Body Mass Index and Association With Cardiovascular Outcomes in Patients With Stable Coronary Heart Disease - A STABILITY Substudy

Abstract

BACKGROUND The obesity paradox states that patients with higher body mass index (BMI) and cardiovascular disease may experience better prognosis. However, this is less clear in patients with coronary heart disease. METHODS AND RESULTS The prospective STABILITY (Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy) trial included 15 828 patients with stable coronary heart disease with 3 to 5 years' follow-up on optimal secondary preventive treatment. BMI was measured at baseline (n=15 785). Associations between BMI and cardiovascular outcomes were evaluated by Cox regression analyses with multivariable adjustments. Mean age was 64±9 years and 19% women. Most risk markers (diabetes, hypertension, inflammatory biomarkers, triglycerides) showed a graded association with higher BMI. The frequency of smoking, levels of high-density lipoprotein, growth differentiation factor 15, and NT-proBNP (N-terminal pro-B-type natriuretic peptide) were higher at lower BMI. Low BMI (<20 kg/m2; n=244 [1.5%]) was associated with doubled risk of total death (hazard ratio [HR], 2.27; 95% CI, 1.60-3.22), cardiovascular death (HR, 2.26; 95% CI, 1.46-3.49), and heart failure (HR, 2.51; 95% CI, 1.35-4.68) compared with BMI of 25 to <30 kg/m2 (n=6752 [42.8%]) as reference. Similarly, high BMI of ≥35 kg/m2 (n=1768 [11.2%]) was associated with increased risk of the same outcomes. A BMI between 20 and <25 kg/m2 was associated with increased risk of cardiovascular death (HR, 1.26; 95% CI, 1.03-1.54) and total death (HR, 1.21; 95% CI, 1.03-1.42). CONCLUSIONS Patients with stable coronary heart disease showed a graded increase in cardiometabolic and inflammatory risk factors with increasing BMI category >25 kg/m2. All-cause and cardiovascular mortality were lowest at BMI of 25 to 35 kg/m2. Underweight with BMI of <20 kg/m2 and very high BMI of ≥35 kg/m2 were strong risk markers for poor prognosis. REGISTRATION URL: https://ichgcp.net/clinical-trials-registry/NCT00799903" title="See in ClinicalTrials.gov">NCT00799903.

Keywords: coronary artery disease; obesity; risk factors.

Figures

Figure 1. Levels of biomarkers (interleukin ‐6, GDF‐15, Troponin T and NT‐proBNP) in relation to categories of BMI.

BMI indicates body mass index; GDF‐15, growth differentiation factor 15; hsTroponin T, high‐sensitivity cardiac troponin T; IL‐6, interleukin 6; and NT‐proBNP, N‐terminal pro‐B‐type natriuretic peptide.

Figure 2. Spline plot shows rates of major cardiovascular event (MACE), cardiovascular (CV) death, myocardial infarction (MI), stroke, total death, hospitalization for heart failure by body mass index (BMI).

(A) Total population. (B) Non‐Asian population. (C) Asian population.

Figure 3. The association of body mass index (BMI) with clinical outcomes.

(A) Basic adjustment model. (B) Fully adjusted. (A) BMI 25 < 30 kg/m2 as reference. Adjusted for age, sex, and randomized treatment. P value denotes difference between groups. (B) BMI of 25 < 30 kg/m2 as reference. Adjusted for age, sex, and randomized treatment, prior percutaneous coronary intervention (PCI)/coronary artery bypass grafting (CABG), prior MI, renal dysfunction, polyvascular disease, diabetes, smoking, stroke/transient ischemic attack (TIA), congestive heart failure, systolic blood pressure, geographic region, chronic obstructive pulmonary disease (COPD), cancer diagnosis and Asian/Japanese origin. P value denotes difference between groups. CV indicates cardiovascular; MACE, major adverse cardiovascular event; and MI, myocardial infarction.