TY - JOUR
T1 - Association of high-density lipoprotein subclasses and incident coronary heart disease
T2 - The Jackson Heart and Framingham Offspring Cohort Studies
AU - Joshi, Parag H.
AU - Toth, Peter P.
AU - Lirette, Seth T.
AU - Griswold, Michael E.
AU - Massaro, Joseph M.
AU - Martin, Seth S.
AU - Blaha, Michael J.
AU - Kulkarni, Krishnaji R.
AU - Khokhar, Arif A.
AU - Correa, Adolfo
AU - D'Agustino, Ralph B.
AU - Jones, Steven R.
N1 - Funding Information:
This work was supported by the National Heart, Lung, and Blood Institute and the National Institute on Minority Health and Health Disparities (JHS; contracts HHSN268201300046C, HHSN268201300047C, HHSN268201300048C, HHSN268201300049C, HHSN268201300050C), with additional support from the National Institute on Biomedical Imaging and Bioengineering; the NIH/NHLBI (Framingham Heart Study; contract no. N01-HC-25195-06) in collaboration with Boston University; the NIH (training grants T32HL007227, T32HL07024 to PHJ and SSM); the Pollin Cardiovascular Prevention Fellowship; the Marie-Josée and Henry R Kravis endowed fellowship (to SSM).
Publisher Copyright:
© 2014 European Society of Cardiology.
PY - 2016/1/1
Y1 - 2016/1/1
N2 - Aims We aimed to clarify the associations of high-density lipoprotein cholesterol (HDL-C) subclasses with incident coronary heart disease (CHD) in two large primary prevention cohorts. Methods We measured cholesterol at baseline from the two major HDL subfractions (larger, more buoyant HDL2 and smaller, denser HDL3) separated by density gradient ultracentrifugation in 4114 (mean age 53.8 years; 64% female) African American participants from the Jackson Heart Study and 818 (mean age 57.3 years, 52% female) predominantly Caucasian participants from the Framingham Offspring Cohort Study. Multivariable adjusted hazard ratios (HRs) for HDL-C and its subclasses were derived from Cox proportional hazards regression models to estimate associations with incident CHD events including myocardial infarction, CHD death, and revascularization. Analyses were performed for each cohort separately and as a combined population. Results In models adjusted for cardiovascular risk factors for the combined population, HDL3-C (HR 0.76 per SD increase; 95% confidence interval (CI), 0.62-0.94; p = 0.01), rather than HDL2-C (HR 0.88 per SD; 95% CI, 0.72-1.09; p = 0.24) drove the inverse association of HDL-C (HR 0.79 per SD; 95% CI, 0.64-0.98; p = 0.03) with CHD. Similar associations were seen in multivariable analyses within each cohort including after adjusting for apolipoprotein A1 in the Jackson Heart Study. Conclusion Smaller, denser HDL3-C levels are primarily responsible for the inverse association between HDL-C and incident CHD in this diverse group of primary prevention subjects. These findings have important implications ranging from considerations of HDL biology to interpretations of clinical trials utilizing HDL-C therapeutics.
AB - Aims We aimed to clarify the associations of high-density lipoprotein cholesterol (HDL-C) subclasses with incident coronary heart disease (CHD) in two large primary prevention cohorts. Methods We measured cholesterol at baseline from the two major HDL subfractions (larger, more buoyant HDL2 and smaller, denser HDL3) separated by density gradient ultracentrifugation in 4114 (mean age 53.8 years; 64% female) African American participants from the Jackson Heart Study and 818 (mean age 57.3 years, 52% female) predominantly Caucasian participants from the Framingham Offspring Cohort Study. Multivariable adjusted hazard ratios (HRs) for HDL-C and its subclasses were derived from Cox proportional hazards regression models to estimate associations with incident CHD events including myocardial infarction, CHD death, and revascularization. Analyses were performed for each cohort separately and as a combined population. Results In models adjusted for cardiovascular risk factors for the combined population, HDL3-C (HR 0.76 per SD increase; 95% confidence interval (CI), 0.62-0.94; p = 0.01), rather than HDL2-C (HR 0.88 per SD; 95% CI, 0.72-1.09; p = 0.24) drove the inverse association of HDL-C (HR 0.79 per SD; 95% CI, 0.64-0.98; p = 0.03) with CHD. Similar associations were seen in multivariable analyses within each cohort including after adjusting for apolipoprotein A1 in the Jackson Heart Study. Conclusion Smaller, denser HDL3-C levels are primarily responsible for the inverse association between HDL-C and incident CHD in this diverse group of primary prevention subjects. These findings have important implications ranging from considerations of HDL biology to interpretations of clinical trials utilizing HDL-C therapeutics.
KW - High-density lipoprotein cholesterol
KW - coronary heart disease
KW - primary prevention
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U2 - 10.1177/2047487314543890
DO - 10.1177/2047487314543890
M3 - Article
C2 - 25062744
AN - SCOPUS:84949844226
SN - 2047-4873
VL - 23
SP - 41
EP - 49
JO - European Journal of Preventive Cardiology
JF - European Journal of Preventive Cardiology
IS - 1
ER -