High-Density Lipoprotein (HDL) Phospholipid Content and Cholesterol Efflux Capacity Are Reduced in Patients With Very High HDL Cholesterol and Coronary Disease.
OBJECTIVE
Plasma levels of high-density lipoprotein cholesterol (HDL-C) are strongly inversely associated with coronary artery disease (CAD), and high HDL-C is generally associated with reduced risk of CAD. Extremely high HDL-C with CAD is an unusual phenotype, and we hypothesized that the HDL in such individuals may have an altered composition and reduced function when compared with controls with similarly high HDL-C and no CAD.


APPROACH AND RESULTS
Fifty-five subjects with very high HDL-C (mean, 86 mg/dL) and onset of CAD at the age of ≈ 60 years with no known risk factors for CAD (cases) were identified through systematic recruitment. A total of 120 control subjects without CAD, matched for race, sex, and HDL-C level (controls), were identified. In all subjects, HDL composition was analyzed and HDL cholesterol efflux capacity was assessed. HDL phospholipid composition was significantly lower in cases (92 ± 37 mg/dL) than in controls (109 ± 43 mg/dL; P=0.0095). HDL cholesterol efflux capacity was significantly lower in cases (1.96 ± 0.39) than in controls (2.11 ± 0.43; P=0.04).


CONCLUSIONS
In people with very high HDL-C, reduced HDL phospholipid content and cholesterol efflux capacity are associated with the paradoxical development of CAD.
['Agarwala|Anandita P|AP|', 'Rodrigues|Amrith|A|', 'Risman|Marjorie|M|', 'McCoy|Mary|M|', 'Trindade|Kevin|K|', 'Qu|Liming|L|', 'Cuchel|Marina|M|', 'Billheimer|Jeffrey|J|', 'Rader|Daniel J|DJ|']
D000368:Aged D002784:Cholesterol D008076:Cholesterol, HDL D003324:Coronary Artery Disease D004951:Esterification D005260:Female D006801:Humans D008075:Lipoproteins, HDL D008297:Male D008875:Middle Aged D012307:Risk Factors
high-density lipoprotein cholesterol coronary artery disease ABC transporters