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High-density lipoprotein cholesterol efflux capacity is not associated with atherosclerosis and prevalence of
Tatjana Josefs1, Kristiaan Wouters2, Uwe J F Tietge3
1Department of Internal Medicine and CARIM School for Cardiovascular Diseases, Maastricht University Medical Centre, Maastricht, The Netherlands; Division of Cardiology, Department of Medicine, New York University School of Medicine, New York, New York.
Insights
Cholesterol Efflux Capacity (CEC) did not correlate with atherosclerosis in individuals with or without diabetes. However, other high-density lipoprotein (HDL) measures like HDL-C and apoA-I showed protective associations in those with diabetes.
Area of Science:
- Cardiovascular Medicine
- Metabolic Disorders
- Lipid Metabolism
Background:
- High-density lipoprotein cholesterol efflux capacity (HDL-CEC) is a proposed atheroprotective factor.
- Its role in atherosclerosis and cardiovascular risk, especially in diabetic individuals, remains unclear.
Purpose of the Study:
- To investigate the association of HDL-CEC and other HDL characteristics with subclinical and clinical atherosclerosis.
- To examine these associations in individuals with elevated cardiovascular disease (CVD) risk and Type 2 Diabetes Mellitus (T2DM).
Main Methods:
- The CODAM observational cohort (n=574) included individuals with elevated CVD risk and T2DM.
- Multiple linear regression analyzed HDL-CEC, HDL-Cholesterol (HDL-C), apolipoprotein A-I (apoA-I), HDL size, and HDL particle number (HDL-P) against carotid intima-media thickness (cIMT), endothelial dysfunction (EnD) Score, prevalent CVD, and history of CV events (CVE).
- Stratified analyses compared associations between individuals with normal glucose metabolism (NGM) and those with disturbed glucose metabolism (prediabetes/T2DM).
Main Results:
- HDL-CEC showed no association with atherosclerosis markers (cIMT, EnD Score) or CVD/CVE.
- HDL-C, apoA-I, HDL size, and HDL-P were inversely associated with EnD Score and CVE.
- HDL size and HDL-P associations with EnD Score were lost in individuals with (pre)diabetes.
- HDL-C and apoA-I were inversely associated with prevalent CVD in individuals with (pre)diabetes.
Conclusions:
- HDL-CEC is not associated with clinical or subclinical atherosclerosis in this cohort.
- Other HDL characteristics demonstrate atheroprotective effects, but these are diminished or altered in individuals with (pre)diabetes.
- Higher HDL-C and apoA-I levels are linked to lower CVD prevalence specifically in the (pre)diabetic subgroup.
Background:
Cholesterol Efflux Capacity (CEC) is considered to be a key atheroprotective property of high-density lipoproteins (HDL). However, the role of HDL-CEC in atherosclerosis and cardiovascular (CV) risk is still controversial, and data in individuals with diabetes are limited.
Objective:
In this study, we have investigated the relationship of CEC and other HDL characteristics with clinical and subclinical atherosclerosis in subjects with elevated cardiovascular diseases (CVD) risk and Type 2 Diabetes Mellitus (T2DM).
Methods:
Using multiple linear regression analyses, we determined the relationship of HDL-CEC with carotid intima-media thickness (cIMT, Z-Score), an endothelial dysfunction (EnD) Score (Z-Score), prevalent CVD (n = 150 cases) and history of CV events (CVE, n = 85 cases) in an observational cohort (CODAM, n = 574, 59.6 ± 0.3 yr, 61.3% men, 24.4% T2DM). Stratified analyses were performed to determine if the associations differed between individuals with normal glucose metabolism (NGM) and those with disturbed glucose metabolism.
Results:
HDL-CEC was not associated with either marker of atherosclerosis (cIMT, EnD Score) nor with CVD or CVE. In contrast, other HDL characteristics that is, HDL-Cholesterol (HDL-C, Z-Score), apolipoprotein A-I (apoA-I, Z-Score), HDL size (Z-Score) and HDL particle number (HDL-P, Z-Score) were inversely and significantly associated with the EnD Score (s -0.226 to -0.097, P < .05) and CVE (ORs 0.61 to 0.68, P < .05). In stratified analyses, HDL size and HDL-P were significantly associated with the EnD Score in individuals with NGM (Pinteraction .039 and .005, respectively), but not in those with (pre)diabetes. HDL-C and apoA-I were inversely associated with prevalent CVD in individuals with (pre)diabetes (Pinteraction = .074 and .034, respectively), but not in those with NGM.
Conclusion:
HDL-CEC is not associated with clinical or subclinical atherosclerosis, neither in the whole population nor in individuals with (pre)diabetes, while other HDL characteristics show atheroprotective associations. The atheroprotective associations of HDL-size and HDL-P are lost in (pre)diabetes, while higher concentrations of HDL-C and apoA-I are associated with a lower prevalence of CVD in (pre)diabetes.
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