Cardiovascular Diabetology最新文献

{"title":"Henagliflozin attenuates adverse ventricular remodeling and improves cardiometabolic parameters in patients with type 2 diabetes and hypertension: real-world evidence from a propensity score-matched analysis.","authors":"Nianfang Luo, Yutao Liu, Yue Zhang, Bingxi Liu, Mengjiao Li, Kangyan Guo, Liuren Zhang, Jingyi Zhang","doi":"10.1186/s12933-026-03285-y","DOIUrl":"10.1186/s12933-026-03285-y","url":null,"abstract":"<p><strong>Background: </strong>Henagliflozin has demonstrated favorable glycemic and metabolic effects in phase III trials. However, real-world evidence regarding its impact on cardiac structure-particularly left ventricular mass index (LVMI)-in patients with type 2 diabetes mellitus (T2DM) and concomitant hypertension remains lacking.</p><p><strong>Methods: </strong>In this single-center, retrospective cohort study, 183 patients with T2DM and hypertension were enrolled. After 1:1 propensity score matching, 132 patients (henagliflozin group, n = 66; control group, n = 66) were included in the primary analysis. The henagliflozin group received henagliflozin 10 mg once daily added to standard-of-care therapy, whereas the control group received standard therapy alone. The primary outcome was the change in LVMI from baseline to 6 months. Secondary outcomes included changes in other echocardiographic parameters (LVEF, E/e', left atrial diameter, LVEDd, IVSd, LVPWT), glycemic indices (FPG, HbA1c), blood pressure, body mass index (BMI), inflammatory markers, and renal function.</p><p><strong>Results: </strong>At 6 months, LVMI decreased in the henagliflozin group (from 87.90 ± 18.32 to 85.28 ± 18.20 g/m²; mean change - 2.62 ± 13.00 g/m²) but increased in the control group (from 83.46 ± 18.22 to 87.81 ± 16.53 g/m²; mean change + 4.35 ± 15.88 g/m²; between-group P = 0.007). Additionally, henagliflozin treatment was associated with significant reductions in left atrial diameter (between-group P = 0.035), E/e' ratio (P = 0.044), interventricular septal thickness (P = 0.030), and left ventricular posterior wall thickness (P = 0.018), as well as a modest increase in LVEF (P = 0.045). Compared with the control group, the henagliflozin group also exhibited greater reductions in fasting plasma glucose (- 0.97 vs. + 0.16 mmol/L; P = 0.037), HbA1c (- 0.42% vs. + 0.04%; P = 0.021), systolic blood pressure (- 9.45 vs. - 1.95 mmHg; P = 0.023), diastolic blood pressure (- 3.38 vs. 0.68 mmHg; P = 0.029), and BMI (- 0.45 vs. 0.00 kg/m²; P = 0.023).</p><p><strong>Conclusions: </strong>In patients with T2DM and hypertension, the addition of henagliflozin to standard therapy over 6 months was associated with significant attenuation of adverse ventricular remodeling-as evidenced by reductions in LVMI, left atrial diameter, and diastolic filling indices-alongside clinically meaningful improvements in glycemic control, blood pressure, and body weight.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":" ","pages":""},"PeriodicalIF":15.6,"publicationDate":"2026-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13640101/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148418961","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":"Frailty may confound the association between MASLD and cardiovascular mortality in people with cardiometabolic risk factors.","authors":"Ruoting Wang, Wenli Li, Jeffrey V Lazarus, Gabriele G Schiattarella, Gregory Y H Lip, Yingxin Liu, Yujiong Chen, Lu Qi, Harriette G C Van Spall, Guowei Li","doi":"10.1186/s12933-026-03284-z","DOIUrl":"10.1186/s12933-026-03284-z","url":null,"abstract":"<p><strong>Background: </strong>While metabolic dysfunction-associated steatotic liver disease (MASLD) has been consistently associated with increased cardiovascular risk in the general population, its association with cardiovascular disease (CVD) mortality in adults with established cardiometabolic risk factor (including obesity, hypertension, diabetes mellitus, or dyslipidemia) remains inconsistent. We aimed to determine whether frailty confounds the MASLD-CVD mortality association.</p><p><strong>Methods: </strong>We analyzed 10,413 US NHANES III adults with ≥ 1 cardiometabolic risk factor. Frailty was quantified using a 49-item frailty index (FI, ranging from 0 [maximal robustness] to 1 [severe frailty]) and categorized into quartiles. Associations between MASLD and CVD mortality were assessed using multivariable Cox proportional hazards models with and without frailty adjustment. Interaction and mediation analyses were also performed.</p><p><strong>Results: </strong>Over a mean follow-up of 23.36 years, 1,375 (13.20%) CVD deaths occurred. Frailty was significantly associated with both MASLD and CVD mortality. There was no evidence of interaction between MASLD and frailty, and mediation analysis showed no indirect effect of MASLD on CVD mortality through frailty. In absence of frailty adjustment, MASLD was not associated with CVD mortality (HR = 0.92, 95% CI: 0.78-1.10). After adjustment for frailty, MASLD was independently associated with higher CVD mortality (HR = 1.19, 95% CI: 1.07-1.32). Stratified by FI quartiles, significant associations were observed only in the higher frailty quartiles (Q3: HR = 1.35, 95% CI: 1.03-1.77; Q4: HR = 1.70, 95% CI: 1.07-2.69). The population attributable fraction of MASLD for CVD mortality was 10.1-12.5% after frailty adjustment.</p><p><strong>Conclusions: </strong>Frailty may confound the MASLD-CVD mortality relationship in people with cardiometabolic risk factors. The association between MASLD and CVD mortality is detected only when frailty is adjusted for.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":" ","pages":""},"PeriodicalIF":15.6,"publicationDate":"2026-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13640381/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148418985","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":"Comparative effectiveness of dual antiplatelet therapy after revascularization in diabetes and chronic limb-threatening ischemia: a target trial emulation study.","authors":"Cheng-Wei Lin, Pi-Hua Liu, Chia-Hung Lin, Chung-Huei Huang, Shih-Yuan Hung, I-Wen Chen, Yi-Chia Chen, Yu-Yao Huang","doi":"10.1186/s12933-026-03290-1","DOIUrl":"10.1186/s12933-026-03290-1","url":null,"abstract":"<p><strong>Background: </strong>Patients with diabetes and chronic limb-threatening ischemia (CLTI) face high risks of adverse limb and cardiovascular events. While post-revascularization dual antiplatelet therapy (DAPT) is generally recommended, the optimal regimen remains uncertain. This study aimed to compare the effectiveness of different DAPT strategies with respect to long-term clinical outcomes.</p><p><strong>Methods: </strong>We conducted a nationwide 90-day landmark observational analysis informed by a target trial framework based on healthcare claims data from Taiwan. The cohort included adults with type 2 diabetes who underwent lower-extremity revascularization for new-onset CLTI between 2016 and 2019. Patients were classified according to the post-procedural DAPT strategy initiated within a 90-day grace period. Inverse probability of treatment weighting (IPTW) was used to balance baseline covariates. The outcomes assessed were lower-extremity amputation (LEA), major adverse limb events (MALE), major adverse cardiovascular events (MACE), and all-cause mortality.</p><p><strong>Results: </strong>The final cohort comprised 1,849 patients (aspirin plus clopidogrel, n = 439; aspirin plus cilostazol, n = 753; clopidogrel plus cilostazol, n = 657). Median follow-up years (IQR) were 2.94 (1.97-4.11) for all-cause mortality, 2.79 (1.62-3.96) for LEA, 2.40 (0.98-3.62) for MALE, and 2.55 (1.24-3.70) for MACE. Following IPTW, baseline characteristics were well balanced. Compared with standard DAPT (aspirin plus clopidogrel), aspirin plus cilostazol was associated with a lower risk of LEA (sHR, 0.672; 95% CI, 0.460-0.981) and MACE (sHR, 0.799; 95% CI, 0.641-0.995). Clopidogrel plus cilostazol did not demonstrate significant limb-related advantages but was associated with a lower incidence of MACE (sHR, 0.790; 95% CI, 0.631-0.989). All-cause mortality was comparable across all three regimens. Notably, in stratified analyses, the clinical benefits of cilostazol-based therapies were attenuated and statistically non-significant among patients receiving dialysis.</p><p><strong>Conclusions: </strong>Among patients with diabetes and CLTI undergoing lower-extremity revascularization, aspirin plus cilostazol was associated with lower risks of LEA and MACE compared with aspirin plus clopidogrel, whereas clopidogrel plus cilostazol was associated with lower MACE but not with significant limb-related benefit. These observational findings suggest that aspirin plus cilostazol may be a favorable DAPT strategy for long-term outcomes in this population; however, further prospective randomized trials are warranted to verify.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":" ","pages":""},"PeriodicalIF":15.6,"publicationDate":"2026-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13632113/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148418933","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":"STIM1-dependent treg dysfunction promotes cardiometabolic HFpEF: insights from patients and animal studies.","authors":"Balaji Srinivas, Alluri Kiran, Hongmei Peng, Jiang Xu, Paula Fortuno, Jennifer May, Ismail El Moudden, Nour-Eddine Rhaleb, John M Herre, Raymond L Benza, Khalid Matrougui","doi":"10.1186/s12933-026-03253-6","DOIUrl":"10.1186/s12933-026-03253-6","url":null,"abstract":"<p><strong>Background: </strong>Heart failure with preserved ejection fraction (HFpEF) arises from chronic cardiometabolic and vascular stress and is increasingly recognized as an inflammatory syndrome with immune dysregulation. Regulatory T cells (Tregs) are critical modulators of cardiovascular inflammation, yet the mechanisms driving Treg dysfunction in HFpEF remain poorly defined. stromal interaction molecule 1 (STIM1)-dependent calcium signaling is a key stress-responsive pathway in immune cells; however, its role in Treg maladaptation during HFpEF remains unknown.</p><p><strong>Methods: </strong>Circulating Tregs from patients with and without HFpEF were analyzed for abundance, STIM1 expression, and stress-associated signaling pathways. To establish causality, mice with Treg-specific deletion of STIM1 (Treg^Stim1-/-) and littermate controls were subjected to a high-fat diet and nitric oxide synthase inhibition (L-NAME) to induce a cardiometabolic HFpEF model. Cardiac diastolic function, vascular reactivity, blood pressure, and exercise capacity were assessed alongside structural remodeling.</p><p><strong>Results: </strong>Patients with HFpEF exhibited reduced circulating Treg numbers accompanied by increased STIM1 expression and activation of apoptotic, inflammatory, and ER stress pathways, consistent with stress-induced Treg instability. In vivo, control mice developed features of HFpEF, including diastolic dysfunction with preserved ejection fraction, hypertension, metabolic dysregulation, endothelial dysfunction, cardiac fibrosis, and impaired exercise tolerance. In contrast, Treg^Stim1-/- mice were protected from these abnormalities. Mechanistically, STIM1 signaling promoted loss of Treg suppressive stability and the acquisition of effector-like inflammatory signaling, including IL-17- and IFN-γ-dependent cardiomyocyte activation, whereas STIM1-deficient Tregs maintained a non-pathogenic phenotype.</p><p><strong>Conclusions: </strong>STIM1-dependent stress signaling drives maladaptive Treg instability that amplifies cardiovascular inflammation and HFpEF progression. These findings identify Treg STIM1 as a key driver of immune-mediated HFpEF progression and provide mechanistic evidence from humans to mice supporting immune-targeted therapeutic strategies.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"25 1","pages":""},"PeriodicalIF":15.6,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13348757/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148410500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of C-reactive protein-triglyceride glucose index and its modified indices with stroke risk in individuals at cardiovascular-kidney-metabolic syndrome stages 0-3: a population-based cohort study.","authors":"Dan Yang, Yan Deng, Zihan Su, Min Zhao","doi":"10.1186/s12933-026-03282-1","DOIUrl":"10.1186/s12933-026-03282-1","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Stroke pathogenesis in Cardiovascular-Kidney-Metabolic (CKM) is driven by a complex interplay of insulin resistance (IR), systemic inflammation, and adiposity. This study investigated whether integrating adiposity-related measures with the inflammation-IR axis could refine stroke risk prediction in individuals at CKM stage 0-3.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A total of 3,348 participants (aged ≥ 45) at CKM stages 0-3 were included from the China Health and Retirement Longitudinal Study (CHARLS). Baseline levels, cumulative exposures, and longitudinal changes were assessed for the original C-reactive protein-triglyceride glucose index (CTI) and seven adiposity-modified CTI indices. Associations with stroke risk were evaluated using Cox proportional hazards models, and potential non-linear relationships were examined using restricted cubic splines. Predictive performance at 3 and 5 years was assessed using fixed-horizon receiver operating characteristic (ROC) analysis. Discrimination was quantified by the area under the curve (AUC) and compared using DeLong's test, while incremental predictive value was further evaluated using the integrated discrimination improvement (IDI) index. Mediation analysis was used to evaluate the potential role of estimated pulse wave velocity (ePWV) in these associations. Subgroup and sensitivity analyses were conducted to test result robustness, and weighted quantile sum (WQS) regression was performed to determine the relative contribution of components within CTI-related indices.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;During follow-up, 263 new cases of stroke were observed (7.9%). In fully adjusted models, participants in the highest tertile of all CTI-related indices had significantly increased stroke risk, with hazard ratios (HRs) ranging from 1.92 (95%CI 1.35-2.73) for original CTI to 2.52 (95%CI 1.76-3.61) for CTI-WHtR. K-means clustering of longitudinal changes identified three trajectory groups; compared with the stable group, both markedly increasing and slowly increasing trajectories of CTI and its modified indices were significantly associated with higher stroke risk. In fixed-horizon ROC analyses, the 3-year AUCs for all indices exceeded 0.70. Among baseline indices, CTI-BRI, CTI-BMI, CTI-WC, and CTI-WHtR showed significantly higher AUCs than the original CTI, whereas only CTI-BMI demonstrated a small but significant improvement in IDI over CTI (IDI = 0.0021, 95% CI 0.0004-0.0038; P = 0.012). Among cumulative indices, cumCTI-BMI and cumCTI-WHtR showed significantly higher 3-year AUCs than cumCTI. CTIs-stroke associations were stronger in advanced CKM stages (2-3). Furthermore, component analysis identified CVAI (29.0% in 2012; 29.3% in 2015) as the primary driver of predictive power. ePWV partially mediated the associations between CTI-related indices and incident stroke, with mediation proportions of 12.44%-21.20%.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;CTI and adiposity-modified CTI ","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":" ","pages":""},"PeriodicalIF":15.6,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13491843/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148403696","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":"Glucagon-like peptide-1 receptor agonists and major limb events in adults with type 2 diabetes and peripheral artery disease: a systematic review and meta-analysis of RCTs and cohort studies.","authors":"Paola Caruso, Nicole Di Martino, Miriam Longo, Lorenzo Scappaticcio, Giuseppe Bellastella, Maria Ida Maiorino, Katherine Esposito, Dario Giugliano","doi":"10.1186/s12933-026-03283-0","DOIUrl":"10.1186/s12933-026-03283-0","url":null,"abstract":"<p><strong>Background: </strong>The impact of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on peripheral artery disease (PAD) remains uncertain. We assessed the association between GLP-1RA use and major limb events in individuals with type 2 diabetes (T2D) and PAD.</p><p><strong>Methods: </strong>We performed a literature search from inception to 31 March 2026 for randomized controlled trials and cohort studies comparing GLP-1RA use versus placebo, active comparators or non-use on lower limb outcomes in individuals with T2D and PAD. The primary outcome was a composite of major limb events, as defined by the investigators of the original studies included in the meta-analysis. Secondary outcomes included lower extremity amputation (LEA), revascularization, gangrene, major adverse cardiovascular events (MACE) and all-cause mortality. Subgroup analyses, leave-one-out sensitivity analyses, and meta-regression analysis were also performed.</p><p><strong>Results: </strong>Twelve studies (2 RCTs and 10 matched cohort studies) with thirteen arms involving 418,282 participants were included. Treatment with GLP-1RAs was associated with a significantly lower risk of major limb events by 27% (thirteen arms, RR 0.73, 95% CI 0.65-0.82). Reduced risks were also observed for LEA (RR 0.76, 95% CI 0.66-0.87), revascularization (RR 0.81, 95% CI 0.77-0.86), gangrene (RR 0.80, 95% CI 0.77-0.85), MACE (RR 0.76, 95% CI 0.63-0.90) and all-cause mortality (RR 0.67, 95% CI 0.61-0.73). Subgroup and sensitivity analyses did not substantially change point estimates.</p><p><strong>Conclusion: </strong>Among adults with T2D and PAD, treatment with GLP-1RAs was associated with a lower risk of major limb events. There is a need of dedicated studies with standardized limb-specific endpoints to confirm the protective role of GLP-1RAs on limb events in people with T2D and PAD.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":" ","pages":""},"PeriodicalIF":15.6,"publicationDate":"2026-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13617921/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148396261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Joint association of Insulin resistance and frailty index with incident ASCVD and MACE in individuals with cardiovascular-kidney-metabolic syndrome stages 0-3: a multi-cohort study.","authors":"Yanqiu Huang, Yadan Xu, Wen Gu, Lijun Chang, Haojia Zhang, Yang Yang, Tian Wang, Tangyi Su, Yangchen Lhamu, Xia Shen, Yang Yang, Hui Wang, Wei Zhou","doi":"10.1186/s12933-026-03275-0","DOIUrl":"10.1186/s12933-026-03275-0","url":null,"abstract":"<p><strong>Background: </strong>While insulin resistance (IR) and frailty are mechanistically intertwined via shared pathways of chronic inflammation and metabolic dysregulation, their synergistic impact on cardiovascular risk has yet to be fully elucidated. We aimed to evaluate the joint association of IR and frailty index (FI) with the risk of incident atherosclerotic cardiovascular disease (ASCVD) and major adverse cardiovascular events (MACE) in individuals with Cardiovascular-Kidney-Metabolic (CKM) syndrome stages 0-3.</p><p><strong>Methods: </strong>This study enrolled 259,714 and 2632 CKM syndrome stages 0-3 from the UK Biobank (UKB), and China Health and Retirement Longitudinal Study (CHARLS). Three IR-related indices, namely the triglyceride-glucose index (TyG), metabolic score for IR (METS-IR), and estimated glucose disposal rate (eGDR), were each combined with two frailty assessments, the FI and physical FI (PFI), yielding six composite IR-FI indices for analysis. In the UKB, MACE and ASCVD were the co-primary outcomes, with heart disease and stroke as secondary outcomes. In the CHARLS, the outcomes included CVD, heart disease, and stroke. Multivariate Cox proportional hazards models, restricted cubic spline analyses, Kaplan-Meier analyses and time-dependent receiver operating characteristic curves were employed to assess associations. Mediation analysis and functional proteomic enrichment provided a framework for exploring the potential biological mechanisms.</p><p><strong>Results: </strong>In the UKB, elevated levels of the IR-FI were associated with increased risks of ASCVD and MACE, with consistent findings observed for CVD, heart disease, and stroke in the CHARLS. Significant positive nonlinear relationships were established for the METS-IR-FI and eGDR-FI regarding cardiovascular outcomes. Mediation analysis revealed that Creactive protein, neutrophils, and leucocyte partially mediated these associations (ratio range: 1.5-12%). Proteomic analyses identified Cytokine-cytokine receptor interaction as a primary regulatory hub, while leukocyte migration, chemotaxis, and neutrophil degranulation were characterized as the central pathological execution mechanisms in this process.</p><p><strong>Conclusions: </strong>The IR-FI are significantly associated with the incidence of cardiovascular events, an association that appears to be mediated through systemic inflammatory pathways. These novel integrated indices represent promising biomarkers for early screening and targeted clinical intervention among individuals with CKM syndrome stages 0-3.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":" ","pages":""},"PeriodicalIF":15.6,"publicationDate":"2026-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13617852/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148396249","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 adipose tissue-plaque crosstalk: omics profiling of perivascular adipose tissues for understanding plaque stability.","authors":"Marija Tomašević, Sandra Vladimirov, Christos Tsatsanis, Eleni Paflioti, Dimitris Kardassis, Isidoros Axiotis, Despoina Lazaridou, Laura Comi, Claudia Giglione, Ana Ninić, Sanja Erceg, Tamara Ratković, Aleksandar Davidović, Marko Milanov, Luka Dodić, Gordana Mihajlović, Paolo Magni, Miron Sopić","doi":"10.1186/s12933-026-03276-z","DOIUrl":"10.1186/s12933-026-03276-z","url":null,"abstract":"<p><p>Atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of global morbidity and mortality, despite significant advances in lipid-lowering and cardiometabolic therapies. Increasing evidence indicates that atherosclerosis cannot be fully understood as a disease confined to the arterial wall, but rather reflects complex interactions between vascular, immune, metabolic, and perivascular compartments. Among these, perivascular adipose tissue (PVAT) has emerged as a critical regulator of vascular homeostasis and plaque biology due to its unique anatomical proximity and functional continuity with the vessel wall. This review summarises current knowledge on the role of PVAT in atherosclerosis, particularly insights gained through omics approaches. We explore how transcriptomics, proteomics, metabolomics, and lipidomics have advanced the structural and functional characterisation of PVAT, revealing pronounced cellular heterogeneity, depot-specific signatures, and dynamic phenotypic plasticity, including brown-to-white adipose tissue transitions. We further examine the molecular and cellular interfaces that mediate PVAT-vascular crosstalk and discuss how PVAT influences key processes relevant to plaque development and stability, including inflammation and immune signaling, extracellular matrix remodeling, cell differentiation and survival, and regulation of vascular tone. Importantly, emerging evidence supports bidirectional communication between PVAT and atherosclerotic plaques, establishing maladaptive feedback loops that may sustain vascular inflammation and contribute to residual cardiovascular risk. Finally, we address translational implications, evaluating the potential of PVAT-derived biomarkers and the therapeutic targeting of PVAT-plaque interaction for improved risk stratification and the development of more precise, tissue-targeted interventions in ASCVD.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":" ","pages":""},"PeriodicalIF":15.6,"publicationDate":"2026-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148396293","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":"Joint longitudinal trajectories of the triglyceride-glucose index combined with BMI and waist-to-height ratio and incident cardiovascular disease: a prospective cohort study from the English longitudinal study of ageing.","authors":"Zhengyang Liu, Qiyu Li, Bo Wang, Ying Zhou, Yuanyuan Dong, Bo Tang, Hongmei Yang, Shasha Yu","doi":"10.1186/s12933-026-03279-w","DOIUrl":"10.1186/s12933-026-03279-w","url":null,"abstract":"<p><strong>Background: </strong>The triglyceride-glucose (TyG) index and its composite obesity indices have been linked to cardiovascular disease (CVD) risk. However, most prior studies relied on single baseline measurements, and few have employed group-based multi-trajectory modeling to capture concurrent longitudinal changes in metabolic and anthropometric indicators. This study aimed to identify joint longitudinal trajectory groups of TyG combined with body mass index (BMI) and waist-to-height ratio (WHtR) using parallel approaches and evaluate their associations with incident CVD in middle-aged and older adults.</p><p><strong>Methods: </strong>This prospective cohort study included 1808 CVD-free participants aged ≥ 50 years from the English Longitudinal Study of Ageing. Group-based multi-trajectory modeling was applied to jointly identify latent trajectory classes using repeated measurements of TyG with BMI and TyG with WHtR across three waves over approximately 8 years. Cox proportional hazards models with four sequential adjustment models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for incident composite CVD, heart disease, and stroke. Subgroup analyses were stratified by age, gender, smoking, diabetes, and hypertension status. Nine sensitivity analyses were conducted to assess robustness.</p><p><strong>Results: </strong>During follow-up, 263 participants (14.5%) developed incident CVD. Four trajectory groups were identified for each approach. In fully adjusted BMI + TyG models, compared with the normal weight-low TyG reference group, composite CVD risk increased progressively across the overweight-moderate TyG (HR 2.31, 95% CI 1.40-3.83), obese-high TyG (HR 2.72, 95% CI 1.63-4.52), and severely obese-high TyG groups (HR 5.06, 95% CI 3.01-8.51). The WHtR + TyG approach demonstrated a consistent dose-response pattern, with HRs of 2.22, 2.75, and 5.12 for ascending risk groups. For stroke, only the highest-risk groups reached statistical significance (HR 6.74 and 5.00, respectively). Formal discriminative comparison showed no significant difference between the two approaches (C-statistic difference 0.003, P = 0.723). All nine sensitivity analyses consistently corroborated the primary findings.</p><p><strong>Conclusions: </strong>Both approaches yield robust and comparable dose-response gradients, supporting further validation of serial TyG-related composite index monitoring for cardiovascular risk stratification in aging populations.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":" ","pages":""},"PeriodicalIF":15.6,"publicationDate":"2026-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13393250/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148389803","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":"Synergistic SGLT2 and GLP-1R targeting alleviates systemic inflammation-induced and M1 monocyte-driven endothelial dysfunction in coronary artery disease.","authors":"Ali Mroueh, Walaa Fakih, Sophie Kerth, Shinnosuke Kikuchi, Chaimae Aboueddahab, Dal-Seong Gong, Midam Choi, Alice Nicolas, Sarah Fass, Antonin Trimaille, Amandine Granier, Adrien Carmona, Said Amissi, Petr Pompach, Min-Ho Oak, Laurence Jesel, Agnes Görlach, Olivier Morel, Valérie Schini-Kerth","doi":"10.1186/s12933-026-03267-0","DOIUrl":"10.1186/s12933-026-03267-0","url":null,"abstract":"<p><strong>Background and objective: </strong>Systemic residual inflammation plays a pivotal role in the pathophysiology of coronary artery disease (CAD). Cardiovascular protection by SGLT2 inhibitors (SGLT2i) and GLP-1 receptor agonists (GLP-1Ra) is associated with reduced inflammatory burden but underlying cellular mechanisms remain incompletely defined. We investigated whether SGLT2i and GLP-1Ra synergistically suppress monocyte activation and prevent both systemic inflammatory mediator-induced and monocyte-driven endothelial dysfunction in CAD.</p><p><strong>Methods and results: </strong>Plasma and circulating monocytes were analyzed in healthy individuals (n = 20), patients with cardiovascular disease without CAD (n = 20), and patients with stable CAD (n = 55), and their effects on endothelial cell responses were assessed. CAD plasma showed increased IL-1β, IL-6, TNF-α, MCP-1, soluble ICAM-1, and VCAM-1, and a proteomic profile enriched in complement, innate immune, and extracellular matrix remodeling pathways. CAD plasma induced oxidative stress in endothelial cells, reduced nitric oxide, increased leukocyte and platelet adhesion, and enhanced procoagulant activity, correlating with circulating TNF-α and sICAM-1. CAD monocytes exhibited a metabolically activated phenotype with increased oxidative stress, mitochondrial activity, glucose and cholesterol uptake, calcium signaling, procoagulant activity, and adhesion to endothelial cells. These changes correlated with circulating TNF-α, sICAM-1, and plasma-induced endothelial dysfunction. CAD monocytes showed increased NF-κB, NOX2, and NLRP3 signaling with reduced CREB/NRF2 pathways, produced elevated levels of pro-inflammatory cytokines, while CAD monocytes-conditioned medium induced endothelial oxidative stress and blunted nitric oxide production. GLP-1Ra or SGLT2i attenuated these effects, while combined treatment provided synergistic protection, reducing CAD plasma-induced endothelial oxidative stress (~ 80%) and restoring endothelial function, reducing CAD monocytes oxidative stress (~ 82%), metabolic activation and pro-thrombotic activity, reprogramming monocytes toward anti-inflammatory phenotype and preventing CAD monocytes-induced endothelial dysfunction.</p><p><strong>Conclusion: </strong>CAD features systemic inflammation that drives monocyte activation and endothelial dysfunction. Combined SGLT2i and GLP-1Ra synergistically suppress monocyte pro-inflammatory and pro-thrombotic activity and subsequently driven endothelial dysfunction.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":" ","pages":""},"PeriodicalIF":15.6,"publicationDate":"2026-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13617697/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148387381","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}