Background: SII and SIRI are two novel systemic inflammation indexes that were suggested in predicting poor outcomes in cancers. However, no studies have examined their effect on cardiovascular diseases (CVDs) and all-cause mortality. Thus, this study aims to investigate associations between SII, SIRI, and the risks for CVDs and all-cause mortality. Methods: A total of 85,154 participants from the Kailuan cohort were included and followed up for incidents of CVDs (including MI, stroke) and all-cause death for 10 years. Multiple Cox regression was used to calculate the adjusted hazard ratios (HRs). Results: During the follow-up period, 4262 stroke events, 1233 MI events, and 7225 allcause deaths were identified, respectively. Compared with the lowest quantile (Q1) of SII or SIRI, after adjusted for most cardiovascular risk factors, both indexes showed positive associations with the risk for stroke (adjusted HRs in Q4 were 1.264 (95% CI: 1.157,1.382) for SII, 1.194 (95% CI: 1.087,1.313) for SIRI), and all-cause death (adjusted HRs in Q4 were 1.246 (95% CI: 1.165,1.331) for SII, 1.393 (95% CI: 1.296,1.498) for SIRI). Additionally, higher SII and SIRI are also associated with increased risk of hemorrhagic stroke and ischemic stroke. Higher SIRI but not SII exhibited a higher MI risk, the adjusted HR in Q4 was 1.204 (1.013,1.431). The significant association remained after additional adjustment for CRP. Subgroup analysis and sensitivity analysis displayed consistent results except for SIRI with MI, where the association did not arrive at significance in subjects aged ≥60. Conclusion: Elevated SII and SIRI increased the risk of stroke, two stroke subtypes, and all-cause death. Higher SIRI, but not SII associated with increased MI incidence, and the association of SIRI was only significant in subjects aged <60.

Background: Preserved ratio impaired spirometry (PRISm), characterized by the decreased forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) with a preserved FEV1/FVC ratio, is highly prevalent and heterogeneous. We aimed to identify the subtypes of PRISm and examine their differences in clinical characteristics, long-term mortality risks, and longitudinal transition trajectories.Methods: A total of 6,616 eligible subjects were included from the English longitudinal study of aging. Two subtypes of the PRISm were identified as mild PRISm (either of FEV1 and FVC &lt;80% predicted value, FEV1/FVC ≥0.7) and severe PRISm (both FEV1 and FVC &lt;80% predicted values, FEV1/FVC ≥0.7). Normal spirometry was defined as both FEV1 and FVC ≥80% predicted values and FEV1/FVC ≥0.7. Hazard ratios (HRs) and 95% CIs were calculated by the multiple Cox regression models. Longitudinal transition trajectories were described with repeated spirometry data.Results: At baseline, severe PRISm had increased respiratory symptoms, including higher percentages of phlegm, wheezing, dyspnea, chronic bronchitis, and emphysema than mild PRISm. After an average of 7.7 years of follow-up, severe PRISm significantly increased the risks of all-cause mortality (HR=1.91, 95%CI = 1.58–2.31), respiratory mortality (HR = 6.02, 95%CI = 2.83–12.84), and CVD mortality (HR = 2.11, 95%CI = 1.42–3.13) compared with the normal spirometry, but no significantly increased risks were found for mild PRISm. In the two longitudinal transitions, mild PRISm tended to transition toward normal spirometry (40.2 and 54.7%), but severe PRISm tended to maintain the status (42.4 and 30.4%) or transition toward Global Initiative for Chronic Obstructive Lung Disease (GOLD)2–4 (28.3 and 33.9%).Conclusion: Two subtypes of PRISm were identified. Severe PRISm had increased respiratory symptoms, higher mortality risks, and a higher probability of progressing to GOLD2–4 than mild PRISm. These findings provided new evidence for the stratified management of PRISm.

Background Previous studies indicated that obesity would accelerate frailty progression. However, obesity is heterogeneous by different metabolic status. The associations of metabolic heterogeneity of obesity with frailty progression remain unclear. Methods A total of 6730 participants from the China Health and Retirement Longitudinal Study (CHARLS) and 4713 from the English Longitudinal Study of Ageing (ELSA) were included at baseline. Metabolic heterogeneity of obesity was evaluated based on four obesity and metabolic phenotypes as metabolically healthy normal weight (MHNW), metabolically unhealthy normal weight (MUNW), metabolically healthy overweight/obesity (MHOO), and metabolically unhealthy overweight/obesity (MUOO). Frailty status was assessed by the frailty index (FI) ranging from 0 to 100 and frailty was defined as FI ≥ 25. Linear mixed-effect models were used to analyse the associations of metabolic heterogeneity of obesity with frailty progression. Results In the CHARLS, MUOO and MUNW presented the accelerated FI progression with additional annual increases of 0.284 (95% CI: 0.155 to 0.413, P < 0.001) and 0.169 (95% CI: 0.035 to 0.303, P = 0.013) as compared with MHNW. MHOO presented no accelerated FI progression (β: -0.011, 95% CI: À0.196 to 0.173, P = 0.904) as compared with MHNW. In the ELSA, the accelerated FI progression was marginally significant for MUOO (β: 0.103, 95% CI: À0.005 to 0.210, P = 0.061) and MUNW (β: 0.157, 95% CI: À0.011 to 0.324, P = 0.066), but not for MHOO (β: -0.047, 95% CI: À0.157 to 0.062, P = 0.396) in comparison with MHNW. The associations of MUOO and MUNW with the accelerated FI progression were stronger after excluding the baseline frail participants in both cohorts. The metabolic status changed over time. When compared with stable MHNW, participants who changed from MHNW to MUNW presented the accelerated FI progression with additional annual increases of 0.356 (95% CI: 0.113 to 0.599, P = 0.004) and 0.255 (95% CI: 0.033 to 0.477, P = 0.024) in the CHARLS and ELSA, respectively. The accelerated FI progression was also found in MHOO participants who transitioned to MUOO (CHARLS, β: 0.358, 95% CI: 0.053 to 0.663, P = 0.022; ELSA, β: 0.210, 95% CI: 0.049 to 0.370, P = 0.011). Conclusions Metabolically unhealthy overweight/obesity and normal weight, but not metabolically healthy overweight/obesity, accelerated frailty progression as compared with metabolically healthy normal weight. Regardless of obesity status, transitions from healthy metabolic status to unhealthy metabolic status accelerated frailty progression as compared with stable metabolically healthy normal weight. Our findings highlight the important role of metabolic status in frailty progression and recommend the stratified management of obesity based on metabolic status.