Dual residual risk of lipid and inflammation: a prospective analysis of RCII on hypertension incidence and cardiovascular prognosis in Chinese and UK populations.

BACKGROUND

Residual cardiovascular risk remains a significant clinical challenge despite the intensive management of conventional risk factors. This study aimed to evaluate the impact of the Remnant Cholesterol-Inflammation Index (RCII)-a novel metric integrating dyslipidemia and systemic inflammation-on the incidence of hypertension and its subsequent cardiovascular sequelae.

METHODS

We leveraged data from two large-scale prospective cohorts. The China Health and Retirement Longitudinal Study (CHARLS) included a cross-sectional cohort for prevalent hypertension (N = 8,650) and a longitudinal incident-hypertension cohort (N = 5,022). The UK Biobank (UKB) included 273,122 participants with hypertension at baseline. Multivariable logistic regression and Cox proportional hazards models were used to assess incident hypertension and long-term adverse outcomes (all-cause mortality, major adverse cardiovascular events [MACE], and cardiovascular death), respectively.

RESULTS

In the CHARLS cohort, high RCII was associated with a higher risk of incident hypertension in the fully adjusted model (OR, 1.346; 95% CI, 1.192-1.519). In quartile analysis, the highest RCII quartile was also associated with incident hypertension compared with the lowest quartile (OR, 1.364; 95% CI, 1.150-1.618; P for trend < 0.001). In the UKB cohort, compared with participants in the lowest RCII quartile, those in the highest quartile had higher risks of MACE (HR, 1.273; 95% CI, 1.232-1.315), all-cause mortality (HR, 1.214; 95% CI, 1.169-1.261), and cardiovascular death (HR, 1.284; 95% CI, 1.205-1.368) in fully adjusted complete-case models. Joint-effect analysis showed that concurrent elevation of remnant cholesterol and systemic inflammation was associated with the highest risk of MACE in UKB (HR, 1.16; 95% CI, 1.12-1.20). Exploratory mediation analyses suggested possible indirect pathways involving insulin resistance and oxidative stress.

CONCLUSIONS

RCII was associated with both incident hypertension and adverse prognosis among hypertensive participants. These findings support RCII as a complementary lipid-inflammatory residual-risk marker; however, external validation and decision-utility studies are needed before clinical implementation.