Impact of neurohormonal blockade on association between body mass index and mortality

Background The prognostic impact of body mass index (BMI) in patients following acute myocardial infarction (AMI) may be altered by neurohormonal blockade. Methods The impact of neurohormonal blockade on the association between BMI and mortality was examined in 5548 patients following AMI (CONSENSUS II), 50% receiving enalapril and 7% beta-blockade, and in 4367 patients with coronary artery disease (CAD) (4S), 79% with prior AMI, 12% receiving ACEi and 67% beta-blockade. Median follow-up was 0.4 and 5.2 years, respectively. Patients were categorized into 4 BMI groups: Underweight, < 22.00; normal-weight, 22.00–24.99; overweight, 25.00–29.99; obese, ≥ 30.00 kg/m2. Multivariable analysis adjusted for demographics, patient history, physical examination, biochemistry and medication. Results CONSENSUS II: Overall, adjusted mortality (n = 301) risk was similar across BMI groups. Comparing overweight with normal-weight patients, the hazard ratios (HRs) for mortality differed significantly (P = 0.028) between patients randomized to placebo (HR 1.41) and enalapril (HR 0.75). 4S Overall, adjusted mortality (n = 421) risk was similar for normal-weight, overweight and obese patients. In a time-dependent analysis for drug use, comparing obese with normal-weight patients, the HRs for mortality differed significantly (P = 0.047) between patients without (HR 1.86) and those with (HR 0.97) neurohormonal blockade. Conclusion In patients after AMI or with CAD, high BMI was associated with increased mortality risk among patients not receiving neurohormonal blockade, but with decreased or neutral mortality risk among those receiving neurohormonal blockade. Tests for interaction indicate that neurohormonal blockade may attenuate the relationship between high BMI and increased mortality risk. Neurohormonal blockade may thus partly explain the so-called obesity paradox.