High-Density Lipoprotein Cholesterol and Particle Concentrations, Carotid Atherosclerosis, and Coronary Events: MESA (Multi-Ethnic Study of Atherosclerosis)

Study Questions:

Are high-density lipoprotein cholesterol (HDL-C) and particle (HDL-P) concentrations independently associated with carotid intima-media thickness (cIMT) and incident coronary heart disease (CHD)?

Methods:

Subjects were enrolled in the MESA (Multi-Ethnic Study of Atherosclerosis) study, a community-based cohort of men and women ages 45-84 years of age, of African American, Hispanic, white, and Chinese American ethnicity. Those with a history of cardiovascular disease at baseline were excluded. The current study also excluded participants on lipid-lowering medications, with elevated triglycerides or missing values for lipids or smoking. HDL-C and HDL-P concentration were examined for associations with cIMT. Additional outcomes of interest included incident CHD (defined as myocardial infarction, CHD death, and angina). Multivariate models were adjusted for age, sex, ethnicity, hypertension, and smoking status.

Results:

A total of 5,598 men and women were included in this analysis. Over a mean follow-up of 6.0 years, 227 CHD events occurred. HDL-C and HDL-P correlated with each other (ρ = 0.69) and LDL-P (ρ = -0.38, -0.25, respectively, p < 0.05 for all). For (1 standard deviation) higher HDL-C (15 mg/dl) or HDL-P (6.64 µmol/L), cIMT differences were -26.1 (95% CI, -34.7 to -17.4) and -30.1 (95% CI, -38.8 to -21.4) µm, and CHD hazard ratios were 0.74 (95% CI, 0.63-0.88) and 0.70 (95% CI, 0.59-0.82), respectively. Adjusted for each other and LDL-P, HDL-C was no longer associated with cIMT (2.3; 95% CI, -9.5 to 14.2 µm) or CHD (0.97; 95% CI, 0.77-1.22), but HDL-P remained independently associated with cIMT (-22.2; 95% CI, -33.8 to -10.6 µm) and CHD (0.75; 95% CI, 0.61-0.93). Interactions by sex, ethnicity, diabetes, and high-sensitivity C-reactive protein were not significant.

Conclusions:

The authors concluded that HDL-P concentration was associated with cIMT and CHD events, while HDL-C was not. These data suggest that potential confounding by related lipids or lipoproteins should be carefully considered when evaluating HDL-related risk.

Perspective:

Although HDL-C and HDL-P concentration are correlated with each other, these data suggest that HDL-P offers a more robust association with CHD risk. The relationship between metabolic parameters such as lipids may be best considered together rather than separately when evaluating risk.

Clinical Topics: Dyslipidemia, Prevention, Vascular Medicine, Lipid Metabolism, Nonstatins, Hypertension

Keywords: Risk, Ethnic Groups, Coronary Artery Disease, Myocardial Infarction, Atherosclerosis, Follow-Up Studies, European Continental Ancestry Group, Lipoproteins, Carotid Artery Diseases, Hispanic Americans, Cholesterol, Incidence, Biological Markers, Cardiology, Hypertension, United States


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