European Heart Journal

BackgroundBoth acute myocardial infarction (AMI) and acute myocarditis are characterised by cardiac troponin release as a marker of cardiomyocyte injury. While peak troponin is widely accepted as a surrogate marker for infarct size in AMI, its relationship with myocardial injury in acute myocarditis is unclear. This study aimed to quantify and compare the association between peak high-sensitivity cardiac troponin and cardiovascular magnetic resonance (CMR) late gadolinium enhancement (LGE) extent in patients with AMI versus acute myocarditis. MethodsPatients undergoing CMR imaging and measurement of high-sensitivity cardiac troponin I during hospital admission were retrospectively included. LGE extent was quantified in grams using the semi-automated expectation-maximization weighted intensity algorithm (EWA). ResultsCompared to patients with acute myocarditis (n=47), patients with AMI (n=49) had higher peak troponin levels (median [interquartile range] 32,470 [3,109-104,699] vs 7,295 [1,857-22,550] ng/L, p=0.002), larger LGE extent (25 [13-56] vs 10 [6-17] g, p<0.001), and lower left ventricular ejection fraction (45 [36- 52] vs 55 [49-58] %, p<0.001). Peak troponin was moderately positively correlated with LGE extent in both AMI (rho=0.56, p<0.001) and acute myocarditis (rho=0.58, p<0.001). However, the ratio of peak troponin to LGE mass was higher in AMI compared to acute myocarditis (1,299 [419-3233] vs 909 [310-1446] ng/L/g, p=0.02). ConclusionsPeak cardiac troponin correlates positively with LGE extent in both AMI and acute myocarditis, but the magnitude of LGE and LV systolic dysfunction is greater in AMI. Also, AMI typically has an approximately 40% greater amount of troponin release per unit LGE mass compared to acute myocarditis. This suggest that troponin-based estimates of myocardial injury size estimated by LGE are not directly interchangeable between ischaemic and inflammatory myocardial diseases.

BackgroundMetabolic vulnerability index (MVX), a novel biomarker of systemic inflammation and metabolic malnutrition, is associated with mortality in patients with cardiovascular diseases. Nevertheless, little is known about its association with cardiometabolic diseases (CMDs) and multimorbidity (CMM). We aimed to examine the associations of MVX with the risk of individual CMDs, their progression to CMM, and all-cause mortality in the general population. MethodsIn a prospective cohort of 218,635 UK Biobank participants free of CMDs, MVX was calculated based on plasma metabolomics data. CMM was defined as coexistence of two or more CMDs, including coronary heart disease (CHD), stroke, and type 2 diabetes mellitus (T2DM). Cox proportional hazard and multi-state models were employed to evaluate the associations of MVX with the risks of individual CMDs, CMM, and all-cause mortality. ResultsDuring a median follow-up of 14.4 years, 27,805 (12.7%) participants developed at least one CMD, 3,006 (1.4%) progressed to CMM, and 14,211 (6.5%) died. Each standard deviation increase of MVX score was associated with 9% (95% confidence interval: 8%-10%), 11% (7%-15%), and 12% (10%-14%) higher risks of developing CMDs, CMM, and mortality, respectively. The MVX-CMM associations were more prominent in females and in the sequential onset pattern of T2DM followed by CHD or stroke. Multi-state model analysis further uncovered consistent associations between higher scores of MVX and higher risks of transitions from CMDs free to CMD, subsequently to CMM, and to death. ConclusionsHigher MVX scores were significantly associated with higher risks of incident CMDs, their progressions to CMM, and all-cause mortality. These results underscored the potential of MVX in the primary prevention and management of CMDs and CMM.

Structured abstractO_ST_ABSBackgroundC_ST_ABSTransthyretin amyloid cardiomyopathy (ATTR-CM) has historically been underdiagnosed but has recently become increasingly recognized due to advances in diagnostic techniques and heightened clinical awareness. Despite this progress, treatment options remain limited, as current approved therapies are costly and not widely accessible. Given the benefits of sodium-glucose cotransporter 2 (SGLT2) inhibitors in broader heart failure (HF) populations, we aimed to evaluate their efficacy in reducing mortality and hospitalizations in ATTR-CM. ObjectivesTo determine whether SGLT2 inhibitors reduce all-cause mortality, CV mortality, and HF hospitalizations in ATTR-CM, offering a potential adjunctive therapy for this undertreated population. MethodsWe performed a systematic review and meta-analysis of SGLT2 inhibitors against SGLT2 inhibitors-naive patients with ATTR-CM. PubMed, Embase, Scopus and Cochrane databases were searched for trials published up to January 31, 2025. Data were extracted from published reports, and quality assessment was performed per Cochrane recommendations. Risk ratios (RRs) with 95% confidence interval (CI) were pooled across trials. Outcomes included all-cause mortality, CV mortality and HF hospitalization. ResultsOut of 177 database results, four observational studies and 5039 patients were included; 2489 (49.39%) received a SGLT2 inhibitor. All-cause mortality (RR 0.44; 95% CI 0.33-0.59; p<0.00001; I{superscript 2}=54%) and CV mortality (RR 0.30; 95% CI 0.16-0.55; p=0.0001; I{superscript 2}=25%) were significantly lower in patients treated with SGLT2 inhibitors compared with control. HF hospitalization (RR 0.68; 95% CI 0.33-1.41; p=0.30; I{superscript 2}=89%) showed a downward trend, yet this was not statistically significant. ConclusionsIn patients with ATTR-CM, SGLT2 inhibitors significantly reduce both all-cause and cardiovascular mortality compared to standard care, suggesting they may serve as a valuable adjunctive therapy for this undertreated population. Although HF hospitalization showed a nonsignificant downward trend, these findings underscore the need for large randomized trials to confirm and expand on these promising results.

BackgroundSodium glucose co-transport inhibitors (SGLT2i), although established heart failure (HF) therapy in acquired heart disease, are not well-studied in adult congenital heart disease (ACHD). We aimed to conduct a systematic review and meta-analysis of SGLT2i therapy in moderate or severe complexity ACHD. MethodsFive databases (Pubmed, Medline, Embase, SCOPUS, and Cochrane) were searched for peer-reviewed journal articles describing SGLT2i HF therapy in moderate or severe complexity ACHD. Outcomes included adverse clinical events, biochemical markers of HF (N-terminal pro-brain natriuretic peptide [NT-proBNP] or BNP), and imaging markers of cardiac function (global longitudinal strain [GLS] and fractional area change [FAC]). Forest plots demonstrated mean study effects as individual and pooled estimates. The impact of heterogeneity on the overall variance was evaluated. ResultsThe systematic review included 10 studies (n=174 patients, 60% male). SGLT2i therapy was associated with a statistically significant improvement in GLS (mean difference -1.6 [-2.4,-0.9]) but not FAC (mean difference +1.86 [-6.2,+9.9]); there was no significant post therapy change in NT-proBNP or BNP (mean difference -240 pg/mL [-516,45] and -52 pg/mL [-129,26], respectively). Heterogeneity for the pooled effects for GLS and FAC was low (I2=0%), although moderate to high for NT-proBNP and BNP (I2=47% and I2=90%, respectively). Data were insufficient for evaluation of SGLT2i impact on clinical outcomes. ConclusionsPooled results across studies suggest that SGLT2i therapy can improve GLS among people with ACHD-HF, however the clinical implications of this observation warrant further study. Randomized controlled trials are now needed to evaluate the impact of SGLT2i therapy in ACHD.

BackgroundHeart failure (HF) is an increasingly common complication among patients with type 2 diabetes (T2D), yet its early detection remains challenging, especially in those with concomitant chronic kidney disease (CKD). NT-proBNP is a key biomarker for diagnosing and prognosticating HF, but its reference thresholds are influenced by renal function, age, and ethnicity. Current guideline cutoffs, largely derived from Western populations, may not apply to Asian patients. MethodsThis retrospective cohort study included 10,587 adults with T2D who underwent NT-proBNP testing between 2006 and 2021 at the National Taiwan University Hospital. Patients with prior HF were excluded. Generalized additive models identified NT-proBNP thresholds associated with HF hospitalization, and Kaplan-Meier analysis validated outcome separation. Subgroup analyses were stratified by age, sex, body mass index (BMI), and estimated glomerular filtration rate (eGFR). ResultsDuring a mean follow-up of 3.5 years, 1,892 (17.9%) patients were hospitalized for HF. NT-proBNP levels of 179 pg/mL (outpatient) and 728 pg/mL (emergency) marked inflection points for rising event risk (log-rank p < 0.0001). Age-specific analyses showed progressive increases in optimal thresholds: from 85 (<50 years old), 150 (50-74 years old) and 290 pg/mL ([&ge;]75 years old) in outpatients, and from 310, 600 and 1,165 pg/mL, respectively, in emergency settings. In the BMI-stratified analysis, NT-proBNP thresholds demonstrated an inverse relation with BMI. Considering renal function, the optimal cutoffs were 100, 310, and 935 pg/mL for eGFR > 60, 30-60, and < 30 mL/min/1.73 m{superscript 2}, respectively; in the emergency cohort, the corresponding thresholds were 290, 835, and 3,905 pg/mL. ConclusionsThis large Asian cohort defines setting- and renal function-specific NT-proBNP thresholds for predicting HF hospitalization in patients with T2D. The lower optimal cutoffs compared with Western guidelines highlight the need for ethnicity-adjusted diagnostic criteria to improve early identification and risk stratification of HF in clinical practice. What is new?O_LIIn a large real-world Asian cohort of patients with type 2 diabetes, we identified setting-specific NT-proBNP thresholds (179 pg/mL outpatient; 728 pg/mL emergency) associated with heart failure hospitalization risk. C_LIO_LIAge-, BMI-, and kidney function-stratified cutoffs revealed substantial heterogeneity in optimal NT-proBNP thresholds. C_LIO_LICompared with guideline-recommended values, Asian-specific thresholds were consistently lower ([~]30-40%), supporting ethnic differences in natriuretic peptide biology. C_LIO_LIA generalized additive model (GAM) captured nonlinear biomarker-risk relationships, enabling data-driven and clinically interpretable cutoff identification. C_LI What are the clinical implications?O_LIUse of ethnicity- and context-specific NT-proBNP thresholds may improve early detection of heart failure in Asian patients with type 2 diabetes. C_LIO_LIIncorporating kidney function and BMI into NT-proBNP interpretation enhances risk stratification, particularly in patients with CKD. C_LIO_LIReliance on Western guideline cutoffs may underestimate heart failure risk in Asian populations. C_LIO_LIThese findings support a precision medicine approach to biomarker interpretation and highlight the need for population-specific guideline refinement. C_LI

ObjectiveTo examine the association between Atherogenic Index of Plasma (AIP) and subclinical myocardial injury (SCMI), and their combined impact on cardiovascular disease (CVD) mortality in the general population. MethodsThis analysis included 7,093 participants without CVD from the Third National Health and Nutrition Examination Survey. AIP was calculated as the logarithmic ratio of triglycerides to HDL cholesterol. Participants were stratified into low or high AIP groups based on the median AIP value (0.958). Electrocardiographic SCMI was defined as Cardiac Infarction/Injury Score [&ge;]10 points. CVD mortality data were obtained from the National Death Index. Multivariable logistic regression models assessed the baseline cross-sectional association between AIP and SCMI, while Cox proportional hazards models examined the relationship between different baseline AIP/SCMI groups and CVD mortality. ResultsHigh AIP was associated with increased odds of SCMI [OR(95% CI): 1.20(1.07-1.35)] in multivariable logistic regression analysis. In multivariable Cox proportional hazard models, compared to participants with low AIP and absent SCMI, those with SCMI had a higher risk of CVD mortality regardless of AIP level [(HR(95% CI) 1.28(1.05-1.57) and 1.33(1.10-1.60)]. However, high AIP without SCMI was not associated with CVD mortality [HR (95% CI) 0.94(0.79-1.11)]. ConclusionsHigh AIP was associated with an increased risk of SCMI. SCMI was linked to a higher risk of CVD mortality regardless of AIP levels, while high AIP was only associated with CVD mortality when SCMI was present, suggesting that the reported adverse outcomes linked to high AIP may be driven by the development of SCMI.

BackgroundVitamin D supplementation has been investigated for potential associations with cardiometabolic risk factors related to cardiovascular disease (CVD); however, findings from randomized controlled trials (RCTs) remain inconsistent. This meta-analysis aimed to assess the effects of vitamin D supplementation on cardiometabolic risk factors--including lipid profile, blood pressure, and glycaemic parameters--and to explore whether age and baseline serum vitamin D concentrations modify these associations. Research Design and MethodsWe conducted a systematic review and meta-analysis of RCTs comparing oral vitamin D supplementation with placebo in adults. PubMed, the Cochrane Library, and ClinicalTrials.gov. Risk of bias was evaluated using the Cochrane tool, and pooled effect sizes with 95% confidence intervals (CIs) were calculated using random-effects models. Results14,051 abstracts were retrieved, of which 45 were used for data analysis. Vitamin D supplementation reduced low-density lipoprotein cholesterol (LDL-C) by 0.136 mmol/L (95%CI: -0.215, -0.56), systolic blood pressure by 2.79 mm Hg (95% CI: -4.648, -0.938), fasting blood glucose by -0.11 (95%CI:-0.185, -0.036), and hemoglobin A1c by 0.164% (95%CI: -0.322, -0.006) compared with placebo. Subgroup analyses revealed reductions in SBP and LDL cholesterol among participants aged [&ge;]55 years and reductions in fasting blood glucose in participants with age < 55 years. While favourable effects on fasting blood glucose and hemoglobin A1c were observed with a baseline blood level of vitamin D of concentrations (<50 nmol/L). ConclusionsVitamin D supplementation may be associated with modest modifications in selected cardiometabolic risk factors; including systolic blood pressure, LDL-cholesterol, fasting blood glucose, and hemoglobin A1c. Age and baseline vitamin D status appear to modulate these effects. The clinical relevance of these modest effects remains uncertain. Well-designed RCTs with standardized protocols are required to clarify potential effect modification by age and baseline vitamin D status. Trial RegistrationPROSPERO (CRD42020165293) FundingThis research received funding from the Hashemite University, P.O. Box 330127, Zarqa 13133, Jordan

BackgroundElevated resting heart rate (HR) and atrial cardiopathy are each linked to higher mortality risk, yet their interrelationship and joint prognostic value remain unclear. MethodsWe analyzed 7,326 adults (mean age 59 {+/-} 13 years) without cardiovascular disease from the Third National Health and Nutrition Examination Survey with available electrocardiograms. Atrial cardiopathy was defined by electrocardiogram as abnormal P-wave axis or deep terminal P-wave negativity in V1. Multivariable logistic regression assessed cross-sectional associations between HR categories and atrial cardiopathy. Cox proportional hazards models evaluated independent and joint associations of HR categories and atrial cardiopathy with all-cause mortality. ResultsAtrial cardiopathy was present in 1,833 participants (13.5%). After adjustment, sinus tachycardia ([&ge;]100 bpm) was associated with higher odds of atrial cardiopathy (OR 1.76, 95% CI 1.06-2.92), whereas sinus bradycardia ([&le;]50 bpm) was associated with lower odds (OR 0.61, 95% CI 0.43-0.84). Each 10-bpm HR increase corresponded to 25% higher odds of atrial cardiopathy. Over a median 13.8-year follow-up, 2,415 deaths (33.0%) occurred. Sinus tachycardia (HR 3.58, 95% CI 2.61-4.91) and atrial cardiopathy (HR 1.27, 95% CI 1.16-1.39) were independently associated with mortality. Individuals with both conditions had the highest risk (HR 4.11, 95% CI 2.63-6.41). Associations varied by age and race. ConclusionsElevated resting HR is associated with higher odds of atrial cardiopathy, and their coexistence confers markedly increased mortality risk. Integrating resting HR into atrial cardiopathy metrics may enable granular population-level risk profiling.

Background and AimSedentary lifestyle and obesity are considered to be significant risk factors that create a pathway for the appearance of the sedentary cardiac phenotype consisting of cardiac atrophy, myocardial stiffening, and altered haemodynamics. Although exercise training has the potential to reverse this detrimental process, the literature data on the magnitude of improvements and the certainty of evidence are inconsistent. This systematic review and meta-analysis aimed to evaluate the effects of exercise interventions on cardiac morphology, systolic/diastolic function, and haemodynamics in sedentary and obesity-prone individuals. MethodIn accordance with the PRISMA guidelines, the study was conducted by searching the PubMed, Web of Science, and Scopus databases from 1990 to 2025 without applying any filters, using Covidence software. As a result of this comprehensive search, 15 randomised controlled trials (RCTs; N=559) comparing exercise training with a control group in sedentary individuals were included in the analysis. Data were pooled using the Standardised Mean Difference (SMD) and a random-effects model. Publication bias and methodological robustness of the results were tested using the Egger regression test, the Trim-and-Fill method, and Leave-One-Out sensitivity analysis. The certainty of the evidence was graded using the GRADE system. ResultsExercise training was associated with a significant reduction in resting HRs and SBPs, which was a strong improvement in the haemodynamic profile. The improvements in SV and LVEF, although on the statistical threshold in the primary analysis, were statistically significant and methodologically stable in the Leave-One-Out sensitivity analysis, which excluded confounding studies. The exercise training was associated with a marked improvement in the E/A ratio and S wave, and the triggering of a physiological athletes heart-like eccentric hypertrophy, defined by improvements in LVMass and LVEDV. The exercise training was associated with diastolic adaptation and mass increase, with HIIT being the most superior method for diastolic adaptation and mass increase, and aerobic exercise being the most effective method for blood pressure reduction. Importantly, the meta-regression analyses revealed two important findings: first, the improvement in blood pressure and diastolic function was independent of weight loss; second, the improvement in structure and function was linearly related to improvements in body composition. ConclusionExercise acts as a cardiac polypill reversing the sedentary phenotype by improving hemodynamics and diastolic function independently of weight loss, while linking structural remodeling to BMI optimization; our data prioritize HIIT for structural/diastolic gains and Aerobic training for blood pressure control.

BackgroundCardiovascular-kidney-metabolic (CKM) syndrome is staged to reflect increasing cardiometabolic risk. Substantial heterogeneity exists within stage 2, which includes individuals with metabolic risk factors or chronic kidney disease (CKD) without established cardiovascular disease and affect nearly half of US adults. This study aimed to develop and validate a sex-specific, clinically pragmatic model to subdivide CKM stage 2 into lower-risk (stage 2a) and higher-risk (stage 2b) subgroups MethodsWe analyzed participants aged [&ge;]18 years with CKM syndrome stage 2 from the 1999-2018 NHANES cycles linked to the US National Death Index. Participants were assigned to development and validation cohorts comprising five survey cycles each. Predictor variables were selected using modified LASSO-regression and Cox-regression model, with cardiovascular mortality as the primary outcome. Model performance was assessed using time-dependent area under the receiver operating characteristic curve (AUC) and the C-statistics. TriNetX database with patient-level data from medical records was analyzed to provide clinical validation using major adverse cardiovascular events (MACE) as the outcome. ResultsStage 2b in women was defined by the presence of at least two of the following: age [&ge;]66 years, CKD, diabetes, or hypertension (AUC 0.79; C-index 0.78). In men stage 2b required at least two of the following: age [&ge;]61 years, CKD, diabetes, or current smoking (AUC 0.73; C-index 0.72). Discrimination was preserved in external validation (women: AUC 0.70, C-index 0.69; men: AUC 0.75, C-index 0.68) with significantly distinct 10-year absolute risk difference of cardiovascular death (women: 4.9% [95% CI 2.2-7.5]; men: 8.5% [95% CI 5.0-12.0]). In TriNetX database, 10-year MACE risk increased from 11.3% to 24.6% in women and from 13.1% to 30.8% in men from stage 2a to stage 2b. ConclusionsSubdividing CKM stage 2 into stages 2a and 2b identifies clinically meaningful differences in cardiovascular risk and may support targeted preventive strategies.

BackgroundElevated resting heart rate is associated with increased mortality, but the underlying mechanisms remain incompletely understood. Subclinical myocardial injury (SCMI), defined by a Cardiac Infarction/Injury Score (CIIS) [&ge;]10, represents silent cardiac damage that predicts poor cardiovascular (CV) outcomes and may partially explain this association. MethodsWe analyzed 7,152 participants from NHANES III who underwent ECG recording and were free of cardiovascular disease. Heart rate was categorized as bradycardia ([&le;]50 bpm), normal (>50-<100 bpm), or tachycardia ([&ge;]100 bpm). Mortality was assessed through National Death Index linkage. Logistic and Cox regression models evaluated associations with SCMI and mortality, respectively, and attenuation was assessed by change in hazard ratios after adjusting for SCMI. ResultsSCMI was present in 1,744 (24.3%) participants. Tachycardia was associated with increased odds of SCMI (adjusted OR 2.34, 95% CI 1.42-3.88). Over 13.9 years median follow-up, 2,311 (32.3%) died from all causes and 933 (13.1%) from CV causes. Tachycardia was associated with increased all-cause mortality (HR 3.58, 95% CI 2.63-4.88) and CV mortality (HR 2.05, 95% CI 1.06-3.79). Adjustment for SCMI attenuated the tachycardia-CV mortality association by 8.6% and all-cause mortality by 5%. Bradycardia was not associated with SCMI or mortality. ConclusionThese findings suggest that SCMI partially mediates the heart rate-mortality relationship and that ECG-based assessment of SCMI may enhance risk stratification in individuals with elevated resting heart rate.

1ObjectiveTo assess the effects of SGLT2 inhibitors on cardiovascular outcomes in HFpEF/HFmrEF. DesignSystematic review, random-effects meta-analysis using Hartung-Knapp, and trial sequential analysis (TSA). Data sourcesMEDLINE, Embase, and CENTRAL; searches updated through August 13, 2025. Eligibility criteriaParallel-group randomized trials enrolling adults with LVEF 40% (HFmrEF 40-49%; HFpEF 50%). Main outcome measuresTime-to-event composite of cardiovascular death or first heart failure hospitalization (primary); Kansas City Cardiomyopathy Questionnaire (KCCQ-TSS), components, and safety (secondary). ResultsTwo dedicated HFpEF trials (n=12,251) reported the primary outcome. The pooled hazard ratio was 0.80 (95% CI 0.73-0.87; I2=0%; 2 0; 95% prediction interval 0.67-0.96). TSA crossed efficacy boundaries and exceeded the diversity-adjusted required information size, indicating conclusive evidence for the composite. Effects were consistent in patients with and without diabetes and across EF 40-49% vs 50% (no significant interactions). KCCQ improved (+2.3 points, 95% CI 1.0-3.6; responders 5 pts: 42% vs 38%). Safety showed more genital mycotic infections, with no increase in serious adverse events or acute kidney injury. ConclusionsSGLT2 inhibitors robustly reduce cardiovascular death/heart failure hospitalization and improve health status in HFpEF/HFmrEF, supporting their role as foundational therapy, irrespective of diabetes status; effects on mortality alone remain imprecise. RegistrationPROSPERO CRD420251167908. Data and code: https://doi.org/10.5281/zenodo.18409428 PROSPEROCRD420251167908 Data availabilityhttps://doi.org/10.5281/zenodo.18409428

BackgroundCardiovascular-Kidney-Metabolic (CKM) syndrome is a progressive spectrum where patients often struggle with daily exercise. The "Weekend Warrior" (WW) pattern offers a flexible alternative, but its efficacy across CKM stages remains unclear. We evaluated the association of accelerometer-derived WW activity with cardiovascular outcomes across CKM Stages 0-3. MethodsThis prospective study included 88,832 UK Biobank participants (CKM Stages 0-3). Physical activity was objectively measured via 7-day accelerometry and categorized by weekly moderate-to-vigorous physical activity (MVPA) volume and pattern: Inactive (<150 min), WW ([&ge;]150 min; [&ge;]50% volume in 1-2 days), or Regularly Active (RA). The primary outcome was incident cardiovascular disease (CVD), a composite of coronary heart disease (CHD), heart failure (HF), stroke, atrial fibrillation (AF), and peripheral artery disease (PAD). ResultsDuring a median 7.5-year follow-up, 9,125 incident CVD events were recorded. In fully adjusted models, both WW and RA patterns were associated with similar risk reductions for total CVD (WW: HR 0.87, 95% CI 0.83-0.91, P < 0.001; RA: HR 0.88, 95% CI 0.83-0.94, P < 0.001) and CHD (WW: HR 0.86, 95% CI 0.80- 0.93, P < 0.001; RA: HR 0.86, 95% CI 0.79-0.93, P < 0.001). Notably, the WW pattern demonstrated unique benefits for AF (HR 0.91, 95% CI 0.85-0.99, P = 0.024) and PAD (HR 0.85, 95% CI 0.78-0.93, P < 0.001). In CKM Stage 3, the WW pattern showed a 38% reduction in total CVD risk (HR 0.62, 95% CI 0.47-0.83, P = 0.001) and marked reductions in HF (HR 0.47, 95% CI 0.24-0.90, P = 0.022) and PAD (HR 0.52, 95% CI 0.31-0.89, P = 0.019). Dose-response analysis revealed a non-linear L-shaped association, with CVD risk reductions plateauing at 200-300 min/week of MVPA. Furthermore, the WW pattern significantly offset the risk conferred by high genetic susceptibility and elevated inflammation (Stage 3 with hs-CRP > 3 mg/L: HR 0.46, 95% CI 0.25-0.84, P = 0.012). Both patterns conferred substantial survival advantages, with the WW pattern showing a 24% lower risk of all-cause mortality (HR 0.76, 95% CI 0.70-0.81, P < 0.001). ConclusionsThe WW pattern is associated with significant reductions in CVD risk and mortality across the CKM spectrum. Concentrating activity into 1-2 days is a feasible, safe, and effective strategy, offering unique vascular protection in advanced disease. For CKM patients, achieving total MVPA volume--ideally 200-300 min/week--should be prioritized over frequency.

Subclinical rheumatic valvular disease is a significant yet underdiagnosed contributor to the global rheumatic heart disease (RHD) burden. Early detection through population screening is essential to prevent its progression to severe RHD. Rhythm changes and prolongations of PR and QTc intervals in the ECG are described in the advanced RHD cases. However, these parameters were not yet studied in asymptomatic RHD. We aimed to investigate the potential of ECG biomarkers for screening RHD in asymptomatic schoolchildren. ECG tracings from 611 schoolchildren aged 10 to 20 years were selected from a cohort screened for RHD in four schools in an RHD-endemic region. Confirmatory diagnoses were based on echocardiographic findings, where 564 (F=326, M=238) were healthy, and 47 (F=28, M=19) were positive for RHD (24 borderline RHD and 23 definite RHD). Independent, blinded reviewers manually annotated the ECGs and PR interval (PR), P-wave dispersion (PWd), and the ratio between the P-wave duration and PR interval (Pw/PR) were analyzed. The mean age of the study cohort at diagnosis was 16.1 {+/-} 2.5 years, and 58% of the participants were females. Atrial fibrillation was seen in 8% (n=4), and prolonged PR in 2% (n=1) of RHD-positive cases. The mean {+/-} std for normals vs RHD is (PR, 138{+/-}19 vs 150{+/-}19), (Pw/PR, 0.75{+/-}0.06 vs 0.71{+/-}0.07), and (PWd, 49{+/-}14 vs 56{+/-}17). The PR (p<0.001), Pw/PR (p<0.001), and PWd (p=0.008) showed a significant difference between healthy and RHD-positive subjects. The PR was increased consistently with severity across age groups above and below 16 years. The PR, PWd, and Pw/PR can serve as non-invasive biomarkers for the screening of RHD in at-risk schoolchildren. Monitoring alterations in these markers at an early stage of RHD is crucial for enabling prompt management and follow-up. It is thus evident that ECG can support an intermittent ambulatory RHD screening in resource-limited settings.

Obstructive sleep apnea (OSA), defined as recurrent episodes of upper airway obstruction during sleep, has been associated with multiple cardiovascular and metabolic comorbidities. While prior studies have demonstrated a link between OSA and adverse cardiovascular outcomes, the strength and nature of this relationship remain controversial. We aimed to investigate the association between OSA and major cardiovascular and metabolic conditions, including myocardial infarction (MI), hypertension (HTN), diabetes mellitus (DM), dyslipidemia, obesity, and chronic kidney disease (CKD), as well as the impact of OSA on in-hospital mortality using a large national dataset. Materials and MethodsWe conducted a retrospective analysis using the National Inpatient Sample (NIS) database from 2016 to 2020, including over 148 million hospital discharge records. Diagnoses were identified using ICD-10 codes. Multivariate logistic regression was performed to assess adjusted odds ratios (aORs) for each outcome, accounting for potential confounders. A separate mortality analysis was conducted to evaluate in-hospital mortality among patients with and without OSA. After adjusting for confounding factors, OSA was not independently associated with an increased risk of MI (STEMI or NSTEMI). However, OSA was significantly associated with increased odds of HTN (aOR: 1.79), DM (aOR: 1.40), dyslipidemia, obesity (aOR: 3.36), morbid obesity (aOR: 8.25), and CKD, all with p < 0.001. In-hospital mortality analysis revealed worse outcomes in patients with cardiovascular comorbidities such as HTN, DM, dyslipidemia, and obesity. OSA may not be directly associated with MI, but it is strongly linked to its major risk factors. It may exert a cardioprotective effect in the context of STEMI, potentially due to ischemic preconditioning or heightened clinical surveillance. Conversely, OSA appears to worsen in-hospital mortality in patients with chronic cardiometabolic conditions, underscoring the need for early diagnosis and integrated management strategies tailored to comorbid risk profiles.

BACKGROUNDSerum uric acid (SUA) has been associated with cardiovascular (CV) and all-cause mortality; however, its interpretation is influenced by renal function. The serum uric acid to creatinine ratio (SUA/sCr) has been proposed as a refined marker, integrating urate burden with renal excretory capacity. Evidence from real-world populations with preserved renal function remains limited. METHODSA retrospective observational analysis was performed using administrative and laboratory databases from nine Italian healthcare entities, covering more than 7.6 million individuals. Eligible subjects were 18-95 years old, with estimated glomerular filtration rate (eGFR) [&ge;]60 mL/min/1.73 m{superscript 2}, serum creatinine (sCr) [&le;]1.8 mg/dL, and no prior urate-lowering therapy. The index date was defined as the first SUA measurement between January 2017 and March 2022. A total of 739,950 participants were stratified into quintiles of SUA/sCr ratio. Outcomes were two-year all-cause mortality and CV events, including ischemic heart disease, heart failure, cerebrovascular disease, and coronary revascularization. RESULTSAll-cause mortality exhibited a U-shaped distribution, with the lowest risk in mid-quintiles and the highest in extreme quintiles (6.2% in quintile 1, 7.0% in quintile 5). Cardiovascular events showed a progressive increase, from 9.9% in quintile 1 to 11.6% in quintile 5. Sex-stratified analyses indicated higher absolute risks in men, whereas women demonstrated steeper relative increases across higher quintiles. In individuals with hyperuricemia, mortality and CV events rose consistently with increasing SUA/sCr values. CONCLUSIONSThe SUA/sCr ratio is an independent predictor of short-term mortality and cardiovascular events in individuals with preserved renal function. Its incorporation into routine risk stratification may support earlier identification of high-risk patients, particularly those with elevated SUA. CLINICAL PERSPECTIVEO_ST_ABSWhat Is New?C_ST_ABSIn this large, real-world study of nearly 740,000 adults with preserved renal function, the serum uric acid to serum creatinine (SUA/sCr) ratio emerged as a strong, independent predictor of two-year all-cause and cardiovascular mortality. The prognostic value of SUA/sCr was particularly evident in patients with hyperuricemia, where higher quintiles were associated with progressively increased risk of death and cardiovascular events. What Are the Clinical Implications?The SUA/sCr ratio, based on two inexpensive and widely available laboratory parameters, provides a practical tool for early cardiovascular risk stratification in patients without overt kidney disease.

Abstract Introduction Cardiovascular disease (CVD) is an important complication of type 2 diabetes (T2D). Current incident CVD-prediction models use single baseline measurements and achieve moderate performance in people with T2D, with C-indices around 0.7. Modern healthcare registries contain repeated measurements of HbA1c, LDL-cholesterol and eGFR, which could carry incremental predictive value. However, the added value of trajectory measures for CVD-risk prediction remains unclear. We aimed to investigate the utility of HbA1c, LDL-cholesterol and eGFR trajectory measures for incident CVD-risk prediction in people with T2D. Methods We studied 83,326 people with T2D from Danish nation-wide registers, who were without a CVD-history at baseline (January 1st 2015), and had [&ge;]2 recorded HbA1c, LDL-cholesterol and eGFR measurements between 2012-2014. Their last measurement was considered as baseline. Across 2012-2014, three types of paired trajectory measures were calculated for each participant (mean & standard deviation (SD), median & interquartile range (IQR), and intercept & slope from a fitted growth model), for HbA1c, LDL-cholesterol, and eGFR, respectively. Reference Cox-regression models for CVD-events (ICD-10 codes assessed prospectively from 2015- 2020) included only baseline measurements (age, sex , age at T2D onset, HbA1c, LDL-cholesterol, HDL-cholesterol, eGFR, and medication use). Next, the paired trajectory measures were sequentially added to the reference model, computing Hazard Ratios, C-indices and Net reclassification index (NRI) with 95% confidence intervals. Lastly, a combined model was fitted. Results At baseline, mean age was 65 (SD{+/-}12), median HbA1c was 48 (mmol/mol, IQR43-56), and 48% were female. During a median 6 years of follow-up 11,280 (14%) people had a CVD-event (ischemic heart disease: 40%; stroke: 32%; heart failure: 24%; CVD-mortality: 5%). Accounting for the reference model, trajectory measures of dispersion and change were associated with CVD-events, with hazard ratios {approx} 1.1 for HbA1c and eGFR, and >1.4 for LDL-cholesterol. Measures centrality did not show an association with CVD events. Addition of trajectory measures produced minimal gains in discrimination (C index {Delta} +0.001-+0.003) but modest improvements in net reclassification (continuous NRI {approx} +3-+9%). Conclusions Trajectory dispersion or change measures for HbA1c, eGFR and especially LDL-cholesterol, easily obtained from routine data, might moderately enhance incident CVD-risk prediction in people with T2D.

Background and AimsDespite advances in reperfusion and medical therapy, survivors of acute myocardial infarction (AMI) remain at risk for adverse left ventricular remodeling (LVR), a precursor to heart failure. Building on prior work outlining 12-month biomarker trajectories linked to early ventricular dysfunction, we aimed to assess whether these circulating biomarkers predict long-term adverse LVR. MethodsWe prospectively enrolled 155 patients experiencing their first AMI. Clinical, biochemical, and echocardiographic data were obtained at pre-percutaneous coronary intervention (pre-PCI), 24 h post-PCI, discharge (day 3), 6 months, and 12 months. Adverse LVR was defined as an increase of [&ge;]15 % in left ventricular end-systolic volume at 12 months. ResultsAdverse LVR occurred in 34 % of patients and was associated with cardiometabolic dysregulation (higher glucose, triglycerides, BMI, HOMA-IR; lower HDL-C). Among the six baseline biomarkers, only insulin-like growth factor-binding protein 2 (IGFBP-2) differed significantly between groups (p = 0.021) and remained independently associated in multivariable analysis (p = 0.036). Inclusion of IGFBP-2 increased the predictive models area under the receiver-operating characteristic curve from 0.735 to 0.801. ConclusionsIGFBP-2 is an independent predictor of adverse LVR following AMI, highlighting the interplay between metabolic dysfunction and maladaptive remodeling. Incorporating IGFBP-2 into clinical risk models could improve stratification and guide precision therapies for high-risk patients.

Structured AbstractO_ST_ABSBackgroundC_ST_ABSCardiogenic shock (CS) remains a leading cause of in-hospital mortality in acute myocardial infarction (AMI). Although advanced age is associated with worse outcomes, the prognostic relevance of chronological age may vary by clinical presentation, particularly in the presence of out-of-hospital cardiac arrest (OHCA). We investigated the prognostic impact of octogenarian status in patients with AMI complicated by cardiogenic shock (AMI-CS). MethodsWe analyzed patients with AMI-CS enrolled in the multicenter Kanagawa-ACuTe cardIoVascular rEgistry (K-ACTIVE) who underwent percutaneous coronary intervention (PCI). Octogenarian status ([&ge;]80 years) was the primary exposure. Multivariable logistic regression was used to evaluate associations with in-hospital mortality, and effect modification by OHCA was assessed. Model performance was evaluated using discrimination and decision curve analysis. ResultsAmong 658 patients with AMI-CS, 177 (26.9%) were octogenarians, and 279 (42.4%) died during hospitalization. In the primary multivariable analysis, octogenarian status was independently associated with higher in-hospital mortality (adjusted odds ratio [aOR], 2.09; 95% CI, 1.33-3.27). This association was evident among patients without OHCA, whereas no clear age-related gradient was observed among those presenting with OHCA. In multivariable models, heart rate and serum albumin provided incremental prognostic information beyond chronological age. ConclusionIn patients with AMI-CS, the prognostic impact of advanced age varies according to clinical presentation. While advanced age confers excess risk among patients without OHCA, its prognostic value appears limited among those presenting after cardiac arrest. These findings support risk stratification strategies that integrate physiological markers beyond chronological age alone to guide individualized clinical decision-making. Key PointsO_LIThe prognostic impact of age in acute myocardial infarction complicated by cardiogenic shock is highly context dependent. Octogenarian status was associated with increased mortality among patients without out-of-hospital cardiac arrest (OHCA), whereas no meaningful association was observed among those presenting with OHCA. C_LIO_LIUnmeasurable vital signs, particularly heart rate, represent clinically meaningful physiological derangement rather than missing data. These parameters added prognostic information beyond that provided by conventional clinical variables. C_LIO_LISerum albumin and heart rate, which are routinely available at presentation, appeared to capture aspects of physiological vulnerability not fully explained by chronological age alone. C_LI Clinical Perspective What Is New?O_LIThe prognostic relevance of age in AMI complicated by cardiogenic shock (AMI-CS) was not uniform and differed according to clinical presentation. Octogenarians exhibit substantially higher mortality among patients without OHCA, whereas age did not meaningfully influence mortality after OHCA. C_LIO_LIUnmeasurable vital signs represent clinically informative, missing-not-at-random indicators of disease severity. Explicit modeling of unmeasurable systolic blood pressure and heart rate strengthened prognostic assessment. C_LIO_LISerum albumin and heart rate provide prognostic information beyond chronological age in AMI-CS. C_LI What Are the Clinical Implications?O_LIChronological age alone should not determine the aggressiveness of care in patients with AMI-CS. C_LIO_LIAmong patients without OHCA, advanced age may identify a biologically vulnerable subgroup that could benefit from timely revascularization and selectively applied mechanical circulatory support. C_LIO_LIIn patients with OHCA, prognosis appears to be driven predominantly by post-cardiac arrest injury rather than age. C_LIO_LIIncorporating serum albumin and heart rate into risk assessment may support more equitable, phenotype-based clinical decision-making. C_LI

BackgroundElevated low-density lipoprotein cholesterol (LDL-C) is a risk factor for cardiovascular disease. Despite available lipid-lowering therapies (LLT), lipid control remains suboptimal. Bempedoic acid offers a non-statin oral treatment for hypercholesterolemia. However, real-world data in Asia are limited. The study aimed to investigate the effectiveness and safety of bempedoic acid in Taiwan. MethodsThis pragmatic phase IV study enrolled 180 patients with inadequately controlled hypercholesterolemia to receive bempedoic acid for 12 weeks in addition to background LLT. The primary endpoint was the percentage change in LDL-C. Secondary endpoints included changes in other lipid parameters, high-sensitivity C-reactive protein (hsCRP), and safety outcomes. ResultsAmong 180 patients, 160 (88.9%) completed the study. The median percentage change in LDL-C from baseline to week 12 was -19% (interquartile range [IQR]: -36.4% to -3.6%), decreasing from 117.5 to 92 mg/dL (p < 0.01). The median percentage changes from baseline to week 12 were -13.3% for non-high-density lipoprotein cholesterol (non-HDL-C), -10.8% for total cholesterol, -11.5% for apolipoprotein B, and -34.0% for hsCRP (all p < 0.01). Minimal effects were noted on triglycerides (+0.2%), HDL-C (-5.5%), and lipoprotein(a) (+2.6%) (all p > 0.05). At week 12, 31.3% of patients achieved LDL-C targets (< 100 mg/dL for primary prevention; < 55 or < 70 mg/dL for secondary prevention). The safety outcomes were consistent with the locally approved label, with no new safety signals identified. ConclusionsBempedoic acid offers an effective and safe oral therapeutic option for Taiwanese patients whose LDL-C levels remain inadequately controlled with existing LLT, including statins. RegistrationURL: https://clinicaltrials.gov/study/NCT06925100; Unique identifier: NCT06925100 Clinical PerspectiveO_ST_ABSWhat Is New?C_ST_ABS{diamondsuit} This pragmatic phase IV study provides the first real-world evidence from Taiwan demonstrating that bempedoic acid leads to clinically meaningful reductions in LDL-C (median percentage change: -19%) at week 12 when added to background lipid-lowering therapy in patients with inadequately controlled hypercholesterolemia. {diamondsuit}Approximately one-third of patients achieved guideline-recommended LDL-C targets within 12 weeks, with a safety profile consistent with the locally approved label and no new safety signals identified. What Are the Clinical Implications?{diamondsuit} Bempedoic acid represents an effective and well-tolerated oral add-on lipid-lowering option for Taiwanese patients who fail to achieve LDL-C goals with existing therapies, including those unable to tolerate or intensify statin treatment.