Cardiovasc Diabetol [JOURNAL]
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200 papers
Joint associations of anthropometric indices and C-reactive protein-triglyceride-glucose index with incident hypertension: a stratified analysis by blood pressure level from the CHARLS, 2011-2020.
Liao C, Liu L, Bao W … +6 more , Lai H, Tian R, Zhang S, He L, Li J, Tu H
Cardiovasc Diabetol · 2026 Mar · PMID 41872856 · Full text
BACKGROUND: Visceral obesity contributes to hypertension through pathways of insulin resistance and inflammation. The joint association of C-reactive protein-triglyceride-glucose index (CTI), which integrates these pathw...
BACKGROUND: Visceral obesity contributes to hypertension through pathways of insulin resistance and inflammation. The joint association of C-reactive protein-triglyceride-glucose index (CTI), which integrates these pathways, and anthropometric indices with incident hypertension remains unclear, especially across different baseline blood pressure. METHODS: The data for this study were obtained from the China Health and Retirement Longitudinal Study (CHARLS) across the 2011 to 2020 survey waves. Participants were stratified based on the median values of anthropometric indices and CTI. The associations with incident hypertension risk were evaluated using Kaplan-Meier curves, multivariable Cox regression, and restricted cubic spline (RCS) methods. Predictive performance was assessed by receiver operating characteristic (ROC) curve analysis, net reclassification improvement (NRI), and integrated discrimination improvement (IDI). Mediation and interaction analyses were conducted to explore potential mediating effects and the robustness of the findings. RESULTS: Among 4,735 eligible participants, the median age was 56 years, and 46.04% were male. During the 9-year follow-up period, 1,852 participants (39.37%) developed hypertension. Cox regression analysis revealed that Compared with subjects with lower levels of both anthropometric indices and CTI, those with higher levels of both exhibited the highest risk of hypertension. Individuals with both BRI and CTI above the median consistently exhibited the highest risk of hypertension across all subgroups: HR = 1.51, 95% CI: 1.33-1.71 in the total population; HR = 1.58, 95% CI: 1.29-1.93 in the normal BP group; and HR = 1.45, 95% CI: 1.23-1.71 in the elevated BP group. After incorporating anthropometric indices and CTI into the basic model, the predictive performance for hypertension was significantly improved. The integrated model of BRI and CTI demonstrated the best overall predictive performance (AUC = 0.747). Mediation analysis revealed that CTI significantly mediated the association between anthropometric indices and hypertension. CONCLUSION: These anthropometric indices and CTI effectively predicted hypertension risk across populations with different baseline blood pressures, both independently and in combination. Among all evaluations, the combination of BRI and CTI emerged as the optimal approach, most robustly associated with incident hypertension and providing the greatest improvement in risk discrimination and reclassification.
Bidirectional association between non-steatotic chronic liver disease and heart disease: the potential link of insulin resistance.
Zhang Y, Wang J, Song K … +1 more , Yao Z
Cardiovasc Diabetol · 2026 Mar · PMID 41865235 · Full text
BACKGROUND: Chronic liver disease (CLD) and heart disease (HD) are major contributors to global morbidity and mortality. Although increasing evidence supports close interactions between the liver and heart, population-ba...
BACKGROUND: Chronic liver disease (CLD) and heart disease (HD) are major contributors to global morbidity and mortality. Although increasing evidence supports close interactions between the liver and heart, population-based longitudinal data evaluating their bidirectional temporal relationship remain limited, particularly beyond metabolic dysfunction–associated steatotic liver disease (MASLD). This study aimed to investigate the bidirectional association between CLD, excluding steatotic liver disease, and HD, and to explore the potential mediating role of insulin resistance (IR) in a nationally representative cohort. METHODS: This longitudinal cohort study utilized data from five waves of the China Health and Retirement Longitudinal Study conducted between 2011 and 2020. Cox proportional hazards models were applied to examine the bidirectional associations between HD and CLD. Mediation analyses were performed to assess whether IR, measured by the triglyceride–glucose (TyG) index and the metabolic score for IR (METS-IR), mediated these associations. Multiple sensitivity and subgroup analyses were conducted to evaluate robustness. RESULTS: Among 6,230 participants free of HD at baseline, CLD was associated with a significantly increased risk of incident HD (HR:1.803, 95% CI 1.376–2.362). Conversely, among 6,917 participants without baseline CLD, HD was associated with a higher risk of developing CLD (HR: 2.303, 95% CI 1.813–2.924). These associations were consistent across predefined subgroups and sensitivity analyses. Mediation analyses indicated that the TyG index and the METS-IR partially mediated the association between HD and incident CLD but not the association between CLD and incident HD. CONCLUSION: In this nationally representative longitudinal study, CLD and HD were bidirectionally associated among middle-aged and older adults. IR partially mediated the pathway from HD to CLD, suggesting asymmetric mechanisms underlying liver–heart interactions. These findings underscore the clinical relevance of the liver–heart axis and highlight the need for integrated strategies to prevent and manage liver and cardiovascular diseases in aging populations.
Circulating cardiometabolic metabolite profiles associated with ambient air pollution and atrial fibrillation risk: a prospective cohort study.
Shi T, Yang C, Fan Z … +20 more , Sieme M, Tangos M, Wu X, Lin M, Huang D, Sasko B, Wintrich J, Khan M, Liu X, Aweimer A, Mügge A, Akin I, van Heerebeek L, El-Battrawy I, Norata GD, Schotten U, Paneni F, Huang K, Yang J, Hamdani N
Cardiovasc Diabetol · 2026 Mar · PMID 41864905 · Full text
BACKGROUND: Ambient air pollution has been linked to atrial fibrillation (AF), yet the underlying metabolic mechanisms remain poorly understood. METHODS: We analyzed 227,324 UK Biobank participants without baseline AF. W...
BACKGROUND: Ambient air pollution has been linked to atrial fibrillation (AF), yet the underlying metabolic mechanisms remain poorly understood. METHODS: We analyzed 227,324 UK Biobank participants without baseline AF. We constructed an air pollution score by aggregating all four pollutants (PM, PM, NO, NO). Nuclear magnetic resonance metabolomics identified a pollution-related metabolic signature through elastic net regression. Associations between air pollutants, the metabolic signature and AF were analyzed using Cox models. Mediation analysis was employed to examine the role of the metabolic signature in the association between air pollutants and AF. RESULTS: During follow-up, 16,235 participants (7.14%) developed AF. We identified 65-metabolite signature significantly associated with air pollution, predominantly comprising lipoprotein lipid concentrations (32.31%), lipoprotein subclasses (15.38%), fatty acids (13.85%), and amino acids (12.31%). Each standard deviation increase in this metabolic signature was associated with 18% higher AF risk (HR = 1.18, 95%CI:1.03-1.35). The metabolic profile mediated 15.45% of the relationship between air pollution and AF, with lipoprotein parameters showing the strongest mediation effects. CONCLUSION: Air pollution-related metabolic signature was independently associated with AF risk and mediated a significant portion of pollution's arrhythmogenic effects. These findings provide novel insights into biological mechanisms linking environmental exposures to AF.
Benefits of sacubitril/valsartan alone and in combination with dapagliflozin in a preclinical female model of cardiometabolic and age-related cardiac dysfunction.
Mele E, Riemma MA, Donniacuo M … +12 more , Telesca M, Sorrentino G, D'Amario D, Scialò F, Cianflone E, Cappetta D, Torella D, Castaldo G, Rossi F, Berrino L, Urbanek K, De Angelis A
Cardiovasc Diabetol · 2026 Mar · PMID 41862954 · Full text
BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) disproportionately affects elderly women and is closely associated with central obesity and metabolic dysfunction. Although sodium-glucose co-transporter...
BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) disproportionately affects elderly women and is closely associated with central obesity and metabolic dysfunction. Although sodium-glucose co-transporter-2 inhibitors (SGLT2i) are recommended in all HFpEF patients, the potential benefit of angiotensin receptor-neprilysin inhibitors (ARNi) alone or in combination with SGLT2i remain underexplored. ARNi may be particularly effective because of the reduced natriuretic peptides availability and heightened renin-angiotensin-aldosterone system (RAAS) activation associated with aging and central obesity, particularly in postmenopausal women. METHODS: Aged female F344 rats, which recapitulate features of metabolic stress, visceral adiposity, and cardiac aging observed in HFpEF patients, were used as a model of dysmetabolic aging heart failure (DAHF). From 15 months of age, animals received long-term treatment with sacubitril/valsartan (S/V; 60 mg/kg/day) alone or in combination with dapagliflozin (D; 0.1 mg/kg/day) for 45 weeks. Cardiac structure and function were assessed by echocardiography and invasive hemodynamic analysis. Histological and molecular analyses of cardiac tissue were used to investigate fibrosis, inflammation, oxidative stress, mitochondrial antioxidant activity, senescence markers, and cardiometabolic signalling pathways. Angiotensin II an Ang-(1–7), NT-pro-BNP, BNP, leptin and aldosterone were measured in plasma by enzyme-linked immunosorbent assay. Freshly isolated cardiomyocytes form young and middle-aged rats were used as in vitro model to investigate the effects of drugs on the AMPK/NAMPT/SIRT1 pathways. RESULTS: Positive effects were observed with S/V monotherapy, but S/V + D combination further improved diastolic function, reduced left ventricular filling pressures, and enhanced chamber compliance. Functional improvements were paralleled by reductions in plasma NT-proBNP and myocardial BNP. Both treatments attenuated cardiac fibrosis and inflammation by downregulating TGF-β1/SMAD3 signalling and pro-inflammatory cytokines (IL-6, TNF-α, NF-κB). Only the combination therapy significantly enhanced endothelial nitric oxide synthase (eNOS) expression and boosted myocardial antioxidant defences. The benefit of S/V + D was associated with reactivation of the Nrf2/Keap1 and the AMPK/NAMPT/SIRT axes and reduced markers of cellular senescence, including p53 acetylation and p21CIP1, and suppressed senescence-related microRNAs. CONCLUSIONS: S/V alone conferred significant myocardial protection which was further amplified when combined with D in a female model of cardiometabolic and age-related cardiac dysfunction. These findings support the hypothesis that long-term S/V + D combination therapy synergistically recruits interconnected antioxidant, metabolic, and anti-senescent pathways, establishing a positive molecular feedback loop. Together, these effects provide mechanistic insight into sex-specific therapeutic strategies and support a precision medicine approach for elderly women with HFpEF and central obesity.
Tryptophan metabolites and stroke risk after acute myocardial infarction in patients with and without metabolic syndrome: insights from a MACCE-based cohort.
Xiu L, Liu Y, Wu P … +10 more , Wang M, Cui H, Zhao J, Cui L, Yu H, Wei G, Fang C, Dai J, Fang S, Yu B
Cardiovasc Diabetol · 2026 Mar · PMID 41857600 · Full text
BACKGROUND: Metabolic syndrome (MetS) obviously increases the risk of major adverse cardiac and cerebrovascular events (MACCE) in patients with acute myocardial infarction (AMI). However, the metabolic mechanisms underly...
BACKGROUND: Metabolic syndrome (MetS) obviously increases the risk of major adverse cardiac and cerebrovascular events (MACCE) in patients with acute myocardial infarction (AMI). However, the metabolic mechanisms underlying this heightened vulnerability remain unclear, and individualized predictive models are limited. OBJECTIVE: To elucidate the role of tryptophan metabolism in MetS-related MACCE risk after AMI and to establish a machine learning model (random forest) for MACCE prediction. METHODS: A total of 3223 AMI patients undergoing percutaneous coronary intervention were enrolled between 2017 and 2021. Through untargeted metabolomics analysis, potential MetS-related metabolites were screened and identified, followed by internal validation of tryptophan metabolites—indole-3-lactic acid (ILA), tryptophan (TRP), kynurenine (KYN), and indole-3-propionic acid (IPA)—in 3190 patients. Cox regression was performed separately for Mets and no-Mets participants to assess the associations of Tryptophan Levels and with a primary focus on stroke risk, and secondary analyses of other MACCE components. A random forest model was constructed to predict MACCE over a 72-month follow-up by integrating metabolic and clinical variables. RESULTS: Patients with MetS exhibited significant disturbances in tryptophan metabolism. Elevated levels of indole-3-lactic acid (ILA), tryptophan (TRP), and kynurenine (KYN) were independently associated with higher stroke risk in MetS patients (adjusted HR per twofold increase: ILA 1.34, TRP 1.46, KYN 1.47; all P < 0.05), but not in non-MetS individuals. The random forest model exhibited good prediction performance (AUC 0.715; 95% CI 0.683–0.747), identifying KYN, indole-3-lactic acid (ILA) as major predictive features. CONCLUSION: Tryptophan metabolic dysregulation, particularly elevated KYN, was associated with a higher risk of stroke in AMI-MetS patients. By integrating untargeted discovery, targeted validation, and machine learning–based modeling, our study provides a novel framework for individualized risk stratification and supports further investigation into the translational potential of metabolic biomarkers in this high-risk cardiometabolic population.
Is there still room for pioglitazone in contemporary type 2 diabetes management?
Caruso I
Cardiovasc Diabetol · 2026 Mar · PMID 41840391 · Full text
Recent real-world evidence comparing glucagon-like peptide-1 receptor agonists (GLP-1RA) with pioglitazone indicates broadly comparable cardiovascular and hepatic outcomes in individuals with type 2 diabetes, with a lowe...
Recent real-world evidence comparing glucagon-like peptide-1 receptor agonists (GLP-1RA) with pioglitazone indicates broadly comparable cardiovascular and hepatic outcomes in individuals with type 2 diabetes, with a lower risk of heart failure among GLP-1RA users. These findings must be interpreted in the context of contemporary guidelines, which increasingly prioritize therapies with cardiometabolic benefits while restricting the role of pioglitazone to selected settings. Despite recognized adverse effects, pioglitazone retains clinical relevance due to its glycaemic efficacy, potential cardio-hepatic benefits, and low cost, particularly in health-care systems with limited access to newer agents. Rather than being interchangeable, pioglitazone and GLP-1RA occupy complementary positions within the current therapeutic landscape, underscoring the importance of individualized treatment selection.
Exercise modulates redox homeostasis in cardiovascular and metabolic diseases: from bench to clinic.
Wang J, Zhang J, Zhang H … +3 more , Yu F, Tian Z, Jia D
Cardiovasc Diabetol · 2026 Mar · PMID 41832545 · Full text
Cardiovascular and metabolic diseases remain the leading causes of global morbidity and mortality, underscoring the critical need for effective preventive and therapeutic strategies. Exercise training is a pivotal compon...
Cardiovascular and metabolic diseases remain the leading causes of global morbidity and mortality, underscoring the critical need for effective preventive and therapeutic strategies. Exercise training is a pivotal component of a healthy lifestyle and an effective non-pharmacological therapeutic strategy for delaying or even reversing disease progression. Growing evidence indicates that disrupted redox homeostasis is a central pathogenic mechanism underlying cardiovascular and metabolic disorders. Exercise exerts multifaceted benefits on redox balance by enhancing endogenous antioxidant capacity, attenuating oxidative stress and inflammation, and promoting mitochondrial biogenesis and metabolic remodeling. Additionally, exercise-induced exerkines modulate redox signaling and homeostasis, enhancing cellular stress response. This review integrates mechanistic insights from preclinical models with evidence from human observational and interventional studies to elucidate how exercise modulates redox homeostasis across molecular, cellular, and systemic levels. A deeper understanding of exercise-redox interactions will not only advance knowledge of disease pathogenesis but also facilitate the development of precision exercise prescriptions to restore redox balance and improve cardiovascular and metabolic health.
Associations of cumulative exposure and dynamic trajectories of cholesterol-HDL-glucose (CHG) index with cardiovascular disease in middle-aged and older Chinese adults: a longitudinal analysis.
Zhang Y, Liu B, Zhu Y … +4 more , Xie Y, Du Y, Xiong P, Lyu Q
Cardiovasc Diabetol · 2026 Mar · PMID 41832529 · Full text
BACKGROUND: A newer and novel index, the Cholesterol, High-Density Lipoprotein, and Glucose (CHG) index, has been proposed as a potential index for metabolic disorders. However, research on the relationship between CHG c...
BACKGROUND: A newer and novel index, the Cholesterol, High-Density Lipoprotein, and Glucose (CHG) index, has been proposed as a potential index for metabolic disorders. However, research on the relationship between CHG changes and cardiovascular disease (CVD) is limited. Our research aims to investigate the association between cumulative exposure and dynamic trajectories of CHG and cardiovascular disease risk. METHODS: Participants aged 45 and older were recruited from the China Health and Retirement Longitudinal Study (CHARLS). CVD was defined as self-reported description. K-means clustering analysis was used to classify dynamic CHG changes, and cumulative CHG (cuCHG) was calculated as follows: cuCHG=(CHG + CHG)/time interval (2012-2015). Cox proportional hazards regression and restricted cubic spline (RCS) regression models were conducted to evaluate the association between cumulative exposure and dynamic trajectories of CHG and CVD risk. RESULTS: A total of 6,171 participants were included in the study, among whom 1,136 (18.4%) experienced incident of CVD. The risk of CVD increased with higher levels of cuCHG. K-means clustering indicated three distinct trajectories CHG variation. Compared to the stable reference group (Cluster 3), participants in the high-risk slowly increasing trajectory (Cluster 2) had a significantly higher risk of CVD (HR = 1.28, 95%CI: 1.10-1.49, P = 0.002). However, the moderate-decreasing trajectory (Cluster 1) was not significantly associated with CVD risk (HR = 1.09, 95%CI: 0.98-1.21, P = 0.126). In the Cox regression analysis, compared with the lowest quartile (Q1), participants in the highest quartile (Q4) had a significantly increased risk of CVD by 22% (HR = 1.22, 95% CI: 1.06-1.40, P = 0.005, adjusted P = 0.007). Furthermore, CVD risk increased progressively across ascending cuCHG quartiles (P for trend < 0.05). RCS analysis demonstrated a linear association between cuCHG and CVD risk (for overall, P < 0.001). CONCLUSION: Our research indicates that both cuCHG and CHG changes are associated with CVD risk in middle-aged and older adults, particularly for those with consistently high-risk CHG levels, which are linked to a significantly increased CVD risk. In clinical practice, monitoring long-term CHG changes and maintaining relatively stable levels may help prevent CVD in this population.
Association between C-reactive protein-triglyceride-glucose index and risk of stroke in different renal function status: a national cohort study.
Xian W, Wu T, Zhao XX … +3 more , Yang Y, Li XY, Wang YL
Cardiovasc Diabetol · 2026 Mar · PMID 41832522 · Full text
BACKGROUND: The C-reactive protein-triglyceride-glucose index (CTI), a novel biomarker integrating inflammation and insulin resistance, has been linked to cardiovascular disease. However, its association with stroke risk...
BACKGROUND: The C-reactive protein-triglyceride-glucose index (CTI), a novel biomarker integrating inflammation and insulin resistance, has been linked to cardiovascular disease. However, its association with stroke risk across varying levels of renal function remains unclear. METHODS: This prospective cohort study included 8,808 participants aged ≥ 45 years from the China Health and Retirement Longitudinal Study (CHARLS), covering the period 2011 to 2018. CTI was calculated as 0.412×Ln (CRP [mg/L]) + Ln (TG [mg/dL]×FPG [mg/dL])/2. Multivariable Cox models and restricted cubic splines were employed to assess the association between CTI and incident stroke. We stratified the analysis by estimated glomerular filtration rate (eGFR) and introduced interaction terms between CTI and eGFR levels to evaluate potential effect modification. RESULTS: The mean age of the participants was 59.48 (9.41) years, and 4098 (46.5%) were male. During a median follow-up of 7 years, 404 (4.6%) stroke events occurred. In the fully adjusted model, each 1-unit increase in CTI was associated with a 15% higher stroke risk [hazard ratios (HR) = 1.15, 95% confidence interval (CI) = 1.00-1.32]. A significant positive linear dose-response relationship was observed (P <0.001, P = 0.289). Notably, we observed significant interaction between CTI and eGFR levels on stroke risk (P = 0.037). The association was markedly stronger in individuals with mildly reduced renal function (eGFR 60-89 mL/min/1.73 m²), where the highest CTI quartile (Q4) had an HR of 2.73 (95% CI: 1.16-6.40) compared to the Q1. Conversely, no significant associations were observed in participants with preserved (eGFR ≥ 90 mL/min/1.73 m²) or moderately-to-severely reduced renal function (eGFR < 60 mL/min/1.73 m²). CONCLUSION: Elevated CTI levels are associated with an increased risk of stroke in middle-aged and older Chinese adults, particularly among individuals with mild renal impairment. By combining inflammatory and metabolic markers, CTI might offer potential clinical value for risk assessment.
Cohort profile: The DIabetes and ST-segment Elevation Myocardial Infarction (DISTEMI) Study.
Möser C, Prystupa K, Schön M … +24 more , Yurchenko I, Bódis KB, Huttasch M, Michelotti F, Kupriyanova Y, Schrauwen-Hinderling V, Granata C, Bönhof GJ, Strom A, Herder C, Dörr D, Trenkamp S, Heilmann G, Bobrov P, Straßburger K, Szendroedi J, Cramer M, Polzin A, Jung C, Kelm M, Burkart V, Wagner R, Roden M, Zaharia OP
Cardiovasc Diabetol · 2026 Mar · PMID 41821026 · Full text
BACKGROUND: Humans with type 2 diabetes and/or metabolic dysfunction-associated steatotic liver disease (MASLD) are at higher risk of ST-segment elevation myocardial infarction (STEMI) and worse prognosis. However, mecha...
BACKGROUND: Humans with type 2 diabetes and/or metabolic dysfunction-associated steatotic liver disease (MASLD) are at higher risk of ST-segment elevation myocardial infarction (STEMI) and worse prognosis. However, mechanisms, prognostic factors and risk subtypes in humans with STEMI and (pre)diabetes with or without MASLD, are not fully understood. METHODS: The DIabetes and ST-segment Elevation Myocardial Infarction (DISTEMI) study is a prospective longitudinal cohort study, recruiting humans with different degrees of glucose tolerance after recent STEMI. This cohort study has the primary objective to detect changes in glycemia and insulin sensitivity derived from the oral glucose tolerance test (OGTT) and their relationships to cardiac function. Secondary objectives address tissue-specific insulin sensitivity and organ function, focusing on adipose tissue, liver and heart. Exploratory objectives comprise multiomic analyses and measures of mitochondrial function and quality of life. At 2 and 12 months after STEMI, participants undergo comprehensive cardiometabolic phenotyping (OGTT, modified Botnia clamp-test, magnetic resonance imaging/spectroscopy/elastography, high-resolution respirometry). Magnetic resonance-based techniques are employed to assess cardiovascular function and structure, adipose tissue distribution, skeletal muscle and hepatic lipid deposition and fibrosis, and hepatic energy metabolism. Exploratory analyses include multiomics of blood, urine, and stool samples. Multiomics analyses shall allow detecting biomarkers for stratification of cardiovascular disease risk. Currently, 100 participants have been included in DISTEMI, of whom 29% have type 2 diabetes. CONCLUSION: The DISTEMI study integrates comprehensive cardiometabolic phenomic with multiomic profiling to identify cardiometabolic STEMI subtypes and predictors of outcomes, and to improve precision risk stratification and targeted prevention. TRIAL REGISTRATION: NCT05046483.
Association of the estimated glucose disposal rate combined with a body shape index with all-cause and cardiovascular-specific mortality among individuals with cardiovascular-kidney-metabolic syndrome.
Fu C, Zhang Z, Li Y … +11 more , Wang F, Li C, Xie Z, Gao X, Sun L, Han B, Wang R, Liu S, Zhang H, Hou J, Zeng Q
Cardiovasc Diabetol · 2026 Mar · PMID 41820961 · Full text
BACKGROUND: Individuals with cardiovascular-kidney-metabolic (CKM) syndrome exhibit a substantially elevated risk of all-cause and cardiovascular-specific mortality. Although estimated glucose disposal rate (eGDR) and a...
BACKGROUND: Individuals with cardiovascular-kidney-metabolic (CKM) syndrome exhibit a substantially elevated risk of all-cause and cardiovascular-specific mortality. Although estimated glucose disposal rate (eGDR) and a body shape index (ABSI) are commonly used indicators for assessing insulin resistance and atherosclerotic risk, respectively, evidence regarding their combined effect on all-cause and cardiovascular-specific mortality in patients with CKM syndrome remains insufficient. Investigating this combined impact may help improve risk stratification in this population. METHODS: This study utilized data from the National Health and Nutrition Examination Survey (NHANES, 1999-2018), including 18,186 individuals with stage 0-4 CKM syndrome. Cox proportional hazards models, Kaplan-Meier curves and subgroup analyses were used to evaluate the associations between eGDR and ABSI and mortality risk. The integrated discrimination improvement (IDI) and net reclassification index (NRI) were used to assess the incremental prognostic value of eGDR and ABSI. Finally, six machine learning algorithms were applied to develop predictive models. RESULTS: During the follow-up period, a total of 2536 all-cause mortality and 790 cardiovascular-specific mortality were documented. After multivariable adjustment, both low eGDR and high ABSI independently predicted mortality risk. Combined analysis revealed that individuals with both Low-eGDR and High-ABSI had the highest mortality risk: all-cause mortality hazard ratio (HR) = 2.79 (95% CI 2.30-3.38) and cardiovascular-specific mortality HR = 4.53 (95% CI 2.96-6.92). However, the interaction effect was not statistically significant. Among the six machine learning algorithms, XGBoost demonstrated the best performance, with areas under the curve (AUC) of 0.877 and 0.850 for predicting all-cause and cardiovascular-specific mortality, respectively. CONCLUSION: Both eGDR and ABSI are independent and combined predictors of mortality risk among individuals with CKM syndrome. Their combined use significantly improves risk stratification and machine learning models provide an effective tool for precise risk assessment in this population.
Epicardial adipose tissue as a determinant of heart failure prognosis: insights across ejection fraction phenotypes.
Nowakowski M, Mazuruk M, Nogajski Ł … +5 more , Mączewski M, Czerwińska H, Kurpias M, Mączewski M, Paterek A
Cardiovasc Diabetol · 2026 Mar · PMID 41803855 · Full text
Epicardial adipose tissue (EAT) is a metabolically active fat depot located between the myocardium and visceral pericardium, directly interacting with cardiomyocytes and coronary vasculature. Emerging evidence suggests t...
Epicardial adipose tissue (EAT) is a metabolically active fat depot located between the myocardium and visceral pericardium, directly interacting with cardiomyocytes and coronary vasculature. Emerging evidence suggests that EAT plays a significant role in the pathophysiology and prognosis of heart failure (HF) across different left ventricular ejection fraction (LVEF) phenotypes. This review summarizes current data on the prognostic role of EAT in HF, including volume, thickness, and density, measured by echocardiography, computed tomography, and cardiac magnetic resonance imaging. In HF with preserved (HFpEF) and mildly reduced ejection fraction (HFmrEF), increased EAT consistently associates with adverse outcomes, including higher rates of hospitalization and mortality, independent of systemic obesity. In HF with reduced ejection fraction (HFrEF), the relationship is more complex, with studies showing both protective and detrimental associations depending on EAT quantity, density, and spatial distribution. EAT also appears to contribute to ventricular arrhythmogenesis, particularly in patients with preserved myocardial structure. Mechanistically, EAT may promote inflammation, fibrosis, and electrophysiological remodeling, while moderate amount EAT may exert metabolic or mechanical protection. Overall, EAT emerges as a promising imaging-derived biomarker for risk stratification in HF, highlighting the need for phenotype-specific evaluation and potential therapeutic targeting. Future studies should focus on EAT quality, remodeling, and its interaction with myocardial tissue to guide individualized HF management.
Comprehensive evaluation of triglyceride glucose index-a body shape index (TyG-ABSI) for incident peripheral artery disease: data-driven phenotyping and machine learning-based risk prediction in the UK Biobank.
Zhao W, Li X, Zhang X … +9 more , Guo Y, Zhang B, Cao Y, Diao Y, Wu Z, Lu C, Chen Z, Lan Y, Li Y
Cardiovasc Diabetol · 2026 Mar · PMID 41803825 · Full text
BACKGROUND: The prevalence of Peripheral Artery Disease (PAD) is rising globally, yet early risk stratification remains challenging due to the limitations of traditional obesity metrics. TyG-ABSI, an index combining Trig...
BACKGROUND: The prevalence of Peripheral Artery Disease (PAD) is rising globally, yet early risk stratification remains challenging due to the limitations of traditional obesity metrics. TyG-ABSI, an index combining Triglyceride-Glucose (TyG) with A Body Shape Index (ABSI), is a novel marker reflecting both functional insulin resistance and structural visceral adiposity. However, its predictive value for PAD remains unexplored in large prospective cohorts. METHODS: We included 390,274 adults from the UK Biobank. Baseline characteristics were analyzed across TyG-ABSI quartiles and PAD status. Associations between TyG-related indices and incident PAD were assessed using multivariable-adjusted Cox regression, Kaplan-Meier survival curves, and restricted cubic splines. Robustness was evaluated via Fine-Gray competing risk models, propensity score matching, subgroup analyses, and external validation in the NHANES database. Consensus k-means clustering, integrating biochemical and insulin resistance markers, identified metabolic phenotypes and stratified PAD risk. Feature selection (LASSO, Boruta, and Minimum Redundancy Maximum Relevance [mRMR]) guided the development of six machine learning models (logistic regression, GBM, XGBoost, AdaBoost, LightGBM, and neural network) for PAD prediction, with interpretability assessed via SHAP analysis. RESULTS: Higher TyG-ABSI and related indices were strongly associated with increased PAD incidence (cumulative incidence at 15 years: 4.16% in the top quartile vs. 0.98% in the bottom quartile; fully-adjusted Hazard Ratio [HR] per 1-SD increase for TyG-ABSI: 1.22, 95% Confidence Interval [CI] 1.17-1.27), which were robust in the NHANES external validation cohort. Clustering analysis revealed four distinct metabolic subgroups, with the highest PAD risk in the insulin resistance/glucose dysfunction cluster (HR vs. healthy phenotype: 7.48, 95% CI 6.82-8.21). Feature selection identified 19 key predictors. Logistic regression provided the most stable and generalizable prediction (validation Area Under the Curve [AUC] = 0.788, 95% CI 0.778-0.798), demonstrating superior generalizability compared to complex ensemble methods. SHAP analysis demonstrated TyG-ABSI, age, and neutrophil count as leading predictors for incident PAD and confirmed the interpretability of the model. CONCLUSION: TyG-ABSI is a robust, independent predictor of long-term PAD risk. Data-driven phenotyping and interpretable machine learning facilitate more precise risk stratification. Logistic regression offers optimal performance and interpretability, holding potential clinical utility for individualized PAD risk prediction.
Reactive carbonyl species in health and chronic disease: from methylglyoxal to an integrative network of metabolic regulation.
Li S, Nawroth PP, Kroll J
Cardiovasc Diabetol · 2026 Mar · PMID 41794756 · Full text
The prevalence of chronic diseases is increasing dramatically, but the metabolism, particularly the pervasive carbonyl stress that accompanies many of these conditions, is rarely considered a potential cause. Reactive ca...
The prevalence of chronic diseases is increasing dramatically, but the metabolism, particularly the pervasive carbonyl stress that accompanies many of these conditions, is rarely considered a potential cause. Reactive carbonyl species are spontaneously generated through a variety of endogenous metabolic reactions, and contain highly reactive carbonyl groups. Methylglyoxal, a prime reactive carbonyl, has been linked to cardiovascular disease, diabetes and its complications, obesity, chronic kidney disease, and ageing. Its detoxification is mainly regulated by the glyoxalase system; however, surprisingly, studies in mice, zebrafish and drosophila with a knockout of glyoxalase 1 showed viable animals with only minor metabolic phenotypes. Importantly, compensatory mechanisms for other potential methylglyoxal-detoxifying enzymes, including aldehyde dehydrogenases and aldo reductases, were identified in glyoxalase 1 knockout animals. Subsequent knockout studies of different Aldehyde-Dehydrogenases and Aldo-Keto-Reductases have demonstrated that Glyoxalase 1 does not solely regulate the metabolism of reactive carbonyl species and organ functions. Instead, other reactive carbonyl species, together with their corresponding detoxification enzymes, exhibit distinct organ susceptibility. These detoxifying enzyme systems are interconnected at multiple levels in a complex and redundant manner, and their dysregulation can lead to chronic pathological conditions. Conceptually, the review aims to focus on future cardiovascular research investigating the specificity of different reactive carbonyl species to their respective detoxification systems and the interplay and organ-specific regulation of these detoxification pathways. The future goal is to develop reactive carbonyl species profiles and markers of inadequate detoxification in order to identify new patient subgroups. Another future challenge will be to establish reactive carbonyl species profiles and corresponding enzyme system activities as biomarkers for predicting, diagnosing and monitoring chronic diseases in translational and clinical contexts. Ultimately, we suggest to develop potent and specific reactive carbonyl species scavengers, as well as detoxifying enzyme activators, and define new patient subgroups with different treatment needs and prognoses.
Dusp15 modulates mtHsp70 Thr116 phosphorylation state to preserve mito-UPR and attenuate cardiac dysfunction in diabetic cardiomyopathy.
Liu Y, Shi H, Li C … +11 more , Zhuang H, Li Y, He X, Jiang Y, Jin Z, Guo Z, Ong S, Wang Y, Chang X, An G, Wang J
Cardiovasc Diabetol · 2026 Mar · PMID 41794713 · Full text
BACKGROUND: Diabetic cardiomyopathy (DCM) involves cardiac dysfunction/remodeling with mitochondrial stress and impaired mitochondrial proteostasis. The role of dual-specificity phosphatases (DUSPs) in these processes re...
BACKGROUND: Diabetic cardiomyopathy (DCM) involves cardiac dysfunction/remodeling with mitochondrial stress and impaired mitochondrial proteostasis. The role of dual-specificity phosphatases (DUSPs) in these processes remains unclear. We examined whether Dusp15 modulates diabetic cardiac injury and whether mtHsp70/mito-UPR-linked proteostasis is involved. METHODS: DCM was induced in mice by high-fat diet (HFD) combined with low-dose streptozotocin (STZ). We studied cardiomyocyte-specific Dusp15 knockout (Dusp15) mice, a Dusp15 gain-of-function line, and high-glucose-treated HL-1 cardiomyocytes. Cardiac function/remodeling were assessed by echocardiography and molecular/histological analyses. Dusp15-mtHsp70 signaling was interrogated by protein interaction assays and mtHsp70 Thr116 genetic models. RESULTS: Dusp15 was reduced in diabetic hearts and associated with impaired contractility. Dusp15 gain-of-function improved cardiac function and reduced remodeling/inflammation, whereas Dusp15 worsened diabetic injury, indicating a cardiomyocyte-necessary role for Dusp15. Dusp15 associated with mtHsp70 and supported mtHsp70-linked mitochondrial proteostasis/mito-UPR in cardiomyocytes. Genetically, mtHsp70 knock-in mice were substantially protected from diabetic cardiac dysfunction/remodeling. Finally, dapagliflozin (DAPA) improved diabetic cardiac outcomes, and its benefit was reduced in Dusp15 mice, suggesting Dusp15 as an important mediator. CONCLUSION: Dusp15 is a stress-responsive regulator that protects against diabetic cardiac dysfunction and remodeling through mtHsp70-associated mito-UPR signaling. Targeting the Dusp15-mtHsp70 axis may represent a therapeutic strategy for diabetic cardiomyopathy.
Impact of glycemic optimization on myocardial steatosis and cardiac remodeling in patients with newly diagnosed type 2 diabetes: a longitudinal study.
Rosales-Rojas Á, Teis A, Gil-Millan P … +9 more , Rossell J, Pedraz-Petrozzi B, Vilades D, Sanchez-Quesada JL, García-Osuna A, Mauricio D, Julve J, Perez A, Alonso N
Cardiovasc Diabetol · 2026 Mar · PMID 41792715 · Full text
BACKGROUND: Cardiac remodeling is common in individuals with type 2 diabetes (T2D) and is influenced by glycemic and metabolic factors. However, myocardial steatosis, a proposed contributor to diabetic cardiomyopathy, ha...
BACKGROUND: Cardiac remodeling is common in individuals with type 2 diabetes (T2D) and is influenced by glycemic and metabolic factors. However, myocardial steatosis, a proposed contributor to diabetic cardiomyopathy, has been inconsistently related to glycemic control. This study aimed to characterize longitudinal changes in myocardial triglyceride content (MTGC) and cardiac remodeling following glycemic optimization in newly diagnosed T2D. METHODS: In this uncontrolled, exploratory longitudinal study, twenty adults with newly diagnosed T2D underwent a 12-month standardized glycemic optimization protocol including insulin, metformin, and empagliflozin, in addition to nutritional and lifestyle counseling. Cardiac magnetic resonance imaging (CMR) and proton magnetic resonance spectroscopy (¹H-MRS) were performed at baseline and after 12 months to assess cardiac structure, function, and MTGC. Longitudinal changes and associations between clinical, biochemical, and imaging parameters were assessed. RESULTS: Participants (mean age 54.8 ± 9 years, 72.3% male) achieved significant reductions in HbA1c levels, body mass index (BMI) and waist circumference (WC). No significant changes in MTGC were found at follow-up (p = 0.23). CMR evaluation revealed increases in left ventricle (LV) ejection fraction (59.0% [54.8-61.5] vs. 63.1% [56.9-66.3], p = 0.01) and decreases in ventricular volumes: (LV) end-systolic volume (29.9 mL/m [26.4-35.1] vs. 27.3 mL/m [22.5-31.7]; p = 0.007), right ventricular (RV) end-systolic volume (30.6 mL/m [25.9-35.7] vs. 28.7 mL/m [25.5-32.6], p = 0.02) and RV end-diastolic volume (76.5 mL/m [64.6-82.4] vs. 72.4 mL/m [66.1-77.7], p = 0.03). The indexed LV mass increased (46.1 g/m [35.1-54.2] vs. 49.5 [39.5-54.3], p = 0.006). No associations were found between HbA1c improvement and the MTGC or CMR parameters. Reductions in BMI and WC were associated with greater left atrial strain (ρ = - 0.78 and - 0.77; p < 0.001), whereas reductions in WC were also associated with greater LV end-diastolic volume (ρ = -0.59; p = 0.024). CONCLUSIONS: In patients with newly diagnosed T2D, 12 months of glycemic optimization was associated with changes in cardiac remodeling parameters despite no detectable changes in myocardial steatosis. The observed cardiac changes were more closely associated with concurrent reductions in adiposity markers than with changes in HbA1c, emphasizing weight management as a key target for early prevention of diabetic cardiomyopathy.
Association between atherosclerotic index of plasma and long-term aortic-related adverse events in type B aortic dissection patients undergoing thoracic endovascular aortic repair.
Li S, Li W, Zhang J … +6 more , Zhao K, Ding Z, Ren J, Hu W, Lu Q, Zhou J
Cardiovasc Diabetol · 2026 Mar · PMID 41787449 · Full text
BACKGROUND: Previous research identifies the atherosclerotic index of plasma (AIP) as a key marker for cardiovascular risk, but its role in predicting outcomes in type B aortic dissection (TBAD) patients after thoracic e...
BACKGROUND: Previous research identifies the atherosclerotic index of plasma (AIP) as a key marker for cardiovascular risk, but its role in predicting outcomes in type B aortic dissection (TBAD) patients after thoracic endovascular aortic repair (TEVAR) is uncertain. This study aimed to investigate the association between AIP and long-term outcomes in TBAD patients after TEVAR. METHODS: This retrospective cohort study included 1335 patients with TBAD who underwent TEVAR. Patients were stratified into tertiles based on AIP levels. The primary endpoints were aortic-related adverse events (ARAEs) at 1 and 5 years after TEVAR. Cox regression analyses were used to evaluate the independent effect of AIP on outcomes. Kaplan-Meier (KM) analysis was conducted to compare the incidence of ARAEs among different groups. Restricted cubic spline (RCS) models were utilized to investigate the nonlinear relationship between AIP and ARAEs, and subgroup analyses assessed the stability of this association. Time-dependent receiver operating characteristic (ROC) curves were applied to assess the predictive accuracy of AIP for ARAEs over a 5-year period. RESULTS: The KM analysis revealed a significantly higher incidence of ARAEs in the high AIP group compared to the low AIP group (P < 0.001). However, no statistically significant differences were found in all-cause mortality and major adverse cardiovascular and cerebrovascular events (MACCEs) (all P > 0.05). Cox regression analysis demonstrated that a high level of AIP was associated with an increased risk of ARAEs (all P < 0.001). Additionally, RCS analysis indicated a linear relationship between AIP and the risk of ARAEs. In subgroup analyses, the timing of operation showed a significant interaction with 1-year ARAEs (P for interaction = 0.008). Time-dependent ROC analysis demonstrated an area under the curve approaching 0.8 throughout the 5-year period. CONCLUSION: Our research indicates that AIP is independently associated with 1-year and 5-year ARAEs in patients with TBAD following TEVAR, providing a novel metabolic perspective for the prognostic evaluation of this population.
Prognostic stratification of cardiovascular risk and cardiac remodeling in prediabetes: a multimodal analysis comparing ADA and WHO/IEC diagnostic criteria.
Zheng Z, Song Y, Cui K … +7 more , He J, Bian X, Song C, Dong Q, Zhu C, Fu R, Dou K
Cardiovasc Diabetol · 2026 Mar · PMID 41776566 · Full text
BACKGROUND: Prediabetes, an intermediate metabolic state preceding diabetes, independently accelerates cardiovascular pathology through dysglycemia-driven mechanisms. This study evaluates the heterogeneous cardiovascular...
BACKGROUND: Prediabetes, an intermediate metabolic state preceding diabetes, independently accelerates cardiovascular pathology through dysglycemia-driven mechanisms. This study evaluates the heterogeneous cardiovascular risk stratification by directly comparing two major diagnostic criteria (ADA vs. WHO/IEC) and assesses the causal cardiovascular consequences of prediabetes, an area requiring further elucidation. METHODS: After excluding participants with baseline cardiovascular disease, the remaining cohort with complete glycemic and relevant assessment data (n = 278,697) was stratified into normoglycemia, prediabetes, and type 2 diabetes mellitus (T2DM). Prediabetes was subsequently classified according to both ADA (fasting plasma glucose, FPG 5.6-6.9 mmol/L and/or glycosylated hemoglobin A1c, HbA1c 5.7-6.4%) and WHO/IEC (FPG 6.1-6.9 mmol/L and/or HbA1c 6.0-6.4%) criteria. Associations with incident cardiovascular disease (CVD), mortality, and cardiac remodeling (via cardiac magnetic resonance, CMR) were assessed using multivariable-adjusted models. Mendelian randomization (MR) tested causality of prediabetes on outcomes. All observational analyses were adjusted for key demographic, lifestyle, and clinical covariates. RESULTS: Over 13.5 years, prediabetes-irrespective of criteria-elevated CVD risk (ADA: HR = 1.14, 95% CI 1.12-1.16; WHO/IEC: HR = 1.23, 95% CI 1.19-1.27), with stronger mortality associations in WHO/IEC-defined individuals. MR analyses confirmed that prediabetes was causally associated with increased CVD (OR 1.01, 95% CI 1.01-1.02), coronary heart disease (OR 1.09, 95% CI 1.02-1.17), myocardial infarction (OR 1.12, 95% CI 1.06-1.19), stroke (OR 1.06, 95% CI 1.02-1.10), and primary hypertension (OR 1.01, 95% CI 1.01-1.02) risks. In an exploratory CMR substudy (n = 2512), early concentric left ventricular remodeling was suggested, particularly under WHO/IEC criteria. Risks were consistently observed across genetic susceptibility strata, though the lack of significant interaction warrants cautious interpretation and further investigation into potential effect modifications. CONCLUSION: These findings highlight the differential prognostic utility of ADA and WHO/IEC criteria for cardiovascular risk stratification in prediabetes.
SLC31A1 exon 1 methylation reduces intracellular copper ion and promotes diabetic cardiac fibrosis.
Song K, Geng HR, Liu ZY … +11 more , Lin LC, Tu B, Sun H, Mao S, Liu P, Sun X, Shi Y, Xuan HY, Yang JJ, Zhao JY, Tao H
Cardiovasc Diabetol · 2026 Mar · PMID 41776560 · Full text
BACKGROUND: Metal homeostasis is linked to cellular organelles modification. Dynamic lipid droplet (LD)-mitochondria interactions contribute to diabetes-related complications. However, little is known about whether and h...
BACKGROUND: Metal homeostasis is linked to cellular organelles modification. Dynamic lipid droplet (LD)-mitochondria interactions contribute to diabetes-related complications. However, little is known about whether and how copper regulates LD-mitochondria contacts in diabetic cardiac fibrosis (CF). METHODS: Leptin receptor-deficient (db/db) mice were used to induce diabetic CF. To investigate target gene function in vivo, AAV9 vectors carrying the cardiac fibroblast-specific POSTN promoter-driven small hairpin RNAs were administered. SLC31A1 overexpression was achieved via AAV9 plasmid specifically targeting cardiac fibroblasts to assess its rescue effect on diabetic CF. In vitro, neonatal mouse primary cardiac fibroblasts were stimulated with high glucose/high fatty acids (HG/HF) to mimic diabetic CF. RESULTS: Lower copper concentrations were accompanied by SLC31A1 downregulation and increased LD-mitochondria contacts in diabetic CF and HG/HF-induced cardiac fibroblasts. Fibroblast-specific SLC31A1 deficiency enhanced the LD-mitochondria contacts, fibroblast proliferation, and diabetic CF. Mechanistically, intracellular copper deficiency inhibited the specific binding of H3K27me3 to the PLIN5 promoter and promoted transcription. Furthermore, enhanced DNMT3A expression increases the DNA methylation level in the exon 1 region of SLC31A1. Increased methylated CpGs recruited MeCP2, suppressing SLC31A1 expression. Conversely, epigenetic repression rescued SLC31A1 expression, resulting in a certain degree of inhibition of diabetic CF. Human diabetic cardiomyopathy (DCM) heart tissue analyses validated our findings. CONCLUSIONS: This study demonstrates the critical role of SLC31A1 exon 1 methylation-mediated copper depletion in promoting diabetic CF, identifying cardiac fibroblast-specific rescue of copper depletion as a potential therapeutic approach for diabetic CF.
Nanocarrier SIroliMus-coated balloon-based percutaneous coronary intervention (PCI) versus drug-eluting stent (DES)-onLy PCI in patients with diabetes mellitus.
Gitto M, Filiberti G, Leone PP … +18 more , Chiarito M, Gurgoglione FL, Tartaglia F, Frazzetto M, Calamita G, Rossi ML, Bernardini V, Reimers B, Regazzoli D, Mangieri A, Gasparini G, Briguori C, Latib A, Stefanini GG, Godino C, Sardella G, Cortese B, Colombo A
Cardiovasc Diabetol · 2026 Mar · PMID 41776495 · Full text
BACKGROUND: Diabetic patients undergoing percutaneous coronary intervention (PCI) frequently have complex coronary artery disease (CAD) and suboptimal outcomes with drug-eluting stents (DES). Sirolimus-coated balloons (S...
BACKGROUND: Diabetic patients undergoing percutaneous coronary intervention (PCI) frequently have complex coronary artery disease (CAD) and suboptimal outcomes with drug-eluting stents (DES). Sirolimus-coated balloons (SCB) have recently been introduced, but comparative data versus DES in diabetic patients with de novo CAD are lacking. METHODS: The SIMPLE-DM study is a pooled analysis of five observational registries including all-comer diabetic patients undergoing PCI for de novo CAD. Patients in the SCB cohort were treated with the phospholipid nanocarrier Magic Touch SCB, while those in the DES cohort received current-generation DES. Propensity score (PS) adjustment was used to balance clinical and angiographic characteristics. The primary endpoint was the 2-year cumulative incidence of target lesion failure (TLF), defined as the composite of cardiac death, target vessel MI (TV-MI), or target lesion revascularization (TLR). RESULTS: A total of 1838 patients were included, 599 treated with SCB-based PCI and 1239 with DES-only PCI. At 2 years, TLF occurred in 9.1% of SCB and 9.9% of DES patients (adj. hazard ratio HR 0.88, 95% confidence interval CI 0.43-1.81, p = 0.736). No significant differences were found in cardiac death, TV-MI or TLR. SCB-based PCI was associated with more favourable outcomes in patients with chronic kidney disease (p for interaction = 0.042) and long lesions (p for interaction = 0.003), whereas DES-only PCI performed better in those with short lesions. CONCLUSIONS: In diabetic patients undergoing PCI for de novo CAD, an SCB-based strategy was associated with comparable 2-year outcomes to DES-only PCI, with signals of potential benefit in the highest clinical and anatomical risk subsets.
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