Xinli Li

Background: Despite advancements in guideline-directed medical therapy (GDMT) for heart failure with reduced ejection fraction (HFrEF), including sodium-glucose cotransporter 2 inhibitors (SGLT2i), the real-world clinical effectiveness of adding the traditional Chinese medicine Qiliqiangxin (QLQX) to contemporary SGLT2i-containing GDMT regimens remains uncertain. This study aims to evaluate the association between QLQX combined with SGLT2i therapy and cardiovascular death or heart failure hospitalization (HHF) in adults with HFrEF.Methods: This nationwide, multi-centre observational cohort study used the Chinese Cardiovascular Association Database–Heart Failure Center from 481 hospitals across 31 provinces and autonomous regions in China. A total of 14,367 adults with HFrEF were categorized into three groups based on treatment received in addition to GDMT: combination group (QLQX plus SGLT2i); QLQX group; SGLT2i group. The primary outcome was a composite of cardiovascular death or heart failure hospitalization (HHF) within a 540-day follow-up. Propensity score matching (PSM) was performed at a 1:1:2 ratio, with inverse probability of treatment weighting (IPTW) used as a sensitivity analysis.Findings: After matching, the cohort included 3,540 patients (885 receiving combination therapy, 885 receiving QLQX, and 1,770 receiving SGLT2i). Compared with SGLT2i therapy without QLQX, combination therapy was associated with a significantly lower risk of the primary composite outcome (HR, 0.814; 95% CI, 0.680–0.974; P = 0.02). This benefit was primarily driven by a 21.7% reduction in HHF (HR, 0.783; 95% CI, 0.634–0.966; P = 0.02), while cardiovascular mortality did not differ significantly (HR, 0.909; P = 0.59). Outcomes for the QLQX group were comparable to those for the SGLT2i group (P = 0.52). These findings remained consistent in the original cohort and IPTW sensitivity analyses. Consistent benefits were validated across various clinical subgroups.Interpretation: In a real-world setting, the addition of QLQX to SGLT2i-containing GDMT was associated with a reduced risk of the composite endpoint of cardiovascular death and HHF in patients with HFrEF compared with SGLT2i-containing GDMT alone. These findings support the potential role of QLQX as an adjunct to standard therapy in HFrEF.

Background:Glycemic abnormalities are highly prevalent in chronic heart failure (CHF) and exacerbate adverse cardiac remodeling. Epicardial fat volume (EFV) and the triglyceride-glucose (TyG) index may both reflect metabolic-cardiovascular interactions, but their combined prognostic utility in CHF patients with dysglycemia remains unexplored.Methods:We analyzed 516 CHF patients stratified by glycemic status: normal glucose (n = 230), prediabetes (n = 174), and diabetes (n = 112). Baseline characteristics, echocardiography (TTE), and cardiac magnetic resonance (CMR) data were assessed. The primary endpoint was defined as a composite of heart-failure hospitalization or all-cause mortality and was evaluated during a follow-up period of up to 3 years. Associations between EFV, TyG index, and primary endpoint were evaluated using stratified, joint, and incremental prognostic models.Results:Diabetic CHF patients were generally older, had higher smoking rates, worse renal function, and poorer nutritional status. CMR and TTE revealed more severe cardiac structural and functional impairments in dysglycemic groups, including reduced left ventricular ejection fraction (LVEF) and elevated EFV. EFV predicted primary endpoint with increasing accuracy across glycemic strata (AUC: 0.631–0.711 at 1–3 years), with the strongest predictive performance in diabetes. A significant correlation between TyG index and EFV was observed in diabetic patients (r = 0.24, p = 0.00021). Joint EFV (cutoff: 74.68 mL/m²) and TyG (median: 8.48) analysis showed that high TyG alone or combined high EFV/TyG conferred the highest the risk of primary endpoint (p for trend < 0.001), while isolated EFV elevation did not. Incorporating EFV into TyG-based models significantly improved prediction (AUC increased from 0.698 to 0.729 at 1 year). Net reclassification and integrated discrimination improvements confirmed the incremental prognostic value of EFV, particularly in diabetes and over longer follow-up.Conclusion:In CHF patients with glycemic dysregulation, EFV and TyG index synergistically enhance clinical endpoint prediction, with EFV providing significant incremental prognostic value beyond TyG. These metrics may improve risk stratification and personalized management in comorbid heart failure and dysglycemia.

Background: Heart failure with preserved ejection fraction (HFpEF) disproportionately affects elderly women, with potential contributions from sex‐specific hormonal and physiological factors. We aimed to evaluate sex‐specific prognostic differences, comorbidity impacts, and guideline‐directed medical therapy effects in elderly patients with HFpEF. Methods: Retrospective analysis of 603 patients (age ≥60 years, male: 51.6%, mean age: 79.10±9.19 years) newly diagnosed with HFpEF at Huadong Hospital, Fudan University (from July 2019 to June 2024) with follow‐up through December 2024. The primary outcome was all‐cause mortality. Results: The overall mortality rate was 14.2/100 person‐years (women: 15.4 versus men: 13.2). Based on the gender and etiology phenotype classification for HFpEF, patients with types I/IV HFpEF had better survival (10.0/12.4 per 100 person‐years) versus those with types II/III/V (17.1/22.9/24.2 per 100 person‐years). Sex‐specific mortality peaks differed, with men having type V in 30.3/100 person‐years and women having type III in 28.2/100 person‐years. In Cox regression analysis, after adjusting for age, sex, body mass index, and hypertension, type 2 diabetes and stages 4 or 5 chronic kidney disease predicted mortality in men only (chronic kidney disease 4 or 5: hazard ratio [HR], 3.24, type 2 diabetes: HR, 2.34; both adjusted P 0.1). After adjusting for age, body mass index, hypertension, type 2 diabetes, and renal dysfunction, angiotensin receptor neprilysin inhibitors reduced mortality in women (HR, 0.57; adjusted P =0.027), while sodium‐glucose cotransporter‐2 inhibitors reduced mortality in men (HR, 0.25; adjusted P =0.021). Conclusions: Mortality patterns, comorbidity impacts, and treatment responses in elderly patients with HFpEF exhibit significant sex disparities. This underscores the need for sex‐tailored management to optimize outcomes. These findings should be interpreted with caution given the retrospective design.

Background: The European Kidney Function Consortium (EKFC) has introduced equations for estimating glomerular filtration rate (eGFR) using serum creatinine (Cr) and cystatin C (Cys). While their diagnostic accuracy is established, their comparative prognostic value for long-term mortality in the general population is not well-defined. This study compared the prognostic performance of three EKFC equations—creatinine-based (EKFC-eGFRcr), cystatin C-based (EKFC-eGFRcys), and the combined (EKFC-eGFRcrcys) model—for predicting all-cause and cardiovascular (CV) mortality. Method: We analyzed a population-based cohort of 4519 participants from the National Health and Nutrition Examination Survey (NHANES) 1999–2002. eGFR was calculated using all three EKFC variations (EKFC-eGFRcr, EKFC-eGFRcys, and EKFC-eGFRcrcys). The primary and secondary endpoints were all-cause and CV mortality, respectively, through December 31, 2019. Predictive improvements were evaluated using integrated discrimination improvement (IDI), net reclassification improvement (NRI), and number needed to measure (NNM). Result: The eGFR value calculated by the EKFC-eGFRcys, EKFC-eGFRcr, and EKFC-eGFRcrcys was 78.92±22.98, 84.45±23.21, and 81.68±22.13 ml/min/1.73m2, respectively. Over a median follow-up of 211 months, all three eGFR models were independent predictors of mortality (all P <0.001). Restricted cubic spline regression revealed significant non-linear, inverse associations between all eGFR measures and adjusted mortality risks (all P for non-linearity < 0.001). Compared to EKFC-eGFRcr, EKFC-eGFRcys significantly improved risk reclassification for all-cause mortality (categorical NRI = 15.9%; 95% CI: 14.1–17.8%; NNM = 7). The combined EKFC-eGFRcrcys also outperformed the creatinine-only model (NRI = 8.9%; NNM = 12). However, EKFC-eGFRcys demonstrated modestly better performance than the combined equation (NRI = 7.0%; NNM = 15), suggesting limited incremental value in adding creatinine to cystatin C. The superiority of EKFC-eGFRcys was primarily driven by improved classification of non-events. Conclusion: The EKFC-eGFRcys equation provides superior prognostic value for all-cause and CV mortality compared to both creatinine-based and combined EKFC equations. Notably, the combined model offered no prognostic advantage over cystatin C alone. These findings highlight the clinical importance of cystatin C-based eGFR for accurate risk stratification in the general population.

Objectives: To examine the risk of severe cardiovascular (CV) events in patients with chronic obstructive pulmonary disease (COPD) across different time periods following COPD exacerbations and the incidence rate of cardiopulmonary events in a real-world setting in China. Design: Retrospective cohort study. Setting: Regional electronic health records database from Yinzhou District of Ningbo City, China. Participants: A total of 14 713 patients aged ≥40 years with a first COPD diagnosis between 1 January 2014 and 1 March 2022. Primary and secondary outcome measures: The risk of severe CV events (ie, hospitalisation and a primary or secondary discharge code for acute coronary syndrome, heart failure decompensation, cerebral ischaemia, arrhythmia and CV-related death) during different exposed time periods following a COPD exacerbation, the incidence rate of overall cardiopulmonary events (ie, severe exacerbation of COPD, all-cause mortality, inpatient CV events, inpatient ischaemic stroke and inpatient tachyarrhythmia/atrial fibrillation) and the incidence rate stratified by COPD exacerbation history. Results: We included a total of 14 713 patients. During a median (IQR) follow-up of 2.8 (4.0) years, 20.1% experienced severe CV events. Compared with the unexposed period, the risk of severe CV events was the highest in the first 10 days following a COPD exacerbation (adjusted HR 10.00, 95% CI 8.16 to 12.25). The risk of severe CV events decreased over time but remained significantly elevated up to 90 days post exacerbation. We found that 32.7% of COPD patients experienced cardiopulmonary events, with a crude incidence rate of 9.38 (95% CI 9.09 to 9.69) per 100 person-years. Conclusion: This study is the largest retrospective cohort study investigating CV and cardiopulmonary events among patients with COPD in China. Our findings highlight an elevated risk of CV events closer to the time of COPD exacerbations and show that nearly one-third of COPD patients experience cardiopulmonary events.

Background Cardiovascular disease (CVD) is a leading cause of death globally, especially in the aging population. As a novel biomarker integrating inflammation and metabolic dysregulation, the C-reactive protein-triglyceride glucose index (CTI) may offer superior risk stratification, but its prognostic value for mortality in the elderly remains unclear. Methods This multi-cohort retrospective study analyzed data from the NHANES (1999–2010), the CHARLS, and the regional Gaoyou datasets, focusing on participants aged ≥ 60 years. Associations between CTI quartiles and all-cause/cardiovascular mortality were assessed using Cox proportional hazards models, Kaplan–Meier curves, and restricted cubic splines. The predictive performance of CTI was compared with other metabolic indices (TyG, TyG-WC, etc.) using time-dependent ROC curves and net reclassification improvement (NRI). Results Among 11,619 elderly participants, higher CTI levels were significantly associated with increased risks of all-cause and cardiovascular mortality across all three cohorts after full adjustment. A J-shaped nonlinear relationship was identified with an inflection point at CTI = 8.31, and subgroup analyses confirmed consistency across most strata. CTI demonstrated superior predictive performance for mortality (AUCs: 0.8445 for all-cause mortality and 0.8208 for cardiovascular mortality) and significantly improved risk reclassification (NRI > 0, p < 0.05) compared with other indices. The effectiveness of the prediction models was respectively verified in different Chinese databases. Sensitivity analyses on dynamic changes indicated that elevated trajectory of CTI represented higher mortality. Conclusion Elevated CTI is a robust and independent predictor of all-cause and cardiovascular mortality in the elderly populations of both the USA and China. Its integration into clinical practice could enhance early risk stratification and guide targeted interventions to mitigate mortality risk in aging adults. Graphical Abstract

Background and purpose: Heart failure (HF) is a global chronic disease that significantly impacts patients’ quality of life and imposes substantial health burdens. Therapeutic strategies for HF with reduced ejection fraction (HFrEF) have advanced rapidly. However, conventional pharmacological treatments remain limited by clinical drawbacks. Traditional Chinese medicine, particularly Qiliqiangxin capsule (QLQX), has emerged as a promising complementary approach in China. To date, a comprehensive and updated systematic review and meta-analysis evaluating the efficacy and safety of QLQX for HFrEF is lacking. Therefore, we conducted this systematic review and meta-analysis to assess the effectiveness and safety of QLQX in treating patients with HFrEF. Methods: A systematic literature search was conducted in PubMed, the Cochrane Library, Web of Science, Wanfang Database, Chinese Biomedical Literature Database, China Science and Technology Journal Database, and China National Knowledge Infrastructure from inception to the latest available date. Two reviewers independently performed study selection, data extraction, and risk-of-bias assessment. Meta-analyses were performed using Review Manager Software 5.4 and Stata 16.0. Results: A total of 40 studies involving 7,367 patients were included. Compared with conventional Western medicine (CWM) alone, QLQX combined with CWM significantly improved New York Heart Association (NYHA) functional class (risk ratio [RR]: 1.22, 95% confidence interval [95% CI]: 1.16–1.29; P < 0.05) and 6-minute walking distance (mean differences [MD]: 58.40, 95% CI: 45.52–71.28; P < 0.05). Additionally, QLQX significantly reduced rehospitalization rates (RR: 0.78, 95% CI: 0.67–0.90; P < 0.05) and N-terminal Pro-B-type natriuretic peptide (NT-proBNP) levels (MD: −276.04, 95% CI: −348.49 to −203.59; P < 0.05). Moderate to high heterogeneity was observed in some outcomes. Subgroup and meta-regression analyses identified treatment duration and sex differences as potential sources of heterogeneity. Conclusions: QLQX combined with CWM appears to be an effective and safe adjunctive therapy for improving clinical outcomes in patients with HFrEF. Although these findings provide supportive evidence, further large-scale, high-quality randomized controlled trials are needed to confirm these results and inform clinical practice.

Background: Cardiovascular multimorbidity (CMM), defined as the coexistence of multiple cardiometabolic diseases, has posed an escalating global health burden associated with premature mortality. Systemic inflammation has been increasingly recognized as a central mechanism linking cardiometabolic diseases, yet the prognostic implications of routine inflammatory and nutritional biomarkers in patients with CMM remained unclear. Methods: This cohort study analyzed 1,928 CMM patients from the National Health and Nutrition Examination Survey (NHANES) and 364 patients from a Chinese cohort (Gaoyou). Ten inflammatory and nutritional parameters were evaluated. Associations with all-cause and cardiovascular mortality were assessed using multivariable Cox regression and restricted cubic splines. Feature selection (SHAP, Boruta, and Lasso) was employed to identify optimal predictors, followed by construction and validation of nomogram and machine learning (ML) models. Results: The systemic inflammation response index (SIRI) emerged as the strongest independent predictor of mortality. Patients in the highest SIRI quartile exhibited significantly increased risks of all-cause mortality (HR = 2.34, 95% CI: 1.88–2.90) and cardiovascular mortality (HR = 2.09, 95% CI: 1.47–2.98), with consistent performance across various subgroups. Nomograms incorporating SIRI demonstrated excellent discrimination (AUCs > 0.7) and clinical utility. Among the ML models, XGBoost achieved the highest predictive efficiency at 60, 120, and 150 months. Conclusion: SIRI, reflecting the combined influence of inflammatory responses and nutritional status, provided an available and independent biomarker for mortality risk stratification in CMM patients. The validated nomograms and web-based prediction tool offered clinicians a practical approach for individualized prognosis and informed future strategies targeting systemic inflammation and nutrition in multimorbidity management.