This study assessed the global burden and trends of cardiovascular diseases attributable to secondhand smoke (CVD-SHS) from 1990 to 2021.

The global burden of disease (GBD) database was utilized to analyze estimated annual percentage change (EAPC), age-standardized mortality rates (ASMR), age-standardized DALY rates (ASDR), disability-adjusted life years (DALYs), and deaths due to CVD-SHS. Subsequently, further analysis was conducted by region, age group, sex, and socio-demographic index (SDI). Finally, Spearman correlation analyses were used to assess the correlation of ASDR and ASMR with SDI.

From 1990 to 2021, global CVD-SHS deaths and DALYs increased by 34.5 and 23.1%, respectively, while ASMR and ASDR decreased by 41.8 and 42.0%. In 2021, CVD-SHS deaths totaled 694,692 (ASMR 8.31/100,000), with DALYs at 16,674,552 (ASDR 194.59/100,000). Regionally, the highest ASDR and ASMR were observed in low-middle and middle SDI regions, with minimal reductions in low SDI regions. Correlation analysis indicated that ASMR and ASDR, as well as their EAPCs, were negatively correlated with SDI. Moreover, CVD-SHS burden was higher in males and older age groups, predominantly affecting those aged 35 and above in lower SDI regions, and those aged 65 and above in high SDI regions.

From 1990 to 2021, the global, regional, and national burden of CVD-SHS showed a paradoxical trend: while ASMR and ASDR declined, the absolute number of deaths and DALYs continued to rise. The burden and its growth rate were negatively correlated with SDI, with the highest impacts observed in low- and middle-SDI regions, males, and older populations. Moreover, stroke-SHS showed a stronger negative correlation with SDI than IHD-SHS, suggesting subtype-specific disparities. These findings highlight the persistent and uneven burden of CVD-SHS worldwide and underscore the need for targeted, region- and disease-specific prevention strategies.

Highlighting arterial stiffness in Community Pharmacies (CPh) has been met with considerable interest in Portugal, Austria, and Spain. TOGETHER aims to evaluate whether empowering hypertensive subjects by determining blood pressure (BP) and vascular aging in CPh increases hypertension (HTN) control, while establishing paths of lasting cooperation between General Practitioners (GP) and CPh.

TOGETHER is a cluster-randomized, prospective study in Portugal, Austria, and Spain. All consecutive subjects entering CPh will be offered BP measurement and ambulatory BP monitoring (ABPM) for those with BP ≥ 140/90 mmHg. CPh will be randomly assigned to a usual care arm (including health education for HTN). In the experimental care group, vascular aging (VA) will be additionally assessed by estimating aortic pulse wave velocity using brachial oscillometry. In this group, health education will include VA, which will also be communicated to GPs. In both groups, HTN will be treated by GPs according to usual clinical practice. A second evaluation with ABPM will be performed after 6 months, and the percentage of patients with controlled hypertension will be compared between both arms. The degree of CPh/GP interaction and patients´ adherence will be assessed through validated surveys.

Five fundamental unmet needs will be addressed by TOGETHER: 1) the lack of HTN screening programs; 2) implementation of the simpler and more informative VA concept ("Your arteries are 10 years older than you"); 3) understanding CV risk on an individual basis (individual VA) should improve patient adherence and reduce physician inertia; 4) implementation of health educational programs, combined with the concept of VA; 5) higher collaboration and development of a team-based approach to HTN care between CPh and GP. The complementary organizational settings and strengths of CPh and GP will allow TOGETHER to create new strategies for the early identification and intervention in uncontrolled HTN, encompassing both lifestyle and medical treatment, while considering social, economic, and behavioral aspects.

https://clinicaltrials.gov/, identifier FP-1533-ROD-SAL-2024-01.

Tobacco smoking constitutes a primary cause of preventable cardiovascular and pulmonary diseases on a global scale. While smoking rates fall, e-cigarette use rises, especially in youth.

Assess effects of smoking, vaping, and dual use on lung function, exercise capacity and quality of life.

Participants were classified into five groups: Control, Cigarette use only, E-cigarettes use only, Ex-cigarette smoker current vaper, and Dual users (use of both e-cigarettes and combustible cigarettes). Participants performed spirometry, six minute walk test (6MWT) and completed health related quality of life (HRQoL) questionnaire.

A total of 222 participants, 86.9% were male, with median age 26 years. Age and body mass index (BMI) showed no significant differences across groups. Cigarette-only and dual users reported 20 cigarettes/day with 5-7 years smoking duration, while e-cigarette use duration was 4-5 years among exclusive vapers, ex-smoker vapers, and dual users. Spirometry revealed impairments: Forced expiratory volume in the first second (FEV₁; % predicted) was lower across groups versus controls (H = 80.69, df = 4, p < 0.001, η ² = 0.35), lowest in dual users. Forced vital capacity (FVC; L) showed no differences, while FVC (% predicted) decreased in smokers and dual users. FEV₁/FVC ratio was reduced (H = 66.54, df = 4, p < 0.001, η ² = 0.29), most in dual users. 6MWT showed no group differences. HRQoL indicated decline in physical functioning (H = 35.11, p < 0.001, η ² = 0.14), role limitations due to physical health social functioning, and emotional wellbeing, lowest in cigarette-only and dual users.

Young adults using cigarettes and e-cigarettes showed impaired lung function and quality of life compared to never-users. Daily dual users showed the greatest declines, while former smokers using e-cigarettes showed intermediate outcomes. Exclusive e-cigarette users exhibited least impairment.

This study employed a multidimensional evaluation framework (of efficacy, safety, and costs) to comprehensively assess the value of Chinese patent medicines (CPMs) combined with Western medicine in treating coronary heart disease (CHD) angina pectoris with Qi deficiency and blood stasis pattern.

Efficacy analysis was based on a network meta-analysis (NMA) of 24 randomized controlled trials (RCTs). Safety was assessed using a standardized framework that graded adverse events via CTCAE v5.0 and synthesized risk profiles into a Composite Safety Score. A pragmatic Cost-Consequence Analysis (CCA) was employed to synthesize direct daily treatment costs with clinical efficacy rankings (SUCRA).

The network meta-analysis of 24 RCTs (n = 2,382) showed that CPMs combined with conventional medicine significantly improved clinical efficacy (OR 3.08, 95% CI: 2.46-3.85). Dengzhan Shengmai Capsule (SUCRA 88.99%) and Shexiang Tongxin Dropping Pill (SUCRA 75.12%) ranked highest in efficacy. Safety analysis using the Composite Safety Score (CSS) identified Yangxinshi Tablet as having the most favorable profile (CSS = 3), whereas Xintong Granule and Qishen Capsule presented higher risks (CSS = 9) due to hepatotoxicity concerns or data gaps. Cost-consequence analysis revealed distinct value profiles: Yangxinshi Tablet offered the lowest daily cost (CNY 6.24) suitable for cost-minimization; Shexiang Tongxin Dropping Pill (CNY 7.28) provided a balanced cost-efficacy ratio; while Dengzhan Shengmai Capsule (CNY 10.86) represented a premium high-efficacy option. Sensitivity analysis confirmed the robustness of efficacy findings but highlighted cost fluctuations in flexible-dose regimens.

Specific CPMs, notably Dengzhan Shengmai Capsule (maximal efficacy), Shexiang Tongxin Dropping Pill (balanced value), and Yangxinshi Tablet (cost-minimization), demonstrate significant therapeutic and economic advantages as add-on therapies. Beyond these clinical findings, this study establishes a multidimensional framework aligned with international regulatory standards, serving as a model for the future pharmacoeconomic integration of TCM into global cardiovascular care.

The study aimed to evaluate long-term medication persistence and adherence to secondary prevention therapies in young ischemic stroke survivors (aged 18-49 years) and identify factors influencing these outcomes.

The single-center prospective cohort study enrolled young ischemic stroke patients (aged 18-49 years) from March 2017 to March 2023. Medication persistence (continuation of all prescribed secondary prevention drugs) and adherence (assessed by the Morisky Medication Adherence Scale-8 (MMAS-8)) were evaluated, with reasons for discontinuation and influencing factors analyzed.

Among 226 patients (median age 35 years, 34.5% female), 80.1% remained persistent with their medication regimen over a median follow-up of 3.9 years. Patients with persistence had higher rates of large artery atherosclerosis (42% vs. 22.2%, p = 0.015) and comorbid diabetes (13.3% vs. 2.2%, p = 0.015). The median MMAS-8 score was 7 (6-7.38), with 24.2% showing high adherence, 63% moderate adherence, and 12.8% poor adherence. Poor adherence was associated with younger age (<35 years, p = 0.018), the absence of large artery atherosclerosis (p = 0.017), and a lower quality of life (p = 0.004). Multivariate analysis revealed that older age (p = 0.043) and large artery atherosclerosis (p = 0.047) were independent predictors of better adherence.

Young ischemic stroke patients demonstrated high medication persistence and moderate adherence, which were influenced by age, stroke etiology, and quality of life. These findings highlight the need for tailored secondary prevention strategies to improve outcomes in this population.

Low-molecular-weight heparin (LMWH) is recommended for thromboprophylaxis in adult intensive care unit (ICU) patients. Despite its widespread use, there is insufficient evidence on the optimal dose, and there appears to be practice variation. Determining the LMWH dosing strategy that most effectively balances the risks of venous thromboembolism (VTE) and bleeding may improve outcomes in ICU patients.

The INCEPT-thromboprophylaxis domain is an investigator-initiated, open-label domain with an integrated feasibility phase on the international, pragmatic, parallel-group, randomised, embedded, multifactorial, adaptive Intensive Care Platform Trial (INCEPT). Adult acutely admitted ICU patients with an indication for thromboprophylaxis will be randomised to a fixed low dose, a fixed intermediate dose or a weight-adjusted dose of LMWH while in the ICU for a maximum of 90 days. The primary outcome is days alive out of hospital at 30 days. Secondary outcomes include 30-, 90- and 180-day all-cause mortality; days alive without life support at 30 and 90 days; days alive out of hospital at 90 days; days free of delirium at 30 days; health-related quality of life and cognitive function at 180 days; VTE and major bleeding during hospital stay at 30 and 90 days; and serious adverse reactions at 30 and 90 days. Analyses will primarily be conducted in the intention-to-treat population using Bayesian statistical models with neutral, weakly informative priors. We will assess feasibility after 300 participants and conduct adaptive analyses after follow-up for the primary outcome of 1500 participants and every additional 500 participants to a maximum of 10,000, with adaptive stopping for superiority/inferiority and practical equivalence (mean difference in the primary outcome < 1 day), and adaptive arm-dropping for superiority/inferiority. Allocation will initially be equal, followed by response-adaptive randomisation with a minimum 25% allocation to each arm. Expected sample sizes across different scenarios range from 2265 to 4892 participants, with approximately 100% probabilities of conclusiveness across scenarios.

INCEPT-thromboprophylaxis will with high probability provide conclusive results and inform clinical practice regarding the dosing of LMWH for thromboprophylaxis in adult acutely admitted ICU patients.

Cardiovascular diseases (CVDs) remain the leading cause of death globally. Statin therapy significantly reduces cardiovascular risk in both primary and secondary prevention; however, real-world implementation of guideline-directed therapy and achievement of target low-density lipoprotein cholesterol (LDL-C) levels remain suboptimal, especially in low- and middle-income settings.

This cross-sectional observational study was conducted at the Hospital and Research Centre, including 198 adults (≥25 years) eligible for statin therapy based on atherosclerotic CVD (ASCVD) risk assessment or established CVD. Patients were categorized into primary or secondary prevention groups. Lipid profiles were assessed to determine LDL-C target attainment (<70 mg/dL) after at least 3 months of statin therapy. Factors contributing to nonachievement of the target LDL-C were analyzed descriptively.

Of 198 patients, 67.7% were eligible for primary prevention, yet only 3.7% were initiated on statins. All secondary prevention patients received statins, but only 4.7% achieved the target LDL-C. The most frequent reasons for nonattainment included inadequate dose escalation (59.0%), low patient perception of therapy importance (52.5%), financial barriers (49.2%), and pill burden (39.3%). True statin intolerance was rare (3.3%). Demographic analysis revealed a mean age of 62.18 ± 12.84 years and a male predominance (80.3%).

This study highlights critical gaps in statin use and LDL-C target attainment in both primary and secondary prevention. Systematic incorporation of ASCVD risk calculators, regular follow-up lipid profiling, structured dose optimization, patient education, and enhanced medication affordability are essential to improving real-world cardiovascular risk reduction and achieving global prevention targets.

Arterionephrosclerosis is characterized by focal global glomerulosclerosis (FGGS), which is a constant feature of aging and hypertension. FGGS begins as normal-appearing glomeruli that undergo tuft contraction (TC) and progress to global glomerulosclerosis (GGS). Kidney tissue from 26 hypertensive and 25 age-matched non-hypertensive patients was analyzed for glomerular volume and for podocyte number using a WT1 antibody. Immunohistochemistry (IHC) was employed to detect the senescence-related biomarkers p16, p21, β-galactosidase (GLB1), and 5-nucleotidase (CD73). Antibodies against annexin 3 (ANXA3), cytokeratin 7, and CD44 were used to evaluate parietal epithelial cell (PEC) activation. The relationships between biomarkers, hypertension, TC, and GGS were quantitatively analyzed. With TC, podocyte numbers decreased in association with increased glomerular p16, p21, GLB1, and CD73 expression. With TC, WT1, CK7, and CD44-expressing PEC increased. TC and GGS expressed senescent markers in hypertensive and non-hypertensive kidneys; however, the frequency of TC (p < 0.01) and GGS (p < 0.001) was greater in hypertensive kidneys, and glomerular expression of senescence markers was correspondingly higher. Additionally, greater p16 and p21 expression was observed in the tubular atrophy of hypertension. As FGGS developed, podocyte depletion, cellular senescence markers, and PEC activation were associated with TC and increased with hypertension.

Muscle atrophy is a common complication of ageing, and many chronic conditions, lacks defined therapeutic interventions. It is still mostly unknown how circular RNAs contribute to muscle atrophy.

circRNA sequencing and quantitative real-time PCR were performed to detect the changed circRNAs in muscle atrophy models and aged muscle. Then the gain-of-function and loss-of-function experiments were used to investigate the function of circSnd1 in muscle atrophy and muscle ageing. Furthermore, we used RIP-MS and RIP assay to determine the downstream and upstream mechanism of circSnd1 in muscle atrophy.

Here, we characterized the function and mechanism of highly species-conserved circRNA derived from staphylococcal nuclease and Tudor domain containing 1 gene (named circSnd1) in muscle atrophy. CircSnd1 is upregulated in many types of muscle atrophy models in both in vivo and in vitro (all p < 0.01). Meanwhile, circSnd1 is also higher expressed in aged muscle in humans (+2.2-fold, n = 5, p < 0.05), mice (+43.96%, n = 6, p < 0.05) and myotubes (+42.21%, n = 6, p < 0.05). Functional analyses show that circSnd1 promotes muscle atrophy and muscle ageing at the cellular level and mouse level while repressing it ameliorates multiple types of muscle atrophy (all p < 0.05). Mechanistically, the RNA binding protein eukaryotic translation initiation factor 4A3 (EIF4A3) can bind to the intron flanking sequence of circSnd1 to induce circSnd1 cyclization and increase circSnd1 expression in muscle atrophy. In addition, circSnd1 promotes the binding between human HLA-F adjacent transcript 10 (FAT10) and eukaryotic translation elongation factor 1 alpha 1 (EEF1A1). FAT10 competes with ubiquitin for binding with EEF1A1, which decreases the ubiquitination of EEF1A1 and stabilizes the protein level of EEF1A1 in muscle cells to promote atrophy.

We have identified circSnd1 as a novel circRNA that promotes muscle atrophy and highlighted its potential as a novel therapeutic target.

In recent years, except for the well-known heart failure with reduced ejection fraction (HFrEF), the incidence of heart failure with preserved ejection fraction (HFpEF) and heart failure with mildly reduced ejection fraction (HFmrEF) among the classification of heart failure (HF) has been increasing. However, due to their complex mechanisms, current research remains insufficient to address clinical needs.

Utilizing wild-type (WT), miR-30a-5p knockout (KO), and overexpression (OE) murine models combined with estrogen modulation and ovariectomy (OVX), this study delineates sex-specific regulatory networks in HF pathogenesis. Female KO mice lost the inherent resistance of WT females to HFpEF induction via 24-week HFD/L-NAME, whereas males exhibited comparable HFpEF susceptibility regardless of genotype, developing hallmark phenotypes including diastolic dysfunction (E/E'), myocardial hypertrophy (heart weight/tibia length), cardiac fibrosis, and hepatic steatosis. Particularly, due to the reduced ejection fraction in KO mice, combined with HFD/L-NAME, the HF phenotype was ultimately manifested as impaired diastolic function and slightly reduced ejection fraction (with the characteristics of HFpEF and HFmrEF). Mechanistically, KO-HF females displayed significant estrogen axis disruption (plasma estradiol and the expression of ERα, ERβ, ESRRA, and PELP1 expression). OVX in WT females validated the importance of estrogen for HFpEF resistance. Transcriptomic profiling identified convergent targets across cardiac (ITGAD, ITGAM, FGA, and FGB) and hepatic tissues (APOA1 and APOB), revealing miR-30a-5p's orchestration of extracellular matrix remodeling (via ITGAD/ITGAM mechanotransduction),fibrinogen-mediated microvascular homeostasis, and APOB-driven metabolic dysregulation. Notably, OE intervention failed to mitigate OVX-induced cardiac/hepatic pathology, implicating estrogen-dependent miR-30a-5p functionality.

These findings establish miR-30a-5p as a crucial sex-specific regulator of HF (mainly HFpEF), operating through estrogen signaling to balance cardiac compliance and metabolic adaptation.