The risk of cardiovascular events with increased apolipoprotein CIII: A systematic review and meta-analysis

BACKGROUND: Apolipoprotein C111 (apoC-Ill) is an atherogenic protein found on HDL, VLDL and LDL. OBJECTIVE: The objective of this study is to review the literature on the association of blood apoCIII level with cardiovascular events and the dose-response relationship for this association. METHODS AND RESULTS: MEDUNE, EMBASE, BIOSIS, CINAHL, Clinicaltrials.gov, greyliterature sources, contact with investigators, and reference lists of studies, without language restrictions, were reviewed. Twelve studies (5 retrospective and 7 prospective) with a total of 3163 cases of cardiovascular events met inclusion criteria for this systematic review. The pooled standardized mean difference showed significantly higher levels of apoC-BI in the non-HDL fraction of plasma (representing apoC-111 in VLDL and LDL) in those with cardiovascular disease compared with controls; no difference for apoC-II1 levels in HDL; and, a trend toward higher total plasma apoC-BI in the cases. Pooled risk estimates from the meta-analysis were 2.48 (1.48-4.32; non-HDL apoC-BI), 1.09 (0.65-1.82; HDL apoC-111), and 1.33 (1.07-1.66; total apoC-111) for a cardiovascular event with a 5-mg/dL increase in apoC-III. CONCLUSIONS: The current body of literature includes several methodologically sound studies that together provide consistent evidence for an association of cardiovascular events with blood apoC-1-11 level in total plasma or in VLDL and LDL. More data are needed to determine importance of levels of apoC-I11 in specific lipoproteins for cardiovascular risk assessment and management and to elucidate the interaction between triglycerides and apoC-LTI in relation to risk of cardiovascular disease. (C) 2015 National Lipid Association. This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/).