Remnant cholesterol inflammation index (RCII) as a potential biomarker for ACPA-negative rheumatoid arthritis: evidence from dual-cohort analysis and serum lipidomics.

Residual Cholesterol Inflammatory Index: A Predictor of Cardiovascular-Kidney-Metabolic Syndrome; Insights from NHANES and CHARLS Cohorts.

Higher remnant cholesterol inflammatory index is associated with increased frailty risk in the UK Biobank

Background Frailty is a major public health concern associated with adverse outcomes. The remnant cholesterol inflammatory index (RCII), a novel biomarker integrating lipid metabolism and systemic inflammation, has been proposed as an indicator of adverse health outcomes. However, little is known about its relationship with frailty. The study aimed to investigate the longitudinal association between RCII and frailty risk in the UK Biobank. Methods A total of 402,850 participants from the UK Biobank were included at baseline. RCII was calculated as remnant cholesterol (RC, mg/dL) × C-reactive protein (CRP, mg/L)/10, and frailty was assessed using the Fried frailty phenotype. Cox proportional hazards regression models were applied to evaluate the association between baseline RCII and incident frailty. Restricted cubic spline (RCS) analyses were used to explore potential nonlinear relationships. To capture cumulative exposure, we additionally analyzed 12,895 participants with the same measurements to examine the relationship between cumulative RCII and frailty risk. Results During a median follow-up of 15.58 years, 2,327 participants (0.58%) developed frailty. Frailty incidence increased progressively across RCII quartiles, from 0.3% in Q1 to 0.9% in Q4 (P for trend <0.001). In the fully adjusted model, each standard deviation increase in RCII was associated with a 11% higher risk of frailty (HR = 1.11, 95% CI: 1.07–1.15). RCS analysis indicated a nonlinear positive relationship, with frailty risk rising more sharply at higher RCII levels. In the 11.68-year subset analysis, 497 participants (3.85%) suffered frailty. Participants in Q4 of cumulative RCII had a significantly higher risk of frailty compared with those in Q1 (HR = 2.34, 95% CI: 1.52–3.60). Subgroup analyses suggested that the association between RCII and frailty was generally consistent across subgroups (P for interaction > 0.05). Conclusion Higher RCII levels, both at baseline and cumulatively, are associated with an increased risk of frailty. RCII may be a promising biomarker for frailty risk stratification and a potential target for early prevention in aging populations.

Disease-specific biomarker value of C-reactive protein and its composite indices in autoinflammatory diseases: an integrated study of multi-modal omics and population cohorts

Background Autoinflammatory diseases (AIDs) are a heterogeneous group of innate immune-driven disorders whose prevalence is rising globally, yet the lack of disease-specific biomarkers continues to hamper accurate disease activity assessment, phenotype stratification, and risk evaluation. C-reactive protein (CRP) is one of the most widely used markers of systemic inflammation, yet its disease-specific expression, clinical correlations, network connectivity, and cellular origin across both adult and pediatric AIDs have not been systematically examined. Methods We established a single-center retrospective cohort including 11 adult and pediatric AIDs and age matched healthy controls. Baseline CRP measurements were obtained before anti-inflammatory or immunosuppressive therapy. We performed multivariate regression and subgroup analyses to examine the associations of CRP and its composite indices, the CRP to lymphocyte ratio (CLR) and CRP to albumin ratio (CAR), with different AIDs. We integrated a public serum proteomic dataset to construct CRP centered protein interaction networks in macrophage activation syndrome. We also analyzed single cell CITE seq and spatial transcriptomic data from healthy human liver to determine the cellular origin of CRP. Results Serum CRP levels showed a disease specific distribution across AIDs, with the highest levels in hyperinflammatory conditions such as AOSD and MAS. CRP correlated with fever, rash, and arthralgia in AOSD, but showed no association with mucosal or articular phenotypes in other diseases. Both CLR and CAR showed stronger associations with disease risk than CRP alone in regression models. Proteomic network analysis positioned CRP as a prominently connected node in the MAS inflammatory interactome. Single cell and spatial transcriptomic data confirmed hepatocytes as the exclusive source of CRP transcripts in healthy human liver. Conclusions These findings indicate a positive association of CRP and its composite indices with AIDs, suggesting their potential as disease-specific biomarkers. Yet, given the single-center retrospective design and lack of external validation, further multi-center prospective studies are required before clinical implementation.

Pan-immune-inflammation value is associated with thyroid autoantibody positivity in a Chinese health examination cohort

Evidence from two large prospective cohorts: variations in remnant cholesterol inflammation index and the risk of cardiometabolic multimorbidity in middle-aged and elderly populations.

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.

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.