Obesity, moderate drinking linked to psoriatic arthritis

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Higher body mass index and moderate – but not heavy – drinking may increase the risk of individuals with psoriasis going on to develop psoriatic arthritis, a study has found.

Around one in five people with psoriasis will develop psoriatic arthritis (PsA), wrote Amelia Green of the University of Bath (England) and coauthors in the British Journal of Dermatology.

Previous studies have explored possible links between obesity, alcohol consumption, or smoking, and an increased risk of developing psoriatic arthritis. However, some of these studies found conflicting results or had limitations such as measuring only a single exposure.

In a cohort study, the Ms. Green and her colleagues examined data from the U.K. Clinical Practice Research Datalink for 90,189 individuals with psoriasis, 1,409 of whom were subsequently also diagnosed with psoriatic arthritis.

The analysis showed a significant association between increasing body mass index (BMI) and increasing odds of developing psoriatic arthritis. Compared with individuals with a BMI below 25 kg/m2, those with a BMI of 25.0-29.9 had a 79% greater odds of psoriatic arthritis, those with a BMI of 30.0-34.9 had a 2.10-fold greater odds, and those with a BMI at or above 35 had a 2.68-fold greater odds of developing psoriatic arthritis (P for trend less than .001). Adjustment for potential confounders such as sex, age, duration and severity of psoriasis, diabetes, smoking, and alcohol use slightly attenuated the association, but it remained statistically significant.

Researchers also examined the cumulative effect of lower BMIs over time, and found that over a 10-year period, reductions in BMI were associated with reductions in the risk of developing PsA, compared with remaining at the same BMI over that time.

“Here we have shown for the first time that losing weight over time could reduce the risk of developing PsA in a population with documented psoriasis,” the authors wrote. “As the effect of obesity on the risk of developing PsA may in fact occur with some delay and change over time, our analysis took into account both updated BMI measurements over time and the possible nonlinear and cumulative effects of BMI, which have not previously been investigated.”

Commenting on the mechanisms underlying the association between obesity and the development of PsA, the authors noted that adipose tissue is a source of inflammatory mediators such as adipokines and proinflammatory cytokines, which could lead to the development of PsA. Increasing body weight also could cause microtraumas of the connective tissue between tendon and bone, which may act as an initiating pathogenic event for PsA.


Moderate drinkers – defined as 0.1–3.0 drinks per day ­– had 57% higher odds of developing PsA when compared with nondrinkers, but former drinkers or heavy drinkers did not have an increased risk.

The study also didn’t see any effect of either past or current smoking on the risk of PsA, although there was a nonsignificant interaction with obesity that hinted at increased odds.

“While we found no association between smoking status and the development of PsA in people with psoriasis, further analysis revealed that the effect of smoking on the risk of PsA was possibly mediated through the effect of BMI on PsA; in other words, the protective effect of smoking may be associated with lower BMI among smokers,” the authors wrote.

Patients who developed PsA were also more likely to be younger (mean age of 44.7 years vs. 48.5 years), have severe psoriasis, and have had the disease for a shorter duration.

The study was funded by the National Institute for Health Research, and the authors declared grants from the funder during the conduct of the study. No other conflicts of interest were declared.

SOURCE: Green A et al. Br J Dermatol. 2019 Jun 18. doi: 10.1111/bjd.18227

 

 

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Higher body mass index and moderate – but not heavy – drinking may increase the risk of individuals with psoriasis going on to develop psoriatic arthritis, a study has found.

Around one in five people with psoriasis will develop psoriatic arthritis (PsA), wrote Amelia Green of the University of Bath (England) and coauthors in the British Journal of Dermatology.

Previous studies have explored possible links between obesity, alcohol consumption, or smoking, and an increased risk of developing psoriatic arthritis. However, some of these studies found conflicting results or had limitations such as measuring only a single exposure.

In a cohort study, the Ms. Green and her colleagues examined data from the U.K. Clinical Practice Research Datalink for 90,189 individuals with psoriasis, 1,409 of whom were subsequently also diagnosed with psoriatic arthritis.

The analysis showed a significant association between increasing body mass index (BMI) and increasing odds of developing psoriatic arthritis. Compared with individuals with a BMI below 25 kg/m2, those with a BMI of 25.0-29.9 had a 79% greater odds of psoriatic arthritis, those with a BMI of 30.0-34.9 had a 2.10-fold greater odds, and those with a BMI at or above 35 had a 2.68-fold greater odds of developing psoriatic arthritis (P for trend less than .001). Adjustment for potential confounders such as sex, age, duration and severity of psoriasis, diabetes, smoking, and alcohol use slightly attenuated the association, but it remained statistically significant.

Researchers also examined the cumulative effect of lower BMIs over time, and found that over a 10-year period, reductions in BMI were associated with reductions in the risk of developing PsA, compared with remaining at the same BMI over that time.

“Here we have shown for the first time that losing weight over time could reduce the risk of developing PsA in a population with documented psoriasis,” the authors wrote. “As the effect of obesity on the risk of developing PsA may in fact occur with some delay and change over time, our analysis took into account both updated BMI measurements over time and the possible nonlinear and cumulative effects of BMI, which have not previously been investigated.”

Commenting on the mechanisms underlying the association between obesity and the development of PsA, the authors noted that adipose tissue is a source of inflammatory mediators such as adipokines and proinflammatory cytokines, which could lead to the development of PsA. Increasing body weight also could cause microtraumas of the connective tissue between tendon and bone, which may act as an initiating pathogenic event for PsA.


Moderate drinkers – defined as 0.1–3.0 drinks per day ­– had 57% higher odds of developing PsA when compared with nondrinkers, but former drinkers or heavy drinkers did not have an increased risk.

The study also didn’t see any effect of either past or current smoking on the risk of PsA, although there was a nonsignificant interaction with obesity that hinted at increased odds.

“While we found no association between smoking status and the development of PsA in people with psoriasis, further analysis revealed that the effect of smoking on the risk of PsA was possibly mediated through the effect of BMI on PsA; in other words, the protective effect of smoking may be associated with lower BMI among smokers,” the authors wrote.

Patients who developed PsA were also more likely to be younger (mean age of 44.7 years vs. 48.5 years), have severe psoriasis, and have had the disease for a shorter duration.

The study was funded by the National Institute for Health Research, and the authors declared grants from the funder during the conduct of the study. No other conflicts of interest were declared.

SOURCE: Green A et al. Br J Dermatol. 2019 Jun 18. doi: 10.1111/bjd.18227

 

 

Higher body mass index and moderate – but not heavy – drinking may increase the risk of individuals with psoriasis going on to develop psoriatic arthritis, a study has found.

Around one in five people with psoriasis will develop psoriatic arthritis (PsA), wrote Amelia Green of the University of Bath (England) and coauthors in the British Journal of Dermatology.

Previous studies have explored possible links between obesity, alcohol consumption, or smoking, and an increased risk of developing psoriatic arthritis. However, some of these studies found conflicting results or had limitations such as measuring only a single exposure.

In a cohort study, the Ms. Green and her colleagues examined data from the U.K. Clinical Practice Research Datalink for 90,189 individuals with psoriasis, 1,409 of whom were subsequently also diagnosed with psoriatic arthritis.

The analysis showed a significant association between increasing body mass index (BMI) and increasing odds of developing psoriatic arthritis. Compared with individuals with a BMI below 25 kg/m2, those with a BMI of 25.0-29.9 had a 79% greater odds of psoriatic arthritis, those with a BMI of 30.0-34.9 had a 2.10-fold greater odds, and those with a BMI at or above 35 had a 2.68-fold greater odds of developing psoriatic arthritis (P for trend less than .001). Adjustment for potential confounders such as sex, age, duration and severity of psoriasis, diabetes, smoking, and alcohol use slightly attenuated the association, but it remained statistically significant.

Researchers also examined the cumulative effect of lower BMIs over time, and found that over a 10-year period, reductions in BMI were associated with reductions in the risk of developing PsA, compared with remaining at the same BMI over that time.

“Here we have shown for the first time that losing weight over time could reduce the risk of developing PsA in a population with documented psoriasis,” the authors wrote. “As the effect of obesity on the risk of developing PsA may in fact occur with some delay and change over time, our analysis took into account both updated BMI measurements over time and the possible nonlinear and cumulative effects of BMI, which have not previously been investigated.”

Commenting on the mechanisms underlying the association between obesity and the development of PsA, the authors noted that adipose tissue is a source of inflammatory mediators such as adipokines and proinflammatory cytokines, which could lead to the development of PsA. Increasing body weight also could cause microtraumas of the connective tissue between tendon and bone, which may act as an initiating pathogenic event for PsA.


Moderate drinkers – defined as 0.1–3.0 drinks per day ­– had 57% higher odds of developing PsA when compared with nondrinkers, but former drinkers or heavy drinkers did not have an increased risk.

The study also didn’t see any effect of either past or current smoking on the risk of PsA, although there was a nonsignificant interaction with obesity that hinted at increased odds.

“While we found no association between smoking status and the development of PsA in people with psoriasis, further analysis revealed that the effect of smoking on the risk of PsA was possibly mediated through the effect of BMI on PsA; in other words, the protective effect of smoking may be associated with lower BMI among smokers,” the authors wrote.

Patients who developed PsA were also more likely to be younger (mean age of 44.7 years vs. 48.5 years), have severe psoriasis, and have had the disease for a shorter duration.

The study was funded by the National Institute for Health Research, and the authors declared grants from the funder during the conduct of the study. No other conflicts of interest were declared.

SOURCE: Green A et al. Br J Dermatol. 2019 Jun 18. doi: 10.1111/bjd.18227

 

 

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Bariatric surgery has mostly positive impact in knee arthroplasty

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Bariatric surgery prior to arthroplasty reduces the likelihood of multiple complications but some risks increase, a large study has found.

KatarzynaBialasiewicz/Thinkstock

The study, led by Yicun Wang, PhD, of Nanjing (China) University was published in the Journal of Arthroplasty. “Generally speaking, bariatric surgery decreases some postoperative complications, decreases length of stay, and lowers mortality,” the study investigators wrote, [but] anemia and blood transfusion seem to be more common in patients with prior bariatric surgery.

They analyzed the effect of bariatric surgery on subsequent arthroplasty in morbidly obese patients in the United States using Nationwide Inpatient Sample 2006-2014 data on total hip arthroplasty (THA) and total knee arthroplasty (TKA). The researchers defined morbid obese patients as those with a body mass index higher than 40 kg/m2.

Among patients who underwent TKA, the researchers compared a group of 9,803 morbidly obese patients with the same number of patients who had undergone bariatric surgery. The two groups were matched by age, sex, income, primary insurance payer, and race.

There were large differences between the bariatric surgery group vs. morbidly obese group: Pulmonary embolism was much more common in the morbid obesity group (odds ratio, 0.22; 95% confidence interval, 0.05-1.03; P = .0346) while blood transfusion was more common in the bariatric surgery group (OR, 1.76; 95% CI, 1.52-2.03; P less than .0001).

For TKA, the researchers used the same approach to analyze 2,540 matched pairs of patients. In the bariatric surgery vs. morbidly obese comparison, pulmonary embolism was more common in the morbidly obese group (OR, 0.34; 95% CI, 0.20-0.57; P less than .0001), as were respiratory complications (OR, 0.45; 95% CI, 0.26-0.78; P = .0032) and death (OR, 0.07; 95% CI, 0.01-0.50; P = .0005). But the bariatric surgery group had higher levels of blood transfusion (OR, 1.87; 95% CI, 1.71-2.04; P less than .0001) and anemia (OR, 1.16; 95% CI, 1.09-1.24; P less than .0001).

Going forward, the researchers write, “future studies on these patients should attempt to evaluate the impact of bariatric surgery on the long-term outcomes of arthroplasty.”

The study was supported by various funders including the National Natural Science Foundation of China, the Natural Science Foundation of Guangdong Province, the Project of Administration of Traditional Chinese Medicine of Guangdong Province and others. No author disclosures are reported.

SOURCE: Wang Y et al. J Arthroplasty. 2019;S0883-5403(19)30667-9.

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Bariatric surgery prior to arthroplasty reduces the likelihood of multiple complications but some risks increase, a large study has found.

KatarzynaBialasiewicz/Thinkstock

The study, led by Yicun Wang, PhD, of Nanjing (China) University was published in the Journal of Arthroplasty. “Generally speaking, bariatric surgery decreases some postoperative complications, decreases length of stay, and lowers mortality,” the study investigators wrote, [but] anemia and blood transfusion seem to be more common in patients with prior bariatric surgery.

They analyzed the effect of bariatric surgery on subsequent arthroplasty in morbidly obese patients in the United States using Nationwide Inpatient Sample 2006-2014 data on total hip arthroplasty (THA) and total knee arthroplasty (TKA). The researchers defined morbid obese patients as those with a body mass index higher than 40 kg/m2.

Among patients who underwent TKA, the researchers compared a group of 9,803 morbidly obese patients with the same number of patients who had undergone bariatric surgery. The two groups were matched by age, sex, income, primary insurance payer, and race.

There were large differences between the bariatric surgery group vs. morbidly obese group: Pulmonary embolism was much more common in the morbid obesity group (odds ratio, 0.22; 95% confidence interval, 0.05-1.03; P = .0346) while blood transfusion was more common in the bariatric surgery group (OR, 1.76; 95% CI, 1.52-2.03; P less than .0001).

For TKA, the researchers used the same approach to analyze 2,540 matched pairs of patients. In the bariatric surgery vs. morbidly obese comparison, pulmonary embolism was more common in the morbidly obese group (OR, 0.34; 95% CI, 0.20-0.57; P less than .0001), as were respiratory complications (OR, 0.45; 95% CI, 0.26-0.78; P = .0032) and death (OR, 0.07; 95% CI, 0.01-0.50; P = .0005). But the bariatric surgery group had higher levels of blood transfusion (OR, 1.87; 95% CI, 1.71-2.04; P less than .0001) and anemia (OR, 1.16; 95% CI, 1.09-1.24; P less than .0001).

Going forward, the researchers write, “future studies on these patients should attempt to evaluate the impact of bariatric surgery on the long-term outcomes of arthroplasty.”

The study was supported by various funders including the National Natural Science Foundation of China, the Natural Science Foundation of Guangdong Province, the Project of Administration of Traditional Chinese Medicine of Guangdong Province and others. No author disclosures are reported.

SOURCE: Wang Y et al. J Arthroplasty. 2019;S0883-5403(19)30667-9.

 

Bariatric surgery prior to arthroplasty reduces the likelihood of multiple complications but some risks increase, a large study has found.

KatarzynaBialasiewicz/Thinkstock

The study, led by Yicun Wang, PhD, of Nanjing (China) University was published in the Journal of Arthroplasty. “Generally speaking, bariatric surgery decreases some postoperative complications, decreases length of stay, and lowers mortality,” the study investigators wrote, [but] anemia and blood transfusion seem to be more common in patients with prior bariatric surgery.

They analyzed the effect of bariatric surgery on subsequent arthroplasty in morbidly obese patients in the United States using Nationwide Inpatient Sample 2006-2014 data on total hip arthroplasty (THA) and total knee arthroplasty (TKA). The researchers defined morbid obese patients as those with a body mass index higher than 40 kg/m2.

Among patients who underwent TKA, the researchers compared a group of 9,803 morbidly obese patients with the same number of patients who had undergone bariatric surgery. The two groups were matched by age, sex, income, primary insurance payer, and race.

There were large differences between the bariatric surgery group vs. morbidly obese group: Pulmonary embolism was much more common in the morbid obesity group (odds ratio, 0.22; 95% confidence interval, 0.05-1.03; P = .0346) while blood transfusion was more common in the bariatric surgery group (OR, 1.76; 95% CI, 1.52-2.03; P less than .0001).

For TKA, the researchers used the same approach to analyze 2,540 matched pairs of patients. In the bariatric surgery vs. morbidly obese comparison, pulmonary embolism was more common in the morbidly obese group (OR, 0.34; 95% CI, 0.20-0.57; P less than .0001), as were respiratory complications (OR, 0.45; 95% CI, 0.26-0.78; P = .0032) and death (OR, 0.07; 95% CI, 0.01-0.50; P = .0005). But the bariatric surgery group had higher levels of blood transfusion (OR, 1.87; 95% CI, 1.71-2.04; P less than .0001) and anemia (OR, 1.16; 95% CI, 1.09-1.24; P less than .0001).

Going forward, the researchers write, “future studies on these patients should attempt to evaluate the impact of bariatric surgery on the long-term outcomes of arthroplasty.”

The study was supported by various funders including the National Natural Science Foundation of China, the Natural Science Foundation of Guangdong Province, the Project of Administration of Traditional Chinese Medicine of Guangdong Province and others. No author disclosures are reported.

SOURCE: Wang Y et al. J Arthroplasty. 2019;S0883-5403(19)30667-9.

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Statins may do double duty as antidepressants

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– The tantalizing prospect that statins could be repurposed as adjunctive antidepressant drugs in a defined subgroup of patients with major depression is finally about to undergo rigorous testing.

Bruce Jancin/MDedge News
Dr. Christian Otte

Several lines of preliminary evidence, including large observational cohort studies as well as three small, short-duration randomized trials, suggest that this might indeed be the case. It’s an extremely attractive possibility, since patients and physicians wish that antidepressant therapy were more effective, statins are among the most widely prescribed drugs worldwide, and their safety profile is thoroughly established. The expectation is that a definitive answer as to whether repurposing of statins as antidepressants is worthwhile will be provided by the SIMCODE trial, recently approved for funding by the German Federal Ministry of Education and Research, Christian Otte, MD, announced at the annual congress of the European College of Neuropsychopharmacology.

SIMCODE is a multicenter, double-blind, placebo-controlled randomized trial to be conducted at eight German academic medical centers. Participants, all of whom must have major depressive disorder and comorbid obesity, will be randomized to simvastatin or placebo on top of standard antidepressant therapy with escitalopram, an SSRI which, like simvastatin, is available as a relatively inexpensive generic, explained Dr. Otte, professor and vice director of the department of psychiatry and psychotherapy at Charite University in Berlin.

For Dr. Otte, SIMCODE will close a circle he helped open with his 2012 report from the Heart and Soul Study, a prospective longitudinal study of nearly 1,000 San Francisco Bay Area patients with coronary heart disease who were assessed annually for depressive symptoms for 6 years. The 65% of patients who were on statin therapy, albeit in nonrandomized fashion, had an adjusted 38% lower risk of developing depression (J Clin Psychiatry. 2012 May;73[5]:610-5).

His was one of seven observational studies involving more than 9,000 patients included in a subsequent meta-analysis showing that statin users were 37% less likely to develop depression than were nonusers (J Affect Disord. 2014 May;160:62-7).

At a symposium on repurposing statins as antidepressants held at ECNP 2019, Dr. Otte was joined by other researchers who have made key contributions in this area. All agreed that the verdict isn’t in yet as to statins’ effectiveness as adjunctive antidepressants, and that the subgroup of patients with major depression who are most likely to gain added antidepressive effect from a statin are those with what the speakers variously described as comorbid cardiometabolic disease, immunometabolic disease, or simply, as in SIMCODE, obesity. These are patients with a high degree of systemic inflammation, which often makes their depression less responsive to standard antidepressant therapies. The working hypothesis is that the pleiotropic anti-inflammatory effects of statins will result in a greater response to conventional antidepressants.

Animal studies point to multiple potential mechanisms by which statins might have antidepressant efficacy in clinical practice, according to Dr. Otte. Beyond their anti-inflammatory effects, these include the drugs’ documented effects on glutamatergic N-methyl-D-aspartate (NMDA) receptors, dopamine receptors, brain-derived neurotrophic factor, glucocorticoid receptors, and hippocampal serotonin 2A receptors.

 

 



Ole Kohler, MD, a psychiatrist at Aarhus (Denmark) University, presented highlights of his eye-popping population-based study of more than 872,000 Danes on an SSRI in 1997-2012, more than 113,000 of whom were on a concomitant statin. The key finding: During roughly 3 years of follow-up, the risk of contact with a psychiatric hospital for depression was 36% lower in the group on concomitant SSRI/statin therapy than in those not on a statin (Am J Psychiatry. 2016 Aug 1;173[8]:807-15).

Bruce Jancin/MDedge News
Dr. Ole Kohler

He was quick to observe that a study such as this is vulnerable to various forms of confounding. This risk can be mitigated to a considerable extent by careful propensity score matching. Of note, however, none of the three studies that have been conducted with propensity score matching, including his own recent study of nearly 194,000 statin users and an equal number of matched nonusers, showed a difference in risk of depression between statin users and nonusers. All three studies were performed in general populations without known depression, leading Dr. Kohler to conclude that it’s unlikely that statins have a role in preventing depression in nondepressed individuals.

The focus should instead be on the possible role of statins in reducing the risk of depression in patients with cardiometabolic disease – that is, heart disease, metabolic syndrome, or type 2 diabetes – where more than a half-dozen cohort studies, including the Heart and Soul Study, have found that statins have a favorable impact, he added.

Estela Salagre, MD, a psychiatrist at the University of Barcelona, has carried out a meta-analysis of the three randomized, double-blind, placebo-controlled trials of add-on statin therapy in patients on standard therapies for moderate to severe depression published to date. She found that statin therapy was associated with a 27% greater reduction in scores on the Hamilton Depression Rating Scale, compared with placebo (J Affect Disord. 2016 Aug;200:235-42). Those findings recently were confirmed in a separate meta-analysis by other investigators using different methodologies (J Affect Disord. 2019 Oct 1;257:55-63).

Bruce Jancin/MDedge News
Dr. Estela Salagre
However, those three randomized trials, while well conducted, have major limitations. They included only 165 participants in total, with just 6-12 weeks of follow-up. Moreover, all three RCTs were performed in one country – Iran – raising questions about their generalizability, Dr. Salagre said.
 

 



Femke Lamers, PhD, presented evidence based on the nearly 3,000-subject longitudinal Netherlands Study of Depression and Anxiety that roughly one-quarter of individuals with major depressive disorder have a distinct subtype of nonmelancholic depression characterized by a clustering of obesity, inflammation, increased appetite, fatigue, hypersomnia, and increased levels of insulin and leptin. She calls it immunometabolic depression. She and her coinvestigators in the international Psychiatric Genomics Consortium have demonstrated that this phenotypic clustering is associated with a shared genetic vulnerability between major depression and obesity (JAMA Psychiatry. 2017 Dec 1;74[12]:1214-25).

Bruce Jancin/MDedge News
Dr. Femke Lamers

“Major depressive disorder is not a one-size-fits-all disorder. There is an immunometabolic form of depression,” declared Dr. Lamers, an epidemiologist at the University of Amsterdam.

All speakers reported having no financial conflicts of interest.

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– The tantalizing prospect that statins could be repurposed as adjunctive antidepressant drugs in a defined subgroup of patients with major depression is finally about to undergo rigorous testing.

Bruce Jancin/MDedge News
Dr. Christian Otte

Several lines of preliminary evidence, including large observational cohort studies as well as three small, short-duration randomized trials, suggest that this might indeed be the case. It’s an extremely attractive possibility, since patients and physicians wish that antidepressant therapy were more effective, statins are among the most widely prescribed drugs worldwide, and their safety profile is thoroughly established. The expectation is that a definitive answer as to whether repurposing of statins as antidepressants is worthwhile will be provided by the SIMCODE trial, recently approved for funding by the German Federal Ministry of Education and Research, Christian Otte, MD, announced at the annual congress of the European College of Neuropsychopharmacology.

SIMCODE is a multicenter, double-blind, placebo-controlled randomized trial to be conducted at eight German academic medical centers. Participants, all of whom must have major depressive disorder and comorbid obesity, will be randomized to simvastatin or placebo on top of standard antidepressant therapy with escitalopram, an SSRI which, like simvastatin, is available as a relatively inexpensive generic, explained Dr. Otte, professor and vice director of the department of psychiatry and psychotherapy at Charite University in Berlin.

For Dr. Otte, SIMCODE will close a circle he helped open with his 2012 report from the Heart and Soul Study, a prospective longitudinal study of nearly 1,000 San Francisco Bay Area patients with coronary heart disease who were assessed annually for depressive symptoms for 6 years. The 65% of patients who were on statin therapy, albeit in nonrandomized fashion, had an adjusted 38% lower risk of developing depression (J Clin Psychiatry. 2012 May;73[5]:610-5).

His was one of seven observational studies involving more than 9,000 patients included in a subsequent meta-analysis showing that statin users were 37% less likely to develop depression than were nonusers (J Affect Disord. 2014 May;160:62-7).

At a symposium on repurposing statins as antidepressants held at ECNP 2019, Dr. Otte was joined by other researchers who have made key contributions in this area. All agreed that the verdict isn’t in yet as to statins’ effectiveness as adjunctive antidepressants, and that the subgroup of patients with major depression who are most likely to gain added antidepressive effect from a statin are those with what the speakers variously described as comorbid cardiometabolic disease, immunometabolic disease, or simply, as in SIMCODE, obesity. These are patients with a high degree of systemic inflammation, which often makes their depression less responsive to standard antidepressant therapies. The working hypothesis is that the pleiotropic anti-inflammatory effects of statins will result in a greater response to conventional antidepressants.

Animal studies point to multiple potential mechanisms by which statins might have antidepressant efficacy in clinical practice, according to Dr. Otte. Beyond their anti-inflammatory effects, these include the drugs’ documented effects on glutamatergic N-methyl-D-aspartate (NMDA) receptors, dopamine receptors, brain-derived neurotrophic factor, glucocorticoid receptors, and hippocampal serotonin 2A receptors.

 

 



Ole Kohler, MD, a psychiatrist at Aarhus (Denmark) University, presented highlights of his eye-popping population-based study of more than 872,000 Danes on an SSRI in 1997-2012, more than 113,000 of whom were on a concomitant statin. The key finding: During roughly 3 years of follow-up, the risk of contact with a psychiatric hospital for depression was 36% lower in the group on concomitant SSRI/statin therapy than in those not on a statin (Am J Psychiatry. 2016 Aug 1;173[8]:807-15).

Bruce Jancin/MDedge News
Dr. Ole Kohler

He was quick to observe that a study such as this is vulnerable to various forms of confounding. This risk can be mitigated to a considerable extent by careful propensity score matching. Of note, however, none of the three studies that have been conducted with propensity score matching, including his own recent study of nearly 194,000 statin users and an equal number of matched nonusers, showed a difference in risk of depression between statin users and nonusers. All three studies were performed in general populations without known depression, leading Dr. Kohler to conclude that it’s unlikely that statins have a role in preventing depression in nondepressed individuals.

The focus should instead be on the possible role of statins in reducing the risk of depression in patients with cardiometabolic disease – that is, heart disease, metabolic syndrome, or type 2 diabetes – where more than a half-dozen cohort studies, including the Heart and Soul Study, have found that statins have a favorable impact, he added.

Estela Salagre, MD, a psychiatrist at the University of Barcelona, has carried out a meta-analysis of the three randomized, double-blind, placebo-controlled trials of add-on statin therapy in patients on standard therapies for moderate to severe depression published to date. She found that statin therapy was associated with a 27% greater reduction in scores on the Hamilton Depression Rating Scale, compared with placebo (J Affect Disord. 2016 Aug;200:235-42). Those findings recently were confirmed in a separate meta-analysis by other investigators using different methodologies (J Affect Disord. 2019 Oct 1;257:55-63).

Bruce Jancin/MDedge News
Dr. Estela Salagre
However, those three randomized trials, while well conducted, have major limitations. They included only 165 participants in total, with just 6-12 weeks of follow-up. Moreover, all three RCTs were performed in one country – Iran – raising questions about their generalizability, Dr. Salagre said.
 

 



Femke Lamers, PhD, presented evidence based on the nearly 3,000-subject longitudinal Netherlands Study of Depression and Anxiety that roughly one-quarter of individuals with major depressive disorder have a distinct subtype of nonmelancholic depression characterized by a clustering of obesity, inflammation, increased appetite, fatigue, hypersomnia, and increased levels of insulin and leptin. She calls it immunometabolic depression. She and her coinvestigators in the international Psychiatric Genomics Consortium have demonstrated that this phenotypic clustering is associated with a shared genetic vulnerability between major depression and obesity (JAMA Psychiatry. 2017 Dec 1;74[12]:1214-25).

Bruce Jancin/MDedge News
Dr. Femke Lamers

“Major depressive disorder is not a one-size-fits-all disorder. There is an immunometabolic form of depression,” declared Dr. Lamers, an epidemiologist at the University of Amsterdam.

All speakers reported having no financial conflicts of interest.

– The tantalizing prospect that statins could be repurposed as adjunctive antidepressant drugs in a defined subgroup of patients with major depression is finally about to undergo rigorous testing.

Bruce Jancin/MDedge News
Dr. Christian Otte

Several lines of preliminary evidence, including large observational cohort studies as well as three small, short-duration randomized trials, suggest that this might indeed be the case. It’s an extremely attractive possibility, since patients and physicians wish that antidepressant therapy were more effective, statins are among the most widely prescribed drugs worldwide, and their safety profile is thoroughly established. The expectation is that a definitive answer as to whether repurposing of statins as antidepressants is worthwhile will be provided by the SIMCODE trial, recently approved for funding by the German Federal Ministry of Education and Research, Christian Otte, MD, announced at the annual congress of the European College of Neuropsychopharmacology.

SIMCODE is a multicenter, double-blind, placebo-controlled randomized trial to be conducted at eight German academic medical centers. Participants, all of whom must have major depressive disorder and comorbid obesity, will be randomized to simvastatin or placebo on top of standard antidepressant therapy with escitalopram, an SSRI which, like simvastatin, is available as a relatively inexpensive generic, explained Dr. Otte, professor and vice director of the department of psychiatry and psychotherapy at Charite University in Berlin.

For Dr. Otte, SIMCODE will close a circle he helped open with his 2012 report from the Heart and Soul Study, a prospective longitudinal study of nearly 1,000 San Francisco Bay Area patients with coronary heart disease who were assessed annually for depressive symptoms for 6 years. The 65% of patients who were on statin therapy, albeit in nonrandomized fashion, had an adjusted 38% lower risk of developing depression (J Clin Psychiatry. 2012 May;73[5]:610-5).

His was one of seven observational studies involving more than 9,000 patients included in a subsequent meta-analysis showing that statin users were 37% less likely to develop depression than were nonusers (J Affect Disord. 2014 May;160:62-7).

At a symposium on repurposing statins as antidepressants held at ECNP 2019, Dr. Otte was joined by other researchers who have made key contributions in this area. All agreed that the verdict isn’t in yet as to statins’ effectiveness as adjunctive antidepressants, and that the subgroup of patients with major depression who are most likely to gain added antidepressive effect from a statin are those with what the speakers variously described as comorbid cardiometabolic disease, immunometabolic disease, or simply, as in SIMCODE, obesity. These are patients with a high degree of systemic inflammation, which often makes their depression less responsive to standard antidepressant therapies. The working hypothesis is that the pleiotropic anti-inflammatory effects of statins will result in a greater response to conventional antidepressants.

Animal studies point to multiple potential mechanisms by which statins might have antidepressant efficacy in clinical practice, according to Dr. Otte. Beyond their anti-inflammatory effects, these include the drugs’ documented effects on glutamatergic N-methyl-D-aspartate (NMDA) receptors, dopamine receptors, brain-derived neurotrophic factor, glucocorticoid receptors, and hippocampal serotonin 2A receptors.

 

 



Ole Kohler, MD, a psychiatrist at Aarhus (Denmark) University, presented highlights of his eye-popping population-based study of more than 872,000 Danes on an SSRI in 1997-2012, more than 113,000 of whom were on a concomitant statin. The key finding: During roughly 3 years of follow-up, the risk of contact with a psychiatric hospital for depression was 36% lower in the group on concomitant SSRI/statin therapy than in those not on a statin (Am J Psychiatry. 2016 Aug 1;173[8]:807-15).

Bruce Jancin/MDedge News
Dr. Ole Kohler

He was quick to observe that a study such as this is vulnerable to various forms of confounding. This risk can be mitigated to a considerable extent by careful propensity score matching. Of note, however, none of the three studies that have been conducted with propensity score matching, including his own recent study of nearly 194,000 statin users and an equal number of matched nonusers, showed a difference in risk of depression between statin users and nonusers. All three studies were performed in general populations without known depression, leading Dr. Kohler to conclude that it’s unlikely that statins have a role in preventing depression in nondepressed individuals.

The focus should instead be on the possible role of statins in reducing the risk of depression in patients with cardiometabolic disease – that is, heart disease, metabolic syndrome, or type 2 diabetes – where more than a half-dozen cohort studies, including the Heart and Soul Study, have found that statins have a favorable impact, he added.

Estela Salagre, MD, a psychiatrist at the University of Barcelona, has carried out a meta-analysis of the three randomized, double-blind, placebo-controlled trials of add-on statin therapy in patients on standard therapies for moderate to severe depression published to date. She found that statin therapy was associated with a 27% greater reduction in scores on the Hamilton Depression Rating Scale, compared with placebo (J Affect Disord. 2016 Aug;200:235-42). Those findings recently were confirmed in a separate meta-analysis by other investigators using different methodologies (J Affect Disord. 2019 Oct 1;257:55-63).

Bruce Jancin/MDedge News
Dr. Estela Salagre
However, those three randomized trials, while well conducted, have major limitations. They included only 165 participants in total, with just 6-12 weeks of follow-up. Moreover, all three RCTs were performed in one country – Iran – raising questions about their generalizability, Dr. Salagre said.
 

 



Femke Lamers, PhD, presented evidence based on the nearly 3,000-subject longitudinal Netherlands Study of Depression and Anxiety that roughly one-quarter of individuals with major depressive disorder have a distinct subtype of nonmelancholic depression characterized by a clustering of obesity, inflammation, increased appetite, fatigue, hypersomnia, and increased levels of insulin and leptin. She calls it immunometabolic depression. She and her coinvestigators in the international Psychiatric Genomics Consortium have demonstrated that this phenotypic clustering is associated with a shared genetic vulnerability between major depression and obesity (JAMA Psychiatry. 2017 Dec 1;74[12]:1214-25).

Bruce Jancin/MDedge News
Dr. Femke Lamers

“Major depressive disorder is not a one-size-fits-all disorder. There is an immunometabolic form of depression,” declared Dr. Lamers, an epidemiologist at the University of Amsterdam.

All speakers reported having no financial conflicts of interest.

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Survival at ‘overweight’ BMI surpasses ‘normal’

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– Middle-aged adults with a body mass index of 25-29 kg/m2 had a significantly better adjusted survival during a median follow-up of nearly 10 years than did people with a “normal” body mass index of 20-24 kg/m2 in a worldwide study of more than 140,000. This finding suggests the current, widely accepted definition of normal body mass index is wrong.*

Mitchel L. Zoler/MDedge News
Dr. Darryl P. Leong

The new findings suggest that the current definition of a “healthy” body mass index (BMI) “should be re-evaluated,” Darryl P. Leong, MBBS, said at the annual Congress of the European Society of Cardiology. The analysis also identified a BMI specifically of 27 kg/m2 as associated with optimal survival among both women and men, “clearly outside the range of 20 to less than 25 kg/m2 that is considered normal,” said Dr. Leong, a cardiologist at McMaster University and the Population Health Research Institute, both in Hamilton, Ont.

Dr. Leong cited three potential explanations for why the new study identified optimal survival with a BMI of 25 to less than 30 kg/m2 among people who were 35-70 years old when they entered the study and were followed for a median of 9.5 years: The current study collected data and adjusted the results using a wider range of potential confounders than in prior studies, the data reflect the impact of contemporary interventions to reduce cardiovascular disease illness and death while past studies relied on data from earlier times when less cardiovascular disease protection occurred, and the current study included people from lower-income countries, although the finding is just as applicable to people who live in high-income countries, who were also included in the study population, noted Salim Yusuf, MBBS, principal investigator for the study.

A BMI of 20-24 kg/m2 “is actually low and harmful,” noted Dr. Yusuf in an interview. Despite recent data consistently showing better survival among people with a BMI of 25-29 kg/m2, panels that have recently written weight guidelines are “ossified” and “refuse to accept” the implications of these findings, said Dr. Yusuf, professor of medicine at McMaster and executive director of the Population Health Research Institute.

The results of the analyses that Dr. Leong reported also showed that BMI paled as a prognosticator for survival when compared with two other assessments of weight: waist/hip ratio, and even more powerful prognostically, a novel measure developed for this analysis that calculates the ratio of hand-grip strength/body weight. Waist/hip ratio adds the dimension of the location of body fat rather than just the amount, and the ratio of grip strength/body weight assesses the contribution of muscle mass to overall weight, noted Dr. Leong. He reported an optimal waist/hip ratio for survival of 0.83 in women and 0.93 in men, and an optimal strength/weight ratio of 0.42 in women and 0.50 in men. This means that a man whose hand-grip strength (measured in kg) is half of the person’s body weight has the best prospect for survival.
 
The study used data collected in PURE (Prospective Urban Rural Epidemiology Study) on 142,410 people aged 35-70 years from any one of four high-income countries, 12 middle-income countries, and five low-income countries. The study excluded people who had at baseline known coronary artery disease, stroke, heart failure, or cancer, and the adjusted analysis controlled for age, sex, region, education, activity, alcohol and tobacco use, and the baseline prevalence of hypertension and diabetes. During follow-up, 9,712 of these people died.

The researchers saw a nadir for mortality among people with a BMI of 25-29 kg/m2 for both cardiovascular and noncardiovascular deaths. In addition, the link between total mortality and BMI was strongest in the subgroup of people on one or more treatments aimed at preventing cardiovascular disease, while it essentially disappeared among people not receiving any cardiovascular disease preventive measures, highlighting that the relationship now identified depends on a context of overall cardiovascular disease risk reduction, Dr. Leong said. The results also showed a very clear, direct, linear relationship between higher BMI and both the incidence of diabetes and cardiovascular disease, as well as increased all-cause and noncardiovascular mortality among people with a BMI of less than 20 kg/m2.

Dr. Yusuf discussed the results of the analysis in a video interview.

The PURE study has received partial funding from unrestricted grants from several drug companies. Dr. Leong has been an advisor to Ferring Pharmaceuticals and has been a speaker on behalf of Janssen. Dr. Yusuf had no disclosures.

 

 

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– Middle-aged adults with a body mass index of 25-29 kg/m2 had a significantly better adjusted survival during a median follow-up of nearly 10 years than did people with a “normal” body mass index of 20-24 kg/m2 in a worldwide study of more than 140,000. This finding suggests the current, widely accepted definition of normal body mass index is wrong.*

Mitchel L. Zoler/MDedge News
Dr. Darryl P. Leong

The new findings suggest that the current definition of a “healthy” body mass index (BMI) “should be re-evaluated,” Darryl P. Leong, MBBS, said at the annual Congress of the European Society of Cardiology. The analysis also identified a BMI specifically of 27 kg/m2 as associated with optimal survival among both women and men, “clearly outside the range of 20 to less than 25 kg/m2 that is considered normal,” said Dr. Leong, a cardiologist at McMaster University and the Population Health Research Institute, both in Hamilton, Ont.

Dr. Leong cited three potential explanations for why the new study identified optimal survival with a BMI of 25 to less than 30 kg/m2 among people who were 35-70 years old when they entered the study and were followed for a median of 9.5 years: The current study collected data and adjusted the results using a wider range of potential confounders than in prior studies, the data reflect the impact of contemporary interventions to reduce cardiovascular disease illness and death while past studies relied on data from earlier times when less cardiovascular disease protection occurred, and the current study included people from lower-income countries, although the finding is just as applicable to people who live in high-income countries, who were also included in the study population, noted Salim Yusuf, MBBS, principal investigator for the study.

A BMI of 20-24 kg/m2 “is actually low and harmful,” noted Dr. Yusuf in an interview. Despite recent data consistently showing better survival among people with a BMI of 25-29 kg/m2, panels that have recently written weight guidelines are “ossified” and “refuse to accept” the implications of these findings, said Dr. Yusuf, professor of medicine at McMaster and executive director of the Population Health Research Institute.

The results of the analyses that Dr. Leong reported also showed that BMI paled as a prognosticator for survival when compared with two other assessments of weight: waist/hip ratio, and even more powerful prognostically, a novel measure developed for this analysis that calculates the ratio of hand-grip strength/body weight. Waist/hip ratio adds the dimension of the location of body fat rather than just the amount, and the ratio of grip strength/body weight assesses the contribution of muscle mass to overall weight, noted Dr. Leong. He reported an optimal waist/hip ratio for survival of 0.83 in women and 0.93 in men, and an optimal strength/weight ratio of 0.42 in women and 0.50 in men. This means that a man whose hand-grip strength (measured in kg) is half of the person’s body weight has the best prospect for survival.
 
The study used data collected in PURE (Prospective Urban Rural Epidemiology Study) on 142,410 people aged 35-70 years from any one of four high-income countries, 12 middle-income countries, and five low-income countries. The study excluded people who had at baseline known coronary artery disease, stroke, heart failure, or cancer, and the adjusted analysis controlled for age, sex, region, education, activity, alcohol and tobacco use, and the baseline prevalence of hypertension and diabetes. During follow-up, 9,712 of these people died.

The researchers saw a nadir for mortality among people with a BMI of 25-29 kg/m2 for both cardiovascular and noncardiovascular deaths. In addition, the link between total mortality and BMI was strongest in the subgroup of people on one or more treatments aimed at preventing cardiovascular disease, while it essentially disappeared among people not receiving any cardiovascular disease preventive measures, highlighting that the relationship now identified depends on a context of overall cardiovascular disease risk reduction, Dr. Leong said. The results also showed a very clear, direct, linear relationship between higher BMI and both the incidence of diabetes and cardiovascular disease, as well as increased all-cause and noncardiovascular mortality among people with a BMI of less than 20 kg/m2.

Dr. Yusuf discussed the results of the analysis in a video interview.

The PURE study has received partial funding from unrestricted grants from several drug companies. Dr. Leong has been an advisor to Ferring Pharmaceuticals and has been a speaker on behalf of Janssen. Dr. Yusuf had no disclosures.

 

 

– Middle-aged adults with a body mass index of 25-29 kg/m2 had a significantly better adjusted survival during a median follow-up of nearly 10 years than did people with a “normal” body mass index of 20-24 kg/m2 in a worldwide study of more than 140,000. This finding suggests the current, widely accepted definition of normal body mass index is wrong.*

Mitchel L. Zoler/MDedge News
Dr. Darryl P. Leong

The new findings suggest that the current definition of a “healthy” body mass index (BMI) “should be re-evaluated,” Darryl P. Leong, MBBS, said at the annual Congress of the European Society of Cardiology. The analysis also identified a BMI specifically of 27 kg/m2 as associated with optimal survival among both women and men, “clearly outside the range of 20 to less than 25 kg/m2 that is considered normal,” said Dr. Leong, a cardiologist at McMaster University and the Population Health Research Institute, both in Hamilton, Ont.

Dr. Leong cited three potential explanations for why the new study identified optimal survival with a BMI of 25 to less than 30 kg/m2 among people who were 35-70 years old when they entered the study and were followed for a median of 9.5 years: The current study collected data and adjusted the results using a wider range of potential confounders than in prior studies, the data reflect the impact of contemporary interventions to reduce cardiovascular disease illness and death while past studies relied on data from earlier times when less cardiovascular disease protection occurred, and the current study included people from lower-income countries, although the finding is just as applicable to people who live in high-income countries, who were also included in the study population, noted Salim Yusuf, MBBS, principal investigator for the study.

A BMI of 20-24 kg/m2 “is actually low and harmful,” noted Dr. Yusuf in an interview. Despite recent data consistently showing better survival among people with a BMI of 25-29 kg/m2, panels that have recently written weight guidelines are “ossified” and “refuse to accept” the implications of these findings, said Dr. Yusuf, professor of medicine at McMaster and executive director of the Population Health Research Institute.

The results of the analyses that Dr. Leong reported also showed that BMI paled as a prognosticator for survival when compared with two other assessments of weight: waist/hip ratio, and even more powerful prognostically, a novel measure developed for this analysis that calculates the ratio of hand-grip strength/body weight. Waist/hip ratio adds the dimension of the location of body fat rather than just the amount, and the ratio of grip strength/body weight assesses the contribution of muscle mass to overall weight, noted Dr. Leong. He reported an optimal waist/hip ratio for survival of 0.83 in women and 0.93 in men, and an optimal strength/weight ratio of 0.42 in women and 0.50 in men. This means that a man whose hand-grip strength (measured in kg) is half of the person’s body weight has the best prospect for survival.
 
The study used data collected in PURE (Prospective Urban Rural Epidemiology Study) on 142,410 people aged 35-70 years from any one of four high-income countries, 12 middle-income countries, and five low-income countries. The study excluded people who had at baseline known coronary artery disease, stroke, heart failure, or cancer, and the adjusted analysis controlled for age, sex, region, education, activity, alcohol and tobacco use, and the baseline prevalence of hypertension and diabetes. During follow-up, 9,712 of these people died.

The researchers saw a nadir for mortality among people with a BMI of 25-29 kg/m2 for both cardiovascular and noncardiovascular deaths. In addition, the link between total mortality and BMI was strongest in the subgroup of people on one or more treatments aimed at preventing cardiovascular disease, while it essentially disappeared among people not receiving any cardiovascular disease preventive measures, highlighting that the relationship now identified depends on a context of overall cardiovascular disease risk reduction, Dr. Leong said. The results also showed a very clear, direct, linear relationship between higher BMI and both the incidence of diabetes and cardiovascular disease, as well as increased all-cause and noncardiovascular mortality among people with a BMI of less than 20 kg/m2.

Dr. Yusuf discussed the results of the analysis in a video interview.

The PURE study has received partial funding from unrestricted grants from several drug companies. Dr. Leong has been an advisor to Ferring Pharmaceuticals and has been a speaker on behalf of Janssen. Dr. Yusuf had no disclosures.

 

 

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Visceral adiposity linked to sixfold increase in masked hypertension

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– Visceral adiposity, but not body mass index or total body fat, significantly correlated with elevated 24-hour ambulatory systolic blood pressure, greater systolic variability, and masked hypertension in a study from the University of Pennsylvania, Philadelphia.

Dr. Jordana B. Cohen

Subjects in the highest quartile of visceral fat had a 6.3-fold greater odds of masked hypertension – normal in the office, but high at home – compared with those in the lowest quartile (95% confidence interval, 1.2-33.1).

The study findings suggest that central obesity, in particular, should trigger 24-hour ambulatory blood pressure monitoring (ABPM). “Every obese person should get a 24-hour” ABPM, but “we really need to be pushing [it] in people who have central adiposity. These are the patients ... we really need to focus on” because of the risk of masked hypertension, a “ticking time bomb” that greatly increases the risk of cardiovascular events, said lead investigator Jordana B. Cohen, MD, an assistant professor of medicine at the university.

The study also helps explain why body mass index (BMI) hasn’t been consistently linked to masked hypertension in previous studies; some studies likely included subjects with high BMIs but not central obesity.

Waist circumference, a marker of visceral adiposity, also correlated with elevated 24-hour systolic pressure and greater variability, but a trend for masked hypertension was not statistically significant, Dr. Cohen reported at the joint scientific sessions of the American Heart Association (AHA) Council on Hypertension, AHA Council on Kidney in Cardiovascular Disease, and American Society of Hypertension.

It’s long been known that visceral fat – fat around the abdominal organs – is metabolically active and associated with greater cardiovascular risk, but its relationship to blood pressure hadn’t been well described, so Dr. Cohen and her team decided to take a look.

They ran whole body dual x-ray absorptiometry scans on 96 hypertensive adults on a stable dose of one antihypertensive drug for at least 2 months and correlated the findings with ABPM. Subjects were an average of 58 years old, almost 60% were women, almost half were black, and 54% were obese, with BMIs of at least 30 kg/m2.

After adjustment for age, sex, race, and antihypertensive class, the team found a significant, linear correlation between visceral fat and mean 24-hour systolic blood pressure. Patients with a visceral adiposity of about 0.1 kg/m2, for instance, had a mean pressure of around 130 mm Hg, compared with patients with more than 0.6 kg/m2, who had a mean of almost 150 mm Hg. Findings were similar for waist circumference over a range of 70-150 cm.

The correlations were weak (r = 0.3), but Dr. Cohen said they might improve with ongoing enrollment. Both measures also correlated with systolic variability.

Overall, the highest quartiles of waist circumference and visceral adiposity correlated with the highest mean systolic pressures and greatest variability, compared with the lowest quartiles. Visceral adiposity was the only measure significantly linked with masked hypertension. Trends in those directions for increasing BMI and total body fat mass were not statistically significant.

Mean BMI in the study was 31.7 kg/m2, and mean waist circumference was 104 cm. Mean 24-hour systolic blood pressure was 135 mm Hg and mean 24-hour systolic variability was 13 mm Hg. Almost 30% of the subjects had masked hypertension. Drug classes included beta-blockers, calcium channel blockers, diuretics, ACE-inhibitors, and angiotensin receptor blockers.

Dr. Cohen plans to investigate drug response versus visceral adiposity once the recruitment goal of 150 subjects is reached.

There was no external funding, and the investigators reported that they didn’t have any relevant disclosures.

aotto@mdedge.com

SOURCE: Cohen JB et al. Joint Hypertension 2019, Abstract P2052.

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– Visceral adiposity, but not body mass index or total body fat, significantly correlated with elevated 24-hour ambulatory systolic blood pressure, greater systolic variability, and masked hypertension in a study from the University of Pennsylvania, Philadelphia.

Dr. Jordana B. Cohen

Subjects in the highest quartile of visceral fat had a 6.3-fold greater odds of masked hypertension – normal in the office, but high at home – compared with those in the lowest quartile (95% confidence interval, 1.2-33.1).

The study findings suggest that central obesity, in particular, should trigger 24-hour ambulatory blood pressure monitoring (ABPM). “Every obese person should get a 24-hour” ABPM, but “we really need to be pushing [it] in people who have central adiposity. These are the patients ... we really need to focus on” because of the risk of masked hypertension, a “ticking time bomb” that greatly increases the risk of cardiovascular events, said lead investigator Jordana B. Cohen, MD, an assistant professor of medicine at the university.

The study also helps explain why body mass index (BMI) hasn’t been consistently linked to masked hypertension in previous studies; some studies likely included subjects with high BMIs but not central obesity.

Waist circumference, a marker of visceral adiposity, also correlated with elevated 24-hour systolic pressure and greater variability, but a trend for masked hypertension was not statistically significant, Dr. Cohen reported at the joint scientific sessions of the American Heart Association (AHA) Council on Hypertension, AHA Council on Kidney in Cardiovascular Disease, and American Society of Hypertension.

It’s long been known that visceral fat – fat around the abdominal organs – is metabolically active and associated with greater cardiovascular risk, but its relationship to blood pressure hadn’t been well described, so Dr. Cohen and her team decided to take a look.

They ran whole body dual x-ray absorptiometry scans on 96 hypertensive adults on a stable dose of one antihypertensive drug for at least 2 months and correlated the findings with ABPM. Subjects were an average of 58 years old, almost 60% were women, almost half were black, and 54% were obese, with BMIs of at least 30 kg/m2.

After adjustment for age, sex, race, and antihypertensive class, the team found a significant, linear correlation between visceral fat and mean 24-hour systolic blood pressure. Patients with a visceral adiposity of about 0.1 kg/m2, for instance, had a mean pressure of around 130 mm Hg, compared with patients with more than 0.6 kg/m2, who had a mean of almost 150 mm Hg. Findings were similar for waist circumference over a range of 70-150 cm.

The correlations were weak (r = 0.3), but Dr. Cohen said they might improve with ongoing enrollment. Both measures also correlated with systolic variability.

Overall, the highest quartiles of waist circumference and visceral adiposity correlated with the highest mean systolic pressures and greatest variability, compared with the lowest quartiles. Visceral adiposity was the only measure significantly linked with masked hypertension. Trends in those directions for increasing BMI and total body fat mass were not statistically significant.

Mean BMI in the study was 31.7 kg/m2, and mean waist circumference was 104 cm. Mean 24-hour systolic blood pressure was 135 mm Hg and mean 24-hour systolic variability was 13 mm Hg. Almost 30% of the subjects had masked hypertension. Drug classes included beta-blockers, calcium channel blockers, diuretics, ACE-inhibitors, and angiotensin receptor blockers.

Dr. Cohen plans to investigate drug response versus visceral adiposity once the recruitment goal of 150 subjects is reached.

There was no external funding, and the investigators reported that they didn’t have any relevant disclosures.

aotto@mdedge.com

SOURCE: Cohen JB et al. Joint Hypertension 2019, Abstract P2052.

 

– Visceral adiposity, but not body mass index or total body fat, significantly correlated with elevated 24-hour ambulatory systolic blood pressure, greater systolic variability, and masked hypertension in a study from the University of Pennsylvania, Philadelphia.

Dr. Jordana B. Cohen

Subjects in the highest quartile of visceral fat had a 6.3-fold greater odds of masked hypertension – normal in the office, but high at home – compared with those in the lowest quartile (95% confidence interval, 1.2-33.1).

The study findings suggest that central obesity, in particular, should trigger 24-hour ambulatory blood pressure monitoring (ABPM). “Every obese person should get a 24-hour” ABPM, but “we really need to be pushing [it] in people who have central adiposity. These are the patients ... we really need to focus on” because of the risk of masked hypertension, a “ticking time bomb” that greatly increases the risk of cardiovascular events, said lead investigator Jordana B. Cohen, MD, an assistant professor of medicine at the university.

The study also helps explain why body mass index (BMI) hasn’t been consistently linked to masked hypertension in previous studies; some studies likely included subjects with high BMIs but not central obesity.

Waist circumference, a marker of visceral adiposity, also correlated with elevated 24-hour systolic pressure and greater variability, but a trend for masked hypertension was not statistically significant, Dr. Cohen reported at the joint scientific sessions of the American Heart Association (AHA) Council on Hypertension, AHA Council on Kidney in Cardiovascular Disease, and American Society of Hypertension.

It’s long been known that visceral fat – fat around the abdominal organs – is metabolically active and associated with greater cardiovascular risk, but its relationship to blood pressure hadn’t been well described, so Dr. Cohen and her team decided to take a look.

They ran whole body dual x-ray absorptiometry scans on 96 hypertensive adults on a stable dose of one antihypertensive drug for at least 2 months and correlated the findings with ABPM. Subjects were an average of 58 years old, almost 60% were women, almost half were black, and 54% were obese, with BMIs of at least 30 kg/m2.

After adjustment for age, sex, race, and antihypertensive class, the team found a significant, linear correlation between visceral fat and mean 24-hour systolic blood pressure. Patients with a visceral adiposity of about 0.1 kg/m2, for instance, had a mean pressure of around 130 mm Hg, compared with patients with more than 0.6 kg/m2, who had a mean of almost 150 mm Hg. Findings were similar for waist circumference over a range of 70-150 cm.

The correlations were weak (r = 0.3), but Dr. Cohen said they might improve with ongoing enrollment. Both measures also correlated with systolic variability.

Overall, the highest quartiles of waist circumference and visceral adiposity correlated with the highest mean systolic pressures and greatest variability, compared with the lowest quartiles. Visceral adiposity was the only measure significantly linked with masked hypertension. Trends in those directions for increasing BMI and total body fat mass were not statistically significant.

Mean BMI in the study was 31.7 kg/m2, and mean waist circumference was 104 cm. Mean 24-hour systolic blood pressure was 135 mm Hg and mean 24-hour systolic variability was 13 mm Hg. Almost 30% of the subjects had masked hypertension. Drug classes included beta-blockers, calcium channel blockers, diuretics, ACE-inhibitors, and angiotensin receptor blockers.

Dr. Cohen plans to investigate drug response versus visceral adiposity once the recruitment goal of 150 subjects is reached.

There was no external funding, and the investigators reported that they didn’t have any relevant disclosures.

aotto@mdedge.com

SOURCE: Cohen JB et al. Joint Hypertension 2019, Abstract P2052.

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Guideline: Blood CO2 can be used to screen for OHS

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Guideline: Blood CO2 can be used to screen for OHS

A blood test for elevated carbon dioxide may be used in screening adults for obesity hypoventilation syndrome, according to new guidelines.

Obese adults with sleep-disordered breathing and increased blood carbon dioxide levels during the day are likely to have obesity hypoventilation syndrome (OHS), a result of shallow or slow breathing that can lead to respiratory failure, heart failure, pulmonary hypertension, and death. Pulmonologists and sleep specialists may be the first to see and diagnose patients with OHS in the outpatient setting, while other cases are diagnosed in the hospital when patients present with hypercapnic respiratory failure.

Screening for OHS usually involves measuring arterial blood gases, which is not standard practice in outpatient clinics. Patients often remain undiagnosed and untreated until late in the course of the disease, according to the American Thoracic Society, which in August published a new diagnosis and management guideline aiming to boost early diagnosis and reduce variability in treatment (Am J Respir Crit Care Med. 2019;200:3,e6–e24).

The guideline authors, led by Babak Mokhlesi, MD, of the University of Chicago, recommend a simpler screening method – measuring serum bicarbonate only – to rule out OHS in obese patients with nighttime breathing problems.

Serum bicarbonate should be measured in obese patients with sleep-disordered breathing and a low likelihood of OHS, Dr. Mokhlesi and colleagues recommend in the guideline. If serum bicarbonate is below 27 mmol/L, it is not necessary to conduct further testing as the patient is unlikely to have OHS.

In patients whose serum bicarbonate is higher than 27 mmol/L, or who are strongly suspected of having OHS at presentation because of severe obesity or other symptoms, arterial blood gases should be measured and a sleep study conducted. The guideline authors said that there is insufficient evidence to recommend that pulse oximetry be used in the diagnostic pathway for OHS.

First-line treatment for stable, ambulatory patients with OHS should be positive airway pressure during sleep, rather than noninvasive ventilation, Dr. Mokhlesi and colleagues concluded. For patients with comorbid obstructive sleep apnea – as many as 70% of OHS patients also have OSA – the first-line treatment should be continuous positive airway pressure (CPAP) at night, the guideline states.

Patients hospitalized with respiratory failure and suspected of having OHS should be discharged with noninvasive ventilation until diagnostic procedures can be performed, along with PAP titration in a sleep lab.

In patients initially treated with CPAP who remain symptomatic or whose blood carbon dioxide does not improve, noninvasive ventilation can be tried, the guidelines say. Finally, patients diagnosed with OHS should be guided to weight loss interventions with the aim of reducing body weight by 25%-30%. This can include referral for bariatric surgery in patients without contraindications.

Dr. Mokhlesi and colleagues acknowledged that all of the recommendations contained in the guideline are classed as “conditional,” based on the quality of evidence assessed.

The American Thoracic Society funded the study. Dr. Mokhlesi and 7 coauthors disclosed financial conflicts of interest, while an additional 13 coauthors had none. Disclosures can be found on the AJRCCM website.

SOURCE: Mokhlesi B et al. Am J Respir Crit Care Med. 2019;200:3,e6-e24

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A blood test for elevated carbon dioxide may be used in screening adults for obesity hypoventilation syndrome, according to new guidelines.

Obese adults with sleep-disordered breathing and increased blood carbon dioxide levels during the day are likely to have obesity hypoventilation syndrome (OHS), a result of shallow or slow breathing that can lead to respiratory failure, heart failure, pulmonary hypertension, and death. Pulmonologists and sleep specialists may be the first to see and diagnose patients with OHS in the outpatient setting, while other cases are diagnosed in the hospital when patients present with hypercapnic respiratory failure.

Screening for OHS usually involves measuring arterial blood gases, which is not standard practice in outpatient clinics. Patients often remain undiagnosed and untreated until late in the course of the disease, according to the American Thoracic Society, which in August published a new diagnosis and management guideline aiming to boost early diagnosis and reduce variability in treatment (Am J Respir Crit Care Med. 2019;200:3,e6–e24).

The guideline authors, led by Babak Mokhlesi, MD, of the University of Chicago, recommend a simpler screening method – measuring serum bicarbonate only – to rule out OHS in obese patients with nighttime breathing problems.

Serum bicarbonate should be measured in obese patients with sleep-disordered breathing and a low likelihood of OHS, Dr. Mokhlesi and colleagues recommend in the guideline. If serum bicarbonate is below 27 mmol/L, it is not necessary to conduct further testing as the patient is unlikely to have OHS.

In patients whose serum bicarbonate is higher than 27 mmol/L, or who are strongly suspected of having OHS at presentation because of severe obesity or other symptoms, arterial blood gases should be measured and a sleep study conducted. The guideline authors said that there is insufficient evidence to recommend that pulse oximetry be used in the diagnostic pathway for OHS.

First-line treatment for stable, ambulatory patients with OHS should be positive airway pressure during sleep, rather than noninvasive ventilation, Dr. Mokhlesi and colleagues concluded. For patients with comorbid obstructive sleep apnea – as many as 70% of OHS patients also have OSA – the first-line treatment should be continuous positive airway pressure (CPAP) at night, the guideline states.

Patients hospitalized with respiratory failure and suspected of having OHS should be discharged with noninvasive ventilation until diagnostic procedures can be performed, along with PAP titration in a sleep lab.

In patients initially treated with CPAP who remain symptomatic or whose blood carbon dioxide does not improve, noninvasive ventilation can be tried, the guidelines say. Finally, patients diagnosed with OHS should be guided to weight loss interventions with the aim of reducing body weight by 25%-30%. This can include referral for bariatric surgery in patients without contraindications.

Dr. Mokhlesi and colleagues acknowledged that all of the recommendations contained in the guideline are classed as “conditional,” based on the quality of evidence assessed.

The American Thoracic Society funded the study. Dr. Mokhlesi and 7 coauthors disclosed financial conflicts of interest, while an additional 13 coauthors had none. Disclosures can be found on the AJRCCM website.

SOURCE: Mokhlesi B et al. Am J Respir Crit Care Med. 2019;200:3,e6-e24

A blood test for elevated carbon dioxide may be used in screening adults for obesity hypoventilation syndrome, according to new guidelines.

Obese adults with sleep-disordered breathing and increased blood carbon dioxide levels during the day are likely to have obesity hypoventilation syndrome (OHS), a result of shallow or slow breathing that can lead to respiratory failure, heart failure, pulmonary hypertension, and death. Pulmonologists and sleep specialists may be the first to see and diagnose patients with OHS in the outpatient setting, while other cases are diagnosed in the hospital when patients present with hypercapnic respiratory failure.

Screening for OHS usually involves measuring arterial blood gases, which is not standard practice in outpatient clinics. Patients often remain undiagnosed and untreated until late in the course of the disease, according to the American Thoracic Society, which in August published a new diagnosis and management guideline aiming to boost early diagnosis and reduce variability in treatment (Am J Respir Crit Care Med. 2019;200:3,e6–e24).

The guideline authors, led by Babak Mokhlesi, MD, of the University of Chicago, recommend a simpler screening method – measuring serum bicarbonate only – to rule out OHS in obese patients with nighttime breathing problems.

Serum bicarbonate should be measured in obese patients with sleep-disordered breathing and a low likelihood of OHS, Dr. Mokhlesi and colleagues recommend in the guideline. If serum bicarbonate is below 27 mmol/L, it is not necessary to conduct further testing as the patient is unlikely to have OHS.

In patients whose serum bicarbonate is higher than 27 mmol/L, or who are strongly suspected of having OHS at presentation because of severe obesity or other symptoms, arterial blood gases should be measured and a sleep study conducted. The guideline authors said that there is insufficient evidence to recommend that pulse oximetry be used in the diagnostic pathway for OHS.

First-line treatment for stable, ambulatory patients with OHS should be positive airway pressure during sleep, rather than noninvasive ventilation, Dr. Mokhlesi and colleagues concluded. For patients with comorbid obstructive sleep apnea – as many as 70% of OHS patients also have OSA – the first-line treatment should be continuous positive airway pressure (CPAP) at night, the guideline states.

Patients hospitalized with respiratory failure and suspected of having OHS should be discharged with noninvasive ventilation until diagnostic procedures can be performed, along with PAP titration in a sleep lab.

In patients initially treated with CPAP who remain symptomatic or whose blood carbon dioxide does not improve, noninvasive ventilation can be tried, the guidelines say. Finally, patients diagnosed with OHS should be guided to weight loss interventions with the aim of reducing body weight by 25%-30%. This can include referral for bariatric surgery in patients without contraindications.

Dr. Mokhlesi and colleagues acknowledged that all of the recommendations contained in the guideline are classed as “conditional,” based on the quality of evidence assessed.

The American Thoracic Society funded the study. Dr. Mokhlesi and 7 coauthors disclosed financial conflicts of interest, while an additional 13 coauthors had none. Disclosures can be found on the AJRCCM website.

SOURCE: Mokhlesi B et al. Am J Respir Crit Care Med. 2019;200:3,e6-e24

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FROM THE AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE

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NICE issues recommendation for dapagliflozin-insulin therapy in type 1 diabetes

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The U.K. National Institute for Health and Care Excellence (NICE) has issued new guidance on the combined usage of dapagliflozin and insulin for treating patients with type 1 diabetes inadequately controlled by insulin alone.

In a review of clinical trials, NICE found that dapagliflozin plus insulin conferred small benefits in hemoglobin A1c, weight loss, and quality of life, compared with insulin alone. These benefits translated to a reduced risk of long-term complications over the lifetime of the patient.

In the new NICE guideline, dual treatment with dapagliflozin and insulin in adults with type 1 diabetes and a body mass index greater than 27 kg/m2 is recommended only when they are receiving insulin doses of more than 0.5 units/kg per day; have undergone an evidence-based, quality-assured education program; and are supervised by a physician specializing in endocrinology and diabetes.

Hemoglobin A1c levels should be assessed after 6 months and at regular intervals after that; if glycemic control is not improved, dapagliflozin should be stopped, as there is an increased risk of diabetic ketoacidosis.

Find the full technology appraisal guidance on the NICE website.

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The U.K. National Institute for Health and Care Excellence (NICE) has issued new guidance on the combined usage of dapagliflozin and insulin for treating patients with type 1 diabetes inadequately controlled by insulin alone.

In a review of clinical trials, NICE found that dapagliflozin plus insulin conferred small benefits in hemoglobin A1c, weight loss, and quality of life, compared with insulin alone. These benefits translated to a reduced risk of long-term complications over the lifetime of the patient.

In the new NICE guideline, dual treatment with dapagliflozin and insulin in adults with type 1 diabetes and a body mass index greater than 27 kg/m2 is recommended only when they are receiving insulin doses of more than 0.5 units/kg per day; have undergone an evidence-based, quality-assured education program; and are supervised by a physician specializing in endocrinology and diabetes.

Hemoglobin A1c levels should be assessed after 6 months and at regular intervals after that; if glycemic control is not improved, dapagliflozin should be stopped, as there is an increased risk of diabetic ketoacidosis.

Find the full technology appraisal guidance on the NICE website.

 

The U.K. National Institute for Health and Care Excellence (NICE) has issued new guidance on the combined usage of dapagliflozin and insulin for treating patients with type 1 diabetes inadequately controlled by insulin alone.

In a review of clinical trials, NICE found that dapagliflozin plus insulin conferred small benefits in hemoglobin A1c, weight loss, and quality of life, compared with insulin alone. These benefits translated to a reduced risk of long-term complications over the lifetime of the patient.

In the new NICE guideline, dual treatment with dapagliflozin and insulin in adults with type 1 diabetes and a body mass index greater than 27 kg/m2 is recommended only when they are receiving insulin doses of more than 0.5 units/kg per day; have undergone an evidence-based, quality-assured education program; and are supervised by a physician specializing in endocrinology and diabetes.

Hemoglobin A1c levels should be assessed after 6 months and at regular intervals after that; if glycemic control is not improved, dapagliflozin should be stopped, as there is an increased risk of diabetic ketoacidosis.

Find the full technology appraisal guidance on the NICE website.

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BPA substitutes bisphenol S and bisphenol F linked to obesity

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Though exposure to the obesogen bisphenol A (BPA) is decreasing, a new study has linked substitute chemicals bisphenol S (BPS) and bisphenol F (BPF) to obesity as well.

“The potential health effects of BPS and other BPA replacement compounds should be monitored going forward, given that human exposure to these compounds is likely to continue to increase in the future,” wrote Melanie H. Jacobson, PhD, of New York University, and coauthors. Their report is in the Journal of the Endocrine Society.

BPA is one of the best known synthetic chemical obesogens, the authors noted. “It enlarges adipocytes and enhances differentiation from mesenchymal cells to adipocytes, inhibits adiponectin function, and is a synthetic estrogen and thereby can have sex-specific effects on body mass,” they explained.

To determine if the BPA analogues, BPS and BPF, could also induce obesity, the researchers analyzed data from 1,831 children and adolescents gathered through the U.S. National Health and Nutrition Examination Surveys from 2013 to 2016. Concentrations of BPA, BPS, and BPF were measured in spot urine samples and they were detected in 97.5%, 87.8%, and 55.2% of samples, respectively.

Log-transformed BPS concentrations were associated with an increased prevalence of general obesity (odds ratio, 1.16; 95% confidence interval, 1.02-1.32), which was defined as being greater than or equal to the 95th percentile of standardized body mass index z scores. BPS concentrations were also associated with an increased prevalence of abdominal obesity (OR, 1.13; 95% CI, 1.02-1.27), as was BPF detection (OR, 1.29; 95% CI, 1.01-1.64).

BPA and total bisphenols were not significantly associated with general or abdominal obesity.

“Though tissue and animal studies of the replacements are lacking, [BPS and BPF] have shown estrogenic activity. Further, BPS has been shown to promote preadipocyte differentiation, raising the possibility that these BPA replacements may induce the same obesogenic effects in humans,” the authors wrote.

They acknowledged that their results should be interpreted cautiously, because they were not able to determine if exposure to bisphenols influences weight gain or if obese children are merely more exposed to those compounds. In addition, because BPS and BPF are metabolized rapidly, spot urine samples cannot accurately reflect long-term exposure levels. Finally, because a good deal of food and beverage packaging contains bisphenols, “those who consume more of these products are more likely to have higher exposure levels,” they wrote.

The study was funded by grants from the National Institutes of Environmental Health Sciences. The authors reported no conflicts of interest.

SOURCE: Jacobson MH et al. J Endocr Soc. 2019 Jul 25. doi: 10.1210/js.2019-00201.

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Though exposure to the obesogen bisphenol A (BPA) is decreasing, a new study has linked substitute chemicals bisphenol S (BPS) and bisphenol F (BPF) to obesity as well.

“The potential health effects of BPS and other BPA replacement compounds should be monitored going forward, given that human exposure to these compounds is likely to continue to increase in the future,” wrote Melanie H. Jacobson, PhD, of New York University, and coauthors. Their report is in the Journal of the Endocrine Society.

BPA is one of the best known synthetic chemical obesogens, the authors noted. “It enlarges adipocytes and enhances differentiation from mesenchymal cells to adipocytes, inhibits adiponectin function, and is a synthetic estrogen and thereby can have sex-specific effects on body mass,” they explained.

To determine if the BPA analogues, BPS and BPF, could also induce obesity, the researchers analyzed data from 1,831 children and adolescents gathered through the U.S. National Health and Nutrition Examination Surveys from 2013 to 2016. Concentrations of BPA, BPS, and BPF were measured in spot urine samples and they were detected in 97.5%, 87.8%, and 55.2% of samples, respectively.

Log-transformed BPS concentrations were associated with an increased prevalence of general obesity (odds ratio, 1.16; 95% confidence interval, 1.02-1.32), which was defined as being greater than or equal to the 95th percentile of standardized body mass index z scores. BPS concentrations were also associated with an increased prevalence of abdominal obesity (OR, 1.13; 95% CI, 1.02-1.27), as was BPF detection (OR, 1.29; 95% CI, 1.01-1.64).

BPA and total bisphenols were not significantly associated with general or abdominal obesity.

“Though tissue and animal studies of the replacements are lacking, [BPS and BPF] have shown estrogenic activity. Further, BPS has been shown to promote preadipocyte differentiation, raising the possibility that these BPA replacements may induce the same obesogenic effects in humans,” the authors wrote.

They acknowledged that their results should be interpreted cautiously, because they were not able to determine if exposure to bisphenols influences weight gain or if obese children are merely more exposed to those compounds. In addition, because BPS and BPF are metabolized rapidly, spot urine samples cannot accurately reflect long-term exposure levels. Finally, because a good deal of food and beverage packaging contains bisphenols, “those who consume more of these products are more likely to have higher exposure levels,” they wrote.

The study was funded by grants from the National Institutes of Environmental Health Sciences. The authors reported no conflicts of interest.

SOURCE: Jacobson MH et al. J Endocr Soc. 2019 Jul 25. doi: 10.1210/js.2019-00201.

 

Though exposure to the obesogen bisphenol A (BPA) is decreasing, a new study has linked substitute chemicals bisphenol S (BPS) and bisphenol F (BPF) to obesity as well.

“The potential health effects of BPS and other BPA replacement compounds should be monitored going forward, given that human exposure to these compounds is likely to continue to increase in the future,” wrote Melanie H. Jacobson, PhD, of New York University, and coauthors. Their report is in the Journal of the Endocrine Society.

BPA is one of the best known synthetic chemical obesogens, the authors noted. “It enlarges adipocytes and enhances differentiation from mesenchymal cells to adipocytes, inhibits adiponectin function, and is a synthetic estrogen and thereby can have sex-specific effects on body mass,” they explained.

To determine if the BPA analogues, BPS and BPF, could also induce obesity, the researchers analyzed data from 1,831 children and adolescents gathered through the U.S. National Health and Nutrition Examination Surveys from 2013 to 2016. Concentrations of BPA, BPS, and BPF were measured in spot urine samples and they were detected in 97.5%, 87.8%, and 55.2% of samples, respectively.

Log-transformed BPS concentrations were associated with an increased prevalence of general obesity (odds ratio, 1.16; 95% confidence interval, 1.02-1.32), which was defined as being greater than or equal to the 95th percentile of standardized body mass index z scores. BPS concentrations were also associated with an increased prevalence of abdominal obesity (OR, 1.13; 95% CI, 1.02-1.27), as was BPF detection (OR, 1.29; 95% CI, 1.01-1.64).

BPA and total bisphenols were not significantly associated with general or abdominal obesity.

“Though tissue and animal studies of the replacements are lacking, [BPS and BPF] have shown estrogenic activity. Further, BPS has been shown to promote preadipocyte differentiation, raising the possibility that these BPA replacements may induce the same obesogenic effects in humans,” the authors wrote.

They acknowledged that their results should be interpreted cautiously, because they were not able to determine if exposure to bisphenols influences weight gain or if obese children are merely more exposed to those compounds. In addition, because BPS and BPF are metabolized rapidly, spot urine samples cannot accurately reflect long-term exposure levels. Finally, because a good deal of food and beverage packaging contains bisphenols, “those who consume more of these products are more likely to have higher exposure levels,” they wrote.

The study was funded by grants from the National Institutes of Environmental Health Sciences. The authors reported no conflicts of interest.

SOURCE: Jacobson MH et al. J Endocr Soc. 2019 Jul 25. doi: 10.1210/js.2019-00201.

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FROM JOURNAL OF THE ENDOCRINE SOCIETY

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Diabetic dyslipidemia with eruptive xanthoma

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Diabetic dyslipidemia with eruptive xanthoma

Figure 1. The patient had multiple pink to yellowish papules 2 to 5 mm in diameter over the extensor surface of the right upper arm (A) and left thigh (B).
A 21-year-old woman with obesity, type 2 diabetes mellitus, and dyslipidemia presented with eruptive lesions on her extremities that first appeared 2 weeks earlier. Yellowish erythematous papules were noted on the extensor surfaces of both arms and thighs (Figure 1).

Figure 2. Biopsy study showed foamy histiocytes (arrows) mixed with streaks of connective tissue (arrowhead) in the dermis, features typical of eruptive xanthoma (hematoxylin and eosin, × 200).
Skin biopsy study showed foamy histiocytes mixed with streaks of connective tissue in the dermis (Figure 2). Her fasting serum triglyceride level was 10,250 mg/dL (reference range < 150) and her hemoglobin A1c level was 12.4% (reference range 4%–5.6%). On further questioning, the patient said that she had stopped taking her prescribed antidiabetic medications and fenofibrate a year previously.

A workup for secondary causes of hypertriglyceridemia was negative for hypothyroidism and nephrotic syndrome. She was currently taking no medications. She had no family history of dyslipidemia, and she denied alcohol consumption.

Based on the patient’s presentation, history, and the results of laboratory testing and skin biopsy, the diagnosis was eruptive xanthoma.

A RESULT OF ELEVATED TRIGLYCERIDES

Eruptive xanthoma is associated with elevation of chylomicrons and triglycerides.1 Hyperlipidemia that causes eruptive xanthoma may be familial (ie, due to a primary genetic defect) or secondary to another disease, or both.

Types of primary hypertriglyceridemia include elevated chylomicrons (Frederickson classification type I), elevated very-low-density lipoprotein (VLDL) (Frederickson type IV), and elevation of both chylomicrons and VLDL (Frederickson type V).2,3 Hypertriglyceridemia may also be secondary to obesity, diabetes mellitus, hypothyroidism, nephrotic syndrome, liver cirrhosis, excess ethanol ingestion, and medicines such as retinoids and estrogens.2,3

Lesions of eruptive xanthoma are yellowish papules 2 to 5 mm in diameter surrounded by an erythematous border. They are formed by clusters of foamy cells caused by phagocytosis of macrophages as a consequence of increased accumulations of intracellular lipids. The most common sites are the buttocks, extensor surfaces of the arms, and the back.4

Eruptive xanthoma occurs with markedly elevated triglyceride levels (ie, > 1,000 mg/dL),5 with an estimated prevalence of 18 cases per 100,000 people (< 0.02%).6 Diagnosis is usually established through the clinical history, physical examination, and prompt laboratory confirmation of hypertriglyceridemia. Skin biopsy is rarely if ever needed.

RECOGNIZE AND TREAT PROMPTLY TO AVOID FURTHER COMPLICATIONS

Severe hypertriglyceridemia poses an increased risk of acute pancreatitis. Early recognition and medical treatment in our patient prevented serious complications.

Treatment of eruptive xanthoma includes identifying the underlying cause of hypertriglyceridemia and commencing lifestyle modifications that include weight reduction, aerobic exercise, a strict low-fat diet with avoidance of simple carbohydrates and alcohol,7 and drug therapy.

The patient’s treatment plan

Although HMG-CoA reductase inhibitors (statins) have a modest triglyceride-lowering effect and are useful to modify cardiovascular risk, fibric acid derivatives (eg, gemfibrozil, fenofibrate) are the first-line therapy.8 Omega-3 fatty acids, statins, or niacin may be added if necessary.8

Our patient’s uncontrolled glycemia caused marked hypertriglyceridemia, perhaps from a decrease in lipoprotein lipase activity in adipose tissue and muscle. Lifestyle modifications, glucose-lowering agents (metformin, glimepiride), and fenofibrate were prescribed. She was also advised to seek medical attention if she developed upper-abdominal pain, which could be a symptom of pancreatitis.

References
  1. Flynn PD, Burns T, Breathnach S, Cox N, Griffiths C. Xanthomas and abnormalities of lipid metabolism and storage. In: Rook’s Textbook of Dermatology. 8th ed. Oxford: Blackwell Science; 2010.
  2. Breckenridge WC, Alaupovic P, Cox DW, Little JA. Apolipoprotein and lipoprotein concentrations in familial apolipoprotein C-II deficiency. Atherosclerosis 1982; 44(2):223–235. pmid:7138621
  3. Santamarina-Fojo S. The familial chylomicronemia syndrome. Endocrinol Metab Clin North Am 1998; 27(3):551–567. pmid:9785052
  4. Melmed S, Polonsky KS, Larsen PR, Kronenberg H. Williams Textbook of Endocrinology. 13th ed. Philadelphia: Elsevier; 2016.
  5. Zak A, Zeman M, Slaby A, Vecka M. Xanthomas: clinical and pathophysiological relations. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2014; 158(2):181–188. doi:10.5507/bp.2014.016
  6. Leaf DA. Chylomicronemia and the chylomicronemia syndrome: a practical approach to management. Am J Med 2008; 121(1):10–12. doi:10.1016/j.amjmed.2007.10.004
  7. Hegele RA, Ginsberg HN, Chapman MJ, et al; European Atherosclerosis Society Consensus Panel. The polygenic nature of hypertriglyceridaemia: implications for definition, diagnosis, and management. Lancet Diabetes Endocrinol 2014; 2(8):655–666. doi:10.1016/S2213-8587(13)70191-8
  8. Berglund L, Brunzell JD, Goldberg AC, et al; Endocrine Society. Evaluation and treatment of hypertriglyceridemia: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2012; 97(9):2969–2989. doi:10.1210/jc.2011-3213
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Yu-Chun Hsueh, MD
Division of Endocrinology and Metabolism, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan

Chuan-Liang Chou, MD
Division of Endocrinology and Metabolism, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan

Ting-I. Lee, MD, PhD
Division of Endocrinology and Metabolism, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University; Department of General Medicine, School of Medicine, College of Medicine, Taipei Medical University; Division of Endocrinology and Metabolism, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan

Address: Ting-I. Lee, MD, PhD, Wan Fang Hospital, Taipei Medical University, 111 Shin Lung Road Section 3, Taipei, Taiwan; agleems29@gmail.com

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Chuan-Liang Chou, MD
Division of Endocrinology and Metabolism, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan

Ting-I. Lee, MD, PhD
Division of Endocrinology and Metabolism, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University; Department of General Medicine, School of Medicine, College of Medicine, Taipei Medical University; Division of Endocrinology and Metabolism, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan

Address: Ting-I. Lee, MD, PhD, Wan Fang Hospital, Taipei Medical University, 111 Shin Lung Road Section 3, Taipei, Taiwan; agleems29@gmail.com

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Yu-Chun Hsueh, MD
Division of Endocrinology and Metabolism, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan

Chuan-Liang Chou, MD
Division of Endocrinology and Metabolism, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan

Ting-I. Lee, MD, PhD
Division of Endocrinology and Metabolism, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University; Department of General Medicine, School of Medicine, College of Medicine, Taipei Medical University; Division of Endocrinology and Metabolism, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan

Address: Ting-I. Lee, MD, PhD, Wan Fang Hospital, Taipei Medical University, 111 Shin Lung Road Section 3, Taipei, Taiwan; agleems29@gmail.com

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Figure 1. The patient had multiple pink to yellowish papules 2 to 5 mm in diameter over the extensor surface of the right upper arm (A) and left thigh (B).
A 21-year-old woman with obesity, type 2 diabetes mellitus, and dyslipidemia presented with eruptive lesions on her extremities that first appeared 2 weeks earlier. Yellowish erythematous papules were noted on the extensor surfaces of both arms and thighs (Figure 1).

Figure 2. Biopsy study showed foamy histiocytes (arrows) mixed with streaks of connective tissue (arrowhead) in the dermis, features typical of eruptive xanthoma (hematoxylin and eosin, × 200).
Skin biopsy study showed foamy histiocytes mixed with streaks of connective tissue in the dermis (Figure 2). Her fasting serum triglyceride level was 10,250 mg/dL (reference range < 150) and her hemoglobin A1c level was 12.4% (reference range 4%–5.6%). On further questioning, the patient said that she had stopped taking her prescribed antidiabetic medications and fenofibrate a year previously.

A workup for secondary causes of hypertriglyceridemia was negative for hypothyroidism and nephrotic syndrome. She was currently taking no medications. She had no family history of dyslipidemia, and she denied alcohol consumption.

Based on the patient’s presentation, history, and the results of laboratory testing and skin biopsy, the diagnosis was eruptive xanthoma.

A RESULT OF ELEVATED TRIGLYCERIDES

Eruptive xanthoma is associated with elevation of chylomicrons and triglycerides.1 Hyperlipidemia that causes eruptive xanthoma may be familial (ie, due to a primary genetic defect) or secondary to another disease, or both.

Types of primary hypertriglyceridemia include elevated chylomicrons (Frederickson classification type I), elevated very-low-density lipoprotein (VLDL) (Frederickson type IV), and elevation of both chylomicrons and VLDL (Frederickson type V).2,3 Hypertriglyceridemia may also be secondary to obesity, diabetes mellitus, hypothyroidism, nephrotic syndrome, liver cirrhosis, excess ethanol ingestion, and medicines such as retinoids and estrogens.2,3

Lesions of eruptive xanthoma are yellowish papules 2 to 5 mm in diameter surrounded by an erythematous border. They are formed by clusters of foamy cells caused by phagocytosis of macrophages as a consequence of increased accumulations of intracellular lipids. The most common sites are the buttocks, extensor surfaces of the arms, and the back.4

Eruptive xanthoma occurs with markedly elevated triglyceride levels (ie, > 1,000 mg/dL),5 with an estimated prevalence of 18 cases per 100,000 people (< 0.02%).6 Diagnosis is usually established through the clinical history, physical examination, and prompt laboratory confirmation of hypertriglyceridemia. Skin biopsy is rarely if ever needed.

RECOGNIZE AND TREAT PROMPTLY TO AVOID FURTHER COMPLICATIONS

Severe hypertriglyceridemia poses an increased risk of acute pancreatitis. Early recognition and medical treatment in our patient prevented serious complications.

Treatment of eruptive xanthoma includes identifying the underlying cause of hypertriglyceridemia and commencing lifestyle modifications that include weight reduction, aerobic exercise, a strict low-fat diet with avoidance of simple carbohydrates and alcohol,7 and drug therapy.

The patient’s treatment plan

Although HMG-CoA reductase inhibitors (statins) have a modest triglyceride-lowering effect and are useful to modify cardiovascular risk, fibric acid derivatives (eg, gemfibrozil, fenofibrate) are the first-line therapy.8 Omega-3 fatty acids, statins, or niacin may be added if necessary.8

Our patient’s uncontrolled glycemia caused marked hypertriglyceridemia, perhaps from a decrease in lipoprotein lipase activity in adipose tissue and muscle. Lifestyle modifications, glucose-lowering agents (metformin, glimepiride), and fenofibrate were prescribed. She was also advised to seek medical attention if she developed upper-abdominal pain, which could be a symptom of pancreatitis.

Figure 1. The patient had multiple pink to yellowish papules 2 to 5 mm in diameter over the extensor surface of the right upper arm (A) and left thigh (B).
A 21-year-old woman with obesity, type 2 diabetes mellitus, and dyslipidemia presented with eruptive lesions on her extremities that first appeared 2 weeks earlier. Yellowish erythematous papules were noted on the extensor surfaces of both arms and thighs (Figure 1).

Figure 2. Biopsy study showed foamy histiocytes (arrows) mixed with streaks of connective tissue (arrowhead) in the dermis, features typical of eruptive xanthoma (hematoxylin and eosin, × 200).
Skin biopsy study showed foamy histiocytes mixed with streaks of connective tissue in the dermis (Figure 2). Her fasting serum triglyceride level was 10,250 mg/dL (reference range < 150) and her hemoglobin A1c level was 12.4% (reference range 4%–5.6%). On further questioning, the patient said that she had stopped taking her prescribed antidiabetic medications and fenofibrate a year previously.

A workup for secondary causes of hypertriglyceridemia was negative for hypothyroidism and nephrotic syndrome. She was currently taking no medications. She had no family history of dyslipidemia, and she denied alcohol consumption.

Based on the patient’s presentation, history, and the results of laboratory testing and skin biopsy, the diagnosis was eruptive xanthoma.

A RESULT OF ELEVATED TRIGLYCERIDES

Eruptive xanthoma is associated with elevation of chylomicrons and triglycerides.1 Hyperlipidemia that causes eruptive xanthoma may be familial (ie, due to a primary genetic defect) or secondary to another disease, or both.

Types of primary hypertriglyceridemia include elevated chylomicrons (Frederickson classification type I), elevated very-low-density lipoprotein (VLDL) (Frederickson type IV), and elevation of both chylomicrons and VLDL (Frederickson type V).2,3 Hypertriglyceridemia may also be secondary to obesity, diabetes mellitus, hypothyroidism, nephrotic syndrome, liver cirrhosis, excess ethanol ingestion, and medicines such as retinoids and estrogens.2,3

Lesions of eruptive xanthoma are yellowish papules 2 to 5 mm in diameter surrounded by an erythematous border. They are formed by clusters of foamy cells caused by phagocytosis of macrophages as a consequence of increased accumulations of intracellular lipids. The most common sites are the buttocks, extensor surfaces of the arms, and the back.4

Eruptive xanthoma occurs with markedly elevated triglyceride levels (ie, > 1,000 mg/dL),5 with an estimated prevalence of 18 cases per 100,000 people (< 0.02%).6 Diagnosis is usually established through the clinical history, physical examination, and prompt laboratory confirmation of hypertriglyceridemia. Skin biopsy is rarely if ever needed.

RECOGNIZE AND TREAT PROMPTLY TO AVOID FURTHER COMPLICATIONS

Severe hypertriglyceridemia poses an increased risk of acute pancreatitis. Early recognition and medical treatment in our patient prevented serious complications.

Treatment of eruptive xanthoma includes identifying the underlying cause of hypertriglyceridemia and commencing lifestyle modifications that include weight reduction, aerobic exercise, a strict low-fat diet with avoidance of simple carbohydrates and alcohol,7 and drug therapy.

The patient’s treatment plan

Although HMG-CoA reductase inhibitors (statins) have a modest triglyceride-lowering effect and are useful to modify cardiovascular risk, fibric acid derivatives (eg, gemfibrozil, fenofibrate) are the first-line therapy.8 Omega-3 fatty acids, statins, or niacin may be added if necessary.8

Our patient’s uncontrolled glycemia caused marked hypertriglyceridemia, perhaps from a decrease in lipoprotein lipase activity in adipose tissue and muscle. Lifestyle modifications, glucose-lowering agents (metformin, glimepiride), and fenofibrate were prescribed. She was also advised to seek medical attention if she developed upper-abdominal pain, which could be a symptom of pancreatitis.

References
  1. Flynn PD, Burns T, Breathnach S, Cox N, Griffiths C. Xanthomas and abnormalities of lipid metabolism and storage. In: Rook’s Textbook of Dermatology. 8th ed. Oxford: Blackwell Science; 2010.
  2. Breckenridge WC, Alaupovic P, Cox DW, Little JA. Apolipoprotein and lipoprotein concentrations in familial apolipoprotein C-II deficiency. Atherosclerosis 1982; 44(2):223–235. pmid:7138621
  3. Santamarina-Fojo S. The familial chylomicronemia syndrome. Endocrinol Metab Clin North Am 1998; 27(3):551–567. pmid:9785052
  4. Melmed S, Polonsky KS, Larsen PR, Kronenberg H. Williams Textbook of Endocrinology. 13th ed. Philadelphia: Elsevier; 2016.
  5. Zak A, Zeman M, Slaby A, Vecka M. Xanthomas: clinical and pathophysiological relations. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2014; 158(2):181–188. doi:10.5507/bp.2014.016
  6. Leaf DA. Chylomicronemia and the chylomicronemia syndrome: a practical approach to management. Am J Med 2008; 121(1):10–12. doi:10.1016/j.amjmed.2007.10.004
  7. Hegele RA, Ginsberg HN, Chapman MJ, et al; European Atherosclerosis Society Consensus Panel. The polygenic nature of hypertriglyceridaemia: implications for definition, diagnosis, and management. Lancet Diabetes Endocrinol 2014; 2(8):655–666. doi:10.1016/S2213-8587(13)70191-8
  8. Berglund L, Brunzell JD, Goldberg AC, et al; Endocrine Society. Evaluation and treatment of hypertriglyceridemia: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2012; 97(9):2969–2989. doi:10.1210/jc.2011-3213
References
  1. Flynn PD, Burns T, Breathnach S, Cox N, Griffiths C. Xanthomas and abnormalities of lipid metabolism and storage. In: Rook’s Textbook of Dermatology. 8th ed. Oxford: Blackwell Science; 2010.
  2. Breckenridge WC, Alaupovic P, Cox DW, Little JA. Apolipoprotein and lipoprotein concentrations in familial apolipoprotein C-II deficiency. Atherosclerosis 1982; 44(2):223–235. pmid:7138621
  3. Santamarina-Fojo S. The familial chylomicronemia syndrome. Endocrinol Metab Clin North Am 1998; 27(3):551–567. pmid:9785052
  4. Melmed S, Polonsky KS, Larsen PR, Kronenberg H. Williams Textbook of Endocrinology. 13th ed. Philadelphia: Elsevier; 2016.
  5. Zak A, Zeman M, Slaby A, Vecka M. Xanthomas: clinical and pathophysiological relations. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2014; 158(2):181–188. doi:10.5507/bp.2014.016
  6. Leaf DA. Chylomicronemia and the chylomicronemia syndrome: a practical approach to management. Am J Med 2008; 121(1):10–12. doi:10.1016/j.amjmed.2007.10.004
  7. Hegele RA, Ginsberg HN, Chapman MJ, et al; European Atherosclerosis Society Consensus Panel. The polygenic nature of hypertriglyceridaemia: implications for definition, diagnosis, and management. Lancet Diabetes Endocrinol 2014; 2(8):655–666. doi:10.1016/S2213-8587(13)70191-8
  8. Berglund L, Brunzell JD, Goldberg AC, et al; Endocrine Society. Evaluation and treatment of hypertriglyceridemia: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2012; 97(9):2969–2989. doi:10.1210/jc.2011-3213
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Weight loss surgery linked to lower CV event risk in diabetes

A ‘preferred treatment option’ in obesity and type 2 diabetes?
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Weight-loss surgery in people with type 2 diabetes and obesity is associated with significant reductions in major adverse cardiovascular events, compared with nonsurgical management, according to data presented at the annual congress of the European Society of Cardiology.

The retrospective cohort study, simultaneously published in JAMA, looked at outcomes in 13,722 individuals with type 2 diabetes and obesity, 2,287 of whom underwent metabolic surgery and the rest of the matched cohort receiving usual care.

At 8 years of follow-up, the cumulative incidence of the primary endpoint – a composite of first occurrence of all-cause mortality, coronary artery events, cerebrovascular events, heart failure, nephropathy, and atrial fibrillation – was 30.8% in the weight loss–surgery group and 47.7% in the nonsurgical-control group, representing a 39% lower risk with weight loss surgery (P less than .001).

The analysis failed to find any interaction with sex, age, body mass index (BMI), HbA1c level, estimated glomerular filtration rate, or use of insulin, sulfonylureas, or lipid-lowering medications.

Metabolic surgery was also associated with a significantly lower cumulative incidence of myocardial infarction, ischemic stroke and mortality than usual care (17% vs. 27.6%).

In particular, researchers saw a significant 41% reduction in the risk of death at eight years in the surgical group compared to usual care (10% vs. 17.8%), a 62% reduction in the risk of heart failure, a 31% reduction in the risk of coronary artery disease, and a 60% reduction in nephropathy risk. Metabolic surgery was also associated with a 33% reduction in cerebrovascular disease risk, and a 22% lower risk of atrial fibrillation.

In the group that underwent metabolic surgery, mean bodyweight at 8 years was reduced by 29.1 kg, compared with 8.7 kg in the control group. At baseline, 75% of the metabolic surgery group had a BMI of 40 kg/m2 or above, 20% had a BMI between 35-39.9, and 5% had a BMI between 30-34.9.

The surgery was also associated with significantly greater reductions in HbA1c, and in the use of noninsulin diabetes medications, insulin, antihypertensive medications, lipid-lowering therapies, and aspirin.

The most common surgical weight loss procedure was Roux-en-Y gastric bypass (63%), followed by sleeve gastrectomy (32%), and adjustable gastric banding (5%). Five patients underwent duodenal switch.

In the 90 days after surgery, 3% of patients experienced bleeding that required transfusion, 2.5% experienced pulmonary adverse events, 1% experienced venous thromboembolism, 0.7% experienced cardiac events, and 0.2% experienced renal failure that required dialysis. There were also 15 deaths (0.7%) in the surgical group, and 4.8% of patients required abdominal surgical intervention.

“We speculate that the lower rate of [major adverse cardiovascular events] after metabolic surgery observed in this study may be related to substantial and sustained weight loss with subsequent improvement in metabolic, structural, hemodynamic, and neurohormonal abnormalities,” wrote Ali Aminian, MD, of the Bariatric and Metabolic Institute at the Cleveland Clinic, and coauthors.

“Although large and sustained surgically induced weight loss has profound physiologic effects, a growing body of evidence indicates that some of the beneficial metabolic and neurohormonal changes that occur after metabolic surgical procedures are related to anatomical changes in the gastrointestinal tract that are partially independent of weight loss,” they wrote.

The authors, however, were also keen to point out that their study was observational, and should therefore be considered “hypothesis generating.” While the two study groups were matched on 37 baseline covariates, those in the surgical group did have a higher body weight, higher BMI, higher rates of dyslipidemia, and higher rates of hypertension.

“The findings from this observational study must be confirmed in randomized clinical trials,” they noted.

The study was partly funded by Medtronic, and one author was supported by the National Institute of Diabetes and Digestive and Kidney Diseases. Five authors declared funding and support from private industry, including from Medtronic, and one author declared institutional grants.

 

SOURCE: Aminian A et al. JAMA 2019, Sept 2. DOI: 10.1001/jama.2019.14231.

Body

 

Despite a focus on reducing macrovascular events in individuals with type 2 diabetes, none of the major randomized controlled trials of glucose-lowering interventions that support current treatment guidelines have achieved this outcome. This study of bariatric surgery in obese patients with diabetes, however, does show reductions in major adverse cardiovascular events, although these outcomes should be interpreted with caution because of their observational nature and imprecise matching of the study groups.

Despite this, the many known benefits associated with bariatric surgery–induced weight loss suggest that for carefully selected, motivated patients with obesity and type 2 diabetes – who have been unable to lose weight by other means – this could be the preferred treatment option.
 

Dr. Edward H. Livingston is the deputy editor of JAMA and with the department of surgery at the University of California, Los Angeles. These comments are adapted from an accompanying editorial (JAMA 2019, Sept 2. DOI:10.1001/jama.2019.14577). No conflicts of interest were declared.

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Despite a focus on reducing macrovascular events in individuals with type 2 diabetes, none of the major randomized controlled trials of glucose-lowering interventions that support current treatment guidelines have achieved this outcome. This study of bariatric surgery in obese patients with diabetes, however, does show reductions in major adverse cardiovascular events, although these outcomes should be interpreted with caution because of their observational nature and imprecise matching of the study groups.

Despite this, the many known benefits associated with bariatric surgery–induced weight loss suggest that for carefully selected, motivated patients with obesity and type 2 diabetes – who have been unable to lose weight by other means – this could be the preferred treatment option.
 

Dr. Edward H. Livingston is the deputy editor of JAMA and with the department of surgery at the University of California, Los Angeles. These comments are adapted from an accompanying editorial (JAMA 2019, Sept 2. DOI:10.1001/jama.2019.14577). No conflicts of interest were declared.

Body

 

Despite a focus on reducing macrovascular events in individuals with type 2 diabetes, none of the major randomized controlled trials of glucose-lowering interventions that support current treatment guidelines have achieved this outcome. This study of bariatric surgery in obese patients with diabetes, however, does show reductions in major adverse cardiovascular events, although these outcomes should be interpreted with caution because of their observational nature and imprecise matching of the study groups.

Despite this, the many known benefits associated with bariatric surgery–induced weight loss suggest that for carefully selected, motivated patients with obesity and type 2 diabetes – who have been unable to lose weight by other means – this could be the preferred treatment option.
 

Dr. Edward H. Livingston is the deputy editor of JAMA and with the department of surgery at the University of California, Los Angeles. These comments are adapted from an accompanying editorial (JAMA 2019, Sept 2. DOI:10.1001/jama.2019.14577). No conflicts of interest were declared.

Title
A ‘preferred treatment option’ in obesity and type 2 diabetes?
A ‘preferred treatment option’ in obesity and type 2 diabetes?

Weight-loss surgery in people with type 2 diabetes and obesity is associated with significant reductions in major adverse cardiovascular events, compared with nonsurgical management, according to data presented at the annual congress of the European Society of Cardiology.

The retrospective cohort study, simultaneously published in JAMA, looked at outcomes in 13,722 individuals with type 2 diabetes and obesity, 2,287 of whom underwent metabolic surgery and the rest of the matched cohort receiving usual care.

At 8 years of follow-up, the cumulative incidence of the primary endpoint – a composite of first occurrence of all-cause mortality, coronary artery events, cerebrovascular events, heart failure, nephropathy, and atrial fibrillation – was 30.8% in the weight loss–surgery group and 47.7% in the nonsurgical-control group, representing a 39% lower risk with weight loss surgery (P less than .001).

The analysis failed to find any interaction with sex, age, body mass index (BMI), HbA1c level, estimated glomerular filtration rate, or use of insulin, sulfonylureas, or lipid-lowering medications.

Metabolic surgery was also associated with a significantly lower cumulative incidence of myocardial infarction, ischemic stroke and mortality than usual care (17% vs. 27.6%).

In particular, researchers saw a significant 41% reduction in the risk of death at eight years in the surgical group compared to usual care (10% vs. 17.8%), a 62% reduction in the risk of heart failure, a 31% reduction in the risk of coronary artery disease, and a 60% reduction in nephropathy risk. Metabolic surgery was also associated with a 33% reduction in cerebrovascular disease risk, and a 22% lower risk of atrial fibrillation.

In the group that underwent metabolic surgery, mean bodyweight at 8 years was reduced by 29.1 kg, compared with 8.7 kg in the control group. At baseline, 75% of the metabolic surgery group had a BMI of 40 kg/m2 or above, 20% had a BMI between 35-39.9, and 5% had a BMI between 30-34.9.

The surgery was also associated with significantly greater reductions in HbA1c, and in the use of noninsulin diabetes medications, insulin, antihypertensive medications, lipid-lowering therapies, and aspirin.

The most common surgical weight loss procedure was Roux-en-Y gastric bypass (63%), followed by sleeve gastrectomy (32%), and adjustable gastric banding (5%). Five patients underwent duodenal switch.

In the 90 days after surgery, 3% of patients experienced bleeding that required transfusion, 2.5% experienced pulmonary adverse events, 1% experienced venous thromboembolism, 0.7% experienced cardiac events, and 0.2% experienced renal failure that required dialysis. There were also 15 deaths (0.7%) in the surgical group, and 4.8% of patients required abdominal surgical intervention.

“We speculate that the lower rate of [major adverse cardiovascular events] after metabolic surgery observed in this study may be related to substantial and sustained weight loss with subsequent improvement in metabolic, structural, hemodynamic, and neurohormonal abnormalities,” wrote Ali Aminian, MD, of the Bariatric and Metabolic Institute at the Cleveland Clinic, and coauthors.

“Although large and sustained surgically induced weight loss has profound physiologic effects, a growing body of evidence indicates that some of the beneficial metabolic and neurohormonal changes that occur after metabolic surgical procedures are related to anatomical changes in the gastrointestinal tract that are partially independent of weight loss,” they wrote.

The authors, however, were also keen to point out that their study was observational, and should therefore be considered “hypothesis generating.” While the two study groups were matched on 37 baseline covariates, those in the surgical group did have a higher body weight, higher BMI, higher rates of dyslipidemia, and higher rates of hypertension.

“The findings from this observational study must be confirmed in randomized clinical trials,” they noted.

The study was partly funded by Medtronic, and one author was supported by the National Institute of Diabetes and Digestive and Kidney Diseases. Five authors declared funding and support from private industry, including from Medtronic, and one author declared institutional grants.

 

SOURCE: Aminian A et al. JAMA 2019, Sept 2. DOI: 10.1001/jama.2019.14231.

Weight-loss surgery in people with type 2 diabetes and obesity is associated with significant reductions in major adverse cardiovascular events, compared with nonsurgical management, according to data presented at the annual congress of the European Society of Cardiology.

The retrospective cohort study, simultaneously published in JAMA, looked at outcomes in 13,722 individuals with type 2 diabetes and obesity, 2,287 of whom underwent metabolic surgery and the rest of the matched cohort receiving usual care.

At 8 years of follow-up, the cumulative incidence of the primary endpoint – a composite of first occurrence of all-cause mortality, coronary artery events, cerebrovascular events, heart failure, nephropathy, and atrial fibrillation – was 30.8% in the weight loss–surgery group and 47.7% in the nonsurgical-control group, representing a 39% lower risk with weight loss surgery (P less than .001).

The analysis failed to find any interaction with sex, age, body mass index (BMI), HbA1c level, estimated glomerular filtration rate, or use of insulin, sulfonylureas, or lipid-lowering medications.

Metabolic surgery was also associated with a significantly lower cumulative incidence of myocardial infarction, ischemic stroke and mortality than usual care (17% vs. 27.6%).

In particular, researchers saw a significant 41% reduction in the risk of death at eight years in the surgical group compared to usual care (10% vs. 17.8%), a 62% reduction in the risk of heart failure, a 31% reduction in the risk of coronary artery disease, and a 60% reduction in nephropathy risk. Metabolic surgery was also associated with a 33% reduction in cerebrovascular disease risk, and a 22% lower risk of atrial fibrillation.

In the group that underwent metabolic surgery, mean bodyweight at 8 years was reduced by 29.1 kg, compared with 8.7 kg in the control group. At baseline, 75% of the metabolic surgery group had a BMI of 40 kg/m2 or above, 20% had a BMI between 35-39.9, and 5% had a BMI between 30-34.9.

The surgery was also associated with significantly greater reductions in HbA1c, and in the use of noninsulin diabetes medications, insulin, antihypertensive medications, lipid-lowering therapies, and aspirin.

The most common surgical weight loss procedure was Roux-en-Y gastric bypass (63%), followed by sleeve gastrectomy (32%), and adjustable gastric banding (5%). Five patients underwent duodenal switch.

In the 90 days after surgery, 3% of patients experienced bleeding that required transfusion, 2.5% experienced pulmonary adverse events, 1% experienced venous thromboembolism, 0.7% experienced cardiac events, and 0.2% experienced renal failure that required dialysis. There were also 15 deaths (0.7%) in the surgical group, and 4.8% of patients required abdominal surgical intervention.

“We speculate that the lower rate of [major adverse cardiovascular events] after metabolic surgery observed in this study may be related to substantial and sustained weight loss with subsequent improvement in metabolic, structural, hemodynamic, and neurohormonal abnormalities,” wrote Ali Aminian, MD, of the Bariatric and Metabolic Institute at the Cleveland Clinic, and coauthors.

“Although large and sustained surgically induced weight loss has profound physiologic effects, a growing body of evidence indicates that some of the beneficial metabolic and neurohormonal changes that occur after metabolic surgical procedures are related to anatomical changes in the gastrointestinal tract that are partially independent of weight loss,” they wrote.

The authors, however, were also keen to point out that their study was observational, and should therefore be considered “hypothesis generating.” While the two study groups were matched on 37 baseline covariates, those in the surgical group did have a higher body weight, higher BMI, higher rates of dyslipidemia, and higher rates of hypertension.

“The findings from this observational study must be confirmed in randomized clinical trials,” they noted.

The study was partly funded by Medtronic, and one author was supported by the National Institute of Diabetes and Digestive and Kidney Diseases. Five authors declared funding and support from private industry, including from Medtronic, and one author declared institutional grants.

 

SOURCE: Aminian A et al. JAMA 2019, Sept 2. DOI: 10.1001/jama.2019.14231.

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Key clinical point: Bariatric surgery may reduce the risk of cardiovascular events in people with type 2 diabetes.

Major finding: Bariatric surgery is associated with a 39% reduction in risk of major cardiovascular events.

Study details: Retrospective cohort study in 13,722 individuals with type 2 diabetes and obesity.

Disclosures: The study was partly funded by Medtronic, and one author was supported by the National Institute of Diabetes and Digestive and Kidney Diseases. Five authors declared funding and support from private industry, including from Medtronic, and one author declared institutional grants.

Source: Aminian A et al. JAMA 2019, September 2. DOI: 10.1001/jama.2019.14231.

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