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Lipoprotein subclasses and coronary artery calcium in postmenopausal women from the healthy women study

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Abstract

Lipoprotein subclass levels may improve the prediction of cardiovascular disease (CAD) in individuals beyond the risk assessment provided by conventional enzymatically determined lipid levels. The objective of this study was to evaluate the associations between nuclear magnetic resonance (NMR) spectroscopy–determined lipoprotein subclasses and coronary calcification in postmenopausal women, and to determine whether the associations were independent of conventional lipid measures. Coronary artery calcification (CAC) was measured by electron beam computed tomography, and lipoprotein subclasses were determined by NMR spectroscopy (Liposcience, Inc., Raleigh, NC), in 286 healthy women (mean age = 61.7), at 8 years postmenopause. CAC was analyzed as categories 0, 1 to 99, and ≥100. The mean CAC was 53 (range, 0 to 1,175), and 54% of the women had 0 scores. Large high-density lipoprotein (HDL) was inversely associated with CAC category, but small HDL was not. All very low-density lipoprotein (VLDL) subclasses—small, medium, and large—were positively associated with CAC (p <0.01). Small low-density lipoprotein (LDL) was positively associated with CAC (p <0.01), but medium and large LDL were not. Smaller LDL particle size (p <0.01) and higher levels of LDL particles (p <0.001) were associated with higher CAC category. In separate ordinal logistic regression models, small LDL, LDL particles, and large VLDL were each positively associated (p <0.05) with higher CAC after adjustment for age, systolic blood pressure (SBP), current smoking, and conventional measures of LDL cholesterol, HDL cholesterol, and triglycerides. These results suggest that the measurement of lipoprotein subclasses may improve the prediction of CAD in postmenopausal women beyond that provided by the conventional lipid panel and CAD risk factors.

Section snippets

Methods

Between 1983 and 1985, 541 premenopausal women, aged 42 to 50 years, were enrolled in the Healthy Women Study (HWS), a longitudinal study of the effects of menopause on cardiovascular risk. The HWS measured standard demographic and cardiovascular risk factors, including triglycerides, total cholesterol, HDL cholesterol, and LDL cholesterol by conventional separation and enzymatic methods.20 When the women were 8 years postmenopause, lipoprotein subclasses and coronary calcification were

Results

Table 1reports participant characteristics at the visit when the women were approximately 8 years postmenopause. The mean age was 61.7 years, with a range of 57 to 66 years, and 13% of the women were current smokers. In these postmenopausal women, the VLDL subclasses were evenly distributed between small, medium, and large particles. However, both LDL and HDL subclasses contained a higher proportion of large particles.

Table 1 also reports the age-adjusted means of the enzymatically determined

Discussion

In these postmenopausal women, increased coronary calcification was associated with higher levels of small LDL and large VLDL, more LDL particles, smaller mean LDL size, and lower levels of large HDL. The associations with small LDL, LDL particles, and large VLDL remained significant after adjustment for LDL cholesterol, triglycerides, HDL cholesterol, age, smoking, and systolic blood pressure. These results suggest that prediction of cardiovascular risk in postmenopausal women may be improved

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    This project was funded by Grant No. 5R01 HL28266-18 from the National Heart, Lung, and Blood Institute (NHLBI) for the Healthy Women Study. Some of these results were presented at the American Heart Association’s 41st Annual Conference on Cardiovascular Disease Epidemiology and Prevention, March 2001. The accompanying abstract was published in Circulation 2001;103:1349–1350.

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