Journal
JOURNAL OF THE AMERICAN HEART ASSOCIATION
Volume 7, Issue 6, Pages -Publisher
WILEY
DOI: 10.1161/JAHA.117.007824
Keywords
apolipoprotein; atherosclerosis; coronary artery calcium; high-density lipoprotein; plaque
Categories
Funding
- National Heart, Lung, and Blood Institute (NHLBI) [R01 HL071739, R21 HL091217]
- National Institute of Diabetes and Digestive and Kidney Diseases [T32 DK 007703]
- National Center for Research Resources [UL1-TR-000040, UL1-TR-001079]
- NHLBI [N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, N01-HC-95169]
- US Environmental Protection Agency through the Science to Achieve Results program [RD831697]
- American Diabetes Association [1-15-JF-30]
- Roche Pharmaceuticals
- William F. Milton Fund, Harvard Medical School
- German Research Foundation
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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 mu m [95% CI, -21.1 to -6.7 mu m]), 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.
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