Cardiovascular Diabetology最新文献

{"title":"Associations of cumulative exposure and dynamic trajectories of the combined atherogenic and frailty index with incident cardiometabolic multimorbidity: a longitudinal analysis based on the China Health and Retirement Longitudinal Study (CHARLS).","authors":"Xianjing Feng, Bi Deng, Yinghuan Pan, Kai Liu, Wanting Lei, Xin Tang, Jian Xia","doi":"10.1186/s12933-026-03235-8","DOIUrl":"10.1186/s12933-026-03235-8","url":null,"abstract":"<p><strong>Background and objective: </strong>The atherogenic index of plasma (AIP) reflects atherogenic dyslipidemia and insulin resistance, whereas the frailty index (FI) quantifies cumulative physiological deficits across multiple organ systems. Although both the AIP and FI are independently associated with cardiometabolic multimorbidity (CMM), the joint impact of the atherogenic index of plasma-frailty index (AIPFI) on the risk of CMM remains unclear. In this study, the associations between baseline levels, cumulative AIPFI and longitudinal changes of AIPFI and the incidence of CMM were evaluated.</p><p><strong>Methods: </strong>Data were obtained from the China Health and Retirement Longitudinal Study (CHARLS). A total of 7995 participants were included in the baseline analysis, and 4,483 participants with repeated biomarker measurements in 2012 and 2015 were included in the longitudinal analysis. AIPFI was calculated via the following formula: AIPFI = AIP × FI. Multivariate Cox proportional hazards models and restricted cubic splines were applied to evaluate the associations of AIPFI with the incidence of CMM. K-means clustering characterized longitudinal AIPFI patterns. The clinical prediction model was performed in both the training and validation cohorts, as validated by receiver operating characteristic curve analysis, calibration curve analysis, and decision curve analysis. The shapley additive explanations (SHAP) method was employed to provide further explanation.</p><p><strong>Results: </strong>A total of 7995 participants were included and followed for a median of 9.0 years, during which 747 (9.3%) incident CMMs occurred. Across quartiles of the AIPFI, the risk of CMM increased progressively, with adjusted HR of 2.46 (95% CI 1.77-3.43) for Q4 compared with those for Q1. In longitudinal analyses (n = 4,483), participants in cluster 2, with persistently high and increasing AIPFI values, presented increased risks of CMM (HR 1.54, 95% CI 1.19-2.01). An elevated cumulative AIPFI was associated with an increased incidence of CMM (HR 1.01, 95% CI 1.01-1.01). The RCS revealed a significant positive nonlinear relationship between the baseline AIPFI and cumulative AIPFI with the risk of CMM (all P < 0.05, and all P for nonlinear values < 0.05). SHAP model analysis revealed hypertension, heart disease, and AIPFI as the most influential predictors.</p><p><strong>Conclusions: </strong>Both baseline and longitudinal changes in the AIPFI were independently associated with the risk of CMM. The incorporation of longitudinal monitoring of the AIPFI into routine health evaluations may enhance population-level CMM risk prediction and support more effective prevention strategies.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":" ","pages":""},"PeriodicalIF":15.6,"publicationDate":"2026-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13465527/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148194612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of 14 triglyceride-glucose (TyG)-related indices with new-onset cardiovascular disease in middle-aged and older adults: evidence from the CHARLS and ELSA aging cohorts.","authors":"Zhang-le Zhu, Hui-Fen Hu","doi":"10.1186/s12933-026-03224-x","DOIUrl":"10.1186/s12933-026-03224-x","url":null,"abstract":"<p><strong>Background: </strong>Cardiovascular disease (CVD) continues to be a predominant contributor to global illness and death rates.Insulin resistance and adiposity are closely linked to cardiometabolic risk, but the comparative value of single-time and cumulative average triglyceride-glucose (TyG)-based indices for predicting new-onset CVD remains uncertain. This study aimed to compare multiple TyG-based indicators, evaluate the contribution of cumulative exposure, and develop a clinically accessible risk-stratification tool.</p><p><strong>Methods: </strong>This longitudinal cohort study incorporated a total of 5,028 middle-aged and older adult participants, drawn from two major national aging surveys: the China Health and Retirement Longitudinal Study (CHARLS) and the English Longitudinal Study of Ageing (ELSA). Cumulative average TyG-based indicators were constructed using two pre-follow-up measurement waves, with follow-up beginning in 2015 for CHARLS and 2008 for ELSA. Seven single-time TyG-based indicators and seven cumulative average indices were evaluated. Cox regression analysis, restricted cubic splines(RCS), random-effects meta-analysis, subgroup analyses, mediation analyses, and predictive performance assessments were performed. A nomogram and web-based prediction tool were developed for 5-year CVD risk estimation.</p><p><strong>Results: </strong>During a median follow-up of 5.0 years in CHARLS and 13.5 years in ELSA, 1,067 incident CVD events occurred. In the pooled cohort, all 14 TyG-based indicators were significantly associated with incident CVD. Composite indices integrating TyG with obesity-related measures generally showed stronger associations and better predictive performance than the TyG index alone. Cumulative average indices provided only modest improvement over their single-time counterparts, with heterogeneity across cohorts. Restricted cubic spline analyses showed nonlinear associations for TyG-BMI and cumTyG-BMI, whereas other indices showed approximately linear associations. CumTyG-BRI showed relatively robust cross-cohort performance, with an HR of 1.54 (95%CI, 1.27-1.86) for Q4 versus Q1 and low between-cohort heterogeneity (I² = 6.6%). Mediation analysis suggested that hypertension partly mediated the association between CumTyG-BRI and CVD risk, accounting for 20.6% of the total effect. A TyG-BRI-based nomogram showed moderate discrimination, with a C-index of 0.679, and was deployed as an online tool for preliminary 5-year CVD risk estimation.</p><p><strong>Conclusions: </strong>CumTyG-BRI may be a relatively robust TyG-related indicator for predicting new-onset CVD across cohorts, with low heterogeneity and an approximately linear association. Hypertension may partly mediate this association. The online tool may support preliminary CVD risk stratification, but further validation is needed before routine clinical use.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":" ","pages":""},"PeriodicalIF":15.6,"publicationDate":"2026-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13459430/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148161839","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Systematic comparison of triglyceride-glucose (TYG)-index with other mortality predictive models in obese patients with different mortality rates.","authors":"Lucia La Sala, Silvia Magnani, Valentina Carlini, Marta Rigoni, Antonio E Pontiroli, Ivan Zanoni","doi":"10.1186/s12933-026-03217-w","DOIUrl":"10.1186/s12933-026-03217-w","url":null,"abstract":"<p><strong>Background: </strong>The Triglyceride-Glucose (TYG)-Index has been increasingly used as a simple surrogate marker of insulin resistance and has been associated with adverse cardiometabolic outcomes in several populations. TYG has gained great attention as a predictive index for mortality, but comparisons with other predictive indexes are unexplored, except for TYG-derived indexes such as TYG-body mass index (TYG-BMI).</p><p><strong>Methods: </strong>We conducted a comparative prognostic study in two independent cohorts of adults with obesity: a general obesity cohort (n = 1,359) and a bariatric surgery cohort (n = 854), both with long-term follow-up approaching 14 years and with different mortality rates (11.5 vs. 5.5%, respectively). We compared TYG index, TYG-BMI index, blood glucose, age, Charlson Index, metabolic syndrome, glucose tolerance, diabetes mellitus, through Cox proportional hazard models with Harrell'C index, and through ROC analysis. We also evaluated the possible incremental predictive value of the above prognostic indexes when combined with blood glucose, the TYG-index, and TYG-BMI index.</p><p><strong>Results: </strong>Across both cohorts, several metabolic and clinical indices were significantly associated with all-cause mortality in univariable analyses. However, age and Charlson Comorbidity Index consistently showed the strongest discrimination and prognostic performance. The various indexes significantly predicted mortality at Cox proportional hazard models (p always < 0.001). Harrell'C index correlated with ROC area under the curves of each index (p < 0.001), and both Harrell and ROC correlated with quality indexes of Cox analysis (LR, p < 0.001) and with quality indexes of linear regression (F, p < 0.001). Findings were directionally consistent in the bariatric surgery cohort, although lower event rates attenuated overall discrimination. The combined use of more indices together was not uniformly useful to increase the predictive value of the above indices.</p><p><strong>Conclusion: </strong>In obesity, TyG-based indices are associated with long-term mortality risk but add limited prognostic value beyond age and multimorbidity burden. These markers may be considered complementary tools for metabolic characterization rather than primary instruments for mortality risk stratification. This study reinforces the concept that various mortality indexes are as valid as, or even more predictive than, TYG index.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":" ","pages":""},"PeriodicalIF":15.6,"publicationDate":"2026-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13455396/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148155358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of adiposity, insulin resistance, and inflammation on cardiometabolic multimorbidity: insights from interaction analyses and metabolic phenotyping in the China health and retirement longitudinal study 2011-2018.","authors":"Lili You, Wenbo Zhao, Meiguang Zheng, Xiaosi Hong, Meng Ren, Wenpeng Li","doi":"10.1186/s12933-026-03234-9","DOIUrl":"10.1186/s12933-026-03234-9","url":null,"abstract":"<p><strong>Background: </strong>Cardiometabolic multimorbidity (CMM) burdens aging populations. Obesity drives CMM via insulin resistance and inflammation, but their nonlinear and combined effects remain unclear. We elucidated how these factors contribute to CMM incidence.</p><p><strong>Methods: </strong>From CHARLS 2011 to 2018, 6,510 participants were enrolled. CMM was defined as ≥ 2 of diabetes, heart disease, and stroke. Cox regression, Kaplan-Meier, and Fine-Gray models were used. Restricted cubic splines (RCS) evaluated nonlinear relationships. Multiplicative and additive interactions were assessed, and mediation analysis with 1,000 bootstraps estimated indirect effects. K-means clustering based on eight standardized variables, including age, body mass index (BMI), waist circumference (WC), triglyceride-glucose (TyG), high-sensitivity C-reactive protein (hs-CRP), systolic blood pressure (SBP), high-density lipoprotein cholesterol (HDL-C), and fasting plasma glucose (FPG), identified metabolic phenotypes carried high CMM risk.</p><p><strong>Results: </strong>Over 7 years, 212 (3.26%) developed CMM. RCS revealed a J-shaped association between WC and CMM. Optimal cut-offs were 60 years for age, 25.6 kg/m² for BMI, 90.6 cm for WC, 8.7 for the TyG index, 154.3 mg/dL for LDL-C, and 0.86 mg/L for hs-CRP. All six parameters independently predicted CMM. No significant additive interactions were found, but dual elevation markedly increased risk. The TyG index mediated 14.6% of the BMI effect and 10.0% of the WC effect on CMM. Clustering identified insulin-resistant and obese-insulin-resistant phenotypes.</p><p><strong>Conclusion: </strong>Optimal cut-offs offer practical screening tools. Dual elevation markedly increases CMM risk and insulin resistance mediates adiposity effects. Clustering identified insulin-resistant and obese-insulin-resistant phenotypes, supporting phenotype-based prevention.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":" ","pages":""},"PeriodicalIF":15.6,"publicationDate":"2026-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13459958/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148155203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adolescent obesity and risk of serious chronic morbidity and mortality in young adulthood: a systematic review of cohorts from national registries.","authors":"Naomi Fliss Isakov, Yulia Balmakov, Laura Sol Grinshpan, Eyal Tsur, Nitzan Issler, Moran Blaychfeld Magnazi, Zivan Aviad Beer, Orit Pinhas-Hamiel, Gilad Twig, Avi Shina","doi":"10.1186/s12933-026-03221-0","DOIUrl":"10.1186/s12933-026-03221-0","url":null,"abstract":"<p><strong>Background: </strong>The rising prevalence of adolescent obesity necessitates a precise understanding of its corresponding risks for severe chronic morbidity and premature mortality during young adulthood and midlife.</p><p><strong>Methods: </strong>We conducted a systematic review of nationwide longitudinal cohort studies, using validated national registries, aimed at assessing the short- and long-term risk of morbidity and mortality associated with adolescent overweight and obesity.</p><p><strong>Results: </strong>We included 38 studies in this systematic review. Adolescent overweight and obesity were associated with severe morbidity and disease related mortality, from young adulthood. Within < 4 years of follow-up and before the age of 25 years, severe adolescent obesity was associated with increased risk of serious morbidity (hazard ratio (HR) = 5.1 among men and HR = 7.3 among women), type 2 diabetes (HR = 27.0 among men, and HR = 45.3 among women), and obesity was associated with type 1 diabetes (HR = 2.0). Before the age of 30 years, adolescent severe obesity was associated with chronic kidney disease (CKD), obesity was associated with colorectal cancer (CRC) and with cardiovascular disease (CVD) mortality. Before the age of 40 years adolescent overweight and obesity were associated with ischemic stroke. Last, before the age of 50 years, adolescent severe obesity was associated with all-cause mortality, obesity was associated with diabetes mortality, and cancer.</p><p><strong>Conclusions: </strong>Adolescent obesity is strongly associated with an elevated hazard for severe disease morbidity and mortality beginning in young adulthood, with associations progressing with obesity severity and time. The findings of this study demonstrate the need for public health mitigation and preventive strategies, which may yield substantial short, and long-term health benefits in this population.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":" ","pages":""},"PeriodicalIF":15.6,"publicationDate":"2026-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13419026/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148154965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between C-reactive protein-triglyceride glucose related indices and all-cause and cardiovascular mortality in individuals with cardiovascular-kidney-metabolic syndrome.","authors":"Wenguang Lai, Yang Zhou, Louyi Xiao, Tingting Zhang, Wenbiao He, Junhao He, Wenjun Gu, Yucui Lin","doi":"10.1186/s12933-026-03228-7","DOIUrl":"10.1186/s12933-026-03228-7","url":null,"abstract":"<p><strong>Background: </strong>The C-reactive protein-triglyceride glucose index (CTI) has been proposed as a biomarker for insulin resistance and inflammation, which contribute to the development of cardiovascular-kidney-metabolic (CKM) syndrome. Waist- circumference-based anthropometric indices have been extensively studied as measures of abdominal obesity, which is strongly associated with mortality risk. This study evaluates the association with mortality of CTI and its combination with several waist circumference based anthropometric indices across stages of CKM.</p><p><strong>Methods: </strong>A total of 10,941 participants were included from NHANES database. CTI and its derivatives (CTI-waist-to-height ratio [CTI-WHtR], CTI-weight-adjusted waist index [CTI-WWI], and CTI-a body shape index [CTI-ABSI]) were calculated. Study outcomes were all-cause and cardiovascular mortality. Cox regression model and restricted cubic spline (RCS) were used to assess the association between the CTI-related indices and outcomes. Receiver operating characteristic (ROC) analyses were performed to show their predictive ability for outcomes. Subgroup analyses were conducted to verify the robustness.</p><p><strong>Results: </strong>During a median follow-up of 12.83 years, 20.3% of patients (n = 2223) died, including 6.3% (n = 693) from cardiovascular causes. After adjustment, higher CTI-related indices were associated with higher risk of all-cause mortality (CTI: HR = 1.21, 95%CI 1.14-1.28; CTI-WHtR: HR = 1.14, 95%CI 1.08-1.21; CTI-WWI: HR = 1.25, 95%CI 1.18-1.33; CTI-ABSI: HR = 1.29, 95%CI 1.22-1.37) and cardiovascular mortality (CTI: sHR = 1.31, 95%CI 1.18-1.45; CTI-WHtR: sHR = 1.29, 95%CI 1.16-1.42; CTI-WWI: sHR = 1.39, 95%CI 1.25-1.55; CTI-ABSI: sHR = 1.40, 95%CI 1.26-1.55). RCS analysis showed that CTI was nonlinearly associated with both all-cause and cardiovascular mortality, whereas CTI-WWI and CTI-ABSI showed linear associations with both outcomes; CTI-WHtR was nonlinearly associated with all-cause mortality but linearly with cardiovascular mortality. ROC analyses revealed that CTI-ABSI had the highest predictive efficacy for all-cause mortality (AUC = 0.711) and cardiovascular mortality (AUC = 0.690). Notably, subgroup analyses revealed that the association between CTI-related indices and mortality was more pronounced in early CKM stages (stages 0-2) than in advanced stages (stages 3-4).</p><p><strong>Conclusion: </strong>Higher CTI-related indices were significantly associated with a higher risk of all-cause and cardiovascular mortality in individuals with CKM syndrome. Among these indices, CTI-ABSI exhibits superior predictive performance, suggesting its potential as practical prognostic biomarkers for CKM patients.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":" ","pages":""},"PeriodicalIF":15.6,"publicationDate":"2026-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13460024/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148155054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Composite C-reactive protein-triglyceride-glucose-adiposity indices and incident cardiovascular disease in the CHARLS cohort: a prospective cohort study.","authors":"Peng Wang, Zhaobin Zheng, Shuang Wang, Jun Qi","doi":"10.1186/s12933-026-03229-6","DOIUrl":"10.1186/s12933-026-03229-6","url":null,"abstract":"<p><strong>Background & aims: </strong>Cardiovascular disease (CVD) is influenced by metabolic dysfunction, chronic inflammation, and adiposity. The C-reactive protein-triglyceride-glucose index (CTI) integrates inflammatory and metabolic information, but the associations of CTI-derived adiposity indices with incident CVD remain insufficiently characterized. We aimed to examine the associations of several CTI-derived adiposity indices with incident CVD and compare their relative performance in a nationwide cohort of middle-aged and older adults.</p><p><strong>Methods: </strong>We analyzed data from 6,161 participants aged ≥ 45 years without baseline CVD from the China Health and Retirement Longitudinal Study (CHARLS). Four CTI-derived adiposity indices were evaluated: CTI-WHtR, CTI-BMI, CTI-BRI, and CTI-WWI. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for incident CVD. Dose-response relationships were assessed using restricted cubic splines (RCS). Kaplan-Meier, discrimination and reclassification, cumulative exposure, trajectory, subgroup, component-outcome, mediation, and sensitivity analyses were also performed.</p><p><strong>Results: </strong>During a median follow-up of 9 years, 1,503 participants (24.39%) developed CVD. Higher levels of CTI-derived adiposity indices were associated with increased CVD risk. In fully adjusted models, participants in the highest quartile had higher CVD risk than those in the lowest quartile for CTI-WHtR (HR = 1.57, 95% CI 1.24-2.00), CTI-BMI (HR = 1.55, 95% CI 1.23-1.97), CTI-BRI (HR = 1.40, 95% CI 1.11-1.78), and CTI-WWI (HR = 1.37, 95% CI 1.08-1.74), with significant trends across quartiles. RCS analyses showed predominantly linear dose-response relationships. Discrimination was modest, with AUCs ranging from 0.558 for CTI-WWI to 0.573 for CTI-WHtR, compared with 0.522 for CTI. All CTI-derived indices improved continuous net reclassification improvement and integrated discrimination improvement beyond the conventional risk factor model. Higher cumulative exposure and higher trajectory clusters of CTI-derived indices were also associated with increased CVD risk. Mediation analyses suggested interrelationships between metabolic-inflammatory dysregulation and adiposity in relation to CVD.</p><p><strong>Conclusions: </strong>CTI-derived adiposity indices were associated with incident CVD in middle-aged and older adults, with CTI-WHtR showing the most consistent overall performance among the evaluated indices. These findings support the epidemiological relevance of integrating metabolic-inflammatory burden with adiposity-related phenotypes in cardiovascular risk assessment.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":" ","pages":""},"PeriodicalIF":15.6,"publicationDate":"2026-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13449330/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148148726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardiac remodeling after bariatric surgery associates with systemic metabolic reprogramming: a longitudinal untargeted metabolomics study.","authors":"Carmine Izzo, Martina Lombardi, Maria Rosaria Rusciano, Alessio Trotta, Cristina Gatto, Valeria Visco, Albino Carrizzo, Mario Masarone, Marcello Persico, Vincenzo Pilone, Luigi Schiavo, Carmine Vecchione, Jacopo Troisi, Michele Ciccarelli","doi":"10.1186/s12933-026-03231-y","DOIUrl":"10.1186/s12933-026-03231-y","url":null,"abstract":"<p><strong>Background: </strong>Obesity is a major contributor to adverse cardiac remodeling, particularly concentric left ventricular remodeling (LVCR), which is associated with diastolic dysfunction and increased cardiovascular risk. Bariatric surgery reverses many obesity-related comorbidities, including structural myocardial alterations. However, the molecular underpinnings of cardiac recovery, particularly metabolomic correlates, remain poorly understood.</p><p><strong>Objective: </strong>This study aimed to characterize longitudinal changes in the serum metabolome of patients undergoing bariatric surgery and to investigate the relationship between these metabolic shifts and the regression of concentric cardiac remodeling.</p><p><strong>Methods: </strong>A cohort of 127 adults with severe obesity was evaluated at baseline and 4, 12, and 24 weeks post-surgery. Echocardiographic parameters were assessed to define cardiac remodeling. Untargeted GC-MS-based metabolomic profiling was performed on serum samples. Multivariate models (PLS-DA), LASSO regression, and pathway enrichment analyses were employed to identify discriminant metabolites and predictors of remodeling outcomes.</p><p><strong>Results: </strong>Changes in cardiac geometry primarily occurred within the first 12 weeks after the intervention and were mainly driven by reductions in relative wall thickness (RWT). Left ventricular mass index (LVMI) showed only modest, non-significant changes at the cohort level, consistent with the predominantly non-hypertrophic baseline profile. Metabolomic profiling showed time-dependent shifts involving amino acid, fatty acid, and ketone metabolism. Patients who experienced early favorable cardiac remodeling after bariatric surgery demonstrated enriched signatures of mitochondrial substrate flexibility, including short-chain fatty acids, branched-chain amino acid metabolites, and dicarboxylic acids. LASSO regression identified specific sets of metabolites associated with reductions in LVMI and RWT.</p><p><strong>Conclusion: </strong>Early geometric cardiac adaptation following bariatric surgery-primarily reflected by reductions in relative wall thickness (RWT), with modest and non-significant changes in LVMI at the cohort level-is associated with coordinated changes in systemic metabolic profiles. These findings suggest potential metabolic correlates of early cardiac adaptation while highlighting substantial interindividual variability. Metabolomic profiling provides insights into individual metabolic trajectories and may inform future strategies for cardiometabolic risk stratification.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":" ","pages":""},"PeriodicalIF":15.6,"publicationDate":"2026-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13491655/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148148685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unraveling 'F' factor: towards a genetic-clinical framework for the musculoskeletal-heart crosstalk in metabolic aging.","authors":"Yunqiao Zhou, Jian Huang, Xinyi Chen, Leqin Xu, Fan Zhang, Chunxiao Bai, Jiju Yang, Fangyang Fan, Yuquan Wang, Bixuan Fang, Tian Wang, Junhao Li, Xiaohong Mu, Jinyu Li","doi":"10.1186/s12933-026-03220-1","DOIUrl":"10.1186/s12933-026-03220-1","url":null,"abstract":"<p><strong>Background: </strong>The rising co-occurrence of cardiometabolic diseases and musculoskeletal degeneration poses a critical challenge to healthy aging, yet the shared biological mechanisms underlying this multimorbidity remain poorly defined. This study aimed to establish an integrative clinical-genetic framework to elucidate the common frailty factor, the 'F' factor, that captures the systemic vulnerability linking cardiometabolic multimorbidity (CMM) and musculoskeletal aging.</p><p><strong>Methods: </strong>Utilizing the prospective China Health and Retirement Longitudinal Study (CHARLS) cohort, we developed and validated novel Frailty-Integrated Indices for CMM risk prediction, evaluated with machine learning models interpreted via SHapley Additive exPlanations (SHAP). Independently, we applied genomic structural equation modeling (Genomic-SEM) to integrate genome-wide association data from six traits-coronary artery disease, type 2 diabetes, hypertension, bone mineral density, frailty, and telomere length-to model a shared latent genetic factor ('F' factor). This was followed by multivariate GWAS, fine-mapping, transcriptome-wide association study (TWAS), gene-based analysis, and functional annotation to prioritize causal genes, pathways, and cell types.</p><p><strong>Results: </strong>Clinically, several Frailty-Integrated Indices significantly improved CMM risk prediction, with the optimal model achieving an AUC of 0.727. Genetically, we modeled a significant shared latent genetic factor ('F' factor), pinpointing novel risk loci and implicating key genes such as APOE and SLC22A3. These genes were enriched in pathways including cellular senescence and cholesterol metabolism and showed specific expression patterns in developmental brain stages and across multi-organ endothelial cells.</p><p><strong>Conclusion: </strong>Our findings provide converging evidence for Musculoskeletal‑Heart crosstalk of metabolic aging and inferred the 'F' factor as a genetic correlate of a transdiagnostic state, which links genetic predisposition to metabolic dysregulation, and systemic functional decline. This work provides a multi-level biological characterization of multimorbidity liability, informing early-risk detection and preventive strategies for complex aging-related comorbidities.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":" ","pages":""},"PeriodicalIF":15.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13440131/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148142750","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Estimated glucose disposal rate outperforms thirteen other insulin resistance indices in predicting new-onset cardiometabolic multimorbidity: a longitudinal study from the china health and retirement longitudinal study (CHARLS) and cross-sectional replication from the national health and nutrition examination survey (NHANES).","authors":"Enfa Zhao, Hang Xie, Ruimeng Wang, Bingtian Dong, Chaoxue Zhang","doi":"10.1186/s12933-026-03218-9","DOIUrl":"10.1186/s12933-026-03218-9","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;The co-occurrence of multiple cardiometabolic conditions has been mechanistically linked to impaired insulin signaling, yet the relative utility of surrogate insulin resistance (IR) markers in stratifying cardiometabolic multimorbidity (CMM) risk has not been systematically established. This study aimed to systematically evaluate and compare the associations of 14 IR indices with CMM incidence in a longitudinal Chinese cohort, with external replication in a U.S. nationally representative sample.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;This study included 8,522 participants from the China Health and Retirement Longitudinal Study (CHARLS) without CMM at baseline (2011). CMM was defined as the concurrent presence of at least two of the following three cardiometabolic conditions: type 2 diabetes, heart disease, and stroke. All 14 IR indices were evaluated both at baseline and as cumulative time-weighted averages derived from repeated measurements in 2011 and 2015. Associations between IR indices and CMM risk were examined using multivariable logistic regression, with dose-response relationships characterized through restricted cubic spline (RCS) modeling. Discriminatory capacity was quantified via receiver operating characteristic (ROC) curve analysis, complemented by net reclassification improvement (NRI) and integrated discrimination improvement (IDI) metrics. To verify the robustness of primary findings, Cox proportional hazards regression and pre-defined subgroup analyses were performed as supplementary sensitivity analyses. External cross-sectional replication was performed in the National Health and Nutrition Examination Survey (NHANES; 1999-2018).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;During follow-up through 2020, 591 CHARLS participants (6.9%) developed incident CMM. After comprehensive covariate adjustment, each of the 14 surrogate IR indices demonstrated statistically significant and independent associations with incident CMM risk. eGDR and SPISE demonstrated significant inverse associations, indicating that higher values reflect greater insulin sensitivity and lower CMM risk (cumulative eGDR per SD: OR 0.51, 95% CI 0.41-0.65; cumulative SPISE per SD: OR 0.64, 95% CI 0.54-0.75), whereas the remaining 12 indices showed significant positive associations. RCS analyses revealed predominantly linear dose-response relationships across most indices, except for TyHGB and TyG-AIP, which exhibited significant non-linearity. eGDR achieved the highest discriminatory performance at both baseline (AUC: 0.716) and cumulative (AUC: 0.727) assessments, significantly outperforming TyG (all P &lt; 0.001), and yielded the greatest NRI and IDI improvements among all 14 indices. These findings were consistently replicated in the NHANES cross-sectional validation: eGDR and SPISE again demonstrated the strongest inverse associations (eGDR per SD: OR 0.598, 95% CI 0.499-0.717; SPISE per SD: OR 0.704, 95% CI 0.614-0.807), and eGDR achieved the highes","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":" ","pages":""},"PeriodicalIF":15.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13390194/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148142768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}