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The risk of cardiovascular events with increased apolipoprotein CIII: A systematic review and meta-analysis
Moritz C Wyler von Ballmoos1, Bernhard Haring2, Frank M Sacks3
1Division of Cardiothoracic Surgery, Department of Surgery, Froedtert Memorial Hospital, Medical College of Wisconsin, Milwaukee, WI, USA.
Insights
Elevated apolipoprotein C-III (apoC-III) levels in blood, particularly in VLDL and LDL, are linked to increased cardiovascular events. This systematic review confirms a significant association between higher apoC-III and heart disease risk.
Area of Science:
- Cardiovascular Science
- Lipid Metabolism
- Biomarker Research
Background:
- Apolipoprotein C-III (apoC-III) is identified as an atherogenic protein present on HDL, VLDL, and LDL particles.
- Understanding the role of apoC-III in cardiovascular disease pathogenesis is crucial for risk stratification.
Purpose of the Study:
- To systematically review existing literature on the association between blood apoC-III levels and cardiovascular events.
- To investigate the dose-response relationship between apoC-III and cardiovascular risk.
Main Methods:
- A comprehensive literature search was conducted across multiple databases (MEDLINE, EMBASE, etc.) and grey literature sources.
- Twelve studies (5 retrospective, 7 prospective) involving 3163 cardiovascular events were included in this systematic review and meta-analysis.
- Pooled analyses examined apoC-III levels in different lipoprotein fractions (non-HDL, HDL, total plasma) and their association with cardiovascular events.
Main Results:
- Significantly higher apoC-III levels were observed in the non-HDL fraction (VLDL and LDL) of plasma among individuals with cardiovascular disease compared to controls.
- No significant difference in apoC-III levels was found in the HDL fraction.
- A 5-mg/dL increase in apoC-III was associated with a 2.48-fold increased risk of cardiovascular events in the non-HDL fraction and a 1.33-fold increased risk in total plasma.
Conclusions:
- Consistent evidence supports an association between blood apoC-III levels (total plasma, VLDL, and LDL) and cardiovascular events.
- Further research is needed to clarify the role of apoC-III in specific lipoproteins for cardiovascular risk assessment and management.
- Elucidating the interaction between triglycerides and apoC-III in cardiovascular disease risk requires additional investigation.
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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