Cardiovascular Diabetology最新文献

{"title":"STIM1-mediated Treg instability in HFpEF: a new immunological target emerges?","authors":"Anna Planavila, Albert Blasco-Roset","doi":"10.1186/s12933-026-03317-7","DOIUrl":"10.1186/s12933-026-03317-7","url":null,"abstract":"<p><p>Heart failure with preserved ejection fraction (HFpEF) accounts for nearly half of all heart failure cases and remains a major unmet clinical challenge. Increasing evidence supports the view of HFpEF as a systemic inflammatory syndrome driven by aging and cardiometabolic comorbidities, including obesity, hypertension, and chronic kidney disease. Within this framework, regulatory T cells (Tregs), which are essential for maintaining immune tolerance and limiting excessive inflammation, have emerged as important modulators of disease progression. However, the mechanisms underlying Treg dysfunction in HFpEF have remained poorly understood. In this issue, Srinivas et al. identify stromal interaction molecule 1 (STIM1)-dependent calcium signaling as a critical regulator of Treg instability in HFpEF. The authors show that patients with HFpEF exhibit reduced circulating Treg numbers, increased STIM1 expression, and activation of endoplasmic reticulum stress, apoptotic, and inflammatory pathways. Using a cardiometabolic murine model and Treg-specific STIM1 knockout mice, they establish a causal role for Treg-intrinsic STIM1 signaling in disease development. These findings position STIM1 as a molecular link between cardiometabolic stress, immune dysregulation, and cardiac remodeling. They further support the concept that immune-cell plasticity is a major determinant of HFpEF pathogenesis and suggest that preserving Treg stability may represent a novel therapeutic strategy. Although important questions remain regarding disease timing, clinical translation, and sex-specific effects, this work advances our understanding of HFpEF as an immune-mediated disorder and identifies STIM1-dependent calcium signaling as a promising therapeutic target.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"25 1","pages":""},"PeriodicalIF":15.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13428441/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148653194","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":"Effect of empagliflozin on copeptin levels in patients with recent acute coronary syndrome and newly detected dysglycaemia: a post-hoc analysis of the SOCOGAMI randomized controlled trial.","authors":"Elena Fortin, Olle Melander, Giulia Ferrannini, Per Näsman, Anna Norhammar, Lars Rydén, Stina Smetana, Malin Svensson, Linda Mellbin","doi":"10.1186/s12933-026-03312-y","DOIUrl":"10.1186/s12933-026-03312-y","url":null,"abstract":"<p><strong>Background: </strong>Copeptin, a surrogate marker for vasopressin secretion, is associated with cardiovascular disease, insulin resistance and dysglycaemia. The cardioprotective effects of sodium-glucose cotransporter 2 inhibitors (SGLT2i) may involve vasopressin modulation through fluid redistribution, but whether this effect persists long-term in high-cardiovascular-risk patients with newly detected dysglycaemia remains unknown.</p><p><strong>Methods: </strong>In this post-hoc analysis of the SOCOGAMI double-blind, placebo-controlled trial, 42 patients (mean age 67.5 years, 19% females) with impaired glucose tolerance or newly detected type 2 diabetes following an ACS and no heart failure were randomized to empagliflozin 25 mg/day (n = 20) or placebo (n = 22) for 7 months. Copeptin was measured during oral glucose tolerance tests (OGTT) at baseline, after 7 months on-treatment, and 3 months after treatment withdrawal. Treatment effects were assessed by repeated-measures ANOVA with treatment × time interaction and linear mixed-effects models.</p><p><strong>Results: </strong>Haematocrit, but not copeptin, showed a significant between-group difference at 7 months (p = 0.03 and p = 0.63, respectively). Both markers returned toward baseline after treatment withdrawal, but the overall treatment × time interaction was not significant for either (p = 0.72 and p = 0.64 respectively). Results were unchanged after accounting for a baseline imbalance in diuretic use (35% vs. 14%). Copeptin was not associated with the glucose-lowering effect of empagliflozin and no differential copeptin response during the OGTT across groups or visits was observed. In exploratory analyses, copeptin correlated with arterial pulse wave velocity at baseline (rs = 0.40, unadjusted p = 0.03).</p><p><strong>Conclusions: </strong>In this post-hoc analysis, empagliflozin treatment was not associated with statistically significant sustained vasopressin secretion in post-ACS patients with newly detected dysglycaemia and preserved cardiac function. Due to the limited power and the absence of early on-treatment sampling these findings cannot exclude AVP modulation and warrant confirmation in adequately powered studies.</p><p><strong>Trial registration: </strong>EudraCT number 2015-004571-73.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"25 1","pages":""},"PeriodicalIF":15.6,"publicationDate":"2026-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13411128/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148599385","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":"Longitudinal inflammatory-metabolic-adiposity burden and incident heart failure across cardiovascular-kidney-metabolic stages: a prospective cohort study.","authors":"Fangyi Dai, Yong Dai","doi":"10.1186/s12933-026-03310-0","DOIUrl":"10.1186/s12933-026-03310-0","url":null,"abstract":"<p><strong>Background: </strong>Heart failure remains a major health burden among older adults. Although systemic inflammation, metabolic dysregulation, and central adiposity are individually recognized as heart failure risk factors, composite biomarkers capturing their longitudinal convergence and interaction with cardiovascular-kidney-metabolic (CKM) staging remain unexplored.</p><p><strong>Objectives: </strong>To investigate the association of longitudinal CTGW composite index (C-reactive protein × triglyceride-glucose index × waist-to-height ratio) trajectories and cumulative burden with incident heart failure, and to examine effect modification by baseline CKM stage.</p><p><strong>Methods: </strong>This prospective cohort study included 1946 participants aged 50 years and older from the English Longitudinal Study of Ageing, free of heart failure at Wave 2 (2004-2005), followed through Wave 8 (2016-2017). Group-based multi-trajectory modeling jointly classified longitudinal CRP, triglycerides, glucose, and WHtR across three waves. Cumulative CTGW burden was quantified using the trapezoidal rule. Cox proportional hazards regression with sequential adjustment and restricted cubic spline analyses were employed.</p><p><strong>Results: </strong>Over a median follow-up spanning 12 years, 113 participants (5.8%) developed incident heart failure. Three distinct trajectories were identified: low-stable (n = 697, 35.8%), moderate-metabolic (n = 943, 48.5%), and high-inflammatory (n = 306, 15.7%). In fully adjusted models, the high-inflammatory trajectory conferred the greatest risk (HR = 2.69, 95% CI 1.46-4.93, P = 0.001), followed by the moderate-metabolic trajectory (HR = 1.96, 95% CI 1.17-3.29, P = 0.011). For cumulative burden, the highest quartile was significantly associated with incident heart failure (HR = 2.35, 95% CI 1.31-4.24, P = 0.004; P for trend < 0.001), with each standard deviation increase corresponding to 19% higher risk (HR = 1.19, 95% CI 1.04-1.36, P = 0.014). A nonlinear dose-response relationship was confirmed (P for nonlinearity = 0.032), with the risk threshold identified at approximately 8.2. Stratified analyses revealed significant effect modification by CKM stage (P for interaction = 0.031), with the strongest association observed in Stage 3-4 (HR = 2.37, 95% CI 1.24-4.53, P = 0.009). Subgroup analyses demonstrated consistent effect directions across age, sex, BMI, and comorbidity strata without significant interactions.</p><p><strong>Conclusions: </strong>Longitudinal CTGW trajectories and cumulative burden are independently associated with incident heart failure in a nonlinear dose-response manner, with the association amplified across advancing CKM stages, supporting the CTGW composite index as a potential integrative biomarker for heart failure risk stratification.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"25 1","pages":""},"PeriodicalIF":15.6,"publicationDate":"2026-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13540904/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148886672","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 the triglyceride-glucose index with subclinical left ventricular dysfunction in type 2 diabetes mellitus: mediation by myocardial energetic efficiency and resting perfusion.","authors":"Li Jiang, Yuan Li, Hua-Yan Xu, Xue-Ming Li, Ke Shi, Jin Wang, Shi-Qin Yu, Yu Jiang, Han Fang, Wei-Feng Yan, Ying-Kun Guo, Zhi-Gang Yang","doi":"10.1186/s12933-026-03308-8","DOIUrl":"10.1186/s12933-026-03308-8","url":null,"abstract":"<p><strong>Background: </strong>The triglyceride-glucose(TyG) index, a surrogate marker of insulin resistance, has been linked to cardiac dysfunction; however, its underlying associated pathways in patients with type 2 diabetes mellitus(T2DM) remain unclear. This study used cardiac magnetic resonance(CMR) to explore the association of TyG index with subclinical left ventricular(LV) myocardial dysfunction and whether imaging indicators statistically mediate this relationship.</p><p><strong>Methods: </strong>In this retrospective cross-sectional study, a total of 235 T2DM patients who underwent CMR examination were included and assigned to three groups based on the tertiles of their TyG indexes as follows: low(< 8.73, n = 78), moderate(8.73-9.36, n = 79), and high TyG index(≥ 9.36, n = 78) groups. LV geometry, function, myocardial energetic efficiency index (MEEi), resting first-pass perfusion, and global peak strain in radial(GRPS), circumferential(GCPS), and longitudinal(GLPS) directions were measured. Univariate and multivariate linear regression models and exploratory mediation analysis were used to analyze the associations of TyG index on LV global strain.</p><p><strong>Results: </strong>Compared with the low and moderate TyG index groups, the high TyG index group had significantly higher LV remodeling index, lower LV global function index, lower MEEi, impaired resting myocardial perfusion, and reduced LV global peak strain (all p ≤ 0.002). Multivariate analysis showed that TyG index remained independently associated with reduced LV strain after adjusting for confounders (GRPS β = -0.261; GCPS β = 0.271; GLPS β = 0.381; all p < 0.001). And MEEi and upslope were also independently associated with reduced LV GRPS and GLPS (all p < 0.05). Further mediation analysis revealed the statistically mediated proportions of the association between the TyG index and LV global strain were 8.2-8.6% for MEEi and 4.3% to 12.5% for upslope. In model comparison analyses, the TyG index demonstrated substantially better model fit than either component alone across all strain directions (all Akaike Information Criterion difference > 150).</p><p><strong>Conclusions: </strong>In patients with T2DM, a higher TyG index is independently associated with decreased LV global strain, and this relationship is statistically mediated by reduced MEEi and impaired resting perfusion upslope. These findings generate hypotheses regarding myocardial energetics and resting perfusion as potential pathways associated with diabetic myocardial dysfunction that warrant prospective investigation.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"25 1","pages":""},"PeriodicalIF":15.6,"publicationDate":"2026-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13435890/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148668429","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":"Baseline, repeated-measure burden, and two-time-point patterns of the triglyceride-glucose index-visceral lipid ratio (TyG-VLR) and incident cardiovascular disease in cardiovascular-kidney-metabolic (CKM) syndrome stages 0-3: a longitudinal China Health and Retirement Longitudinal Study (CHARLS) analysis.","authors":"Ao-Men Lu, Hao-Jie Han, Qian Xu, Shuang-Ke Bai","doi":"10.1186/s12933-026-03302-0","DOIUrl":"10.1186/s12933-026-03302-0","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Cardiovascular-kidney-metabolic (CKM) syndrome stages 0-3 define a population without overt clinical cardiovascular disease (CVD) but with accumulating metabolic, adiposity, lipid, and kidney-related risk. We evaluated whether baseline triglyceride-glucose-visceral lipid ratio (TyG-VLR), repeated-measure TyG-VLR burden, and two-time-point TyG-VLR patterns were associated with incident CVD and CVD subtypes in CHARLS.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Data were obtained from the China Health and Retirement Longitudinal Study (CHARLS), with follow-up through the 2020 wave. CKM stages were operationalized using CHARLS-available measures of adiposity, prediabetes, diabetes, hypertension, dyslipidemia, chronic kidney disease, metabolic syndrome, predicted CVD risk, and clinical CVD status. TyG-VLR was calculated as TyG multiplied by the visceral lipid ratio (VLR; LDL-C × Chinese visceral adiposity index). Repeated-measure TyG-VLR burden was calculated as the average of Wave 1 and Wave 3 values multiplied by the interval between assessments before the landmark follow-up period. K-means clustering of standardized Wave 1 and Wave 3 TyG-VLR identified two-time-point patterns based on the available repeated measurements. Cox proportional hazards models, dose-response analyses, marker-specific comparisons, and prespecified sensitivity analyses were performed.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The baseline analytic cohort included 7,132 participants with CKM stages 0-3 and 1,688 incident CVD events; the median follow-up for CVD was 9.00 years (IQR, 7.00-9.00). The repeated-measure/two-time-point cohort included 4,111 participants and 777 incident CVD events; the median landmark follow-up was 5.00 years (IQR, 4.92-5.00). Each 1-SD increase in baseline TyG-VLR was associated with incident CVD (HR 1.15, 95% CI 1.10-1.21), heart disease (HR 1.11, 95% CI 1.05-1.18), and stroke (HR 1.21, 95% CI 1.12-1.31). Repeated-measure TyG-VLR burden was associated with CVD (HR 1.21, 95% CI 1.12-1.30), and the highest two-time-point pattern group had greater CVD risk than the lowest group (HR 1.51, 95% CI 1.22-1.85). Restricted cubic spline and Kaplan-Meier analyses showed graded CVD risk patterns, whereas marker-specific comparisons showed that TyG-VLR performed broadly similarly to VLR, CVAI, and TyG-CVAI. Incremental discrimination beyond traditional factors and adapted CKM stage was modest. Associations remained consistent in inverse probability-weighted, multiple-imputation, alternative-formulation, and competing-risk analyses.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;In middle-aged and older adults with adapted CKM syndrome stages 0-3, higher baseline TyG-VLR, repeated-measure TyG-VLR burden, and higher two-time-point TyG-VLR patterns were associated with incident CVD, particularly stroke. TyG-VLR may be interpreted as an epidemiological marker of combined metabolic, lipid, and adiposity burden, with potential value for population-level risk charact","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"25 1","pages":""},"PeriodicalIF":15.6,"publicationDate":"2026-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13452125/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148696972","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":"Treatment with dapagliflozin and empagliflozin reduces concentrations of N4-acetylcytidine in plasma, a biomarker associated with vascular damage.","authors":"Arne Gessner, Dennis Kannenkeril, Agnes Bosch, Joanna M Harazny, Martin F Fromm, Hannah Klinkhammer, Christian Staerk, Andreas Mayr, Roland E Schmieder, Renke Maas","doi":"10.1186/s12933-026-03292-z","DOIUrl":"10.1186/s12933-026-03292-z","url":null,"abstract":"<p><strong>Background: </strong>Inhibitors of the sodium-glucose cotransporter 2 (SGLT2) provide cardiovascular and renal protection in both diabetic and non-diabetic patients at least in part independently of glycaemic control. Some underlying mechanisms for these clinically beneficial effects were suggested, but the picture is far from complete. In this study we aimed to apply untargeted metabolomics in order to identify new mechanistic leads.</p><p><strong>Methods: </strong>Plasma and 24-hour urine samples of 48 diabetic patients taken before and after 6 weeks of treatment from two prospective, randomized, double-blind, placebo-controlled, cross-over trials with dapagliflozin or empagliflozin were used. Additionally, plasma and urine samples of 24 diabetic patients from a prospective, randomized, controlled, parallel-arm, interventional, open-label, single centre study with either empagliflozin and linagliptin or metformin and insulin glargine for 12 weeks were used for confirmation. Changes of metabolite patterns in plasma and urine were determined by untargeted high-resolution mass spectrometry. Moreover, parameters of arterial stiffness and retinal vascular remodelling were correlated with treatment effects of the SGLT2 inhibitors on the modified nucleoside N4-acetylcytidine (ac4C), a potential biomarker for the activity of the enzyme N-acetyltransferase 10 (NAT10).</p><p><strong>Results: </strong>In accordance with previously reported results treatment with SGLT2 inhibitors led to a reduction of glucose (log₂fc: - 0.23, adj. p < 0.01) and uric acid (log₂fc: - 0.23, adj. p < 0.001), while 3-hydroxybutyric acid (log₂fc: 0.84, adj. p < 0.001) and 3-hydroxybutyrylcarnitine (log₂fc: 0.57, adj. p < 0.001) were increased in plasma. As a new finding, plasma concentrations of ac4C were reduced (log₂fc: - 0.32, adj. p < 0.001) by SGLT2 inhibitors but not by the non-SGLT2 inhibiting glucose lowering treatment. Reduction of urinary concentrations of ac4C corresponded to its reduction in plasma in groups treated with the SGLT2 inhibitors. Wall thickness of retinal arterioles and central systolic blood pressure were significantly correlated to ac4C in plasma.</p><p><strong>Conclusions: </strong>Treatment with dapagliflozin and empagliflozin reduced plasma concentrations of ac4C, which was correlated with parameters for vascular health. These exploratory findings may indicate inhibition of NAT10 activity as a potential contributor to the beneficial effects on cardiovascular and renal health by SGLT2 inhibitors.</p><p><strong>Trial registrations: </strong>http://www.</p><p><strong>Clinicaltrials: </strong>gov : NCT02383238, NCT02471963, NCT02752113.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"25 1","pages":""},"PeriodicalIF":15.6,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13401296/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148583823","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":"Genetically proxied glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide receptor pathway modulation is associated with favorable aging phenotypes: a drug-target Mendelian randomization study.","authors":"Jiang Li, Jie Li, Xiaoqin Xu, Ningjian Wang, Yingli Lu, Bin Wang","doi":"10.1186/s12933-026-03304-y","DOIUrl":"10.1186/s12933-026-03304-y","url":null,"abstract":"<p><strong>Background: </strong>Glucagon-like peptide-1 receptor (GLP1R) agonists and dual glucose-dependent insulinotropic polypeptide receptor/glucagon-like peptide-1 receptor (GIPR/GLP1R) agonists are established treatments for diabetes and obesity, but their potential effects on biological aging remain uncertain.</p><p><strong>Methods: </strong>In this drug target Mendelian randomization study, we assessed the associations of genetically proxied modulation of GLP1R, GIPR, and dual GIPR/GLP1R pathways with four aging phenotypes, including frailty index, phenotypic age (PhenoAge) acceleration, telomere length, and longevity.</p><p><strong>Results: </strong>Glycated hemoglobin (HbA1c) lowering via GIPR, modeling the glucose-lowering effect of variants in GIPR loci, was consistently associated with a lower frailty index (primary dataset: β = - 0.10 [95% CI: - 0.18, - 0.02]; replication dataset: - 0.14 [- 0.27, - 0.01]), reduced PhenoAge acceleration (primary: - 0.82 [- 1.17, - 0.48]; replication - 1.04 [- 1.81, - 0.27]), longer telomere length (primary: 0.06 [0.003, 0.11]; replication: 0.09 [0.002, 0.19]), and greater odds of longevity (primary: odds ratio [OR] = 2.90 [95% CI: 1.93, 4.36]; replication: 6.54 [2.92, 14.65]). Body mass index (BMI) lowering via GIPR, modeling appetite-suppressing and weight-reducing effects of variants, was associated with a lower frailty index (primary: - 0.07 [- 0.13, - 0.01]; replication: - 0.19 [- 0.35, - 0.04]) and higher odds of longevity (primary: 2.11 [1.22, 3.66]). In contrast, HbA1c lowering via GLP1R was associated exclusively with longevity (primary: OR = 3.72 [2.25, 6.18]; replication: 16.53 [4.28, 63.80]), whereas BMI lowering via GLP1R was not associated with any aging phenotype. Analyses of dual GIPR/GLP1R yielded results broadly similar to those for GIPR, with the exception of a null effect on frailty index.</p><p><strong>Conclusions: </strong>Genetically proxied HbA1c- and BMI-lowering effects through GLP1R- and GIPR-related pathways were favorably associated with aging phenotypes, with broader associations observed for HbA1c lowering. Further clinical studies are warranted to clarify the relevance of these pathways to healthy aging.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"25 1","pages":""},"PeriodicalIF":15.6,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13504813/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148817226","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 body mass index reduction and epicardial adipose tissue changes across pharmacological and lifestyle interventions: a multilevel meta-regression analysis.","authors":"Aleksandra Mączyńska, Piotr Olbryś, Mateusz Smoliński, Miłosz Rosa, Marta Kacperska, Milena Froń, Paweł Leśniewski, Oliwia Łuniewska, Adam Sander, Maciej Mączewski, Hanna Czerwińska, Aleksandra Paterek, Michał Mączewski","doi":"10.1186/s12933-026-03299-6","DOIUrl":"https://doi.org/10.1186/s12933-026-03299-6","url":null,"abstract":"<p><strong>Background: </strong>Epicardial adipose tissue (EAT) is a metabolically active visceral fat depot implicated in cardiometabolic disease. Although EAT reductions are commonly attributed to weight loss, the extent to which EAT change is explained by body mass index (BMI) reduction versus intervention-specific effects remains unclear.</p><p><strong>Methods: </strong>We performed a systematic review and multilevel meta-regression of interventional studies reporting pre- and post-intervention changes in EAT and BMI. MEDLINE, Embase, and Cochrane CENTRAL were searched from inception to April 2026. Standardized mean change using pre-test standardization (SMCR) was calculated for both outcomes. Multilevel meta-regression assessed the association between BMI and EAT change while adjusting for intervention class, follow-up duration, and imaging modality. BMI-adjusted residual analyses were used descriptively to evaluate deviations from model-predicted EAT responses.</p><p><strong>Results: </strong>Forty-two studies comprising 50 intervention arms and 1,890 participants were included. Across all interventions, both EAT and BMI decreased significantly. In the multivariable meta-regression model, BMI reduction was associated with EAT reduction (β = 0.19, p = 0.03), although BMI explained only a limited proportion of variability in EAT response. Intervention class remained a significant moderator of EAT change (p < 0.001). Larger observed reductions in EAT were seen with dietary interventions, GLP-1 receptor agonists, and bariatric surgery. In descriptive residual analyses, dietary interventions and GLP-1 receptor agonists demonstrated greater-than-predicted reductions in EAT relative to the overall study-level BMI-EAT relationship. These findings should be interpreted cautiously because intervention-specific comparisons were exploratory and do not constitute formal comparative efficacy estimates.</p><p><strong>Discussion: </strong>EAT reduction is only partially explained by systemic weight loss, and substantial heterogeneity exists across intervention classes. These findings support the concept that EAT remodeling may be influenced by factors beyond generalized adiposity reduction. However, intervention-specific patterns observed in this study are descriptive and hypothesis-generating and require confirmation in adequately powered comparative studies. Moreover, overall certainty of evidence was low for pooled EAT reduction and very low for intervention-specific comparative patterns.</p><p><strong>Trial registration: </strong>PROSPERO (CRD420261367140).</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":" ","pages":""},"PeriodicalIF":15.6,"publicationDate":"2026-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148497168","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":"Lipoprotein(a), insulin resistance, and cardiovascular outcomes in metabolic dysfunction-associated steatotic liver disease.","authors":"Bingtian Dong, Yuping Chen, Fang He, Biao Li, Biao Wu, Zhengdong Chen, Enfa Zhao, Yongjian Chen, Chaoxue Zhang","doi":"10.1186/s12933-026-03294-x","DOIUrl":"10.1186/s12933-026-03294-x","url":null,"abstract":"<p><strong>Background: </strong>Metabolic dysfunction-associated steatotic liver disease (MASLD) is associated with increased cardiovascular disease (CVD) risk. Lipoprotein(a) [Lp(a)] and insulin resistance (IR) are established cardiovascular risk factors, yet their joint associations with cardiovascular outcomes in MASLD remain poorly understood.</p><p><strong>Methods: </strong>We analyzed data from the UK Biobank and included 101,348 adults with MASLD for CVD mortality analyses and 94,089 individuals without baseline CVD for incident CVD analyses. IR was assessed using the triglyceride-glucose (TyG) index. Participants were categorized according to Lp(a) levels (< 125 vs. ≥ 125 nmol/L) and TyG index (low vs. high, defined by the 75th percentile) and further classified into four joint Lp(a)/IR groups, with low Lp(a)/low IR serving as the reference group. Cox proportional hazards models were used to evaluate associations of Lp(a), TyG, and their combined categories with incident CVD and CVD mortality.</p><p><strong>Results: </strong>During a median follow-up of 15.7 years, elevated Lp(a) and higher TyG levels were each independently associated with increased risks of incident CVD and CVD mortality, regardless of each other's status. In the fully adjusted model, each SD increase in Lp(a) was associated with a 14% higher risk of CVD mortality (HR, 1.14; 95% CI 1.10-1.19; P < 0.001) and a 9% higher risk of incident CVD (HR, 1.09; 95% CI, 1.07-1.11; P < 0.001). Similarly, each SD increase in TyG was associated with a 27% higher risk of CVD mortality (HR, 1.27; 95% CI 1.21-1.34; P < 0.001) and a 9% higher risk of incident CVD (HR, 1.09; 95% CI 1.07-1.12; P < 0.001). Compared with participants in the reference group with Lp(a) < 125 nmol/L and low IR, those with concomitantly elevated Lp(a) and high IR exhibited the highest cardiovascular risk, with adjusted HRs of 2.04 (95% CI 1.63-2.55) for CVD mortality and 1.49 (95% CI 1.35-1.64) for incident CVD (both P < 0.001), with a significant dose-response trend across groups (P for trend < 0.001). These associations remained consistent across subgroups stratified by age, sex, obesity, diabetes, and hypertension.</p><p><strong>Conclusions: </strong>Elevated Lp(a) and IR were independently associated with adverse cardiovascular outcomes in MASLD, with the highest risk observed among individuals with concomitant elevations in both markers.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":" ","pages":""},"PeriodicalIF":15.6,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13393937/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148469059","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":"Associations of cumulative exposure and dynamic trajectories of the cholesterol-HDL-glucose index and its obesity-related derivatives with cardiovascular disease: a nationwide prospective cohort study.","authors":"Han Wang, Guirong Song, Guorong Li, Dongmei Hu, Ying Zhang, Zhuowei Sun, Chenxi Zhai, Dongyong Zhang, Xiao Tang","doi":"10.1186/s12933-026-03295-w","DOIUrl":"10.1186/s12933-026-03295-w","url":null,"abstract":"<p><strong>Background: </strong>Integrating metabolic biomarkers with anthropometric indicators has been shown to enhance the discriminative capacity for cardiovascular disease (CVD). However, the impact of the cholesterol-HDL-glucose index (CHG) and its derivatives on CVD risk remains unclear. This study aimed to investigate the associations of CHG and its derivatives with CVD and to compare their discriminative performance.</p><p><strong>Methods: </strong>This prospective study included 3,359 CVD-free participants from the China Health and Retirement Longitudinal Study (CHARLS). Repeated measurements obtained in 2011 and 2015 were used to derive cumulative exposure and longitudinal trajectory patterns of CHG and its derivatives. Associations of baseline values, cumulative exposure, and longitudinal trajectories of these indicators with incident CVD and stroke were examined using Cox proportional hazards regression models.</p><p><strong>Results: </strong>During a median follow-up of 5 years, 466 participants (13.9%) developed CVD. Both CHG and its derivatives were significantly associated with CVD across baseline measurements, cumulative exposure, and longitudinal trajectories. Cumulative CHG derivatives showed significantly better discriminative power than isolated cumulative CHG (Delong's test P < 0.05), with the highest associations observed for cumulative CHG-waist circumference (HR = 1.29) and cumulative CHG-Chinese visceral adiposity index (HR = 1.28). Regarding trajectory patterns, participants with stably high CHG-CVAI exhibited the greatest risk compared with those maintaining stable low levels (HR = 1.79), followed by CHG-WC (HR = 1.65). Additionally, ascending and declining trajectories of both CHG-CVAI and CHG-WC were associated with increased CVD risk (ascending CHG-CVAI: HR = 1.79; declining CHG-CVAI: HR = 1.54; ascending CHG-WC: HR = 1.45; declining CHG-WC: HR = 1.54).</p><p><strong>Conclusions: </strong>CHG and its derivatives were strongly associated with incident CVD, with CHG-CVAI and CHG-WC exhibiting the most pronounced associations. Moreover, ascending and declining trajectories of CHG-CVAI and CHG-WC were linked to higher risk, highlighting the importance of tracking dynamic increases while also accounting for baseline metabolic status. These indicators may facilitate the identification of individuals at elevated risk for CVD.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":" ","pages":""},"PeriodicalIF":15.6,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13487984/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148469101","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}