The findings highlight a unique susceptibility of the cardiovascular system to low-level inflammation, overshadowing the contribution of sleep disturbances, and identified model-based turning points reflect an inflection in mortality risk, suggesting a potential threshold effect in systemic inflammation.
Abstract
Physical functional limitations and sleep disturbances frequently co-occur in older adults, yet their joint mortality risks and the potential nonlinear dynamics of systemic inflammation remain unclear. This study investigated the joint associations of health behavior profiles (physical function and sleep) and the systemic immune-inflammation index (SII) with mortality, focusing on exploring nonlinear relationships. Data were obtained from 4548 individuals who participated in the National Health and Nutrition Examination Survey (2011–2014). Survey-weighted Cox proportional hazards models and restricted cubic splines with change-point diagnostics were used to characterize exposure-response relationships. Compared with healthy controls, participants with physical functional limitations exhibited >2-fold increases in the risks of all-cause mortality (hazard ratio: 2.44) and cardiovascular mortality (hazard ratio: 2.46). Concurrent sleep disturbances conferred minimal additional risk. The association of SII value with mortality was nonlinear. Risk remained stable at lower SII values but increased sharply beyond identified model-based turning points (SII ≈ 447–644 for all-cause mortality; SII ≈ 332–643 for cardiovascular mortality). Physical functional limitations are robustly associated with mortality, overshadowing the contribution of sleep disturbances. The identified model-based turning points reflect an inflection in mortality risk, suggesting a potential threshold effect in systemic inflammation. Specifically, the findings highlight a unique susceptibility of the cardiovascular system to low-level inflammation. Given the observational nature of this study, these turning points are exploratory and warrant external validation.
Cardiovascular–kidney–metabolic (CKM) syndrome carries high mortality risk. Whether A Body Shape Index (ABSI), Weight-Adjusted Waist Index (WWI), Systemic Inflammation Response Index (SIRI), and Systemic Immune-Inflammation Index (SII) mediate the associations of Dietary Inflammatory Index (DII) and Composite Dietary Antioxidant Index (CDAI) with mortality in this population remains unknown. We included 21,420 adults with CKM from National Health and Nutrition Examination Survey 1999 to 2018 with mortality follow-up through December 31, 2019. DII and CDAI were calculated from 24-hour dietary recalls. Survey-weighted Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause and cardiovascular mortality, modeling DII and CDAI as continuous variables and tertiles. Restricted cubic splines and 2-piecewise Cox models assessed nonlinearity. Mediation analyses evaluated indirect effects through ABSI, WWI, SIRI, and SII. During follow-up, 3532 all-cause and 1103 cardiovascular deaths occurred. In fully adjusted models, higher DII was associated with increased all-cause mortality (HR per 1-unit increase: 1.06, 95% CI: 1.04–1.09) and cardiovascular mortality (HR: 1.06, 95% CI: 1.02–1.10); the highest versus lowest tertile was associated with HRs of 1.27 (95% CI: 1.16–1.39) and 1.27 (95% CI: 1.08–1.49), respectively. Higher CDAI was associated with lower all-cause and cardiovascular mortality; the highest versus lowest tertile showed HRs of 0.84 (95% CI: 0.77–0.93) and 0.78 (95% CI: 0.65–0.93), respectively. Nonlinearity was observed between CDAI and all-cause mortality (P = .017). The percentage mediated by ABSI, WWI, SIRI, and SII ranged from approximately 4% to 9% for the association with all-cause mortality. In adults with CKM, DII and CDAI were independently associated with mortality outcomes, and ABSI, WWI, SIRI, and SII mediated a modest proportion of the association with all-cause mortality. Further studies are needed to confirm these findings.
Adults with prediabetes or diabetes and cardiovascular disease (CVD) face a substantial burden of premature mortality. Chronic inflammation, malnutrition and vascular aging are key pathways linking dysglycaemia and CVD to adverse outcomes. The Advanced Lung Cancer Inflammation Index (ALI) reflects systemic inflammation and nutritional status, while estimated pulse wave velocity (ePWV) serves as a surrogate of vascular aging. However, their independent and joint associations with mortality in dysglycemic adults with CVD remain unclear.
NHANES 1999–2018 data comprising 101,316 participants were analyzed. After exclusions, adults ≥ 20 years with prediabetes/diabetes and CVD were included (
n
= 1,992). ALI and ePWV were analysed as continuous variables and cross-classified using maximally selected cut-points. Survey-weighted Cox models, restricted cubic splines and subgroup/sensitivity analyses were applied. Time-dependent receiver operating characteristic curves and C-indices were used to compare prognostic discrimination.
Higher ALI was inversely associated with all-cause, cardiovascular, and premature mortality, whereas higher ePWV was positively associated with all-cause and cardiovascular mortality. Per 10-unit increment in ALI, fully adjusted hazard ratios (HRs) were 0.899 (95% CI 0.872–0.928) for all-cause mortality, 0.938 (0.885–0.995) for cardiovascular mortality, and 0.889 (0.837–0.945) for premature mortality. For ePWV, the corresponding HRs per 1 m/s increment were 1.139 (1.072–1.211) for all-cause mortality and 1.216 (1.102–1.341) for cardiovascular mortality. In joint analyses, combined ALI–ePWV categories showed a risk gradient: participants with high ALI/low ePWV had the lowest risks of all-cause mortality (HR 0.382, 95% CI 0.280–0.520), cardiovascular mortality (HR 0.379, 95% CI 0.228–0.630), and premature mortality (HR 0.402, 95% CI 0.245–0.659) compared with those with low ALI/high ePWV.
ALI and ePWV provide complementary information on systemic inflammation–nutrition status and vascular ageing, and their combined categories define distinct risk strata for mortality in adults with dysglycaemia and CVD. Their combined categories may help characterize mortality-risk heterogeneity and inform future risk-assessment studies in this high-risk population.
Xi-Cheng Zhang, Jiajie Guo, Feng Luo et al.· BMC Cardiovascular Disorders· 0 citations
Background Anti-inflammatory dietary patterns are associated with a lower risk of several chronic diseases, but their association with all-cause mortality in Chinese older adults is unknown. In this first study of a Chinese population, we investigated this association and its joint effects with physical activity, to inform strategies for healthy longevity. Methods This analysis included 6,468 participants aged ≥65 years from the Chinese Longitudinal Healthy Longevity Survey. Anti-inflammatory diet was assessed using the anti-inflammatory diet index (AIDI), which was derived from data collected via a simplified food frequency questionnaire. Physical activity was assessed by a self-reported questionnaire. We used Cox proportional hazards regression models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results During a median follow-up of 7 years, 4,117 deaths occurred. After multivariable adjustment, compared with participants in the lowest tertile of the AIDI, those in the highest tertile had a lower risk of all-cause mortality (HR = 0.85; 95%CI: 0.77-0.94). Each one standard deviation increase in the AIDI was associated with a 8% lower risk of mortality. Joint analyses further showed that a high AIDI combined with regular exercise, or with high leisure activity, was associated with a significantly lower mortality risk. Conclusions Adherence to an anti-inflammatory diet was associated with reduced mortality risk in Chinese older adults. The findings underscore the value of integrating both dietary and physical activity strategies to promote healthy longevity.
Minghui Sun, Tian Li, Ling Cong et al.· Frontiers in Immunology· 0 citations
Diabetes is a major global health burden, with chronic inflammation playing a central role in its progression and complications. The pan-immune-inflammation value (PIV) is a novel composite biomarker reflecting systemic immune inflammation. However, its prognostic value for mortality in individuals with diabetes remains unclear.
We conducted a retrospective cohort analysis using the nationally representative National Health and Nutrition Examination Survey (NHANES) data, including participants aged ≥ 20 with available PIV data. PIV was calculated using a validated equation and then log-transformed (ln) before analysis. Multivariable Cox regression models were employed to evaluate this association. We further explored the dose-response relationship using restricted cubic splines (RCS) and threshold analysis to identify potential non-linear effects. The robustness of findings was confirmed through subgroup and sensitivity analyses, and the potential mediating role of estimated glomerular filtration rate (eGFR) was investigated.
During a median follow-up of 94.9 months, 2,549 deaths were recorded, including 727 attributable to cardiovascular diseases. Elevated lnPIV levels were strongly associated with increased all-cause and cardiovascular mortality. Critical thresholds were identified at lnPIV values of 5.056 for all-cause mortality and 5.586 for cardiovascular mortality. These core associations were stable across all subgroup and sensitivity analyses. Furthermore, mediation analysis estimated that eGFR accounted for 5.1% and 6.4% of the lnPIV-associated risk for all-cause and cardiovascular mortality, respectively.
Pan-immune-inflammation value was found to be independently associated with increased risks of all-cause and cardiovascular mortality in individuals with diabetes, characterized by a nonlinear association and a distinct threshold effect. These findings suggest that PIV could serve as a practical biomarker for risk stratification, potentially identifying patients who may benefit from more intensive management of both inflammation and renal function.
Chen Fu, Jiaer Gao, Yijie Mao et al.· Archives of Medical Science· 0 citations
BACKGROUND
Cardiovascular-kidney-metabolic (CKM) syndrome is a systemic disorder manifested as the interconnected dysregulation of cardiovascular disease, chronic kidney disease, and metabolic abnormalities. Systemic inflammation was identified as an important contributor to CKM syndrome. Based on data from the National Health and Nutrition Examination Survey (NHANES), this research sought to explore associations between the inflammation burden index (IBI) and the risk of CKM syndrome (specifically stages 3-4).
METHODS
This research used data from six NHANES cycles (1999-2010). CKM stages were constructed based on the American Heart Association recommendations, with stages 3-4 classified as advanced CKM syndrome. Weighted multivariable logistic regression was used to investigate associations between IBI and CKM stages 3-4. Restricted cubic splines were employed to evaluate potential nonlinear relationships. Subgroup analyses stratified by age, sex, and body mass index were performed. Moreover, sensitivity analyses were conducted.
RESULTS
In total, 13,830 participants were included. Among them, 3322 were in CKM stages 3-4. In the fully adjusted model, IBI was positively associated with the risk of CKM stages 3-4 [odds ratio (OR) = 1.026, 95% confidence interval (CI): 1.008-1.044, P = 0.005]. In the sensitivity model excluding patients with hypertension and diabetes (Model 4), the association remained significant (OR = 1.030, 95% CI: 1.014-1.047, P < 0.001). RCS analyses further indicated a significant nonlinear dose-response relationship between IBI and the risk of CKM stages 3-4 (P for nonlinearity <0.001). This association remained reliable in subgroup and sensitivity analyses.
CONCLUSIONS
Elevated IBI is independently associated with a higher risk of CKM syndrome. As a composite inflammatory index that integrates multiple inflammatory cells and acute-phase proteins, IBI holds promise for identifying individuals at high risk for advanced CKM syndrome.
Yixuan Wu, Mei Li, Zhen Fang et al.· Metabolic Syndrome and Relat...· 0 citations
It is suggested that higher CMI may indicate a greater risk of cognitive decline in older adults, and diabetes status significantly modified the CMI–GCF relationship.
Ying Liu, Qian Hu, Qin Li et al.· Medicine· 0 citations
