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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 μm]), whereas  HDL  containing apoC‐ III  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.

journal of the american heart association

High‐Density Lipoprotein Subspecies Defined by Apolipoprotein C‐ III  and Subclinical Atherosclerosis Measures: MESA (The Multi‐Ethnic Study of Atherosclerosis)