An enhanced cardio-protective effect of nanoparticles loaded with active components from Polygonum orientale L. against isoproterenol-induced myocardial ischemia in rats.

In this study, nanoparticles loaded with active components from Polygonum orientale L. (PO), a traditional Chinese herb known for its anti-myocardial ischemic properties, were investigated for cardio-protective properties. Specifically, OVQ-Nanoparticles (OVQ-NPs) with Orientin (Ori), Vitexin (Vit), and Quercetin (Que) was obtained by double emulsion-solvent evaporation method. The OVQ-NPs exhibited a spherical shape, with a uniform size distribution of 136.77 ± 3.88 nm and a stable ζ-potential of -13.40 ± 2.24 mV. Notably, these nanoparticles exhibited a favorable sustained-release characteristic, resulting in an extended circulation time within the living organism. Consequently, the administration of these nanoparticles resulted in significant improvements in electrocardiograms and heart mass index of myocardial ischemic rats induced by isoproterenol, as well as decreased serum levels of CK, LDH, and AST. Furthermore, the results of histopathological examination, such as H&E staining and TUNEL staining, confirmed a reduced level of cardiac tissue pathology and apoptosis. Moreover, the quantification of biochemical indicators (SOD, MDA, GSH, NO, TNF-α, and IL-6) demonstrated that OVQ-NPs effectively mitigated myocardial ischemia by regulating oxidative stress and inflammatory pathways. In conclusion, OVQ-NPs demonstrate promising therapeutic potential as an intervention for myocardial ischemia, providing a new perspective on traditional Chinese medicine treatment in this area.

Association between polycyclic aromatic hydrocarbons exposure with red cell width distribution and ischemic heart disease: insights from a population-based study.

This study investigates the association between polycyclic aromatic hydrocarbon (PAH) exposure, red blood cell distribution width (RDW), and ischemic heart disease (IHD) in a sample of 3003 participants from the National Health and Nutrition Examination Survey (NHANES). We hypothesize that RDW may mediate the effect of hydroxylated PAHs (OH-PAH) on IHD. Logistic regression models reveal significant associations between increased urinary PAH metabolite concentrations and IHD, as well as positive associations between PAH metabolites and RDW. Weighted Quantile Sum (WQS) regression and Bayesian Kernel Machine Regression (BKMR) analyses confirm the significant associations of the OH-PAH mixture with IHD and RDW. Mediation analysis demonstrates that RDW partially mediates the relationship between PAH exposure and IHD, accounting for 2-4.6% of the total effects. Our findings highlight the potential underlying mechanisms linking PAH exposure, RDW, and IHD and emphasize the importance of addressing environmental pollutants like PAHs in maintaining cardiovascular health and informing public health policies.

Myocardial energy balance and metabolism as causes of myocardial ischemia.

The current approach to myocardial ischemia has been influenced by the misconception of a close link between ischemia and coronary atherosclerotic obstructions. Recent guidelines have, however, acknowledged the multifactorial nature of this condition, with an identifiable cause present in less than half of angina patients, and a large fraction with angina of unknown origin. Because of this background, focusing on cardiac energy metabolim offers new opportunities to manage myocardial ischemia even when its cause is unknown.

Cardioprotective Effect of 2-Ethyl-3-Hydroxy-6-Methylpyridinium 2-Nitroxysuccinate Against Adrenaline/Hydrocortisone-Induced Myocardial Ischemia in Mice: Modulation of Free-Radical Processes in Biomembranes and Monoamine Oxidase A Activity.

Oxidative stress (OS) plays a key role in the development of cardiovascular diseases (CVD) in three major ways: reactive oxygen species (ROS)-induced reduction of nitric oxide (NO) bioavailability, ROS-induced inflammation and ROS-induced mitochondrial dysfunction. Oxidation of lipid molecules under the action of ROS leads to damage to membrane structures, changes the functioning of membrane-bound enzymes, and impairs membrane permeability and stability. An increase in OS results in the occurrence of endothelial dysfunction and drug tolerance, side effects, requiring discontinuation of drugs. All of these are significant problems of cardiotherapy. Therefore, the search for new alternative NO donors continues. The present research was aimed at studying the protective effect of 2-ethyl-3-hydroxy-6-methylpyridinium 2-nitroxysuccinate (NS) on the cardiovascular system on mouse myocardial ischemia (MI) model. The NS hybrid molecule includes a synthetic vitamin B6 analog 2-ethyl-3-hydroxy-6-methylpyridine (an antioxidant) and 2-nitroxysuccinic acid (a source of nitric oxide). Using the electron paramagnetic resonance (EPR) method and biochemical methods, we showed that the pronounced ability of NS to release NO is favorably combines with the capacity to prevent OS due to mechanisms such as suppression of the lipid peroxidation (LPO) process, antiradical activity and inhibition of the mitochondrial membrane-bound monoamine oxidase A (MAO-A). Using histological methods, we established that the administration of NS (10 mg/kg, i.p.) reduces the number of ischemic fibers and protects cardiomyocytes against ischemia injury. Thus, the complex protective effect allows us to consider NS as an alternative NO donor and a candidate for the development of a new pharmaceutical agent for the treatment of CVD.

Association between long-term exposure to ambient air pollution and lesion ischemia in patients with atherosclerosis.

BACKGROUND AND AIMS: Air pollution has been associated with coronary artery disease. The underlying mechanisms were understudied, especially in relation to coronary stenosis leading to myocardial ischemia. Advances in computed tomography (CT) allow for novel quantification of lesion ischemia. We aim to investigate associations between air pollution exposures and fractional flow reserve on CT (CT-FFR), a measure of coronary artery blood flow. METHODS: CT-FFR, which defines a ratio of maximal myocardial blood flow compared to its normal value (range: 0-100%), was characterized in 2017 patients with atherosclerosis between 2015 and 2017. Exposures to ozone (O3), nitrogen dioxide (NO2), and fine particulate matter (PM2.5) were estimated using high-resolution exposure models. Linear and logistic regression models were used to assess the association of each air pollutant with CT-FFR and with the prevalence of clinically relevant myocardial ischemia (CT-FFR <75%). RESULTS: Participants were on average 60.1 years old. Annual mean O3, NO2, PM2.5 were 61, 47 and 60 µg/m3, respectively. Mean CT-FFR value was 76.9%. In the main analysis, a higher level of O3 was associated with a lower CT-FFR value (-1.74%, 95% CI: -2.85, -0.63 per 8 µg/m3) and a higher prevalence of myocardial ischemia (odds ratio: 1.32, 95% CI: 1.05-1.65), adjusting for potential confounders such as risk factors and plaque phenotypes, independent of the effects of exposure to NO2 and PM2.5. No associations were observed for PM2.5 or NO2 with CT-FFR. CONCLUSIONS: Long-term exposure to O3 is associated with lower CT-FFR value in atherosclerotic patients, indicating higher risk of lesion ischemia.

Combined exposure to multiple air pollutants and incident ischemic heart disease in individuals with and without type 2 diabetes: A cohort study from the UK Biobank.

BACKGROUND: Air pollution and type 2 diabetes (T2D) are both associated with an increased risk of ischemic heart disease (IHD). Little is known about the combined effects of multiple air pollutants on IHD risk, especially among individuals with T2D. We sought to assess the association of combined exposure to multiple air pollutants with incident IHD and examine the modification effect of T2D. METHODS: This study included 388780 individuals (20036 individuals with T2D) free of cardiovascular disease and cancer from the UK Biobank. The combined exposure to multiple air pollutants, including particulate matter (PM) with diameters ≤ 2.5 µm (PM2.5), PM with diameters between 2.5 and 10 µm (PMcoarse), PM with diameters ≤ 10 µm (PM10), nitrogen dioxide (NO2), and nitrogen dioxides (NOx), was assessed by creating a weighted air pollution score (APS), with a higher APS representing a higher level of air pollution exposure. Hazard ratios (HR) and 95 % confidence intervals (CI) for incident IHD were assessed by multivariable-adjusted Cox proportional hazard models. RESULTS: During a median of 12.9 years of follow-up, 27333 incident IHD cases were observed. Compared with the lowest tertile of the APS, the multivariable-adjusted HR (95 % CI) of IHD risk for the highest tertile was 1.13 (1.03-1.23) among individuals with T2D, while the HR was 1.06 (1.03-1.10) among individuals without T2D. Additionally, the associations between APS and IHD incidence showed a linear relationship among individuals with T2D (nonlinearity: P = 0.37), whereas a non-linear relationship was observed among individuals without T2D (nonlinearity: P = 0.02). For the joint analysis, individuals in the highest tertile of APS and with T2D had a 54 % higher risk of IHD compared to individuals in the lowest tertile of APS and without T2D, with a significant additive interaction (Pinteraction < 0.01). The proportion of relative excess risk was 17 % due to the interaction in categorical analyses. CONCLUSIONS: The combined exposure to multiple air pollutants has been associated with an elevated risk of incident IHD, and the association is more pronounced among individuals with T2D.

PLGA nanoparticles enhanced cardio-protection of scutellarin and paeoniflorin against isoproterenol-induced myocardial ischemia in rats.

This study aims to examine the impact of the microfluidic preparation process on the quality of poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) co-delivered with scutellarin (SCU) and paeoniflorin (PAE) in comparison to a conventional emulsification method and to evaluatethe potential cardio-protective effect of SCU-PAE PLGA NPs produced through emulsification method. As compared with microfluidics, the nanoparticles prepared by emulsification method exhibited a smaller size, higher encapsulation efficiency, higher drug loading and lower viscosity for injection. Subsequently, a rat myocardial ischemia (MI) was established using male Sprague-Dawley (SD) rats (250 ± 20 g) subcutaneously injected with 85 mg/kg isoproterenol (ISO) for two consecutive days. The pharmacokinetic findings demonstrated that our SCU-PAE PLGA NPs exhibited prolonged blood circulation time in MI rats, leading to increased levels of SCU and PAE in the heart. This resulted in significant improvements in electrocardiogram and cardiac index, as well as reduced serum levels of CK, LDH, AST. Histopathological analysis using H&E and TUNEL staining provided further evidence of improved cardiac function and decreased apoptosis. Additionally, experiments measuring SOD, MDA, GSH, NO, TNF-α and IL-6 levels indicated that SCU-PAE PLGA NPs may effectively treat MI through oxidative stress and inflammatory pathways, thereby establishing it as a promising therapeutic intervention.

CYP2C19 Polymorphism in Ischemic Heart Disease Patients Taking Clopidogrel After Percutaneous Coronary Intervention in Egypt.

BACKGROUND: Cardiovascular diseases (CVDs) are considered a leading cause of death worldwide. Allelic variation in the CYP2C19 gene leads to a dysfunctional enzyme, and patients with this loss-of-function allele will have an impaired clopidogrel metabolism, which eventually results in major adverse cardiovascular events (MACE). Ischemic heart disease patients (n = 102) who underwent percutaneous cardiac intervention (PCI) followed by clopidogrel were enrolled in the present study. METHODS: The genetic variations in the CYP2C19 gene were identified using the TaqMan chemistry-based qPCR technique. Patients were followed up for 1 year to monitor MACE, and the correlations between the allelic variations in CYP2C19 and MACE were recorded. RESULTS: During the follow-up, we reported 64 patients without MACE (29 with unstable angina (UA), 8 with myocadiac infarction (MI), 1 patient with non-STEMI, and 1 patient with ischemic dilated cardiomyopathy (IDC)). Genotyping of CYP2C19 in the patients who underwent PCI and were treated with clopidogrel revealed that 50 patients (49%) were normal metabolizers for clopidogrel with genotype CYP2C19*1/*1 and 52 patients (51%) were abnormal metabolizers, with genotypes CYP2C19*1/*2 (n = 15), CYP2C19*1/*3 (n = 1), CYP2C19*1/*17 (n = 35), and CYP2C19*2/*17 (n = 1). Demographic data indicated that age and residency were significantly associated with abnormal clopidogrel metabolism. Moreover, diabetes, hypertension, and cigarette smoking were significantly associated with the abnormal metabolism of clopidogrel. These data shed light on the inter-ethnic variation in metabolizing clopidogrel based on the CYP2C19 allelic distribution. CONCLUSION: This study, along with other studies that address genotype variation of clopidogrel-metabolizing enzymes, might pave the way for further understanding of the pharmacogenetic background of CVD-related drugs.

Cardiovascular and Cerebrovascular Safety of Ranibizumab, Bevacizumab, and Aflibercept in Ocular Diseases: An Analysis of the US Food and Drug Administration Adverse Event Reporting System (FAERS) Database.

The cardiovascular and cerebrovascular safety of ranibizumab, bevacizumab, and aflibercept for ocular diseases is unclear. This study aimed to evaluate and compare the cardiovascular and cerebrovascular safety in patients receiving ranibizumab, bevacizumab, and aflibercept for ocular disease. A cross-sectional study was conducted from 2017 (Q1) to 2021 (Q4) in the US Food and Drug Administration Adverse Event Reporting System (FAERS) database. The outcomes of interest were central nervous system vascular disorders, ischemic heart disease, hypertension, pulmonary hypertension, torsade de pointes/QT prolongation, embolic and thrombotic events, cardiac arrhythmias, cardiac failure, and cardiomyopathy. Data mining was performed by a disproportional method with a compression, using compressed reporting odds ratios (sRORs) with 95% confidence intervals (CIs) to measure signals. The results showed 1462 cardiovascular and cerebrovascular events associated with aflibercept, 834 with ranibizumab, and 150 with bevacizumab. Ranibizumab, bevacizumab, and aflibercept were linked to central nervous system vascular disorders (sROR, 5.57[95%CI, 4.95-6.26] vs sROR, 2.23 [95%CI, 1.75-2.85] vs sROR, 2.73[95%CI, 2.43-3.06]), ischemic heart disease (sROR, 3.31[95%CI, 2.65-4.13] vs sROR, 1.98 [95%CI, 1.24-3.16] vs sROR, 3.00 [95%CI, 2.46-3.65]), embolic and thrombotic (sROR, 3.36 [95%CI, 3.04-3.72] vs sROR, 2.16 [95%CI, 1.70-2.74] vs sROR, 5.25 [95%CI, 4.82-5.72]). Both ranibizumab and bevacizumab produced hypertension (sROR, 1.73 [95%CI, 1.41-2.12] vs sROR, 1.46 [95%CI, 1.03-2.06]) and arrhythmias (sROR, 2.82 [95%CI, 1.99-3.99] vs sROR, 2.13 [95%CI, 1.08-4.22]) signals. The signals of heart failure were detected in ranibizumab (sROR, 5.64 [95%CI, 4.08-7.79]) and aflibercept (sROR, 2.80 [95%CI, 2.03-3.86]). Ranibizumab, bevacizumab, and aflibercept for ocular disease have different safety profiles in cardiovascular and cerebrovascular. The overall cardiovascular and cerebrovascular risk of the patient should be thoroughly assessed in order to select the safest drug for treatment.

Impact of air pollution on ischemic heart disease: Evidence, mechanisms, clinical perspectives.

Ambient air pollution, and especially particulate matter (PM) air pollution <2.5 µm in diameter (PM2.5), has clearly emerged as an important yet often overlooked risk factor for atherosclerosis and ischemic heart disease (IHD). In this review, we examine the available evidence demonstrating how acute and chronic PM2.5 exposure clinically translates into a heightened coronary atherosclerotic burden and an increased risk of acute ischemic coronary events. Moreover, we provide insights into the pathophysiologic mechanisms underlying PM2.5-mediated atherosclerosis, focusing on the specific biological mechanism through which PM2.5 exerts its detrimental effects. Further, we discuss about the possible mechanisms that explain the recent findings reporting a strong association between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, increased PM2.5 exposure, and morbidity and mortality from IHD. We also address the possible mitigation strategies that should be implemented to reduce the impact of PM2.5 on cardiovascular morbidity and mortality, and underscoring the strong need of clinical trials demonstrating the efficacy of specific interventions (including both PM2.5 reduction and/or specific drugs) in reducing the incidence of IHD. Finally, we introduce the emerging concept of the exposome, highlighting the close relationship between PM2.5 and other environmental exposures (i.e.: traffic noise and climate change) in terms of common underlying pathophysiologic mechanisms and possible mitigation strategies.

Particulate Air Pollution Exposure and Stroke among Adults in Israel.

Stroke is the second most common cause of death and disability in the world. Many studies have found fine particulate matter (PM2.5) exposure to be associated with an increased risk of atherosclerotic cardiovascular disease, mostly focusing on ischemic heart disease and acute myocardial infarction. In a national analysis conducted in Israel-an area with unique climate conditions and high air pollution levels, we estimated the association between short-term PM2.5 exposure and ischemic stroke, intracerebral hemorrhage (ICH), or transient ischemic attacks (TIA). Using the Israeli National Stroke Registry, we obtained information on all stroke cases across Israel in 2014-2018. We obtained daily PM2.5 exposures from spatiotemporally resolved exposure models. We restricted the analytical data to days in which PM2.5 levels did not exceed the Israeli 24 h standard (37.5 µg/m3). We repeated the analysis with a stratification by sociodemographic characteristics and comorbidities. For all outcomes, the exposure-response curves were nonlinear. PM2.5 exposure was associated with a higher ischemic stroke risk, with larger effect estimates at higher exposure levels. Although nonsignificant, the exposure-response curve for TIA was similar. The associations with ICH were nonsignificant throughout the PM2.5 exposure distribution. The associations with ischemic stroke/TIA were larger among women, non-Jewish individuals, older adults, and individuals with diabetes, hypertension, and ischemic heart disease. In conclusion, short-term PM2.5 exposure is associated with a higher risk for ischemic stroke and possibly TIA, even when PM2.5 concentrations do not exceed the Israeli air quality guideline threshold. Vulnerability to the air pollution effects differed by age, sex, ethnicity, and comorbidities.

Role of DPP4 and DPP4i in Glucose Homeostasis and Cardiorenal Syndrome.

The objective of the review led to the pursuit of adopting dipeptidyl peptidase-4 inhibitors (DPP4i) as a novel pharmacotherapy in diabetes mellitus (DM) and cardiorenal syndrome (CRS). The CRS is defined as the co-existence of myocardial ischemia with renal failure. At present, the commercially available drugs enhance insulin secretion or action. However, most of the drugs are associated with adverse effects, such as weight gain or hypoglycemia. As a result, newer therapies with better safety and efficacy profiles are being explored. The DPP4 protease enzyme is involved in cardiovascular and renal diseases in association with over-expressed cytokines. The novel characteristic of DPP4i is to control the elevated blood glucose levels in response to nutrient ingestion without causing hypoglycemia. Also, DPP4i are indirectly involved in reducing myocardial ischemia by promoting cardioprotective peptides. They protect the glucagon-like peptide 1 (GLP-1) from the deteriorating effect of the DPP4 enzyme. The GLP-1 receptors (GLP-1R) are abundantly expressed in renal and cardiovascular tissue. The overexpression of GLP-1R will confer protection of the heart and kidney during CRS. DPP4i were found to significantly clear plasma glucose by the simultaneously activating natural thrombolytic system and increasing insulin levels. They can be used in the early stages of the disease, including pre-diabetes or obesity combined with impaired incretin response, while the combination of DPP4i with metformin or thiazolidinediones as insulin sensitizers offers an additional improvement in the treatment of DM. With its positive attributes in a host of associated parameters of interest, DPP4i are studied extensively in the present review.

Treatment inequity in antiplatelet therapy for ischaemic heart disease in patients with advanced chronic kidney disease: releasing the evidence vacuum.

Chronic kidney disease (CKD) is a global health problem and an independent risk factor for cardiovascular morbidity and mortality. Despite evidence-based therapies significantly improving cardiovascular mortality outcomes in the general population and those with non-dialysis-dependent CKD, this risk reduction has not translated to patients with end-stage kidney disease (ESKD). Absent from all major antiplatelet trials, this has led to insufficient safety data for P2Y12 inhibitor prescriptions and treatment inequity in this subpopulation. This review article presents an overview of the progression of research in understanding antiplatelet therapy for ischaemic heart disease in patients with advanced CKD (defined as eGFR <30 mL/min/1.73 m2). Beyond trial recruitment strategies, new approaches should focus on registry documentation by CKD stage, risk stratification with biomarkers associated with inflammation and haemorrhage and building a knowledge base on optimal duration of dual and single antiplatelet therapies.

What is the context? Patients with kidney disease are more likely to experience a heart attack than those without.Those with advanced kidney disease have a higher risk of death following a heart attack.Over the past two decades, advances in treatment following a heart attack have reduced the risk of death, however this has not translated to those with advanced kidney disease.Progression of kidney disease influences antiplatelet (e.g. clopidogrel) treatment efficacy.What is new?This contemporary review analyses registry and trial data to highlight some of the issues surrounding treatment inequity in patients with advanced kidney disease.This article describes potential mechanisms by which progression of kidney disease can influence clotting, bleeding and antiplatelet treatments.What is the impact?Further research into antiplatelet therapy for patients with advanced kidney disease is required.Registry and trial data can improve upon classification of kidney disease for future research.Future trials in antiplatelet therapy for advanced kidney disease are anticipated.

Integration of metabolomics and transcriptomics to reveal anti-chronic myocardial ischemia mechanism of Gualou Xiebai decoction.

ETHNOPHARMACOLOGICAL RELEVANCE: Gualou Xiebai decoction (GLXB), a well-known classic traditional Chinese medicine formula, is a recorded and proven therapy for the management of cardiac diseases. However, its pharmacological characteristics and mechanism of action are unclear. MATERIALS AND METHODS: The effects of GLXB and its mechanism of action in an isoprenaline-induced rat model of chronic myocardial ischemia (CMI) were investigated by incorporating metabonomics and transcriptomics. Meanwhile, the echocardiographic evaluation, histopathological analysis, serum biochemistry assay, TUNEL assay and western blot analysis were detected to revealed the protective effects of GLXB on CMI. RESULTS: The results of echocardiographic evaluation, histopathological analysis and serum biochemistry assay revealed that GLXB had a significantly cardioprotective performance by reversing echocardiographic abnormalities, restoring pathological disorders and converting the serum biochemistry perturbations. Further, the omics analysis indicated that many genes and metabolites were regulated after modeling and GLXB administration, and maintained the marked "high-low" or "low-high" trends. Meanwhile, the results from integrated bioinformatics analysis suggested that the interaction network mainly consisted of amino acid and organic acid metabolism. The results of TUNEL assay and western blot analysis complemented the findings of integrated analysis of metabolomics and transcriptomics. CONCLUSION: These findings suggested that GLXB has a curative effect in isoproterenol-induced CMI in rats. Integrated analysis based on transcriptomics and metabolomics studies revealed that the mechanism of GLXB in alleviating CMI was principally by the regulation of energy homeostasis and apoptosis, which was through a multi-component and multi-target treatment modality.

Androgen-deprivation therapy and risk of death from cardio-vascular disease in prostate cancer patients: a nationwide lithuanian population-based cohort study.

Purpose: The main purpose of this study was to evaluate the risk of CVD mortality in the national cohort of patients diagnosed with prostate cancer and treated with ADT compared with the ADT non-users.Materials and methods: We performed a retrospective cohort study of patients aged 40-79 years and diagnosed with prostate cancer between 1 January 2012 and 31 December 2016 using the Lithuanian Cancer registry data. In total, 13 343 prostate cancer patients were included in the final study cohort who exclusively used gonadotropin-releasing hormone agonists. The primary outcomes that were registered during the follow-up of this study were overall CVD death.Results: There was a higher risk of CVD death in the cohort of patients treated with ADT than in ADT non-users (HR 2.14, 95% CI [1.86-2.45], p < 0.001). Moreover, there was an increased risk of death from ischemic heart disease and stroke (HR 1.42, 95% CI [1.16-1.73] and 1.70, 95% CI [1.18-2.45], respectively) among ADT users. Finally, the risk of CVD-related mortality was highest in the 70-79 age group of ADT users (HR 4.78, 95% CI [3.79-6.04]).Conclusions: This study shows that ADT usage is associated with increased CVD-related mortality risk for patients diagnosed with prostate cancer compared with ADT non-users. The highest mortality risk was found for ischemic heart disease and stroke. CVD-related mortality was increased in the elder group of patients also.

Long-term exposure to ozone and cardiovascular mortality in China: a nationwide cohort study.

BACKGROUND: The evidence for a causal relationship between long-term ozone exposure and cardiovascular mortality is inconclusive, and most published data are from high-income countries. We aimed to investigate the association between long-term exposure to ozone and cardiovascular mortality in China, the most populous middle-income country. METHODS: We did a nationwide cohort study comprising Chinese adults aged 18 years and older from the 2010-11 China Chronic Disease and Risk Factors Surveillance project; participants were followed up until Dec 31, 2018, or the date of death. Data on participants' deaths were obtained through linkage to the Disease Surveillance Point system, a national death registration database. Residential ozone exposure was estimated with a previously developed random forest model. We applied stratified Cox proportional hazards models to estimate the associations of ozone with mortality due to overall cardiovascular diseases, ischaemic heart disease, and stroke. The models were stratified by age and sex and adjusted for a set of individual-level and regional covariates. Warm-season average ozone concentration for the previous 1-3 years was added as a time-varying variable. We also did subgroup analyses by age, sex, level of education, smoking status, urban or rural residence, and geographical region. FINDINGS: Data were analysed for 96 955 participants. The warm-season average ozone concentration during the follow-up period was 89·7 µg/m3 (SD 14·4). In the fully adjusted models, we observed significant and positive associations between ozone and mortality from overall cardiovascular diseases (hazard ratio [HR] 1·093 [95% CI 1·046-1·142] per 10 µg/m3 increase in warm-season ozone concentrations), ischaemic heart disease (1·184 [1·099-1·276] per 10 µg/m3 increase in warm-season ozone concentrations), and stroke (1·063 [1·002- 1·128] per 10 µg/m3 increase in warm-season ozone concentrations). After adjusting for fine particulate matter, the associations with overall cardiovascular disease and ischaemic heart disease mortality were almost unchanged, whereas the association with stroke mortality lost statistical significance. The association of long-term ozone exposure with cardiovascular mortality was more prominent in people aged 65 years and older than in those younger than 65 years. We did not find any effect modification of sex, level of education, smoking status, urban or rural residence, and geographical region. We observed an almost linear exposure-response relationship between ozone and cardiovascular mortality. INTERPRETATION: This study is, to the best of our knowledge, the first nationwide cohort study to show that long-term ozone exposure contributes to elevated risks of cardiovascular mortality, particularly from ischaemic heart disease, in a middle-income setting. The exposure-response function generated from this study could potentially inform future air quality standard revisions and environmental health impact assessments. FUNDING: National Natural Science Foundation of China.

The Influence of Environmental Air Pollution on Ventricular Arrhythmias: A Scoping Review.

INTRODUCTION: Exposure to air pollution is a recognised risk factor for cardiovascular disease and has been associated with supraventricular arrhythmias. The effect of air pollution on ventricular arrhythmias is less clear. This scoping review assessed the effects of particulate and gaseous air pollutants on the incidence of ventricular arrhythmias. METHODS: MEDLINE and EMBASE databases were searched for studies assessing the effects of air pollutants on ventricular tachycardia and ventricular fibrillation. These pollutants were particulate matter (PM) 2.5, PM10, Nitrogen Dioxide (NO2), Carbon Monoxide (CO), Sulphur Dioxide (SO2), and Ozone (O3). RESULTS: This review identified 27 studies: nine in individuals with implantable cardioverter defibrillators, five in those with ischaemic heart disease, and 13 in the general population. Those with ischaemic heart disease appear to have the strongest association with ventricular arrhythmias in both gaseous and particulate pollution, with all three studies assessing the effects of PM2.5 demonstrating some association with ventricular arrythmia. Results in the general and ICD population were less consistent. CONCLUSION: Individuals with ischaemic heart disease may be at an increased risk of ventricular arrhythmias following exposure to air pollution.

Using Distributed Lag Non-Linear Models to Estimate Exposure Lag-Response Associations between Long-Term Air Pollution Exposure and Incidence of Cardiovascular Disease.

Long-term air pollution exposure increases the risk for cardiovascular disease, but little is known about the temporal relationships between exposure and health outcomes. This study aims to estimate the exposure-lag response between air pollution exposure and risk for ischemic heart disease (IHD) and stroke incidence by applying distributed lag non-linear models (DLNMs). Annual mean concentrations of particles with aerodynamic diameter less than 2.5 µm (PM2.5) and black carbon (BC) were estimated for participants in five Swedish cohorts using dispersion models. Simultaneous estimates of exposure lags 1-10 years using DLNMs were compared with separate year specific (single lag) estimates and estimates for lag 1-5- and 6-10-years using moving average exposure. The DLNM estimated no exposure lag-response between PM2.5 total, BC, and IHD. However, for PM2.5 from local sources, a 20% risk increase per 1 µg/m3 for 1-year lag was estimated. A risk increase for stroke was suggested in relation to lags 2-4-year PM2.5 and BC, and also lags 8-9-years BC. No associations were shown in single lag models. Increased risk estimates for stroke in relation to lag 1-5- and 6-10-years BC moving averages were observed. Estimates generally supported a greater contribution to increased risk from exposure windows closer in time to incident IHD and incident stroke.

Pharmacological evaluation of cardioprotective potential of Berberis orthobotrys Bien.ex Aitch.

The resurgence of scrutiny in plant-based medicine is mainly due to the current widespread belief that "green medicine" is safe and more dependable than the expensive synthetic drugs. The current study was focused to evaluate the anti-myocardial ischemic potential of Berberis orthobotrys Bien ex Aitch against chemically induced myocardial ischemia in animal models. Myocardial ischemia was instigated in Sprague Dawley rats of either sex (250-450g) by administration of Isoproterenol (ISO) and doxorubicin (DOX) at doses of 25mg/kg b.w and 15mg/kg b.w. respectively. The protective effect of the plant extract was explored by pretreating a group of animals with aqueous methanolic extract of Berberis orthobotrys roots at a dose of 50mg/kg b.w. (orally) for 10 days in ISO-ischemic model while for doxorubicin ischemic model; the study was conducted for 14 days. The findings of the study revealed that serum levels of cardiac marker enzymes were significantly increased (p<0.0001) followed by the administration of Isoproterenol and doxorubicin whereas the pretreatment with aqueous methanolic plant extract had significantly (p<0.0001) prevented the rise in the same, as compared to both intoxicated groups. The statistical analysis of the study led to the conclusion that Berberis orthobotrys possesses cardio protective potential against chemically induced myocardial ischemia.