Cardiovascular Mortality Research Articles

Anthracyclines, which are key to many chemotherapeutic protocols, have been associated with increased vascular stiffness, a major factor associated with cardiovascular morbidity and mortality. There is no evidence-based intervention to prevent anthracycline-associated vascular dysfunction. To investigate whether atorvastatin pretreatment is associated with attenuation of the anthracycline-induced increase in aortic stiffness. This study is a secondary analysis of a double-blind, randomized clinical trial (Statins to Prevent the Cardiotoxicity From Anthracyclines [STOP-CA]). Enrollment occurred between January 25, 2017, and September 10, 2021, with the last follow-up on October 10, 2022. Primary analyses were reported on August 8, 2023. STOP-CA was a multicenter trial across 9 academic centers in the US and Canada. Participants were patients with newly diagnosed lymphoma scheduled to undergo anthracycline-based chemotherapy with no clinical indication for a statin. Atorvastatin (40 mg, once daily) or placebo for 12 months. This subanalysis of the STOP-CA trial includes post hoc end points with cardiac magnetic resonance imaging-derived aortic arch pulse wave velocity (PWV) and aortic distensibility (AD). An intention-to-treat approach was applied. The proportions of participants with a 1 SD or more increase in PWV and a 1 SD or more decrease in ascending aortic distensibility (AAD) were calculated in each group over 12 months. An increase in PWV of 0.15 m per second or more, a previously defined annual rate in individuals of similar age, was also assessed as a secondary end point. Of the 300 participants (150 randomized to atorvastatin and 150 randomized to placebo), 152 (mean [SD] age, 51 [17] years; 72 female [47%]; 82 treated with atorvastatin) had paired PWV data, and 168 had paired AD data. The PWV values remained similar in the atorvastatin group (mean [SD], 6.5 [1.9] vs 6.5 [2.0] m per second) but increased in the placebo group (5.7 [1.8] vs 6.8 [2.0] m per second) over 12 months. A 1 SD or more increase (0.8 m per second) in PWV was observed among 4 of 82 patients (5%) with atorvastatin and 35 of 70 patients (50%) with placebo (odds ratio, 0.05; 95% CI, 0.02 to 0.16; P < .001) at 12 months. A 1 SD or more decrease (1.8 × 10-3 mm Hg-1) in AAD was observed among 6 of 88 patients (7%) with atorvastatin and in 14 of 80 patients (18%) with placebo. A 1 SD or more increase in PWV was associated with a mean left ventricular ejection fraction decline of 2.70% (95% CI, -4.65% to -0.81%; P = .006). Pretreatment with atorvastatin was associated with preservation of vascular function among patients with lymphoma undergoing anthracycline-based chemotherapy. ClinicalTrials.gov Identifier: NCT02943590.

Background: Patients with End-Stage Renal Disease (ESRD) experience an exceptionally high burden of cardiovascular morbidity and mortality that is not fully explained by traditional risk factors. The gut-kidney-heart axis has emerged as a critical pathophysiological paradigm, implicating gut dysbiosis and the resultant accumulation of gut-derived uremic toxins as key non-traditional risk factors for cardiovascular disease (CVD) in this population. Methods: A systematic literature search was conducted in PubMed, Google Scholar, Semantic Scholar, Springer, Wiley Online Library to identify observational studies investigating the association between markers of gut dysbiosis (microbial composition, diversity, and gut-derived metabolites including indoxyl sulfate, p-cresyl sulfate, trimethylamine N-oxide, indole-3-acetic acid [IAA], and phenylacetylglutamine [PAGln]) and cardiovascular complications in adult patients with ESRD. Study selection followed PRISMA guidelines. Data on study design, population characteristics, dysbiosis markers, and cardiovascular outcomes were extracted. The methodological quality of included studies was assessed using the Newcastle-Ottawa Scale. Results: Seventeen primary observational studies, comprising over 4,100 patients, were included. The evidence consistently demonstrated significant associations between gut dysbiosis and adverse cardiovascular outcomes. Lower gut microbial diversity was a strong predictor of all-cause and cardiovascular mortality. Elevated serum levels of IS, PCS, TMAO, IAA, and PAGln were independently associated with increased risks of all-cause mortality, cardiovascular mortality, major adverse cardiovascular events (MACE), heart failure, arterial stiffness, and vascular calcification. Furthermore, circulating endotoxin, a marker of intestinal barrier dysfunction, was linked to systemic inflammation, atherosclerosis, and myocardial injury. Discussion: The synthesized evidence supports a mechanistic cascade wherein the uremic milieu of ESRD drives profound gut dysbiosis. This leads to the overproduction of uremic toxins and compromises intestinal barrier integrity, facilitating the systemic translocation of these toxins and other pro-inflammatory bacterial products. These circulating factors subsequently promote cardiovascular pathology through the induction of systemic inflammation, oxidative stress, endothelial dysfunction, and direct cellular toxicity in vascular and myocardial tissues. Conclusion: Gut dysbiosis is significantly and consistently associated with a wide spectrum of adverse cardiovascular outcomes in patients with ESRD. These findings underscore the gut as a central organ in the pathophysiology of uremic cardiovascular disease and highlight the gut-kidney-heart axis as a crucial therapeutic target for mitigating the excessive cardiovascular risk in this vulnerable population.

Cardiovascular-kidney-metabolic (CKM) syndrome is a systemic condition driven by inflammation. The red blood cell distribution width-to-albumin ratio (RAR) has emerged as a novel marker of systemic inflammation, but its prognostic value in CKM remains unclear. We analyzed 9135 participants from National Health and Nutrition Examination Survey 2007 to 2016 with mortality data obtained from the National Death Index. Weighted Cox proportional hazards models assessed the association between RAR and mortality. Generalized additive models, time-dependent receiver operating characteristic curves, and Fine-Gray competing risk models were used for further evaluation. Over a median follow-up of 91.95 months, 987 deaths occurred, including 241 cardiovascular deaths. Based on an optimal cutoff (RAR = 3.33), participants were stratified into higher and lower RAR groups. The weighted Cox proportional hazards model revealed that individuals with higher RAR had significantly increased risks of all-cause mortality (hazard ratio 2.30, 95% confidence interval [CI] 1.95-2.70) and cardiovascular mortality (hazard ratio 3.26, 95% CI 2.40-4.42). Generalized additive models demonstrated a positive association between RAR and mortality. The main findings remained consistent in the sensitivity analyses. The area under the curve values for predicting all-cause mortality at 1, 3, 5, and 10 years were 0.756, 0.717, 0.708, and 0.695, respectively; the corresponding area under the curves for cardiovascular mortality were 0.708, 0.729, 0.737, and 0.714, respectively. Furthermore, even after accounting for noncardiovascular deaths as competing risk factors, The Fine-Gray model revealed that RAR was an independent predictor of cardiovascular mortality (subdistribution hazard ratio 1.68, 95% CI 1.38-2.04). Elevated RAR independently increases the risk of all-cause and cardiovascular mortality in patients with CKM stages 1 to 4.

The global rise in type 2 diabetes mellitus (T2DM) underscores the importance of early prevention in primary care. This study examined how changes in glucose tolerance and the presence of neuropsychiatric disorders relate to cardiovascular outcomes (CVO) and mortality. In a 10-year longitudinal study, 1,069 general practice patients (mean age 62.9 years; 51% male) underwent standard 2-hour glucose tolerance tests (GTT). Data on lifestyle, cardiovascular risk factors, comorbidities, and neuropsychiatric diagnoses (MINI Interview) were collected. The difference between baseline and follow-up GTT values (GTTdiff) was analyzed in relation to cardiovascular events and mortality. Patients who died had significantly higher GTTdiff (mean 1.37 mmol/L) compared to those with CVO (0.95 mmol/L) or without events (0.81 mmol/L; p = .002). Kaplan-Meier analysis showed shorter survival in patients with Major Depressive Episode (MDE) and GTTdiff > 3 mmol/L (7.43 years) versus those without MDE (8.76 years). Greater glucose variability and comorbid depression are associated with increased cardiovascular mortality. Interventions targeting both glucose control and mental health may improve outcomes in non-diabetic primary care populations.

Estimated glomerular filtration rates (eGFRs) can differ according to whether creatinine or cystatin C is used for the eGFR calculation, but the prevalence and importance of these differences remain unclear. To evaluate the prevalence of a discordance between cystatin C-based eGFR (eGFRcys) and creatinine-based eGFR (eGFRcr), identify characteristics associated with greater discordance, and evaluate associations of discordance with adverse outcomes. Participants in the Chronic Kidney Disease Prognosis Consortium (CKD-PC). Participants with concurrent cystatin C and creatinine measurements and clinical outcome measurement. Between April 2024 and August 2025, data were synthesized using individual-level meta-analysis. The primary independent measurement was a large negative eGFR difference (eGFRdiff), defined as an eGFRcys that was at least 30% lower than eGFRcr. Secondary (dependent) outcomes included all-cause and cardiovascular mortality, atherosclerotic cardiovascular disease, heart failure, and kidney failure with replacement therapy. A total of 821 327 individuals from 23 outpatient cohorts (mean [SD] age, 59 [12] years; 48% female; 13.5% with diabetes; 40% with hypertension) and 39 639 individuals from 2 inpatient cohorts (mean [SD] age, 67 [16] years; 31% female; 30% with diabetes; 72% with hypertension) were included. Among outpatient participants, 11% had a large negative eGFRdiff (range, 3%-50%). Among inpatients, 35% had a large negative eGFRdiff. Among outpatient participants, at a mean (SD) follow-up of 11 (4) years, a large negative eGFRdiff, compared with an eGFRdiff between -30% and 30%, was associated with higher rates of all-cause mortality (28.4 vs 16.8 per 1000 person-years [PY]; hazard ratio [HR], 1.69 [95% CI, 1.57-1.82]), cardiovascular mortality (6.1 vs 3.8 per 1000 PY; HR, 1.61 [95% CI, 1.48-1.76]), atherosclerotic cardiovascular disease (13.3 vs 9.8 per 1000 PY; HR, 1.35 [95% CI, 1.27-1.44]), heart failure (13.2 vs 8.6 per 1000 PY; HR, 1.54 [95% CI, 1.40-1.68]), and kidney failure with replacement therapy (2.7 vs 2.1 per 1000 PY; HR, 1.29 [95% CI, 1.13-1.47]). In the CKD-PC, 11% of outpatient participants and 35% of hospitalized patients had an eGFRcys that was at least 30% lower than their eGFRcr. In the outpatient setting, presence of eGFRcys at least 30% lower than eGFRcr was associated with significantly higher rates of all-cause mortality, cardiovascular events, and kidney failure.

Age-Specific Associations Between Adiposity and Mortality in U.S. Adults, 1999-2018.

Modernising Acute PE and VTE Management: Meta-Analysis of Newer Anticoagulants Versus Traditional Therapy on Recurrence and Mortality.

Objective Glycated hemoglobin (HbA1c) variability is a crucial indicator for evaluating the stability of long-term glycemic control in patients with diabetes mellitus. This study aimed to clarify the association between HbA1c variability and the risk of incident cardiovascular disease (CVD) and mortality in patients with type 2 diabetes mellitus (T2DM) through a systematic review, thereby providing evidence-based support for the early prevention of adverse cardiovascular events in T2DM patients. Methods We systematically searched the PubMed, Web of Science, The Cochrane Library, and Embase databases for studies on the association between HbA1c variability and cardiovascular outcomes in patients with T2DM, published from the establishment of each database up to August 5, 2025. Cardiovascular outcomes included the incidence of CVD and CVD-related mortality. Two researchers independently conducted literature screening, data extraction, and risk of bias assessment. Meta-analysis was performed using Review Manager 5.3 software, with hazard ratio (HR) or odds ratio (OR) as the effect size. Results A total of 31 cohort studies were included, covering 545,956 participants from 13 countries and regions. The results of the meta-analysis showed that a higher coefficient of variation (CV) of HbA1c was significantly associated with an increased risk of cardiovascular events (HR = 1.32, 95% CI: 1.18–1.49, P &amp;lt; 0.00001; OR = 1.39, 95% CI: 1.22–1.57, P &amp;lt; 0.00001), and also significantly elevated the risk of mortality (HR = 1.35, 95% CI: 1.16–1.57, P &amp;lt; 0.00001). The standard deviation (SD) of HbA1c was also significantly correlated with a higher risk of cardiovascular events (HR = 1.27, 95% CI: 1.17–1.38, P &amp;lt; 0.00001; OR = 1.30, 95% CI: 1.07–1.57, P = 0.008) and a significant increase in mortality risk (HR = 1.27, 95% CI: 1.17–1.37, P&amp;lt;0.00001). The hemoglobin glycation index (HGI) was significantly associated with the risk of cardiovascular events in terms of HR (HR = 1.36, 95% CI: 1.14–1.62, P = 0.0006), but no statistical significance was observed in terms of OR (OR = 1.47, 95% CI: 0.98–2.20, P = 0.06). In contrast, the HbA1c variability score (HVS) showed no significant association with either the risk of cardiovascular events (HR = 1.31, 95% CI: 0.97–1.78, P = 0.08) or mortality risk (HR = 1.00, 95% CI: 0.76–1.31, P = 1.00). Conclusions HbA1c variability is positively associated with the risk of adverse cardiovascular events in patients with T2DM. Among the indicators of HbA1c variability, the coefficient of variation (CV), standard deviation (SD), and hemoglobin glycation index (HGI) can serve as significant predictors for the risk of cardiovascular disease (CVD) occurrence and mortality. However, the HbA1c variability score (HVS) did not show significant predictive value in this study. Systematic Review Registration https://www.crd.york.ac.uk/prospero/ , identifier CRD420251132972.

Most prior studies assessed heatwave-related mortality using daily mean temperature as an indicator, limiting the ability to differentiate between daytime and nighttime heat effects. We collected individual mortality records with corresponding residential exposure data on daily temperature, relative humidity and ozone during warm seasons from 2016 to 2022 in Jiulongpo district, Chongqing, China. Heatwaves were categorized into three types: those defined by daily maximum temperature, daily minimum temperature, and a combination of both. A time-stratified case-crossover design was applied to assess the associations between heatwaves and mortality. During the study period, 17552 deaths were recorded. We observed that heatwaves defined by combined temperature thresholds were associated with the highest mortality risks, with odds ratios (ORs) ranging from 1.08 (95% CI: 1.01-1.15) to 1.32 (95% CI: 1.17-1.48) under different heatwave definitions. For heatwaves defined by daily maximum temperature, ORs ranged from 1.06 (95% CI: 0.98-1.14) to 1.13 (95% CI: 1.03-1.24), while heatwaves defined by daily minimum temperature showed ORs ranging from 1.04 (95% CI: 0.99-1.10) to 1.27 (95% CI: 1.13-1.43). Exposure to heatwaves was consistently associated with increased risks of all-cause and cardiovascular mortality, but not respiratory mortality. The associations were stronger among men and under higher ozone conditions compared to their counterparts. Exposure to heatwaves significantly increased mortality risks, with the highest risks observed for compound heatwaves involving both daytime and nighttime heat. These findings underscore that the health risks associated with nighttime heat exposure should not be overlooked.

Muscle loss is linked to multiple adverse outcomes, but its impact on rheumatoid arthritis (RA) prognosis is unclear. This study aimed to examine the association between muscle mass and mortality in RA patients. RA patients from the NHANES database were followed for survival until December 31, 2021. Muscle mass was measured using dual X-ray absorptiometry, low muscle mass was defined as appendicular skeletal muscle mass index (ASMI) < 7.0kg/m² in men or < 5.5kg/m² in women. The relationship between ASMI and mortality was analyzed using weighted Cox regression. The study included 892 participants (weighted mean [SE] age 52.22 [0.59] years, 57.36% female). During a median (SE) follow-up of 11.44 (0.33) years, 291 deaths (32.62%) were recorded, of which 197 (28.23%) were attributed to cardiovascular disease. In fully adjusted models, a 1kg/m²increase in ASMI was associated with decreased all-cause and cardiovascular mortality risk by 34% (HR = 0.66, 95% CI 0.50-0.86) and 40% (HR = 0.60, 95% CI 0.38-0.93), respectively. When ASMI stratified, RA with low muscle mass had a 1.42-fold higher risk of all-cause mortality (HR = 1.42, 95% CI 1.01-2.00) and a 2.58-fold higher risk of cardiovascular mortality (HR = 2.58, 95% CI 1.18-5.62) than those with normal muscle mass. Restricted cubic spline analysis showed a nonlinear association between ASMI and cardiovascular (Pnonlinear = 0.04) but not for all-cause mortality (Pnonlinear = 0.25). Muscle loss in RA patients is linked to higher mortality risk, underscoring the need to recognize its harmful effects.

The reliability of a decision model to guide decision making depends on its ability to accurately predict patient outcomes. We present results of an external validation of the MicroSimulation Core Obesity Model (MS-COM) that was developed to compare the cost effectiveness of obesity management interventions in adults. We updated a 2018 systematic literature review of economic models in overweight and obesity and conducted additional targeted searches to identify suitable sources and outcomes to validate against MS-COM in people with overweight or obesity with or without type 2 diabetes. We extracted baseline characteristics and cardiovascular and mortality outcomes, where these were closely matched with MS-COM, and incidence of type 2 diabetes. We performed external-dependent (sources used in MS-COM) and external-independent (sources not used in MS-COM) validation. The extent of concordance between predicted and observed outcomes was assessed using the coefficient of determination (R2), ordinary least-squares linear regression line (OLS LRL), mean absolute percentage error, root mean square percentage error and mean squared log of accuracy ratio. Ninety-nine potential independent validation sources were identified from 6381 screened records, of which nine studies reported cardiovascular and mortality outcomes that were closely matched with MS-COM, along with two studies that reported type 2 diabetes incidence (number of endpoints=106). The dependent validation of cardiovascular and mortality outcomes (N=18), based on the QRisk3 risk equation (normoglycaemia/prediabetes population) and UKPDS 82 (type 2 diabetes population), showed a good linear correlation with observed outcomes (R2=0.99 and 0.98, respectively). There was some slight overprediction of QRisk3 (OLS LRL slope=1.11) and underprediction of UKPDS 82 (OLS LRL slope=0.97). The independent validation of cardiovascular and mortality outcomes also showed a good linear correlation with observed outcomes, particularly in adults with normoglycaemia/prediabetes (R2=0.90; OLS LRL slope=0.86); however, an independent validation of type 2 diabetes incidence showed a poorer fit with some degree of underprediction (R2=0.74; OLS LRL slope=0.66). Mean error estimates were lower in the dependent validation, showing good concordance between predicted and observed values. External validation of MS-COM showed good concordance with dependent and independent sources, suggesting the model accurately predicts obesity-related complications in an overweight/obese population with normoglycaemia/prediabetes and type 2 diabetes.

Vitamin D deficiency is associated with increased cardiovascular morbidity and mortality through pathways that foster atherosclerosis. This review aims to clarify the relationship between serum vitamin D and peripheral artery disease (PAD), while evaluating the prognostic implications and diagnostic utility of vitamin D deficiency in PAD patients. Patients with PAD, displayed significantly lower serum vitamin D levels compared to non-PAD individuals, mean difference (MD), - 2.12ng/mL (95%CI:-4.13 to - 0.12). Individuals with vitamin D deficiency (< 20 ng/mL) exhibited a higher prevalence of PAD relative to those with insufficient or sufficient levels, odds ratio (OR), 1.52 (95%CI:1.07-2.18). Unadjusted prognostic factor analysis displayed an increased hazard for PAD occurrence among deficient patients, hazard ratio (HR), 1.04 (95%CI:1.02-1.06), an outcome that failed to retain its statistical significance upon parameter adjustment, adjusted HR, 1.01 (95%CI:0.99-1.03). Diagnostic accuracy analysis displayed the poor performance of the 20ng/mL threshold with pooled sensitivity and specificity of 0.76 (95%CI:0.55-0.90) and 0.34 (95%CI:0.17-0.57). Further analysis identified a negative predictive value (NPV) of 94% for the 19.65ng/mL threshold, indicating a 6% prevalence of PAD above this cutoff. While this review displayed both decreased vitamin D concentrations for PAD patients and an increased prevalence of PAD among patients with vitamin D deficiency, the prognostic effect of vitamin D on the development of PAD remains inconclusive. Despite the poor performance of vitamin D deficiency as a diagnostic marker, the NPV displayed by the analysis further supports the possible association between vitamin D deficiency and PAD.

Abstract Purpose of Review To review the complex bidirectional relationship between epilepsy and cardiovascular disease (CVD), focusing on shared risk factors, cardiovascular morbidity and mortality in people with epilepsy (PWE), the cardiac effects and interactions of antiseizure medications (ASMs), and management considerations in patients with coexisting cardiac conditions. Recent findings Recent large-scale studies demonstrate that PWE have approximately double the cardiovascular mortality of the general population, largely driven by modifiable factors such as hypertension, diabetes, and associated lifestyle factors. Enzyme-inducing ASMs (carbamazepine, phenytoin, phenobarbital) increase dyslipidemia and reduce statin efficacy, while sodium channel blockers can affect cardiac conduction and, in susceptible patients, increase arrhythmia risk. Valproate shows a mixed cardiovascular profile, and low dose fenfluramine appears safe with close echocardiographic surveillance. Accurate differentiation of seizure versus syncope and coordinated perioperative care to allow safe surgical and neurostimulation interventions even in patients with cardiac implantable electronic devices. Summary Epilepsy and CVD frequently coexist and share modifiable risk factors that should be targeted to reduce morbidity and mortality. Non–enzyme-inducing ASMs and cautious use of sodium-channel blockers are preferred in patients with cardiac disease. Multidisciplinary care, cardiac monitoring when indicated, and integrated neuro-cardiology collaboration are essential for optimizing outcomes in this growing patient population.

Non-ST-segment elevation acute coronary syndrome (NSTE-ACS) is a major contributor to cardiovascular mortality, yet reliable tools for individualized mortality prediction remain limited. Machine learning offers the potential to enhance prognostic accuracy in this high-risk population. A total of 1,495 patients with NSTE-ACS who underwent percutaneous coronary intervention (PCI) were retrospectively analyzed. Eight clinical and laboratory variables were selected through univariate and multivariate logistic regression. Five machine learning models-logistic regression, random forest, XGBoost, LightGBM, and naïve Bayes-were constructed. Model performance was evaluated using area under the curve (AUC) and calibration curves. Age, diabetes mellitus, and ejection fraction were identified as independent predictors of all-cause mortality. Among all models, LightGBM achieved the highest AUC (0.847), followed by XGBoost (0.822), both of which demonstrated superior discrimination and calibration compared to traditional logistic regression and other algorithms. Calibration analysis showed excellent agreement between predicted and observed mortality in both training and test cohorts. Gradient boosting models, particularly LightGBM and XGBoost, significantly improve mortality prediction in NSTE-ACS patients after PCI. These models may facilitate more accurate risk stratification and guide personalized post-procedural management strategies in clinical practice.

Aortic dissection and aneurysm are deadly complications of hypertension and remain important causes of cardiovascular mortality. Due to the rise in prevalence of hypertension in the United States, it is critically important that we analyze mortality trends for vascular emergencies. Using national data from the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiological Research, we analyzed mortality from the age of 25 up through 85 years and older from the period between 1999 and 2020. Crude mortality rates, age-adjusted mortality rates, and yearly percent change and the corresponding 95% confidence intervals were estimated. From 113,728 reported deaths due to aortic dissection and aneurysm and hypertension during the study interval, mortality trends indicated a mortality rate initially decreasing from 2.42 in 2001 to 2.27 in 2015, and subsequently increasing to 2.67 in 2015-2020, representing a total rise from 1.64 in 1999 to a level of 2.67 in 2020. Mortality was higher among males than females throughout the period, at levels of 3.87 and 1.77 per 100,000 in 2020. Disparities by race and ethnicity also emerged, as non-Hispanic Black race showed the maximum mortality, followed by non-Hispanic Asian and non-Hispanic White, and much lower among Hispanics and in non-Hispanic American Indian. Geographic variations also became apparent, as evidenced by the West reporting the maximum mortality burden. These findings indicate that after reductions observed in the past, mortality from aortic dissection and aneurysm related to hypertension has increased in recent years, emphasizing the importance of targeted prevention interventions.

This scoping review aimed to map the scientific literature on mortality related to climate change and environmental manifestations in the Mediterranean region, explore the different methodological approaches used, identify research gaps, and suggest future research directions. This scoping review was conducted following the Joanna Briggs Institute (JBI) recommendations and the Preferred Reporting Items for Scoping Reviews (PRISMA-ScR). We included articles that examined the association between floods, wildfires, Saharan dust outbreaks, particulate matter (PM), urban heat islands (UHI), compound effects, and mortality. Most studies have been conducted in Euro-Mediterranean countries, with limited studies in the remaining Mediterranean countries. Regression analysis and descriptive designs predominated, while spatial and mixed-methods designs were less frequently used. Flood mortality rates were higher in northeastern Spain, southern France, and northern Italy. The primary cause of flood mortality was drowning, with a seasonal west-east gradient. Furthermore, lagged exposure to PM10 and PM2.5 from wildfires was associated with cardiovascular and respiratory mortality in most countries. Additionally, Saharan dust exposure was associated with total and respiratory mortality, especially during dust intrusion days. Likewise, Ozone exposure was principally associated with total and cardiovascular mortality. Furthermore, PM10 and ozone increased heat mortality when compounding in most of the studied Euro-Mediterranean cities. Our results showed substantial variability in mortality rates and causes associated with different climate change and environmental manifestations across the Mediterranean region. These findings highlight the urgent need for standardized and high-resolution mortality data to assess the health impacts of these hazards in understudied countries where health reporting is scarce.

Introduction: Myocardial infarction remains a major global cause of death and disability, and cardiac rehabilitation is a cornerstone of secondary prevention aimed at improving survival and health-related quality of life. Objective: To evaluate the effectiveness of multidisciplinary cardiac rehabilitation in improving survival and health-related quality of life after myocardial infarction, and to compare outcomes across delivery models, programme components, and key patient subgroups. Methods: We conducted a systematic review following PRISMA 2020 across PubMed, Scopus, Web of Science, Cochrane Library, LILACS, ClinicalTrials.gov, and ICTRP (January 2016–December 2025). Eligible studies enrolled adults with confirmed myocardial infarction, compared structured cardiac rehabilitation with usual care or no rehabilitation, and reported survival and/or validated quality-of-life outcomes. Two reviewers independently performed screening, data extraction, and risk-of-bias assessment; certainty was appraised using GRADE. Results and Discussion: Twenty-two studies were included, encompassing randomized trials, cohort analyses, and meta-analyses focused on post–myocardial infarction populations. Participation and especially completion of rehabilitation were consistently associated with lower all-cause and cardiovascular mortality, fewer rehospitalisations, and clinically relevant improvements in exercise capacity and health-related quality of life. Home-based, hybrid, and tele-rehabilitation models were generally non-inferior to centre-based programmes, supporting flexible delivery without loss of efficacy. Benefits were observed across age groups, with emerging data supporting circadian-sensitive scheduling and comprehensive psychosocial integration. Heterogeneity in programme intensity, duration, and components explains variability in effect sizes; overall certainty of evidence was moderate to high for mortality and moderate for quality-of-life outcomes. Conclusion: Cardiac rehabilitation after myocardial infarction confers clinically meaningful gains in survival and health-related quality of life. Routine referral at discharge, strategies to optimise adherence and completion, and scalable hybrid or home-based models should be prioritised to expand equitable access and durability of benefits.

Cardiovascular disease is the leading cause of death among women worldwide. Metabolic syndrome is more prevalent after menopause. The decline in estrogen during this transition promotes adverse metabolic and vascular changes, substantially elevating cardiovascular risk. However, evidence on the impact of metabolic syndrome on cardiovascular risk in postmenopausal women remains limited. This study utilized data from the Kailuan cohort, which initially enrolled 32959 women. After matching participants by age in a 1:2 ratio, a total of 5210 postmenopausal women were included, with a median follow-up of 15.53 years. Multivariable Cox proportional hazards models were employed to evaluate the associations between metabolic syndrome and incident cardiovascular disease, including cerebrovascular disease and myocardial infarction, while adjusting for confounding variables. Stratified and sensitivity analyses were conducted to validate the robustness of the findings. During follow-up there were 398 incident CVD events (MetS-: 197; MetS+: 201). After full adjustment, MetS was associated with a two-fold higher CVD risk (HR 2.01, 95% CI 1.64-2.46). Comparable associations were observed for the subtypes: cerebrovascular disease (HR, 1.83; 95% CI, 1.47-2.27) and myocardial infarction (HR, 3.28; 95% CI, 1.97-5.46). The association was strongest in women with early menopause (⟨45 years) (HR 3.86, 95% CI 1.29-11.53). Among MetS components, elevated fasting blood glucose appeared the largest contributor: excluding the glucose component reduced the overall MetS-CVD HR from 2.01 to 1.82 (95% CI 1.48-2.24). Results were robust in sensitivity analyses. Postmenopausal women with metabolic syndrome have significantly higher risks of cardiovascular disease. In subgroup analyses, these findings were more pronounced among those with early menopause or elevated fasting blood glucose. In Conclusion, the findings underscore the importance of early detection of metabolic syndrome and targeted prevention strategies to reduce cardiovascular morbidity and mortality in this high risk population.

Background: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia worldwide and a major cause of cardiovascular morbidity and mortality. Despite major therapeutic advances, the molecular determinants of AF initiation and persistence remain incompletely defined.  Methods: Current genomic and functional evidence were synthesised from large-scale genome-wide association studies (GWAS), transcriptomic, proteomic, and epigenomic investigations. Key molecular pathways implicated in calcium handling, fibrosis, and transcriptional regulation were reviewed with reference to translational models.  Results: Over one hundred AF-associated loci have been identified, most located within non-coding regulatory regions. The 4q25 locus near PITX2 shows the strongest and most reproducible association. Variants at this site influence calcium- handling proteins (SERCA2, RyR2) and modulate atrial electrophysiology. Integrative multi-omic analyses reveal disturbed Wnt, Notch, and BMP signalling, enhanced atrial fibrosis, and altered metabolic gene expression. Polygenic risk scores improve AF prediction beyond traditional risk factors.  Conclusions: AF results from the interaction of genetic predisposition and environmental stressors that converge on shared molecular pathways controlling calcium flux, structural remodelling, and inflammation. Translational integration of genomic and physiological data offers a pathway towards precision-based prevention and therapy.

Introduction: Hypertension remains one of the leading modifiable risk factors for cardiovascular morbidity and mortality worldwide. Emerging data indicate that the gut microbiota influences vascular tone, renal sodium handling, and systemic inflammation through metabolites and immune pathways. Clarifying this relationship could open novel avenues for prevention and treatment of hypertension. Objective: The primary objective was to synthesize mechanistic and clinical evidence linking gut microbiota composition and function to blood pressure regulation. Secondary objectives included identification of key microbial taxa and metabolites, evaluation of probiotic and dietary interventions on blood pressure, comparison of human and animal data, and assessment of evidence certainty using standardized approaches. Methods: We searched PubMed, Scopus, Web of Science, Cochrane Library, LILACS, ClinicalTrials.gov, and ICTRP for studies published in the last five years, extending to ten years if fewer than ten eligible human studies were found. Inclusion criteria prioritized human studies assessing gut microbiota or microbiota-modifying interventions with blood pressure outcomes, while mechanistic animal and in vitro studies were considered for biological plausibility. Data were extracted according to PRISMA principles, and the certainty of evidence was appraised with the GRADE framework. Results and Discussion: Of 1,243 records identified, 21 studies met the inclusion criteria, comprising 12 human studies and 9 mechanistic animal or in vitro investigations. Cross-sectional human data frequently associated reduced microbial diversity and altered taxa with higher blood pressure, while mechanistic studies implicated short-chain fatty acids, salt-sensitive immune modulation, and barrier dysfunction. Probiotic and prebiotic trials demonstrated modest blood pressure reductions, though heterogeneity in strains, dosing, and duration limited firm clinical conclusions. Conclusion: Current evidence supports a biologically plausible gut microbiota–blood pressure axis with preliminary signals for benefit from microbiota-modifying strategies. Standardization of microbiome methods, adequately powered randomized trials with blood pressure as a primary endpoint, and integration of metabolomics and diet assessments are needed to define clinical utility.