Cardiovascular risk in relation to body mass index and use of evidence-based preventive medications in patients with or at risk of atherothrombosis

Aim: Explore the relation between body mass index (BMI) and cardiovascular disease, and the influence of optimal medical therapy (OMT) on this relationship.

Methods and results: 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). Optimal medical therapy was defined as the use of the four cardioprotective medication classes (statins, ACE inhibitors/angiotensin II receptor blockers, β-blockers, and antiplatelet agents). The main outcomes were all-cause mortality, cardiovascular (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 HRs were observed, respectively, in Grade II and Grade 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.

Conclusion: 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.