Association of remnant cholesterol with cardiovascular disease events in patients with diabetes: a dose-response systematic review and meta-analysis of adjusted models

Abstract

Aims: This review aimed to examine the dose-response relationship between remnant cholesterol (RC) levels and CVD events in individuals with diabetes as well as high-to-low status of RC levels, highlighting its potential clinical significance.<br /> Data synthesis: This systematic review and meta-analysis followed the PRISMA guidelines and the PICO framework. The protocol was registered in PROSPERO (CRD420251031888). A comprehensive search was conducted up to April 10, 2025. Outcomes were pooled using random-effects models, and dose-response relationships were assessed with restricted cubic splines (RCS). Our meta-analysis pooled data from 2,276,576 participants included in fifteen studies. Higher remnant cholesterol compared with referenced level was associated with higher cardiovascular events, including: MACE, as defined including non-fatal myocardial infarction (MI), stroke, CVD death, and revascularization (Pooled HR = 1.64 (95 CI: 1.16-2.30, I-2 = 91.7)), revascularization (Pooled HR = 1.44 (95 CI: 1.22-1.70)), and ischemic stroke (Pooled HR = 1.12 (95 CI: 1.01-1.24)). Relationship with allcause mortality, non-fatal MI, and atherosclerotic cardiovascular disease (ASCVD) was not significant. Dose-response analysis with RCS model revealed a statistically significant relationship between remnant cholesterol and the risk of MACE (p < 0.0001), myocardial infarction (p = 0.0008) ischemic stroke (p < 0.05).<br /> Conclusions: Higher remnant cholesterol levels are associated with increased cardiovascular risk in diabetes. The dose-response analysis supports its role as an important biomarker for cardiovascular risk, suggesting a potential for clinical use alongside traditional lipid markers.