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Metabolically healthy obese still at elevated cardiovascular risk

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Understanding cardiovascular risk in complex phenotypes

Recently, studies have consistently placed metabolically healthy obese individuals between metabolically healthy lean and metabolically unhealthy obese individuals in terms of cardiovascular disease risk, occult cardiac dysfunction, and type 2 diabetes. Thus, either metabolic dysfunction or elevated body mass index appears to increases CVD risk factors.

Often, one or two metabolic risk factors in normal weight individuals are dismissed as unimportant because they are of healthy weight; however, these data suggest that the normal-weight group is at similar risk, compared with overweight, and at times, obese individuals, when metabolic abnormalities are present. The study not only definitively counters the concept of metabolically benign obesity but also demonstrates great risk to normal weight individuals if metabolic dysfunction is present. Thus, we would suggest an increased need for screening in the normal-weight population.

Jennifer W. Bea, PhD, is from the Collaboratory for Metabolic Disease Prevention and Treatment in Tucson, Ariz., and Nancy K. Sweitzer, MD, is chief of the division of cardiology at the Sarver Heart Center. These comments are taken from an accompanying editorial (J Am Coll Cardiol. 2017 Sep 19;70:1438-40. doi. org/10.1016/j.jacc.2017.07.742). No conflicts of interest were declared.



Obese individuals with no metabolic abnormalities, such as dyslipidemia, high blood pressure, or high blood sugar levels, still have a higher risk of cardiovascular disease than do metabolically healthy people of normal weight, new data suggests.

“Our study robustly challenges the assertion that MHO [metabolically healthy obese] is a benign condition and adds to the evidence base that MHO is a high-risk state for future CVD events,” wrote Rishi Caleyachetty, MD, of the University of Birmingham, England, and his coauthors online (J Am Coll Cardiol. 2017, Sep 11. doi. 10.1016/j.jacc.2017.07.763).

Dr. Caleyachetty and his associates reported findings from a population-based study using the electronic health records of nearly 3.5 million individuals aged 18 years or older who were free of cardiovascular disease at baseline.

Overall, 15% of the population were classified as being metabolically healthy obese, meaning that they had a body mass index (BMI) of at least 30 kg/m2 with no sign of diabetes, hypertension, or hyperlipidemia, and 26% were overweight with no metabolic abnormalities. Despite their lack of metabolic disease, these obese individuals still had a significant 49% higher risk of coronary heart disease, 7% higher risk of cerebrovascular disease, and 96% higher risk of heart failure, compared with normal-weight individuals with no metabolic disease, after researchers adjusted for age, sex, smoking status, and social deprivation.

Individuals who were overweight but metabolically healthy had a 30% increased risk of ischemic heart disease, 11% increased risk of heart failure, and the same risk of cerebrovascular disease as normal-weight, healthy individuals.

They also saw an increasing risk of ischemic heart disease, cerebrovascular disease, heart failure, and peripheral vascular disease with each additional metabolic abnormality, even among underweight and normal-weight individuals, and suggested that a focus on screening overweight and obese individuals only could miss metabolic abnormalities in many patients.

Overweight and obese individuals without metabolic disease had a significantly lower risk of peripheral vascular disease, compared with healthy normal-weight individuals. The authors said this was a surprising finding but suggested cigarette smoking could be a confounding factor, as this is associated with both peripheral vascular disease and lower BMI.

“In sensitivity analyses restricted to individuals who were obese with no metabolic abnormalities and reported never smoking cigarettes, risk for PVD [peripheral vascular disease] was increased, compared [with] normal-weight individuals with no metabolic abnormalities,” Dr. Caleyachetty and his coinvestigators wrote.

Over the mean follow-up of 5.4 years, 5.6% of initially metabolically healthy obese individuals developed diabetes, 11.5% developed hyperlipidemia and 10.5% developed hypertension. In contrast, among the metabolically healthy overweight individuals at baseline, 1.9% developed diabetes, 9.4% developed hyperlipidemia, and 7.2% developed hypertension.

While the analysis adjusted for sex, the authors did note that women who were overweight or obese but metabolically healthy had stronger positive associations than did males with cerebrovascular disease and heart failure.

“Clinicians need to be aware that individuals who would otherwise be considered nonobese, based on a normal BMI, can have metabolic abnormalities, and therefore also be at high risk for CVD events,” the investigators concluded.

No conflicts of interest were declared.

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