Abstract
HDL cholesterol (HDL-C) is inversely associated with risk for CVD in the general population. However, the metabolic pathways leading to high HDL (hyperalphalipoproteinemia) are complex, and some patients with high HDL-C are not protected against atherosclerotic disease. The purpose of this study was to determine the associations between CVD risk factors, especially HDL subpopulations, and subclinical vascular disease in patients with high HDL-C. Community-dwelling adult subjects with and without CAD between the ages of 18 – 80 years with HDL-C levels above 60 mg/dl were recruited for this study (n=46, 34 women and 12 men, mean age 58.7 ± 9.7 years). After an overnight fast, blood was obtained for measurement of lipids, inflammatory markers and lipoproteins by NMR spectroscopy (Liposcience, NC) and 2D-gel analysis. Far wall common carotid artery intimal-medial thickness (IMT) was measured using carotid ultrasonography. None of the subjects were taking statins. The lipid levels (mean ± SD) were total cholesterol 225.6 ± 37.9 mg/dl, triglycerides 77.9 ± 29.4 mg/dl, HDL 90.4 ± 22.5 mg/dl and LDL 119.6 ± 33.4 mg/dl. Carotid IMT values were normally distributed, with a range of 0.46 –1.1 mm. Unadjusted pairwise-correlations showed that carotid IMT was significantly associated with LDL particle number ( p< 0.03), HDL subpopulations by 2D-gel analysis [α-3: p< 0.005; α-4: p< 0.04; and preα-1: p< 0.03], C-reactive protein ( p< 0.03), sVCAM-1 ( p< 0.02), age ( p< 0.0008), systolic blood pressure ( p< 0.02), heart rate ( p< 0.02) and corneal arcus ( p< 0.04). Carotid IMT was not associated with any traditional lipid level, gender or history of CAD. In a multiple regression model, age ( p =0.0007), α-3 ( p< 0.008) and CRP ( p< 0.03) were significant independent predictors of carotid IMT in this population. Thus, in subjects with hyperalphalipoproteinemia, increased small, dense HDL (α-3) and CRP levels were associated with increasing carotid IMT, suggesting heterogeneity in the role of HDL particles on subclinical atherosclerosis.
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