TY - JOUR
T1 - High-density lipoprotein cholesterol and particle concentrations, carotid atherosclerosis, and coronary events
T2 - MESA (Multi-Ethnic Study of Atherosclerosis)
AU - MacKey, Rachel H.
AU - Greenland, Philip
AU - Goff, David C.
AU - Lloyd-Jones, Donald
AU - Sibley, Christopher T.
AU - Mora, Samia
N1 - Funding Information:
Dr. Mackey was supported by a research grant from LipoScience, Inc. to the University of Pittsburgh. The grant was unrestricted because LipoScience exercised no control over the design, management, analysis, or interpretation of the data, or in the preparation, review, or approval of the paper. This research was supported by contracts N01-HC-95159 through N01-HC-95169 from the National Heart, Lung, and Blood Institute , an unrestricted grant from LipoScience, Inc. , and by grant K08 HL094375 to Dr. Mora. Dr. Goff is a research consultant for a clinical trial of a glucose lowering medication marketed by Merck; and a Data and Safety Monitoring Board member for a clinical trial of a glucose lowering medication marketed by Takeda. Dr. Mora received a research grant from AstraZeneca ; and honorarium/consultant fees from Pfizer, Abbott, Quest Diagnostics, and AstraZeneca. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
PY - 2012/8/7
Y1 - 2012/8/7
N2 - Objectives: The purpose of this study was to evaluate independent associations of high-density lipoprotein cholesterol (HDL-C) and particle (HDL-P) concentrations with carotid intima-media thickness (cIMT) and incident coronary heart disease (CHD). Background: HDL-C is inversely related to CHD, and also to triglycerides, low-density lipoprotein particles (LDL-P), and related metabolic risk. HDL-P associations with CHD may be partially independent of these factors. Methods: In a multiethnic study of 5,598 men and women ages 45 to 84 years old, without baseline CHD, excluding subjects on lipid-lowering medications, triglycerides >400 mg/dl, or missing values, we evaluated associations of HDL-C and nuclear magnetic resonance spectroscopy-measured HDL-P with cIMT and incident CHD (myocardial infarction, CHD death, and angina, n = 227 events; mean 6.0 years follow-up). All models were adjusted for age, sex, ethnicity, hypertension, and smoking. Results: HDL-C and HDL-P correlated with each other (ρ = 0.69) and LDL-P (ρ = -0.38, -0.25, respectively, p < 0.05 for all). For (1 SD) higher HDL-C (15 mg/dl) or HDL-P (6.64 μmol/l), cIMT differences were - 26.1 (95% confidence interval [CI]: -34.7 to -17.4) μm and -30.1 (95% CI: -38.8 to - 21.4) μm, and CHD hazard ratios were 0.74 (95% CI: 0.63 to 0.88) and 0.70 (95% CI: 0.59 to 0.82), respectively. Adjusted for each other and LDL-P, HDL-C was no longer associated with cIMT (2.3; 95% CI: - 9.5 to 14.2 μm) or CHD (0.97; 95% CI: 0.77 to 1.22), but HDL-P remained independently associated with cIMT (-22.2; 95% CI: - 33.8 to -10.6 μm) and CHD (0.75; 95% CI: 0.61 to 0.93). Interactions by sex, ethnicity, diabetes, and high-sensitivity C-reactive protein were not significant. Conclusions: Adjusting for each other and LDL-P substantially attenuated associations of HDL-C, but not HDL-P, with cIMT and CHD. Potential confounding by related lipids or lipoproteins should be carefully considered when evaluating HDL-related risk.
AB - Objectives: The purpose of this study was to evaluate independent associations of high-density lipoprotein cholesterol (HDL-C) and particle (HDL-P) concentrations with carotid intima-media thickness (cIMT) and incident coronary heart disease (CHD). Background: HDL-C is inversely related to CHD, and also to triglycerides, low-density lipoprotein particles (LDL-P), and related metabolic risk. HDL-P associations with CHD may be partially independent of these factors. Methods: In a multiethnic study of 5,598 men and women ages 45 to 84 years old, without baseline CHD, excluding subjects on lipid-lowering medications, triglycerides >400 mg/dl, or missing values, we evaluated associations of HDL-C and nuclear magnetic resonance spectroscopy-measured HDL-P with cIMT and incident CHD (myocardial infarction, CHD death, and angina, n = 227 events; mean 6.0 years follow-up). All models were adjusted for age, sex, ethnicity, hypertension, and smoking. Results: HDL-C and HDL-P correlated with each other (ρ = 0.69) and LDL-P (ρ = -0.38, -0.25, respectively, p < 0.05 for all). For (1 SD) higher HDL-C (15 mg/dl) or HDL-P (6.64 μmol/l), cIMT differences were - 26.1 (95% confidence interval [CI]: -34.7 to -17.4) μm and -30.1 (95% CI: -38.8 to - 21.4) μm, and CHD hazard ratios were 0.74 (95% CI: 0.63 to 0.88) and 0.70 (95% CI: 0.59 to 0.82), respectively. Adjusted for each other and LDL-P, HDL-C was no longer associated with cIMT (2.3; 95% CI: - 9.5 to 14.2 μm) or CHD (0.97; 95% CI: 0.77 to 1.22), but HDL-P remained independently associated with cIMT (-22.2; 95% CI: - 33.8 to -10.6 μm) and CHD (0.75; 95% CI: 0.61 to 0.93). Interactions by sex, ethnicity, diabetes, and high-sensitivity C-reactive protein were not significant. Conclusions: Adjusting for each other and LDL-P substantially attenuated associations of HDL-C, but not HDL-P, with cIMT and CHD. Potential confounding by related lipids or lipoproteins should be carefully considered when evaluating HDL-related risk.
KW - cardiovascular disease
KW - high-density lipoprotein cholesterol
KW - high-density lipoprotein particles
KW - lipids
KW - lipoproteins
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U2 - 10.1016/j.jacc.2012.03.060
DO - 10.1016/j.jacc.2012.03.060
M3 - Article
C2 - 22796256
AN - SCOPUS:84864767131
SN - 0735-1097
VL - 60
SP - 508
EP - 516
JO - Journal of the American College of Cardiology
JF - Journal of the American College of Cardiology
IS - 6
ER -