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Subfractions of High-Density Lipoprotein-Cholesterol and Carotid Intima-Media Thickness: The Northern Manhattan Study
Eduard Tiozzo1, Hannah Gardener2, Barry I Hudson2
1From the Department of Psychiatry and Behavioral Sciences, Miller School of Medicine (E.T.), Department of Neurology, Miller School of Medicine (E.T., H.G., C.D., D.D.-M., C.B.W., R.L.S., T.R.), Division of Endocrinology, Diabetes and Metabolism (B.I.H.), Diabetes Research Institute and Lipid Disorder Clinic (R.B.G.), and Department of Public Health Sciences (R.L.S.), University of Miami, FL; Department of System Medicine, University of Rome Tor Vergata, Rome, Italy (D.D.-M.); Biomarker Discovery and Advanced Technologies (BioDAT), IRCCS San Raffaele Pisana, Rome, Italy (D.D.-M.); Karolinska Institute, Department of Neurobiology, Care Sciences and Society, Stockholm, Sweden (M.C.); Department of Neurology, Columbia University College of Physicians and Surgeons, New York, NY (M.S.V.E.); Department of Biostatistics (Y.K.C.) and Department of Epidemiology (M.D.), Mailman School of Public Health, Columbia University, New York, NY; and Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS-UMR1153), Paris, France (M.D.). etiozzo@miami.edu.
Insights
High-density lipoprotein cholesterol (HDL-C) subfractions, particularly HDL2-C, are inversely associated with carotid intima-media thickness (cIMT). This relationship is more pronounced in individuals with diabetes mellitus, suggesting HDL2-C may be a better vascular risk marker.
Area of Science:
- Cardiovascular Disease Research
- Lipid Metabolism Studies
- Vascular Biology
Background:
- Recent drug trials question the antiatherosclerotic hypothesis of high-density lipoprotein-cholesterol (HDL-C).
- Total HDL-C levels may not be the optimal target for intervention.
- HDL-C subfractions might serve as superior markers for vascular risk assessment.
Purpose of the Study:
- To investigate the relationship between HDL2-C and HDL3-C subfractions and carotid intima-media thickness (cIMT).
- To assess vascular risk markers in a population-based cohort.
Main Methods:
- Cross-sectional study of 988 stroke-free participants from the Northern Manhattan Study.
- HDL-C subfractions measured by precipitation; cIMT assessed via high-resolution carotid ultrasound.
- Multiple linear regression models used to analyze associations between HDL-C subfractions and cIMT.
Main Results:
- HDL2-C and total HDL-C were inversely associated with cIMT after adjusting for risk factors.
- The inverse association between HDL2-C and cIMT was more pronounced in participants with diabetes mellitus.
- No significant association was found between HDL3-C and cIMT.
Conclusions:
- HDL2-C demonstrated a greater impact on cIMT compared to HDL3-C in this urban population.
- The antiatherosclerotic effect of HDL2-C was particularly significant in individuals with diabetes.
- Further research is warranted to elucidate the clinical relevance and antiatherosclerotic mechanisms of HDL-C subfractions.
Background And Purpose:
Recent drug trials have challenged the high-density lipoprotein-cholesterol (HDL-C) antiatherosclerotic hypothesis, suggesting that total level of HDL-C may not be the best target for intervention. 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 relationship 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 2 SDs, β=-0.017, P=0.001 and β=-0.012, P=0.03, respectively). The same inverse association was more pronounced among those with diabetes mellitus (per 2SDs, HDL2-C: β=-0.043, P=0.003 and HDL-C: β=-0.029, P=0.02). HDL3-C was not associated with cIMT.
Conclusions:
HDL2-C had greater effect on cIMT than HDL3-C in this large urban population. The effect of HDL2-C was especially pronounced among individuals with diabetes mellitus. More research is needed to determine antiatherosclerotic effects of HDL-C subfractions and their clinical relevance.
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