Background: Accumulating evidence suggests a substantial contribution of remnant cholesterol (RC) to residual risk for the development or relapse of atherosclerotic cardiovascular disease (ASCVD). We aimed to evaluate the association of RC levels with ASCVD risk by different risk categories and methods of RC assessment. We also assessed available evidence of the effects of lipid-lowering therapies (LLTs) on RC levels.
Methods: English-language searches of Medline, PubMed, and Embase (inception to 31 January 2023); ClinicalTrials.gov (October 2022); and reference lists of studies and reviews. Studies reporting on the risk of the composite endpoint [all-cause mortality, cardiovascular mortality, and major adverse cardiac events (MACE)] by RC levels were included. Moreover, we searched for studies reporting differences in RC levels after the administration of LLT(s).
Results: Among n = 29 studies with 257,387 participants, we found a pooled linear (pooled HR: 1.27 per 1-SD increase, 95% CI: 1.12-1.43, P < 0.001, I2 = 95%, n = 15 studies) and non-linear association (pooled HR: 1.59 per quartile increase, 95% CI: 1.35-1.85, P < 0.001, I2 = 87.9%, n = 15 studies) of RC levels and the risk of M ACE both in patients with and without established ASCVD. Interestingly, the risk of MACE was higher in studies with directly measured vs. calculated RC levels. In a limited number of studies and participants, LLTs reduced RC levels.
Conclusion: RC levels are associated with ASCVD risk both in primary and secondary prevention. Directly measured RC levels are associated with ASCVD risk more evidently. Available LLTs tend to decrease RC levels, although the clinical relevance of RC decrease merits further investigation.
Prospero registration: CRD42022371346.
Keywords: CV death; Cardiovascular disease; Ischemic stroke; Meta-analysis; Myocardial infarction; Remnant cholesterol.
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