The "2026 AHA/ACC/ACS/ASNC/HRS/SCA/SCCT/SCMR/SVM Guideline for Perioperative Cardiovascular Management for Noncardiac Surgery" provides recommendations to guide clinicians in the perioperative cardiovascular evaluation and management of adult patients undergoing noncardiac surgery.

A comprehensive literature search was conducted from August 2022 to March 2023 to identify clinical studies, reviews, and other evidence conducted on human subjects that were published in English from MEDLINE (through PubMed), EMBASE, the Cochrane Library, the Agency for Healthcare Research and Quality, and other selected databases relevant to this guideline.

Recommendations from the "2014 ACC/AHA Guideline on Perioperative Cardiovascular Evaluation and Management of Patients Undergoing Noncardiac Surgery" have been updated with new evidence consolidated to guide clinicians; clinicians should be advised this guideline supersedes the previously published 2014 guideline. In addition, evidence-based management strategies, including pharmacological therapies, perioperative monitoring, and devices, for cardiovascular disease and associated medical conditions, have been developed.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is associated with chronic low-grade inflammation and an increased risk of cardiovascular disease. Early identification of subclinical cardiometabolic alterations remains challenging because standardized protocols integrating dietary inflammatory assessment with objective cardiovascular imaging are limited. This protocol describes a reproducible workflow for evaluating the association between dietary inflammatory potential and early cardiometabolic alterations in adults with confirmed MASLD. Participants are enrolled according to standardized eligibility criteria, and hepatic steatosis is confirmed by ultrasonography. Dietary intake is assessed using a validated semi-quantitative food frequency questionnaire (FFQ), from which the Dietary Inflammatory Index (DII) is calculated using the original literature-derived methodology. Cardiometabolic assessment includes anthropometric measurements, fasting biochemical analyses, calculation of the triglyceride-to-high-density lipoprotein cholesterol (TG/HDL-C) ratio and the Atherogenic Index of Plasma (AIP), enzyme-linked immunosorbent assay (ELISA) quantification of inflammatory biomarkers, transthoracic echocardiographic assessment of left ventricular diastolic function using tissue Doppler-derived E/e', and bilateral carotid ultrasonography for measurement of carotid intima-media thickness (CIMT). Standardized acquisition procedures, predefined quality-control checkpoints, and data-validation steps are incorporated to ensure methodological consistency and reproducibility. Representative results demonstrate the standardized data generated by the protocol, including DII classification, inflammatory biomarker profiles, echocardiographic indices, and CIMT measurements, and do not imply confirmatory biological associations. This protocol provides a detailed, reproducible methodological framework for conducting clinical and translational studies investigating the relationship between dietary inflammatory burden and early cardiometabolic alterations in adults with MASLD.

The treatment goals of cardiovascular diseases are focused primarily on LDLc. ML-based LDLc estimation methods offer a superior, reliable alternative to traditional formulas. This study aims to evaluate the performance of ML-based LDLc estimation models and compare their accuracy to direct LDLc and conventionally used formulas.

ML models based on Elastic Net based Formula, Elastic Net based Formula, Random Forest(RDF), eXtreme Gradient Boost, Multiple Layer Perceptron Regressor (MLP) were developed based on 61,444 patient datapoints i.e. 36,866-internal dataset and 24,578-external dataset. The performance of model evaluated in data subsets based on Total Cholesterol and TG levels. These subsets were evaluated i.e. adjusted R2, MSE, RMSE, Mean Absolute Error, % Bias along with evaluation matrix score (EMS)-based ranking and Subset-Integrated EMS (SI-EMS).

Based on the EMS and SI-EMS, MLP model was depicted to be the best model for overall dataset as well as all subsets. Bland Altmann plot showed all ML models Highly Reliable based on Bias and Trend (r). Among the formulas, Martin's is only Highly Reliable. Classification Validation Score (CVS) depicted better performance of ML models than their counterparts except when classifying Very High LDL. MLP was in top five methods with equivalent CVS to top models.

Based on the SI-EMS, ML models and formula were evaluated, MLP neural network performed the best to estimate LDLc levels and the web application constructed by utilizing best model could be a potential aid to clinicians and laboratories in estimating LDL values closer to the actual measurement.

Early diastolic dysfunction precedes the development of HFpEF, but the molecular events that initiate this process remain poorly defined. HFpEF arises in the setting of systemic comorbidities such as obesity (OB), hypertension, hyperglycaemia (HG), and sleep apnoea, which often coexist and make it difficult to distinguish their individual contributions to early cardiac remodelling. Here, we aimed to define the early, comorbidity-specific mechanisms that initiate diastolic dysfunction across major HFpEF-associated conditions.

We performed single-nucleus RNA sequencing (snRNA-seq) of left ventricles from mouse models of OB, systemic arterial hypertension (SAH), chronic intermittent hypoxia (CIH), and HG at the time point corresponding to early diastolic impairment. Findings were validated by qRT-PCR, immunohistochemistry, and targeted interventions.OB and HG induced the most extensive transcriptional remodelling, affecting cardiomyocytes, fibroblasts, endothelial cells, and macrophages, while SAH and CIH produced comparatively more modest changes. Cardiomyocytes developed comorbidity-specific stress programmes, with glucocorticoid receptor (GR)-driven activation in OB, combined FoxO and GR signalling in HG, mitochondrial and sarcomeric remodelling in hypertension, and minimal changes in hypoxia. Fibroblasts and endothelial cells in OB and HG mice adopted profibrotic and angiogenesis-impaired profiles, and macrophages polarized towards GR-regulated or immunomodulatory states, depending on the comorbidity. Correction of OB at mid-life improved ventricular relaxation, delayed HFpEF onset, and reduced GR target expression. Direct GR inhibition through overexpression of the lncRNA GAS5 or with mifepristone treatment rescued diastolic function independently of weight loss. In HG mice, CnAβ1 overexpression reduced baseline expression of FoxO target genes, corrected atrophy, but did not prevent FoxO target induction under HG or restore relaxation.

Early diastolic dysfunction arises through comorbidity-specific molecular programmes. OB-induced GR activation emerges as a causal and actionable driver of diastolic dysfunction. These findings provide mechanistic insight into comorbidity-specific pathways in HFpEF and support the development of stratified therapeutic approaches.

Degenerative mitral regurgitation (DMR) due to valve prolapse predominates in men, but sex-specific differences are poorly understood due to a lack of quantitative and sex-stratified studies.

The international MIDA-Q (Mitral Regurgitation International Database-Quantitative) registry enrolled 3274 men and 2331 women with greater than or equal to mild DMR prospectively quantified, comprehensively characterized, and long-term follow-up.

Women were more symptomatic despite lower effective regurgitant orifice (ERO, 27±18 versus 38±22 mm², standardized mean difference 0.54; P<0.0001) and regurgitant volume (46±26 versus 61±31 mL/beat, standardized mean difference 0.52; P<0.0001), even for similar mitral lesions. With increasing ERO, women showed lower regurgitant volume, higher heart rate, lower blood pressure, but left ventricular size response in women was smaller in absolute measures while larger when body surface area normalized, with higher ejection fraction and cardiac index (all P<0.0001). Incidence of mitral valve surgery was similar in symptomatic women and men, but lower in asymptomatic women versus men (adjusted hazard ratio, 0.80 [0.69-0.94]; P=0.008) for similar ERO, linked to smaller left ventricular diastolic absolute diameter (P<0.0001). Excess mortality under medical management (of severe versus mild ERO) was similar in women (adjusted hazard ratio, 1.67 [1.24-2.24]; P=0.0007) and men (adjusted hazard ratio, 1.63 [1.27-2.09]; P<0.0001) and versus expected survival (2.12 [1.51-2.98] in women and 2.27 [1.75-2.94] in men). However, moderate ERO (20-39 mm²) was associated with significant excess mortality in women (1.47 [1.19-1.77] versus mild). In men, the corresponding hazard ratio did not reach statistical significance. Postoperative survival was similar in men and women.

Women with DMR present with lower ERO and regurgitant volume than men and with considerable adaptive differences to increasing DMR severity versus men. Asymptomatic women are less referred to surgery than men of similar DMR severity, linked to smaller absolute left ventricular size. Severe DMR by similar quantitative thresholds causes similar excess mortality in men and women; moderate quantitative DMR shows a trend for higher excess mortality versus expected in women than men, requiring further confirmation. These data emphasize the importance of quantitative DMR and left ventricular remodeling assessment in men and women for appropriate clinical management.

Cardiovascular disease is a major cause of death in individuals with chronic kidney disease; thus, improving its prediction is critical for cardiovascular disease risk reduction. Studies have not assessed whether a polygenic risk score (PRS) of coronary heart disease (CHD) developed from genetic studies in the general population can improve cardiovascular disease risk prediction in individuals with chronic kidney disease, especially when PRS is added to the American Heart Association Predicting Risk of Cardiovascular Disease EVENTs (PREVENT) equations.

Focusing on a 10-year composite CHD event, we applied PRSs of CHD obtained from the polygenic score catalog to the multi-center CRIC (Chronic Renal Insufficiency Cohort) participants, selected the best-performing PRS and evaluated the added value of the best PRS while accounting for PREVENT linear predictors. Three Cox proportional hazard models were fitted with PRS only, PREVENT predictors only, and PRS+PREVENT risk factors. We evaluated the prediction accuracy, discrimination, and calibration of the combined model compared with the PREVENT model.

A PRS of CHD was significantly associated with a 21% hazard of CHD in the PRS+PREVENT risk model (95% CI, [1.06-1.39], 2-sided Wald test P=5.5×10^-3). The PRS+PREVENT model demonstrated a higher area under the curve (72.4% [95% CI, 0.66-0.79] versus 70.8% [95% CI, 0.64-0.77]), better discrimination ability, and improved calibration compared with the PREVENT model predictors. Individuals were more correctly classified in prediction quartiles using the PRS+PREVENT model for the 10-year CHD event proportions.

Our results demonstrate the added value of a CHD PRS to the PREVENT risk prediction models in individuals with chronic kidney disease. The combined PRS+PREVENT model has the potential to improve clinical decisions on disease prevention and treatment strategies.

Accurate low-density lipoprotein cholesterol (LDL-C) assessment in young adulthood is critical for atherosclerotic cardiovascular disease (ASCVD) prevention, yet the optimal estimation equation remains uncertain. We compared the Friedewald, Martin-Hopkins, and Sampson equations for evaluating long-term ASCVD risks.

We included participants from 7 population-based cohorts within the International Childhood Cardiovascular Cohort Consortium who had LDL-C measurements in young adulthood (aged 20-39 years) and follow-up data for incident ASCVD. LDL-C levels were estimated using the Friedewald, Martin-Hopkins, and Sampson equations. For each pair of equations, participants were categorized into concordant (normal/normal, elevated/elevated) and discordant (normal/elevated, elevated/normal) groups based on LDL-C classifications (normal <130 mg/dL versus elevated ≥130 mg/dL). ASCVD events (myocardial infarction, stroke, transient ischemic attack, ischemic heart failure, angina, peripheral artery disease, carotid intervention, abdominal aortic aneurysm, coronary revascularization) were adjudicated from medical records. Associations between discordance and incident ASCVD were estimated using Fine-Gray regressions.

Among 10 550 participants (56.8% females; mean baseline age [SD], 29.8 [4.3] years), 376 ASCVD events occurred over a mean follow-up of 22.7 years. Elevated LDL-C by all equations was associated with ASCVD events (subdistribution hazards ratio [95% CI]: Martin-Hopkins, 1.69 [1.35-2.12]; Sampson, 1.52 [1.22-1.90]; Friedewald, 1.47 [1.17-1.84]). Total discordance ranged from 2.3% to 2.9%. Compared with the concordant normal LDL-C group, normal LDL-C by Friedewald but elevated by Martin-Hopkins had higher ASCVD risks (3.32 [1.94-5.66]), with no excess risk in the reverse discordance (1.19 [0.47-3.05]). Normal Friedewald but elevated Sampson LDL-C had higher ASCVD risks (1.69 [0.93-3.05]); no participants had the reverse discordance. Normal Sampson LDL-C but elevated Martin-Hopkins LDL-C had higher ASCVD risks (3.94 [1.80-8.64]), whereas the reverse discordance showed no increased risk (0.86 [0.39-1.91]).

The Martin-Hopkins equation provides more accurate LDL-C-based risk classification, identifying high-risk young adults missed by other equations and minimizing misclassification of those at normal risk.

Ferroptosis has been recognized as an important pathological mechanism underlying ischemic stroke (IS). However, the precise mechanisms underlying the neuroprotective effects of Hydroxysafflor yellow A (HSYA) in IS remain unclear.

Therefore, this study aimed to investigate the protective effects of HSYA against IS and explore the underlying ferroptosis-related mechanisms.

An integrated strategy combining network pharmacology, molecular docking, molecular dynamics simulations, and a middle cerebral artery occlusion (MCAO) mouse model was employed to elucidate the neuroprotective mechanisms of HSYA. Neurological deficit scores, infarct volume, histopathology, oxidative stress, and ferroptosis-related molecules were evaluated. For in vivo validation, mice were randomly assigned to the sham, MCAO, Ras-selective lethal (RSL), HSYA, and RSL + HSYA groups (n = 12 per group). Ras-selective lethal 3 (RSL3) was used as a glutathione peroxidase 4 (GPX4) inhibitor in the RSL and RSL + HSYA groups.

Network pharmacology identified GPX4 and Ferritin Heavy Chain 1 (FTH1) as potential ferroptosis-related targets of HSYA in IS. Docking analysis showed favorable binding affinities of HSYA toward GPX4 (-9.3 kcal/mol) and FTH1 (-9.1 kcal/mol), and molecular dynamics simulations further supported the stability of the HSYA-GPX4 and HSYA-FTH1 complexes. In vivo experiments showed that HSYA significantly improved neurological deficit score, reduced infarct volume, and alleviated histopathological damage in MCAO mice (p < 0.01 or p < 0.05). Moreover, HSYA significantly decreased malondialdehyde (MDA) and reactive oxygen species (ROS) levels while increasing superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities (p < 0.01 or p < 0.05). HSYA significantly upregulated the mRNA and protein levels of GPX4, FTH1, and mitochondrial ferritin (FTMT) (p < 0.01 or p < 0.05). Notably, HSYA significantly increased the relative protein expression of GPX4 compared with the MCAO group (p < 0.01). Furthermore, RSL3 partially attenuated the protective effects of HSYA on cerebral injury, oxidative stress, and the expression of GPX4, FTH1, and FTMT (p < 0.01 or p < 0.05). Collectively, the present study demonstrates that HSYA confers neuroprotection against IS, at least in part, through regulation of GPX4-associated ferroptosis pathways.

HSYA provides significant neuroprotection against IS. These effects may be mediated, at least in part, through GPX4-associated ferroptosis pathways and the maintenance of iron homeostasis, thereby advancing understanding of its antioxidant mechanisms and supporting its therapeutic potential for IS.

Post-stroke depression (PSD) is a prevalent psychological complication among stroke survivors. Exercise intervention, as a non-pharmacological therapeutic approach, plays a crucial role in the rehabilitation of PSD. This study aimed to systematically evaluate the efficacy of various exercise intervention models and exercise doses on PSD through a network meta-analysis. The findings are expected to provide personalized exercise recommendations for patients with PSD and further promote the integration of exercise therapy into stroke rehabilitation.

This study was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Relevant randomized controlled trials (RCTs) published up to April 2025 were retrieved from PubMed, Cochrane, Embase, Ovid, and Web of Science databases. Data analysis was performed using R statistical software.

Exercise interventions lasting less than 8 weeks, performed at least five times per week, and with individual sessions of 30 minutes or less, demonstrated the most significant improvement in PSD symptoms. As the exercise dose increased, the antidepressant effects of mixed aerobic exercise (MAE), combined exercise (CE), resistance training (RT), high-intensity interval training (HIIT), moderate-intensity continuous training (MICT), traditional martial arts (TOMA), and yoga (YOGA) all exhibited a continuous downward trend. Among these, resistance training (RT) showed the most significant decline, with no subsequent rebound effect.

All exercise intervention models effectively alleviate PSD symptoms, with resistance training emerging as the most effective single exercise modality. However, the optimal exercise dose for resistance training remains to be established. Further clinical studies are warranted to clarify the dose-response relationship and optimize exercise dose PSD management.

PROSPERO (CRD420251012962).