Abstract
BACKGROUND: Apolipoprotein CIII (apoCIII) is an 8.8-kDa apolipoprotein peptide found on HDL, VLDL and LDL. OBJECTIVE: To systematically review current evidence on the association of blood apoCIII level with cardiovascular events, and to evaluate whether the current literature suggests a dose-response relationship for this association. DATA SOURCES : MEDLINE, EMBASE, BIOSIS, CINAHL, Clinicaltrials.gov, grey-literature sources, contact with investigators, and reference lists of studies, without language restrictions. STUDY SELECTION: Publications were selected if they investigated the association between blood apoCIII level and coronary heart disease, myocardial infarction, stroke, or sudden death from stroke or myocardial infarction. Data including study and patient characteristics, apoCIII level, and outcomes were extracted independently by two investigators. DATA SYNTHESIS AND RESULTS: 10 studies (6 case-control, 4 cohort studies) with a total of 1469 cases of cardiovascular events met inclusion criteria. Four studies compared apoCIII levels and showed higher blood levels in subjects with a cardiovascular event. The other six studies calculated adjusted estimates of relative risks of 1.82-3.88 (total apoCIII), 2.25-8.87 (non-HDL apoCIII), and 0.64-2.57 (HDL apoCIII) for cardiovascular events. Random-effects meta-analyses were performed with summarized dose-response data where applicable. All studies showed a positive, significant association of apoCIII with cardiovascular disease. Risk estimates demonstrate a monotonous, graded increase in risk of cardiovascular disease with increasing levels of apoCIII and are beyond what could reasonably be explained by residual confounding alone. CONCLUSION: The current body of literature includes several methodologically sound studies that together provide consistent evidence for an independent association of cardiovascular events with blood apoCIII level. Available data suggest that apoCIII is an independent risk factor for cardiovascular events. Further data is needed in order to determine the significance of the location and amount of apoCIII on specific lipoproteins in cardiovascular risk management.
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