Moritz C Wyler von Ballmoos1, Bernhard Haring2, Frank M Sacks3. 1. Division of Cardiothoracic Surgery, Department of Surgery, Froedtert Memorial Hospital, Medical College of Wisconsin, Milwaukee, WI, USA. Electronic address: mcwvb@post.harvard.edu. 2. Department of Internal Medicine I, Comprehensive Heart Failure Center, University of Würzburg, Bavaria, Germany. 3. Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Abstract
BACKGROUND: Apolipoprotein CIII (apoC-III) 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 apoC-III level with cardiovascular events and the dose-response relationship for this association. METHODS AND RESULTS: MEDLINE, EMBASE, BIOSIS, CINAHL, Clinicaltrials.gov, grey-literature 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-III in the non-HDL fraction of plasma (representing apoC-III in VLDL and LDL) in those with cardiovascular disease compared with controls; no difference for apoC-III levels in HDL; and, a trend toward higher total plasma apoC-III in the cases. Pooled risk estimates from the meta-analysis were 2.48 (1.48-4.32; non-HDL apoC-III), 1.09 (0.65-1.82; HDL apoC-III), and 1.33 (1.07-1.66; total apoC-III) 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-III level in total plasma or in VLDL and LDL. More data are needed to determine importance of levels of apoC-III in specific lipoproteins for cardiovascular risk assessment and management and to elucidate the interaction between triglycerides and apoC-III in relation to risk of cardiovascular disease.
BACKGROUND:Apolipoprotein CIII (apoC-III) 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 apoC-III level with cardiovascular events and the dose-response relationship for this association. METHODS AND RESULTS: MEDLINE, EMBASE, BIOSIS, CINAHL, Clinicaltrials.gov, grey-literature 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-III in the non-HDL fraction of plasma (representing apoC-III in VLDL and LDL) in those with cardiovascular disease compared with controls; no difference for apoC-III levels in HDL; and, a trend toward higher total plasma apoC-III in the cases. Pooled risk estimates from the meta-analysis were 2.48 (1.48-4.32; non-HDL apoC-III), 1.09 (0.65-1.82; HDL apoC-III), and 1.33 (1.07-1.66; total apoC-III) 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-III level in total plasma or in VLDL and LDL. More data are needed to determine importance of levels of apoC-III in specific lipoproteins for cardiovascular risk assessment and management and to elucidate the interaction between triglycerides and apoC-III in relation to risk of cardiovascular disease.
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