Search Results (1,391)

Aims: Coronary heart disease (CHD) associated with rheumatoid arthritis (RA) is a primary driver of mortality in RA patients. In this study, we sought to establish a combined rat model of CHD and RA by integrating cardiac ischemia/reperfusion (I/R), high-fat diet (HFD), and intradermal administration of bovine type II collagen emulsified in complete Freund’s adjuvant. The aim of constructing this model is to investigate and analyze the pathogenesis of RA-induced CHD under the modulation of HFD and cardiac I/R exposure. Methods and Results: Sixty-four male Sprague–Dawley rats were randomly categorized into eight groups (n = 8 per group): control, I/R, HFD, collagen-induced arthritis (CIA), I/R + CIA, HFD + CIA, I/R + HFD, and I/R + HFD + CIA groups (n = 8 per group). We applied Synchrotron radiation-based X-ray micro-computed tomography (micro-CT) to observe the structural changes within the model over time. To further elucidate molecular mechanisms, transcriptome RNA-seq analysis was carried out to identify key signaling pathways, with particular emphasis on the homeostasis of Toll-like receptor 4 (TLR4)/Myd88 signaling in the ischemic myocardium. Furthermore, we conducted in vivo shRNA-mediated knockdown of polymerase I and transcription release factor (PTRF) and evaluated the co-localization of PTRF and TLR4 through immunofluorescence experiments. It is worth mentioning that our rat model of RA-induced (CHD) under a high-fat diet effectively manifested the relevant pathological features that align with the Traditional Chinese Medicine (TCM) definition of “bi” syndrome. The results indicate that the combined stimulation of HFD and CIA significantly elevated cardiac injury markers (CK-MB, LDH, CRP, and c-TNT) and was accompanied by a more severe expansion of the infarct area and increased cardiomyocyte apoptosis compared to the I/R group alone. In addition, the histopathological evaluation revealed significantly aggravated myocardial inflammation and fibrosis deposition, accompanied by extensive areas of tissue damage, further indicating a state of heightened inflammation and severe cardiac degenerative changes. Consistently, myocardial tissues from rats in the I/R + CIA + HFD group exhibited robust activation of the TLR4/MyD88 signaling pathway and a pronounced elevation in the p-JNK/JNK ratio. Moreover, pronounced co-localization between PTRF and TLR4 was evident in small vessels surrounding the infarcted myocardium. Importantly, AAV-mediated knockdown of PTRF attenuated the HFD- and CIA-induced exacerbation of myocardial injury in I/R rats. Conclusions: We successfully established a rat model of CHD with rheumatic syndrome using I/R in combination with RA and HFD. The present findings suggest that the PTRF-related TLR4/MyD88-JNK signaling pathway may act as an important regulatory mechanism underlying myocardial injury aggravated by combined HFD and CIA stimulation. Full article

Background/Objectives: Epidemiological studies over the first decades of the 21st century have reported a decrease in cardiovascular disease (CVD) morbidity and mortality. Changes in coronary care for acute myocardial infarction (AMI) over these years, including the COVID-19 pandemic period, have been less studied in Eastern and Central Europe. The study aimed to assess changes in coronary care—the time of medical assistance and treatment—for AMI patients over 2000–2023 in urban Kaunas residents aged 25–64. Methods: The data source was study cases from the Kaunas Ischemic Heart Disease Registry (Registry)—Kaunas city residents aged 25–64 years included in the Registry according to MONICA project protocol evaluation methodologies. Data were analyzed by sex and age group (25–54 and 55–64 years). Descriptive statistics (chi-square and z-score values) were used to evaluate the data; the significance level was p < 0.05. A logistic regression analysis was performed to assess the odds ratios of death within 28 days across six time periods. Results: The proportion of AMI patients hospitalized up to 2 h from the onset of pain accounted for about one-fifth of all hospitalized patients in 2000–2016, while in 2017–2023, it significantly decreased. In 2017–2023, compared with 2000–2004 and 2009–2016, significantly fewer men who developed AMI were hospitalized within the first 2 h of emergency presentation (p < 0.05). Over the whole study period, fewer women with AMI were hospitalized within the first 2 h of pain as compared to men (p < 0.05). There were no significant differences in time from pain onset to hospitalization between the age groups. At the same time, from 2009 to 2012, more young AMI patients were hospitalized within the first 2 h (p < 0.05). Percutaneous coronary angioplasty (PTCA) with stenting (PCI) increased 30 times from 2000–2004 to 2020–2023. PCI has been the most available treatment for men with AMI since 2009 and stayed stable from 2013 (66.0%) until 2023 (72.1%). Women with AMI tended to get less PCI, PTCA, and coronary artery bypass grafting (CABG) than men. The pre-pandemic and COVID-19 periods did not differ in the proportions of reperfusion treatment methods used in both men and women. Thrombolysis was very rare, and since 2017, it has not been used in Kaunas because PCI has become more accessible. PCI (2000–2016) and CABG (2009–2016) were more prevalent among the 25–54-year-old AMI patients (p < 0.05). From 2017 to 2023, there were no differences between age groups in the reperfusion procedures used, nor were there differences in treatment between these groups during the pre-pandemic (2017–2019) and peri-COVID-19 pandemic (2020–2023) periods. Conclusions: In Kaunas, the treatment of patients with AMI has improved significantly over the past 20 years. The use of PCI has increased greatly, and the rate of CABG surgery stayed stable, while only every fifth patient has been admitted to the hospital in a timely manner. Men were more likely to receive PCI, and older patients were more likely to undergo CABG. Compared to the period of 2000–2004, the chance of dying within 28 days after AMI was significantly lower in 2017. Full article

Ischemic heart disease (IHD) remains a leading cause of death globally. This study aims to analyze the burden of IHD in Central Asia and in individual countries of the region from 1990 to 2021, through a comparison of trends in incidence, prevalence, mortality, and disability-adjusted life years. Using data from the Global Burden of Disease (GBD) 2021 study, we extracted annual estimates for the Central Asian region, Kazakhstan, Kyrgyzstan, Uzbekistan, Tajikistan, Turkmenistan, Georgia, Armenia, Azerbaijan, and Mongolia. Metrics were reported as age-standardized rates per 100,000 population. Temporal trends were quantified using Average Annual Percent Change based on joinpoint regression models. A stratification by sex and age groups was done. Central Asia consistently maintained a higher IHD burden than the global average. While global age-standardized incidence rates per 100,000 population fell, Central Asia’s rates per 100,000 population rose from 641.97 in 1990 to 801.56 in 2021. Age-standardized death rates per 100,000 population in the region peaked in the mid-1990s following the dissolution of the Soviet Union but decreased overall from 320.47 in 1990 to 265.51 in 2021. However, this remains significantly higher than the 2021 global rate per 100,000 population of 108.73. Uzbekistan exhibited the highest growth in prevalence and incidence rates per 100,000 population, while Georgia demonstrated the largest reduction in DALYs rates per 100,000 population. Men demonstrated a higher burden across most metrics, although the sex gap narrowed in older populations. Central Asia faces rising incidence rates of IHD and burden levels that far exceed global averages. The significant heterogeneity among countries suggests that region-wide generalizations are insufficient and highlights the critical need for targeted, country-specific prevention programs and health system interventions. Full article

Objective: Atherosclerotic renal artery stenosis (ARAS) is increasingly prevalent among aging populations and in patients with diabetes, hyperlipidemia, aortoiliac obstructive disease, coronary artery disease, and/or hypertension. Patients with severe ARAS are at a substantially elevated risk of cardiovascular disease, recurrent congestive heart failure, stroke, ischemic nephropathy, and chronic kidney disease. Therefore, the ARAS-TR study aims to evaluate the effect of renal artery stenting on the clinical outcomes in patients with severe ARAS and renovascular hypertension. Materials: This study was conducted as a multicenter, prospective study between July 2024 and September 2025. It encompassed 278 patients with angiographically confirmed severe ARAS who underwent renal artery stent implantation. Patients were subsequently monitored for 6 months. A paired-samples t-test was used to compare continuous variables pre- and post-intervention, while categorical variables were analyzed using the Pearson chi-square test and Fisher’s exact test. Results: The mean age of the patients was 63.6 [±13.4] years, and the male gender ratio was 52.5%. After renal artery stenting, systolic and diastolic blood pressures decreased significantly at the 6-month follow-up compared with the pre-procedure levels (SBP 166.99 [21.24] vs. 135.40 [15.69], p < 0.001; DBP 96.28 [13.03] vs. 80.39 [11.03], p < 0.001, respectively). GFR (61.23 [28.33] vs. 63.35 [26.36], p = 0.029) and creatinine (1.40 [0.93] vs. 1.29 [0.66], p = 0.004) levels improved compared to baseline. The mean number of antihypertensive drugs required for patients to remain normotensive decreased significantly (3.19 [1.04] vs. 2.48 [1.13], p < 0.001) during the follow-up period. Conclusions: Percutaneous renal artery intervention appears to be a promising and safe strategy for carefully selected high-risk patients presenting with severe ARAS, renovascular hypertension, and non-atrophic kidneys. In this specific clinical context, restoring renal artery patency through percutaneous stenting was associated with improved renal function and observed reduction in the burden of antihypertensive drugs required to sustain normotension. Full article

Colchicine has emerged as a prominent anti-inflammatory candidate in cardiovascular medicine, supported by a hierarchy of evidence spanning chronic and acute coronary syndromes, post-myocardial infarction care, revascularization, atrial fibrillation, pericardial disease, heart failure, peripheral arterial disease, and mechanistic translational models. Across this literature, the most mature study architecture and the strongest clinical support are derived from completed randomized trials in chronic coronary disease and secondary prevention, where colchicine has been shown to prevent major cardiovascular events (MACEs) when added to standard of care. The clearest clinical benefits are the reduction in non-fatal ischemic events in atherosclerotic disease, prevention of recurrent pericarditis and postoperative atrial fibrillation, and attenuation of inflammatory and plaque-related markers. By contrast, mixed or lower-tier evidence renders its application less consistent in acute coronary syndromes, ST-elevation MI (STEMI), percutaneous coronary intervention (PCI)-related hard outcomes, and heart failure, while a definitive mortality benefit has not been demonstrated. Overall, colchicine is best understood as a targeted clinical adjunct whose value depends heavily on precise indication, timing, dose, gastrointestinal tolerability, and the maturity of the supporting evidence. Full article

Heart failure (HF) is a clinical syndrome characterized by structural or functional cardiac abnormalities that impair ventricular filling or ejection, leading to inadequate systemic perfusion and elevated intracardiac pressures. Current epidemiological estimations declare approximately 26 million patients affected worldwide are living with HF. While ischemic heart disease remains the primary etiology, there is a wide range of behavioural factors that significantly influence disease onset and progression. This review focuses on the evidence for established risk factors, including smoking, excessive alcohol consumption, obesity, physical inactivity, poor diet, sleep disorders, and psychological stress. Furthermore, we discuss other novel determinants such as electronic nicotine delivery systems (ENDS), cannabis, high-dose caffeine, and psychostimulants. The basic mechanistic pathways, including endothelial dysfunction, oxidative stress, neurohormonal activation, and direct myocardial toxicity, are also pointed out and reviewed in this paper. The aim of this study is to integrate epidemiological data with pathophysiological insights to identify priority targets for primary prevention and highlight areas for future research. Full article

Heart failure (HF) and myocardial infarction (MI) are interconnected syndromes with overlapping pathogenic pathways, including ischemia, neurohormonal activation, and maladaptive remodeling. Hypoxia-response genes, lipid-handling genes, and extracellular matrix (ECM) genes each influence these processes. Understanding their integrated roles can uncover biomarkers and targets. A systematic literature search was conducted (PubMed, Web of Science, and Scopus; 2000–2026; English-only, following PRISMA guidelines) to identify studies on key genes in hypoxia signaling, lipid metabolism, and ECM remodeling in MI/HF. Acute hypoxia (via HIFs) orchestrates metabolic adaptation and inflammation, but chronic HIF activation drives fibrosis and dysfunction. In parallel, genes controlling triglyceride and cholesterol handling (e.g., LPL, APOC3) influence energy supply and vascular risk. Variants in these genes modulate plasma lipids and MI/HF risk. For example, genetic loss-of-function in APOC3 lowers triglycerides and reduces coronary risk. ECM-related genes (e.g., COL4A1, LRP1) govern fibrosis and vascular integrity. Mutations in COL4A1 cause cardiomyocyte hypertrophy and severe fibrosis, while LRP1 regulates matrix remodeling and is upregulated in ischemic myocardium. Throughout, gene functions span acute repair versus chronic maladaptation. Findings derive from mixed sources: rodent models and cell studies demonstrate mechanistic links, while human genetics and cohorts link gene variants to HF/MI outcomes. Many promising biomarkers (e.g., circulating ITGA1) are preliminary, lacking large prospective validation. Not all cited therapeutic ideas have been tested in the treatment of human cardiac disease. The literature mix of species, models, and patient cohorts introduces heterogeneity. Full article

Background/Objectives: Frank’s sign (FS), an acquired diagonal earlobe crease, has been associated with underlying cardiovascular (CV) disease. Pneumonia, a leading cause of hospitalization, may trigger CV events. FS may help identify patients at increased risk of CV complications following pneumonia. We aimed to evaluate the association between FS and CV events following pneumonia. Methods: We conducted a single-center prospective cohort study of internal medicine patients hospitalized with community-acquired pneumonia at a secondary hospital in Switzerland, followed for 18 months. FS was assessed at inclusion by trained investigators. Baseline characteristics were recorded. The primary outcome was a composite of CV endpoints: new-onset atrial fibrillation/flutter, myocardial infarction, hospitalization for heart failure, peripheral arterial ischemic events, or stroke. Events were identified through hospital records and general practitioner data between 2020 and 2023. Results: Among 203 patients (median age 76.0 years [IQR 65.0 to 83.0]; 41.4% female), 71.2% had FS. During follow-up, 103 CV events occurred. In univariate Cox analysis, FS was associated with an increased hazard of CV events (p = 0.042). After adjustment for confounders, FS was not significantly associated with CV events (HR 0.97; 95% CI 0.59–1.59). Only a history of CV disease and CV risk factors were associated with an increased hazard of subsequent cardiovascular events following pneumonia. Conclusions: In this population of patients hospitalized with pneumonia, Frank’s sign was not independently associated with cardiovascular events and appears to reflect underlying cardiovascular risk burden. It should not be interpreted as an independent prognostic marker. Full article

Healthcare-associated infections (HAIs) are clinically relevant complications in critically ill stroke patients, particularly in neurological intensive care settings, where severe neurological injury, dysphagia, immobilization, invasive device exposure, and prolonged hospitalization increase infection susceptibility. Romanian data focused on deceased stroke patients admitted to neurological intensive care units remain limited. This retrospective descriptive single-center hospital-based study, supported by focused literature contextualization, was conducted in the Neurological Intensive Care Unit of the Brașov County Emergency Clinical Hospital, Romania. Adult stroke patients who died during hospitalization over a six-year observation period were included. Clinical data were extracted from a working hospital database and analyzed descriptively after data cleaning and harmonization. The final cohort comprised 190 deceased stroke patients; ischemic stroke was documented in 69.5% and hemorrhagic stroke in 28.9%. Hypertension (73.7%) and ischemic heart disease and/or previous myocardial infarction (60.0%) were the most frequently recorded comorbidities. Pneumonia was the dominant documented infectious complication, recorded in 52.6% of patients, followed by urinary tract infection (11.6%), pressure sore-related infection (4.7%), and sepsis-related coding (6.8%). The median in-hospital survival interval was 6 days (IQR 3.0–10.75). Because year-by-year stratification was not sufficiently robust, the temporal component was interpreted only in aggregate form. These findings provide a descriptive hospital-based profile of documented infectious complications in a fatal stroke ICU cohort and support the need for more standardized infection documentation and better linkage between clinical and microbiological data in neurocritical care settings. Full article

Ischemic heart disease (IHD) remains the leading cause of chronic heart failure (HF) worldwide, yet the biological processes underlying this transition are not fully elucidated. Growing evidence indicates that chronic, low-grade inflammation acts as a pivotal link between ischemic injury and progressive myocardial dysfunction. Our review is the most up-to-date and structured synthesis on the pathophysiological pathways, biomarkers, and therapeutic implications of subclinical inflammation in patients with IHD at risk of developing HF. Following acute or repetitive ischemic episodes, persistent immune activation—mediated through interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α)—promotes endothelial dysfunction, microvascular instability, and extracellular matrix remodeling. These mechanisms culminate in ventricular stiffness, diastolic impairment, and adverse structural remodeling, even when left ventricular ejection fraction is preserved. Biomarkers such as Galectin-3, cancer antigen 125 (CA125), and high-sensitivity C-reactive protein (hsCRP) provide valuable insight into the interplay between fibrosis, congestion, and systemic inflammatory load, supporting early detection of subclinical myocardial injury. Advanced imaging modalities, including strain echocardiography and cardiac magnetic resonance imaging (MRI) mapping, enhance the phenotypic characterization of inflammatory cardiomyopathy. Understanding and targeting these inflammatory pathways may open new avenues for precision-based prevention and treatment, ultimately improving outcomes across the IHD–HF continuum. Full article

Background and Objectives. Over the past two decades, 28-day acute myocardial infarction (AMI) case-fatality rates have declined globally due to improved treatment and secondary prevention. This study aimed to evaluate AMI case-fatality levels and trends in the Kaunas population aged 25–64 from 2000 to 2023. Materials and Methods. Data were obtained from the population-based Kaunas Ischemic Heart Disease Registry, operating under the WHO MONICA standards. The study included adults with AMI or coronary heart disease death registered within 28 days from the onset of AMI. Case-fatality was defined as the proportion of AMI deaths among all AMI cases. Trends were assessed using JoinPoint regression. Results. From 2000 to 2023, 28-day AMI case-fatality in males showed no significant change, while in females it increased by 2.5% per year (p = 0.002). In-hospital AMI case-fatality remained stable in both sexes. Males had higher average AMI case-fatality rates than females in both age groups (25–54 and 55–64). Only females aged 55–64 showed a significant rise in AMI case-fatality (3.0%/year, p = 0.002). A trend change point was identified in 2006 for males (no significant trend) and in 2010 for females, after which the AMI case-fatality rates increased. Among males, in-hospital AMI case-fatality decreased significantly from 2015 to 2023 (14.7%/year). Conclusions. Over the two decades, 28-day AMI case-fatality among 25–64-year-old-persons remained unchanged in males but increased in females. In-hospital AMI case-fatality showed no major change in either sex. Males consistently had higher AMI case-fatality rates with age. While aging did not affect AMI case-fatality trends in males, rates rose significantly among older females. Full article

Background: Rheumatic diseases (RDs) are associated with increased cardiovascular morbidity, including a 40% higher risk of atrial fibrillation (AF). While ablation has become the cornerstone of rhythm control, its safety in patients with rheumatic diseases remains poorly defined. Methods: Adults with a primary admission diagnosis of AF catheter ablation from 2016 to 2022 were identified using the National Inpatient Sample. We excluded patients with other forms of supraventricular tachycardia, pacemaker/defibrillator procedures, and atrioventricular junction ablations. Sociodemographic, clinical characteristics, and outcomes were compared between groups. Multivariate logistic regression adjusted for age, race, sex, and potential comorbid confounders was used to assess for independent associations. Results: A weighted total of 48,855 patients were included, 2.5% of which had RD. These patients were predominantly female, older, and had higher rates of renal dysfunction, hypertension, heart failure, history of stroke, ischemic heart disease, heart failure, and obstructive sleep apnea (all p < 0.001). Patients with RD had higher complication rates (12.9% vs. 8.8%, p < 0.001); specifically, bleeding (p < 0.001), infection (p = 0.008), pericardial (p = 0.003), and respiratory complications (p < 0.001). RDs were not found to be an independent predictor of complications, though there was a trend towards more complications (odds ratio 1.43, 95% confidence interval 0.97–2.11, p = 0.070). Conclusions: Patients with RD undergoing AF ablation were older, female, and had higher rates of comorbidities. This translated to higher unadjusted periprocedural complications in patients with rheumatic diseases. While RDs were not independently associated with adverse outcomes, a trend towards increased complications was observed. Full article

Background/Objectives: Fractional flow reserve (FFR) is the reference standard for assessing the functional significance of intermediate coronary stenoses and guiding revascularization. Although a universal ischemic threshold is applied to all epicardial vessels, potential physiological differences between coronary territories remain insufficiently explored. The aim of this study was to evaluate whether the functional significance of intermediate coronary stenoses differs according to coronary artery and to assess the clinical outcomes of FFR-guided deferral across coronary territories. Methods: This single-center retrospective study included patients who underwent single-vessel FFR assessment for angiographically intermediate lesions between 2019 and 2022. Patients with left main disease or multivessel physiological assessment were excluded. Clinical characteristics, FFR values, and long-term outcomes were analyzed according to the investigated coronary artery. Major adverse cardiovascular events (MACE) were defined as a composite of death, myocardial infarction, and urgent revascularization. Results: A total of 310 patients (corresponding to 310 coronary arteries) were included: 211 LAD, 68 RCA, and 31 LCX lesions. Overall, 18.7% of lesions had a positive FFR (≤0.80). The only variable identified in univariable analysis as being associated with FFR positivity was the coronary artery evaluated (p < 0.001). Positive FFR values were observed in 24.6% of LAD lesions, compared with 8.8% in the RCA and none in the LCX. Among patients with negative FFR for whom revascularization was deferred, five-year MACE-free survival was similar across coronary territories (p = 0.12). Conclusions: The functional significance of intermediate coronary stenoses varies according to the coronary territory, with LAD lesions more frequently reaching ischemic thresholds. However, deferral of revascularization based on negative FFR is associated with favorable long-term outcomes across all vessels, supporting a vessel-specific physiological interpretation of coronary stenoses. Full article

Background/Objectives: Type 2 diabetes mellitus (T2DM) is a multisystemic disease with overlapping metabolic, renal, and cardiovascular effects. Within the Diabetic@ project, which aims to characterize individuals with T2DM using real-world data extracted from electronic health records (EHRs), this substudy sought to develop a predictive model for two-year heart failure (HF) risk. Methods: Multicenter, retrospective study including T2DM individuals across eight Spanish hospitals (2013–2018). Data were extracted exclusively from EHRs’ unstructured free text using clinical natural language processing (cNLP) and mapped to SNOMED CT. At inclusion, individuals were categorized as having or not prevalent HF (pHF). Predictive modeling was performed in non-pHF to assess two-year risk of developing HF, termed incident HF (iHF). Logistic regression (LR), decision trees, random forest, and XGBoost were compared, selecting for accuracy and interpretability. Results: Of 588,756 individuals with T2DM, 84,197 (14.3%) had pHF. Among non-pHF, 353,371 (60%) were used for model development (90.7% training, 9.3% validation). iHF occurred in 13.6% of the training set and 11.4% of the validation set. Ischemic heart disease was present in 16.2% overall, 37.9% in pHF, and 12.6% in non-pHF. Glycosylated hemoglobin data was rarely reported (<15%). LR achieved the best performance (AUC-ROC 0.73) using 27 predictors. Reduced 12- and clinically refined 9-predictor models performed similarly, with the latter implemented in a web-based tool. Conclusions: Unstructured data from EHRs enabled development of a two-year HF risk model for individuals with T2DM, underscoring the potential of cNLP for risk stratification across the cardiovascular–renal–metabolic spectrum. Full article

Background/Objectives: Determining the cardiovascular cause of death, particularly distinguishing ischemic from congestive mechanisms, remains challenging in forensic practice, especially in early ischemia without definitive histological findings. Proteomic techniques and molecular profiling may provide complementary diagnostic information beyond conventional autopsy. Methods: We applied an untargeted high-resolution proteomic approach to postmortem cardiac tissue samples from cardiovascular (ischemic and congestive) and non-cardiovascular deaths. Identified proteins were analyzed using bioinformatic and differential expression workflows. Selected candidates were evaluated in peripheral blood samples for translational validation using statistical modeling, including regression analyses and receiver operating characteristic (ROC) curve assessment. Results: A total of 572 proteins were identified. Although no proteins fulfilled strict exclusivity criteria for a single cause-of-death group, differential expression analysis revealed distinct molecular patterns distinguishing ischemic, congestive, and non-cardiovascular deaths. Thirty-one proteins were differentially expressed between ischemic and congestive cases, including α-1 antitrypsin (AAT), plasma levels did not demonstrate statistically significant discrimination. In contrast, plasma Apolipoprotein A-IV (ApoA-IV) levels were significantly associated with ischemic death in regression models, and ROC analysis yielded a cutoff point with complete separation between ischemic and selected non-cardiovascular cases. However, the limited sample size warrants cautious interpretation due to potential overfitting. Conclusions: Postmortem cardiac proteomic profiling reveals biologically coherent molecular signatures associated with different cardiovascular causes of death. Although further validation in larger independent cohorts is required, ApoA-IV emerges as a promising candidate biomarker for ischemic cardiac death. Multimarker proteomic strategies may complement traditional autopsy to enhance diagnostic accuracy in forensic investigations, particularly in cases with equivocal morphological findings. Full article