Cardiovasc Diabetol [JOURNAL]
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200 papers
Prognostic stratification with composite insulin resistance-inflammation biomarkers in patients with chronic kidney disease and coronary artery disease across glycemic statuses.
Ye Z, Xie E, Song C … +4 more , Zhang R, Wang H, Wu C, Dou K
Cardiovasc Diabetol · 2026 Mar · PMID 41772566 · Full text
BACKGROUND: Patients with chronic kidney disease (CKD) and coronary artery diseases (CAD) have a poor long-term prognosis. Although insulin resistance (IR) and systemic inflammation are well-established drivers of cardio...
BACKGROUND: Patients with chronic kidney disease (CKD) and coronary artery diseases (CAD) have a poor long-term prognosis. Although insulin resistance (IR) and systemic inflammation are well-established drivers of cardiovascular risk, the prognostic value of their composite assessment across the glycemic spectrum in patients with CKD and CAD remains undetermined. This study aimed to evaluate the prognostic utility of composite IR-inflammation biomarkers for predicting mortality in patients with CKD and CAD stratified by glycemic status. METHODS: 1353 patients with CKD and CAD were enrolled from National Health and Nutrition Examination Survey (NHANES) data (1999-2018). Composite biomarkers (TyG-hsCRP, TyG-CRP, and C-reactive Protein-Triglyceride Glucose Index [CTI]) were calculated. Patients were categorized by glycemic status (normoglycemia, prediabetes, diabetes) based on WHO/IEC criteria. The endpoint was all-cause and cardiovascular disease (CVD) death. Statistical analyses included Cox regression, Nelson-Aalen cumulative hazard plots with Log-rank test, restricted cubic splines, ROC curves, and reclassification metrics, adjusted for demographics, comorbidities, and treatments. Subgroup and sensitivity analyses ensured robustness. RESULTS: Over a median follow-up of 63-months, 744 all-cause and 323 CVD deaths occurred. Adjusted models showed elevated composite indices linked to higher mortality (e.g., CTI HR 1.43 [95% CI 1.24-1.65] for all-cause; HR 1.32 [1.06-1.64] for CVD). CTI provided good discrimination (AUC 0.700) and reclassification (IDI 0.010; NRI 0.196 for all-cause). The predictive utility of all three composite biomarkers was most pronounced in patients with diabetes, whereas CTI retained the strong association with all-cause mortality in normoglycemic and prediabetic patients. Risk stratification using both CTI and glycemic status identified patients with diabetes and high CTI as having the highest all-cause (HR 1.63 [1.22-2.17]) and CVD (HR 1.37 [0.88-2.14]) death risk. CONCLUSION: Composite biomarkers integrating IR and inflammation, particularly CTI, significantly enhance mortality prediction in patients with CKD and CAD. The predictive utility is modulated by underlying glycemic status, enabling refined risk stratification and potentially guiding tailored management strategies for this complex patient population.
Association of the C-reactive protein-triglyceride-glucose index with metabolic dysfunction-associated steatotic liver disease and long-term all-cause and cardiovascular mortality: evidence from two nationwide prospective cohort studies.
Jin XF, Su ZJ, Zhong JF … +25 more , Wang J, Shi BJ, Liu ZY, Li PS, Xiong X, Xu SQ, Qiu C, Xiao Y, Li SB, Tong WH, Ge JP, Li HX, Liu XY, Li ZZ, Kong XR, Chen JL, Wen XJ, Sun P, Chen PP, Li YY, Chen Y, Mao LT, Peng ZH, Li H, Zhang T
Cardiovasc Diabetol · 2026 Mar · PMID 41772559 · Full text
BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is closely linked to cardiometabolic disorders, and cardiovascular disease is the leading cause of death among affected individuals. Identifyin...
BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is closely linked to cardiometabolic disorders, and cardiovascular disease is the leading cause of death among affected individuals. Identifying simple biomarkers that capture metabolic-inflammatory burden and predict long-term mortality in MASLD remains a clinical priority. The C-reactive protein-triglyceride-glucose index (CTI) integrates inflammation, dyslipidaemia, and glycaemic status, but its relevance to MASLD and long-term mortality has not been fully elucidated. METHODS: We conducted a multi-stage investigation using two nationally representative cohorts from the United States and China. Cross-sectional associations between CTI and MASLD were assessed in the National Health and Nutrition Examination Survey (NHANES) and the China Health and Retirement Longitudinal Study (CHARLS). Prospective associations of CTI with cardiovascular and all-cause mortality among participants with MASLD were examined utilising multivariable Cox proportional hazards models, restricted cubic splines, threshold analyses, and competing risk models. Causal mediation analyses were performed to measure the mediating functions of diabetes, hypertension, and body mass index. Extensive sensitivity analyses using alternative MASLD definitions and analytic strategies were conducted to assess robustness. Results from NHANES were externally validated in CHARLS. RESULTS: Higher CTI levels were strongly and nonlinearly associated with the presence of MASLD in both cohorts. Among individuals with MASLD, elevated CTI was associated with significantly increased risks of all-cause and cardiovascular mortality. Each unit increase in CTI in NHANES was linked to a 57% increased risk of cardiovascular death (HR 1.57, 95% CI 1.24-1.99) and a 47% increased risk of all-cause death (hazard ratio [HR] 1.47, 95% confidence interval [CI] 1.28-1.69) in fully adjusted models. A pronounced threshold effect was observed, with mortality risk rising sharply once CTI exceeded approximately 5.6. Consistent associations with all-cause mortality were observed in CHARLS. Mediation analyses indicated that diabetes accounted for a substantial proportion of the association between CTI and mortality, whereas body mass index played a minimal mediating role. CONCLUSIONS: CTI is a robust metabolic-inflammatory marker associated with MASLD and long-term all-cause and cardiovascular mortality across diverse populations. The strong mediating role of diabetes underscores the central importance of glycaemic dysfunction in cardiometabolic risk. As a readily obtainable index, CTI may aid in cardiometabolic risk stratification among individuals with MASLD.
Correction: Prognostic role of sarcopenia in heart failure patients.
Armentaro G, Vitale C, Cassano V … +12 more , Magurno M, Panza A, Scarcelli MR, Pastura CA, Severini G, Mazza E, Hribal ML, Andreozzi F, Pujia A, Montalcini T, Rosano GMC, Sciacqua A
Cardiovasc Diabetol · 2026 Feb · PMID 41761309 · Full text
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Comparative efficacy of tirzepatide and glucagon-like peptide-1 receptor agonists on cardiovascular outcomes in patients with type 2 diabetes: a systematic review and network meta-analysis.
Shokravi A, Seth J, Mancini GBJ
Cardiovasc Diabetol · 2026 Feb · PMID 41761267 · Full text
BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are widely used therapies for cardiovascular risk reduction in type 2 diabetes (T2D). With the emergence of the SURPASS-CVOT trial, tirzepatide (a dual GIP...
BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are widely used therapies for cardiovascular risk reduction in type 2 diabetes (T2D). With the emergence of the SURPASS-CVOT trial, tirzepatide (a dual GIP/GLP-1 receptor agonist) has entered the therapeutic landscape; however, its comparative effect on cardiovascular outcomes compared to placebo and individual GLP-1RAs remains undefined. METHODS: We conducted a systematic review and frequentist network meta-analysis (NMA) of RCTs enrolling adults with type 2 diabetes (T2D) and established atherosclerotic cardiovascular disease (ASCVD) or high cardiovascular (CV) risk. Eligible RCTs evaluated tirzepatide or GLP-1RAs and reported major adverse cardiovascular events (MACE), CV mortality, all-cause mortality, non-fatal myocardial infarction (MI) or non-fatal stroke. A class-level NMA was conducted to estimate the incremental benefit of tirzepatide and GLP-1RAs over placebo, and an agent-level NMA was conducted to explore differences between tirzepatide and individual GLP-1RA agents. Subgroup analyses, including established cardiovascular disease populations, and leave-one-out sensitivity analyses were performed. RESULTS: Eleven trials met inclusion criteria (10 GLP-1RA trials and 1 tirzepatide trial [SURPASS-CVOT]). In the class-level analysis, tirzepatide significantly reduced MACE (HR 0.79, 95% CI 0.69-0.91), CV mortality (HR 0.77, 95% CI 0.66-0.90), all-cause mortality (HR 0.74, 95% CI 0.65-0.83), non-fatal MI (HR 0.77, 95% CI 0.61-0.97), and non-fatal stroke (HR 0.79, 95% CI 0.64-0.97) compared to placebo. Formal statistical comparisons between tirzepatide and the GLP-1RA class could not be performed within the constraints of the NMA; however, point estimates across outcomes numerically favored tirzepatide compared with placebo. In the agent-level analysis, tirzepatide reduced MACE compared to placebo (HR 0.81, 95% CI 0.70-0.94) and lixisenatide (HR 0.79, 95% CI 0.65-0.97). Subgroup and sensitivity analyses did not substantially change point estimates. CONCLUSION: Among adults with T2D and established ASCVD or high CV risk, class-level analysis demonstrated that tirzepatide significantly reduced the risk of cardiovascular events compared to placebo; at the agent-level, tirzepatide demonstrated comparable efficacy to individual GLP-1RAs. These findings suggest that tirzepatide provides cardiovascular benefit at least comparable to established GLP-1RAs, supporting its emerging role in cardiovascular risk reduction in T2D.
Circulating protein biomarkers of physical fitness associated with cardiometabolic risk in women after gestational diabetes: a PONCH study.
Kristiansson E, Holmäng A, Wallenius K … +5 more , Chung HS, Hess S, Pettersson S, Madsen K, Andersson-Hall U
Cardiovasc Diabetol · 2026 Feb · PMID 41761218 · Full text
BACKGROUND: Women with prior gestational diabetes mellitus (GDM) have an elevated risk of developing cardiometabolic diseases, including type 2-diabetes and cardiovascular disease. While physical fitness is protective, c...
BACKGROUND: Women with prior gestational diabetes mellitus (GDM) have an elevated risk of developing cardiometabolic diseases, including type 2-diabetes and cardiovascular disease. While physical fitness is protective, circulating molecular biomarkers linking fitness to long-term metabolic health in this population remain poorly understood. This study aimed to identify serum proteins associated with aerobic capacity and muscle strength 10 years after GDM, and explore their biological functions related to cardiometabolic risk. METHODS: We assessed aerobic fitness (VO2peak), peak fat oxidation, and maximal isometric muscle strength of five muscle groups in 38 women from the post-GDM PONCH-cohort. Serum proteins were analysed using mass spectrometry-based proteomics. Associations between proteins, fitness variables, and clinical markers were tested using Spearman correlations with FDR correction, and age- and medication-adjusted sensitivity analysis. Group differences across four fitness-level groups (defined by aerobic fitness and muscle strength) and glycaemic status groups were analysed using linear regression models and Kruskal-Wallis tests, with age- and medication-adjusted sensitivity analyses. Exercise responsiveness of selected proteins was assessed in an independent cohort of untrained men undergoing six weeks of supervised aerobic training (n = 28), with pre-post changes assessed using Wilcoxon signed-rank tests. RESULTS: Thirty-five proteins were associated with at least one fitness variable, of which 21 remained significant after age- and medication-adjusted sensitivity analysis. Nine proteins correlated with both VO2peak and muscle strength. Identified proteins mapped to key cardiometabolic pathways, including metabolic regulation, immune response, complement activation, oxidative stress, and extracellular matrix remodelling. Five proteins (PON3, IGF1, CRISP3, COL6A3, C3) emerged as particularly interesting, showing the largest and most consistent effect sizes across fitness variables and associations with central adiposity, blood lipids, blood pressure, and insulin resistance. Stratified analysis across the four fitness-level groups identified IGF1, PON3, and PRG4 as markers of higher overall-fitness. In the independent training cohort, nine of the fitness-associated proteins changed following aerobic training without significant weight-loss. CONCLUSIONS: This study identified circulating proteins linked to physical fitness and cardiometabolic health in women after GDM. These findings suggest fitness-associated serum proteins may serve as biomarkers of early metabolic dysfunction and potential targets for exercise-based prevention of T2D and cardiovascular disease.
Metabolic dysfunction-associated steatotic liver disease is associated with vascular dysfunction in type 1 diabetes.
Mertens J, Stoop T, Dirinck E … +3 more , Francque S, Heuten H, De Block C
Cardiovasc Diabetol · 2026 Feb · PMID 41742207 · Full text
BACKGROUND & AIMS: Metabolic dysfunction-associated steatotic liver disease (MASLD) is linked to atherosclerotic cardiovascular disease (ASCVD). Markers of arterial stiffness and subclinical atherosclerosis (carotid-femo...
BACKGROUND & AIMS: Metabolic dysfunction-associated steatotic liver disease (MASLD) is linked to atherosclerotic cardiovascular disease (ASCVD). Markers of arterial stiffness and subclinical atherosclerosis (carotid-femoral pulse wave velocity [cfPWV], and carotid-intima media thickness [CIMT]) and endothelial dysfunction (flow-mediated dilation [FMD], nitroglycerine-induced dilation [NID]) are potential ASCVD predictors. This study examined the correlation between vasculopathy and MASLD in type 1 diabetes (T1D). METHODS: We conducted cross-sectional vascular assessments in non-smoking adults with T1D without ASCVD. MASLD was determined by ultrasound and transient elastography. FIB-4 was calculated as a marker of fibrosis. ASCVD risk scores were assessed using the Steno Type 1 Risk Engine. Subjects were included in a 2:1 control-to-case ratio and matched for age and diabetes duration. RESULTS: We examined 105 subjects, of whom 30 had MASLD. Mean age was 51.7 ± 15.7 years, mean diabetes duration was 29.9 ± 14.3 years. 50% were male, mean HbA1c was 55.1 ± 9.5 mmol/mol (7.2 ± 0.9%). MASLD was associated with lower NID (15.3 ± 6.3 vs. 20.1 ± 7.5%, p = 0.003). NID and cfPWV were more often impaired in people with MASLD (53.3% vs. 28.4%, p = 0.018, 56.7% vs. 35.1%, p = 0.043, respectively). In adjusted multivariable logistic regression, MASLD was associated with increased cfPWV (OR 8.30, 95% CI 1.25-55.2, p = 0.029), as was age, sex and mean arterial pressure. cfPWV and CIMT strongly correlated with 5-year ASCVD risk (cfPWV ρ = 0.76, CIMT ρ = 0.81, p < 0.001), as did FIB-4 (ρ = 0.74, p < 0.001). CIMT (0.93), cfPWV (0.88) and FIB-4 (0.88) yielded the highest AUROC to identify significant ASCVD risk. CONCLUSIONS: cfPWV is the most robust vascular marker associated with MASLD in people with T1D. cfPWV, CIMT and FIB-4 correlated strongly to incident 5-year ASCVD risk. Sven Francque, Hilde Heuten and Christophe De Block have claimed equal senior authorship.
SGLT2 inhibitors reduce the salt sensitivity of blood pressure in type 2 diabetes via enhanced postprandial natriuresis.
Chiriacò M, Tricò D, Sacchetta L … +8 more , Nesti L, Cimbalo N, Santoni L, Gallo S, Baldi S, Scozzaro T, Giannoni A, Natali A
Cardiovasc Diabetol · 2026 Feb · PMID 41736122 · Full text
BACKGROUND: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) lower blood pressure (BP) and provide cardiovascular protection. In animal models, SGLT2i blunt sodium-induced BP elevation, but this effect remains unexplor...
BACKGROUND: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) lower blood pressure (BP) and provide cardiovascular protection. In animal models, SGLT2i blunt sodium-induced BP elevation, but this effect remains unexplored in humans. We investigated whether SGLT2i reduce the salt sensitivity of BP in patients with type 2 diabetes (T2D) and explored the underlying mechanisms. METHODS: In an open-label, non-randomized study, 26 patients with T2D (14 on treatment with SGLT2i, 12 controls) completed two sequential 7-day dietary phases consisting of a very-low-sodium background diet with the addition of either high sodium (HS, + 4,800 mg/day) or low sodium (LS, + 1,200 mg/day). Changes in twenty-four hour ambulatory BP monitoring (24-hour ABPM), postprandial natriuresis and diuresis, plasma renin and aldosterone concentrations, glycosuria, and hydration were assessed. RESULTS: The median change in systolic BP between HS and LS diets was greater in controls (median [IQR] Δ24-h SBP: +5.6 [2.0, 20.3] mmHg, p = 0.005), than in the SGLT2i group (Δ24-h SBP: -1.2 [-3.6, 4.2] mmHg, p = 0.594; p = 0.007 between groups). Diastolic BP changes showed similar patterns (Δ24-h DBP: +4.6 [1.3, 9.8] mmHg vs. -1.2 [-3.1, 1.4] mmHg; p = 0.002 between groups). SGLT2i-treated participants showed enhanced postprandial natriuresis during both HS (median [IQR]: 55.0 [28.3, 126.6] µEq/min vs. -0.7 [-148.6, 109.0] µEq/min; p = 0.049) and the LS diet (18.4 [1.3, 42.2] µEq/min vs. -14.5 [-30.2, 15.7] µEq/min; p = 0.046), and postprandial diuresis during the HS diet (median [IQR]: 0.52 [0.10, 1.18] ml/min vs. -0.21 [-0.58, 0.45] ml/min p = 0.041). In response to the LS diet, renin and aldosterone levels increased markedly in controls but not in SGLT2i-treated patients. Hydration and glycosuria were unchanged and unrelated to natriuretic responses. CONCLUSIONS: In T2D, treatment with SGLT2 inhibitors is associated with a reduced BP response to high sodium intake, accompanied by enhanced postprandial sodium and water excretion, along with attenuated neurohormonal activation. These findings identify physiological associations that may contribute to the BP-lowering and cardiovascular protective effects of SGLT2 inhibition. TRIAL REGISTRATION: NCT06007157 (registered on 18/08/2023).
Novel epigenetic marks of insulin resistance trajectories in a longitudinal study of childhood obesity.
Anguita-Ruiz A, Torres-Martos Á, Bustos-Aibar M … +9 more , Setó-Llorens A, Ruiz-Ojeda FJ, Moreno LA, Gil Á, Gil-Campos M, Bueno G, Leis R, Alcalá-Fdez J, Aguilera CM
Cardiovasc Diabetol · 2026 Feb · PMID 41736036 · Full text
BACKGROUND: Childhood obesity is a major global public-health challenge. Insulin resistance (IR) is a critical driver of later cardiometabolic alterations. A comprehensive understanding of the molecular mechanisms underl...
BACKGROUND: Childhood obesity is a major global public-health challenge. Insulin resistance (IR) is a critical driver of later cardiometabolic alterations. A comprehensive understanding of the molecular mechanisms underlying the initial development of childhood IR is essential for timely prevention and intervention. In this study, we aimed to assess the association between IR and blood DNA methylation in a longitudinal study from childhood into adolescence. METHODS: The PUBMEP study included a longitudinal core of 90 children with paired blood samples collected at both pre-pubertal and pubertal stages. For cross-sectional analyses, this sample was expanded to 99 pre-pubertal and 129 pubertal participants. IR status was defined according to clinically relevant sex- and pubertal stage specific HOMA-IR cut-offs, as recommended by pediatric expert clinicians. Genotype data was obtained with the Infinium Global Screening Array, and blood DNA methylation sites with the Infinium MethylationEPIC BeadChip. Epigenome-wide associations with IR status and trajectories were tested using linear models in the longitudinal and cross-sectional sets. FDR-adjusted significant CpG sites were assessed with sex- and age-standardised cardiometabolic z-scores (adiposity, lipids, blood pressure, glycaemia and IR) at each stage. mQTL analyses were performed to identify genetic variants that drive IR-associated methylation signals. RESULTS: We identified 120 CpG sites related to obesity-associated IR in the context of pubertal transition that remained significant after global FDR correction (FDR < 0.05). These CpG sites showed distinct methylation profiles that tracked IR trajectories from prepuberty to puberty, with consistent differences across children whose IR improved, worsened or remained stable, with several of them also related to cardiometabolic traits at pubertal stage, including adiposity measures, blood pressure and glycaemic indices. Among the FDR-significant CpG sites with biological relevance for IR, methylation at CpG sites annotated to SLC2A9, PEPD, TSC2, EGLN3, EHD2 and VASN showed consistent associations with pubertal HOMA-IR z-score and, for several loci, with adiposity and blood pressure measures, with methylation changes paralleling IR worsening, improvement or stability across puberty. An mQTL look-up in GoDMC identified 25 cis SNP CpG associations corresponding to 20 of the 120 CpG sites, including CpG sites in SLC2A9 and TSC2, indicating that only a fraction of these IR-associated CpG sites is likely to be partly influenced by nearby genetic variants. CONCLUSION: This longitudinal EWAS in children with obesity shows that specific blood DNA methylation signatures mirror IR status and track its evolution across the pubertal transition, with opposing methylation trajectories distinguishing improving from persistent IR. The identification of CpG sites at VASN, SLC2A9, PEPD, EGLN3, EHD2 and TSC2 links IR trajectories to pathways involved in vascular signalling, urate transport, extracellular matrix remodelling, and hypoxia sensing and nutrient signalling. Complementary mQTL analyses suggest that while some of this epigenetic variation is influenced by local genetic factors, a substantial component is likely acquired in response to metabolic and external exposures. If replicated and functionally characterised, these findings may help refine our understanding of the early molecular architecture of obesity-related IR and inform future strategies for cardiometabolic risk assessment and timing of preventive interventions.
Opposing functions of miR-155-5p and Socs1 drive vascular inflammation in diabetes-accelerated atherosclerosis.
Kavanagh M, Herrero Del Real I, Prieto I … +5 more , Alvarez-Moreno R, Egido J, Lopez-Franco O, Lázaro I, Gomez-Guerrero C
Cardiovasc Diabetol · 2026 Feb · PMID 41736028 · Full text
BACKGROUND: Diabetes accelerates atherosclerosis by driving persistent vascular inflammation. MicroRNA-155 (miR-155) is a post-transcriptional regulator of inflammatory genes, while suppressor of cytokine signaling 1 (So...
BACKGROUND: Diabetes accelerates atherosclerosis by driving persistent vascular inflammation. MicroRNA-155 (miR-155) is a post-transcriptional regulator of inflammatory genes, while suppressor of cytokine signaling 1 (Socs1) limits Janus kinase (JAK)/signal transducer and activator of transcription (STAT)-mediated cytokine responses. We explored how the imbalance between miR-155-5p and Socs1 contributes to atherosclerotic plaque progression in diabetes. METHODS: Apolipoprotein E knockout (ApoE-/-) mice were studied in two settings: age-dependent atherosclerosis progression under non-diabetic conditions, and streptozotocin-induced diabetes to model accelerated atherosclerosis. Diabetic mice received a miR-155-5p inhibitor, a Socs1-expressing adenovirus, or respective controls. Lesion size, composition, and gene expression were analyzed. Cultured vascular smooth muscle cells (VSMCs) and macrophages were transfected with miR-155-5p mimic/inhibitor and Socs1 siRNA/plasmid to assess inflammatory responses, phenotypes, and efferocytosis under diabetic-like conditions. RESULTS: During atherosclerosis progression, vascular miR-155-5p inversely correlated with Socs1 and positively with lesion size, while Socs1 correlated negatively with plaque burden. In diabetic mice, miR-155-5p inhibition reduced lesion area, lipid/collagen and macrophage/VSMC ratios, pro-inflammatory cytokines, M1 macrophages and synthetic VSMC markers, while increasing Socs1, M2 and contractile VSMC genes. Socs1 gene transfer reproduced these effects by reducing miR-155-5p and Stat1 expression, and lesion size. In vitro, miR-155-5p mimic suppressed Socs1, activated STAT1 and inflammatory phenotypes in macrophages and VSMCs, whereas miR-155-5p inhibition had opposite effects. Socs1 silencing amplified inflammation, and its overexpression counteracted miR-155-5p actions. Moreover, miR-155-5p inhibition reduced soluble Mer receptor tyrosine kinase (MerTK) in plaques and macrophages, indicating improved efferocytosis, whereas the mimic promoted macrophage MerTK shedding and impaired apoptotic cell clearance. CONCLUSION: Reciprocal regulation between miR-155-5p and Socs1 influences vascular inflammation, phenotypic changes, and defective efferocytosis in a diabetic context. Targeting this axis may restore resolution mechanisms and enhance plaque stability in diabetes-associated vascular disease.
From global guidelines for cardio-kidney-metabolic diseases management to national implementation: perspectives from the guideline workshop taskforce.
Wanner C, Cosentino F, Barnard-Kelly K … +24 more , Battelino T, Blüher M, Boll HN, Brosius FC, Busetto L, Ceriello A, Gavin JR, Giorgino F, Green J, Ji L, Kellerer M, Koob S, Lalic N, Marx N, Nedungadi P, Parkin CG, Rodbard HW, Rydén L, Saboo B, Sheu WH, Standl E, Tacke F, Topsever P, Schnell O
Cardiovasc Diabetol · 2026 Feb · PMID 41731496 · Full text
International guidelines define standards of care for type 2 diabetes (T2D), obesity, cardiovascular disease (CVD), metabolic dysfunction-associated steatotic liver disease (MASLD) and chronic kidney disease (CKD). Yet i...
International guidelines define standards of care for type 2 diabetes (T2D), obesity, cardiovascular disease (CVD), metabolic dysfunction-associated steatotic liver disease (MASLD) and chronic kidney disease (CKD). Yet implementation at the national level remains inconsistent, leading to persistent gaps between evidence-based recommendations and real-world practice. Key barriers include linguistic and cultural adaptation, limited communication to clinicians, and siloed regulatory and reimbursement processes. Addressing these challenges requires coordinated strategies, such as concise translations, digital platforms and decision-support tools, integration into medical education, and structured monitoring and evaluation frameworks with feedback and incentives. Equitable and sustainable access further depends on coordination between medical societies, governmental authorities, payers, and patient representatives. Evidence from existing initiatives shows that systematic, context-sensitive approaches can measurably improve care. Building on these lessons, this Commentary recommends priorities for national implementation to ensure that guidelines move more effectively from publication to practice and realise their full potential to improve patient outcomes.
The cholesterol, high-density lipoprotein, and glucose (CHG) index as a novel metabolic marker for predicting adverse outcomes in myocardial infarction survivors: insights from two large prospective cohorts.
Song Y, Chen X, Chang Z … +9 more , Bian X, He J, Li B, Zheng Z, Wang C, Lin Z, Zhu C, Fu R, Dou K
Cardiovasc Diabetol · 2026 Feb · PMID 41731494 · Full text
BACKGROUND: Post-myocardial infarction (MI) patients remain at high risk of mortality and recurrent cardiovascular events. Metabolic disorders in patients after MI are closely related to high residual cardiovascular risk...
BACKGROUND: Post-myocardial infarction (MI) patients remain at high risk of mortality and recurrent cardiovascular events. Metabolic disorders in patients after MI are closely related to high residual cardiovascular risk. The cholesterol, high-density lipoprotein, and glucose (CHG) index, calculated as Ln {[TC (mg/dL) × FBG (mg/dL)]/[2 × HDL-C (mg/dL)]}, is a recently proposed composite metabolic index. This study aimed to investigate the association between the CHG index and adverse outcomes in MI populations. METHODS: This study included two cohorts: 16,959 individuals with a history of MI from the UK Biobank and 6,253 post-MI patients with coronary artery disease from Fuwai Hospital. The primary endpoints in the UK Biobank cohort were all-cause mortality and cardiovascular mortality. In the Fuwai Hospital cohort, the primary endpoint was major adverse cardiovascular events (MACE, including all-cause mortality, non-fatal MI, and ischemia-mediated revascularization) and hard endpoint (including cardiovascular mortality and non-fatal MI). Cox proportional hazards models, Kaplan-Meier curves, and restricted cubic splines (RCS) were used to evaluate the associations between the CHG index and the endpoints. Time-dependent receiver operating characteristic (ROC) curves were employed to assess the predictive performance. RESULTS: In the UK Biobank cohort (median follow-up of 13.4 years), after multivariate adjustment, compared to the Q1 of the CHG index, Q4 showed significantly increased risks of all-cause mortality (HR: 1.39, 95% CI: 1.33-1.41) and cardiovascular mortality (HR: 1.42, 95% CI: 1.14-1.74). In the Fuwai Hospital cohort (median follow-up of 3.1 years), the CHG Q4 group also demonstrated a significantly elevated risk of MACE (HR: 1.37, 95% CI: 1.17-1.61) and hard endpoint (HR: 1.87, 95% CI: 1.24-2.81). Kaplan-Meier curves showed significant separation in cumulative event rates across CHG quartiles in both cohorts (log-rank P < 0.05). RCS analyses demonstrated positive linear associations between CHG and all outcomes in both cohorts. Time-dependent ROC curves showed that the CHG index consistently outperformed the TyG index model in predicting adverse outcomes (all FDR-adjusted P < 0.05). CONCLUSIONS: In two large independent cohorts of individuals with prior MI, the CHG index was independently associated with risks of adverse events. While its independent discriminative power is modest, the index serves as a valuable adjunctive tool that enhances risk reclassification, warranting further validation in prospective clinical settings to confirm its utility in secondary prevention.
Triglyceride glucose index-a body shape index (TyG-ABSI) outperforms traditional obesity indices in predicting all-cause and cardiovascular mortality in metabolic-dysfunction associated steatotic liver disease: the mediating role of biological aging.
Yang G, He W, Qiu X … +5 more , Shen S, Li P, Feng Y, Zhang J, Xiang B
Cardiovasc Diabetol · 2026 Feb · PMID 41724967 · Full text
BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is burdened by significant all-cause and cardiovascular mortality, yet simple and effective predictive indices for long-term outcomes are curre...
BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is burdened by significant all-cause and cardiovascular mortality, yet simple and effective predictive indices for long-term outcomes are currently lacking. In this study, we investigated the prognostic value of the triglyceride glucose-a body shape index (TyG-ABSI), a novel composite of insulin resistance and visceral adiposity, for mortality in MASLD. METHODS: This prospective cohort study included 7515 adults with MASLD from the National Health and Nutrition Examination Survey (NHANES, 1999-2018). MASLD was defined as a Fatty Liver Index ≥ 60 accompanied by at least one cardiometabolic risk factors. The primary outcomes were all-cause mortality (ACM) and cardiovascular mortality (CVM). Kaplan-Meier survival curves, multivariable Cox regression, restricted cubic splines (RCS), and receiver operating characteristic (ROC) analyses were employed to evaluate the predictive value of TyG-ABSI. Additionally, subgroup, sensitivity, and mediation analyses were conducted to verify robustness and explore underlying mechanisms. RESULTS: During a median follow-up of 138 months, 1368 all-cause and 376 cardiovascular deaths were recorded. TyG-ABSI demonstrated improved predictive accuracy compared to TyG, TyG-BMI, TyG-WC, and TyG-WHtR, as evidenced by higher AUC values and significant Net Reclassification Improvement（NRI). In fully adjusted models, participants in the highest TyG-ABSI quartile faced significantly elevated risks of ACM (HR 1.49, 95% CI 1.03-2.14) and CVM (HR 2.32, 95% CI 1.02-5.30) relative to the lowest quartile. RCS analysis indicated a linear dose-response relationship, and the associations remained robust across subgroup and sensitivity analyses. Mediation analysis revealed that accelerated biological aging significantly mediated mortality risks, with KDM and HD explaining 24.75% and 32.15% of ACM, and 34.89% and 46.53% of CVM, respectively. CONCLUSIONS: TyG-ABSI serves as a robust, independent predictor of mortality in patients with MASLD, outperforming traditional TyG-related metrics. The association is significantly associated with the pathway of accelerated biological aging, highlighting the utility of TyG-ABSI for enhanced risk stratification in clinical practice.
Association between estimated glucose disposal rate and cause-specific mortality among individuals with metabolic dysfunction-associated steatotic liver disease.
Lai W, Zhou Y, Xiao L … +4 more , Zhang T, He W, Gu W, Lin Y
Cardiovasc Diabetol · 2026 Feb · PMID 41724963 · Full text
BACKGROUND: Insulin resistance (IR) serves as a core pathophysiological factor among patients with metabolic dysfunction-associated steatotic liver disease (MASLD) and has an adverse impact on prognosis. As a reliable in...
BACKGROUND: Insulin resistance (IR) serves as a core pathophysiological factor among patients with metabolic dysfunction-associated steatotic liver disease (MASLD) and has an adverse impact on prognosis. As a reliable indicator of IR, the estimated glucose disposal rate (eGDR) is associated with cardiometabolic risk and mortality. However, the prognostic significance of eGDR in MASLD remains unclear. This study aims to examine the association between eGDR and cause-specific mortality in patients with MASLD. METHODS: Totally 6,847 patients with MASLD were included from the National Health and Nutrition Examination Survey (NHANES) 1999-2018. Patients were divided into four groups based on eGDR quartiles. The study outcomes were all-cause, cardiovascular and diabetes mortality. Restricted cubic splines (RCS) and the Cox proportional hazard model were used to evaluate the associations between eGDR and outcomes. Receiver operating characteristic (ROC) analyses were conducted to show its predictive ability for outcomes. Subgroup analyses were conducted to evaluate the robustness of performance. RESULTS: During the median follow-up of 8.8 years, 19.6% patients (n = 1,345) experienced death, with 6.5% (n = 443) cardiovascular mortality, and 1.3% (n = 89) diabetes mortality. After adjusting for confounders, higher eGDR level was significantly associated with lower risk of all-cause mortality (HR = 0.94, 95% CI: 0.92-0.97, P < 0.001), cardiovascular mortality (HR = 0.90, 95% CI:0.85-0.95, P < 0.001), and diabetes mortality (HR = 0.70, 95% CI: 0.62-0.80, P < 0.001). ROC analyses showed that the eGDR had a significant but modest predictive performance for all-cause mortality (AUC = 0.606) and cardiovascular mortality (AUC = 0.631), with a moderate performance for diabetes mortality (AUC = 0.729). Among different subgroups, the association between the eGDR and the risk of cause-specific mortality was similar to the main results. CONCLUSION: Higher eGDR levels are independently associated with reduced risks of all-cause, cardiovascular, and diabetes mortality among patients with MASLD, highlighting the prognostic relevance of insulin resistance in this population. The modest discriminative performance of eGDR further supports its role in cardiometabolic risk stratification.
Erythrocytosis after SGLT2 inhibitor initiation and anticoagulated outcomes in atrial fibrillation: a real-world analysis with counterfactual modeling.
Qi Z, Liu J, Gu T … +7 more , Wu N, Liu J, Zhao J, Tse G, Lip GYH, Chen KY, Liu T
Cardiovasc Diabetol · 2026 Feb · PMID 41724932 · Full text
BACKGROUND: Erythrocytosis has emerged as a hematologic response to sodium–glucose cotransporter 2 (SGLT2) inhibitor therapy, yet its occurrence and potential impact on bleeding and thromboembolic outcomes among patients...
BACKGROUND: Erythrocytosis has emerged as a hematologic response to sodium–glucose cotransporter 2 (SGLT2) inhibitor therapy, yet its occurrence and potential impact on bleeding and thromboembolic outcomes among patients with atrial fibrillation receiving anticoagulant therapy remain unknown. METHODS: We conducted a population-based cohort study using the Tianjin Health and Medical Data Platform, including adults with atrial fibrillation (AF) receiving oral anticoagulants from 2011 to 2024. In Part 1, employing a new-user design with a stratified pseudo-time strategy, SGLT2 inhibitor initiation was compared with non-use for incident erythrocytosis, estimated by Poisson regression to calculate incidence rate ratios. In Part 2, restricted to SGLT2 inhibitor users, erythrocytosis served as the exposure for thromboembolic and bleeding outcomes, analyzed with Fine–Gray and Cox models. Active comparator analyses, propensity score matching, subgroup and sensitivity analyses, and counterfactual mediation and decision modeling tested robustness and individualized treatment thresholds. RESULTS: Among 47,401 eligible patients with AF receiving anticoagulant therapy, a stratified pseudo-time strategy was applied to minimize immortal time bias, identifying 39,190 patients for analysis (mean age 72.5 ± 9.7 years; 48.1% female). Of these, 6,697 were SGLT2 inhibitor users. Erythrocytosis occurred in 11.3% of users compared with 3.1% of non-users within 6 ± 2 months, corresponding to an adjusted incidence rate ratio of 3.85 (95% CI 2.78–5.31). In the full follow-up, erythrocytosis was independently associated with a higher risk of thromboembolic events (Model 5 aHR 2.34, 95% CI 1.39–3.94; p = 0.001) but this was not statistically significant for bleeding (aHR 1.42, 95% CI 0.81–2.49; p = 0.22). Subgroup and sensitivity analyses yielded consistent results across age, sex, kidney function, and anticoagulant type. Mediation and counterfactual analyses indicated that the hemoglobin rise acted primarily as a risk marker rather than a causal mediator. CONCLUSIONS: SGLT2 inhibitor-associated erythrocytosis is a frequent hematological response in patients with AF receiving anticoagulant therapy and marks a phenotype predisposed to thromboembolism rather than bleeding. Based on counterfactual mediation analysis, the rise in hemoglobin levels likely represents a risk marker rather than a causal mediator, warranting early monitoring for personalized risk management.
Proteomics-derived organ-specific aging clusters predict macrovascular and microvascular complications in diabetes.
Yuan S, Lin Z, Song Y … +4 more , Shi K, Guan J, Zhao Z, Dou K
Cardiovasc Diabetol · 2026 Feb · PMID 41692750 · Full text
BACKGROUND: Aging is intrinsically linked to diabetes pathogenesis, yet evidence gaps persist regarding organ-specific aging and risks of long-term diabetes complications. This study aims to estimate the association betw...
BACKGROUND: Aging is intrinsically linked to diabetes pathogenesis, yet evidence gaps persist regarding organ-specific aging and risks of long-term diabetes complications. This study aims to estimate the association between plasma proteomics-based organ-specific aging and risks of long-term diabetes complications. METHODS: This cohort study quantified biological age gaps (residuals from linear regression of predicted versus chronological age) across 11 organ systems in 1979 baseline diabetes patients based on plasma proteomic profiling (Olink Explore 3072) of 2916 proteins and three validated different aging models. Extreme aging was defined as > 1.5 standard deviation from organ-specific mean age gaps. Multivariable Cox models assessed incident complication risks in 1707 complication-free patients. RESULTS: During a median follow-up time of 12.71 years, 356 incident all-cause deaths (20.86%), 348 incident cardiovascular disease (CVD) (20.39%), 227 incident diabetic retinopathy (DR) (13.30%), 88 incident peripheral artery disease (PAD) (5.16%), and 280 incident chronic kidney disease (CKD) (16.40%) occurred. Extreme cardiac aging showed strongest CVD risk association (adjusted HR: 2.92, 95% CI: 2.13, 3.99; P < 0.001), with significant brain (adjusted HR: 1.43, 95% CI: 1.06, 1.92; P = 0.019), arterial (adjusted HR: 1.59, 95% CI: 1.06, 2.39; P = 0.024), and pancreatic (adjusted HR: 1.35, 95% CI: 1.04, 1.77; P = 0.027) aging associations. Each complication demonstrated distinct organ-aging signatures. The association remains robust and consistent across three distinct aging models. Patients with baseline extreme aging in more than 3 organs faced significantly higher risks of incident diabetes complications compared to those with no or only one to three extremely aged organs. Additive interaction analysis revealed synergistic effects of organ aging on complications risk in diabetes. For example, concurrent heart and muscle aging substantially elevated CVD risk with a relative excess risk due to interaction (RERI) of 3.49 (95% CI: 0.74, 8.16) and an attributable proportion (AP) of 0.58 (95% CI: 0.14, 0.74). CONCLUSIONS: Proteomics-based organ aging assessment identifies significant complication-specific vulnerability patterns and substantially elevated risks with multiorgan involvement, supporting comprehensive aging evaluation for diabetes risk stratification. These findings require further validation in larger and more diverse populations and warrant more precise characterization of organ-specificity to enhance their robustness and generalizability.
Epicardial fat remodeling in end-stage heart failure with reduced ejection fraction.
Mączewski M, Załęska-Kocięcka M, Nowakowski M … +15 more , Mazuruk M, Nogajski Ł, Czerwińska H, Gronek I, Smoliński M, Świstak A, Kurpias M, Łuniewska O, Kacperska M, Pilzak F, Wojdyńska Z, Michałowska I, Mączewski M, Paterek A, Leszek P
Cardiovasc Diabetol · 2026 Feb · PMID 41692740 · Full text
BACKGROUND: Epicardial adipose tissue (EAT) transformation in heart failure with reduced ejection fraction (HFrEF) is poorly understood, which limits its potential as a therapeutic target and prognostic factor. The aim o...
BACKGROUND: Epicardial adipose tissue (EAT) transformation in heart failure with reduced ejection fraction (HFrEF) is poorly understood, which limits its potential as a therapeutic target and prognostic factor. The aim of our study was to characterize EAT in patients with HFrEF at the histological, computed tomography (CT) imaging and radiomic level to better understand its transformation in HFrEF. METHODS: We enrolled 70 patients with HFrEF who were scheduled for implantation of a left ventricular assist device (LVAD) or orthotopic heart transplantation (OHT). Fifty non-heart failure (HF) subjects served as controls. All participants underwent contrast- or non-contrast-enhanced chest CT imaging for EAT analysis. Left ventricular myocardial cones with overlying EAT were obtained from LVAD patients during surgery, from explanted OHT hearts, and from 20 unused healthy donor hearts for histological analysis. RESULTS: While total EAT volume did not differ between non-HF and HFrEF subjects, its density assessed in CT images, was higher in HFrEF. Moreover, periventricular EAT exhibited density gradient, with the densest voxels immediately adjacent to the myocardium (over up to 1 mm). This density gradient was extended to almost 3 mm in LV EAT in HFrEF patients. Histological analysis showed that adipocytes also exhibited a characteristic cell size gradient, with smaller cells adjacent to the myocardium, more pronounced than in non-HF subjects; moreover, median LV EAT adipocyte size was smaller in HFrEF vs. non-HF patients. However, EAT fibrosis and blood vessel density did not differ between non-HF and HFrEF subjects. Both histological analysis and radiomic analysis of CT images revealed that EAT was more heterogeneous in HFrEF than in non-HF subjects. These changes were most pronounced in LV EAT, but other EAT depots (RV and periatrial) were also affected. CONCLUSIONS: LV EAT in HFrEF contains smaller adipocytes and has higher density in CT images, exhibits pronounced cell size/density gradient and is more heterogeneous than in non-HF subjects. Thus LV EAT undergoes complex remodeling in HFrEF. Further studies are needed to elucidate the mechanisms driving this remodeling, determine whether it can be therapeutically targeted, and assess which parameters may have prognostic value in patients with HFrEF.
Prognostic impact of metformin in diabetic patients undergoing a percutaneous coronary intervention (PCI): protective effect is modified by procedural complexity.
Zheng Z, Wang Z, He J … +3 more , Song Y, Song W, Dou K
Cardiovasc Diabetol · 2026 Feb · PMID 41691210 · Full text
BACKGROUND: Metformin, a widely prescribed glucose-lowering agent, has demonstrated cardiovascular benefits in patients with diabetes who do not have established atherosclerotic cardiovascular disease. However, evidence...
BACKGROUND: Metformin, a widely prescribed glucose-lowering agent, has demonstrated cardiovascular benefits in patients with diabetes who do not have established atherosclerotic cardiovascular disease. However, evidence regarding its role specifically in patients with diabetes undergoing percutaneous coronary intervention (PCI) remains limited. This study therefore aimed to evaluate the prognostic association of metformin use in this high‑risk population and to explore its potential interaction with procedural complexity. METHODS: From January 2017 to December 2018, 11,585 diabetic patients undergoing PCI at Fuwai hospital were consecutively enrolled in our study. Patients were categorized into four groups according to metformin use and PCI complexity. The primary endpoint was major adverse cardiovascular and cerebrovascular events (MACCEs), including cardiovascular death, non-fatal myocardial infarction (MI), non-fatal stroke, and unplanned revascularization. RESULTS: After a follow-up of 3 years, a total of 1292 MACCEs were recorded. Overall, metformin use was observed to be associated with a lower incidence of 3-year MACCEs (adjusted HR 0.80, 95%CI 0.70–0.92) after multivariable adjustment. Significantly lower incidence of MACCEs was observed in patients undergoing non-complex PCI (adjusted HR 0.65, 95% CI: 0.53–0.79), while such protective effect of metformin didn’t exist in complex PCI patients (adjusted HR 1.00, 95%CI: 0.83–1.21). Significant interaction between metformin and PCI complexity was found with regard to the 3-year MACCE rate (Pinteraction = 0.003; adjusted Pinteraction = 0.002). CONCLUSIONS: In this observational study, there was significant difference in the efficacy of metformin in diabetic patients undergoing complex or non-complex PCI. Metformin use was associated with improved prognosis in patients with diabetes undergoing non-complex PCI.
The association of C-reactive protein-triglyceride-glucose index with cardiometabolic multimorbidity in middle-aged and older adults: evidence from two cohort studies.
Lin Y, Tao J, Wang H … +4 more , Guan H, Liu X, Dong X, Gao W
Cardiovasc Diabetol · 2026 Feb · PMID 41688996 · Full text
BACKGROUND: Cardiometabolic multimorbidity (CMM) is increasingly common among middle-aged and older adults, but there remains a lack of simple risk indicators that can simultaneously reflect inflammatory and metabolic bu...
BACKGROUND: Cardiometabolic multimorbidity (CMM) is increasingly common among middle-aged and older adults, but there remains a lack of simple risk indicators that can simultaneously reflect inflammatory and metabolic burden. The C-reactive protein-triglyceride-glucose index (CTI) has been proposed as a novel biomarker that integrates insulin resistance and inflammatory status. This study aimed to assess the association of CTI and its cumulative exposure with CMM. METHODS: This study conducted the primary analyses using the 2011 baseline cross-sectional data and the 2011-2020 prospective follow-up data from the China Health and Retirement Longitudinal Study (CHARLS), and additionally performed longitudinal supplementary analyses by calculating cumulative CTI over 2011-2015 within CHARLS. An external longitudinal validation was conducted using the 2002-2012 cohort from the UK English Longitudinal Study of Ageing (ELSA), and cross-population cross-sectional replication was further performed using the 2001-2010 data from the US National Health and Nutrition Examination Survey (NHANES). Multivariable logistic regression, Cox proportional hazards models, Kaplan-Meier curves, and restricted cubic spline analyses were used to examine the associations of CTI with the prevalence and incident risk of CMM, and cumulative CTI from 2011 to 2015 was calculated in CHARLS for supplementary analyses; meanwhile, receiver operating characteristic (ROC) curves were used to evaluate the predictive performance of CTI for 4-year CMM occurrence, and prespecified subgroup analyses were conducted to test the robustness of the findings. RESULTS: In the CHARLS prospective cohort, among 10,863 participants free of CMM at baseline, 1698 incident CMM cases (15.6%) occurred during approximately 9 years of follow-up. In the primary model, each 1-unit increase in baseline CTI was associated with a 71% higher risk of CMM (HR = 1.71, 95% CI 1.39-2.11), and the hazard ratio comparing the highest with the lowest quartile of CTI was 1.33 (95% CI 0.94-1.88); in the 2015 baseline subcohort, each 1-unit increase in cumulative CTI was associated with an HR of 1.02 (95% CI 1.00-1.05). Cross-sectional analyses in CHARLS and NHANES both showed a significant positive association between CTI and CMM prevalence, with a dose-response relationship. After adding CTI to a model containing traditional risk factors, the area under the receiver operating characteristic curve (AUC) for 4-year CMM prediction increased from 0.753 to 0.778. In the external longitudinal validation, 3129 participants from the ELSA cohort were included, among whom 406 incident CMM cases occurred during follow-up (13.0%). In the primary model, each 1-unit increase in CTI was associated with an HR of 1.59 (95% CI 0.99-2.55), and participants in the highest quartile had a higher risk than those in the lowest quartile (HR = 2.22, 95% CI 1.06-4.62), with a significant trend test (P for trend = 0.027), indicating that the direction of the association was consistent with that observed in CHARLS. CONCLUSIONS: CTI and its cumulative exposure level are closely associated with both the prevalence and incidence risk of CMM, and these findings were further supported by validation in the independent longitudinal ELSA cohort. As a simple composite index derived from routinely measured indicators, CTI may help identify individuals at high risk of CMM and provide a reference for early risk stratification and intervention in middle-aged and older populations.
Stress hyperglycemia ratio in coronary artery disease: a systematic review and meta-analysis of severity and prognosis.
Wang C, Liang S, Zhang J … +7 more , Lang Q, Huang X, Liu L, Liu J, Yi Y, Tian L, Yu X
Cardiovasc Diabetol · 2026 Feb · PMID 41688977 · Full text
BACKGROUND: The stress hyperglycemia ratio (SHR), calculated as the ratio of admission blood glucose to estimated average glucose derived from glycated hemoglobin, quantifies the degree of relative hyperglycemia during a...
BACKGROUND: The stress hyperglycemia ratio (SHR), calculated as the ratio of admission blood glucose to estimated average glucose derived from glycated hemoglobin, quantifies the degree of relative hyperglycemia during acute physiological stress. This systematic review and meta-analysis aimed to synthesize the current evidence on the association between SHR and the anatomical severity and clinical prognosis of coronary artery disease (CAD). METHODS: PubMed, EMBASE, Web of Science, and the Cochrane Library were systematically searched for studies published from inception to January 24, 2026. Cross-sectional, retrospective, and prospective cohort studies involving patients with CAD were included. Outcomes related to CAD severity comprised large thrombus burden, multi-vessel disease, non-target lesion progression, and in-stent restenosis. The primary outcome for CAD prognosis was major adverse cardiovascular events (MACE). Data were pooled using random-effects models to estimate hazard ratios (HRs) or odds ratios (ORs) and their 95% confidence intervals (CIs). CAD is classified into acute coronary syndrome (ACS) and chronic coronary syndrome (CCS). RESULTS: Nine studies evaluating CAD severity and thirty-one studies assessing CAD prognosis met the inclusion criteria. SHR was significantly associated with multiple markers of increased CAD severity. In the ACS subgroup, pooled analysis indicated that the highest SHR levels were significantly associated with an increased risk of MACE (HR: 1.60, 95% CI 1.41-1.81, P < 0.00001; OR: 1.58, 95% CI 1.19-2.11, P = 0.002). This prognostic value was confirmed in continuous variable analyses (HR: 1.59, 95% CI 1.27-2.00; OR: 3.50, 95% CI 1.47-8.32 per unit increment). Similarly, in the CCS subgroup, patients in the highest SHR category exhibited a higher risk of MACE (HR: 1.95, 95% CI 1.50-2.52; P < 0.00001), a finding consistent across continuous analyses (HR: 1.87, 95% CI 1.64-2.12, P < 0.00001 per unit increment). Consistently significant associations were observed across various secondary endpoints and additional subgroups. CONCLUSION: The current evidence suggests that SHR can reflect the anatomical complexity of CAD patients and serves as a valuable, easily accessible tool for risk stratification in this population.
Timing-dependent anti-inflammatory effects of empagliflozin in monocyte-derived macrophages from post-myocardial infarct patients with type 2 diabetes.
Cliff CL, Shah MU, Ward JK … +4 more , Inghels M, Lee K, Squires PE, Hills CE
Cardiovasc Diabetol · 2026 Feb · PMID 41680826 · Full text
BACKGROUND AND OBJECTIVE: Inflammation drives early recurrent cardiovascular risk in type 2 diabetes mellitus (T2DM) patients following acute myocardial infarction (AMI), particularly within 30-90 days post-discharge. So...
BACKGROUND AND OBJECTIVE: Inflammation drives early recurrent cardiovascular risk in type 2 diabetes mellitus (T2DM) patients following acute myocardial infarction (AMI), particularly within 30-90 days post-discharge. Sodium-glucose co-transporter 2 (SGLT2) inhibitors such as empagliflozin (EMPA) provide cardiometabolic benefits, but their anti-inflammatory effects and optimal timing after AMI remain unclear. Given the prognostic role of systemic markers like the neutrophil-to-lymphocyte ratio, we investigated whether early initiation of EMPA modulates NOD-like receptor protein-3 (NLRP3) inflammasome activity and inflammatory responses in monocyte-derived macrophages (MDMs) from T2DM-AMI patients. METHODS: Sixty-six participants were randomised to receive EMPA either at discharge (Arm-A) or following a 90-day delay (Arm B). Clinical data and biological samples were collected over 180 days. CD14+ MDMs and plasma were obtained at days 0, 30, and 90 (EMPA vs. no EMPA), and days 90, 120, and 180 (early vs. delayed). Inflammatory and metabolic markers were assessed using RT-qPCR, luminescence-based caspase-1 and ATP assays, and targeted immunoassays. RESULTS: Early EMPA administration was associated with reduced NLRP3 priming (IL1β mRNA) and activation (caspase-1 activity), potentially linked to decreased release of ATP, a danger associated molecular pattern (DAMP). In the absence of EMPA, pro-inflammatory cytokines (TNFα, IL6, MCP1) and M1 macrophage markers (e.g., CD80) either increased or remained unchanged over time. Early EMPA treatment appeared to stabilise or reduce their expression. Markers of cell senescence (p21, IL8, BCL2) were also modulated. Plasma levels of senescence-associated markers (MMP9, OPN, Serpin E1) remained largely unchanged, highlighting the importance of evaluating macrophage-specific responses. CONCLUSION: Early empagliflozin administration in T2DM-AMI patients was associated with modulation of NLRP3-related inflammatory and senescence pathways in patient-derived macrophages, benefits observed when cells were stimulated ex-vivo with an inflammatory stimulus. These findings provide mechanistic insight into the timing-dependent anti-inflammatory effects of EMPA and underscore its potential for immediate post-AMI use to reduce inflammation and lower residual cardiovascular risk, supporting further clinical investigation.
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