Background and aims Lower extremity amputation (LEA) is a critical public health issue predominantly caused by diabetes mellitus (DM) and peripheral arterial disease (PAD). Switzerland faces a growing diabetes burden amid suboptimal glycemic control. The aim was to analyze LEA trends in Switzerland (2013-2023), comparing diabetic and non-diabetic populations to inform targeted prevention and management strategies. Methods A retrospective, nationwide analysis of Swiss hospital discharge data from 2013 to 2023 was conducted. LEA cases were identified via Swiss surgical procedure codes and stratified by diabetes status using ICD-10-GM diagnosis codes. Age-standardized incidence rates and amputation proportions were computed, with Poisson regression models to evaluate risk factors. Outcomes including in-hospital mortality and re-amputation rates were assessed.From 2013 to 2023, 30,047 lower extremity amputations were performed in Switzerland, with 60% occurring in patients with diabetes and 85% being minor amputations. Crude annual numbers increased, but age-standardized rates remained stable. Patients with diabetes had a 56% higher adjusted risk than those without. Amputation proportions in diabetes-related hospitalizations decreased over time, driven by a reduction in minor amputations, while major amputations remained stable. In-hospital mortality was 4.3%, lowest in type 1 diabetes, and 13% experienced re-amputation within 36 months. Conclusions Lower-extremity amputation remains a preventable complication; improved diabetes control and access to early, multidisciplinary foot care are critical to further reduce avoidable limb loss in Switzerland.
Background:Cigarette smoking is a leading cause of cardiopulmonary disease through chronic inflammation, but individual studies on its effects on cardio-inflammatory biomarkers have yielded inconsistent results. This meta-analysis synthesizes evidences of smoking on cardio-inflammatory biomarkers. Methods:A systematic search was conducted across PubMed, Scopus, Web of Science, and MagIran up to April 22, 2026. Case-control studies measuring the effect of smoking on specific blood biomarkers (CK-MB, E-selectin, P-selectin, TnI, TnT, hsCRP, ICAM-1, VCAM-1, NT-proBNP) were included. Data were analyzed using a random effects model to calculate unstandardized mean differences. Subgroup analyses were performed by smoking status, gender, and health status. A total of 55 studies comprising 116,147 participants were included. Results:Meta-analysis revealed that smoking was associated with significant increases in CK-MB levels, E-selectin, ICAM-1, NT-proBNP, hsCRP, P-selectin, TnI, and TnT. For VCAM-1, the analysis was inconclusive due to wide confidence intervals. Subgroup analysis showed that current smokers had widespread biomarker elevations, whereas former smokers showed significant changes only in hsCRP and P-selectin. Gender-specific analyses indicated more pronounced biomarker elevations in males. By health status, smoking elevated six biomarkers in healthy individuals but only ICAM-1 and hsCRP in those with cardiopulmonary disease. This study confirms that smoking promotes a pro-inflammatory state and subclinical heart damage, as shown by a distinct biomarker profile. The impact varies by exposure and sex, being most severe in current smokers and males, with lingering effects after cessation. Conclusion:These findings provide a mechanistic link for smoking-related cardiopulmonary risk and reinforce the importance of cessation programs.
Background:Anemia is a prevalent comorbidity in chronic obstructive pulmonary disease (COPD), yet prior studies have predominantly focused on all-cause mortality, leaving the non-linear relationship between hemoglobin and mortality-and clinically actionable thresholds-undefined. We aimed to identify distinct hemoglobin thresholds associated with cardiovascular and all-cause mortality and evaluate hemoglobin as a prognostic risk indicator in COPD. Methods:This prospective cohort study utilized data from seven NHANES cycles (2005-2018), including 1338 U S. adults with COPD representing approximately 7.7 million non-institutionalized COPD patients. Weighted Cox proportional hazards models and restricted cubic spline analysis were conducted to explore the association between hemoglobin level and mortality in COPD. Results:The weighted prevalence of anemia among U.S. adults with COPD was 10.5%. Anemia was significantly associated with all-cause mortality (HR = 2.32, 95% CI: 1.85-2.92) and cardiovascular mortality (HR = 3.75, 95% CI: 2.06-6.83). Each 1 g/dL hemoglobin increment was associated with 17% and 22% risk reductions, respectively. RCS analysis identified nonlinear relationships with thresholds at 12.5 g/dL for all-cause and 13.0 g/dL for cardiovascular mortality. Findings remained robust across all sensitivity analyses. Conclusions:Anemia and lower hemoglobin levels were independently associated with significantly increased risks of all-cause and cardiovascular mortality. Hemoglobin thresholds of 12.5 g/dL and 13.0 g/dL were identified for all-cause and cardiovascular mortality, respectively, as prognostic indicators warranting further validation. These findings underscore the importance of hemoglobin assessment in risk stratification; however, interventional studies are needed to determine whether correction of anemia improves survival in this population.
Background Aboriginal and Torres Strait Islander Australians experience substantially higher rates of cardiovascular disease (CVD), premature mortality, and related healthcare expenditure than non-Indigenous Australians. Improved management of modifiable risk factors, including hypercholesterolaemia, may reduce this excess burden. Inclisiran is a small interfering RNA therapy that provides sustained reductions in low-density lipoprotein cholesterol (LDL-C). Its cost-effectiveness as an earlier secondary prevention strategy in high-risk populations remains uncertain. We evaluated the cost-effectiveness of earlier addition of inclisiran to statin therapy for Aboriginal and Torres Strait Islander Australians with established CVD. Methods A health economic analysis was undertaken from the Australian healthcare system perspective. A 25-year Markov cohort state-transition model with annual cycles was developed using the best available Australian epidemiological and cost data. Aboriginal and Torres Strait Islander Australians with established CVD and hypercholesterolaemia were modelled to receive inclisiran plus statin therapy or statin therapy alone. Model outputs included the incremental cost-effectiveness ratio (ICER), non-fatal CVD events avoided, and quality-adjusted life years (QALYs) gained. Deterministic sensitivity analyses were performed. Results Among an estimated 12,180 eligible individuals, earlier inclisiran use was modelled to avert 6401 non-fatal CVD events and gain 23,730 QALYs over 25 years, at an additional cost of AUD 1.16 billion (AUD 46.3 million annually; 0.32% of annual Australian CVD expenditure). The ICER was AUD 48,808-per-QALY gained. Cost-effectiveness improved with lower inclisiran pricing and earlier treatment initiation. Conclusions In this modelled analysis, earlier addition of inclisiran to statin therapy may represent a cost-effective secondary prevention strategy for Aboriginal and Torres Strait Islander Australians with established CVD. Earlier access could reduce projected cardiovascular burden and may inform future reimbursement, guideline, and equity-focused prevention policy in Australia.
Background:Cardiac rehabilitation (CR) is a cornerstone of secondary prevention, yet long-term real-world data on outpatient programs remain limited. We report the long-term experience of a high-volume centre, evaluating clinical profiles, temporal trends, and functional and metabolic outcomes of patients undergoing outpatient CR. Methods:We analysed 1461 consecutive patients enrolled in the Niguarda Hospital outpatient CR program from 2012 to 2025. Demographic, clinical, angiographic, biochemical, hemodynamic, functional, and pharmacological data were collected at admission and discharge. Results:Acute coronary syndrome was the leading indication (70.8%), though its prevalence declined over time, paralleled by a progressive rise in chronic coronary syndrome and non-ischemic indications. Patients became older and more comorbid, yet consistently achieved significant improvements in functional capacity (Δ6MWT +28.4 ± 24.4%, p < 0.001), left ventricular ejection fraction (from 53.3 to 55.2%, p < 0.001), and lipid profile (LDL cholesterol from 99.6 ± 42.0 to 64.8 ± 26.2 mg/dL, p < 0.001). Rates of complete revascularization increased markedly, smoking patterns shifted toward cessation, and uptake of advanced cardioprotective therapies rose substantially. Despite reduced volumes and higher baseline complexity during COVID-19 (2020-21), CR effectiveness was preserved. Conclusions:Over 13 years, outpatient CR consistently delivered robust functional and metabolic benefits, even in an increasingly older and more complex population. Shifts in patient characteristics, improved revascularization rates, and evolution of pharmacological therapy underscore the expanding role of CR as a comprehensive, guideline-driven component of modern cardiovascular care.
Background Individuals with mental disorders face substantially reduced life expectancy, with cardiovascular disease (CVD) as the leading cause of premature death, likely due to a complex interplay of multiple factors. Prior studies examining whether patients with comorbid mental illness receive guideline-concordant pharmacological secondary prevention of ischemic heart disease (IHD) and cerebrovascular disease (CeVD) at rates comparable to those without psychiatric diagnoses are few and yielded inconsistent findings. Methods We conducted a retrospective cross-sectional analysis of statutory health insurance data for 2019–2022 (n = 238,616 adults with IHD or CeVD). Secondary prevention was defined as concurrent prescription of a lipid-modifying agent and an antiplatelet therapy or anticoagulant. Propensity score matching combined with logistic regression was used to estimate adjusted odds ratios (ORs) across all ICD-10 F-chapters (F0–F9) and for severe mental illness (SMI). Results Patients with any mental disorder had significantly higher odds of receiving secondary prevention for IHD (OR 1.18) and CeVD (OR 1.17) than those without. SMI was associated with even higher odds (IHD: OR 1.36; CeVD: OR 1.32). Diagnosis-specific subgroup analysis yielded no substantial differences between different mental disorders. Conclusion In general, prescription rates of pharmacological secondary prevention were higher in patients with comorbid mental disorders compared to patients without mental comorbidity. Factors other than pharmacological undertreatment – such as lifestyle-related prevention and physical health monitoring – may play a more central role in addressing the excess cardiovascular mortality burden in individuals with mental illness.
Background Optimal anticoagulation during elective percutaneous coronary intervention (PCI) remains uncertain, particularly in East Asian populations with lower body weight and increased bleeding susceptibility. We investigated the association of body weight and unfractionated heparin (UFH) dose with periprocedural bleeding during elective PCI. Methods and Results This retrospective single-center study included 348 Japanese patients undergoing elective PCI. Patients received either fixed-dose UFH (10,000 U) or weight-adjusted UFH (100 U/kg). Within the fixed-dose group, patients were stratified according to weight-adjusted UFH exposure (≥150 vs. <150 U/kg). The primary endpoint was Bleeding Academic Research Consortium (BARC) type 1 or 2 bleeding. Bleeding events were less frequent in the low-dose than in the high-dose group (24% vs. 40%, P < 0.001). No significant differences in major cardiovascular events were observed during follow-up. In multivariable analysis, lower body weight was associated with increased bleeding risk (OR 0.948, 95% CI 0.905–0.994, P = 0.027), whereas UFH dose was not independently associated with bleeding. Conclusions Lower body weight may be more closely associated with periprocedural bleeding than UFH dose during elective PCI. Careful bleeding risk assessment may therefore be warranted in patients with low body weight undergoing PCI.
Peripheral artery disease (PAD) contributes disproportionately to disability, limb loss, and premature mortality, and U.S. major amputation rates have risen in the past decade among increasingly younger adults. Traditional risk tools incompletely explain these trends. We propose to examine a hypothesis generating risk-stacked model in which three interacting layers: 1) genetic susceptibility via lipoprotein(a) [Lp(a)]; 2) cardiovascular-kidney-metabolic syndrome (CKM; chronic kidney disease/diabetes mellitus/insulin resistance); and 3) social determinants of health (SDOH) jointly influence PAD incidence, phenotype at presentation (critical limb-threatening ischemia), and outcomes (major adverse limb events [MALE], including amputation). We summarize the independent and joint associations of elevated Lp(a), CKM/diabetes mellitus/insulin resistance, and adverse SDOH with PAD onset and MALE and practice-level implementation strategies (one-time Lp(a) testing, SDOH screening/routing, intensified preventive therapies). We hypothesize that high Lp(a) and diabetes/insulin resistance synergize to impair collateralization and promote thrombosis-prone plaque biology, while adverse SDOH delay diagnosis and limit access to guideline-directed care, together driving worse PAD outcomes. This conceptual framework supports universal one-time Lp(a) measurement, aggressive prevention, and embedded SDOH workflows while informing trials of equity-focused delivery models for patients with PAD. These factors may refine PAD risk stratification and align prevention resources to those at highest risk of limb loss.
Background and rationale:Tocotrienol-rich fraction (TRF), a naturally occurring mixture of four tocotrienol isoforms (α-, β-, γ-, and δ-tocotrienol) derived principally from palm oil, constitutes a structurally and functionally distinct sub-family of vitamin E with demonstrably superior biological activity compared with α-tocopherol. Diabetes mellitus (DM) and its principal macrovascular complication, cardiovascular disease (CVD), remain the leading drivers of global morbidity and mortality, with an estimated 529 million adults currently affected and projections exceeding 1.3 billion by 2050. The shared pathological substrate of diabetic CVD-comprising reactive oxygen species (ROS)-mediated oxidative stress, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)-driven chronic inflammation, insulin resistance, dyslipidaemia, and endothelial dysfunction represents a multi-target landscape ideally suited to TRF's pleiotropic pharmacology. Objective:This narrative review synthesises the molecular mechanisms, preclinical evidence, and available clinical data underpinning TRF as a nutraceutical intervention for diabetes-associated CVD, and identifies critical gaps requiring further investigation. Key findings:TRF exerts cardioprotection through five mechanistically distinct axes: (i) direct scavenging of ROS and inhibition of lipid peroxidation via superior membrane integration conferred by its unsaturated isoprenoid side chain; (ii) suppression of NF-κB signalling and downstream pro-inflammatory mediators including tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1 beta (IL-1β); (iii) HMG-CoA reductase inhibition with consequent reductions in low-density lipoprotein (LDL) cholesterol and triglycerides; (iv) restoration of nitric oxide (NO) bioavailability and attenuation of vascular adhesion molecules (intercellular adhesion molecule-1 [ICAM-1], vascular cell adhesion molecule-1 [VCAM-1]); and (v) peroxisome proliferator-activated receptor-gamma (PPAR-γ) and PPAR-α agonism, enhancing insulin sensitivity and fatty acid oxidation. Clinical meta-analysis confirms significant glycated haemoglobin (HbA1c) reduction (standardised mean difference [SMD] -0.44; 95% confidence interval [CI] -0.82 to -0.02; p = 0.03) and consistent lipid-profile improvements at doses of 200-420 mg/day in type 2 diabetes mellitus (T2DM) patients. Conclusion:TRF occupies a unique mechanistic niche among nutraceuticals by simultaneously addressing all five core pathological drivers of diabetic CVD. Current clinical evidence supports its role as a meaningful glycaemic and cardioprotective adjunct. Adequately powered randomised controlled trials (RCTs) with primary cardiovascular endpoints, standardised formulations, and combination strategies with established antidiabetic agents are required to translate TRF into evidence-based clinical practice.
Background:Aortic stiffness is a proxy for cardiovascular risk, but the methods are technically demanding. Ultrasound-based assessment of aortic wall strain patterns is established in abdominal aortic aneurysms but has never been described in the non-aneurysmal aorta. This study aimed to describe a workflow for ultrasound-derived strain mapping of the non-aneurysmal abdominal aorta and assess technical applicability, acquisition reproducibility, and age-related strain patterns. Methods:In this cross-sectional proof-of-concept study, healthy volunteers underwent ultrasound scanning of their non-aneurysmal abdominal aortas with standard equipment. Three independent operators scanned each participant. The ultrasound acquisitions were saved as short videos, or cine-loops, and were analysed off-line with prototype software to extract mean strain, strain heterogeneity, and circumferential strain patterns. Acquisition reproducibility was assessed with extended Bland-Altman statistics, and associations with age group and sex were analysed using regression models and functional data analysis. Results:Fifty-seven volunteers were included, generating 171 cineloops; all were suitable for strain analysis. Mean strain decreased with age from 8.70% in participants aged <30 years to 3.90% in those aged >50 years (P < .001), and strain heterogeneity was associated with age (P = .01). Mean strain and heterogeneity were not associated with sex. Inter-operator limits of agreement were ±1.5 mm for diameter, ±1.64 percentage points for mean strain, and ±0.18 for heterogeneity index. Conclusion:Ultrasound-derived strain mapping of the non-aneurysmal abdominal aorta is applicable and shows acceptable acquisition reproducibility. The method describes age-related differences in aortic strain, supporting validation as a future tool for assessing aortic stiffness and cardiovascular risk.
Background:Glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium-glucose cotransporter-2 inhibitors (SGLT2i) have established cardiometabolic benefits and are increasingly used in combination, including in patients without diabetes. Although both drug classes have been studied extensively for metabolic and cardiovascular outcomes, their effects on cardiac arrhythmias, particularly in non-diabetic obese patients, remain poorly defined. Objective:To compare arrhythmia outcomes in non-diabetic obese patients receiving combined GLP-1RA and SGLT2i therapy versus GLP-1RA alone, with particular focus on time-dependent changes in atrial and ventricular arrhythmia risk. Methods:We performed a retrospective real-world cohort study of non-diabetic obese adults treated with either combined GLP-1RA and SGLT2i therapy or GLP-1RA alone. Cohorts were balanced through propensity score matching. The primary outcome was composite arrhythmia. Secondary outcomes included atrial fibrillation/flutter, ventricular tachycardia, and ventricular fibrillation. Outcomes were assessed at 60 months, with additional longitudinal analyses from 6 months through 96 months to better define the timing of benefit and the evolution of arrhythmia risk. Results:At 60 months, combination therapy was associated with 17.5% lower odds of composite arrhythmia compared with GLP-1RA alone, OR 0.825 (0.731-0.932). This benefit emerged by 24 months and persisted through 96 months. The reduction in the primary outcome was driven mainly by lower atrial arrhythmia burden, with atrial fibrillation/flutter occurring 17.9% less often in the combination group at 60 months, OR 0.821 (0.722-0.934); this benefit became apparent by 18 months and remained present through 96 months. In contrast, ventricular tachycardia was more frequent in the combination group during earlier follow-up intervals, including 6, 12, 18, and 24 months, but this difference was not sustained and became similar between groups around 60 months, OR 1.186 (0.943-1.491), and persisted through 96 months. Ventricular fibrillation remained comparable between groups throughout the follow-up period. Conclusions:In non-diabetic obese patients, combined GLP-1RA and SGLT2i therapy was associated with lower long-term odds of composite arrhythmia compared with GLP-1RA alone, largely driven by a reduction in atrial fibrillation/flutter. An increased ventricular tachycardia risk with combination therapy appeared to diminish over time, while ventricular fibrillation remained unchanged. These findings suggest that combination therapy may have a favorable long-term electrophysiologic profile in non-diabetic obesity and highlight the importance of time-dependent analysis when evaluating arrhythmia outcomes with cardiometabolic therapies.
Background Acute myocardial infarction (AMI) remains a leading cause of death worldwide and in Colombia. Beyond survival, AMI can markedly impair health-related quality of life (HRQoL), yet the prognostic value of HRQoL measured during the index hospitalization remains insufficiently explored, particularly in middle-income countries. Methods We conducted a prospective cohort study of 1093 adults with type 1 myocardial infarction admitted to a tertiary referral center in Colombia between 2023 and 2025. HRQoL was assessed within 24 h of admission using the EuroQol 5-Dimension 3-Level (EQ-5D-3L) instrument and the EuroQol Visual Analogue Scale (EQ-VAS). Multivariable Poisson regression with robust variance was used to estimate adjusted risk ratios (RRs) for one-year mortality and rehospitalization. Results At 12 months, all-cause mortality was 4.3% and rehospitalization was 2.6%. Impairment in the mobility domain was independently associated with higher risks of mortality (RR = 1.80; p = 0.045) and rehospitalization (RR = 2.22; p = 0.031). Percutaneous coronary intervention (RR = 0.28; p < 0.001) and male sex (RR = 0.54; p = 0.034) were associated with lower mortality risk. Conclusion Baseline HRQoL assessed during hospitalization for AMI was associated with one-year mortality and rehospitalization. Mobility limitations identified patients at higher risk and may complement conventional clinical risk stratification.
Background:Home-Based Cardiac Telerehabilitation (HBCTR) is a potential alternative to center-based programs, but its effectiveness remains unclear. This meta-analysis evaluated the impact of this treatment on clinical outcomes and patient-reported quality of life (QoL). Methods:We searched Cochrane Central, Google Scholar, and PubMed until September 1, 2025, for studies evaluating HBCTR versus usual care. The primary clinical outcomes were 6 min walk test (6 MWT), VO2max, and left ventricular ejection fraction (LVEF). Outcomes were pooled as mean differences (MD), standardized mean differences (SMD) for QoL, and risk ratios (RR) for binary data using RevMan 5.4.1 (random-effects). Quality assessment was performed using the ROB-2 scale, and publication bias was analyzed using funnel plots. Results:Twelve studies comprising 1392 patients were included. HBCTR significantly improved 6MWT distance (MD: 18.76; 95% CI: 10.35-27.18; p < 0.0001), VO2max (MD: 3.53; 95% CI: 2.42-4.65; p < 0.00001), and LVEF (MD: 2.03; 95% CI: 0.15-3.91; p = 0.03). Significant reductions were observed in systolic blood pressure (MD: -3.09 mmHg; 95% CI: -5.50 to -0.69; p = 0.01), alongside improved medication adherence (RR: 1.25; 95% CI: 1.08-1.43; p = 0.002). QoL outcomes showed small and inconsistent improvements, while lipid parameters, anxiety, and depression demonstrated no consistent benefit. Conclusion:Compared to usual care, HBCTR improved functional capacity, systolic BP, VO2 max, LVEF, and adherence, while mental health and lipid outcomes remained inconclusive.
