Primary Low Level of High-Density Lipoprotein Cholesterol and Risks of Coronary Heart Disease, Cardiovascular Disease, and Death: Results From the Multi-Ethnic Study of Atherosclerosis

Abstract

Prior studies observing associations between low levels of high-density lipoprotein (HDL) cholesterol and cardiovascular disease (CVD) have often been conducted among persons with metabolic or other lipid abnormalities. In this study, we investigated the association between primary low HDL cholesterol and coronary heart disease (CHD), CVD, and all-cause death after adjustment for confounders in the Multi-Ethnic Study of Atherosclerosis (MESA). Participants who were free of clinical CVD were recruited from 6 US research centers from 2000 to 2002 and followed for a median duration of 10.2 years. We defined "primary low HDL cholesterol" as HDL cholesterol level <40 mg/dL (men) or <50 mg/dL (women), triglyceride level <100 mg/dL, and low-density lipoprotein cholesterol level <100 mg/dL (n = 158). We defined an "optimal" lipid profile as HDL cholesterol ≥40 mg/dL (men) or ≥50 mg/dL (women) and triglycerides and low-density lipoprotein cholesterol <100 mg/dL (n = 780). For participants with primary low HDL cholesterol versus those with an optimal lipid profile, adjusted hazard ratios for total CHD, CVD, and death were 2.25 (95% confidence interval (CI): 1.20, 4.21; P = 0.011), 1.93 (95% CI: 1.11, 3.34; P = 0.020), and 1.11 (95% CI: 0.67, 1.84; P = 0.69), respectively. Participants with primary low HDL cholesterol had higher risks of CHD and CVD than participants with optimal lipid profiles but no difference in survival after a median 10.2 years of follow-up.

Keywords: cardiovascular disease; coronary disease; hyperlipidemia; lipids; lipoproteins.

Figure 1.

Unadjusted probability of coronary heart disease (CHD) events for participants with primary low levels of high-density lipoprotein cholesterol (HDL-C) as compared with those with optimal lipid profiles (P < 0.001 by log-rank test), Multi-Ethnic Study of Atherosclerosis, 2000–2012. Primary low HDL-C was defined as HDL-C <50 mg/dL for women or <40 mg/dL for men, triglycerides <100 mg/dL, and low-density lipoprotein cholesterol <100 mg/dL. An optimal lipid profile was defined as HDL-C ≥40 mg/dL for men or ≥50 mg/dL for women, triglycerides <100 mg/dL, and low-density lipoprotein cholesterol <100 mg/dL.

Figure 2.

Unadjusted probability of cardiovascular disease (CVD) events for participants with primary low levels of high-density lipoprotein cholesterol (HDL-C) as compared with those with optimal lipid profiles (P = 0.001 by log-rank test), Multi-Ethnic Study of Atherosclerosis, 2000–2012. Primary low HDL-C was defined as HDL-C <50 mg/dL for women or <40 mg/dL for men, triglycerides <100 mg/dL, and low-density lipoprotein cholesterol <100 mg/dL. An optimal lipid profile was defined as HDL-C ≥40 mg/dL for men or ≥50 mg/dL for women, triglycerides <100 mg/dL, and low-density lipoprotein cholesterol <100 mg/dL.

Figure 3.

Unadjusted probability of all-cause death for participants with primary low levels of high-density lipoprotein cholesterol (HDL-C) as compared with those with optimal lipid profiles (P = 0.57 by log-rank test), Multi-Ethnic Study of Atherosclerosis, 2000–2012. Primary low HDL-C was defined as HDL-C <50 mg/dL for women or <40 mg/dL for men, triglycerides <100 mg/dL, and low-density lipoprotein cholesterol <100 mg/dL. An optimal lipid profile was defined as HDL-C ≥40 mg/dL for men or ≥50 mg/dL for women, triglycerides <100 mg/dL, and low-density lipoprotein cholesterol <100 mg/dL.