Body Mass Index and Cardiovascular Risk Markers: A Large Population Analysis

Abstract

Background/Objectives. An elevated body mass index (BMI) has been added to the new American Heart Association atherosclerotic cardiovascular disease (ASCVD) risk model. Our goal in this study was to examine the relationships between BMI and traditional and non-traditional ASCVD risk factors. Methods. We measured levels of blood glucose, insulin, lipids, lipoproteins, sterols, fatty acids, markers of inflammation and oxidative stress, and hormones in 226,000 middle-aged and elderly subjects (55% women) and associated those parameters to BMI in 5 groups (BMI 20-25, 25.1-30, 30.1-35, 35.1-40, and >40 kg/m²). Results. BMI and age were inversely correlated in both sexes. All of the traditional and non-traditional ASCVD risk markers, except low-density lipoprotein cholesterol (LDL-C), changed significantly in unfavorable ways in both sexes with increasing BMI. The largest changes were observed in the high sensitivity C-reactive protein, which increased 6- and 8-fold, and insulin, which increased 4- and 3-fold between the lowest and highest BMI groups in men and women, respectively. Although the LDL-C levels changed little, small dense LDL-C and triglyceride levels increased significantly with increasing BMI. Markers of cholesterol synthesis were positively associated with BMI, while markers of cholesterol absorption and omega-3 fatty acids were inversely associated with BMI. Concentrations of high-density lipoprotein cholesterol (HDL-C) and the athero-protective, large-size HDL particles were also inversely associated with BMI. Our analysis indicated that the associations between an elevated BMI and unfavorable changes in major ASCVD risk factors were independent of age in both sexes. Moreover, we observed that ASCVD risk factors started changing unfavorably with increasing BMI even in the normal weight range (BMI 20-25 kg/m²). Conclusions. An elevated BMI is associated with unfavorable changes in traditional and non-traditional ASCVD risk factors independent of age. Therefore, maintaining a normal BMI, preferably by an active lifestyle, and, if necessary, weight-managing medication, is very important to avoid developing conditions leading to ASCVD.

Keywords: ASCVD; cholesterol absorption; cholesterol production; fatty acids; inflammation; lipids; lipoprotein particles; lipoproteins; obesity.

Figure 1

Age and LDL-C levels of subjects with or without ASCVD, grouped by BMI. Panel (A), men; panel (B), women. Subjects were divided into 5 BMI categories: 20–25 kg/m²; 25.1–30 kg/m²; 30.1–35 kg/m²; 35.1–40 kg/m²; >40 kg/m². Data points represent median level +/− standard error. Age was significantly different between consecutive BMI groups in both sexes. Abbreviations: ASCVD, atherosclerotic cardiovascular disease; BMI, body mass index; LDL-C, low-density lipoprotein cholesterol. The figures demonstrate that in this population, ASCVD women were significantly younger than men in each BMI group and that BMI was inversely associated with age in the ASCVD and non-ASCVD groups in both sexes.

Figure 2

Scatter plot of ASCVD risk markers versus BMI. Panel (A), men (n = 101,982); panel (B), women (n = 124,018). Subjects having BMI 20–40 kg/m² were stratified into 10 groups by 2-unit intervals of BMI. All variables were age-adjusted. Median levels were calculated and percent changes from the first decile were plotted against the median BMI of each interval. Abbreviations: ASCVD, atherosclerotic cardiovascular disease; BMI, body mass index; CRP, C-reactive protein; DM, diabetes mellitus; HDL-C, high-density lipoprotein cholesterol; HT, hypertension; INS, insulin; LDL-C, low-density lipoprotein cholesterol; TGs, triglycerides. The plots demonstrate the differences in the associations between BMI and major ASCVD risk factors in men and women after adjusting data for age.