The association between remnant cholesterol and cardiovascular events: A systematic review and meta-regression.

BACKGROUND

Despite extensive efforts to lower low-density lipoprotein cholesterol (LDL-C), cardiovascular disease remains highly prevalent. Remnant cholesterol (RC) has been proposed as a potentially more relevant therapeutic target.

OBJECTIVE

To evaluate the association between RC reduction and cardiovascular outcomes in randomized controlled trials (RCTs) of cholesterol- and triglyceride-lowering therapies, assessing whether RC independently influences cardiovascular risk.

METHODS

Cochrane Central and Embase were searched for RCTs with ≥1000 participants and ≥2 years' planned duration that assessed cholesterol- or triglyceride-lowering therapies vs placebo, usual care, or other lipid-lowering drugs in adults. Two reviewers independently extracted data and evaluated methodological quality. Meta-analysis and meta-regression were performed.

RESULTS

Forty-three RCTs met the inclusion criteria; most had some risk of bias, and evidence certainty was moderate. Meta-analysis showed absolute risk reductions of 0.4% (95% CI 0.1%-0.6%) for all-cause mortality, 1.3% (95% CI 1.1%-1.6%) for myocardial infarction, and 0.4% (95% CI 0.2%-0.6%) for stroke in treatment vs control groups. Meta-regression demonstrated no association between RC reduction and any clinical outcome, whereas LDL-C and non-high-density lipoprotein cholesterol reductions were associated with risk reduction.

CONCLUSION

RC reduction was not associated with cardiovascular benefit. This contrasts with observational and Mendelian randomization (MR) studies, likely reflecting methodological differences; MR estimates lifelong genetically mediated exposure and may not reliably predict the effects of short-term pharmacological lipid lowering.