Cardiovascular Diabetology最新文献

{"title":"Correction: BDH1 overexpression alleviates diabetic cardiomyopathy through inhibiting H3K9bhb-mediated transcriptional activation of LCN2.","authors":"Bu-Tuo Xu, Sheng-Rong Wan, Qi Wu, Yi-Hang Xing, Yan-Qiu He, Wei Huang, Yang Long, Chunxiang Zhang, Yong Xu, Zong-Zhe Jiang","doi":"10.1186/s12933-026-03214-z","DOIUrl":"https://doi.org/10.1186/s12933-026-03214-z","url":null,"abstract":"","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"25 1","pages":""},"PeriodicalIF":10.6,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147856086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-cell insights into maladaptive endothelial plasticity and therapeutic targets in diabetic vascular complications.","authors":"Noura S Alnuaimi, Lena Lößlein, Mira Mousa, Thanumol Abdul Khader, Ayesha Alkhaaldi, Sarah K Azzam, Amaryllis H Van Craenenbroeck, Syed Salman Ashraf, Peter Carmeliet, Habiba Alsafar","doi":"10.1186/s12933-026-03187-z","DOIUrl":"https://doi.org/10.1186/s12933-026-03187-z","url":null,"abstract":"<p><p>Endothelial plasticity, the capacity of endothelial cells (ECs) to reversibly alter their phenotype in response to environmental cues, typically enables adaptive vascular remodeling and tissue homeostasis. In diabetes, this plasticity becomes maladaptive, driving pathological transitions across interconnected axes: dysregulated angiogenesis with barrier destabilization, inflammatory reprogramming through immune-endothelial crosstalk, metabolic dysfunction spanning mitochondrial stress to senescence, and endothelial-to-mesenchymal transition with fibrosis. In this review, we synthesize mechanistic insights across endothelial state transitions and highlight how single-cell approaches have reframed diabetic vascular disease as a disorder of maladaptive endothelial plasticity. By integrating single-cell insights from diabetic mouse models and human patient samples, we demonstrate that restoring adaptive endothelial plasticity requires coordinated multi-dimensional intervention targeting the intersecting pathways that perpetuate pathological transitions, timed to disease stage and calibrated to vascular bed-specific context. For example, combining metabolic therapies such as GLP-1 receptor agonists or SGLT2 inhibitors with anti-inflammatory agents targeting IL-17A or IL-1β, pairing anti-VEGF treatments with inhibitors of MFAP4 or ANGPTL4 to overcome angiogenic bypass pathways, or coupling senolytics, such as UBX1325, with anti-fibrotic strategies like TGF-β or SETD7 inhibition to prevent irreversible EndoMT. We identify candidate therapeutic targets across angiogenic, inflammatory, metabolic, and fibrotic domains, and highlight critical knowledge gaps, most notably the limited characterization of human diabetic ECs, that must be addressed to translate these insights into effective clinical strategies for preventing diabetic vascular complications.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":" ","pages":""},"PeriodicalIF":10.6,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147833953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associations of nine insulin resistance-related indices with the incidence and progression of cardiovascular-liver-metabolic multimorbidity: a large prospective cohort study.","authors":"Chaonan Sun, Hao Li, Ke Zhou, Qida He, Yueping Shen, Shaowei Ma, Bin Li","doi":"10.1186/s12933-026-03201-4","DOIUrl":"https://doi.org/10.1186/s12933-026-03201-4","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Cardiovascular-liver-metabolic (CLM) diseases are interrelated, yet prior studies have mostly examined single-disease outcomes. We aimed to investigate the associations of insulin resistance (IR)-related indices with the incidence and progression of CLM multimorbidity (CLMM), while secondarily evaluating comparative predictive performance and exploring potential biological domains.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;This prospective study included 371,207 UK Biobank participants from England, Scotland, and Wales who were recruited between 2006 and 2010 and were free of CLM diseases at baseline. CLMM was defined as the coexistence of ≥ 2 CLM conditions. Outcomes were ascertained through linkage to national inpatient hospital records and death registries. Nine IR-related indices were computed, including the triglyceride-glucose (TyG) index and its derivatives (e.g., TyG-WC and TyG-WHtR). Associations with CLMM incidence and progression were assessed using Cox proportional hazards and multistate models. Secondary predictive analyses assessed incremental value and discrimination, and exploratory mediation analyses examined whether inflammatory, hepatic, and renal biomarkers were statistically related to the associations between IR-related indices and CLMM risk.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;During a median follow-up of 16.4 years, 8651 participants developed CLMM. All nine IR-related indices were positively associated with both CLMM incidence and progression (all P &lt; 0.001), with TyG-WHtR and TyG-WC demonstrating comparatively stronger associations. For incident CLMM, each SD increase in TyG-WHtR and TyG-WC was associated with hazard ratios (HRs) of 2.08 (95% CI 2.04-2.12) and 2.14 (95% CI 2.10-2.19), respectively. In multistate analyses, each SD increase in TyG-WHtR and TyG-WC was associated with 59% (HR 1.59, 95% CI 1.58-1.60) and 62% (HR   1.62, 95% CI 1.61-1.63) higher risks of transitioning from a healthy state to a first CLM disease, 44% (HR  1.44, 95% CI 1.41-1.46) and 44% (HR 1.44, 95% CI 1.41-1.47) higher risks of progressing to CLMM, and 24% (HR 1.24, 95% CI 1.15-1.34) and 22% (HR 1.22, 95% CI 1.13-1.31) higher risks of progression to triple CLM diseases, respectively. Secondary predictive analyses indicated that all indices significantly improved incremental value and discrimination, with TyG-WHtR and TyG-WC exhibiting comparatively better performance (all P &lt; 0.001). Biomarkers reflecting systemic inflammation and liver- and kidney-related function might statistically contribute to the observed associations, although these findings are exploratory and primarily hypothesis-generating.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Nine IR-related indices were positively associated with the incidence and progression of CLMM, with TyG-WHtR and TyG-WC showing comparatively stronger associations and better predictive performance. These findings support their relevance for comparative CLMM risk assessment, while further valid","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":" ","pages":""},"PeriodicalIF":10.6,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147833990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CVOT Summit Report 2025: advances along the cardiovascular-kidney-metabolic disease continuum.","authors":"Oliver Schnell, Arnav Agarwal, Michel Azizi, Dennis Ballwieser, Katharine Barnard-Kelly, Tadej Battelino, Dennis Ballwieser, Matthias Blüher, Elisabetta Bugianesi, Ana Cebrian, Antonio Ceriello, Pratik Choudhary, Thomas Danne, Colin M Dayan, Stefano Del Prato, Robert H Eckel, Paola Fioretto, Timothy Garvey, Jennifer B Green, Hiddo J L Heerspink, Rury R Holman, Baruch Itzhak, Stephan Jacob, Pardeep S Jhund, Linong Ji, Parminder K Judge, Kamlesh Khunti, Marko Korenjak, Andrew J Krentz, Ekaterini Lambrinou, Peter Libby, Julia K Mader, Johannes F E Mann, Nikolaus Marx, Chantal Mathieu, John J V McMurray, Dirk Müller-Wieland, Nikolaos Papanas, Dipesh C Patel, Andreas F H Pfeiffer, Susanne Reger-Tan, Helena W Rodbard, Giuseppe M C Rosano, Banshi Saboo, Naoki Sato, Scott D Solomon, Eberhard Standl, Frank Tacke, Pinar Topsever, Christoph Wanner, Sean Wharton, Veronika Young","doi":"10.1186/s12933-026-03140-0","DOIUrl":"10.1186/s12933-026-03140-0","url":null,"abstract":"<p><p>The 11th Cardiovascular Outcome Trial (CVOT) Summit: Congress on Cardiovascular, Kidney, and Metabolic Outcomes was held virtually on November 20-21, 2025. The Summit provided a multidisciplinary forum to review and discuss recent outcome trials investigating emerging pharmacological therapies targeting diseases of the cardiovascular-kidney-metabolic (CKM) continuum. This report highlights the unique developments of 2025 discussed during the Summit, including the first head-to-head CVOT (SURPASS-CVOT), the growing evidence base for combination therapies across the disease spectrum, new insights into the inflammatory component of the CKM syndrome, and relevant policy developments. The first part of this report summarizes pioneering clinical trials addressing combination therapy with finerenone and empagliflozin (CONFIDENCE), the oral glucagon-like peptide-1 (GLP-1) receptor agonists orforglipron (ATTAIN-1), and the aldosterone synthase inhibitor (ASI) baxdrostat (BaxHTN). The second part presents recent guideline and policy developments discussed by experts in endocrinology, diabetology, cardiology, nephrology, hepatology, and general practice. In addition, advances in medical technology, particularly in continuous glucose and ketone monitoring, are highlighted, as well as emerging therapies for diseases of the CKM continuum. These include pharmacological agents for a broad spectrum of metabolic disorders such as metabolic liver disease and type 1 Diabetes (T1D) alongside emphasis on the importance of early detection and innovative treatment strategies. The 12th Cardiovascular Outcome Trial Summit will be held virtually on 19-20 November 2026 ( http://www.cvot.org ).</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"25 1","pages":""},"PeriodicalIF":10.6,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13147710/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147833979","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":"Phenotypic clustering of newly diagnosed type 2 diabetes in a Mediterranean cohort.","authors":"Berta Fernandez-Camins, Bogdan Vlacho, Marina Idalia Rojo-López, Minerva Granado-Casas, Mònica Gratacòs, Marta Ortega-Bravo, Maria Cendros-Massioui, Flavio Palmieri, Alexandre Perera-LLuna, Josep Franch-Nadal, Dídac Mauricio","doi":"10.1186/s12933-026-03198-w","DOIUrl":"https://doi.org/10.1186/s12933-026-03198-w","url":null,"abstract":"<p><strong>Background: </strong>Current diagnostic criteria for type 2 diabetes (T2D) capture disease heterogeneity poorly, and do not reliably predict progression, complications, or treatment response. The phenotypic clustering model proposed by Ahlqvist et al. identified five T2D subtypes using six clinical variables at diagnosis, each associated with distinct metabolic profiles and complication risks. Although this framework has been replicated in several cohorts, evidence in Mediterranean populations is lacking.</p><p><strong>Methods: </strong>We conducted a prospective cohort study in Catalonia (Northeast Spain) including adults with newly diagnosed T2D recruited between March 2022 and January 2026. Using baseline data, we evaluated the Ahlqvist clustering approach. Autoantibody-positive individuals were classified as severe autoimmune diabetes (SAID), and sex-stratified k-means clustering (k = 4) was applied to autoantibody-negative participants. Cluster separation and stability were assessed using principal component analysis and silhouette analyses.</p><p><strong>Results: </strong>A final total number of 991 individuals with newly diagnosed T2D were included in the analysis. Autoantibodies were present in 67 subjects (6.8%), thereby being classified as SAID. Among the remaining 924 participants, sex-stratified k-means clustering (k = 4) identified clusters with metabolic profiles consistent with the classical subtypes: mild age-related diabetes (MARD, n = 326), severe insulin-resistant diabetes (SIRD, n = 241), mild obesity-related diabetes (MOD, n = 206), and severe insulin-deficient diabetes (SIDD, n = 151). However, cluster separation was modest, and bootstrap stability was limited (Jaccard 0.555-0.718). In an unconstrained analysis, apart from the autoimmune diabetes group, silhouette optimisation identified three clusters as the most internally optimal structure, corresponding broadly to obesity/insulin-resistant (C1, n = 347), insulin-deficient (C2, n = 186), and age-related (C3, n = 391) phenotypes. Stability was substantially higher for the three-cluster solution (Jaccard 0.799-0.863). Concordance between the Ahlqvist and data-driven models was moderate (ARI = 0.473), with MOD individuals distributed across the other clusters.</p><p><strong>Conclusions: </strong>The Ahlqvist clustering architecture could be approximated in this Mediterranean cohort at diagnosis, but internal stability of the five-cluster solution was limited. In this population, a four-cluster structure showed substantially better internal validity. These findings support the feasibility of phenotypic subclassification of T2D while underscoring the importance of evaluating population-specific cluster structures and their clinical relevance in longitudinal studies.</p><p><strong>Trial registration: </strong>NCT05333718.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":" ","pages":""},"PeriodicalIF":10.6,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147833987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of bempedoic acid in the management of dyslipidaemia in people with diabetes: an expert opinion of Italian diabetologists.","authors":"Massimo Federici, Raffaella Buzzetti, Riccardo Candido, Salvatore De Cosmo, Angela Pirillo, Giuseppina Russo, Giorgio Sesti, Angelo Avogaro","doi":"10.1186/s12933-026-03185-1","DOIUrl":"https://doi.org/10.1186/s12933-026-03185-1","url":null,"abstract":"<p><p>Diabetes mellitus is a rapidly growing global health challenge and a major driver of atherosclerotic cardiovascular disease (ASCVD). Dyslipidaemia, highly prevalent in both type 1 and type 2 diabetes, plays a central role in this excess cardiovascular risk and often persists despite statin therapy. Although statins remain the cornerstone of lipid management, many patients with diabetes do not achieve recommended low-density lipoprotein cholesterol (LDL-C) goals. Therefore, there is a need for effective, safe, and practical adjunctive therapies. Bempedoic acid is a first-in-class oral ATP-citrate lyase inhibitor with liver-specific activation, resulting in significant LDL-C reduction without relevant muscle-related adverse effects. Across clinical trials, including the CLEAR programme, bempedoic acid has demonstrated consistent LDL-C lowering, as well as reductions in apolipoprotein B and non-HDL-C, and favourable effects on the inflammatory marker high-sensitivity C-reactive protein (hs-CRP), with similar efficacy in patients with and without diabetes. Importantly, the CLEAR Outcomes trial showed a significant reduction in major adverse cardiovascular events in statin-intolerant patients, almost half of whom had diabetes, without adverse effects on glycaemic control. This article summarises the evidence supporting the use of bempedoic acid in people with diabetes, proposes its therapeutic positioning within contemporary lipid-lowering algorithms, and highlights its role as an effective oral option, aiming to provide practical and nationally relevant guidance for lipid management in people with diabetes. By helping to reduce residual cardiovascular risk and bridge treatment gaps in patients who may not be eligible for or have access to PCSK9 inhibitors, bempedoic acid represents a valuable addition to personalised lipid management strategies aimed at lowering cardiovascular morbidity and mortality in this high-risk population.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":" ","pages":""},"PeriodicalIF":10.6,"publicationDate":"2026-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147811454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The association between triglyceride glucose-frailty index and cardiometabolic multimorbidity among Chinese middle-aged and older adults: a national prospective cohort study.","authors":"Xinjiang Hou, Guaijuan Wang, Yan Gao","doi":"10.1186/s12933-026-03191-3","DOIUrl":"https://doi.org/10.1186/s12933-026-03191-3","url":null,"abstract":"<p><strong>Background: </strong>Cardiometabolic multimorbidity (CMM) poses a growing global health burden, yet few studies have combined the Triglyceride-Glucose (TyG) index, which reflects metabolic dysfunction, with the Frailty Index (FI), which captures physiological reserve and aging-related vulnerability, to assess CMM risk. Given their complementary biological information, this study examines whether a composite TyG-FI index is associated with incident CMM and whether it improves risk stratification beyond established factors.</p><p><strong>Methods: </strong>This prospective cohort study analyzed data from Chinese adults aged ≥ 45 years in the 2011-2020 waves of the China Health and Retirement Longitudinal Study (CHARLS). To assess the association between the TyG-FI index and incident CMM, we used Kaplan-Meier survival curves and multivariable Cox proportional-hazards models adjusted for potential confounders; restricted cubic spline analyses were employed to explore non-linear relationships. Predictive performance was evaluated using eight machine-learning algorithms: CatBoost, Extra Trees, Random Forest (RANGER), XGBoost, Recursive Partitioning (RPART), k-Nearest Neighbors (KKNN), Neural Network (NNET), and Support Vector Machine (SVM). Subgroup and sensitivity analyses were conducted to test the robustness of the results across population subgroups and modeling choices.</p><p><strong>Results: </strong>The analytic cohort comprised 2961 adults. Kaplan-Meier curves showed a graded, significant increase in cumulative CMM incidence across TyG‑FI quartiles (log‑rank P < 0.001). In multivariable Cox models, each unit increase in TyG‑FI was associated with a 1.80-fold higher CMM risk (HR = 1.80, 95% CI 1.57-2.05; P < 0.001); participants in the highest quartile had markedly elevated risk versus the lowest (Q4 vs. Q1 HR = 7.86, 95% CI 4.16-14.86). Restricted cubic spline analyses revealed significant non-linear relationships (P for non-linearity < 0.001), showing a J-shaped association between TyG-FI and CMM with threshold effects at TyG-FI ≈ 0.7 and cumulative TyG-FI ≈ 2.7. Subgroup analyses indicated stronger associations in participants < 60 years and in normotensive individuals. TyG-FI demonstrated better predictive performance for CMM than TyG index or FI alone, with improved C-statistic, Integrated Discrimination Improvement (IDI), and Net Reclassification Improvement (NRI). Among machine-learning models, RANGER performed best (AUC ≈ 0.81), and SHAP analysis identified cumulative and baseline TyG-FI as the primary predictors. Findings were robust in sensitivity analyses.</p><p><strong>Conclusions: </strong>TyG-FI exhibits non‑linear, threshold-defined associations with incident CMM and age‑dependent effect modification. Machine‑learning models incorporating TyG-FI show strong predictive performance. TyG-FI assessment may facilitate cost‑effective risk stratification for CMM and guide targeted prevention.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":" ","pages":""},"PeriodicalIF":10.6,"publicationDate":"2026-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147811415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Sirtuins and regulatory miRNAs as epigenetic determinants of empagliflozin-mediated recovery after acute myocardial infarction.","authors":"Anna Nowak-Szwed, Ceren Eyileten, Zofia Wicik, Sara Ahmadova, Jeff Palatini, Jolanta Siller-Matula, Dirk von Lewinski, Harald Sourij, Marek Postula","doi":"10.1186/s12933-026-03161-9","DOIUrl":"10.1186/s12933-026-03161-9","url":null,"abstract":"","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"25 1","pages":""},"PeriodicalIF":10.6,"publicationDate":"2026-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13137614/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147811430","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":"Joint association of atherogenic index of plasma and estimated glucose disposal rate with new-onset cardiovascular disease risk in individuals with cardiovascular-kidney-metabolic syndrome stages 0-3: a 9-year nationwide prospective cohort study.","authors":"Yuhang Fan, Zhibo Si, Miaomiao Wei, Yumeng Gu, Xin Li","doi":"10.1186/s12933-026-03200-5","DOIUrl":"https://doi.org/10.1186/s12933-026-03200-5","url":null,"abstract":"<p><strong>Background: </strong>The atherogenic index of plasma (AIP) and estimated glucose disposal rate (eGDR) are two composite indices derived from routine metabolic measurements and are associated with cardiocerebrovascular disease risk. In individuals with Cardiovascular-Kidney-Metabolic (CKM) syndrome stages 0-3, however, it remains unclear whether joint stratification by these markers helps summarize gradients of cardiovascular disease, heart disease, and stroke risk beyond single-marker assessment.</p><p><strong>Methods: </strong>Using data from the China Health and Retirement Longitudinal Study (CHARLS), 5,925 participants without CVD at the start and in CKM stages 0-3 were analyzed. Participants were grouped by median AIP and/or eGDR values. Kaplan-Meier curves and Cox models assessed the link between these indicators and new CVD, heart disease, and stroke cases. Furthermore, both multiplicative and additive interactions between AIP and eGDR were assessed. The predictive value was assessed using the time-dependent Harrell's C index, integrated discrimination improvement (IDI), and net reclassification improvement (NRI).</p><p><strong>Results: </strong>A cohort of 5,925 participants aged 45 years and older (mean age: 57.92 ± 8.52 years) was analyzed, with 54.65% of the cohort being female. During the nine-year follow-up period, 1,467 (24.76%) participants developed incident CVD, including 1,106 (18.67%) with heart disease and 525 (8.86%) with stroke. The high AIP and low eGDR group had the highest risk, with CVD hazard ratios (HRs) of 1.35 (95% CI 1.14-1.59), heart disease HRs of 1.32 (95% CI 1.08-1.62), and stroke HRs of 1.59 (95% CI 1.19-2.12), using the low AIP and high eGDR group as the reference. Neither multiplicative nor additive interaction was statistically significant. The combined application of AIP and eGDR provided a modest improvement in predictive capability for cardiovascular disease, heart disease, and stroke.</p><p><strong>Conclusion: </strong>In individuals with CKM stages 0-3, combined AIP and eGDR stratification captured gradients of cardiovascular risk. The combined application of these indicators may provide modest incremental value for risk stratification within CKM stages, thereby aiding in the identification of high-risk individuals during the early stages of CKM.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":" ","pages":""},"PeriodicalIF":10.6,"publicationDate":"2026-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147811439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardiovascular-kidney-metabolic syndrome: a comprehensive review of pathophysiology, epidemiology, diagnosis, and management.","authors":"Stanislovas S Jankauskas, Klara Komici, Fahimeh Varzideh, Luigi Simone Aversa, Urna Kansakar, Maria Luisa D'Onghia, Shivangi Pande, Pasquale Mone, Gaetano Santulli","doi":"10.1186/s12933-026-03177-1","DOIUrl":"https://doi.org/10.1186/s12933-026-03177-1","url":null,"abstract":"<p><p>Cardiovascular-kidney-metabolic (CKM) syndrome is a multisystem condition integrating metabolic dysfunction, chronic kidney disease (CKD), and cardiovascular disease into a unified framework. CKM syndrome encompasses progressive metabolic derangements, renal injury, and cardiovascular remodeling, which interact to amplify morbidity and mortality. Lifestyle interventions (including structured weight loss, dietary modification, physical activity, and sleep optimization) form a cornerstone of prevention and management. Pharmacologic strategies targeting the renin-angiotensin-aldosterone system, sodium-glucose cotransporter 2 inhibitors, glucagon-like peptide-1 receptor agonists, and lipid-lowering therapies provide additional multisystem benefits. In this comprehensive review, we systematically examine the most updated evidence on CKM syndrome, in terms of pathophysiology, epidemiology, clinical manifestations, diagnostic evaluation, and therapeutic strategies. We also highlight future research directions and precision medicine approaches.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":" ","pages":""},"PeriodicalIF":10.6,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}