Global Burden Of Cardiovascular Disease Research Articles

The Burden of Cardiovascular Disease attributable to High Fasting Plasma Glucose：Findings From the Global Burden of Disease Study 2019

AimHigh fasting plasma glucose (HFPG) is a key risk factor for cardiovascular disease (CVD). Few studies have evaluated the CVD burden attributable to HFPG globally. It is urgent to investigate the current epidemiological pattern and past trends of CVD attributable to HFPG. MethodsWe used the Global Burden of Disease Study (GBD) 2019 to describe the CVD burden attributable to HFPG in 2019 and evaluate temporal trends between 1990 and 2019. ResultsGlobal Disability-Adjusted Life Years (DALYs) cases and death cases of HFPG-related CVD were approximately 72,591,163 and 3,763,298 in 2019, with an increase of 107.4% and 114.6% compared with 1990, respectively. Despite the increases, the age-standardized DALYs rate (ASDAR) and age-standardized death rate (ASDR) of HFPG-related CVD contributed to 895.2 per 100,000 people and 48.4 per 100,000 people in 2019, with an estimated annual percentage change (EAPC) of ﹣0.22 and ﹣0.31, respectively, from 1990. The highest ASDAR and ASDR of HFPG-related CVD were in 2019 observed in the low-middle‐SDI (Socio‐demographic Index) and middle‐SDI regions. Low‐SDI and some low-middle‐SDI regions showed an increase in ASDAR and ASDR of HFPG-related CVD from 1990 to 2019. Males are more affected by HFPG-related CVD than females across all years. The CVD burden attributable to HFPG in the elderly are higher than those in the young in 2019. The main causes of the global CVD burden attributable to HFPG in 2019 were ischemic heart disease, stroke, and peripheral arterial disease. ConclusionThe CVD burden attributable to HFPG remains a serious public health challenge threatening human health worldwide. It is necessary to develop more targeted and specific strategies to reduce CVD burden attributable to HFPG, especially in males, elderly, and lower SDI regions.

Rising Cardiovascular Mortality Despite Increased Resource Utilization: Insights From the Nationwide Inpatient Sample Database.

Introduction The global burden of cardiovascular disease (CVD) has risen over the past decade, potentially escalating resource utilization, morbidity, and mortality. We analyzed trends in hospitalization for CVDs, outcomes of hospitalizations, and the impact of the COVID-19 pandemic on CVDhospitalizations between 2016 and 2020. Methods Adult CVD hospitalizations recorded in the2016-2020 nationwide inpatient sample (NIS) were identified using major diagnostic categories (MDC- class 5). The NIS is the largest all-payer repository of all hospitalizations in the USA within a calendar year. We compared sociodemographic factors andoutcomes (mortality, length of stay, and hospital charges) of CVD hospitalization before and during the pandemic using Pearson's χ2 tests.We used Stata ranking commands and ICD-10 (10th revision of the International Statistical Classification of Diseases and Related Health Problems) codes to identify the most recurring diagnoses associated with CVD mortality during the study period.Trends in mortality and resource use were assessed using theJonckheere-Terpstra trend test. Hospital charges wereadjusted for inflationusing the Medical Expenditure Panel Survey index. We used stepwise multivariate logistic regression analyses(P ≤ 0.05 for entry; P > 0.10 for removal) to identify covariates associated with cardiovascular mortality during the study period. Results Hospitalizations for CVDs rose from 4,283,502 in 2016 to 4,635,246 in 2019 (Ptrend< 0.001) and declined to 3,865,399 in 2020. 452,930 mortalities were recorded during the study period. In-hospital mortality rose from 111,090 (2.6%) in 2016 to 118,825 (2.8%) in 2020 (Ptrend< 0.001). Compared with the prepandemic years, mortality rates were higher during the pandemic (108,231 [2.8%] vs. 445,373 [2.5%]; P<0.001), and increased in hospitalizations for hypertensive heart disease with chronic kidney disease (CKD) (15,585[14.4%] vs. 45,873 [10.3%]; P<0.001), hypertensive heart disease with heart failure (7,468 [6.9%] vs. 21,378 [4.8%]), ventricular tachycardia (2,056 [1.9%] vs. 7,571 [1.7%]; P=0.022), and peripheral angiopathy with gangrene (1,191 [1.1%] vs. 3,118 [0.7%]; P<0.001). CVD hospitalizations totaled 80.3 million hospital days and 39.7 million hospital procedures during the period. The mean number of procedures (3 vs. 2) and mean length of hospital stay (5.6 vs. 4.5 days) increased during the pandemic (P<0.001). The mean hospital cost for CVD increased from US$ 69,394 in 2016 to US$ 89,728 in 2020 (Ptrend< 0.001). Conclusion CVD mortality increased despite increased resource use over the study period. Hospitalizations during the pandemic had poorer mortality and resource use outcomes than those in the preceding years.

The IRG1–itaconate axis protects from cholesterol-induced inflammation and atherosclerosis

Atherosclerosis is fueled by a failure to resolve lipid-driven inflammation within the vasculature that drives plaque formation. Therapeutic approaches to reverse atherosclerotic inflammation are needed to address the rising global burden of cardiovascular disease (CVD). Recently, metabolites have gained attention for their immunomodulatory properties, including itaconate, which is generated from the tricarboxylic acid-intermediate cis-aconitate by the enzyme Immune Responsive Gene 1 (IRG1/ACOD1). Here, we tested the therapeutic potential of the IRG1-itaconate axis for human atherosclerosis. Using single-cell RNA sequencing (scRNA-seq), we found that IRG1 is up-regulated in human coronary atherosclerotic lesions compared to patient-matched healthy vasculature, and in mouse models of atherosclerosis, where it is primarily expressed by plaque monocytes, macrophages, and neutrophils. Global or hematopoietic Irg1-deficiency in mice increases atherosclerosis burden, plaque macrophage and lipid content, and expression of the proatherosclerotic cytokine interleukin (IL)-1β. Mechanistically, absence of Irg1 increased macrophage lipid accumulation, and accelerated inflammation via increased neutrophil extracellular trap (NET) formation and NET-priming of the NLRP3-inflammasome in macrophages, resulting in increased IL-1β release. Conversely, supplementation of the Irg1-itaconate axis using 4-octyl itaconate (4-OI) beneficially remodeled advanced plaques and reduced lesional IL-1β levels in mice. To investigate the effects of 4-OI in humans, we leveraged an ex vivo systems-immunology approach for CVD drug discovery. Using CyTOF and scRNA-seq of peripheral blood mononuclear cells treated with plasma from CVD patients, we showed that 4-OI attenuates proinflammatory phospho-signaling and mediates anti-inflammatory rewiring of macrophage populations. Our data highlight the relevance of pursuing IRG1-itaconate axis supplementation as a therapeutic approach for atherosclerosis in humans.

Bridging Metabolic-Associated Steatotic Liver Disease and Cardiovascular Risk: A Potential Role for Ketogenesis.

The prevalence of cardiovascular diseases (CVDs) is a growing global health concern. Recent advances have demonstrated significant reductions in acute cardiovascular events through the management of modifiable cardiovascular risk factors. However, these factors are responsible for about 50% of the global cardiovascular disease burden. Considering that CVDs are one of the top mortality causes worldwide, the concept of residual cardiovascular risk is an important emerging area of study. Different factors have been proposed as sources of residual risk markers, including non-HDL particles characterization, as well as inflammation measured by serum and imaging technics. Among these, metabolic-associated steatotic liver disease (MASLD) remains controversial. Two opposing viewpoints contend: one positing that fatty liver disease merely reflects classical risk factors and thus adds no additional risk and another asserting that fatty liver disease independently impacts cardiovascular disease incidence. To address this dilemma, one hypothetical approach is to identify specific hepatic energy-yielding mechanisms and assess their impact on the cardiovascular system. Ketogenesis, a metabolic intermediate process particularly linked to energy homeostasis during fasting, might help to link these concepts. Ketogenic metabolism has been shown to vary through MASLD progression. Additionally, newer evidence supports the significance of circulating ketone bodies in cardiovascular risk prediction. Furthermore, ketogenic metabolism modification seems to have a therapeutic impact on cardiovascular and endothelial damage. Describing the relationship, if any, between steatotic liver disease and cardiovascular disease development through ketogenesis impairment might help to clarify MASLD's role in cardiovascular risk. Furthermore, this evidence might help to solve the controversy surrounding liver steatosis impact in CVD and might lead to a more accurate risk assessment and therapeutic targets in the pursuit of precision medicine.

Moderate-Intensity Swimming Alleviates Oxidative Injury in Ischemic Heart

The global burden of cardiovascular diseases is indisputable, as it claims nearly 18 million lives a year. In this current study, we aimed to prove that exercise, a cornerstone in cardiovascular disease management, emerges as a powerful tool in the pathology of myocardial ischemia. Male rats were divided into three groups: pre-swimming training + isoproterenol (ISO) treated, isoproterenol-treated, and control-sedentary. Myocardial infarction was induced by the subcutaneous injection of 1.0 mg/kg ISO. After the subsequent rest period, the animals swam for 3 weeks, every day for 25 min. At the end of the experiment, the serum levels of atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP), as well as the cardiac concentrations of reactive oxygen species (ROS), catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD) were determined. Our results indicate that both cardiac injury biomarkers (ANP, BNP) and ROS levels were significantly lower in swimming rats compared to the sedentary animals. Moreover, the level of enzymatic components of the intracellular antioxidant system, CAT, SOD, and GPx were increased in swimming animals after ISO-induced myocardial infarction. Our findings support the fact that moderate-intensity swimming training can be efficiently used to prevent myocardial infarction-induced ischemic injury, by inhibiting ROS production and strengthening intracellular antioxidant defense.

Global burden of cardiovascular diseases attributed to low physical activity: An analysis of 204 countries and territories between 1990 and 2019

BackgroundLow physical activity is a major risk factor for cardiovascular diseases (CVDs). This study aimed to estimate the global, regional, national, and sex-age-specific burden of CVDs attributed to low physical activity from 1990 to 2019. MethodsWe leveraged data from the Global Burden of Disease Study 2019 to compute the number of fatalities, disability-adjusted life years (DALYs), age-adjusted mortality rates (ASMR), and age-adjusted DALY rates (ASDR) attributed to CVDs resulting from low physical activity. Furthermore, we scrutinized the trends and correlations of these metrics in connection with the socio-demographic index (SDI) across 21 regions and 204 countries and territories. ResultsThe global deaths and DALYs due to CVDs caused by low physical activity increased from 371,042.96 [95 % UI: 147,621.82–740,490] and 6,282,524.95 [95 % UI: 2,334,970.61–13,255,090.08] in 1990 to 639,174.92 [95 % UI: 272,011.34–1,216,528.4] and 9,996,080.17 [95 % UI: 4,130,111.16–20,323,339.89] in 2019, respectively. The corresponding ASMR and ASDR decreased from 12.55 [95 % UI: 5.12–24.23] and 181.64 [95 % UI: 71.59–374.01] in 1990 to 8.6 [95 % UI: 3.68–16.28] and 127.52 [95 % UI: 53.07–256.55] in 2019, respectively. Deaths and DALYs attributed to low physical activity were initially higher in males but shifted to females after 70–74 age group. Both genders had increasing death rates, peaking at 80–84 age group. Most CVDs deaths and DALYs number are caused by ischemic heart disease. The highest burden of CVDs attributed to low physical activity was observed in North Africa and the Middle East. The lowest burden was observed in Oceania and High-income Asia Pacific. There was a distinctive 'n-shape' relationship between the regional SDI and the ASDR of CVDs attributed to low physical activity from 1990 to 2019. ConclusionThe global impact of CVDs stemming from low physical activity remains substantial and demonstrates substantial regional disparities. As individuals age, this burden becomes more prominent, particularly among females. Efficacious interventions are imperative to promote physical activity and mitigate the risk of CVDs across diverse populations and regions.

Plasma Lipid Profile and Apolipoproteins in Patients with Coronary Artery Diseases and Healthy Persons, in Sana'a City, Yemen

Background: Cardiovascular disease (CVD) is the primary cause of all disease loads and accounts for almost half of all fatalities. The early detection of coronary artery disease (CAD) has drawn a lot of attention because it is anticipated that the global burden of cardiovascular disease will rise by almost 75% by 2020. They are easily oxidized, which causes an increase in affinity for arterial proteoglycans and a decrease in affinity for LDL receptors. It demonstrates significant CAD importance.&#x0D; Objective: The measurement of plasma lipid profiles and apolipoproteins (ApoA-1, ApoB, and Apo B/A-1 ratio) in healthy individuals and patients suffering from coronary artery disease.&#x0D; Methods: In this cross-sectional comparative study, 90 Yemeni subjects aged 45 to 70 years were divided into three groups: Group I: 30 cases as CAD positive (CAD+). Group II: 30 cases CAD negative (CAD -). Group III: 30 healthy person was as control. A standardized questionnaire was administered to collect demographic and clinical data from participants. Venous blood (10 ml) was collected from each individual and divided into two portions. The first portion was 5 ml in plain tubes, ApoA-1 and Apo B vacuum tubes for freezing at -20°C until analysis. 5ml in a plain tube for measuring fasting blood glucose, and lipid profile.&#x0D; Results: ApoB and Apo B/A ratios were significantly higher in CAD+ and CAD− subjects compared to controls. In addition, ApoB and Apo B/A ratios were significantly higher in CAD+ subjects compared to CAD- subjects. (P. value =0.002). In contrast, Apo A-1 was significant in CAD+ compared to CAD- and controls, and not significantly different between CAD and controls P. value = (0.001, 0.032). Furthermore, FBS and LDL-c were significantly higher in CAD+ compared to CAD subjects (P value = 0.05). In contrast, HDL-c was significantly lower in CAD+ compared to CAD and controls, with no significant difference between CAD and controls (P value=0.038, 0.004, 0.70). However, TG was not substantially different between CAD- and controls, but it was significantly greater in CAD+ compared to controls (P. value =0.002, 0.09, 0.31). Nevertheless, there was no difference in TC between study groups (P. value = 0.08, 0.12, 0.98).&#x0D; Conclusions: The degree of CAD is significantly positively correlated with WHR. More important than overall obesity, abdominal obesity is a risk factor for coronary heart disease (CHD). A significant positive connection has been observed between the Apo B/Apo A ratio and CAD. One thing to think about as a CAD risk factor is Apo B.

The global burden of cardiovascular diseases and type 2 diabetes attributable to low physical activity, 1990-2019: an analysis from the global burden of disease study.

Cardiovascular diseases (CVD) and type 2 diabetes (T2D) account for the majority of the burden of noncommunicable disease caused by low physical activity (LPA). In order to inform future interventions, this study aims to assess the burden and trends in mortality and disability-adjusted life years (DALYs) of CVD and T2D attributable to LPA by year, location, sex, and age from 1990 to 2019. Mortality, DALYs, and their age-standardised rates (ASMR, ASDR) for CVD and T2D attributable to LPA were retrieved from Global Burden of Disease (GBD) 2019. The estimated annual percentage changes (EAPCs) were calculated using linear regression model to describe the trend over time. From 1990 to 2019, the number of deaths caused by both CVD and T2D due to LPA increased significantly globally. However, the overall ASMR and ASDR for CVD declined over this same period [EAPC for ASMR (CVD) = -1.44 (95% CI: -1.50-1.38), EAPC for ASDR (CVD) = -1.30 (95% CI: -1.35 to -1.25)]. In terms of disparities, ASMR (CVD) and ASDR (CVD) in North Africa and the Middle East were consistently higher than the global average; also, the sex difference in ASMR was greatest in Central Asia. ASMR among people aged 25-44 in high Socio-Demographic Index (SDI) region has increased significantly over the past three decades. ASMR (T2D) due to LPA showed an increasing trend year by year, with EAPC = 0.26 (95% CI: 0.13-0.39), and this rate increased faster in males than in females. Consistent with cardiovascular diseases, ASMR of type 2 diabetes attributable to LPA increased among people aged 25-44, while decreased in other age groups in high SDI region. Interventions targeting LPA are warranted in controlling the burden of cardiovascular diseases and type 2 diabetes. Countries should adapt strategies to their local contexts, considering the sex and age differences among their populations. The 25-44 age group should be given special attention to prevent the disease burden from worsening among younger people.

1379. Evaluation of Cardiovascular Disease Risk among People Living with HIV in Lebanon

Abstract Background Since the introduction of antiretroviral therapy (ART), People Living with HIV (PLHIV) have become more prone to developing chronic illnesses, such as cardiovascular diseases (CVD), than to suffer from AIDS related conditions. The global burden of CVD associated with HIV has tripled over the last two decades, especially in low/middle income countries. Scarce data exist on the prevalence of CVD and CVD risk factors among PLHIV in the Middle East and North Africa (MENA) region. Therefore, we aim to examine the prevalence of CVD risk factors and calculate the CV risk in a cohort of PLHIV in Lebanon. Methods This is a retrospective chart review conducted between 2018 and 2023 at an HIV clinic in a tertiary care center in Lebanon. The study population includes adult subjects receiving ART and with at least 6 months of undetectable viral loads. Data included demographics, laboratory values, HIV-specific data, and review of traditional CVD risk factors. Atherosclerotic Cardiovascular Disease (ASCVD) risk score was calculated using the American College of Cardiology Risk Estimator Plus, to estimate patients’ 10-year risk for developing ASCVD. Descriptive statistics were implemented to summarize the cohort’s characteristics and the prevalence of CVD risk factors. Results A total of 85 HIV-infected subjects were included in the analysis. Subjects’ characteristics are summarized in table 1. The majority were males (89.4%), and the mean age was 43.31±12.28 years. The prevalence of smoking, alcohol consumption, and illicit drug use was 70.6%, 54.1%, and 20%, respectively. The mean BMI was 26.1±5 kg/m². Additionally, 20.2 % of subjects had dyslipidemia, 6% had diabetes, and 15.5% had hypertension. The mean current CD4 cell count was 687.83 ±356 cells/ml. The cohort had a mean ASCVD risk score of 8.8%, higher than that of age-matched population (mean ASCVD risk score of US firefighters aged 40-44 years is 1.8%). Conclusion This study shows the prevalence of traditional CVD risk factors among PLHIV receiving effective ART in Lebanon. The cohort mean ASCVD risk score indicates an intermediate risk for developing CVD over the next decade. in the MENA region, we need larger studies to inform on the prevalence of CVD among PLHIV, and to develop guidelines to mitigate the risk. Disclosures All Authors: No reported disclosures

Abstract 16714: An Injectable Thermo-Responsive Hydrogel as a Tool for Cardiac Tissue Engineering Efforts: In vitro and in vivo Biocompatibility Assessment

Background: Heart failure (HF) is a major contributor to the global burden of cardiovascular disease. Current treatments for HF do not regenerate muscle nor function and so cardiac transplantation remains the only definitive treatment for HF. Thus, novel therapies for HF are still needed. To overcome this limitation, we engineered an injectable thermo-responsive hydrogel that transitions from a liquid-solution to a gel-based matrix upon reaching body temperature allowing for a liquid injection rapidly followed by gel localization. Previously, we demonstrated the potential of our hydrogel for cardiac tissue applications using primary cardiomyocytes. Goal: The goal of this project is to assess the biocompatibility of the thermo-responsive hydrogel with human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) and its effect on mice heart tissue. Methods: 3D cell culture: 9x104 hiPSC-CM were encapsulated for 21 days using 150μl of hydrogel solution (1.5% w/w) and cell function was assessed afterwards. Mouse intracardial injection: a left thoracotomy was performed via the fourth intercostal space in an adult C57BL/6 mouse model. Then, three injections of 10 μl of either (i) lipofectamine, (ii) hydrogel (1% w/w) or (ii) saline were injected into the left ventricle anterior wall. After injections, the thoracotomy site was closed, and the animals recovered. Four weeks post inject the tissues were harvested and prepared for studies. Results: We found that our hydrogel promotes hiPSC-CMs alignment, elongation with increased Cx43 localization and improved contraction function when compared with traditional 2D fibronectin controls. Furthermore, the in-vivo biocompatibility in mice (intracardial injection) proved that our hydrogel is well tolerated by cardiac tissue. Conclusion: Our results indicated that the injectable thermos-responsive hydrogel is a biocompatible material with potential to be used in cardiac tissue engineering efforts.

Temporal Trends of Enrollment by Sex and Race in Major Cardiovascular Randomized Clinical Trials

BackgroundWomen and racialized minorities continue to be underrepresented in cardiovascular (CV) trial outcomes data, despite comprising a significant global burden of CV disease. This study evaluated the impact of trial characteristics on the temporal enrollment of women and racialized minorities in prominent CV trials published in the period 1986-2023. MethodsMEDLINE was searched for CV trials published in The Lancet, the Journal of the American Medical Association, and the New England Journal of Medicine. Participant and investigator demographics, types of interventions, clinical indications, and funding sources were compared according to the enrollment of women or racialized minorities. ResultsFrom 799 studies, including 4,071,921 patients, the enrollment of women and racialized minorities significantly increased from 1986 to 2023 (both P ≤ 0.001). Although the enrollment of women varied by trial indication, comprising 25.0% of coronary artery disease, 35.2% of noncoronary and/or vascular disease, 13.8% of heart failure, 17.0% of arrhythmia, and 28.7% of other CV trials (P ≤ 0.001), it did not differ by peer-reviewed vs industry funding. First authors who were women were more likely than first authors who were men to enroll significantly more women (P = 0.01). ConclusionsActive efforts to increase diverse enrollment, along with improved reporting, including of sex and race, in future CV trials may increase the generalizability of their findings and applicability to global populations.

Comprehensive analysis of dyslipidemia states associated with fat in the pancreas

BackgroundThe global burden of cardiovascular diseases continues to rise, and it is increasingly acknowledged that guidelines based on traditional risk factors fail to identify a substantial fraction of people who develop cardiovascular diseases. Fat in the pancreas could be one of the unappreciated risk factors. This study aimed to investigate the associations of dyslipidemia states with fat in the pancreas. MethodsAll participants underwent magnetic resonance imaging on the same 3.0 T scanner for quantification of fat in the pancreas, analyzed as both binary (i.e., fatty change of the pancreas) and continuous (i.e., intra-pancreatic fat deposition) variables. Statistical analyses were adjusted for body mass index, glycated hemoglobin, fasting insulin, ethnicity, age, and sex. ResultsThere were 346 participants studied. On most adjusted analyses, high-density lipoprotein cholesterol dyslipidemia was significantly associated with both fatty change of the pancreas (p = 0.010) and intra-pancreatic fat deposition (p = 0.008). Neither low-density lipoprotein cholesterol dyslipidemia nor triglyceride dyslipidemia were significantly associated with fatty change of the pancreas and intra-pancreatic fat deposition. The absence of any dyslipidemia was inversely associated with both fatty change of the pancreas (p = 0.016) and intra-pancreatic fat deposition (p < 0.001). ConclusionsDyslipidemias are uncoupled when it comes to the relationship with fat in the pancreas, with only high-density lipoprotein cholesterol dyslipidemia having a consistent and strong link with it. The residual cardiovascular diseases risk may be attributed to fatty change of the pancreas.

Exploring the perspectives of pharmaceutical experts and healthcare practitioners on senolytic drugs for vascular aging-related disorder: a qualitative study.

Objective: The field of targeting cellular senescence with drug candidates to address age-related comorbidities has witnessed a notable surge of interest and research and development. This study aimed to gather valuable insights from pharmaceutical experts and healthcare practitioners regarding the potential and challenges of translating senolytic drugs for treatment of vascular aging-related disorders. Methods: This study employed a qualitative approach by conducting in-depth interviews with healthcare practitioners and pharmaceutical experts. Participants were selected through purposeful sampling. Thematic analysis was used to identify themes from the interview transcripts. Results: A total of six individuals were interviewed, with three being pharmaceutical experts and the remaining three healthcare practitioners. The significant global burden of cardiovascular diseases presents a potentially large market size that offer an opportunity for the development and marketability of novel senolytic drugs. The pharmaceutical sector demonstrates a positive inclination towards the commercialization of new senolytic drugs targeting vascular aging-related disorders. However potential important concerns have been raised, and these include increasing specificity toward senescent cells to prevent off-site targeting, thus ensuring the safety and efficacy of these drugs. In addition, novel senolytic therapy for vascular aging-related disorders may encounter competition from existing drugs that treat or manage risk factors of cardiovascular diseases. Healthcare practitioners are also in favor of recommending the novel senolytic drugs for vascular aging-related disorders but cautioned that its high cost may hinder its acceptance among patients. Besides sharing the same outcome-related concerns as with the pharmaceutical experts, healthcare practitioners anticipated a lack of awareness among the general public regarding the concept of targeting cellular senescence to delay vascular aging-related disorders, and this knowledge gap extends to healthcare practitioner themselves as well. Conclusion: Senolytic therapy for vascular aging-related disorders holds great promise, provided that crucial concerns surrounding its outcomes and commercial hurdles are effectively addressed.

Innate Immune Pathways in Atherosclerosis-From Signaling to Long-Term Epigenetic Reprogramming.

Innate immune pathways play a crucial role in the development of atherosclerosis, from sensing initial danger signals to the long-term reprogramming of immune cells. Despite the success of lipid-lowering therapy, anti-hypertensive medications, and other measures in reducing complications associated with atherosclerosis, cardiovascular disease (CVD) remains the leading cause of death worldwide. Consequently, there is an urgent need to devise novel preventive and therapeutic strategies to alleviate the global burden of CVD. Extensive experimental research and epidemiological studies have demonstrated the dominant role of innate immune mechanisms in the progression of atherosclerosis. Recently, landmark trials including CANTOS, COLCOT, and LoDoCo2 have provided solid evidence demonstrating that targeting innate immune pathways can effectively reduce the risk of CVD. These groundbreaking trials mark a significant paradigm shift in the field and open new avenues for atheroprotective treatments. It is therefore crucial to comprehend the intricate interplay between innate immune pathways and atherosclerosis for the development of targeted therapeutic interventions. Additionally, unraveling the mechanisms underlying long-term reprogramming may offer novel strategies to reverse the pro-inflammatory phenotype of immune cells and restore immune homeostasis in atherosclerosis. In this review, we present an overview of the innate immune pathways implicated in atherosclerosis, with a specific focus on the signaling pathways driving chronic inflammation in atherosclerosis and the long-term reprogramming of immune cells within atherosclerotic plaque. Elucidating the molecular mechanisms governing these processes presents exciting opportunities for the development of a new class of immunotherapeutic approaches aimed at reducing inflammation and promoting plaque stability. By addressing these aspects, we can potentially revolutionize the management of atherosclerosis and its associated cardiovascular complications.

A combination of strongly associated prothrombotic single nucleotide polymorphisms could efficiently predict venous thrombosis risk.

Venous thrombosis (VT) is multifactorial trait that contributes to the global burden of cardiovascular diseases. Although abundant single nucleotide polymorphisms (SNPs) provoke the susceptibility of an individual to VT, research has found that the five most strongly associated SNPs, namely, rs6025 (F5 Leiden), rs2066865 (FGG), rs2036914 (F11), rs8176719 (ABO), and rs1799963 (F2), play the greatest role. Association and risk prediction models are rarely established by using merely the five strongly associated SNPs. This study aims to explore the combined VT risk predictability of the five SNPs and well-known non-genetic VT risk factors such as aging and obesity in the Hungarian population. SNPs were genotyped in the VT group (n = 298) and control group (n = 400). Associations were established using standard genetic models. Genetic risk scores (GRS) [unweighted GRS (unGRS), weighted GRS (wGRS)] were also computed. Correspondingly, the areas under the receiver operating characteristic curves (AUCs) for genetic and non-genetic risk factors were estimated to explore their VT risk predictability in the study population. rs6025 was the most prevalent VT risk allele in the Hungarian population. Its risk allele frequency was 3.52-fold higher in the VT group than that in the control group [adjusted odds ratio (AOR) = 3.52, 95% CI: 2.50-4.95]. Using all genetic models, we found that rs6025 and rs2036914 remained significantly associated with VT risk after multiple correction testing was performed. However, rs8176719 remained statistically significant only in the multiplicative (AOR = 1.33, 95% CI: 1.07-1.64) and genotypic models (AOR = 1.77, 95% CI: 1.14-2.73). In addition, rs2066865 lost its significant association with VT risk after multiple correction testing was performed. Conversely, the prothrombin mutation (rs1799963) did not show any significant association. The AUC of Leiden mutation (rs6025) showed better discriminative accuracy than that of other SNPs (AUC = 0.62, 95% CI: 0.57-0.66). The wGRS was a better predictor for VT than the unGRS (AUC = 0.67 vs. 0.65). Furthermore, combining genetic and non-genetic VT risk factors significantly increased the AUC to 0.89 with statistically significant differences (Z = 3.924, p < 0.0001). Our study revealed that the five strongly associated SNPs combined with non-genetic factors could efficiently predict individual VT risk susceptibility. The combined model was the best predictor of VT risk, so stratifying high-risk individuals based on their genetic profiling and well-known non-modifiable VT risk factors was important for the effective and efficient utilization of VT risk preventive and control measures. Furthermore, we urged further study that compares the VT risk predictability in the Hungarian population using the formerly discovered VT SNPs with the novel strongly associated VT SNPs.

Burden of illness, risk factor and physical activity in cardiovascular disease- A review

Cardiovascular illness encompasses a group of diseases affecting the blood vessels and the structure of the heart, and it remains one of the most prevalent non-communicable diseases worldwide. Over the years, the rate of death from cardiovascular diseases has shown a significant decline in several high-income countries, primarily due to reductions in risk factors and advancements in cardiovascular disease management. Nonetheless, the global burden of cardiovascular diseases remains substantial, with an estimated 55 million deaths occurring in 2017, out of which 17.7 million were attributed to cardiovascular disease. The focus of this review is to explore the burden of illness, risk factors, and physical activity levels in populations affected by cardiovascular diseases. Studies have identified 14 potentially modifiable risk factors that were strongly associated with cardiovascular disease and mortality, surpassing the significance of body mass index (BMI), as evidenced by the PURE (Prospective Urban and Rural Epidemiology) study and prior research. While cardiovascular deaths have decreased in several developed countries, there has been a significant increase in low- and middle-income countries. Physical activity has emerged as a critical factor in reducing the risk of mortality and major cardiovascular events, regardless of the type of physical activity and other risk factors. The Physical Activity Guidelines (PAG) for Americans in 2008 recommended a range of moderate and vigorous physical activity and highlighted its inverse association with all-cause mortality, cardiovascular disease mortality, and incident CVD. Emphasizing the importance of physical activity, this low-cost approach holds tremendous potential in reducing deaths and cardiovascular diseases on a global scale. Overall, this review highlights the ongoing global challenge of cardiovascular diseases and underscores the importance of preventive measures, including promoting physical activity, to improve cardiovascular health and reduce the burden of illness worldwide.

Aspirin for Secondary Prevention of Cardiovascular Disease in 51 Low-, Middle-, and High-Income Countries

Aspirin is an effective and low-cost option for reducing atherosclerotic cardiovascular disease (CVD) events and improving mortality rates among individuals with established CVD. To guide efforts to mitigate the global CVD burden, there is a need to understand current levels of aspirin use for secondary prevention of CVD. To report and evaluate aspirin use for secondary prevention of CVD across low-, middle-, and high-income countries. Cross-sectional analysis using pooled, individual participant data from nationally representative health surveys conducted between 2013 and 2020 in 51 low-, middle-, and high-income countries. Included surveys contained data on self-reported history of CVD and aspirin use. The sample of participants included nonpregnant adults aged 40 to 69 years. Countries' per capita income levels and world region; individuals' socioeconomic demographics. Self-reported use of aspirin for secondary prevention of CVD. The overall pooled sample included 124 505 individuals. The median age was 52 (IQR, 45-59) years, and 50.5% (95% CI, 49.9%-51.1%) were women. A total of 10 589 individuals had a self-reported history of CVD (8.1% [95% CI, 7.6%-8.6%]). Among individuals with a history of CVD, aspirin use for secondary prevention in the overall pooled sample was 40.3% (95% CI, 37.6%-43.0%). By income group, estimates were 16.6% (95% CI, 12.4%-21.9%) in low-income countries, 24.5% (95% CI, 20.8%-28.6%) in lower-middle-income countries, 51.1% (95% CI, 48.2%-54.0%) in upper-middle-income countries, and 65.0% (95% CI, 59.1%-70.4%) in high-income countries. Worldwide, aspirin is underused in secondary prevention, particularly in low-income countries. National health policies and health systems must develop, implement, and evaluate strategies to promote aspirin therapy.

Particulate Matter Pollution Remains a Threat for Cardiovascular Health: Findings From the Global Burden of Disease 2019.

Background Particulate matter (PM) pollution is a significant risk factor for cardiovascular diseases, causing substantial disease burden and deaths worldwide. This study aimed to investigate the global burden of cardiovascular diseases attributed to PM from 1990 to 2019. Methods and Results We used the GBD (Global Burden of Disease) study 2019 to investigate disability-adjusted life-years (DALYs), years of life lost (YLLs), years lived with disability (YLDs), and deaths attributed to PM as well as its subgroups. It was shown that all burden measures' age-standardized rates for PM were in the same decreasing trend, with the highest decline recorded for deaths (-36.7%). However, the all-age DALYs increased by 31%, reaching 8.9 million in 2019, to which YLLs contributed the most (8.2 million [95% uncertainty interval, 7.3 million-9.2 million]). Men had higher deaths, DALYs, and YLLs despite lower years lived with disability in 2019 compared with women. There was an 8.1% increase in the age-standardized rate of DALYs for ambient PM; however, household air pollution from solid fuels decreased by 65.4% in the assessed period. Although higher in men, the low and high sociodemographic index regions had the highest and lowest attributed YLLs/YLDsratio for PM pollution in 2019, respectively. Conclusions Although the total age-standardized rate of DALYs for PM-attributed cardiovascular diseases diminished from 1990 to 2019, the global burden of PM on cardiovascular diseases has increased. The differences between men and women and between regions have clinical and policy implications in global health planning toward more exact funding and resource allocation, in addition to addressing inequity in health care access.

Examining the Use of a Polypill in Cardiovascular Disease Prevention.

Cardiovascular disease (CVD) is a significant cause of death worldwide. To address the global burden of CVD and its risk factors, the polypill, an all-in-one therapy that combines multiple existing medications for preventing CVD and reducing CVD events (such as angiotensin-converting enzyme inhibitor, beta-blocker, statin, or aspirin) into a single combination pill, has emerged as a potential strategy to improve CVD prevention. Clinical trials on the polypill have found that polypill use is associated with significant reductions in CVD events and risk factors in both patients with established CVD and at risk of developing CVD, suggesting a potential benefit in primary and secondary CVD prevention. The polypill has also been demonstrated to be a cost-effective therapy that may potentially increase treatment accessibility, affordability, and availability particularly in low- and middle-income countries. Further, patients on polypill therapy have shown high rates of treatment compliance, with significant improvements in medication adherence for patients with low baseline compliance. Given its potential advantages and benefits, the polypill may become a promising therapy for the prevention of CVD.

NON ISCHEMIC CARDIOMYOPATHY – A CASE REPORT

Cardiomyopathies are a group of diseases characterized by the structural and functional abnormalities of the heart muscles in the absence of other illnesses that might be responsible for the observed myocardial anomaly. Hypertrophic and dilated cardiomyopathies are the most prevalent types. Rare types include restrictive cardiomyopathy and restrictive cardiomyopathy with arrhythmia. Dilated cardiomyopathy has a documented prevalence of 36 cases per 100,000 population in Europe and North America, and its yearly incidence varies between 5 and 7.9 cases per 100,000 population. Non-ischemic dilated cardiomyopathy, which causes heart failure, dramatically increases the global burden of cardiovascular diseases. For both men and women, acute dilated cardiomyopathy is mainly brought on by myocarditis. This case was present in Aga Khan University Hospital; and was selected to be reported. The diagnosis in the case scenario is non-ischemic cardiomyopathy associated with heart failure and pulmonary oedema.