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Association of High-Density Lipoprotein-Cholesterol Versus Apolipoprotein A-I With Risk of Coronary Heart Disease: The European Prospective Investigation Into Cancer-Norfolk Prospective Population Study, the Atherosclerosis Risk in Communities Study, and

TitleAssociation of High-Density Lipoprotein-Cholesterol Versus Apolipoprotein A-I With Risk of Coronary Heart Disease: The European Prospective Investigation Into Cancer-Norfolk Prospective Population Study, the Atherosclerosis Risk in Communities Study, and
Publication TypeJournal Article
Year of Publication2017
Authorsvan Capelleveen JC, Bochem AE, S Boekholdt M, Mora S, Hoogeveen RC, Ballantyne CM, Ridker PM, Sun W, Barter PJ, Tall AR, Zwinderman AH, Kastelein JJP, Wareham NJ, Khaw K-T
Secondary AuthorsG Hovingh K
JournalJ Am Heart Assoc
Volume6
Issue8
Date Published2017 Aug 03
ISSN2047-9980
KeywordsAged, Antineoplastic Agents, Apolipoprotein A-I, Aspirin, Cardiovascular Diseases, Cholesterol, HDL, Coronary Disease, Double-Blind Method, England, Female, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Neoplasms, Platelet Aggregation Inhibitors, Prognosis, Prospective Studies, Risk Factors, Vitamin E, Women's Health
Abstract

BACKGROUND: The contribution of apolipoprotein A-I (apoA-I) to coronary heart disease (CHD) risk stratification over and above high-density lipoprotein cholesterol (HDL-C) is unclear. We studied the associations between plasma levels of HDL-C and apoA-I, either alone or combined, with risk of CHD events and cardiovascular risk factors among apparently healthy men and women.

METHODS AND RESULTS: HDL-C and apoA-I levels were measured among 17 661 participants of the EPIC (European Prospective Investigation into Cancer)-Norfolk prospective population study. Hazard ratios for CHD events and distributions of risk factors were calculated by quartiles of HDL-C and apoA-I. Results were validated using data from the ARIC (Atherosclerosis Risk in Communities) and WHS (Women's Health Study) cohorts, comprising 15 494 and 27 552 individuals, respectively. In EPIC-Norfolk, both HDL-C and apoA-I quartiles were strongly and inversely associated with CHD risk. Within HDL-C quartiles, higher apoA-I levels were not associated with lower CHD risk; in fact, CHD risk was higher within some HDL-C quartiles. ApoA-I levels were associated with higher levels of CHD risk factors: higher body mass index, HbA1c, non-HDL-C, triglycerides, apolipoprotein B, systolic blood pressure, and C-reactive protein, within fixed HDL-C quartiles. In contrast, HDL-C levels were consistently inversely associated with overall CHD risk and CHD risk factors within apoA-I quartiles (

CONCLUSIONS: Our findings demonstrate that apoA-I levels do not offer predictive information over and above HDL-C. In fact, within some HDL-C quartiles, higher apoA-I levels were associated with higher risk of CHD events, possibly because of the unexpected higher prevalence of cardiovascular risk factors in association with higher apoA-I levels.

CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00000479.

DOI10.1161/JAHA.117.006636
Alternate JournalJ Am Heart Assoc
PubMed ID28775061
PubMed Central IDPMC5586475
Grant ListMR/N003284/1 / MRC_ / Medical Research Council / United Kingdom
G1000143 / MRC_ / Medical Research Council / United Kingdom
MC_UU_12015/1 / MRC_ / Medical Research Council / United Kingdom
G0401527 / MRC_ / Medical Research Council / United Kingdom
UM1 CA182913 / CA / NCI NIH HHS / United States
R01 CA047988 / CA / NCI NIH HHS / United States
R01 HL080467 / HL / NHLBI NIH HHS / United States
R01 HL117861 / HL / NHLBI NIH HHS / United States
RC1 HL099355 / HL / NHLBI NIH HHS / United States