Search Results (1,335)

Public health impacts of non-optimal temperatures and air pollution have received insufficient attention in Southeast Europe, one of the most air-polluted regions in Europe, simultaneously pressured by climate change. This study employed a multimodal approach to characterize the microclimate and air quality and conduct a health impact assessment in the three biggest cities in Bulgaria. Simulation of atmospheric thermo-hydrodynamics and assessment of urban microclimate relied on the Weather Research and Forecasting model. Concentrations of fine particulate matter (PM_2.5) and nitrogen dioxide (NO₂) were calculated with a land-use regression model. Ischemic heart disease (IHD) hospital admissions were linked to daily measurements at background air quality stations. The results showed declining trends in PM_2.5 but persistent levels of NO₂, especially in Sofia and Plovdiv. Distributed lag nonlinear models revealed that, in Sofia and Plovdiv, PM_2.5 was associated with IHD hospitalizations, with a fifth of cases in Sofia attributable to PM_2.5. For NO₂, an increased risk was observed only in Sofia. In Sofia, the risk of IHD was increased at cold temperatures, while both high and low temperatures were associated with IHD in Plovdiv and Varna. Short-term effects were observed in response to heat, while the effects of cold weather took up to several weeks to become apparent. These findings highlight the complexity of exposure–health interactions and emphasize the need for integrated policies addressing traffic emissions, urban design, and disease burden. Full article

Background: Cardiac rehabilitation (CR) and mechanics are individually associated with cardiovascular outcomes in ischemic heart disease (IHD); however, their interaction remains less defined. We hypothesized that a 36-session CR program improves cardiac strain and torsional mechanics in IHD patients. Methods: Ninety IHD patients on guideline-directed medical therapy with complete revascularization were prospectively enrolled, of which 27 electively completed a 36-session standardized exercise CR program. Speckle-tracking echocardiography was utilized to assess left ventricular (LV) global longitudinal strain (GLS) and peak twist, and right ventricular free wall strain (RVFWS) at baseline and after program completion. Participants were propensity-scoring matched 1:1 with 27 patients who declined participation (No-CR). Results: Clinical characteristics were similar between groups (mean age: 63 ± 10 years, 82% male, 31% three-vessel coronary artery disease). When compared with baseline, the CR group experienced a significant improvement in LV GLS (−14.9 ± 2.9 vs. −16.2 ± 3.1%, p = 0.003), with a numerical but non-significant increase in peak LV twist (14.4 ± 7.4 vs. 16.8 ± 5.3°, p = 0.162). The No-CR group showed significant deterioration in RVFWS (−22.9 ± 4.6% vs. −19.3 ± 5.4%, p = 0.009), with no other changes including in GLS (−14.8 ± 3.1 vs. −15 ± 3.3%, p = 0.831). Follow-up comparisons between CR versus No-CR revealed significantly greater peak LV twist (16.8 ± 5.3 vs. 12.1 ± 4.2°, p = 0.001) and a healthier RVFWS (−22.2 ± 4.5 vs. −19.3 ± 5.4, p = 0.044) in CR participants. Conclusions: CR in patients with IHD improved LV GLS and, compared with No-CR, conferred better LV twist and RVFWS. Full article

The heart exhibits inherently nonlinear and chaotic electrical dynamics, making the early detection of myocardial ischemia (MI) challenging using traditional electrocardiography (ECG) or standard magnetocardiography (MCG). In this study, we propose an engineering-oriented framework that integrates classical nonlinear dynamics with machine-learning-based analysis, termed the Magnetocardiography Chaotic Dynamics Map (MCDM), to reconstruct nonlinear phase-space trajectories from 36-channel MCG recordings and capture differences in reconstructed nonlinear dynamics associated with ischemic conditions. Morphological and quantitative analyses of the MCDM patterns reveal marked differences between healthy and ischemic subjects. Using a machine-learning classifier trained on HOG and LBP descriptors, the proposed MCDM-based model achieved an accuracy of 92.19%, a sensitivity of 88.75%, a specificity of 95.63%, an F1-score of 91.91%, and an AUC of 89.80%, demonstrating effective discriminative capability for early ischemia screening. Owing to its computational simplicity and noninvasive nature, the proposed MCDM framework represents a promising tool for scalable screening of ischemic heart disease. Full article

Ischemic heart disease (IHD) remains a leading cause of morbidity and mortality worldwide. Myocardial ischemia–reperfusion injury (MIRI) is a significant contributor to cardiac tissue damage, resulting from an abrupt reduction in blood flow that leads to a reduction in the supply of oxygen and nutrients. The resulting hypoxia triggers severe cellular injury and impairs organ function. Hypoxia-inducible factors (HIFs) play a central role in maintaining oxygen homeostasis in mammalian tissues. As primary oxygen sensors, HIFs trigger the transcriptional activation of a wide range of genes that facilitate cellular adaptation to reduced oxygen availability and assist in minimizing ischemic damage. Mitochondria are particularly vulnerable to hypoxic stress and are a major source of reactive oxygen species (ROS) during I/R injury. Stabilization of HIFs has been shown to reduce loss of cardiomyocytes under these conditions, highlighting the importance of HIF-dependent pathways in preserving mitochondrial integrity and promoting cell survival. Collectively, these observations suggest that hypoxia, HIF signaling, and mitochondrial dysfunction are tightly interconnected processes in the pathogenesis of IHD. This review, therefore, focuses on the interaction between hypoxia-driven HIF responses and mitochondrial regulation, emphasizing their implications for therapeutic strategies in managing IHD. Full article

Background: Cardiac ischemia (CI) remains a leading cause of death worldwide, prompting an ongoing search for new treatment options. This study explored and compared the preventive cardioprotective effects of polyphenols extracted from red (RGP) and white grape pomace (WGP) against isoproterenol (ISO)-induced myocardial ischemia, with a focus on their antioxidant and anti-inflammatory properties. Materials and Methods: Fifty male Wistar rats were divided into five groups: I—Saline, II—Saline+ISO, III—Ramipril+ISO, IV—WGP+ISO, and V—RGP+ISO. CI was induced in Groups II–V with ISO (45 mg/kg, on day 13), a dose widely used to reproducibly induce myocardial ischemic injury in experimental models. Electrocardiographic parameters, serum oxidative markers, cytokines, and tissue homogenates from the liver and heart were analyzed on day 14. Results: ISO significantly shortened the RR interval and increased the ventricular rate, without significant modulation by any treatment. The reduction in R-wave amplitude caused by ISO was lessened in all treated groups, with RGP showing values closer to Saline (RGP+ISO vs. Saline, p = 0.329). No differences were found among groups for PR segment, QRS duration, QT, or QTc intervals. Furthermore, all treated groups (III–V) showed significant improvements in oxidative and inflammatory markers compared to Saline+ISO (p < 0.05), with RGP demonstrating the strongest antioxidant activity by maintaining MDA and NO levels close to Saline (RGP+ISO vs. Saline, p > 0.05), while WGP exhibited superior anti-inflammatory effects in cardiac tissue by preserving IL-6 and IL-1β levels comparable to controls (WGP+ISO vs. Saline, p > 0.05). Conclusions: Grape pomace, especially RGP, may offer cardioprotection by decreasing oxidative stress, while WGP more effectively reduces inflammation. The complementary antioxidant and anti-inflammatory effects observed suggest that combining GP extracts may represent a promising hypothesis for future cardiovascular research. Full article

Background/Objectives: Cardiovascular (CV) and cerebrovascular diseases, primarily attributed to atherosclerosis, stand as leading global causes of morbidity and mortality. This study aims to evaluate the impact of preclinical atherosclerosis parameters, including intima-media thickness (IMT) and arterial stiffness, in a seven-year follow-up of 100 patients with CV risk factors but no known history of CV or cerebrovascular diseases. Methods: Between April 2014 and December 2015, 100 patients presenting with suspected ischemic heart disease were enrolled. The study integrates the color Doppler examination of the supra-aortic trunks with the evaluation of preclinical parameters of atherosclerosis, such as intima-media thickness (IMT), βeta index, and pulse wave velocity (PWV), as well as echocardiographic evaluations, including global longitudinal strain (GLS). CV risk factors, metabolic syndrome, and insulin resistance were assessed and measured for each patient using the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR). Two- and seven-year follow-ups assessed various CV events. Results: The study population comprised 67% males and 33% females. Metabolic syndrome, impaired fasting glycemia and hypertension were prevalent. The mean value of IMT was 1.21 ± 0.26 mm, and PWV was 8.47 ± 2.14 m/s. The 7-year follow-up identified IMT, PWV, and HOMA-IR as strong positive predictors of cardiovascular events, with PWV emerging as a particularly sensitive indicator of early events. Conclusions: Insulin resistance and cardiovascular risk factors may contribute to early alterations in myocardial and vascular function, even in the absence of overt disease. PWV, as a recognized surrogate marker of arterial stiffness, may serve as a sensitive tool for the early prediction of cardiovascular events. A comprehensive screening, including the assessment of markers indicating subclinical vascular alterations, along with the implementation of preventive interventions, is crucial for populations at risk. Full article

Ischemic heart disease (IHD) remains a leading cause of global morbidity and mortality despite advances in prevention, diagnosis, and therapy. Traditional clinical risk scores and biomarkers often fail to fully capture the complex molecular processes underlying atherosclerosis, myocardial infarction, and ischemic cardiomyopathy, leaving substantial residual risk. MicroRNAs have emerged as promising regulators and biomarkers of cardiovascular disease, among which microRNA-21 (miR-21) has attracted particular attention. MiR-21 is deeply involved in key pathophysiological mechanisms of IHD, including endothelial dysfunction, vascular inflammation, vascular smooth muscle cell proliferation, plaque development and vulnerability, cardiomyocyte survival, and myocardial fibrosis. Accumulating clinical evidence suggests that circulating miR-21 holds diagnostic value across the ischemic continuum, from stable coronary artery disease to acute coronary syndromes, myocardial infarction, and ischemic heart failure. Moreover, miR-21 demonstrates prognostic relevance, correlating with plaque instability, adverse remodeling, heart failure progression, and long-term cardiovascular outcomes. Preclinical studies further indicate that miR-21 represents a double-edged therapeutic target, offering cardio protection in acute ischemic injury while contributing to fibrosis and maladaptive remodeling if dysregulated. This narrative review summarizes current evidence on the diagnostic, prognostic, and therapeutic utility of miR-21 in IHD, highlighting its clinical promise as well as key limitations and future translational challenges. Full article

Particulate matter (PM) is a significant contributor to air pollution-associated negative health effects, and cardiovascular disease patients are more susceptible to air pollution-mediated damage of the heart and vessels. The present study investigated the protective effects against PM-induced cardiovascular damage by classic cardiovascular drugs, as used for the standard therapy of cardiovascular disease patients. Male C57BL/6J mice were exposed to ambient PM_2.5 (<2.5 µm) for 3 days with or without treatment with the cholesterol-lowering drug atorvastatin (20 mg/kg/d) or the angiotensin-converting enzyme (ACE) inhibitor captopril (50 mg/kg/d). Both drugs mitigated PM_2.5-induced systolic blood pressure increases and partially prevented endothelial dysfunction, as reflected by a mixed effect on endothelial nitric oxide synthase phosphorylation. Both drugs ameliorated reactive oxygen species (ROS) formation and phagocytic nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX-2) expression in the vasculature of PM_2.5-exposed mice. Pulmonary ROS levels showed a minor improvement by the treatments, whereas Nox2 mRNA expression was not diminished. Only captopril showed some anti-inflammatory effects in the heart and lung of PM_2.5-exposed mice, whereas both drugs failed to reduce systemic inflammation measured in plasma. These findings offer new insights into potential mitigation strategies for PM_2.5-induced cardiovascular complications, particularly for patients at higher cardiovascular risk, like those with coronary artery or ischemic heart disease or hypertension. Full article

For the past decade, cell-based therapies have been the focus of research to investigate their potential to treat ischemic heart disease. The translation to human clinical studies depends on the demonstration of therapeutic efficacy and safety, particularly when transplanted in the subacute and chronic post-MI phase. A number of studies were identified that reported the effect of hiPSC-CMs on cardiac outcomes when transplanted at least 7 days post-myocardial infarction. The mean sample size of the published studies was 30 (±17) animals with a mean follow-up duration of 51 (±37) days. hiPSC-CM transplantation enhanced systolic function through augmented myocardial contractility, decreased infarct size, attenuated ventricular remodeling, and enhanced angiogenesis in the infarct and border zones in both small and large animal models. This effect was enhanced by co-transplantation with cells of vascular or adipose origin and is associated with high expression of VEGF in most studies. Despite this effect, transplanted hiPSC-CMs were structurally immature with limited survival at the endpoint. Epicardial delivery was associated with better efficacy outcomes and lower rates of arrhythmia. No study reported teratoma formation or immune rejection. From the current literature, there appears to be no consensus on the extent to which hiPSC-CMs improved systolic function, nor the degree to which this arises directly from integration of the new myocardium or from a paracrine-mediated mechanism. The nature of this paracrine mechanism and ways to improve the maturity and survival of implanted cardiomyocytes are issues that have yet to be resolved. In summary, while therapeutic benefit from cell therapy is clear, further research is required to establish whether the key mechanisms require a cellular component. Full article

Background: Left ventricular systolic dysfunction (LVSD) is a major determinant of prognosis in patients with ischemic heart disease. Electrocardiography (ECG) is widely available, inexpensive, and may aid in identifying patients at risk. We hypothesized that a composite score derived from multiple established ECG markers could improve the detection of LVSD in patients with stable angina. Methods: In this single-center, cross-sectional study, 177 patients undergoing elective coronary angiography for stable angina were included. Patients were classified as LVSD-negative (n = 123) or LVSD-positive (n = 54) based on echocardiographic ejection fraction. ECG parameters, including fragmented QRS, pathologic Q waves, R-wave peak time, QRS duration, and frontal QRS–T angle, were assessed. Independent predictors of LVSD were identified using multivariate logistic regression. A composite ECG score was constructed by assigning one point to each abnormal parameter. Model robustness was evaluated using bootstrap resampling (1000 iterations) and 10-fold cross-validation. Results: Multivariable analysis identified prior stent implantation, fragmented QRS, pathological Q waves, R-wave peak time, frontal QRS–T angle (log-transformed), and QRS duration as independent predictors of LVSD. ROC analysis demonstrated good discriminatory performance for R-wave peak time (AUC 0.804), QRS duration (AUC 0.649), and frontal QRS–T angle (AUC 0.825) measurements. The composite ECG score showed a stepwise association with LVSD: a score of ≥2 yielded high sensitivity (88%) and negative predictive value (97%), whereas a score of ≥3 provided high specificity (100%) and positive predictive value (100%). Bootstrap resampling and cross-validation confirmed model stability and strong discriminatory performance (mean AUC, 0.964; accuracy, 0.91). Conclusions: A simple composite ECG score integrating multiple established ECG markers is associated with the robust detection of LVSD in patients with stable angina. Although not a substitute for echocardiography, this score may support early risk stratification and help identify patients who warrant further imaging evaluations. External validation in larger and more diverse populations is required before routine clinical implementation of this model. Full article

Despite significant improvements in revascularization strategies and medical management, ischemic heart disease (IHD) remains the top cause of mortality and disability worldwide. The myocardium lacks regenerative capacity and consequently, recovery depends on re-establishing microvascular integrity and sustaining angiogenesis to preserve viable myocardium. Emerging and novel bioengineering approaches, such as stem cells, extracellular vesicles (EVs), and matrix-based strategies, seek to address this unmet need by promoting neovascularization and structural restoration. However, clinical translation remains limited by poor engraftment, product variability, and arrhythmogenic risk. Large animal models provide a clinically relevant platform to thoroughly investigate these interventions and ideally enhance their translational potential. This review discusses cellular approaches leveraging stem and progenitor cells and acellular modalities using extracellular vesicles, growth factors, or extracellular matrix-based scaffolds with an emphasis on large animal translational models and clinical trials. Full article

Background and Objectives: Despite huge reductions in the incidence and mortality of cardiovascular disease (CVD) during the last decades, ischemic heart disease (IHD) is globally still a leading cause of death. Although females experience higher mortality, the clinical IHD guidelines do not distinguish between sexes, and despite added diagnostic procedures after introduction of computed coronary arteriography (CTA) the differences remain. This study aimed to describe and evaluate the effect, outcomes and sex disparities of the large number of diagnostic procedures not leading to invasive treatments. Materials and Methods: The study included 274,617 first-entry patients submitted to invasive coronary arteriography (ICA) or CTA 2000–2020, from the mandatory Western Denmark Heart Registry. Mortality was evaluated with Kaplan–Meier curves and further compared to background population. Results: Females constituted 34.1% of all first-entry diagnostic procedures but only 25.5% of those who subsequently underwent invasive treatment, demonstrating a substantially lower treatment rate compared to males. All-cause 10-year mortality was higher in females after treatment 1.26 (1.23–1.30) but lower in the non-treated patients 0.71 (0.67–0.72) at all time points. Comparing to the background population, all non-treated patients revealed lower mortality in all indications, except valves. Conclusions: Despite being referred for coronary diagnostication according to their CVD prevalence, females received less invasive treatments than males and presented with substantially higher mortality after invasive treatments. In variance, non-invasive treated females demonstrated significantly better survival than men both in intra-study comparisons and in assessment with background population mortality. Full article

Purpose: While migraine is linked to increased cerebrovascular risk, its association with non-arteritic anterior ischemic optic neuropathy (NAION) remains underexplored. Methods: We conducted a retrospective case–control study using population-based electronic medical records. NAION patients were compared to propensity score-matched controls regarding migraine prevalence and clinical characteristics. Results: From 2001 to 2022, among 6,566,619 patients, 1629 NAION cases (mean age 67 ± 13 years; 45% female) and 6433 propensity matched controls were identified. The prevalence of migraine was similar in both groups (3.8% vs. 3.3%, p = 0.3). Among migraine patients, those with NAION (n = 62, age 62 ± 11) and controls (n = 212, age 60 ± 11) had comparable baseline characteristics, except for congestive heart failure (9.7% vs. 2.4%, p = 0.027). Within the NAION cohort, migraineurs (n = 64) were younger (62 ± 12 vs. 67 ± 13 years, p < 0.001), and had lower rates of diabetes mellitus (35% vs. 57%, p < 0.001) and peripheral vascular disease (1.6% vs. 9.6%, p = 0.03). Female migraineurs developed NAION at a younger age than females without migraine (60 ± 12 vs. 69 ± 12 years, p < 0.001); no such difference was seen in males. Multinomial logistic regression revealed that migraine was independently associated with younger age at NAION onset, particularly in patients aged <59 (OR = 5.8, p = 0.001) compared with those >70. An independent 1:4 migraine to non-migraine matched cohort (n = 310) showed similar age-dependent trends. Conclusions: While migraine was not more prevalent among NAION patients, females with migraine developed NAION at a younger age and had fewer vascular comorbidities. Congestive heart failure was more prevalent among migraine patients who developed NAION, suggesting a potential contributory role of systemic hypoperfusion. Full article

Background: Obesity is a major health concern worldwide and the World Health Organization (WHO) has declared it a global epidemic. We aimed to analyze temporal trends of obesity prevalence worldwide. Methods: We used data of “The Global Health Observatory” of the WHO and analyzed data from the Global Burden of Disease (GBD) Study 2023. Obesity prevalence (crude estimates) among adults in different worldwide WHO regions and temporal trends from 1976 and 2016 were analyzed. Results: Obesity prevalence showed large regional differences. In 2016, obesity prevalence was highest in the WHO European region and the region of the Americas, at more than 20%, whereas prevalence was lower in the WHO African region, the WHO Western Pacific region and the WHO South-East Asia region, at less than 10%. The absolute increase from 1976 to 2016 comprised an increase of 19.7% in the region of the Americas, of 14.8% and 14.2% in the WHO European region and the WHO Eastern Mediterranean region, followed by 7.3% in the WHO African region, 6.0% in the WHO Western Pacific region, and 4.2% in the WHO South-East Asia region. We observed a substantially higher prevalence of obesity in females. High BMI has risen sharply in rank worldwide, now ranging among the top six global risk factors for death. Major BMI-related causes include ischemic heart disease, type 2 diabetes mellitus, hypertensive heart disease, and ischemic stroke. Conclusions: Obesity prevalence showed large regional differences and was highest in Europe and America. The prevalence of obesity increased worldwide between 1976 and 2016. Obesity prevalence was higher in females than in males. The importance of obesity for premature death increased between 1990 and 2023. Full article

The cardiac extracellular matrix (ECM) is a dynamic, tissue-specific scaffold essential for cardiovascular development, homeostasis, and disease. Once considered a passive structural framework, the ECM is now recognized as an active regulator of mechanical, electrical, and biochemical signaling in the heart. Its composition evolves from embryogenesis through adulthood, coordinating cardiomyocyte maturation, chamber formation, and postnatal remodeling. In pathological states, diverse stimuli—including ischemia, pressure or volume overload, metabolic dysfunction, and aging—disrupt ECM homeostasis, triggering fibroblast activation, myofibroblast transformation, and maladaptive collagen deposition. These processes underpin myocardial fibrosis, a key driver of impaired contractility, diastolic dysfunction, arrhythmogenesis, and heart failure across ischemic and non-ischemic cardiac diseases. ECM alterations also exhibit age- and sex-specific patterns that influence susceptibility to cardiovascular pathology. Advances in imaging and circulating biomarkers have improved fibrosis assessment, though limitations persist. Therapeutic strategies targeting ECM remodeling, including modulation of profibrotic signaling pathways, non-coding RNAs, cellular therapies, and nano-delivery systems, show promise but remain largely experimental. Collectively, expanding knowledge of ECM biology highlights its central role in cardiovascular physiology and pathology and underscores the need for targeted diagnostic and therapeutic innovations. Full article