Cardiovascular Diabetology最新文献

{"title":"Exploring the impact of metabolic comorbidities on epicardial adipose tissue in heart failure with preserved ejection fraction.","authors":"Nassiba Menghoum, Maria Chiara Badii, Martin Leroy, Marie Parra, Clotilde Roy, Sibille Lejeune, David Vancraeynest, Agnes Pasquet, Dulce Brito, Barbara Casadei, Christophe Depoix, Gerasimos Filippatos, Damien Gruson, Frank Edelmann, Vanessa M Ferreira, Renaud Lhommel, Masliza Mahmod, Stefan Neubauer, Alexandre Persu, Stefan Piechnik, Kristian Hellenkamp, Ignatios Ikonomidis, Bartosz Krakowiak, Burkert Pieske, Elisabeth Pieske-Kraigher, Fausto Pinto, Piotr Ponikowski, Michele Senni, Jean-Noël Trochu, Nancy Van Overstraeten, Rolf Wachter, Bernhard L Gerber, Jean-Luc Balligand, Christophe Beauloye, Anne-Catherine Pouleur","doi":"10.1186/s12933-025-02688-7","DOIUrl":"10.1186/s12933-025-02688-7","url":null,"abstract":"<p><strong>Background: </strong>Heart failure (HF) with preserved ejection fraction (HFpEF) is increasingly prevalent worldwide due to aging and comorbidities. Epicardial adipose tissue (EAT), favored by diabetes and obesity, was shown to contribute to HFpEF pathophysiology and is an emerging therapeutic target. This study explored the relationship between ventricular EAT measured by cardiovascular magnetic resonance (CMR), metabolic factors, and imaging characteristics in controls, pre-HF patients, and HFpEF patients.</p><p><strong>Methods: </strong>Patients from a Belgian cohort enrolled from December 2015 to June 2017 were categorized by HF stage: pre-HF (n = 16), HFpEF (n = 104) and compared to matched controls (n = 26) and to pre-HF (n = 191) from the Beta3-LVH cohort. Biventricular EAT volume was measured in end-diastolic short-axis cine stacks. In the Belgian cohort, associations between EAT, HF stage, and various biological and imaging markers were explored. The clinical endpoint was a composite of mortality or first HF hospitalization in the HFpEF group.</p><p><strong>Results: </strong>EAT significantly differed between groups, with higher values in HFpEF patients compared to pre-HF and controls (72.4 ± 20.8ml/m<sup>2</sup>vs. 55.0 ± 11.8ml/m<sup>2</sup> and 48 ± 8.9ml/m<sup>2</sup>, p < 0.001) from the Belgian cohort and to pre-HF (52.0 ± 15.0 ml/m<sup>2</sup>, p < 0.001) from the Beta3-LVH cohort. Subsequent analyses focused on the Belgian cohort. In contrast to atrial fibrillation, diabetes prevalence and body mass index (BMI) did not differ between pre-HF and HFpEF patients. Multivariable logistic regression and random forest classification identified EAT, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and H<sub>2</sub>FPEF score as strong markers of HFpEF status. EAT was significantly correlated with H<sub>2</sub>FPEF score (r = 0.41, p = 0.003), BMI (r = 0.30, p < 0.001), high-sensitive troponin T (r = 0.41, p < 0.001), NT-proBNP (r = 0.37, p < 0.001), soluble suppression of tumorigenicity-2 (sST2) (r = 0.30, p < 0.001), E/e' ratio (r = 0.33, p < 0.001), and left ventricular global longitudinal strain (r = 0.35, p < 0.001). In HFpEF patients, diabetes, ischemic cardiomyopathy, and elevated sST2 were independently associated with elevated EAT. In contrast with diabetes and BMI, increased EAT was not associated with prognosis.</p><p><strong>Conclusions: </strong>EAT assessed by CMR was significantly higher in HFpEF patients compared to controls and pre-HF patients, irrespective of diabetes and BMI. EAT was moderately associated with HFpEF status. HFpEF patients with elevated EAT exhibited a marked diabetic, ischemic, and inflammatory profile, highlighting the potential role of drugs targeting EAT.</p><p><strong>Trial registration: </strong>Characterization of Heart Failure With Preserved Ejection Fraction; Assessment of Efficacy of Mirabegron, a New beta3-adrenergic Receptor in the Prevention of Heart Failure (Beta3_LVH).</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"24 1","pages":"134"},"PeriodicalIF":8.5,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11929347/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143691323","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":"Eplerenone, diabetes, and chronic kidney disease in patients hospitalized for acute heart failure: findings from the EARLIER trial.","authors":"Masatake Kobayashi, Akira Yamashina, Kazuhiro Satomi, Masataka Watanabe, Ryu Takagi, Ayako Tezuka, Shin Ito, Masanori Asakura, Masafumi Kitakaze","doi":"10.1186/s12933-025-02659-y","DOIUrl":"10.1186/s12933-025-02659-y","url":null,"abstract":"<p><strong>Background: </strong>Mineralocorticoid receptor antagonists (MRAs) are often underutilized in patients with heart failure (HF), particularly those with diabetes and/or chronic kidney disease (CKD). However, the impact of concurrent diabetes and CKD on the efficacy and safety of eplerenone in acute HF remains uncertain.</p><p><strong>Methods: </strong>The EARLIER trial enrolled patients with acute HF, who were randomized to receive eplerenone or placebo for 6 months. Patients were categorized based on the presence of diabetes and/or CKD (defined by eGFR < 45 ml/min/1.73 m² or UACR ≥ 30 mg/g), and the associations between diabetes/CKD categories and cardiovascular outcomes were assessed. The effects of eplerenone on HF-related outcomes (i.e., cardiovascular death, HF hospitalization, worsening HF, or out-of-hospital diuretic intensification) and adverse events were also assessed across diabetes/CKD status.</p><p><strong>Results: </strong>Among 300 patients (mean age 67 ± 13 years; 73% male), 39% had diabetes, mean estimated glomerular filtration rate was 63 ± 18 ml/min/1.73 m², median urine albumin-to-creatinine ratio was 34 mg/g (13-84 mg/g), and 58% had CKD. Patients with both diabetes and CKD (26%) had a higher risk of cardiovascular death and/or hospitalization compared to those without either disease (HR, 95% CI = 2.57, 1.29-5.12; P = 0.007, P-for-interaction = 0.049), and poor prognosis persisted after adjusting for covariates (i.e., natriuretic peptide) (adjusted-HR, 95% CI = 2.33, 1.12-4.84; P = 0.02). Furthermore, the effects of eplerenone on HF-related outcomes and adverse events were consistent regardless of diabetes/CKD categories (all-P-for interaction > 0.05).</p><p><strong>Conclusions: </strong>In patients with acute HF, the combination of diabetes and CKD was associated with an increased risk of cardiovascular events. However, the efficacy and safety of eplerenone were not influenced by diabetes and CKD status.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"24 1","pages":"136"},"PeriodicalIF":8.5,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11929252/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143691321","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":"Impact of glycemic control metrics on short- and long-term mortality in transcatheter aortic valve replacement patients: a retrospective cohort study from the MIMIC-IV database.","authors":"Qingyun Yu, Qingan Fu, Xiaowei Ma, Huijian Wang, Yunlei Xia, Yue Chen, Penghui Li, Yue Li, Yanqing Wu","doi":"10.1186/s12933-025-02684-x","DOIUrl":"10.1186/s12933-025-02684-x","url":null,"abstract":"<p><strong>Background: </strong>Glycemic control is critical for managing transcatheter aortic valve replacement (TAVR) patients, especially those in intensive care units (ICUs). Emerging metrics such as the hemoglobin glycation index (HGI), stress hyperglycemia ratio (SHR), and glycemic variability (GV) offer advanced insights into glucose metabolism. However, their prognostic implications for short- and long-term outcomes post-TAVR remain underexplored.</p><p><strong>Methods: </strong>This retrospective cohort study analyzed 3342 ICU-admitted TAVR patients via the MIMIC-IV database. Patients were stratified into tertiles for HGI, SHR, and GV levels. Survival analyses, including Kaplan‒Meier curves, Cox proportional hazards models and restricted cubic splines (RCSs), were used to assess associations between glycemic control metrics and 30-day and 365-day all-cause mortality in these patients. Sensitivity analyses, subgroup assessments, and external validation were also performed to verify the study findings.</p><p><strong>Results: </strong>During follow-up, 1.6% and 6.9% of patients experienced 30-day and 365-day mortality after TAVR, respectively. In the fully adjusted cox regression model, lower HGI (HR 1.48, 95% CI 1.05-2.09, P = 0.025) and higher SHR (HR 1.63, 95% CI 1.15-2.32, P = 0.006) were most significantly associated with an increased risk of 365-day mortality. Higher SHR was also significantly associated with an increased risk of 30-day mortality in patients (HR 2.92, 95% CI 1.32-6.45, P = 0.008). Both lower (HR 0.59, 95% CI 0.38-0.92, P = 0.019) and higher GV levels (HR 1.43, 95% CI 1.06-1.93, P = 0.020) were associated with the risk of 365-day mortality.</p><p><strong>Conclusions: </strong>In critically ill TAVR patients, glycemic control metrics are closely associated with long-term all-cause mortality. The HGI, SHR, and GV provide prognostic insights into clinical outcomes that surpass conventional glucose measurements. These findings highlight the importance of personalized glycemic management strategies in improving TAVR patient outcomes.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"24 1","pages":"135"},"PeriodicalIF":8.5,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11929336/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143691325","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 triglyceride-glucose index trajectories with the risk of worsening heart failure in elderly patients with chronic heart failure and type 2 diabetes: a competing risk analysis.","authors":"Yingying Lai, Cailong Lin, Xindong Liu, Yuting Liu, Hua Cai, Nannan Zhao, Yushuo Gao, Ziyi Yi, Jianyu Huang, Min Li, Lin Xu","doi":"10.1186/s12933-025-02687-8","DOIUrl":"10.1186/s12933-025-02687-8","url":null,"abstract":"<p><strong>Background: </strong>The triglyceride-glucose index serves as a dependable biomarker for gauging insulin resistance linked to cardiovascular disease. Our study was designed to investigate how the trajectory of the triglyceride-glucose index relates to the risk of worsening heart failure and overall mortality in patients aged 60 years and older with chronic heart failure and type 2 diabetes.</p><p><strong>Methods: </strong>This study enrolled 466 patients who had ≥ 3 medical exams. The formula for calculating the triglyceride-glucose index was ln (fasting triglycerides [mg/dL] × fasting blood glucose [mg/dL]/2). The trajectory of the triglyceride-glucose index in longitudinal analysis was analyzed via linear mixed models. The relationships between the trajectory of the TyG index and the risk of worsening heart failure and overall mortality were analyzed via competing Cox regression analysis and mixed-effects Cox regression analysis.</p><p><strong>Results: </strong>After the variables adjustment, compared with the first quartile group, the adjusted hazard ratios for worsening heart failure in top quartile group were 2.40 (1.35-3.28) for 10-year follow-up, and 2.09 (1.22-3.58) for overall follow-up duration. The adjusted hazard ratios for overall mortality in top quartile group were 1.99 (1.56-3.14) for 10-year follow-up, and 1.87 (1.22-2.88) for overall follow-up duration. Compared with the low decreasing trajectory, adjusted hazard ratios for worsening heart failure of high decreasing trajectory were 1.37 (1.10-1.71) for the 5-year follow-up, 1.78 (1.10-2.88) for 10-year follow-up, and 1.67 (1.04-2.68) for overall follow-up duration. The adjusted hazard ratios for overall mortality were 2.16 (1.39-3.35) for 10-year follow-up, and 2.23 (1.46-3.40) for overall follow-up duration.</p><p><strong>Conclusion: </strong>During follow-up, a higher baseline level of TyG index and a high decreasing trajectory were independently associated with long-term worsening heart failure and an increased risk of overall mortality.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"24 1","pages":"131"},"PeriodicalIF":8.5,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11929357/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143676776","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 triglyceride glucose-body mass index and the trajectory of cardio-renal-metabolic multimorbidity: insights from multi-state modelling.","authors":"Haoxian Tang, Jingtao Huang, Xuan Zhang, Xiaojing Chen, Qinglong Yang, Nan Luo, Hanyuan Lin, Jianan Hong, Shiwan Wu, Cuihong Tian, Mengyue Lin, Junshuang Tang, Jiasheng Wen, Pan Chen, Liwen Jiang, Youti Zhang, Kaihong Yi, Xuerui Tan, Yequn Chen","doi":"10.1186/s12933-025-02693-w","DOIUrl":"10.1186/s12933-025-02693-w","url":null,"abstract":"<p><strong>Background: </strong>Although some studies have examined the association between the triglyceride glucose-body mass index (TyG-BMI) and cardiovascular outcomes in the cardio-renal-metabolic (CRM) background, none have explored its role in the progression of CRM multimorbidity. In addition, prior research is limited by small sample sizes and a failure to account for the competitive effects of other CRM diseases.</p><p><strong>Methods: </strong>In this study, data obtained from the large-scale, prospective UK Biobank cohort were used. CRM multimorbidity was defined as the new-onset of ischemic heart disease, type 2 diabetes mellitus, or chronic kidney disease during follow-up. Multivariable Cox regression was used to analyse the independent association between TyG-BMI and each CRM multimorbidity (first, double, or triple CRM diseases). The C-statistic was calculated for each model, and a restricted cubic spline was applied to assess the dose-response relationship. A multi-state model was used to investigate the association between TyG-BMI and the trajectory of CRM multimorbidity (from baseline [without CRM disease] to the first CRM disease, the first CRM disease to double disease, and double disease to triple disease), with disease-specific analyses.</p><p><strong>Results: </strong>This study included 349,974 participants, with a mean age of 56.05 (standard deviation [SD], 8.08), 55.93% of whom were female. Over a median follow-up of approximately 14 years, 56,659 (16.19%) participants without baseline CRM disease developed at least one CRM disease, including 8451 (14.92%) who progressed to double CRM disease and 789 (9.34%) who further developed triple CRM disease. In the crude model, each SD increase in TyG-BMI was associated with a 47% higher risk of the first CRM disease, a 72% higher risk of double CRM disease, and a 95% higher risk of triple CRM disease, with C-statistics of 0.625, 0.694, and 0.764, respectively. Multi-state model analysis showed a 32% increased risk of new CRM disease, a 24% increased risk of progression to double CRM disease, and a 23% increased risk of further progression for those with double CRM diseases. TyG-BMI was significantly associated with the onset of all individual first CRM diseases (except for stroke) and with the transition to double CRM disease. Significant interactions were also observed, but TyG-BMI remained significantly associated with CRM multimorbidity across subgroups. Sensitivity analyses, including varying time intervals for entering states and an expanded CRM definition (including atrial fibrillation, heart failure, peripheral vascular disease, obesity, and dyslipidaemia), confirmed these findings.</p><p><strong>Conclusion: </strong>TyG-BMI remarkably influences the onset and progression of CRM multimorbidity. Incorporating it into CRM multimorbidity prevention and management could have important public health implications.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"24 1","pages":"133"},"PeriodicalIF":8.5,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11929281/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143676774","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":"Accelerometer-derived \"weekend warrior\" physical activity pattern and incident type 2 diabetes.","authors":"Zhi Cao, Jiahao Min, Chenjie Xu","doi":"10.1186/s12933-025-02676-x","DOIUrl":"10.1186/s12933-025-02676-x","url":null,"abstract":"<p><strong>Background: </strong>The guidelines provided by the World Health Organization (WHO) recommend a minimum of 150 min/week of moderate-to-vigorous physical activity (MVPA) for optimal overall health benefits. However, it remains unclear whether there are differential effects on the risk of incident type 2 diabetes (T2D) between concentrated and evenly distributed physical activity (PA) patterns. We aimed to investigate the associations of accelerometer-derived weekend warrior and regularly active pattern with risk of T2D.</p><p><strong>Methods: </strong>A total of 84,656 general participants from the UK Biobank with validated accelerometry data and free of T2D was included. Data on PA was collected using the Axivity AX3 wrist-based triaxial accelerometer worn for one week. Participants were categorized into three PA patterns: inactive (< 150 min/week of MVPA), weekend warrior (≥ 150 min/week with ≥ 50% of total MVPA occurring within 1-2 days), and regularly active (≥ 150 min/week but not meeting weekend warrior criteria).</p><p><strong>Results: </strong>During a median follow-up of 8.4 years, 2464 cases of T2D were documented. In multivariable-adjusted models, the weekend warrior pattern (hazard ratio [HR] 0.75; 95% confidence interval [CI] 0.67-0.84) and the regularly active pattern (HR 0.80, 95% CI 0.69-0.94) exhibited a comparable lower risk of T2D compared to physically inactive participants. When stratified by genetic risk score (PRS) of T2D, the weekend warrior pattern was associated with T2D in the higher PRS group (HR 0.78, 95% CI 0.67-0.91), intermediate PRS group (HR 0.78, 95% CI 0.62-0.97) and lowest PRS group (HR 0.59, 95% CI 0.43-0.80).</p><p><strong>Conclusions: </strong>Engaging in the weekend warrior pattern is associated with a similarly lower risk of T2D to the regularly active pattern, even among individuals with high genetic risk. These findings highlight the weekend warrior pattern as a significant and flexible alternative in preventive intervention strategies for T2D, particularly for those unable to maintain daily activity routines.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"24 1","pages":"130"},"PeriodicalIF":8.5,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11929297/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143676852","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":"The impact of hypercortisolism beyond metabolic syndrome on left ventricular performance: a myocardial work analysis.","authors":"Floran Sahiti, Mario Detomas, Vladimir Cejka, Kristina Hoffmann, Götz Gelbrich, Stefan Frantz, Mathias Kroiss, Peter U Heuschmann, Stefanie Hahner, Martin Fassnacht, Timo Deutschbein, Stefan Störk, Caroline Morbach","doi":"10.1186/s12933-025-02680-1","DOIUrl":"10.1186/s12933-025-02680-1","url":null,"abstract":"<p><strong>Background and aims: </strong>Endogenous Cushing's syndrome (CS) is characterized by an unfavorable cardiovascular (CV) and metabolic risk profile, but the potential adverse effects of hypercortisolism on myocardial function are not well known. Myocardial Work analysis is a new echocardiographic method that utilizes left ventricular pressure-strain loops to quantify cardiac performance independent of afterload.</p><p><strong>Methods and results: </strong>In a cross-sectional analysis, we compared four groups: patients with overt endogenous CS (n = 31, mean age 47 ± 12 years, 71% women), patients with endogenous CS in long-term remission after medical cure (CS-LTR; n = 49, 53 ± 12 years, 78% women), healthy subjects (n = 439; 49 ± 11 years, 57% women), and individuals with metabolic syndrome (n = 305, 59 ± 10 years, 37% women). Both CS patient groups exhibited a CV risk pattern and metabolic profile worse than healthy subjects but better than individuals with metabolic syndrome. Analyses adjusted for sex and age revealed higher Wasted Work both in overt CS (median; quartiles: 105 mmHg%; 74, 147) and CS-LTR (97 mmHg%; 69, 158), respectively, when compared to healthy individuals (75 mmHg%; 54, 109, p < 0.01) or individuals with metabolic syndrome (95 mmHg%, 65, 136, p < 0.05), resulting in compromised Work Efficiency (p < 0.05).</p><p><strong>Conclusion: </strong>Left ventricular performance is compromised in overt CS beyond alterations found in individuals with metabolic syndrome sharing equal CV risk factors and remains so despite biochemical remission during the LTR period. Myocardial Work analysis is suited to detect the subtle yet clinically relevant differences between different phenotypes of myocardial involvement.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"24 1","pages":"132"},"PeriodicalIF":8.5,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11929293/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143676762","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":"Piezo1 deletion mitigates diabetic cardiomyopathy by maintaining mitochondrial dynamics via ERK/Drp1 pathway.","authors":"Weipin Niu, Xin Liu, Bo Deng, Tianying Hong, Cuifen Wang, Yameng Yan, Jiali Liu, Yuehua Jiang, Jing Li","doi":"10.1186/s12933-025-02625-8","DOIUrl":"10.1186/s12933-025-02625-8","url":null,"abstract":"<p><strong>Objective: </strong>Increasing evidence highlights the critical role of Piezo1 in cardiovascular diseases, with its expression upregulated in diabetic heart. However, the involvement of Piezo1 in the pathogenesis of diabetic cardiomyopathy (DCM) remains unclear. This study aims to elucidate the regulatory role of Piezo1 in mitochondrial dynamics within the context of DCM and to investigate the underlying mechanisms.</p><p><strong>Methods: </strong>We constructed cardiac-specific knockout of Piezo1 (Piezo1^∆Myh6) mice. Type 1 diabetes was induced using streptozotocin (STZ) injection while type 2 diabetes was established through a high-fat diet combined with STZ. Echocardiography assessed left ventricular function, histological evaluations used HE and Masson staining to examine cardiac pathology in Piezo1^fl/fl controls, Piezo1^∆Myh6 controls, Piezo1^fl/fl diabetic and Piezo1^∆Myh6 diabetic mice. Mitochondrial function including oxygen species level, mitochondrial morphology, and respiration rate were also assessed.</p><p><strong>Results: </strong>Our findings revealed that Piezo1 expression was upregulated in the myocardium of diabetic mice and in high-glucose-treated cells. Cardiac-specific knockout of Piezo1 improved cardiac dysfunction and ameliorated cardiac fibrosis in diabetic mice. Moreover, Piezo1 deficiency also attenuated mitochondrial impairment. Piezo1^fl/fl diabetic mice exhibited increased calpain activity and excessive mitochondrial fission mediated by Drp1 and obvious reduced fusion; however, Piezo1 deficiency restored calpain levels and mitochondrial dysfunction. These observations were also corroborated in H9C2 cells and neonatal mouse cardiomyocytes. Cardiac-specific knockout of Piezo1 increased phosphorylation of Drp1 and ERK1/2 in vivo and in vitro. Piezo1 knockout or treatment with inhibitor improved mitochondrial function.</p><p><strong>Conclusions: </strong>This study provides the first evidence that Piezo1 is elevated in DCM through the modulation of mitochondrial dynamics, which is reversed by Piezo1 deficiency. Thus, Piezo1 inhibition may provide a promising therapeutic strategy for the treatment of DCM.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"24 1","pages":"127"},"PeriodicalIF":8.5,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11927149/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669194","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":"Evaluation of glycemic status and subclinical atherosclerosis in familial hypercholesterolemia subjects with or without LDL receptor mutation.","authors":"Francesco Di Giacomo Barbagallo, Giosiana Bosco, Maurizio Di Marco, Sabrina Scilletta, Nicoletta Miano, Marco Musmeci, Marina Martedì, Ana M González-Lleó, Daiana Ibarretxe, Ernestina Marianna De Francesco, Roberta Malaguarnera, Antonino Di Pino, Luís Masana, Francesco Purrello, Salvatore Piro, Roberto Scicali","doi":"10.1186/s12933-025-02683-y","DOIUrl":"10.1186/s12933-025-02683-y","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Familial hypercholesterolemia (FH) is a genetic condition characterized by elevated LDL-C and increased cardiovascular risk. Beyond LDL-C levels, the impact of genotype on glucose homeostasis has not been well evaluated. We aimed to evaluate the impact of genotype on glycemic status and on atherosclerotic injury in FH subjects.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We conducted a cross-sectional study on 322 FH subjects not on lipid-lowering therapy and without history of cardiovascular disease. Biochemical and genetic analyses as well as vascular profile assessment were obtained from all subjects. The study population was divided into two groups according to genotype: LDL receptor (LDLR) group and non-LDLR (NLDLR) group.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The LDLR group exhibited a higher prevalence of low glycemic status (LGS) than the NLDLR group (44.1% vs. 26%, p &lt; 0.01), whereas a high glycemic status (HGS) was more prevalent in the NLDLR group compared with LDLR group (74% vs. 55.9%, p &lt; 0.01). The NLDLR group exhibited a higher prevalence of peripheral atherosclerotic plaques than the LDLR group (93.4% vs. 73%, p &lt; 0.05), while coronary artery calcification (CAC) presence was more prevalent in the LDLR group compared with the NLDLR group (74.7% vs. 48%, p &lt; 0.01). In a secondary analysis the study population was stratified into three groups based on LDLR genotype: NLDLR, LDLR defective, LDLR null groups. The prevalence of LGS progressively increased from the NLDLR to the LDLR null group, while HGS showed an inverse trend (p for trend &lt; 0.05). Peripheral atherosclerotic plaque prevalence decreased from the NLDLR to the LDLR null group (p for trend &lt; 0.05), while CAC prevalence increased progressively in the three groups (p for trend &lt; 0.01). Logistic regression analysis showed that FH groups with an LDLR mutation were inversely associated with HGS (p for both &lt; 0.01) and the LDLR null group exhibited the strongest association.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;FH subjects with NLDLR mutations exhibited a worse glycemic profile, while null LDLR mutations showed the strongest inverse association with HGS. The integrations of genetic, lipid and glucose data could be useful to better identify the metabolic profile and the atherosclerosis distribution in FH subjects.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Research insights: &lt;/strong&gt;WHAT IS CURRENTLY KNOWN ABOUT THIS TOPIC?: Familial hypercholesterolemia (FH) is characterized by elevated LDL-C levels. LDLR null mutations protected pancreatic β-cells from cholesterol accumulation. NGS has improved FH diagnosis by analysis of all genes implicated in the lipid disorder. WHAT IS THE KEY RESEARCH QUESTION?: What is the impact of FH genotype (monogenic with or without LDLR mutation/polygenic) on glycemic status? WHAT IS NEW?: FH population was characterized by a heterogeneous glycemic profile according to LDLR mutation. LDL-C and plasma glucose could modulate the distribution of subclinical atheroscle","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"24 1","pages":"126"},"PeriodicalIF":8.5,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11927314/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669192","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":"Dysglycaemia is associated with the pattern of valvular calcification in micro-computed tomography analysis: an observational study in patients with severe aortic stenosis.","authors":"Magdalena Kopytek, Kamila W Undas, Jacek Tarasiuk, Sebastian Wroński, Michał Ząbczyk, Joanna Natorska","doi":"10.1186/s12933-025-02691-y","DOIUrl":"10.1186/s12933-025-02691-y","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Diabetes mellitus (DM) has been shown to increase the rate of aortic stenosis (AS) progression. However, the impact of impaired plasma glucose on valvular calcification remains poorly understood. Using ex vivo micro-computed tomography (micro-CT), we aimed to determine whether plasma glucose, glycated haemoglobin (HbA&lt;sub&gt;1c&lt;/sub&gt;), or concentrations of advanced glycation end products (AGEs) and their soluble receptor (sRAGE) are associated with a specific pattern of valvular calcification in severe AS.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;In this case-control study, 14 (48%) normoglycaemic patients with AS were compared to 15 individuals (52%) with elevated glucose levels (≥ 5.6 mmol/L), all with HbA&lt;sub&gt;1c&lt;/sub&gt; ≤ 6.5%. Stenotic aortic valves obtained surgically were analysed using micro-CT to assess structure of tissue mineralization. Calcium volume (CV), surface volume (SV), CV/SV ratio, and trabecular thickness (TbTh) were evaluated. Plasma AGEs and sRAGE were assessed by ELISAs. DM patients or those using antidiabetic agents were excluded from the study.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Patients with impaired and high glucose, including 10 (67%) with glucose between 5.6 and 6.9 mmol/L and 5 (33%) ranging from 7 to 7.6 mmol/L, exhibited higher HbA&lt;sub&gt;1c&lt;/sub&gt; (+ 17%) and AGEs levels (+ 44.6%), but not sRAGE compared to those with normal glucose. Patients with impaired and high glucose had also 19.2% higher maximal transvalvular pressure gradient (PG&lt;sub&gt;max&lt;/sub&gt;) and 9.3% higher peak transvalvular velocity (V&lt;sub&gt;max&lt;/sub&gt;) compared to normoglycaemic individuals. Micro-CT indices correlated with fasting glucose, HbA&lt;sub&gt;1c&lt;/sub&gt;, and AGEs levels (all p &lt; 0.05), but not with sRAGE (p &gt; 0.05). Valves extracted from patients with impaired and high glucose exhibited higher mineralization volume, folding, and structural integrity, as reflected by increased CV (+ 127.6%), CV/SV ratio (+ 59%) and calcium deposits microarchitecture as indicated by about 50% higher TbTh, compared to normoglycaemic patients. When patients with AS were divided into three groups based on their glucose levels (&lt; 5.5 mmol/L, 5.6-6.9 mmol/L, and 7.0-7.6 mmol/L), micro-CT analysis showed more distinct structural differences among the groups. The valves in the highest glucose group were the most severely affected. Micro-CT parameters were also associated with both transvalvular pressure gradients (PG&lt;sub&gt;mean&lt;/sub&gt; and PG&lt;sub&gt;max&lt;/sub&gt;), V&lt;sub&gt;max&lt;/sub&gt; and aortic valve area (all p &lt; 0.05).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Strict glycaemic control could potentially reduce the rate of valve mineralization and calcium deposit accumulation in patients with AS.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Research insights: &lt;/strong&gt;WHAT IS CURRENTLY KNOWN ABOUT THIS TOPIC?: Diabetes mellitus (DM) is a risk factor for the progression of aortic stenosis (AS). Accumulation of advanced glycation end products (AGEs) enhances glycation of valvular proteins. WHAT IS THE KEY RESEARCH Q","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"24 1","pages":"129"},"PeriodicalIF":8.5,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11927127/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669191","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}