A “Cardioprotective” Effect of Overweight and Obesity?

Study Questions:

What is the relationship between body mass index (BMI) and cardiovascular disease (CVD), and what is the influence of optimal medical therapy (OMT) on this relationship?

Methods:

This was a post hoc analysis of the Reduction of Atherothrombosis for Continued Health (REACH) cohort. The REACH registry is a prospective, multicenter, international study. A total of 690,555 consecutive outpatients at least 45 years old with ≥3 risk factors for atherosclerosis and patients with documented CVD were enrolled between 2003 and 2004. Patients were followed up to 4 years. Patients were categorized according to baseline BMI. OMT was defined as the use of all four of the following: statins, angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs), beta-blockers, and antiplatelet agents (including aspirin). Outcomes in this post hoc analysis were all-cause mortality, cardiovascular (CV) mortality, and CV events (death, stroke, or myocardial infarction).

Results:

The analytic sample for this analysis included 54,285 patients (n = 9,779 in primary prevention and n = 44,506 in secondary prevention). For both primary and secondary prevention, a reverse J-shaped curve described the relationship between BMI and the incidence of CVD with the lowest mortality and CV event rates observed in either obese or overweight subjects, whereas underweight subjects displayed a markedly increased CV risk. Although the proportion of patients on OMT increased with BMI from 10.1% to 36% (p < 0.001), the apparent CV protection conferred by obesity persisted in patients receiving OMT.

Conclusions:

The cardioprotective effect of overweight and obesity in both primary and secondary prevention is not explained by a confounding role of OMT.

Perspective:

The authors provide evidence of an ‘obesity paradox’ in this post hoc analysis of the REACH registry, and add value by providing an argument against the confounding role of OMT. Certainly, these data should not dissuade physicians from recommending weight loss in obese patients, but further therapies may be necessary at the extremes of BMI to assuage CV risk. And, as the authors conclude, ‘Further studies of the relationship between BMI and CVD are required with special focus on the effect of fatness versus fitness on CV risk.’

Clinical Topics: Diabetes and Cardiometabolic Disease, Prevention

Keywords: Adrenergic beta-Antagonists, Angiotensin Receptor Antagonists, Angiotensin-Converting Enzyme Inhibitors, Aspirin, Atherosclerosis, Metabolic Syndrome X, Myocardial Infarction, Obesity, Overweight, Platelet Aggregation Inhibitors, Primary Prevention, Risk Factors, Secondary Prevention, Stroke, Thrombosis


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