Cardiovascular Risk in Relation to Body Mass Index and Use of Evidence-Based Preventive Medications

Study Questions:

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


Patients from the REACH cohort, an international, prospective cohort of patients with or at high risk of atherosclerosis with documentation of potential confounders, including treatments and risk factors, were followed up to 4 years (n = 54,285). Patients were categorized according to baseline BMI (ranging from underweight to Grade III obesity). OMT was defined as the use of the four cardioprotective medication classes (statins, angiotension-converting enzyme inhibitors/angiotensin II receptor blockers, beta-blockers, and antiplatelet agents). The main outcomes were all-cause mortality, CV mortality, and CV events.


In primary and secondary prevention, a reverse J-shaped curve best described the relationship between BMI categories and the incidence of the various outcomes. In secondary prevention, the highest adjusted risks were observed for underweight patients (1.97, p < 0.01; and 1.29, p = 0.03, for CV mortality and CV events) and the lowest hazard ratios were observed, respectively, in Grade II and III obese patients (0.73, p < 0.01; and 0.80, p < 0.01). 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.


An obesity paradox was observed in both primary and secondary CV prevention patients. The intensity of use of evidence-based preventive medications does not account for the paradoxical CV protection associated with obesity. At extremes of BMI, further interventions beyond OMT may be needed to reduce CV risk.


The obesity paradox has been shown in most of the CV and metabolic conditions that are associated with obesity including heart failure (heart failure with reduced ejection fraction and heart failure with preserved ejection fraction), acute coronary syndrome, cerebrovascular accident/transient ischemic attack, diabetes, atrial fibrillation, and each of the surgical and catheter-based CV interventions. This infers that the obesity cause/effect-contribution relationship may be true, but once present inadequate nutrient energy, one or more adipocyte-derived substances, or decreasing skeletal muscle mass plays a role in the outcome variables. The study was unique in that it demonstrated that improved outcome associated with mild to moderate obesity was not the result of greater use of evidence-based therapies. However, suboptimal medical therapy was associated with decreasing ‘CV protection’ in those who were overweight at baseline. Further observational studies are necessary, particularly those in whom the results are not derived simply from the weight/BMI at baseline.

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