High-density lipoprotein subspecies defined by apolipoprotein C-III and subclinical atherosclerosis measures: MESA (The Multi-Ethnic Study of Atherosclerosis)

Background--Apolipoprotein C-III (apoC-III), a small proinflammatory protein present on 6% to 7% of high-density lipoprotein (HDL) particles, defines a subspecies of HDL adversely associated with coronary heart disease in primarily white cohorts. In a multi-ethnic population free of clinical cardiovascular disease, we evaluated the relationship between apoC-III-defined HDL subspecies and subclinical markers of atherosclerotic pathology. Methods and Results--We investigated cross-sectional associations between apolipoprotein A-I concentrations of apoC-III- defined HDL subspecies, measured via ELISA and imaging measures of subclinical atherosclerosis, among 4659 participants in the MESA (The Multi-Ethnic Study of Atherosclerosis) at baseline (2000-2002). HDL particles containing and lacking apoC-III were divergently associated with coronary artery calcification in women (P-heterogeneity=0.002) but not in men (P-heterogeneity=0.31) and with carotid plaque score (P-heterogeneity=0.02) and intima-media thickness (P-heterogeneity=0.06) in the overall study population. HDL lacking apoC-III was inversely associated with all outcome measures (coronary artery calcification, women: odds ratio per SD=0.81 [95% confidence interval [CI], 0.73-0.90]; carotid plaque, overall: odds ratio per SD=0.92 [95% CI, 0.84-1.00]; intima-media thickness, overall: mean difference per SD=-14.0 μm [95% CI, -21.1 to -6.7 lm]), whereas HDL containing apoCIII was positively associated (coronary artery calcification, women: odds ratio=1.10 [95% CI, 0.99-1.22]; plaque, overall: odds ratio=1.10 [95% CI, 1.01-1.19]) or unassociated. Neither total HDL nor HDL subspecies was associated with changes in subclinical atherosclerosis measures up to 10 years later. Conclusions--The presence of apoC-III defined a subspecies of HDL not inversely associated with baseline measures of subclinical atherosclerosis, supporting a role of apoC-III in the pathophysiology of cardiovascular disease.