Pioglitazone attenuates cardiovascular remodeling cadmium-induced through the MAPK pathway.

Integrating UPLC-Q-TOF-MS/MS, feature-based molecular networking, network pharmacology, and molecular docking to investigate the mechanism of Persicae Ramulus against myocardial ischemia.

Adipsin alleviates cold exposure-induced coronary microvascular dysfunction through a Gα13-dependent mechanism.

Alterations in cardiovascular biomarkers and gut microbiome associated with night shift work: Insights from the Chinese platform workers study.

Cardiovascular disease-associated admissions in patients with Cystic Fibrosis: A 7-Year U.S. National Inpatient Sample Analysis.

Excess aldosterone is a key driver of cardiovascular, renal, and metabolic injury, promoting hypertension, myocardial fibrosis, proteinuria, and progressive chronic kidney disease (CKD). Conventional therapies, renin-angiotensin-aldosterone system (RAAS) inhibitors, and mineralocorticoid receptor antagonists attenuate downstream receptor signaling but do not suppress aldosterone biosynthesis, allowing residual hormonal activity that perpetuates tissue damage. The long-term efficacy, endocrine selectivity, and clinical significance of directly inhibiting aldosterone synthesis, however, remain only partly defined, particularly with respect to sustained aldosterone suppression, preservation of cortisol production, and applicability across diverse cardiorenal disorders. This review provides a comprehensive and mechanistically focused synthesis of preclinical and clinical evidence on aldosterone synthase inhibitors (ASIs), examining their pharmacologic specificity, hormonal effects, and emerging therapeutic potential in primary aldosteronism (PA), resistant hypertension, and CKD. Next-generation ASIs-including baxdrostat, lorundrostat, dexfadrostat phosphate, and vicadrostat-demonstrate >100-fold selectivity for CYP11B2 over CYP11B1, enabling potent and reversible aldosterone suppression while maintaining cortisol biosynthesis. Across early-phase trials, these agents consistently reduce aldosterone concentrations, lower systolic and diastolic blood pressure, decrease albuminuria, and normalize potassium balance in PA, with favorable safety and minimal hypothalamic-pituitary-adrenal axis disturbance. Collectively, these findings position ASIs as a selective and mechanistically coherent therapeutic strategy that addresses residual aldosterone activity beyond conventional RAAS blockade. Although current evidence relies largely on surrogate endpoints, ongoing phase III outcome trials will determine whether ASIs can translate mechanistic promise into durable cardiovascular and renal protection, potentially redefining the therapeutic landscape of aldosterone-mediated diseases.

The study by Inam et al. published in this issue of the Pakistan Heart Journal gives valuable evidence linking cannabis use with heart failure, especially heart failure with reduced ejection fraction (HFrEF). Conducted at Hayatabad Medical Complex, Peshawar the cross sectional study of 380 patients found that HFrEF was more common in cannabis users (60%) than in non-users (50%) (p = 0.03) [1]. These findings are consistent with recent international studies showing that cannabis users have higher rates of arrhythmia, myocardial dysfunction, and hospital admission. Importantly, users in this Pakistani cohort were generally younger, suggesting that cannabis may contribute to early cardiovascular injury [2-9]. Cannabis can affect the heart through several mechanisms by sympathetic activation, oxidative stress, endothelial injury, and vascular inflammation. It can also worsen metabolic stress in patients with hypertension or diabetes. When combined these factors may accelerate left ventricular dysfunction and heart failure progression [2-9]. Clinicians should routinely ask patients with heart failure about cannabis use especially younger individuals with unexplained systolic dysfunction. Counselling to stop cannabis use should be integrated into cardiac rehabilitation and outpatient care programs [2-9]. From a public health perspective cannabis should be recognised as a modifiable cardiovascular risk factor, similar to smoking or alcohol. Public awareness efforts and heart failure registries can incorporate cannabis screening to guide education, prevention and early intervention [2-9]. Although this was a single centre study, it provides an important foundation for larger national and regional research to explore dose response relationships and the reversibility of cardiac injury after cessation. In summary Inam et al. remind clinicians and policymakers that cannabis is not harmless. It can harm the heart and should be regarded as a preventable cause of heart failure, particularly among younger people. AUTHORS' CONTRIBUTION AKN, BM, and MTM: Concept and design, data acquisition, interpretation, drafting, final approval, and agree to be accountable for all aspects of the work. Acknowledgment: None. Funding: No specific grant for this research from any public, commercial, or not-for-profit funding agency References Inam S, Saeed I, Khan QA, Aamir M, Din HNU, Khan O. Prevalence and Incidence of Heart Failure among Cannabis Users: A Cross-Sectional Study. Pak Heart J. 2025;58(04):414-420. DOI: 10.47144/phj.v58i4.2970 Chandy M, Jimenez-Tellez N, Wu JC. The relationship between cannabis and cardiovascular disease: clearing the haze. Nat Rev Cardiol. 2025; 22: 467-481. DOI: 10.1038/s41569-025-01121-6 Storck W, Elbaz M, Vindis C, Déguilhem A, Lapeyre-Mestre M, Jouanjus E. Cardiovascular risk associated with the use of cannabis and cannabinoids: a systematic review and meta-analysis. Heart. 2025;111(22):1047-1056. DOI: 10.1136/heartjnl-2024-325429 Kamel I, Mahmoud AK, Twayana AR, Younes AM, Horn B, Dietzius H. Myocardial infarction and cardiovascular risks associated with cannabis use. JACC Advances. 2025; DOI: 10.1016/j.jacadv.2025.101698. American College of Cardiology. Cannabis Users Face Substantially Higher Risk of Heart Attack. Press Release. March 17, 2025. Available at: https://www.acc.org British Medical Journal Group. Cannabis Use Linked to Doubling in Risk of Cardiovascular-Disease Death. BMJ News. June 2025. Dhillon BK, Sombans S, Verma R, et al. Cannabis use among young females admitted for heart failure in the United States. Circulation. 2023; 147(Suppl 1): AP580. Patel RS, Gonzalez MD, Ajibawo T, Baweja R. Cannabis use disorder and increased risk of arrhythmia-related hospitalization in young adults. Am J Addict. 2021; 30(6): 578-584. DOI: 10.1111/ajad.13215 Richards JR, Blohm E, Toles KA, Jarman AF, Ely DF, Elder JW. The association of cannabis use and cardiac dysrhythmias: a systematic review. Clin Toxicol (Phila). 2020 Sep;58(9):861-869. DOI: 10.1080/15563650.2020.1743847

Salt-sensitive hypertension (SSH) is a physiologically distinct blood pressure phenotype in which blood pressure rises disproportionately in response to sodium intake. Traditionally studied in older hypertensive individuals, SSH is now recognized in apparently healthy young adults, where it silently drives early cardiovascular injury. The burden is disproportionately high among South Asians due to genetic predisposition, high-sodium dietary patterns, and environmental risk enhancers. The stealth of SSH lies in its asymptomatic course. Vascular stiffening, endothelial dysfunction, microvascular damage, and left ventricular remodelling can develop years before overt hypertension. Yet, detection is hindered by the absence of practical, cost-effective, and standardized diagnostic tools. Gold-standard salt-loading and depletion tests are too resource-intensive for routine care, while surrogate measures such as urinary sodium excretion or dietary recall are imprecise and inconsistently applied. The burden is disproportionately high among South Asians due to genetic predisposition, high-sodium dietary patterns, and environmental risk enhancers. Compounding the problem, SSH is almost entirely absent from global and regional hypertension guidelines, meaning young adults at risk are neither screened nor counselled. As a result, a silent epidemic of subclinical cardiovascular damage is progressing unchecked. This thematic review synthesizes epidemiological, mechanistic, and clinical literature to highlight the diagnostic dilemma and the lack of formal guidance on SSH in young adults. Drawing from cardiology, nephrology, genetics, and public health research, it examines how SSH escapes detection, why the risks are higher in South Asian populations, and what emerging innovations could bridge current gaps. The objective is not to present prescriptive solutions but to illuminate the urgent need for recognition, diagnostic innovation, and policy integration to prevent irreversible cardiovascular damage in the formative decades of life.

Abstract This paper studies the impact of wildfire smoke on workplace injuries among agricultural workers, using workers' compensation claims between 2007 and 2020. We find a substantial increase in agricultural‐worker injuries attributable to smoke‐induced PM 2.5 and wildfire smoke. Specifically, a 10 μg/m 3 increase in daily PM 2.5 exposure from wildfire smoke increases traumatic injuries by 2.9% and respiratory and cardiovascular injuries by 18.97%. We examine nonlinearities in the dose–response relationship and find that the health impacts of PM 2.5 vary across concentration levels. The effects of smoke on traumatic injuries are largest among the oldest workers (aged 60 and above) and the youngest workers (under 30), relative to those in middle age. We find that injuries occur even at levels of PM 2.5 deemed safe under current regulations. Our back‐of‐the‐envelope calculation suggests that in 2020 alone, wildfire smoke was responsible for approximately 244 additional agricultural worker injuries in California compared to a hypothetical scenario without smoke.

The international popularity of cannabis and the shifting legal landscape have propelled conversationsaround its medical and recreational use to the forefront of public discussion. Clinicians face increased questions from patients, though there is a lack of clear medical consensus on several conditions for which cannabis is commonly used. As of 2025, key indications for cannabis and cannabinoid use are nausea and vomiting induced by chemotherapy, loss of appetite due to HIV/AIDS, Dravet syndrome, Lennox-Gastaut syndrome, seizures associated with tuberous sclerosis, and multiple sclerosis spasticity. We reviewed current evidence for cannabis and cannabinoid treatment of chronic noncancer pain, insomnia, and psychiatric and neurologic disorders. We also considered current inconclusive evidence for cannabis to treat opioid use disorder and neurological disorders. Risks associated with cannabis and cannabinoid use include addiction, decreased neurocognitive function (particularly in adolescents) cannabinoid hyperemesis syndrome, psychosis, perinatal complications, cardiovascular and pulmonary disorders, as well as physical injury risks, such as falls and motor vehicle accidents. As public and clinical interest in cannabis grows, clinicians must evaluate potential harms alongside benefits relevant to the medical condition for which cannabis is being considered. Anecdotal experiences and commercial claims, whether positive or negative, and however compelling, must be eschewed in favor of research findings and facts to guide clinical decision‑making.

Red cell distribution width (RDW) is a routinely reported hematological parameter that reflects the degree of variability in the size of circulating erythrocytes, known as anisocytosis. Historically, RDW has been utilized primarily as a supporting index in the differential diagnosis of anemias; however, emerging evidence over the last two decades has established its strong association with inflammation, oxidative stress, nutritional deficiencies, and systemic disease burden. Among non-communicable disorders, cardiovascular diseases (CVDs) have been prominently linked with elevated RDW, suggesting its significant utility as a cost-effective and widely accessible prognostic biomarker. Numerous clinical and epidemiological studies have demonstrated that increased RDW values correlate with higher mortality and adverse clinical outcomes in acute and chronic heart failure, coronary artery disease, myocardial infarction, peripheral arterial disease, hypertension, and atrial fibrillation. Although RDW is not disease-specific, its prognostic value is gaining recognition because of its pathophysiological links to key mechanisms implicated in cardiovascular injury, including impaired erythropoiesis, chronic low-grade inflammation, reduced iron mobilization, malnutrition, renal impairment, and systemic oxidative stress. As a component of a standard complete blood count (CBC), RDW possesses substantial clinical relevance due to its accessibility, affordability, and applicability in primary healthcare, emergency settings, and tertiary cardiovascular care. This review aims to explore the prognostic significance of RDW in major cardiovascular conditions, summarize current evidence regarding its pathophysiological interplay with CVD, and discuss its limitations and future role in clinical risk stratification and precision cardiology

Climate change has become one of the greatest challenges facing the world today. The impacts of climate change on human health can be felt through increasing extreme temperatures, the spread of infectious diseases, and increased air pollution. The aim of this research is to determine the impact of climate change on public health. A literature search was conducted through several electronic databases, including Google Scholar and PubMed, to capture articles published from 2020 to June 2025. The article selection process involved several stages of identification and screening based on title and abstract, followed by an assessment of the eligibility of full-text articles based on inclusion and exclusion criteria. All selection stages were documented using a PRISMA flowchart.The results of this study revealed direct and indirect health impacts. It can be concluded that climate change on public health can be influenced by disruptions to physical, biological, and ecological systems, including disruptions originating domestically and internationally. The health impacts of these disruptions include increased respiratory and cardiovascular diseases, injuries and premature deaths related to extreme weather events, changes in the prevalence and geographic distribution of food- and waterborne diseases and other infectious diseases, and threats to mental health.

ObjectivesThis study assessed the prognostic impact of cardiovascular injuries in patients with isolated chest trauma primarily involving the respiratory system.MethodsWe retrospectively reviewed the Japan Trauma Data Bank records (2004-2019). Patients with isolated chest trauma were categorized into the respiratory or cardiovascular injury group according to the highest abbreviated injury scale score. The effect of cardiovascular injuries in the respiratory injury group was analysed using a multivariable logistic regression analysis.ResultsAmong the 8048 patients in the respiratory injury group, those with minor cardiac injury had a higher mortality rate than those without (15% vs 7%; P = .027); those with severe vascular injury (most commonly thoracic aorta) had a 76% mortality rate. The multivariable analysis indicated older age (adjusted odds ratio [adjOR]: 1.01, 95% CI: 1.00-1.01, P = .016), penetrating injury (adjOR: 2.19, 95% confidence interval [CI]: 1.40-3.43, P = .002), higher new injury severity score (adjOR: 3.89, 95% CI: 3.16-4.78, P < .001), coexistence of cardiac (adjOR: 2.68, 95% CI: 1.51-4.76, P < .001) or vascular injuries (adjOR: 3.36, 95% CI: 1.93-5.83, P < .001), and tracheobronchial injuries (adjOR: 2.10, 95% CI: 1.15-3.82, P = .015) with the highest abbreviated injury scale scores were significantly associated with increased odds of in-hospital mortality.ConclusionsMinor cardiac or severe vascular injuries significantly increased mortality in patients with isolated chest trauma primarily involving the respiratory system. Assessment of both respiratory and coexisting cardiovascular injuries is essential for clinical management.

ObjectiveTo characterise and quantify the mortality risks for a range of causes after tropical cyclones in nine countries and territories.DesignTwo stage, time series study.SettingNine countries or territories (Australia, Brazil, Canada, South Korea, Mexico, New Zealand, the Philippines, Taiwan, and Thailand), covering tropical, subtropical, and extra-tropical regions.ParticipantsGeneral populations living in regions with tropical cyclones in the nine countries or territories, 2000-19.Main outcomes measuresExcess mortality risk of cardiovascular diseases, respiratory diseases, infectious diseases, injuries, neuropsychiatric disorders, renal diseases, digestive diseases, diabetes, and neoplasms as the leading cause of death. Wind speed and rainfall profiles were quantified with a physics based tropical cyclone field model.Results14.8 million deaths and 217 tropical cyclone events in communities from the nine countries or territories were included in the analysis. Mortality risks from various causes consistently increased after tropical cyclones, with peaks occurring within the first two weeks after the cyclone, followed by a rapid decline. During the first two weeks after a tropical cyclone, the highest increases were seen in mortality from renal diseases and injuries, with a cumulative relative risk of 1.92 (95% confidence interval (CI) 1.63 to 2.26) and 1.21 (1.12 to 1.30), respectively, for each additional tropical cyclone day. Relatively more modest risks were found for mortality from diabetes (cumulative relative risk 1.15, 95% CI 1.08 to 1.21), neuropsychiatric disorders (1.12, 1.05 to 1.19), infectious diseases (1.11, 1.05 to 1.17), digestive diseases (1.06, 1.02 to 1.09), respiratory diseases (1.04, 1.00 to 1.08), cardiovascular diseases (1.02, 1.01 to 1.04), and neoplasms (1.02, 1.00 to 1.04). Mortality risks were substantially higher in communities with greater levels of deprivation and in those with historically fewer tropical cyclones, especially for renal, infectious, and digestive diseases, as well as for diabetes. Rainfall related to tropical cyclones had a more consistent increasing exposure-response relation with mortality risks, particularly for deaths related to respiratory, cardiovascular, and infectious diseases.ConclusionsAfter tropical cyclones, mortality risk increased variably for different causes, populations, and regions. Integrating epidemiological evidence into the development of management systems for climate extremes is urgently needed, particularly in regions with higher levels of deprivation and in those with historically fewer tropical cyclones. These measures are necessary to improve the adaptive capacity in responding to the growing risks and shifting activity of tropical cyclones in a warming climate.

The EGR1/miR-199a-3p/mTOR axis: A crucial pathway in the amplification of myocardial damage under intermittent hypoxic conditions.

Early Echocardiographic and Serum Biomarkers Predict Thrombotic Microangiopathy, Endotheliopathy, and Survival After Pediatric Hematopoietic Stem Cell Transplant.

Immune cell dynamics and their role in cardiac injury: Mechanisms and therapeutic implications.

Primary hypertension in childhood tracks into adulthood and is associated with increased cardiovascular risk. Studies conducted in individuals aged <18 years, an age group without many of the confounding comorbid cardiovascular disease risk factors in adults, provide an opportunity to explore early cardiovascular target-organ injury. Youths (n=132, mean age, 15.8 years) were stratified by blood pressure (BP) as low-BP, mid-BP, and high-BP and by left ventricular mass index as low-and high left ventricular mass index. Systemic circulating RNA, microRNA, and methylation profiles in peripheral blood mononuclear cells and deep proteome profiles in serum were determined using high-throughput sequencing techniques. Invitro cell culture experiments assessed angiotensin II- and microRNA-mediated Vash1 (vasohibin-1 protein) regulation and Vash1-mediated hypertrophic response. In high-BP youths, transcriptomics analysis identified 7 differentially expressed genes, including elevated VASH1 transcripts but correspondingly diminished levels of its microRNA (microRNA-24-3p and microRNA-335-5p). Invitro experiments revealed that either angiotensin II treatment, microRNA-24-3p or microRNA-335-5p overexpression, reduced endogenous VASH1 transcript levels. In contrast, exogenous Vash1 protein treatment induced cellular hypertrophy. Hypermethylation of GSE1, POTE1, and MN1; hypomethylation of MAD1L1 and SH3BP4; elevated Protein Z and diminished Superoxide dismutase 3 protein levels were observed in mid-BP and high-BP+high-left ventricular mass index groups. In youths with high-BP and high-left ventricular mass index, HYAL1 transcripts and Hyaluronidase 1 protein were elevated, suggesting the significant involvement of extracellular matrix in cardiovascular target-organ injury. The integration of multiomics data in this unique pediatric population during the early phase of high BP provides evidence of molecular changes that reveal both potential drug targets and strategies for ameliorating BP-mediated cardiovascular target-organ injury.

BackgroundSelf-rated health status is a subjective but important indicator of an individual’s perception of overall health. However, it remains unclear whether lifestyle may mediate or modify the association of self-rated health status with overall and cause-specific mortality.MethodsThis prospective cohort analysis included 401,410 US adults from the National Institutes of Health-AARP Diet and Health Study. Self-rated health was categorized as “very good to excellent,” “good,” or “poor to fair.” A healthy lifestyle was defined by a normal body mass index, never smoking, moderate alcohol consumption, adequate physical activity, and a higher diet quality score. Hazard ratios (HRs) and 95% confidence intervals (CIs) for overall and cause-specific mortality were estimated using multivariable-adjusted Cox models.ResultsDuring a median follow-up of 23.6 years, we ascertained 181,776 deaths. Compared with individuals reporting “very good to excellent” health, those reporting “poor to fair” health had an elevated risk of overall mortality (HR = 1.90, 95% CI: 1.87–1.93) as well as mortality from cardiovascular disease (CVD), heart disease, stroke, cancer, respiratory disease, diabetes, infection, and injuries and accidents (risk increment ranged from 24% to 361%). Mediation analysis showed that 5.1% to 33.6% of the observed associations were mediated by lifestyle. Self-rated health was more strongly associated with overall mortality than traditional risk factors except smoking. Compared with individuals reporting “very good to excellent” health who adhered to a healthier lifestyle, those reporting “poor to fair” health with a less healthy lifestyle experienced a significantly elevated risk of overall mortality and mortality from CVD, heart disease, cancer, and respiratory disease (relative excess risk due to interaction > 0).ConclusionsPoor self-rated health was significantly associated with higher risk of overall and cause-specific mortality, and these associations were partially mediated by lifestyle. A positive additive interaction between self-rated health and lifestyle was noted for overall mortality and for mortality from CVD, heart disease, cancer, and respiratory disease. These findings underscore the clinical importance of self-rated health and suggest that lifestyle modification may improve health and longevity, particularly among individuals with low or moderate self-rated health.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12916-025-04399-y.

BackgroundResearch has shown that workers in non-standard (eg, temporary and part-time) employment experience poorer health outcomes than their permanent, full-time counterparts. However, previous studies have overlooked important differences in the quality of non-standard employment. To address this gap, we examined associations between a diverse typology of employment quality and mortality in Canada.MethodsThe 2006 Canadian Health and Environment Cohort (n=2 805 550) was linked to death records from 2006 to 2019. Employment quality was assessed according to an empirical typology describing five distinct employment arrangements: standard (secure and gainful), portfolio (demanding but gainful), marginal (limited hours and earnings), intermittent (sporadic and unstable) and precarious (insecure and low paying). Poisson regression models estimated covariate-adjusted associations between employment quality, all-cause and cause-specific (cancer, cardiovascular and unintentional injury) mortality, by sex/gender.ResultsWe observed a graded association between employment quality and mortality. Mortality rates were lowest among workers in standard and portfolio employment. Mortality rates were highest among workers in precarious employment, with workers in marginal and intermittent employment occupying intermediate positions along the risk gradient. Associations varied by sex/gender, with larger absolute and relative mortality inequalities among men.ConclusionsOur findings reinforce the need to move away from a binary view of jobs as either ‘standard’ or ‘precarious’, encouraging a more nuanced understanding of contemporary employment arrangements and their health-related consequences. Policy interventions that promote access to high-quality jobs and protect workers exposed to precarious employment may yield substantial improvements in population health, including longevity.