Observational studies have linked inflammatory cytokines to cardiometabolic disorders; however, whether these associations reflect causal effects across interconnected organ systems remains unclear.

This Mendelian randomization (MR) study investigates causality between 91 inflammatory cytokines and multiorgan dysfunction across cardiovascular, kidney, and metabolic systems in the cardiovascular-kidney-metabolic (CKM) syndrome era.

Genetic instruments associated with 91 inflammatory cytokines were obtained from the Olink Target Inflammation panel across 11 European-ancestry cohorts. The inverse variance weighting (IVW) method was considered as the main analysis, complemented by sensitivity analyses including MR-Egger and weighted median methods.

Genetically predicted levels of inflammatory cytokines showed widespread causal associations across CKM-related traits. Specifically, 31 cytokines were associated with cardiovascular outcomes, 26 with kidney traits, 10 with obesity-related traits, and 21 with diabetes-related traits, yielding a total of 60 cytokines with at least one significant association. Notably, FGF5 and IL6 emerged as paradoxical regulators, exerting opposing effects across different organ systems, while MCSF was consistently identified as a pan-vascular risk amplifier for cardiovascular diseases.

This comprehensive MR analysis reveals substantial causal heterogeneity in inflammatory cytokine effects across cardiovascular, kidney, and metabolic systems. These findings highlight the clinical importance of tissue- and context-specific inflammatory modulation, supporting the development of precision therapeutic strategies for CKM syndrome.

The SUMMIT trial showed that the long-acting glucose-dependent insulinotropic polypeptide receptor and glucagon-like peptide-1 receptor agonist tirzepatide decreased risk of cardiovascular death or worsening heart failure (HF) in patients with obesity-related heart failure with preserved ejection fraction (HFpEF). Women outnumber men with HFpEF, and there are sexual dimorphisms in the relationships between body fat and pathophysiology that could influence response to tirzepatide.

This study aims to compare baseline characteristics and effects of tirzepatide on primary and other endpoints in women and men with obesity-related HFpEF.

In the SUMMIT trial, 731 patients with NYHA functional class II-IV HFpEF and body mass index (BMI) ≥30 kg/m² were randomly assigned to tirzepatide (n = 364) or placebo (n = 367). The primary outcomes were time to cardiovascular death or worsening HF and change in Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score (KCCQ-CSS) at 52 weeks. Key secondary outcomes included changes in 6-minute walk distance (6MWD), C-reactive protein, and body weight at 52 weeks. Baseline characteristics and effects of tirzepatide on primary and secondary endpoints were contrasted by sex.

Compared with men (n = 338, 46.2%), women with obesity-related HFpEF (n = 393, 53.8%) had greater BMI, waist to height ratio (WHtR), symptom severity (higher NYHA functional class, lower KCCQ-CSS), and poorer exercise capacity (lower 6MWD), whereas men had greater left ventricular remodeling and paracardiac fat. Greater baseline BMI or WHtR were correlated with lower KCCQ-CSS and 6MWD in women and men, with no interaction, but higher WHtR was associated with poorer kidney function exclusively in women (interaction P = 0.043). The effect of tirzepatide on the risk of worsening HF or cardiovascular death did not differ in women and men (HR: 0.66 and 0.61, respectively, interaction P = 0.81), with no heterogeneity of effect on KCCQ-CSS at 52 weeks (8.1- and 5.5-point placebo-corrected improvement, respectively, interaction P = 0.43) or 6MWD (18 m and 15 m placebo-corrected improvement, respectively, interaction P = 0.76). Among patients randomized to tirzepatide, decreases in body weight on treatment were more strongly associated with improvements in KCCQ-CSS in women than men (interaction P = 0.0058).

Compared with men, women with obesity-related HFpEF have greater adiposity, symptom severity, and poorer exercise capacity but lower left ventricular mass and paracardiac fat deposition. Despite these differences, tirzepatide resulted in consistent benefits across multiple domains of HF severity that did not differ by sex. (A Study of Tirzepatide [LY3291876] in Participation With Heart Failure With Preserved Ejection Fraction [HFpEF] and Obesity [SUMMIT]; NCT04847557).

Arterial hypertension is a major cardiovascular risk factor (CVRF) associated with increased risk of cardiotoxicity in cancer patients.

The aim of this study was to determine the prevalence of hypertension in patients with newly diagnosed cancer and compare it with the prevalence in the general population.

Data were derived from the CONNECT-POL registry, the largest prospective Polish study assessing the burden of cardiovascular problems among cancer patients. Inclusion criteria were adult age and newly diagnosed breast, lung, colorectal, or prostate cancer. The occurrence of CVRF and cardiovascular diseases were recorded during a cardiology consultation.

Between October 2023 and February 2025 in 11 centers 1523 patients were enrolled - 951 women, 572 men, at median age 67 (interquartile range 16) years. The most frequent CVRF was arterial hypertension, present in 949 patients (62.3%). The prevalence of hypertension reached 79.1% in colorectal, 75.1% in prostate, 69.4% in lung, and 50.1% in breast cancer. In multivariable analysis, hypertension was independently associated with age, body weight, dyslipidemia, diabetes, obesity and colon cancer compared to other cancer types. After age standardization to the structure of the WOBASZ II study, the prevalence of hypertension was higher among patients with colorectal (P = 0.045) and lung (P = 0.002) cancer compared with general population.

The prevalence of hypertension in cancer patients is very high compared to the general population and varies by cancer type, being highest in colorectal cancer and lowest in breast cancer patients. These results highlight the importance of routine blood pressure monitoring and encouraging home blood pressure monitoring in patients scheduled for oncological therapy.

Major adverse cardio- and cerebrovascular events (MACCE) are critical determinants of clinical outcomes in older patients. However, the relationship between nutritional status and the prognosis of cardiovascular and cerebrovascular diseases remains underexplored. This meta-analysis investigates the association of commonly used nutritional scores with MACCE in older adults. A systematic search of the Cochrane Library, Embase, PubMed, and Web of Science was conducted up to November 28, 2025, to identify clinical studies examining nutritional scores and MACCE in older adults. The primary outcome was the risk of MACCE. Meta-analyses were performed using RStudio to pool hazard ratios (HRs) with their corresponding 95% confidence intervals (CIs) to quantify the association between various nutritional scores and MACCE. Our meta-analysis included 28 studies comprising 80,860 individuals. Data were stratified based on derivation from univariate or multivariate Cox regression. Pooled results from multivariate-adjusted data revealed that malnutrition, as assessed by the geriatric nutritional risk index (GNRI: HR [95% CI]: 1.38 [1.22, 1.55]), the prognostic nutritional index (PNI: 1.34 [1.02, 1.76]), and the nutritional risk index (NRI: 1.37 [1.08, 1.73]), was significantly associated with an elevated risk of MACCE. Furthermore, increasing scores on the controlling nutritional status (CONUT) index (1.19 [1.12, 1.26]) and decreasing scores on the GNRI (0.95 [0.93, 0.98]) and PNI (0.95 [0.93, 0.97]) were each significantly correlated with a higher risk of MACCE. In conclusion, nutritional scores demonstrate a significant association with the risk of MACCE and its secondary outcomes in the older population.

Stroke remains a leading cause of death and long-term disability. Yet, much of its burden is preventable through earlier and more intensive management of vascular and cardiovascular-kidney-metabolic risk factors. Primary prevention is challenging as the first clinical event is often unpredictable and may manifest as stroke, myocardial infarction, heart failure, or peripheral arterial disease. Contemporary tools, therefore, estimate overall cardiovascular risk rather than stroke risk in isolation. The goal of this review is to emphasize that effective stroke prevention requires a shift toward global cardiovascular risk assessment and to highlight the potential clinical utility of newer risk prediction tools. The predicting risk of cardiovascular disease events equations, developed by the American Heart Association, update absolute risk estimation by modeling overall cardiovascular disease risk using sex-specific, race-free equations that incorporate kidney function, account for competing noncardiovascular death, and optionally include neighborhood deprivation. External validations suggest improved calibration compared with pooled cohort equations, supporting a more reliable estimation of absolute treatment benefit. For clinicians managing patients at risk for stroke, predicting risk of cardiovascular disease events is most useful when the clinical question is how aggressively to optimize risk factors before the first event, including decisions about blood pressure, lipid-lowering therapy, cardiovascular-kidney-metabolic management, and patient communication using 10-year, 30-year, and risk age outputs. Key limitations include its focus on overall rather than cause-specific cardiovascular risk, lack of stroke mechanism-specific estimates, absence of major nonatherosclerotic stroke drivers such as atrial fibrillation, and lack of imaging-stratified treatment-effect estimates. Predicting the risk of cardiovascular disease events' ultimate clinical impact and equity will depend on implementation within electronic health record workflows, autopopulated inputs, treatment pathways tied to estimated risk, and complementary cause-specific evaluation when clinically indicated.

Titin truncating variants (TTNtv) represent the most common genotype underlying dilated cardiomyopathy but are also detected in the general population, exhibiting incomplete penetrance and marked phenotypic variability. This heterogeneity complicates clinical interpretation and risk stratification. Emerging molecular evidence suggests that truncating location within the gene may influence disease mechanisms. We aimed to investigate whether TTNtv location also affects clinical phenotype and prognosis.

We established an international multicenter registry of phenotypically affected carriers of pathogenic or likely pathogenic TTNtv. Patients were classified into 3 groups: A-band, Z/I-band, and M-band. A case-control study assessed the enrichment of TTNtv across regions. The primary outcome was a composite of all-cause mortality and heart transplantation. Secondary outcomes included: (1) sudden cardiac death or major ventricular arrhythmias and (2) heart failure-related death/heart transplantation/left ventricular assist device implantation.

The study included 467 patients (81% probands, 73% male, median age 47 years, 81% dilated cardiomyopathy phenotype). Most carried TTNtv in the A-band (80% versus 15% Z/I-band and 5% M-band). All groups showed enrichment compared with GnomAD, with greater Bayesian-estimated penetrance for A-band variants. Over a median follow-up of 83 months, the primary end point was similar across groups. However, the risk of sudden cardiac death/major ventricular arrhythmias was significantly higher in M-band carriers (45% M-band versus 23% Z/I-band versus 12% A-band; P=0.001), especially as the first disease manifestation. Band location independently predicted sudden cardiac death/major ventricular arrhythmias risk, whereas left ventricular ejection fraction was predictive only in A- and Z/I-band groups.

TTNtv are differently enriched across the gene in patients with dilated cardiomyopathy/nondilated left ventricular cardiomyopathy. Penetrance and risk of sudden cardiac death/major ventricular arrhythmias differ according to variant location, supporting the TTN truncation site as a parameter that should be considered for personalized risk stratification in TTN cardiomyopathy.

Accurate assessment of left ventricular ejection fraction (LVEF) is fundamental to the diagnosis, risk stratification and management of cardiovascular diseases. Cardiac magnetic resonance imaging (CMR) is the established reference standard, while echocardiography and global longitudinal strain (GLS) provide widely accessible alternatives. This study compared LVEF by CMR, two-dimensional echocardiography (2D Echo), three-dimensional echocardiography (3D Echo) and GLS in patients with cardiovascular diseases at a Northeast Indian tertiary care centre.

A hospital-based prospective observational comparative study enrolled 50 patients with confirmed cardiovascular pathology at Assam Medical College and Hospital (AMCH), Dibrugarh. Cardiac magnetic resonance imaging was performed on a Siemens Magnetom Avanto 1.5 T scanner; echocardiography employed the Philips Affiniti CVx system. Agreement was assessed by Bland-Altman analysis and intraclass correlation coefficient (ICC).

The mean CMR-LVEF was 48.5 ± 12.3%. 2D Echo showed a mean positive bias of +2.7 percentage points (95% limits of agreement [LoA]: -8.5% to +13.9%; ICC 0.89) and 3D Echo showed superior agreement (bias +1.3%; LoA -6.2% to +8.8%; ICC 0.93). Upward reclassification by 2D Echo occurred in 26% of patients. Global longitudinal strain strongly correlated with CMR-LVEF (r = -0.87, p < 0.001) and identified subclinical dysfunction in 35% of patients with preserved LVEF (≥50%).

Cardiac magnetic resonance remains the reference standard for LVEF quantification. 3D Echo shows significantly superior agreement with CMR versus 2D Echo. Global longitudinal strain provides incremental diagnostic value beyond LVEF. A tiered multimodality imaging strategy with selective CMR confirmation at clinical decision boundaries is recommended.

The dependence of the acquisition of the coronary artery calcification score (CACS) on computed tomography (CT) has drawbacks, including the ethical concerns of radiation exposure in the care of patients with non-cardiovascular diseases, where CACS has been shown to correlate with its prognosis. Significant heterogeneities exist between patients with and without coronary artery calcification (CAC). Mathematical formulae using medical history and common, non-invasive test results enable cheap, ready assessment of CAC and subsequent research into how it can be used for clinical decision making.

694 patient records of visits to Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College from 2009 to 2023 were partitioned into a training (visited before 2023) and an independent validation set (visited in 2023). With age, gender, current smoking, diabetes, low-density lipoprotein cholesterol (LDL-C), reduced renal function, usage of statins and aspirin as candidate predictors, five logistic regression models were built under two paradigms. Bootstrap resampling was employed for internal validation, followed by external validation and calibration on the validation set. Models built under each paradigm were compared, followed by head-to-head comparison of the "best" models built under each paradigm with a comprehensive criteria involving both model performance and predictor parsimony.

694 records were used for modeling, with 536 and 158 records in the training and validation set respectively. Model 1 (c statistic upon external validation: 0.77) outperformed other models built under Paradigm 1 while Models 4 (c statistic upon external validation: 0.79) and 5 (c statistic upon external validation: 0.79) built under Paradigm 2 outperformed Model 1. Model 5 was more parsimonious in predictors. All models were well calibrated.

With gender, current smoking, LDL-C, age, diabetes and reduced renal function as predictors, Model 5 outperformed other models and was hence recommended for further use. By assessing the presence of CAC with medical history and blood test results instead of CT, our model offers an approach to immediate, radiation-free assessment of CAC, which may further unleash the clinical utility of CAC in clinical practice that may have remained unraveled.

The left atrium (LA) plays a crucial role in maintaining left ventricular filling. Additionally, LA function serves as a key indicator for evaluating and grading the severity of left ventricular diastolic dysfunction. Increasing evidence demonstrates that LA function and volume are vital imaging indicators for various cardiovascular conditions. However, conventional volumetric parameters have limitations. They cannot adequately depict the phase-dependent characteristics and complex dynamics of LA activity. Recently, cardiac magnetic resonance feature tracking (CMR-FT) has emerged as an effective tool for quantifying LA strain. This technique offers superior reproducibility, lacks acoustic window constraints, and provides enhanced spatial resolution. CMR-FT-derived LA strain enables the early detection of atrial mechanical injury. Furthermore, it precisely reflects atrial phasic functional changes. These capabilities offer novel insights into the diagnosis, management, prognostic stratification, and therapeutic efficacy assessment of cardiovascular diseases. This review summarizes current research advances in LA strain assessment via CMR-FT and further provides perspectives on its clinical applications.

High-mobility group box 1 (HMGB1), a damage-associated molecular pattern (DAMP), has increasingly been implicated in the pathogenesis of various cardiovascular diseases. This study aimed to elucidate the relationship between circulating HMGB1 levels and the development of heart failure (HF).

This single-center cross-sectional study enrolled 412 patients presenting with chest tightness or pain at the Department of Cardiovascular Medicine, First Affiliated Hospital of Nanchang University, between January and July 2025. The relationship between HMGB1 and HF occurrence was evaluated using Spearman's correlation analysis, logistic regression models, restricted cubic spline (RCS) plots, and receiver operating characteristic (ROC) curves. Subgroup analyses were also performed to assess the robustness of the findings.

Of the 412 enrolled patients, 343 were included in the final analysis after application of the exclusion criteria; 151 were diagnosed with HF, and 192 served as controls. Serum HMGB1 levels were significantly higher in the HF group than in the control group (1.53 ng/mL vs 0.93 ng/mL; p < 0.001). Spearman's correlation analysis revealed significant positive correlations between HMGB1 levels and left ventricular end-diastolic diameter (LVEDD), left atrial diameter (LAD), and the systemic inflammatory response index (SIRI), and a significant negative correlation with left ventricular ejection fraction (LVEF) (all p < 0.05). In the univariate logistic regression analysis, elevated HMGB1 levels were strongly associated with increased HF risk (odds ratio [OR] = 2.942, 95% confidence interval [CI]: 2.113-4.095; p < 0.001). This association remained significant in multivariable models after sequential adjustment for demographic, clinical, and laboratory covariates, with a fully adjusted OR of 2.273 (95% CI: 1.410-3.663; p < 0.001). Restricted cubic spline (RCS) analysis confirmed a linear dose-response relationship between HMGB1 levels and HF risk (p for nonlinearity = 0.174). ROC analysis showed that HMGB1 alone had good predictive value for HF (area under the curve [AUC] = 0.736), outperforming individual traditional markers. Furthermore, a combined model incorporating HMGB1, LVEF, LVEDD, LAD, and SIRI achieved superior predictive accuracy (AUC = 0.807). Finally, subgroup analyses showed that only sex exhibited a significant interaction, while interactions for all other variables were non significant interaction ( p for interaction > 0.05), indicating that this relationship was robust and independent of major clinical variables.

The levels of HMGB1 elevation were significantly related to the occurrence of HF, which may serve as a potential biomarker for the development of innovative therapeutic strategies in patients with heart failure.