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Metabolically healthy obesity is not without risk
Recent research has focused on the CV effects of metabolically healthy obesity.
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Debate in the cardiology and endocrinology communities has intensified surrounding how to classify and treat obese adults who display no signs of CVD. There is evidence that these patients may have CV risk, despite having no components of the metabolic syndrome.
While some recent research has demonstrated that approximately one-third of obese adults may not be at increased risk for metabolic complications, one study published in the Journal of the American College of Cardiology in April found that obese individuals classified as “metabolically healthy” have a higher prevalence of coronary artery calcification compared with normal-weight adults.
The term “metabolically healthy obesity” has come into widespread use, but, there is no consensus on a precise definition, or on whether it is a real condition or a myth.
Norbert Stefan
Daniel Bessesen
A viewpoint article in The Lancet Diabetes and Endocrinology by Norbert Stefan, MD, from the Institute for Diabetes Research and Metabolic Diseases in Tubingen, Germany, defined metabolically healthy obesity as a BMI ≥30 in the presence of no major CV risk factors. According to Stefan, in these patients, the risk for CVD is no higher than that of nonobese adults, and they have a lower risk for CV morbidity and mortality than obese adults who do have major CV risk factors.
Other criteria for metabolically healthy obesity, according to Stefan, include obese people without abdominal obesity based on waist circumference, a lack of metabolic syndrome components, insulin sensitivity based on a homeostatic model assessment of insulin resistance (HOMA-IR), and a high level of cardiorespiratory fitness.
"Not everybody with a BMI of ≥30 has the same risk," Daniel Bessesen, MD, from the University of Colorado School of Medicine and Anschutz Health and Wellness Center, said in an interview. "There are other metabolic factors, BP, blood sugar, lipid levels and inflammation, that all play into the ultimate health effects of a person's weight."
Higher CAC present
However, a subanalysis of the Kangbuk Samsung Health Study in South Korea, published in JACC, raised doubts as to whether obese adults with no traditional CVD risk factors are actually at reduced risk.
Yoosoo Chang, MD, of Kangbuk Samsung Hospital, Seoul, Korea, and colleagues evaluated 14,828 metabolically healthy adults (defined as absence of any of the components of the metabolic syndrome and HOMA-IR <2.5) aged 30 to 59 years without known CVD. Examinations were conducted between 2010 and 2012, including measurement of coronary artery calcification (CAC) scores via CT.
Chang and colleagues found that the presence of CAC was higher among metabolically healthy obese participants compared with metabolically healthy normal-weight participants. Multivariable analysis yielded a significant association between elevated CAC scores and obesity (CAC score ratio=2.26; 95% CI, 1.48-3.43 for obese vs. normal weight). Further analysis revealed that adjustment for metabolic risk factors eliminated the significance of the association, particularly after adjustment for LDL (CAC score ratio=1.24; 95% CI, 0.79-1.96 for obese vs. normal weight).
In addition, Chang and colleagues found that links between obesity and CAC were not influenced by age, sex, exercise level, tobacco consumption, alcohol consumption or Framingham risk score.
“These findings provide strong support to the hypothesis that [metabolically healthy obesity] is not a harmless condition,” Chang and colleagues wrote. “Furthermore, the association between [metabolically healthy obesity] and CAC scores was largely mediated by residual levels of cardiometabolic risk factors, suggesting that the concept of [metabolically healthy obesity] may be an artifact of the cutoffs used to define metabolic abnormalities and of the parameters included in the definition of [metabolically healthy obesity]. As a consequence, physicians should adequately address the increased risk of CVD in [metabolically healthy obese] individuals, in addition to counseling them about healthy weight and lifestyle.”
Risk for CV events
A systematic review and meta-analysis by Caroline K. Kramer, MD, PhD, of Mount Sinai Samuel Lunenfeld-Tanenbaum Research Institute, Toronto, came to similar conclusions. “Compared with metabolically healthy normal-weight individuals, obese persons are at increased risk for adverse long-term outcomes even in the absence of metabolic abnormalities, suggesting that there is no healthy pattern of increased weight,” they wrote in Annals of Internal Medicine.
Kramer and colleagues found that in studies with less than 10 years of follow-up, metabolically healthy obese adults did not have increased risk for all-cause mortality or CV events compared with normal-weight metabolically healthy adults; however, these participants did have increased risk for all-cause mortality or CV events in studies with 10 or more years of follow-up. There was no difference in outcomes among metabolically unhealthy people regardless of weight.
Bessesen said, however, that the data from Kramer’s analysis may not be reliable because the researchers did not include data on lifestyle and physical fitness. He also noted that the Look AHEAD trial was stopped early because weight loss did not have an effect on mortality among patients with type 2 diabetes.
“The number of people who had CV events in that study was much lower than the researchers anticipated,” he said. “One interpretation is that weight management is just one of many strategies to lower CVD — including taking lipid-lowering medicines, treating BP and lowering blood sugars. And, it may be that if a group of people in that study were physically active and had all their risk factors managed well, the benefits of weight loss are fairly modest compared to that.”
Risk for HF
Caroline M.
Apovian
There is also evidence that metabolically healthy obese adults may be at increased risk for HF. Bjørn Mørkedal, MD, PhD, from Norwegian University in Trondheim, Norway, and colleagues published a recent study in JACC that investigated the relationship between metabolically healthy obesity with acute MI and HF. According to their research, obese adults had an elevated risk for HF regardless of metabolic status. The researchers found that the risk was particularly high in those with long-lasting or severe obesity. They did not, however, find increased risk for acute MI among metabolically healthy obese adults compared with metabolically healthy normal-weight adults.
“Metabolically healthy obese have less CV risk because of lower risk of developing type 2 diabetes, hypertension [and] elevated lipids; however, they may still develop right-sided HF from the direct effects of excess adipose tissue on the heart and lungs,” Caroline M. Apovian, MD, of Boston University School of Medicine and Boston Medical Center, said in an interview. – by Erik Swain, with reporting by Suzanne Bryla Reist
Kramer CK. Ann Intern Med. 2013;159:758-769.
Mørkedal B. J Am Coll Cardiol. 2014;63:1071-1078.
Stefan N. Lancet Diabetes Endocrinol. 2013;2:152-162.
The Look AHEAD Research Group. N Engl J Med. 2013;369:145-154.
Disclosures: Apovian reports financial ties with Abbott Nutrition, Allergan, Amylin, Arena, Aspire Bariatrics, Eli Lilly, EnteroMedics, GI Dynamics, GlaxoSmithKline, Johnson & Johnson Services, Merck, MetaProteomics, Novo Nordisk, NutriSystem, Orexigen Therapeutics, Sanofi-Aventis and Zafgen. Bessesen is on the Data Safety Monitoring Board for EnteroMedics. Chang, Kramer, Mørkedal and Stefan report no relevant financial disclosures.