Remnant cholesterol predicts adverse clinical outcomes in patients with hypertension: a post hoc analysis of the ALLHAT

Background and purpose: Remnant cholesterol (RC) has been proposed to play a role in regulating the residual cardiovascular risk in individuals with atherosclerotic cardiovascular disease (ASCVD), yet the underlying mechanisms remain elusive. This study aimed to investigate the role of RC in both hypertensive and statin-treated populations. Methods: A total of 25,709 hypertensive patients from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) were included. Cox regression analyses were performed to examine the relationship between RC concentrations and the occurrence of ASCVD. Results: Over a median follow-up duration of 3.36 years, a total of 5,584 individuals experienced incident ASCVD. The adjusted hazard ratio (HR) was 1.17 (95% confidence interval [95% CI]: 1.09–1.25; P < 0.001) for the highest RC level in relation to ASCVD incidence, compared with the lowest tertile. Individuals with low-density lipoprotein cholesterol (LDL-C)/high RC and high LDL-C/high RC had a 1.14-fold (95% CI: 1.05–1.23; P = 0.001) and 1.21-fold (95% CI: 1.13–1.31; P < 0.001) increased risk of ASCVD, respectively, relative to those with LDL-C/low RC. The subgroup analysis indicated that in both the White population and hypertensive individuals with age below 65 years, statin treatment has demonstrated significant reductions in the incidence of ASCVD events. Cumulative and time-weighted average (TWA) RC showed positive but imprecise associations with ASCVD. Conclusions: RC was significantly associated with ASCVD, independent of the LDL-C level or conventional risk factors. In addition, White participants and participants aged <65 years showed a potentially greater association between statin treatment and lower ASCVD risk.