DETERMINANTS OF HIGH DENSITY LIPOPROTEIN CHOLESTEROL SUBFRACTIONS IN POST MENOPAUSAL WOMEN (CORONARY HEART DISEASE, ESTROGEN)

The level of high density lipoprotein cholesterol (HDL-C) is a primary risk factor for Coronary Heart Disease (CHD) in older women. Recently, the heterogeneous nature of HDL has been recognized and it has been suggested that the HDL-C:CHD relationship may primarily reflect the HDL(,2)-C subfraction.

The current research was designed to examine the epidemiology of HDL-C, HDL(,2)-C and HDL(,3)-C in postmenopausal women. More specifically, the relationship of age, physical activity, alcohol consumption, cigarette smoking, obesity and exogenous estrogen use to the levels of HDL-C subfractions, as well as, possible underlying biological mechanisms, was examined in 256 postmenopausal women, not on estrogen therapy and 48 postmenopausal women on estrogen.

Estrogen users had significantly higher total HDL-C and HDL(,2)-C levels than non-estrogen users, independent of differences in obesity, physical activity and alcohol consumption. There was no difference in HDL(,3)-C levels.

The primary factors related to the total HDL-C were exogenous estrogen dose, obesity and alcohol consumption. Independent determinants of HDL(,2)-C included estrogen dose and the degree of obesity and of HDL(,3)-C, alcohol consumption. Smokers had significantly lower levels of HDL(,2)-C after controlling for obesity and alcohol consumption. Differential relationships were observed with physical activity depending upon which activity measure was used. Activity as measured by objective monitors was positively related to HDL(,2)-C while activity measured by survey, was related to HDL(,3)-C. In the multivariate analysis, smoking or activity were related to the HDL-C subfractions.

The biological mechanism by which these environmental factors are associated with HDL-C levels are not fully understood. The degree to which hepatic microsomal enzyme induction by environmental factors determines HDL-C levels was examined. Serum glutamic oxyloacetic transaminase (SGOT) was positively related to HDL(,3)-C levels independent of triglyceride levels and alcohol consumption. Inclusion of SGOT into the regression models reduced the alcohol and HDL(,3)-C relationship suggesting that at least, in part, the association with alcohol reflected an alternation in liver function.

Exogenous estrogen use was positively associated with HDL(,2)-C and HDL(,2)-C was inversely related to SGOT. Controlling for estrogen dose removed the previous relationship of HDL(,2)-C with SGOT, suggesting that the liver may play a key role in mediating the relationship of environmental factors to HDL(,2)-C.