Remnant Cholesterol Variability and Incident Ischemic Stroke in the General Population

Background: Studies have demonstrated that remnant cholesterol is correlated with the risk of ischemic stroke. However, it is unknown whether visit-to-visit variability in remnant cholesterol concentration affects ischemic stroke. We sought to examine the role of remnant cholesterol variability in the subsequent development of ischemic stroke in the general population. Methods: We performed a post hoc analysis including eligible participants from the Kailuan Study cohort who underwent 3 health examinations and were free of atrial fibrillation, myocardial infarction, stroke, cancer, or known lipid-medication use from 2006 to 2010. Participants were followed up until the end of 2017. Variability was quantified as variability independent of the mean, average real variability, and SD. Multivariate analysis was performed using the Fine and Gray competing risk model to estimate subhazard ratios assuming death as a competing risk. Results: The final study cohort comprised 38 556 participants. After a median follow-up of 7.0 years, 1058 individuals were newly diagnosed with ischemic stroke. After adjusting for age (time scale), sex, smoking status, alcohol consumption, physical activity, hypertension, diabetes, family history of cardiovascular disease, body mass index, estimated glomerular filtration rate, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, and mean remnant cholesterol, the highest quartile (quartile 4) of variability independent of the mean of remnant cholesterol was associated with an increased ischemic stroke risk compared with the lowest quartile (quartile 1), (subhazard ratio, 1.27 [95% CI, 1.06–1.53]). For each 1-SD increase in variability independent of the mean of remnant cholesterol, the risk increased by 9% (subhazard ratio, 1.09 [95% CI, 1.03–1.16]). The association was also significant using average real variability and SD as indices of variability. Conclusions: Greater remnant cholesterol variability was associated with a higher risk of ischemic stroke in the general population.