Cardiovascular Diabetology最新文献

{"title":"Predictive value of the combined triglyceride-glucose and frailty index for cardiovascular disease and stroke in two prospective cohorts.","authors":"Yi-Chang Zhao, Shi-Qi Wu, Jia-Kai Li, Zhi-Hua Sun, Bi-Kui Zhang, Rao Fu, Miao Yan","doi":"10.1186/s12933-025-02880-9","DOIUrl":"10.1186/s12933-025-02880-9","url":null,"abstract":"<p><strong>Background: </strong>The triglyceride-glucose (TyG) index is a validated surrogate for insulin resistance, while frailty reflects cumulative physiological decline. The combined impact of TyG-Frailty Index (TyGFI) has not been adequately explored. This study aimed to investigate the association between TyGFI and the risk of cardiovascular disease (CVD) and stroke.</p><p><strong>Methods: </strong>A total of 5448 participants from the China Health and Retirement Longitudinal Study (CHARLS) and 1139 participants from the U.S. National Health and Nutrition Examination Survey (NHANES) were included. Multivariable logistic regression models were used to estimate associations with CVD and stroke, adjusting for demographic, clinical, and lifestyle covariates. Restricted cubic spline (RCS) and subgroup analyses were employed to examine dose-response relationships and interaction effects.</p><p><strong>Results: </strong>Higher TyGFI levels were associated with older age, adverse metabolic parameters, and increased prevalence of hypertension, diabetes, and dyslipidemia. In fully adjusted models, the highest TyGFI quartile was significantly associated with increased risks of CVD (CHARLS: OR 15.09, 95% CI 9.65-23.60; NHANES: OR 4.98, 95% CI 2.04-12.19) and stroke (CHARLS: OR 21.12, 95% CI 6.44-69.23; NHANES: OR 12.98, 95% CI 2.58-65.17), with consistent dose-response trends confirmed by RCS analyses. Subgroup analyses further demonstrated the robustness of these associations across diverse demographic and clinical strata.</p><p><strong>Conclusions: </strong>TyGFI is a strong and independent predictor of CVD and stroke in two nationally representative cohorts. By integrating metabolic and functional risk dimensions, TyGFI provides a more comprehensive risk stratification tool, with significant implications for early identification and prevention of cardiovascular events in aging populations.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"24 1","pages":"318"},"PeriodicalIF":10.6,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12323107/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144783570","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":"Erythrocytosis incidence and thromboembolic risk in heart failure with reduced ejection fraction treated with SGLT2 inhibitors: a nationwide register-based cohort study.","authors":"Abdullahi Ahmed Mohamed, Camilla Fuchs Andersen, Daniel Mølager Christensen, Lise Da Riis-Vestergaard, Milan Mohammad, Mariam Elmegaard, Casper Binding, Christian Torp-Pedersen, Tor Biering-Sørensen, Morten Lock Hansen, Lars Køber, Andreas Glenthøj, Jesper Jensen, Charlotte Andersson, Morten Schou, Gunnar Gislason","doi":"10.1186/s12933-025-02871-w","DOIUrl":"10.1186/s12933-025-02871-w","url":null,"abstract":"<p><strong>Background: </strong>Sodium-glucose cotransporter-2 inhibitors (SGLT2i) increase haemoglobin and haematocrit levels, potentially causing secondary erythrocytosis-defined as a haemoglobin level above 16.5 g/dL in men and 16.0 g/dL in women-which is associated with an elevated thromboembolic risk. This study investigated the incidence of erythrocytosis and its association with thromboembolic events in patients with heart failure with reduced ejection fraction (HFrEF) treated with SGLT2i.</p><p><strong>Methods: </strong>In this nationwide cohort study, we included 3138 patients with new-onset HFrEF who initiated SGLT2i treatment after diagnosis, and 3138 propensity score-matched untreated controls. Haemoglobin was measured at baseline and six-month follow-up. Erythrocytosis incidence at follow-up was assessed using Poisson regression. Cox models were used to evaluate the association between erythrocytosis and one-year risk of fatal and non-fatal thromboembolic events (myocardial infarction, stroke, pulmonary embolism, or deep venous thrombosis), stratified by SGLT2i treatment.</p><p><strong>Results: </strong>Erythrocytosis developed in 207 patients (3.3%). Incidence was higher among SGLT2i-treated patients (109.5 vs. 26.8 per 1000 person-years), with an adjusted incidence rate ratio of 4.10 (95% CI 2.95-5.83). No significant association was observed between erythrocytosis and one-year thromboembolic risk in the total population (HR: 0.85 95% CI 0.44-1.65), even when stratified by SGLT2i-treated (HR: 0.81 95% CI 0.38-1.74) and untreated patients (HR: 0.75, 95% CI 0.19-3.05) (interaction P = 0.77).</p><p><strong>Conclusion: </strong>Although erythrocytosis incidence was higher in SGLT2i-treated HFrEF patients, it was not associated with an increased one-year thromboembolic risk.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"24 1","pages":"314"},"PeriodicalIF":10.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12317550/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144764625","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":"Metabolomic profiling reveals interindividual metabolic variability and its association with cardiovascular-kidney-metabolic syndrome risk.","authors":"Meng Zhou, Wenxiu Sun, Yuhan Gao, Bei Jiang, Tianwei Sun, Rui Xu, Xiujuan Zhang, Qian Wang, Qiuhui Xuan, Shizhan Ma","doi":"10.1186/s12933-025-02881-8","DOIUrl":"10.1186/s12933-025-02881-8","url":null,"abstract":"<p><strong>Background and objective: </strong>Cardiovascular-Kidney-Metabolic (CKM) syndrome reflects the interrelated pathophysiology of obesity, insulin resistance, type 2 diabetes, chronic kidney disease, and cardiovascular disease. Conventional CKM staging often detects risk only after substantial organ dysfunction and may overlook early metabolic heterogeneity. This study aimed to employ plasma metabolomics to identify metabolic subtypes linked to CKM severity and explore early biomarkers for high-risk individuals.</p><p><strong>Methods: </strong>A cross-sectional study was conducted involving 163 adults, which included 86 individuals clinically staged as CKM 0-3 according to the criteria proposed by the American Heart Association (AHA). Plasma samples underwent untargeted metabolomic and lipidomic profiling using liquid chromatography-mass spectrometry (LC-MS). Unsupervised clustering identified metabolic subtypes, with validation via random forest analysis. Group differences were assessed using orthogonal partial least squares-discriminant analysis (OPLS-DA) and logistic regression classifiers.</p><p><strong>Results: </strong>A total of 390 metabolites, categorized into 9 superclasses and 30 subclasses, were identified. Three distinct metabolic clusters emerged: Cluster 1 (glycerophospholipid-enriched), Cluster 2 (fatty acyl-dominant), and Cluster 3 (glycolipid-enriched). At the individual differential metabolite level, Cluster 1 exhibited a generally low metabolic status, Cluster 2 demonstrated an intermediate metabolic profile, and Cluster 3 showed a high metabolic status. High-risk CKM individuals were predominantly assigned to Cluster 3 (p < 0.001). Within each cluster, OPLS-DA effectively differentiated high- and low-risk individuals based on lipid profiles, highlighting triglycerides, fatty acids, phosphatidylcholines, sphingolipids, and acylcarnitines as key discriminators. Secondary clustering among stage 3 of CKM patients revealed substantial metabolic heterogeneity. A panel of 20 metabolites achieved high diagnostic performance for stage 3 of CKM individual (AUC = 0.875).</p><p><strong>Conclusions: </strong>Untargeted plasma metabolomic profiling reveals distinct metabolic subtypes corresponding to CKM severity and uncovers marked heterogeneity within the high-risk group. Key metabolite signatures may enhance early risk stratification and support more personalized management strategies beyond conventional CKM staging.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"24 1","pages":"315"},"PeriodicalIF":10.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12317516/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144764626","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 the C-reactive protein-triglyceride glucose index and new-onset coronary heart disease among metabolically heterogeneous individuals.","authors":"Yafang Chen, Wenjun Jia, Jianmin Guo, Han Yang, Xi Sheng, Liping Wei, Jiao Li","doi":"10.1186/s12933-025-02876-5","DOIUrl":"10.1186/s12933-025-02876-5","url":null,"abstract":"<p><strong>Background: </strong>The C-reactive protein-triglyceride glucose index (CTI) integrates inflammatory and metabolic markers and is closely associated with the incidence of coronary heart disease (CHD) and hypertension. However, its clinical utility among metabolically heterogeneous populations remains unclear. This study aims to investigate the association between CTI and new-onset CHD and to assess the potential value of combining CTI with the C-reactive protein-albumin-lymphocyte (CALLY) index in improving the identification of such clinical diagnoses.</p><p><strong>Methods: </strong>This study included 2237 participants, categorized into four obesity and metabolic phenotypes: metabolically healthy normal weight, metabolically healthy overweight/obese, metabolically unhealthy normal weight (MUNW), and metabolically unhealthy overweight/obese. The association between the CTI and new-onset CHD was analyzed using logistic regression, accounting for potential confounders. Subgroup analyses stratified by glucose metabolic states, age, and gender were performed, and multiple statistical methods were further employed to investigate the mediating role of the CALLY index and the incremental value of CTI in combination with the CALLY index for enhancing the identification of new-onset CHD.</p><p><strong>Results: </strong>The analysis demonstrated a robust association between the CTI and new-onset CHD (P < 0.001), with the highest sensitivity observed in MUNW individuals. The CALLY index was identified as a partial mediator of this relationship, emphasizing the critical role of immune-inflammatory processes in CHD. Notably, individuals with a high CTI (≥ 9.887) and a low CALLY index (< 1.221) showed the strongest association with CHD diagnoses at admission (OR = 2.36, 95% CI: 2.06-2.69). The integration of the CTI and CALLY indices was significantly associated with a stronger discriminatory ability for new-onset CHD.</p><p><strong>Conclusion: </strong>The CTI demonstrated a significant statistical association with new-onset CHD diagnoses among metabolically heterogeneous individuals. Its combination with the CALLY index further enhanced diagnostic discrimination, supporting its potential utility in individualized identification and refined clinical assessment.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"24 1","pages":"316"},"PeriodicalIF":10.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12317589/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144764622","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 C-reactive protein-triglyceride glucose index with the incidence and mortality of cardiovascular disease: a retrospective cohort study.","authors":"Yu Sun, Yu Guo, Shiyin Ma, Zhi Mao, Deguo Meng, Kaige Xuan, Ruogu Lu, Xudong Pan, Xiaoyan Zhu","doi":"10.1186/s12933-025-02835-0","DOIUrl":"10.1186/s12933-025-02835-0","url":null,"abstract":"<p><strong>Background: </strong>The C-reactive protein-triglyceride-glucose index (CTI) has emerged as an innovative composite marker for evaluating metabolic-inflammatory dysregulation, integrating markers of insulin resistance and systemic inflammation. However, the association between CTI and cardiovascular disease (CVD) or its mortality has rarely been studied. This study sought to examine CTI's associations with CVD mortality, CVD incidence, and all-cause mortality.</p><p><strong>Methods: </strong>This study included 8,679 adults from the National Health and Nutrition Examination Survey (NHANES) 2001-2010, 2015-2018. The CTI was derived as: 0.412* Ln (CRP [mg/L]) + Ln (TG [mg/dl] × FPG [mg/dl])/2, with participants categorized into quartiles. We employed Kaplan-Meier curves, cox proportional hazards model, logistic regression analyses, and restricted cubic spline (RCS) to evaluate CTI's associations with CVD mortality, total CVD incidence, and all-cause mortality across sex-stratified, age-specific, and glycemic subgroups.</p><p><strong>Results: </strong>In this study, CTI was significantly and positively associated with CVD mortality, total CVD incidence, and all-cause mortality. CTI significantly predicted both CVD mortality (HR 2.28 [1.69-3.24]) and all-cause mortality (HR 2.14 [1.76-2.55]). Additionally, the CTI index correlated with the risk of total CVD (OR 2.85, 95% CI 2.32-3.52), congestive heart failure (OR 3.66, 95% CI 2.46-5.35), coronary heart disease (OR 2.82, 95% CI 1.95-3.97), angina pectoris (OR 2.85, 95% CI 1.89-4.22), heart attack (OR 2.59, 95% CI 1.89-3.52), and stroke (OR 2.86, 95% CI 2.00-3.85). Specifically, the association was similar between male and female, and similar in young participants and elderly participants. In different glycemic status, high levels of CTI were found to be linked to an increased risk of CVD in individuals without diabetes mellitus (DM). However, this association was not observed in individuals with DM.</p><p><strong>Conclusions: </strong>Our analysis revealed that elevated CTI levels were significantly associated with CVD incidence and mortality. CTI may emerge as a unique predictive marker for CVD risk.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"24 1","pages":"313"},"PeriodicalIF":10.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12317521/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144764623","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":"Blood plasma proteome-wide association study implicates novel proteins in the pathogenesis of multiple cardiovascular diseases.","authors":"Jia-Hao Wang, Shan-Shan Dong, Wei Huang, Hao-An Wang, Shao-Shan Liu, Xiaoyi Ma, Ren-Jie Zhu, Wei Shi, Hao Wu, Ke Yu, Tian-Pei Zhang, Cong-Ru Wang, Yan Guo, Hanzhong Xue, Tie-Lin Yang","doi":"10.1186/s12933-025-02847-w","DOIUrl":"10.1186/s12933-025-02847-w","url":null,"abstract":"<p><strong>Background: </strong>Cardiovascular diseases (CVD) are the leading cause of global mortality, yet current treatments benefit only a subset of patients. To identify new potential treatment targets, we conducted the first proteome wide association study (PWAS) for 26 CVDs using plasma proteomics data from the largest cohort to date (53,022 individuals in the UK Biobank Pharma Proteomics Project (UKB-PPP)).</p><p><strong>Methods and results: </strong>We calculated single nucleotide polymorphism (SNP)-protein weights using the UKB-PPP dataset and integrated these weights with genome-wide association study (GWAS) summary statistics for 26 CVDs across three categories (16 cardiac, 5 venous, and 5 cerebrovascular diseases) in up to 1,308,460 individuals. PWAS was performed using the Functional Summary-based Imputation (FUSION) framework to identify protein-disease associations. Replication was conducted in two independent human plasma proteomic datasets (comprising 7213 and 3301 participants, respectively). We identified 155 proteins associated with CVDs and further Mendelian randomization analysis revealed 72 proteins with evidence of a causal association. Of these, 26 out of 35 available proteins were validated. Notably, 33 of the 72 proteins were not previously implicated in GWAS of CVDs. For example, PROC was found to be associated with venous thromboembolism (P = 6.32 × 10^-7). We further conducted longitudinal analyses using plasma proteomics data and peripheral blood mononuclear cells single cell RNA-seq data. The results showed that 90.63% (29/32) of the detected proteins exhibited stable plasma expression, and 18 genes displayed stable expression in at least one cell type, particularly in CD14+ monocytes. We also utilized these proteins to construct disease diagnostic models, and notably, models for 14 out of 18 diseases achieved an area under the curve (AUC) exceeding 0.8, indicating promising diagnostic potential.</p><p><strong>Conclusions: </strong>We identified 72 proteins that causally influence CVD risk, providing new mechanistic insights into CVD and may prove to be promising targets as CVD therapeutics.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"24 1","pages":"312"},"PeriodicalIF":10.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12317611/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144764624","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":"Efficacy and safety of dapagliflozin in patients hospitalized with COVID-19 with and without type 2 diabetes: a prespecified analysis of the DARE-19 randomized trial.","authors":"Mohammad Abdel Jawad, Remo H M Furtado, Russell Esterline, Jan Oscarsson, Samvel B Gasparyan, Gary G Koch, Felipe Martinez, Omar Mukhtar, Subodh Verma, Anna Maria Langkilde, Philip Ambery, Shachi Patel, Kensey Gosch, Sheryl L Windsor, Ronaldo V P Soares, Diogo D F Moia, Matthew Aboudara, Ali Javaheri, J F Kerr Saraiva, Lilia Nigro Maia, Otavio Berwanger, Andrew J Sauer, Mikhail N Kosiborod","doi":"10.1186/s12933-025-02875-6","DOIUrl":"10.1186/s12933-025-02875-6","url":null,"abstract":"<p><strong>Background: </strong>Although several previous studies tested SGLT2 inhibitors in the setting of an acute, non-cardiovascular illness, detailed information on their efficacy and safety among participants with and without type 2 diabetes (T2D) from double-blind randomized trials is lacking. In this secondary prespecified analysis of the Dapagliflozin in Respiratory Failure in Patients with COVID-19 (DARE-19) trial, we sought to evaluate the safety and efficacy of initiating dapagliflozin during acute illness with COVID-19 in patients with and without T2D.</p><p><strong>Methods: </strong>The DARE-19 trial randomized 1250 patients hospitalized with COVID-19 and cardiometabolic risk factors to dapagliflozin or placebo. T2D was present in 636/1250 (50.9%) of the cohort. Dual primary outcomes were evaluated: prevention (time to new or worsened organ dysfunction or death) and a hierarchical composite outcome of recovery (change in clinical status by day 30). Key biomarkers (serum bicarbonate, estimated glomerular filtration rate [eGFR], hematocrit, and glucose) and safety were assessed in participants with and without T2D during index hospitalization.</p><p><strong>Results: </strong>Among patients with T2D, the prevention outcome occurred in 10.9% receiving dapagliflozin versus 13.9% receiving placebo (hazard ratio [HR] 0.76, 95% CI 0.49-1.18). In patients without diabetes, the event rate was 11.5% with dapagliflozin versus 13.3% with placebo (HR 0.86, 95% CI 0.55-1.35; interaction p = 0.668). For the primary recovery outcome, no significant differences were observed between dapagliflozin and placebo groups regardless of diabetes status (interaction p = 0.222). Close laboratory monitoring revealed similarities in serum bicarbonate, eGFR, or hematocrit for the dapagliflozin and placebo groups, irrespective of T2D status. Any serious adverse event was reported in 12·7% of patients in the dapagliflozin group, 14·3% in the placebo group among patients with T2D, and in 8·5% of patients in the dapagliflozin group, and 11·9% in the placebo group in patients without T2D. Diabetes ketoacidosis was reported in two patients with T2D in the dapagliflozin group.</p><p><strong>Conclusions: </strong>Initiating dapagliflozin in patients hospitalized for acute COVID-19 was well tolerated and safe, irrespective of T2D status. Serum biomarker levels remained stable and comparable between treatment groups, indicating no increased risk of adverse metabolic or renal effects with dapagliflozin in this clinical scenario.</p><p><strong>Trial registration: </strong>The trial was registered on ClinicalTrials.gov (NCT04350593).</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"24 1","pages":"307"},"PeriodicalIF":10.6,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12312311/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144752455","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":"Microvascular dysfunction across organs in heart failure with preserved ejection fraction: the PROSE-HFpEF case-control study.","authors":"Jerremy Weerts, Blanche L M Schroen, Arantxa Barandiarán Aizpurua, Tos T J M Berendschot, Lloyd Brandts, Carroll A B Webers, Sami O Simons, Steven J R Meex, Ronald Henry, Carla J H van der Kallen, Hans-Peter Brunner-La Rocca, Christian Knackstedt, Stephane R B Heymans, Rudolf A de Boer, Vanessa P M van Empel, Alfons J H M Houben","doi":"10.1186/s12933-025-02850-1","DOIUrl":"10.1186/s12933-025-02850-1","url":null,"abstract":"<p><strong>Background: </strong>Systemic microvascular dysfunction is proposed as a key pathophysiological process in heart failure with preserved ejection fraction (HFpEF). This study compared microvasculature across vascular beds in HFpEF patients and controls.</p><p><strong>Methods: </strong>This prospective, case-control study included subjects ≥ 60years. HFpEF patients were diagnosed in an expert centre. Controls without HF were selected from the Maastricht Study, a population cohort enriched with diabetes mellitus. Microvascular assessments included central retinal venular/arteriolar calibres (CRVE/CRAE), flicker-light-induced retinal dilation, skin microvascular flowmotion and heat-induced hyperemia, and urinary albumin-to-creatinine ratio (UACR). Group differences were evaluated with confounder-adjustments (age, sex, blood pressure, body mass index, diabetes, haemoglobin, smoking). Interactions with sex and diabetes mellitus were tested, and stratified analyses were performed when significant interactions were present.</p><p><strong>Results: </strong>Microvascular assessments were performed in 138 HFpEF patients and 2140 controls. Microvascular differences were present between groups in all vascular beds. However, confounder-adjusted analyses attenuated differences. Confounder-adjusted analyses indicated that HFpEF patients versus controls still had retinal differences: narrower CRVE (- 8.1 μm, p = 0.008) and narrower CRAE trend (- 3.5 μm, p = 0.073), but similar flicker-light-induced retinal venular/arteriolar dilation (- 0.23%, p = 0.392; - 0.18%, p = 0.593, respectively). Confounder-adjusted analyses showed similar skin flowmotion measures (i.e. endothelial power - 0.09log(PU²), p = 0.181), and heat-induced hyperemia (0.02log(%), p = 0.605) between groups. UACR remained higher in HFpEF after confounder adjustments (0.56log(g/mol), p = < 0.001). Interaction analyses revealed that female patients had narrower CRVE versus controls (p_int=0.023; females - 13.8 μm, p < 0.001; males 1.2 μm, p = 0.812). Patients had lower skin endothelial flowmotion power only when diabetes was co-occurring (p_int=0.048; - 0.36 log(PU² ), p = 0.014). UACR was higher in male and female patients versus controls, but was more pronounced in males (p_int=0.002).</p><p><strong>Conclusions: </strong>HFpEF patients showed microvascular differences versus controls across all vascular beds studied. However, confounder-adjusted differences remained significant in eyes and kidneys. The findings across multiple organs support that MVD is likely a more systemic process than only local MVD in HFpEF, and possible sex-specific underlying pathophysiology.</p><p><strong>Registration: </strong>URL: https://onderzoekmetmensen.nl ; Unique identifier: NL7655.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"24 1","pages":"310"},"PeriodicalIF":10.6,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12312529/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144752473","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":"Hypoglycemia and glycemic variability in acute myocardial infarction: the lesser-known aspects of glycemic control.","authors":"Claudia Lucci, Alessandro Marongiu, Stefano Genovese, Mario Mazza, Nicola Cosentino, Giancarlo Marenzi","doi":"10.1186/s12933-025-02862-x","DOIUrl":"10.1186/s12933-025-02862-x","url":null,"abstract":"<p><p>Glucose abnormalities are common in patients with acute myocardial infarction (AMI) and significantly influence prognosis. While acute hyperglycemia on admission has long been recognized as a predictor of adverse outcomes, growing evidence suggests that hypoglycemia and glycemic variability (GV) are equally, if not more, prognostically relevant. These glycemic excursions, whether spontaneous or iatrogenic, are associated with increased risks of mortality, reinfarction, heart failure, and arrhythmias. The underlying mechanisms include sympathetic overactivation, endothelial dysfunction, inflammation, oxidative stress, thrombogenesis, and electrophysiological instability. Despite their clinical significance, hypoglycemia and GV remain insufficiently addressed in current AMI management protocols. Glycemic variability is often assessed through heterogeneous metrics-such as standard deviation, coefficient of variation, and mean amplitude of glycemic excursions, limiting comparability across studies. Additionally, reliance on intermittent glucose monitoring hinders accurate detection of hypoglycemic episodes, particularly those that are asymptomatic or nocturnal. The interaction between acute glycemic fluctuations and myocardial ischemia is also poorly understood, and the efficacy of interventions specifically targeting these disturbances remains to be established. Moreover, while observational studies have linked both hypoglycemia and GV with poor outcomes in AMI, interventional trials specifically targeting these abnormalities are lacking. This review aims to synthesize current evidence on the clinical and prognostic significance of hypoglycemia and GV in patients with AMI, offering an integrative overview of their prevalence, underlying mechanisms, and impact on outcomes, while highlighting key knowledge gaps and directions for future research.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"24 1","pages":"309"},"PeriodicalIF":10.6,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12312239/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144752457","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":"Specific targeting of adipose tissue metabolism is superior to caloric restriction in treating obesity-related HFpEF.","authors":"Simon Sedej, Alina Stockner, Renate Schreiber, Abhinav Diwan, Rolf Breinbauer, Mahmoud Abdellatif","doi":"10.1186/s12933-025-02879-2","DOIUrl":"10.1186/s12933-025-02879-2","url":null,"abstract":"<p><p>Obesity is a modifiable major driver of heart failure with preserved ejection fraction (HFpEF), the most common and rapidly increasing form of heart failure. Current metabolic therapies, such as caloric restriction and incretin-based drugs, have shown promise in treating obesity-related HFpEF. However, these interventions neither specifically nor selectively improve adipose tissue metabolism, which is a key etiological factor in HFpEF that may offer a pathway to safer and more effective treatment strategies. Towards this end, we found that genetic inhibition of adipose triglyceride lipase (ATGL) specifically in adipocytes is sufficient to prevent the development of obesity-related HFpEF, and that pharmacological inhibition of ATGL using atglistatin effectively treats established disease. Atglistatin selectively inhibits ATGL in adipose tissue, but not in the heart, leading to superior reduction in adiposity and greater improvement in diastolic dysfunction compared to caloric restriction. These observations underscore the therapeutic potential of selectively targeting adipose tissue, independent of the effects of body weight loss. Mechanistically, atglistatin attenuates HFpEF-associated elevation of inflammatory cytokines, especially IL-1β levels in adipose tissue, more effectively than caloric restriction. In sum, these findings identify dysregulated adipose tissue metabolism as a causal factor and therapeutic target in maladaptive fat-heart crosstalk driving obesity-related HFpEF.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"24 1","pages":"311"},"PeriodicalIF":10.6,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12312238/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144752474","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}