Separate and Joint Associations of Remnant Cholesterol Accumulation and Variability With Carotid Atherosclerosis: A Prospective Cohort Study

BACKGROUND: We aimed to examine separate and joint associations of remnant cholesterol (RC) accumulation and variability with the risk of carotid atherosclerosis (CAS) in the general population. METHODS AND RESULTS: A total of 6213 participants who underwent 3 sequential health examinations during 2010 to 2015 were enrolled and were followed up until December 31, 2021. Cumulative RC (cumRC) and RC variability among the 3 visits were the exposure of interest in our study. Adjusted Cox models were performed to calculate the hazard ratio (HR) and 95% CI. C‐statistics, integrated discrimination improvement, and the net reclassification index were used to estimate the incremental predictive ability. During a median follow‐up of 4.00 years, 2613 participants developed CAS. Higher cumRC (HR, 1.33 [95% CI, 1.17–1.52]) and greater RC variability (HR, 1.22 [95% CI, 1.08–1.39]) were significantly associated with elevated risk of CAS, independent of traditional cardiovascular risk factors and low‐density lipoprotein cholesterol. Participants were divided into 4 groups according to the median of cumRC and RC variability to assess their joint associations. Compared with “low cumRC and low variability,” “high cumRC and high variability” had the highest risk of CAS, followed by “high cumRC and low variability” and “low cumRC and high variability.” Finally, joint assessment of RC accumulation and variability had the significantly highest incremental effect on the predictive value of CAS versus single‐time‐point measures of RC. CONCLUSIONS: Excessive cumRC levels and greater RC variability were each independently associated with higher incidence of CAS, and their coexistence could further yield significantly higher risks.