Dual residual risk of lipid and inflammation: a prospective analysis of RCII on hypertension incidence and cardiovascular prognosis in Chinese and UK populations.
Findings support RCII as a complementary lipid-inflammatory residual-risk marker; however, external validation and decision-utility studies are needed before clinical implementation.
Abstract
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.
RCII exhibited an independent and positive association with CKM risk in the US and Chinese populations, with consistent dose-response and nonlinear trends, and may be a practical and integrative biomarker for identifying individuals with an increased CKM risk.
Mengchen Zhang, Linlin Huang, Tian Zhang et al.· Anatolian journal of cardiol...· 0 citations
Background Emerging research has associated non-conventional lipid indices with hypertension risk; however, the joint contribution of these lipid metrics and inflammatory biomarkers to hypertension susceptibility remains unclear. Using a nationally representative cohort, we aimed to examine the independent associations of non-conventional lipid indices and their inflammatory composites with incident hypertension. Methods We included 6891 participants from the China Health and Retirement Longitudinal Study (2011–2020). We used multivariable Cox proportional hazards regression to assess the association between baseline and cumulative non-conventional lipid-inflammatory parameters and incident hypertension. We used restricted cubic spline modelling to characterise dose-response relationships. We evaluated receiver operating characteristic curves, net reclassification improvement, and integrated discrimination improvement as secondary conditional analyses. Results Over a median follow-up of 7.79 years, 2532 incident hypertension cases occurred. Higher tertiles of non-conventional lipid indices were associated with progressively increased hypertension risk. In the primary model, elevated baseline and cumulative non-conventional lipid metrics were associated with a higher risk of hypertension across all composite indices. The lipoprotein combine index-C-reactive protein showed the largest effect size (hazard ratio = 1.59; 95% confidence interval = 1.44–1.75). Composite indices demonstrated modest incremental discrimination over individual measures (area under the curve range = 0.55–0.58). Conclusions Non-conventional lipid indices are independently associated with incident hypertension among middle-aged and older Chinese adults. Composite lipid-inflammatory markers provide modest incremental prognostic information beyond conventional lipids, though their standalone discriminatory performance is weak.
Mengjie Zhao, Miaoran Wang, Zirong Li et al.· Journal of Global Health· 0 citations
Background Hypertension frequently coexists with poor cardiovascular health (CVH), yet whether the inflammatory potential of habitual diet, captured by the Dietary Inflammatory Index (DII), relates to CVH and to subsequent adverse cardiovascular events in this population remains unclear. Methods A discovery analysis was performed in 12,376 hypertensive adults from NHANES (2005–2018), with suboptimal CVH defined as a Life’s Essential 8 (LE8) score < 80. External validation used a single-center retrospective cohort of 1,053 Chinese hypertensive patients who underwent percutaneous coronary intervention (PCI); because an LE8 ≥ 80 is rarely attained in this high-risk secondary-prevention population, suboptimal CVH was defined as LE8 < 60. Multivariable logistic regression, restricted cubic spline, subgroup, and mediation analyses examined the DII–CVH association in both cohorts; NHANES analyses incorporated complex survey design weights. In the PCI cohort, Cox proportional-hazards models assessed the associations of DII and LE8 with major adverse cardiovascular events (MACE), all-cause mortality, recurrent myocardial infarction (MI), and repeat revascularization. Results In NHANES, higher DII was independently associated with suboptimal CVH [fully adjusted odds ratio (OR) 1.39, 95% confidence interval (CI) 1.30–1.50; OR 3.84, 95% CI 2.67–5.52 for the highest versus lowest DII tertile], with a linear dose–response. A consistent association was observed in the PCI cohort: each one-unit increase in DII conferred 29% higher odds of suboptimal CVH (fully adjusted OR 1.29, 95% CI 1.19–1.39; OR 2.99, 95% CI 2.11–4.22 for the highest versus lowest tertile), with a linear dose–response. DII independently predicted MACE [hazard ratio (HR) 1.19, 95% CI 1.10–1.28], recurrent MI (HR 1.24, 95% CI 1.10–1.39), repeat revascularization (HR 1.14, 95% CI 1.02–1.28), and all-cause mortality (HR 1.19, 95% CI 1.04–1.35). Conclusion Higher dietary inflammatory potential is linearly associated with poorer CVH across two demographically and clinically distinct hypertensive cohorts and predicts adverse cardiovascular events in patients with established coronary disease, warranting prospective evaluation.
Jianchun Zhang, Yuwei Qiang, Ping Li et al.· Frontiers in Nutrition· 0 citations
Background Cardiometabolic multimorbidity (CMM) has become a major global public health challenge. Although dyslipidemia and chronic low-grade inflammation are known to contribute to cardiometabolic diseases, their long-term cumulative combined effects on the risk of CMM remain poorly understood. This study aimed to evaluate the associations of cumulative lipid-inflammatory indices with incident CMM in a large prospective cohort. Methods A total of 25,376 participants from the Kailuan cohort were included and followed up until December 31, 2023. Nine cumulative lipid-inflammatory exposure indices were constructed via trapezoidal area-under-the-curve calculation using repeated measurements from 2006 to 2010. The primary outcome was incident CMM, defined as the concurrence of at least two cardiometabolic diseases including type 2 diabetes, ischemic heart disease and stroke. Multivariable Cox regression, restricted cubic spline analyses, competing-risk models, and subgroup analyses were applied. Results During a median follow-up of 13.0 years, 481 incident CMM events were documented. All nine cumulative lipid-inflammatory indices were independently and positively associated with an elevated risk of CMM in a dose-response manner. Incorporating these indices into conventional risk model improved risk reclassification and discriminatory ability. Conclusions Elevated cumulative lipid-inflammatory indices are associated with a higher risk of incident CMM. These composite markers may serve as auxiliary indicators for preliminary risk stratification, while causal relationships cannot be confirmed based on this observational cohort alone.
Li-Jun Meng, Haibo Gao, Jing Yang et al.· Frontiers in Endocrinology· 0 citations
OBJECTIVE
While residual cholesterol (RC) and high-sensitivity C-reactive protein (hs-CRP) are independent risk factors for cardiometabolic multimorbidity (CMM), their combined predictive value remains unclear. We investigated the predictive utility of the remnant cholesterol inflammation index (RCII) for CMM incidence.
METHODS
The RCII was derived from 5,870 participants in the China Health and Retirement Longitudinal Study (CHARLS) and 2,295 in the English Longitudinal Study of Ageing (ELSA), calculated as RC (mg/dL) × hs-CRP (mg/L) / 10. Longitudinal analyses in a subcohort (n = 5,966) further assessed the associations between cumulative RCII, changes in RCII and CMM incidence.
RESULTS
Each ln-unit increase in baseline RCII was associated with a 14% (CHARLS: HR 1.14, 95% CI 1.09-1.19) and 21% (ELSA: HR 1.21, 95% CI 1.10-1.34) higher CMM risk. Similarly, cumulative RCII increments raised CMM risk by 20% (CHARLS: HR 1.20, 95% CI 1.11-1.29) and 30% (ELSA: HR 1.30, 95% CI 1.11-1.51). Transition patterns analysis showed that stable high RCII levels conferred the highest CMM risk compared to stable low RCII levels. RCII demonstrated moderate independent predictive capability for CMM and outperformed RC or hs-CRP alone.
CONCLUSION
By integrating lipid and inflammatory pathways, the RCII was significantly associated with incident CMM and may enhance early risk stratification.
Song Wen, Zhonghua Sun, Yanjun Song et al.· Diabetes Research and Clinic...· 0 citations
Cardiovascular-kidney-metabolic (CKM) syndrome integrates metabolic abnormalities, chronic kidney disease, and cardiovascular disease (CVD), with stages 0–3 representing a critical window for primary prevention. Whether the Chinese visceral adiposity index (CVAI) adds predictive value for CVD in this population remains uncertain.
Using data from the China Health and Retirement Longitudinal Study (CHARLS), a nationwide prospective cohort, we included 7,539 participants with CKM stages 0–3. Incident CVD (heart disease or stroke) was the primary outcome. Cox proportional hazards models and restricted cubic splines assessed the association and dose-response relationship, and discrimination was evaluated with the AUC and censoring-adjusted time-dependent AUC, with comparisons against BMI, waist circumference, VAI, and TyG.
Over a median follow-up of 8.0 years, 1,718 incident CVD events were recorded. Each SD increase in CVAI was associated with a 19.5% higher CVD risk (HR, 1.195; 95% CI, 1.135–1.259), with a graded quartile effect (Q4 vs. Q1 HR, 1.585; 95% CI, 1.359–1.848;
P
for trend < 0.001) and a continuous dose-response relationship (
P
for nonlinearity = 0.931). Adding CVAI modestly improved discrimination (AUC, 0.640 to 0.646; DeLong
P
= 0.039), but its AUC was not superior to BMI (0.647) or waist circumference (0.646). Primary CVAI findings remained consistent across subgroup and sensitivity analyses and in competing-risk models, whereas VAI showed no significant independent association.
CVAI is independently and continuously associated with incident CVD in CKM stages 0–3 and may serve as a practical adjunctive tool for early CVD risk stratification.
Long Feng, Geng Yang, He-Song Zeng et al.· Cardiovascular Diabetology· 0 citations
