Cardiovascular Diabetology最新文献

{"title":"The prognostic value of atherogenic index of plasma and thin-cap fibroatheroma among patients with STEMI: an optical coherence tomography prospective cohort study of real world.","authors":"Xiaoxiao Zhao, Runzhen Chen, Nan Li, Linghan Xue, Chen Liu, Peng Zhou, Yi Chen, Shaodi Yan, Li Song, Hanjun Zhao, Jiannan Li, Hongbing Yan","doi":"10.1186/s12933-025-02957-5","DOIUrl":"https://doi.org/10.1186/s12933-025-02957-5","url":null,"abstract":"<p><strong>Background and aim: </strong>This prospective study investigated plaque morphologies based on the underlying culprit lesion pathology in relation to the Atherogenic Index of Plasma (AIP) in patients with acute ST-elevated myocardial infarction (STEMI) who underwent primary percutaneous coronary intervention and optical coherence tomography (OCT) for assessment of culprit lesions. The aim of the study was to elucidate the effects of the AIP index and plaque type on the incidence of major adverse cardiovascular events (MACEs).</p><p><strong>Methods: </strong>A total of 274 patients with STEMI aged ≥ 18 years who underwent pre-intervention OCT imaging of culprit lesions between March 2017 and March 2019 were enrolled. AIP index was calculated using the formula: log 10 (triglycerides [TG]/ high-density lipoprotein cholesterol [HDL-C]). We stratified the cohort into four groups according to the presence of Thin-Cap Fibroatheroma (TCFA), as assessed by OCT, and the cutoff value of AIP: Group I consisted of patients with AIP < cutoff & without TCFA; Group II had AIP < cutoff & with TCFA; Group III included those with AIP > cutoff & without TCFA; and Group IV comprised patients with AIP > cutoff & with TCFA.</p><p><strong>Outcomes: </strong>Patients in Group IV exhibited a higher prevalence of Diabetes Mellitus (p = 0.012), elevated triglyceride-glucose index (TyG) levels (p < 0.001), increased LDL-C levels (p = 0.002), higher triglycerides levels (p < 0.001), and elevated total cholesterol (p = 0.001), indicating accelerated atherosclerosis. Furthermore, individuals within higher tertiles of AIP demonstrated a greater frequency of healing plaques (p = 0.021). Among patients with diabetes mellitus (DM), the AIP index exhibited a correlation with the healing of plaques (p < 0.05). Multivariable Cox regression analysis revealed that the incidence of MACEs among patients in Group IV (AIP > cutoff & with TCFA) increased by compared to those in Group I. Kaplan-Meier analyses confirmed risk stratification for MACEs based on interactions between AIP-TCFA interaction (log-rank p = 0.027), AIP-plaque interaction (log-rank p = 0.033), AIP-mixed plaque interaction (log-rank p = 0.041), AIP-lipid plaque interaction (log-rank p < 0.001), AIP- macrophage interaction (log-rank p = 0.032).</p><p><strong>Conclusion: </strong>Microstructural features observed via OCT for culprit lesions, combined with the AIP index-an important marker for cardiovascular disease-may be utilized clinically to support risk stratification and predict adverse events among STEMI patients.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"24 1","pages":"404"},"PeriodicalIF":10.6,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145343497","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":"Association of estimated glucose disposition rate with aging acceleration and mortality risk in individuals with cardiovascular-kidney-metabolic syndrome: evidence from two large national population-based studies.","authors":"Mo-Yao Tan, Zhen-Ni Jiang, Yao-Qin Li, Zi-Yu Li, Bin Niu","doi":"10.1186/s12933-025-02940-0","DOIUrl":"https://doi.org/10.1186/s12933-025-02940-0","url":null,"abstract":"<p><strong>Objective: </strong>This study investigated the relationship between estimated glucose disposal rate (eGDR), aging acceleration (AgeAccel), and mortality in adults diagnosed with cardiovascular-kidney-metabolic (CKM) stages 1 to 4.</p><p><strong>Methods: </strong>The study utilized data from 4,826 adults with CKM syndrome stages 1 to 4, collected from the National Health and Nutrition Examination Survey (NHANES) conducted during the 2005-2010 survey cycles. The assessment of AgeAccel was performed using two complementary measures: phenotypic AgeAccel (PhenoAgeAccel) and biological AgeAccel (BioAgeAccel). Survey-weighted logistic regression and Cox proportional hazards models were used to assess the associations of eGDR with AgeAccel and mortality risk, respectively. To assess the prognostic value of eGDR for mortality risk, we implemented a suite of nine distinct machine learning models. Additionally, a nomogram was developed to enhance the clinical applicability of our findings. Furthermore, we performed causal mediation analysis to quantify the proportion of the total effect of eGDR on mortality that was mediated through AgeAccel. To ensure the robustness of the results, we replicated our primary analyses using data from the nationally representative China Health and Retirement Longitudinal Study (CHARLS) cohort.</p><p><strong>Results: </strong>Our analysis included 4,826 NHANES participants, among whom we documented 831 all-cause mortality events and 208 cardiovascular disease (CVD)-specific deaths during follow-up. In multivariable-adjusted Cox regression models, each unit increase in eGDR was significantly associated with a 10% reduction in all-cause mortality risk (Hazard ratio [HR] = 0.90, 95% Confidence interval [CI] 0.86-0.93) and a 13% decrease in CVD mortality risk (HR = 0.87, 95% CI 0.81-0.93). Additionally, eGDR showed a negative association with AgeAccel, including both BioAgeAccel (odds ratio [OR] = 0.85, 95% CI 0.82-0.87) and PhenoAgeAccel (OR = 0.78, 95% CI 0.75-0.80). For predicting all-cause mortality from eGDR, the K-Nearest Neighbors (KNN) showed superior discrimination (Area Under the Curve [AUC]: 0.926), exceeding the performance of other machine learning algorithms in a comparative evaluation. Mediation analysis revealed that the protective effect of higher eGDR was partially explained by slower PhenoAgeAccel, with mediation effects accounting for 23.53% and 15.73% of the total impact on all-cause and CVD mortality, respectively.</p><p><strong>Conclusions: </strong>In the CKM population, lower eGDR levels may be associated with both AgeAccel and an increased risk of mortality, with AgeAccel potentially mediating the relationship between eGDR and mortality. These findings suggested that eGDR could serve as a potential predictor and intervention target for delaying aging and reducing mortality risk.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"24 1","pages":"402"},"PeriodicalIF":10.6,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145343533","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":"AI-quantified epicardial adipose tissue and prediction of future myocardial infarction in patients with cardiometabolic disease: a post-hoc analysis from the SCOT-HEART trial.","authors":"Jolien Geers, Nipun Manral, Caroline Park, Guadalupe Flores Tomasino, Kajetan Grodecki, Joel Lenell, Mikolaj Buchwald, Aryabod Razipour, Jacek Kwiecinski, Hidenari Matsumoto, Mohamed Marwan, Stephan Achenbach, Daniel S Berman, Marc R Dweck, David E Newby, Piotr J Slomka, Michelle C Williams, Damini Dey","doi":"10.1186/s12933-025-02946-8","DOIUrl":"https://doi.org/10.1186/s12933-025-02946-8","url":null,"abstract":"<p><strong>Background: </strong>Epicardial adipose tissue is gaining increasing interest as a cardiometabolic imaging biomarker, but its exact role in coronary artery disease is not fully understood. This study aimed to investigate the relationship between epicardial adipose tissue, coronary plaque characteristics, and risk of myocardial infarction in patients with suspected coronary artery disease, and in those with concomitant cardiometabolic disease.</p><p><strong>Methods: </strong>In a post-hoc analysis of the SCOT-HEART trial, epicardial adipose tissue volume and attenuation were quantified automatically from computed tomography (CT) angiography using deep-learning. Quantitative and high-risk coronary plaque characteristics were also assessed. The primary endpoint was fatal or non-fatal myocardial infarction.</p><p><strong>Results: </strong>The study population consisted of 1770 patients (58 ± 9 years, 56% males) of whom 313 (18%) with cardiometabolic disease. Epicardial adipose tissue volume was higher in patients withcardiometabolic disease (123 ± 44 versus 88 ± 36 mL, p < 0.001), and increased with the coronary calcium score (0: 82 ± 35 mL, 1-400: 97 ± 38 mL, > 400: 113 ± 44 mL; p < 0.001), and low-attenuation plaque burden (burden ≤ 4%: 85 ± 36mL, burden > 4%: 103 ± 41mL; p < 0.001), while there were no interactions between these features and epicardial adipose tissue attenuation (p > 0.05 for all). During a median follow-up of 8.6 years, 82 (4.6%) patients experienced myocardial infarction. In the total study cohort, epicardial adipose tissue volume predicted myocardial infarction both in univariable analysis, and after adjustment for established markers of cardiovascular risk. In patients with cardiometabolic disease, epicardial adipose tissue volume independently predicted myocardial infarction after adjustment for clinical risk factors and plaque features but this relationship was not found in those without cardiometabolic disease.</p><p><strong>Conclusions: </strong>CT-derived Epicardial adipose tissue volume correlates with quantitative and high-risk plaque features, and independently predicts risk of myocardial infarction in patients with cardiometabolic disease.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"24 1","pages":"403"},"PeriodicalIF":10.6,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145343570","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":"Stratifying cardiovascular benefits from GLP-1RA: a multisource analysis of patient-level CVOT and real-world data using AI-driven methods.","authors":"Mario Luca Morieri, Enrico Longato, Veronica Sciannameo, Emily Donatiello, Paola Berchialla, Angelo Avogaro, Agostino Consoli, Gian Paolo Fadini","doi":"10.1186/s12933-025-02952-w","DOIUrl":"10.1186/s12933-025-02952-w","url":null,"abstract":"<p><strong>Background: </strong>It remains unclear whether certain individuals with type 2 diabetes (T2D) derive greater cardiovascular benefit from GLP-1 receptor agonists (GLP-1RAs). Here, we integrate individual-level data from cardiovascular outcome trials (CVOTs) and electronic health records (EHRs), applying machine learning methods to confirm the cardiovascular benefits of GLP-1RAs in real-world populations and to identify subgroups with enhanced treatment response.</p><p><strong>Methods: </strong>Data from two CVOTs (LEADER and SUSTAIN-6) and a large real-world study (DARWIN-T2D) were analyzed. We first transposed the hazard ratio (HR) for 3-point major adverse cardiovascular event (3P-MACE) from CVOTs to the real-world population. Then, we used PRISM (Patient Response Identifiers for Stratified Medicine) against 3P-MACE reduction by GLP-1RA in a training/test setting. Findings were validated with external cohorts of new-users of GLP-1RA or comparators (DPP-4 inhibitors or basal insulin).</p><p><strong>Results: </strong>Despite notable differences in clinical characteristics between CVOT and real-world patients, the real-world-transposed HRs for 3P-MACE closely paralleled those from CVOTs. PRISM identified subgroups with differential treatment responses, based on history of myocardial infarction (MI) or stroke and age. Participants aged over 71 years without MI/stroke (41% of the real-world population) had the greatest relative benefit (HR 0.46; 95% CI 0.24-0.89 in the test set) and a greater absolute risk reduction (ARR 4.5%, 95% CI 1.2-7.7) than other subgroups (Gail-Simon p = 0.02). The external validation cohort confirmed these results (HR 0.67; 95% CI 0.51-0.89 and ARR 3.8%, 95% CI 1.5-6.1) showing significant differences in absolute risk reduction (p < 0.05).</p><p><strong>Conclusions: </strong>This study supports the integration of individual data from CVOT with those from EHR to confirm the transposition of results from CVOT to real-world populations, and enables the identification and validation of subgroups with greater cardiovascular benefits from cardioprotective treatment such as GLP-1RA treatment. This precision medicine approach represents a new framework for deploying cardiovascular prevention strategies in T2D.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"24 1","pages":"401"},"PeriodicalIF":10.6,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12535053/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145312178","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 role of insulin resistance in the longitudinal progression from NAFLD to cardiovascular-kidney-metabolic disease.","authors":"Chao Hou, Xiangling Yuan, Min Peng, Xuan Shi, Dahong Yang, Fang Wang, Ke Song, Gelin Xu, Jianzhong Shi","doi":"10.1186/s12933-025-02953-9","DOIUrl":"10.1186/s12933-025-02953-9","url":null,"abstract":"<p><strong>Background and objective: </strong>This study aimed to elucidate the role of insulin resistance in the progression from non-alcoholic fatty liver disease (NAFLD) to cardiovascular-kidney-metabolic (CKM) diseases, and to explore the potential influence of lifestyle factors.</p><p><strong>Methods: </strong>This study included participants free of NAFLD and CKM diseases from the UK Biobank. Insulin resistance was assessed using the TyG index. CKM diseases include ischemic stroke (IS), ischemic heart disease (IHD), type 2 diabetes (T2D), and chronic kidney disease (CKD). Markov multi-state models were used to assess the associations between the TyG index and disease transitions.</p><p><strong>Results: </strong>Among 377,757 participants (median age 57 years), 4949 developed NAFLD over a median follow-up of 13.6 years. Of these, 12.65% progressed to T2D, 9.11% to IHD, 8.63% to CKD, and 4.61% to IS. Elevated TyG levels significantly accelerated transitions from NAFLD to first-onset CKM disease (HR = 1.25, 95% CI 1.05-1.49), double CKM disease (HR = 1.46, 95% CI 1.19-1.80), and triple CKM disease (HR = 1.81, 95% CI 1.28-2.55). Similar progression risk increases were observed for individual CKM components: T2D (HR = 1.41, 95% CI 1.11-1.78), CKD (HR = 1.37, 95% CI 1.08-1.75), and IS (HR = 1.70, 95% CI 1.27-2.27). A J-shaped dose-response relationship was identified. Transitions risk remained pronounced among individuals with healthy sleep and regular physical activity.</p><p><strong>Conclusions: </strong>Insulin resistance independently accelerated the progression from NAFLD to CKM diseases, particularly ischemic stroke. Healthy sleep and regular physical activity failed to offset this detrimental impact.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"24 1","pages":"398"},"PeriodicalIF":10.6,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12522269/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145298556","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":"Epicardial adipose tissue volume and arterial stiffness in people living with diabetes: the METAB-CV-PWV study.","authors":"Omar Nouhou Koutcha, Sopio Tatulashvili, Nanthara Sritharan, Pierre Boutouyrie, Imen Rezgani, Marouane Boubaya, Mohamed Lamine Mariko, Lucie Allard, Meriem Sal, Coralie Bloch-Queyrat, Mohamed Zerguine, Pierre-Yves Brillet, Zouhour El Fekih, Rosa-Maria Bruno, Hélène Bihan, Emmanuel Cosson","doi":"10.1186/s12933-025-02933-z","DOIUrl":"10.1186/s12933-025-02933-z","url":null,"abstract":"<p><strong>Introduction: </strong>Epicardial adipose tissue (EAT) and arterial stiffness are determinants of excess risk of cardiovascular disease in persons with diabetes. This study aimed to evaluate the relationship between both of these conditions in a cohort of patients with diabetes.</p><p><strong>Materials and methods: </strong>A part retrospective, part prospective non-interventional cohort study of people living with diabetes who had (i) a computed tomography scan to measure both their coronary artery calcium score and EAT volume (proprietary prototype, GE HealthCare), and (ii) a finger-to-toe pulse wave velocity (PWV) measurement to assess arterial stiffness. The study's ClinicalTrials.gov identifier is NCT05681533.</p><p><strong>Results: </strong>A total of 345 participants (198 men, mean age (± standard deviation (SD)) 55.6 ± 12.6 years) were included; 73.6% had type 2 diabetes and 41.6% had obesity. Median duration of diabetes was 12 [interquartile range (IQR) 6-20] years. The median PWV was 8.0 [IQR 7.0-10.0] m/sec and median EAT volume was 84.9 [IQR 61.8-114.3] cm³. A positive correlation was observed between EAT volume and PWV (r = 0.37 [95% confidence interval (95%CI) 0.27-0.45], p < 0.001). EAT volume was associated with PWV tertile: specifically, participants in the first (≤ 7.0 m/sec), second, and third (> 9.0 m/sec) tertiles had, respectively, EAT volumes of 76.3 [IQR 50.3-100.6] cm³, 82.5 [IQR 64.4-107.3] cm³, and 100.2 [IQR 77.3-134.6] cm³ (p < 0.001 for all three). After adjustment for age, mean blood pressure, body mass index and diabetes type, each 10 cm³ increase in EAT volume was associated with a 14% increase in the probability of belonging to the third PWV tertile (odds ratio 1.14 [95%CI 1.06 - 1.21]; p < 0.001).</p><p><strong>Conclusion: </strong>EAT volume was associated with arterial stiffness in people living with diabetes. This association suggests that systemic inflammatory and metabolic mechanisms, through EAT and/or other associated ectopic adipose tissues, may contribute to an increased risk of cardiovascular disease.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"24 1","pages":"400"},"PeriodicalIF":10.6,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12522805/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145298400","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":"Safety, pharmacokinetics and pharmacodynamics of Plozasiran in Chinese healthy volunteers.","authors":"Fangfang Wang, Dong You, Xiaoye Niu, Jack Shi, Ye Li, Lihang Qi, Haiyan Li","doi":"10.1186/s12933-025-02929-9","DOIUrl":"10.1186/s12933-025-02929-9","url":null,"abstract":"<p><strong>Background: </strong>Plozasiran (VSA001, ARO-APOC3) is an RNA interference therapy that targets Apolipoprotein C3 (APOC3), a key regulator of lipoprotein metabolism. The study aimed at assessing the safety, tolerability, pharmacokinetics (PK), and pharmacodynamic (PD) profiles of plozasiran in Chinese healthy volunteers (HVs).</p><p><strong>Methods: </strong>In this double-blind, placebo-controlled, phase I clinical study, a total of 24 Chinese adult HVs received single subcutaneous (SC) injection of 25 mg, 50 mg plozasiran or placebo on day 1. Safety, tolerability, PK and PD profiles were accessed during a follow-up period of 85 days.</p><p><strong>Results: </strong>Eighteen HVs received plozasiran (25 mg: n = 9; 50 mg: n = 9) and 6 HVs received placebo. Plozasiran was well tolerated in Chinese HVs. No death, no severe adverse events or treatment-emergent adverse events (TEAEs) leading to discontinuation were observed. TEAEs were reported in 9 of 18 HVs from plozasiran group and in 1 of 6 HVs from placebo group. All TEAEs were transient and recovered autonomously, except for 2 subjects with 4 TEAEs from plozasiran group needed concomitant medications. After SC injection, plozasiran was rapidly absorbed and quickly eliminated in the plasma. Maximum geomean serum concentration was 102 ng/mL (CV%:36.4%) and 216 ng/mL (58.1%) for 25 mg and 50 mg group, respectively. The median T_max of the 25 mg and 50 mg groups was 3 h (2.00, 6.02) and 6 h (1.00, 6.00), respectively. The geomean AUC_0-t was 971 ng*h/mL (21.1%) and 2016 ng*h/mL (29.5%), and AUC_0-∞ was 999 ng*h/mL (20.80%) and 2148 ng*h/mL (27.0%), respectively. The geomean CL/F, V_z/F and t_1/2 of plozasiran 25 and 50 mg groups were 25.0 L/h (20.80%) and 23.3 L/h (27.0%), 120 L (41.8%) and 100 L (41.8%), 3.33 h (27.0%) and 2.99 h (22.0%), respectively. After subcutaneous injection of plozasiran, the concentrations of APOC3 and triglyceride (TG) decreased substantially in both treatment groups, reaching a steady-state level simultaneously (Days 8-29), which persisted until the end of the study (EOS). Maximum mean decreases in APOC3 were observed on day 29; 79.0% and 95.1% from baseline for 25 mg and 50 mg group, respectively, with corresponding reductions of TG of 64.5% and 71.3%. In addition, increase in HDL-C, and decreases in non-HDL-C, ApoB, LDL-C and VLDL-C were observed in plozasiran group. No noticeable change of PD parameters was observed in placebo group.</p><p><strong>Conclusions: </strong>Plozasiran at 25 and 50 mg was well tolerated with acceptable safety profile in Chinese HVs. Safety, PK and PD profiles observed in the present study were consistent with the data reported from clinical studies conducted outside China.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"24 1","pages":"399"},"PeriodicalIF":10.6,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12523034/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145298453","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":"Genetic variation in the glucagon-like peptide-1 receptor protein encoding region is associated with higher heart rate variability, but not with neurodegeneration of the brain, retina, and peripheral nerves: The Maastricht study.","authors":"Frank C T van der Heide, Indra L M Steens, Archana Singh-Manoux, Séverine Sabia, Tan Lai Zhou, Sebastian Köhler, Miranda T Schram, Carla J H van der Kallen, Tos T J M Berendschot, Carroll A B Webers, Marleen M J van Greevenbroek, Anke Wesselius, Ilja C W Arts, Jacobus F A Jansen, Walter H Backes, Thomas T van Sloten, Gabriëlla A M Blokland, Coen D A Stehouwer","doi":"10.1186/s12933-025-02888-1","DOIUrl":"10.1186/s12933-025-02888-1","url":null,"abstract":"<p><strong>Background: </strong>Degeneration of organ-specific nervous systems precede major clinical conditions such as heart failure, dementia, diabetic retinopathy, and diabetic neuropathy. Glucagon-like peptide-1 receptor (GLP1R) agonists may have neuroprotective effects, independent of their glucose-lowering effects, and as such may be tools for early prevention of neurodegeneration. We investigated whether genetic variation in the GLP1R protein encoding region, assessed using a genetic score, was associated with neurodegeneration measured in the heart, brain, retina, and peripheral nerves.</p><p><strong>Methods: </strong>Data from up to 7446 individuals from The Maastricht Study were used (mean [standard deviation (SD)] age 59.5 ([8.7] years, 49.4% men, and 20.0% with type 2 diabetes [by design]). A GLP1R score (0-8 points) was calculated using four genetic variants located in the GLP1R protein encoding region, with putative functional consequences on GLP1R activity (rs1042044, rs1004280, rs10305423, rs880067). Multivariable regression analysis was used to examine the associations between GLP1R genetic score and neural measures of the heart (time- and frequency-domain heart rate variability [HRV]), brain (magnetic resonance imaging-assessed local and global structural connectivity indices, brain volume, and global cognitive performance), retina (retinal nerve fiber layer thickness and retinal sensitivity) and peripheral nerves (conduction velocity). Associations were adjusted for age, sex, and HbA1c. Interaction with sex, age, and glucose metabolism status was examined.</p><p><strong>Results: </strong>In fully adjusted analyses, higher GLP1R genetic score (corresponding to higher predicted GLP1R protein expression) was significantly associated with higher time-domain HRV (per SD higher GLP1R score, 0.031 (0.006, 0.056) SD) and similarly, but not statistically significantly, with higher frequency-domain HRV (0.024 (- 0.001, 0.048) SD). The GLP1R genetic score was not significantly associated with brain, retinal, or peripheral nerves measures. Associations did not consistently differ as a function of age, sex, or glucose metabolism status.</p><p><strong>Conclusions: </strong>Higher putative GLP1R protein expression, assessed from genetic variation in the GLP1R protein encoding region, was significantly associated with lower levels of neurodegeneration in the heart, but not in the brain, retina, and peripheral nerves. Future clinical trials should test whether use of GLP1R agonists can contribute to prevention of cardiac autonomic nerve degeneration and associated clinical disease.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"24 1","pages":"397"},"PeriodicalIF":10.6,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12519852/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145291234","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":"Activated protein C ameliorates diabetes-induced atherosclerosis by sustaining macrophage efferocytosis.","authors":"Saira Ambreen, Amna Arif, Saikal Shamkeeva, Ahmed Elwakiel, Surinder Pal, Shihai Jiang, Muhammad Asad Farhan, Zuhir Halloul, John H Griffin, Berend Isermann, Khurrum Shahzad","doi":"10.1186/s12933-025-02965-5","DOIUrl":"10.1186/s12933-025-02965-5","url":null,"abstract":"<p><p>Macrophage efferocytosis, essential for the resolution of inflammation and plaque stability in atherosclerosis, is impaired in diabetes. Thrombomodulin (TM) and endothelial protein C receptor (EPCR), key mediators of protein C activation (PC), have vasculoprotective and anti-inflammatory roles, yet their involvement in macrophage efferocytosis in diabetes-induced atherosclerosis remains unclear. Here, we demonstrate that expression of EPCR was reduced in atherosclerotic lesions of diabetic patients compared to non-diabetic controls. In parallel, efferocytosis was impaired in atherosclerotic lesions and in monocytes derived macrophages of diabetic patients. In vitro, treatment with activated PC (aPC) or its cytoprotective selective variant (3K3A-aPC) restored high glucose-impaired macrophage efferocytosis. Mechanistic studies revealed that aPC restored efferocytosis through Arginase-1 and modulation of Rac1-ATF6 signaling. Additionally, macrophage protease-activated receptor 1 (PAR1) was identified as the key receptor mediating aPC's effects on efferocytosis. Mimicking biased PAR-1 signaling via parmodulin-2 reverses glucose impaired efferocytosis. In vivo, aPC treatment of diabetic ApoE^-/- mice increased MerTK expression in atherosclerotic lesions. aPC's vasculoprotective effects, including the reduction of plaque size, were abrogated upon MerTK inhibition using morpholinos, underscoring the pivotal role of MerTK in mediating aPC's atheroprotective actions. These findings suggest that impaired TM-PAR1-aPC signaling contributes to defective macrophage efferocytosis in diabetes-associated atherosclerosis and that aPC-based therapies may offer a novel strategy to enhance macrophage function and prevent diabetes induced atherosclerosis.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"24 1","pages":"396"},"PeriodicalIF":10.6,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12519743/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145285714","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 glucometabolic status on type 4a myocardial infarction in patients with non-ST-segment elevation myocardial infarction: the role of stress hyperglycemia ratio.","authors":"Matteo Armillotta, Luca Bergamaschi, Francesco Angeli, Marta Belmonte, Marcello Casuso Alvarez, Angelo Sansonetti, Damiano Fedele, Sara Amicone, Lisa Canton, Davide Bertolini, Andrea Impellizzeri, Francesca Bodega, Nicole Suma, Francesco Pio Tattilo, Daniele Cavallo, Ornella Di Iuorio, Khrystyna Ryabenko, Andrea Rinaldi, Francesco Saia, Gianni Casella, Jacopo Lenzi, Paola Rucci, Pasquale Paolisso, Carmine Pizzi","doi":"10.1186/s12933-025-02837-y","DOIUrl":"10.1186/s12933-025-02837-y","url":null,"abstract":"<p><strong>Background: </strong>Type 4a myocardial infarction (MI) is a relevant complication in non-ST-segment elevation myocardial infarction (NSTEMI) patients undergoing percutaneous coronary intervention (PCI). While glucometabolic status has been linked to type 4a MI in chronic coronary syndromes, data in the acute setting are lacking. This study aimed to assess the association of glucometabolic parameters-admission blood glucose (ABG), glycated hemoglobin (HbA1c) and stress hyperglycemia ratio (SHR)-with type 4a MI in NSTEMI patients undergoing PCI and evaluate their independent predictive role.</p><p><strong>Methods: </strong>Consecutive NSTEMI patients undergoing PCI from the AMIPE multicenter prospective registry (NCT03883711) with stable or falling pre-procedural cardiac troponin levels were analyzed. The optimal glucometabolic predictor of type 4a MI among ABG, HbA1c and SHR was identified using receiver operating characteristic analysis. The best cut-off for each parameter was derived using Youden's index. Regression analysis and Kaplan-Meier curves were performed to identify independent predictors of type 4a MI and their prognostic implications.</p><p><strong>Results: </strong>The study population included 1005 patients (mean age 70.3 ± 12.5 years, 25.5% females), with 45.9% having diabetes mellitus. SHR showed a significantly higher accuracy (AUC 0.69, 95% CI 0.65-0.73) in predicting type 4a MI compared with ABG and HbA1c (p < 0.001), with an optimal cut-off of 1.14, consistent across diabetic and non-diabetic patients. SHR > 1.14 was independently associated with type 4a MI (aOR = 2.73; 95% CI 1.70-4.42; p < 0.001), unlike ABG and HbA1c, and was also linked to an increased risk of long-term major adverse cardiovascular events (p < 0.001).</p><p><strong>Conclusions: </strong>SHR emerged as a strong predictor of type 4a MI in NSTEMI patients undergoing PCI, outperforming other glucometabolic markers.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"24 1","pages":"394"},"PeriodicalIF":10.6,"publicationDate":"2025-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12514836/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145273891","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}