Background and Purpose: Recent drug trials have challenged the “HDL-cholesterol anti-atherosclerotic hypothesis”, suggesting that total levels of HDL-C may not be best target for intervention. HDL-cholesterol (HDL-C) subfractions may be better markers of vascular risk than total levels of HDL-C. The objective of this cross-sectional study was to investigate the relation between HDL2-C and HDL3-C fractions and carotid intima-media thickness (cIMT) in the population-based Northern Manhattan Study.
Methods: We evaluated 988 stroke-free participants (mean age 66±8 years; 60% women; 66% Hispanic, and 34% Non-Hispanic) with available data on HDL-C subfractions using precipitation method and cIMT assessed by a high-resolution carotid ultrasound. The associations between HDL-C subfractions and cIMT were analyzed by multiple linear regression models.
Results: The mean HDL2-C was 14 ± 8 mg/dl, HDL3-C 32 ± 8 mg/dl, and the mean total HDL-C was 46 ±14 mg/dl. The mean cIMT was 0.90 ± 0.08 mm. After controlling for demographics and vascular risk factors, HDL2-C and total HDL-C were inversely associated with cIMT (per 2SDs, beta= -0.012, p=0.03 and beta= -0.012, p=0.04, respectively). The same inverse association was more pronounced among those with diabetes (per 2SDs, HDL2-C: beta= -0.036, p=0.04; HDL-C: beta= -0.032, p=0.04). HDL3-C was inversely associated with cIMT but the association was not significant (per 2SDs, beta= -0.008, p=0.13) after adjustment.
Conclusions: HDL2-C had greater effect on cIMT then HDL3-C in this urban population. This effect was especially pronounced among individuals with diabetes. More research in needed to determine anti-atherosclerotic effects of HDL-C subfractions and clinical relevance of raising their levels.