Associations of HDL phospholipids and paraoxonase activity with coronary heart disease in postmenopausal women

A low high-density lipoprotein-cholesterol (HDL-C) is an established indicator for increased risk of coronary heart disease (CHD). Multiple functional relationships between HDL and CHD have been discussed. We tested the clinical relevance of some of these relationships in a cross-sectional coronary angiography (CA) study of 87 post-menopausal women between 48 and 73 years. In addition to established cardiovascular risk factors we measured concentrations of phosphatidylcholine (PC) and sphingomyelin (SPM) in HDL as indirect markers of cholesterol efflux capacity, the serum activity of the paraoxonase (PON) as a measure of the antioxidative capacity and serum concentrations of insulin/C-peptide and C-reactive protein (CRP) as indirect markers of insulin sensitivity and inflammation, respectively. Upon multivariate analysis of data from 55 women with angiographically assessed CHD differed from 32 women with angiographically excluded CHD, HDL-SPM had the strongest association with the presence of CHD among all HDL-related parameters. It was also the only HDL-related parameter which had a significant and independent correlation with the number of coronary stenoses. As HDL-SPM was previously shown to correlate with cholesterol efflux capacity of plasma, we conclude that reduced cholesterol efflux capacity is an important factor accounting for the inverse association between HDL-cholesterol and CHD.