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.