Lean body mass is associated with increased incidence of mortality and cardiovascular morbidity in hypertensive patients with coronary artery disease: The International Verapamil SR-Trandolapril Study (INVEST)

Obesity increases CV risk, but has not been examined in patients with hypertension (HTN) and CAD with well managed BP. We evaluated the impact of baseline body mass index (BMI) on CV risk in INVEST. INVEST randomized 22,576 CAD HTN patients (mean age 66) to a verapamil SR (Ve) or atenolol (At) strategy with follow-up for 61,835 patient years. Dose titration and additional drugs (trandolapril and/or HCTZ) targeted BP control and organ protection. Primary outcome (PO)- death, nonfatal MI, or nonfatal stroke- was equivalent comparing strategies. Higher BMI decreased risk for PO (HR 0.98, 95% CI 0.97, 0.98) using a Cox proportional hazards model with BMI as a continuous variable. Patients in the lowest baseline BMI cohort (<25 kg/m2) had the highest rate of PO and death despite having the greatest BP reduction and highest BP control (table). Clinically significant interactions were observed between lower BMI and increasing age (p<0.001), current smoking (p=0.095), and prior stroke/TIA (p=0.024). BMI Cohort (kg/m2) BP = blood pressure; MI = myocardial infarction; TIA = transient ischemic attack. Lean CAD HTN patients treated with Ve or At strategies have high mortality and CV morbidity compared to patients with higher BMI, despite better BP control. Increasing age, smoking, and stroke/TIA contribute to worse clinical outcome in this lean cohort.