who were initiated on an SGLT2 inhibitor had 1.30-fold, 2.13-fold, and 3.08-fold higher risks of having a nonvertebral fracture, a lower limb amputation, and a genital infection, respectively, compared with patients who were initiated on a GLP-1 agonist, after a mean on-treatment time of 7.5 months,

Risks of DKA, hypovolemia, hypoglycemia, and severe UTI were similar in both groups.

Patients initiated on an SGLT2 inhibitor versus a GLP-1 agonist had a lower risk of AKI (hazard ratio, 0.93) equivalent to 6.75 fewer cases of AKI per 1,000 patients per year.

Patients had higher risks for lower limb amputation, genital infections, and nonvertebral fractures with SGLT2 inhibitors versus GLP-1 agonists across most of the prespecified subgroups by age, sex, cardiovascular disease, heart failure, and use of metformin, insulin, or sulfonylurea, but with wider confidence intervals.

Dr. Fu was supported by a Rubicon grant from the Dutch Research Council and has reported no relevant financial relationships. Disclosures for the other authors are listed with the article.

A version of this article originally appeared on Medscape.com.

A new study provides the first comprehensive safety profile of sodium-glucose cotransporter 2 (SGLT2) inhibitors in U.S. patients with chronic kidney disease (CKD) and type 2 diabetes receiving routine care and suggests that the benefits outweigh the risks.

Starting therapy with an SGLT2 inhibitor versus a glucagon-like peptide-1 (GLP-1) receptor agonist was associated with more lower limb amputations, nonvertebral fractures, and genital infections, but these risks need to be balanced against cardiovascular and renoprotective benefits, according to the researchers.

The analysis showed that there would be 2.1 more lower limb amputations, 2.5 more nonvertebral fractures, and 41 more genital infections per 1,000 patients per year among those receiving SGLT2 inhibitors versus an equal number of patients receiving GLP-1 agonists, lead author Edouard Fu, PhD, explained to this news organization in an email.

“On the other hand, we know from the evidence from randomized controlled trials that taking an SGLT2 inhibitor compared with placebo lowers the risk of developing kidney failure,” said Dr. Fu, who is a research fellow in the division of pharmacoepidemiology and pharmacoeconomics at Brigham and Women’s Hospital, Boston.

“For instance,” he continued, “in the DAPA-CKD clinical trial, dapagliflozin versus placebo led to 29 fewer events per 1,000 patients per year of the composite outcome (50% decline in estimated glomerular filtration rate [eGFR], kidney failure, cardiovascular or kidney death).”

In the CREDENCE trial, canagliflozin versus placebo led to 18 fewer events per 1,000 person-years for the composite outcome of doubling of serum creatinine, kidney failure, and cardiovascular or kidney death.

And in the EMPA-KIDNEY study, empagliflozin versus placebo led to 21 fewer events per 1,000 person-years for the composite outcome of progression of kidney disease or cardiovascular death.

“Thus, benefits would still outweigh the risks,” Dr. Fu emphasized.
 

‘Quantifies absolute rate of events among routine care patients’

“The importance of our paper,” he summarized, “is that it quantifies the absolute rate of events among routine care patients and may be used to inform shared decision-making.”

The analysis also found that the risks of diabetic ketoacidosis (DKA), hypovolemia, hypoglycemia, and severe urinary tract infection (UTI) were similar with SGLT2 inhibitors versus GLP-1 agonists, but the risk of developing acute kidney injury (AKI) was lower with an SGLT2 inhibitor.

“Our study can help inform patient-physician decision-making regarding risks and benefits before prescribing SGLT2 inhibitors in this population” of patients with CKD and diabetes treated in clinical practice, the researchers conclude, “but needs to be interpreted in light of its limitations, including residual confounding, short follow-up time, and the use of diagnosis codes to identify patients with CKD.”

The study was recently published in the Clinical Journal of the American Society of Nephrology.
 

Slow uptake, safety concerns

SGLT2 inhibitors are recommended as first-line therapy in patients with type 2 diabetes and CKD who have an eGFR equal to or greater than 20 mL/min per 1.73 m², and thus are at high risk for cardiovascular disease and kidney disease progression, Dr. Fu and colleagues write.

However, studies report that as few as 6% of patients with CKD and type 2 diabetes are currently prescribed SGLT2 inhibitors in the United States.

This slow uptake of SGLT2 inhibitors among patients with CKD may be partly due to concerns about DKA, fractures, amputations, and urogenital infections observed in clinical trials.

However, such trials are generally underpowered to assess rare adverse events, use monitoring protocols to lower the risk of adverse events, and include a highly selected patient population, and so safety in routine clinical practice is often unclear.

To examine this, the researchers identified health insurance claims data from 96,128 individuals (from Optum, IBM MarketScan, and Medicare databases) who were 18 years or older (65 years or older for Medicare) and had type 2 diabetes and at least one inpatient or two outpatient diagnostic codes for stage 3 or 4 CKD.

Of these patients, 32,192 had a newly filled prescription for an SGLT2 inhibitor (empagliflozin, dapagliflozin, canagliflozin, or ertugliflozin) and 63,936 had a newly filled prescription for a GLP-1 agonist (liraglutide, dulaglutide, semaglutide, exenatide, albiglutide, or lixisenatide) between April 2013, when the first SGLT2 inhibitor was available in the United States, and 2021.

The researchers matched 28,847 individuals who were initiated on an SGLT2 inhibitor with an equal number who were initiated on a GLP-1 agonist, based on propensity scores, adjusting for more than 120 baseline characteristics.

Safety outcomes were based on previously identified potential safety signals.

Patients who were initiated on an SGLT2 inhibitor had 1.30-fold, 2.13-fold, and 3.08-fold higher risks of having a nonvertebral fracture, a lower limb amputation, and a genital infection, respectively, compared with patients who were initiated on a GLP-1 agonist, after a mean on-treatment time of 7.5 months,

Risks of DKA, hypovolemia, hypoglycemia, and severe UTI were similar in both groups.

Patients initiated on an SGLT2 inhibitor versus a GLP-1 agonist had a lower risk of AKI (hazard ratio, 0.93) equivalent to 6.75 fewer cases of AKI per 1,000 patients per year.

Patients had higher risks for lower limb amputation, genital infections, and nonvertebral fractures with SGLT2 inhibitors versus GLP-1 agonists across most of the prespecified subgroups by age, sex, cardiovascular disease, heart failure, and use of metformin, insulin, or sulfonylurea, but with wider confidence intervals.

Dr. Fu was supported by a Rubicon grant from the Dutch Research Council and has reported no relevant financial relationships. Disclosures for the other authors are listed with the article.

A version of this article originally appeared on Medscape.com.

A new study provides the first comprehensive safety profile of sodium-glucose cotransporter 2 (SGLT2) inhibitors in U.S. patients with chronic kidney disease (CKD) and type 2 diabetes receiving routine care and suggests that the benefits outweigh the risks.

Starting therapy with an SGLT2 inhibitor versus a glucagon-like peptide-1 (GLP-1) receptor agonist was associated with more lower limb amputations, nonvertebral fractures, and genital infections, but these risks need to be balanced against cardiovascular and renoprotective benefits, according to the researchers.

The analysis showed that there would be 2.1 more lower limb amputations, 2.5 more nonvertebral fractures, and 41 more genital infections per 1,000 patients per year among those receiving SGLT2 inhibitors versus an equal number of patients receiving GLP-1 agonists, lead author Edouard Fu, PhD, explained to this news organization in an email.

“On the other hand, we know from the evidence from randomized controlled trials that taking an SGLT2 inhibitor compared with placebo lowers the risk of developing kidney failure,” said Dr. Fu, who is a research fellow in the division of pharmacoepidemiology and pharmacoeconomics at Brigham and Women’s Hospital, Boston.

“For instance,” he continued, “in the DAPA-CKD clinical trial, dapagliflozin versus placebo led to 29 fewer events per 1,000 patients per year of the composite outcome (50% decline in estimated glomerular filtration rate [eGFR], kidney failure, cardiovascular or kidney death).”

In the CREDENCE trial, canagliflozin versus placebo led to 18 fewer events per 1,000 person-years for the composite outcome of doubling of serum creatinine, kidney failure, and cardiovascular or kidney death.

And in the EMPA-KIDNEY study, empagliflozin versus placebo led to 21 fewer events per 1,000 person-years for the composite outcome of progression of kidney disease or cardiovascular death.

“Thus, benefits would still outweigh the risks,” Dr. Fu emphasized.
 

‘Quantifies absolute rate of events among routine care patients’

“The importance of our paper,” he summarized, “is that it quantifies the absolute rate of events among routine care patients and may be used to inform shared decision-making.”

The analysis also found that the risks of diabetic ketoacidosis (DKA), hypovolemia, hypoglycemia, and severe urinary tract infection (UTI) were similar with SGLT2 inhibitors versus GLP-1 agonists, but the risk of developing acute kidney injury (AKI) was lower with an SGLT2 inhibitor.

“Our study can help inform patient-physician decision-making regarding risks and benefits before prescribing SGLT2 inhibitors in this population” of patients with CKD and diabetes treated in clinical practice, the researchers conclude, “but needs to be interpreted in light of its limitations, including residual confounding, short follow-up time, and the use of diagnosis codes to identify patients with CKD.”

The study was recently published in the Clinical Journal of the American Society of Nephrology.
 

Slow uptake, safety concerns

SGLT2 inhibitors are recommended as first-line therapy in patients with type 2 diabetes and CKD who have an eGFR equal to or greater than 20 mL/min per 1.73 m², and thus are at high risk for cardiovascular disease and kidney disease progression, Dr. Fu and colleagues write.

However, studies report that as few as 6% of patients with CKD and type 2 diabetes are currently prescribed SGLT2 inhibitors in the United States.

This slow uptake of SGLT2 inhibitors among patients with CKD may be partly due to concerns about DKA, fractures, amputations, and urogenital infections observed in clinical trials.

However, such trials are generally underpowered to assess rare adverse events, use monitoring protocols to lower the risk of adverse events, and include a highly selected patient population, and so safety in routine clinical practice is often unclear.

To examine this, the researchers identified health insurance claims data from 96,128 individuals (from Optum, IBM MarketScan, and Medicare databases) who were 18 years or older (65 years or older for Medicare) and had type 2 diabetes and at least one inpatient or two outpatient diagnostic codes for stage 3 or 4 CKD.

Of these patients, 32,192 had a newly filled prescription for an SGLT2 inhibitor (empagliflozin, dapagliflozin, canagliflozin, or ertugliflozin) and 63,936 had a newly filled prescription for a GLP-1 agonist (liraglutide, dulaglutide, semaglutide, exenatide, albiglutide, or lixisenatide) between April 2013, when the first SGLT2 inhibitor was available in the United States, and 2021.

The researchers matched 28,847 individuals who were initiated on an SGLT2 inhibitor with an equal number who were initiated on a GLP-1 agonist, based on propensity scores, adjusting for more than 120 baseline characteristics.

Safety outcomes were based on previously identified potential safety signals.

Patients who were initiated on an SGLT2 inhibitor had 1.30-fold, 2.13-fold, and 3.08-fold higher risks of having a nonvertebral fracture, a lower limb amputation, and a genital infection, respectively, compared with patients who were initiated on a GLP-1 agonist, after a mean on-treatment time of 7.5 months,

Risks of DKA, hypovolemia, hypoglycemia, and severe UTI were similar in both groups.

Patients initiated on an SGLT2 inhibitor versus a GLP-1 agonist had a lower risk of AKI (hazard ratio, 0.93) equivalent to 6.75 fewer cases of AKI per 1,000 patients per year.

Patients had higher risks for lower limb amputation, genital infections, and nonvertebral fractures with SGLT2 inhibitors versus GLP-1 agonists across most of the prespecified subgroups by age, sex, cardiovascular disease, heart failure, and use of metformin, insulin, or sulfonylurea, but with wider confidence intervals.

Dr. Fu was supported by a Rubicon grant from the Dutch Research Council and has reported no relevant financial relationships. Disclosures for the other authors are listed with the article.

A version of this article originally appeared on Medscape.com.

Disparities in statin use in minority populations persist regardless of insurance status and 10-year atherosclerotic cardiovascular disease risk.

Those are among the findings of a study that sampled a national population database and has provided robust data and granular details on those disparities.

The researchers reported in JAMA Cardiology that the overall prevalence of statin use was 25.5%, and that it varied significantly between defined ethnic groups: 20% for Blacks, 15.4% for Hispanics, and 27.9% for Whites (P < .001). Statin use rates by Asian participants, at 25.5%, didn’t differ significantly from use by Whites.

University of Utah Intermountain Health

“We know that there are racial and ethnic disparities in the use of guideline-indicated statins after having established heart disease, but it was unknown if these disparities existed in the use of guideline-indicated statins for prevention of heart disease in those who just have risk factors,” lead author Joshua Jacobs, PharmD, a clinical pharmacist of cardiovascular medicine at University of Utah Intermountain Healthcare, said in written comments. “Additionally, race is included in the guideline-recommended risk factor calculation in an effort to reduce these disparities.”

Dr. Jacobs and colleagues evaluated statins for use in primary prevention, building upon previous single-center or diabetes-only cohort studies. What makes their study different from previous studies evaluating disparities in statin use is its use of temporal trends or current 10-year predicted ASCVD risk categorization, he said.

Using data from the National Health and Nutrition Examination Survey (NHANES), the researchers performed a serial, cross-sectional analysis of 3,417 participants that they said represented 39.4 million U.S. adults after applying sampling weights for age, gender, and race and ethnicity. In the weighted sample, 62.2% were men. In terms of self-reported race and ethnicity, 4.2% were of Asian descent, 12.7% were Black, 10.1% were Hispanic, and 73% were White.

Study participants completed a standardized questionnaire given by trained interviewers and also went to mobile examination centers where physical, anthropomorphic, and laboratory measurements, including height, weight, LDL cholesterol, and fasting blood glucose were collected. Pill bottle review also verified participants’ self-reported medication use.

The study noted that for primary prevention of atherosclerotic cardiovascular disease (ASCVD), the 2018 American College of Cardiology/American Heart Association Guideline recommends statins for, among other patient factors, elevated 10-year predicted ASCVD risk. The study divided ASCVD risk strata into three groups – 5% to less than 7.5%, 7.5% to less than 20%, and more than 20% – based on the 2018 ACC/AHA guideline and used pooled cohort equation to calculate 10-year ASCVD risk, which the guideline endorses.

Gaps persist despite ASCVD risk

The analysis found no statistically significant difference within each ASCVD risk strata between the White and Asian groups. But although statin use increased proportionately across each higher risk group, the gap widened noticeably in the highest risk group (more than 20% 10-year risk) between Whites, used as the reference at 37.6%, and Blacks (23.8%; prevalence ratio, .90; 95% confidence interval, .82-.98) and Hispanics (23.9%; PR, .90; 95% CI, .81-.99).

The study also evaluated a number of social determinants of health factors. Health insurance and access to routine health care were significantly associated with greater statin use in Black, Hispanic, and White participants; marital status and food insecurity were not. However, even when variables such as education, household income, and health insurance were applied, statin use was still significantly higher in Whites than in Blacks and Hispanics. For those with health insurance, statin use was 28.6% (95% CI, 25-32), 21.1% (95% CI, 17.3-25.4) and 19.9% (95% CI, 15.9-24.5), respectively.

The study noted that the pooled cohort equation-guided approach to statins for primary prevention, which the 2018 ACC/AHA guideline endorsed, should promote greater use of statins among Black patients. “Equitable use of statin therapy for prevention of heart disease is needed for Black and Hispanic adults,” Dr. Jacobs said. “Improvements in access to care, such as having a routine primary care clinician and health insurance, may decrease these health disparities.”

UT Southwestern Medical Center

A goal of the study was to identify if disparities in statin use held up across different risk groups, senior author Ambarish Pandey, MD, said in an interview. Use of the NHANES data makes this study unique among analyses of statin use disparities, he said.

“A lot of the work that has been done previously has focused on secondary prevention among patients who have atherosclerotic cardiovascular disease or have focused on single-center or hospital-based cohorts and have not really focused on a national representative cohort like NHANES,” said Dr. Pandey, of the UT Southwestern Medical Center, Dallas.

The next step is to do community-based participatory research focusing on different implementation strategies to increase the uptake of preventive statin use among Black and Hispanic communities, Dr. Jacobs said.

Dr. Jacobs has no relevant relationships to disclose. Dr. Pandey disclosed relationships with Gilead Sciences, Applied Therapeutics, Myovista, Tricog Health, Eli Lilly, Cytokinetics, Rivus, Roche Diagnostics, Pieces Technologies, Palomarin, Emmi Solutions, and Axon.

Disparities in statin use in minority populations persist regardless of insurance status and 10-year atherosclerotic cardiovascular disease risk.

Those are among the findings of a study that sampled a national population database and has provided robust data and granular details on those disparities.

The researchers reported in JAMA Cardiology that the overall prevalence of statin use was 25.5%, and that it varied significantly between defined ethnic groups: 20% for Blacks, 15.4% for Hispanics, and 27.9% for Whites (P < .001). Statin use rates by Asian participants, at 25.5%, didn’t differ significantly from use by Whites.

University of Utah Intermountain Health

“We know that there are racial and ethnic disparities in the use of guideline-indicated statins after having established heart disease, but it was unknown if these disparities existed in the use of guideline-indicated statins for prevention of heart disease in those who just have risk factors,” lead author Joshua Jacobs, PharmD, a clinical pharmacist of cardiovascular medicine at University of Utah Intermountain Healthcare, said in written comments. “Additionally, race is included in the guideline-recommended risk factor calculation in an effort to reduce these disparities.”

Dr. Jacobs and colleagues evaluated statins for use in primary prevention, building upon previous single-center or diabetes-only cohort studies. What makes their study different from previous studies evaluating disparities in statin use is its use of temporal trends or current 10-year predicted ASCVD risk categorization, he said.

Using data from the National Health and Nutrition Examination Survey (NHANES), the researchers performed a serial, cross-sectional analysis of 3,417 participants that they said represented 39.4 million U.S. adults after applying sampling weights for age, gender, and race and ethnicity. In the weighted sample, 62.2% were men. In terms of self-reported race and ethnicity, 4.2% were of Asian descent, 12.7% were Black, 10.1% were Hispanic, and 73% were White.

Study participants completed a standardized questionnaire given by trained interviewers and also went to mobile examination centers where physical, anthropomorphic, and laboratory measurements, including height, weight, LDL cholesterol, and fasting blood glucose were collected. Pill bottle review also verified participants’ self-reported medication use.

The study noted that for primary prevention of atherosclerotic cardiovascular disease (ASCVD), the 2018 American College of Cardiology/American Heart Association Guideline recommends statins for, among other patient factors, elevated 10-year predicted ASCVD risk. The study divided ASCVD risk strata into three groups – 5% to less than 7.5%, 7.5% to less than 20%, and more than 20% – based on the 2018 ACC/AHA guideline and used pooled cohort equation to calculate 10-year ASCVD risk, which the guideline endorses.

Gaps persist despite ASCVD risk

The analysis found no statistically significant difference within each ASCVD risk strata between the White and Asian groups. But although statin use increased proportionately across each higher risk group, the gap widened noticeably in the highest risk group (more than 20% 10-year risk) between Whites, used as the reference at 37.6%, and Blacks (23.8%; prevalence ratio, .90; 95% confidence interval, .82-.98) and Hispanics (23.9%; PR, .90; 95% CI, .81-.99).

The study also evaluated a number of social determinants of health factors. Health insurance and access to routine health care were significantly associated with greater statin use in Black, Hispanic, and White participants; marital status and food insecurity were not. However, even when variables such as education, household income, and health insurance were applied, statin use was still significantly higher in Whites than in Blacks and Hispanics. For those with health insurance, statin use was 28.6% (95% CI, 25-32), 21.1% (95% CI, 17.3-25.4) and 19.9% (95% CI, 15.9-24.5), respectively.

The study noted that the pooled cohort equation-guided approach to statins for primary prevention, which the 2018 ACC/AHA guideline endorsed, should promote greater use of statins among Black patients. “Equitable use of statin therapy for prevention of heart disease is needed for Black and Hispanic adults,” Dr. Jacobs said. “Improvements in access to care, such as having a routine primary care clinician and health insurance, may decrease these health disparities.”

UT Southwestern Medical Center

A goal of the study was to identify if disparities in statin use held up across different risk groups, senior author Ambarish Pandey, MD, said in an interview. Use of the NHANES data makes this study unique among analyses of statin use disparities, he said.

“A lot of the work that has been done previously has focused on secondary prevention among patients who have atherosclerotic cardiovascular disease or have focused on single-center or hospital-based cohorts and have not really focused on a national representative cohort like NHANES,” said Dr. Pandey, of the UT Southwestern Medical Center, Dallas.

The next step is to do community-based participatory research focusing on different implementation strategies to increase the uptake of preventive statin use among Black and Hispanic communities, Dr. Jacobs said.

Dr. Jacobs has no relevant relationships to disclose. Dr. Pandey disclosed relationships with Gilead Sciences, Applied Therapeutics, Myovista, Tricog Health, Eli Lilly, Cytokinetics, Rivus, Roche Diagnostics, Pieces Technologies, Palomarin, Emmi Solutions, and Axon.

Disparities in statin use in minority populations persist regardless of insurance status and 10-year atherosclerotic cardiovascular disease risk.

Those are among the findings of a study that sampled a national population database and has provided robust data and granular details on those disparities.

The researchers reported in JAMA Cardiology that the overall prevalence of statin use was 25.5%, and that it varied significantly between defined ethnic groups: 20% for Blacks, 15.4% for Hispanics, and 27.9% for Whites (P < .001). Statin use rates by Asian participants, at 25.5%, didn’t differ significantly from use by Whites.

University of Utah Intermountain Health

“We know that there are racial and ethnic disparities in the use of guideline-indicated statins after having established heart disease, but it was unknown if these disparities existed in the use of guideline-indicated statins for prevention of heart disease in those who just have risk factors,” lead author Joshua Jacobs, PharmD, a clinical pharmacist of cardiovascular medicine at University of Utah Intermountain Healthcare, said in written comments. “Additionally, race is included in the guideline-recommended risk factor calculation in an effort to reduce these disparities.”

Dr. Jacobs and colleagues evaluated statins for use in primary prevention, building upon previous single-center or diabetes-only cohort studies. What makes their study different from previous studies evaluating disparities in statin use is its use of temporal trends or current 10-year predicted ASCVD risk categorization, he said.

Using data from the National Health and Nutrition Examination Survey (NHANES), the researchers performed a serial, cross-sectional analysis of 3,417 participants that they said represented 39.4 million U.S. adults after applying sampling weights for age, gender, and race and ethnicity. In the weighted sample, 62.2% were men. In terms of self-reported race and ethnicity, 4.2% were of Asian descent, 12.7% were Black, 10.1% were Hispanic, and 73% were White.

Study participants completed a standardized questionnaire given by trained interviewers and also went to mobile examination centers where physical, anthropomorphic, and laboratory measurements, including height, weight, LDL cholesterol, and fasting blood glucose were collected. Pill bottle review also verified participants’ self-reported medication use.

The study noted that for primary prevention of atherosclerotic cardiovascular disease (ASCVD), the 2018 American College of Cardiology/American Heart Association Guideline recommends statins for, among other patient factors, elevated 10-year predicted ASCVD risk. The study divided ASCVD risk strata into three groups – 5% to less than 7.5%, 7.5% to less than 20%, and more than 20% – based on the 2018 ACC/AHA guideline and used pooled cohort equation to calculate 10-year ASCVD risk, which the guideline endorses.

Gaps persist despite ASCVD risk

The analysis found no statistically significant difference within each ASCVD risk strata between the White and Asian groups. But although statin use increased proportionately across each higher risk group, the gap widened noticeably in the highest risk group (more than 20% 10-year risk) between Whites, used as the reference at 37.6%, and Blacks (23.8%; prevalence ratio, .90; 95% confidence interval, .82-.98) and Hispanics (23.9%; PR, .90; 95% CI, .81-.99).

The study also evaluated a number of social determinants of health factors. Health insurance and access to routine health care were significantly associated with greater statin use in Black, Hispanic, and White participants; marital status and food insecurity were not. However, even when variables such as education, household income, and health insurance were applied, statin use was still significantly higher in Whites than in Blacks and Hispanics. For those with health insurance, statin use was 28.6% (95% CI, 25-32), 21.1% (95% CI, 17.3-25.4) and 19.9% (95% CI, 15.9-24.5), respectively.

The study noted that the pooled cohort equation-guided approach to statins for primary prevention, which the 2018 ACC/AHA guideline endorsed, should promote greater use of statins among Black patients. “Equitable use of statin therapy for prevention of heart disease is needed for Black and Hispanic adults,” Dr. Jacobs said. “Improvements in access to care, such as having a routine primary care clinician and health insurance, may decrease these health disparities.”

UT Southwestern Medical Center

A goal of the study was to identify if disparities in statin use held up across different risk groups, senior author Ambarish Pandey, MD, said in an interview. Use of the NHANES data makes this study unique among analyses of statin use disparities, he said.

“A lot of the work that has been done previously has focused on secondary prevention among patients who have atherosclerotic cardiovascular disease or have focused on single-center or hospital-based cohorts and have not really focused on a national representative cohort like NHANES,” said Dr. Pandey, of the UT Southwestern Medical Center, Dallas.

The next step is to do community-based participatory research focusing on different implementation strategies to increase the uptake of preventive statin use among Black and Hispanic communities, Dr. Jacobs said.

Dr. Jacobs has no relevant relationships to disclose. Dr. Pandey disclosed relationships with Gilead Sciences, Applied Therapeutics, Myovista, Tricog Health, Eli Lilly, Cytokinetics, Rivus, Roche Diagnostics, Pieces Technologies, Palomarin, Emmi Solutions, and Axon.