Ischemic Cardiovascular Disease Research Articles

Quantitative Proteomics Reveal That Metabolic Improvement Contributes to the Cardioprotective Effect of T89 on Isoproterenol-Induced Cardiac Injury.

BackgroundT89, a traditional Chinese medicine, has passed phase II, and is undergoing phase III clinical trials for treatment of ischemic cardiovascular disease by the US FDA. However, the role of T89 on isoproterenol (ISO)-induced cardiac injury is unknown. The present study aimed to explore the effect and underlying mechanism of T89 on ISO-induced cardiac injury.MethodsMale Sprague-Dawley rats received subcutaneous injection of ISO saline solution at 24 h intervals for the first 3 days and then at 48 h intervals for the next 12 days. T89 at dose of 111.6 and 167.4 mg/kg was administrated by gavage for 15 consecutive days. Rat survival rate, cardiac function evaluation, morphological observation, quantitative proteomics, and Western blotting analysis were performed.ResultsT89 obviously improved ISO-induced low survival rate, attenuated ISO-evoked cardiac injury, as evidenced by myocardial blood flow, heart function, and morphology. Quantitative proteomics revealed that the cardioprotective effect of T89 relied on the regulation of metabolic pathways, including glycolipid metabolism and energy metabolism. T89 inhibited the enhancement of glycolysis, promoted fatty acid oxidation, and restored mitochondrial oxidative phosphorylation by regulating Eno1, Mcee, Bdh1, Ces1c, Apoc2, Decr1, Acaa2, Cbr4, ND2, Cox 6a, Cox17, ATP5g, and ATP5j, thus alleviated oxidative stress and energy metabolism disorder and ameliorated cardiac injury after ISO. The present study also verified that T89 significantly restrained ISO-induced increase of HSP70/HSP40 and suppressed the phosphorylation of ERK, further restored the expression of CX43, confirming the protective role of T89 in cardiac hypertrophy. Proteomics data are available via ProteomeXchange with identifier PXD024641.ConclusionT89 reduced mortality and improves outcome in the model of ISO-induced cardiac injury and the cardioprotective role of T89 is correlated with the regulation of glycolipid metabolism, recovery of mitochondrial function, and improvement of myocardial energy.

Omentin-1: a biomarker in large artery ischaemic stroke patients

BackgroundOmentin-1 is a novel adipocytokine that is related to atherosclerosis-based ischaemic cardiovascular disease and stroke. Previous studies have linked its lower levels with poor stroke outcomes. We aimed to assess the level of serum omentin-1 as a prognostic marker in patients with large artery ischaemic stroke.MethodsFifty ischaemic stroke patients suffering large artery ischaemic stroke and another 50 subjects without a prior history of strokes were recruited. All participants were subjected to neurological examinations, echocardiography and laboratory investigations including a lipid profile and HBA1c. Carotid intima-media thickness (IMT) was measured for all participants. Stroke patients were evaluated by the National Institute of Health Stroke Scale (NIHSS) and the modified Rankin Scale (mRS). Infarction volume was measured by magnetic resonance image (MRI) and serum level of omentin-1 was gauged for all participants.ResultsCarotid IMT significantly increased in stroke patients compared to control subjects. While serum omentin-1 levels were higher in control non-diabetic subjects, they were lower in diabetic patients with ischaemic stroke. Serum omentin-1 levels were inversely correlated with NIHSS, carotid IMT, infarction volume and mRS scores in all stroke patients. Serum omentin-1 level less than 24.5 ng/ml showed 93.7%sensitivity and 44.4% specificity in prediction of poor stroke outcome while values less than 27.8 ng/ml in non-diabetic stroke patients had sensitivity and specificity with 87.5% and 55.6% respectively.ConclusionLower levels of serum omentin-1 are associated with increased ischaemic stroke severity and poor functional outcome.

The Risk of Fasting Triglycerides and its Related Indices for Ischemic Cardiovascular Diseases in Japanese Community Dwellers: the Suita Study.

Aim: A prospective cohort study in a Japanese urban general population was performed to investigate whether triglyceride (TG) and its related indices were associated with the risk for the incidence of ischemic cardiovascular disease (CVD) after the adjustment for low-density lipoprotein cholesterol (LDL-C) in Asian community dwellers. Methods: A 15.1-year prospective cohort study was performed in 6,684 Japanese community dwellers aged 30–79 years without a history of CVD and whose fasting TG levels were ＜400 mg/dL. After adjusting for covariates, including LDL-C, the multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of the deciles (D) of TG and those of 1-standard deviation (SD) increment of log-transformed TG (1-SD of TG) according to LDL-C level (≥ 140 and ＜140 mg/dL) for ischemic CVD incidence were estimated. The multivariable-adjusted HRs and 95%CIs of the quintiles (Q) of TG, TG/HDL-C, and the cardiometabolic index (CMI) for ischemic CVD were also estimated. Results: In 101,230 person-years, 464 ischemic CVD cases occurred. For D 10 of TG, the HR (95%CI) was 1.56 (1.05–2.32), and for 1-SD of TG, it was 1.30 (1.00–1.70) in participants with LDL-C ＜140 mg/dL and 1.07 (0.77–1.50) in those with LDL-C ≥ 140 mg/dL. For Q 5 of the CMI, the multivariable-adjusted HR was higher than those of TG and TG/HDL-C. Conclusions: Fasting TG was an independent predictor for ischemic CVD incidence after adjusting for LDL-C in Japanese community dwellers with TG ＜400 mg/dL. Among TG, TG/HDL-C, and the CMI, the CMI could be the most powerful predictor for ischemic CVD.

The P-type ATPase transporter ATP7A promotes angiogenesis by limiting autophagic degradation of VEGFR2

VEGFR2 (KDR/Flk1) signaling in endothelial cells (ECs) plays a central role in angiogenesis. The P-type ATPase transporter ATP7A regulates copper homeostasis, and its role in VEGFR2 signaling and angiogenesis is entirely unknown. Here, we describe the unexpected crosstalk between the Copper transporter ATP7A, autophagy, and VEGFR2 degradation. The functional significance of this Copper transporter was demonstrated by the finding that inducible EC-specific ATP7A deficient mice or ATP7A-dysfunctional ATP7Amut mice showed impaired post-ischemic neovascularization. In ECs, loss of ATP7A inhibited VEGF-induced VEGFR2 signaling and angiogenic responses, in part by promoting ligand-induced VEGFR2 protein degradation. Mechanistically, VEGF stimulated ATP7A translocation from the trans-Golgi network to the plasma membrane where it bound to VEGFR2, which prevented autophagy-mediated lysosomal VEGFR2 degradation by inhibiting autophagic cargo/adapter p62/SQSTM1 binding to ubiquitinated VEGFR2. Enhanced autophagy flux due to ATP7A dysfunction in vivo was confirmed by autophagy reporter CAG-ATP7Amut -RFP-EGFP-LC3 transgenic mice. In summary, our study uncovers a novel function of ATP7A to limit autophagy-mediated degradation of VEGFR2, thereby promoting VEGFR2 signaling and angiogenesis, which restores perfusion recovery and neovascularization. Thus, endothelial ATP7A is identified as a potential therapeutic target for treatment of ischemic cardiovascular diseases.

PHYTOCHEMICAL SCREENING AND EVALUATION OF THE ANTIHYPERCHOLESTEROLEMIC ACTIVITY OF THE CAKE OF SAFOU (DACRYODES EDULIS) IN RATS (RATTUS NORVEGICUS)

Safou (Dacryodes edulis) is consumed by the Ivorian population for its therapeutic virtues. The present study aims to make known the phytochemical composition and antihypercholesterolemic activity of safou cake. For this, phytochemical screening of the aqueous extract of the pulp cake of the safou was carried out. In addition, the antihypercholesterolemic activity of cake was tested in rats (Rattus norvegicus). Results obtained indicate that the aqueous extract of cake contains secondary metabolites such as polyphenols, flavonoids, saponins, polyterpenes and sterols and alkaloids. Moreover, this extract allowed, at a dose of 300 mg / kg of PC, to decrease the blood concentration of compounds such as VLDL-C, LDL-C, triglycerides, total cholesterol and total lipids.On the other hand, at a dose of 100 mg / kg of PC of this extract, the blood level of HDL-C increased significantly in hypercholesterolemic rats (PË‚0.05). This study confirms the antihypercholesterolemic activity of safou cake.Therefore, safou cake could be used to prevent oxidative stress, arterosclerosis, high blood pressure, diabetes and ischemic cardiovascular disease.

Aspirin and omega-3 fatty acid status interact in the prevention of cardiovascular diseases in Framingham Heart Study

BackgroundThe roles of omega-3 (n3) fatty acids [eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] and low-dose aspirin in the primary prevention of ischemic cardiovascular disease (CVD) are controversial. Since omega-3 (n3) fatty acids and aspirin affect cyclooxygenase activity in platelets, there could be a clinically-relevant effect of aspirin combined with a particular n3 fatty acid level present in each individual. MethodsRBC EPA+DHA, arachidonic acid (AA) and docosapentaenoic acid (DPA) were measured in 2500 participants without known CVD in the Framingham Heart Study. We then tested for interactions with reported aspirin use (1004 reported use and 1494 did not) on CVD outcomes. The median follow-up was 7.2 years. ResultsHaving RBC EPA+DHA in the second quintile (4.2–4.9% of total fatty acids) was associated with significantly reduced risk for future CVD events (relative to the first quintile, <4.2%) in those who did not take aspirin (HR 0.54 (0.30, 0.98)), but in those reporting aspirin use, risk was significantly increased (HR 2.16 (1.19, 3.92)) in this quintile. This interaction remained significant when adjusting for confounders. Significant interactions were also present for coronary heart disease and stroke outcomes using the same quintiles. Similar findings were present for EPA and DHA alone but not for DPA and AA. ConclusionsThere is a complex interaction between aspirin use and RBC EPA+DHA levels on CVD outcomes. This suggests that aspirin use may be beneficial in one omega-3 environment but harmful in another, implying that a personalized approach to both aspirin use and omega-3 supplementation may be needed.

Pneumonia hospitalizations and the subsequent risk of incident ischaemic cardiovascular disease in Chinese adults.

Acute respiratory infections have been associated with a transient increase in cardiovascular risk. However, whether such an association persists beyond 1 month and the potential modifying effect of cardiovascular risk factors on such an association are less well established. The China Kadoorie Biobank enrolled 512 726 participants aged 30-79 years from 10 areas across China during 2004-2008. By the end of 2017, a total of 5444 participants with new-onset ischaemic heart disease (IHD) and 4846 with ischaemic stroke (IS) who also had at least a record of hospitalization for pneumonia during follow-up were included. We used a self-controlled case-series method and calculated the age- and season-adjusted relative incidences (RIs) and 95% confidence intervals (CIs) for ischaemic cardiovascular disease (CVD) after pneumonia. The risk of ischaemic CVD increased during days 1-3 after pneumonia hospitalization, with an RI (95% CI) of 4.24 (2.92-6.15) for IHD and 1.85 (1.02-3.35) for IS. The risk gradually reduced with longer duration since pneumonia hospitalization but remained elevated until days 92-365 for IHD (1.23, 1.12-1.35) and days 29-91 for IS (1.25, 1.05-1.48). Pre-existing cardiovascular risk factors amplified the associations between pneumonia and ischaemic CVD risks, such as chronic obstructive pulmonary disease for both IHD and IS, and diabetes and smoking for IHD (all Pinteraction < 0.05). Besides, the risk of ischaemic CVD was also higher among the participants aged ≥70 years (Pinteraction < 0.001 for IHD and 0.033 for IS). Among middle-aged and older Chinese adults, pneumonia hospitalization was associated with both short- and long-term increases in ischaemic CVD risk for ≤1 year.

Positive Effect of Andrographolide Induced Autophagy on Random-Pattern Skin Flaps Survival.

Random-pattern skin flap replantation is generally used in the reconstruction of surgical tissues and covering a series of skin flap defects. However, ischemia often occurs at the flap distal parts, which lead to flap necrosis. Previous studies have shown that andrographolide (Andro) protects against ischemic cardiovascular diseases, but little is known about the effect of Andro on flap viability. Thus, our study aimed to building a model of random-pattern skin flap to understand the mechanism of Andro-induced effects on flap survival. In this study, fifty-four mice were randomly categorized into the control, Andro group, and the Andro+3-methyladenine group. The skin flap samples were obtained on postoperative day 7. Subsequently, the tissue samples were underwent a series of evaluations such as changes in the appearance of flap tissue, the intensity of blood flow, and neovascularization density of skin flap. In our study, the results revealed that Andro enhanced the viability of random skin flaps by enhancing angiogenesis, inhibiting apoptosis, and reducing oxidative stress. Furthermore, our results have also demonstrated that the administration of Andro caused an elevation in the autophagy, and these remarkable impact of Andro were reversed by 3-methyladenine (3-MA), the most common autophagy inhibitor. Together, our data proves novel evidence that Andro is a potent modulator of autophagy capable of significantly increasing random-pattern skin flap survival.

Longitudinal association of dietary fat intake with cardiovascular events in a prospective cohort study in Eastern Mediterranean region

We examined the association of dietary fats intake with the 13-year risk of cardiovascular disease (CVD) among Iranian population. Totally 5432 participants of Isfahan Cohort Study (ICS) aged ≥ 35 years were included in the current study. The frequency of dietary fats including hydrogenated vegetables oil (HVO), non-hydrogenated vegetables oil (nHVO), olive oil, ghee, and animal fats during the preceding year were assessed using a validated food frequency questionnaire. After adjustment for potential confounders, individuals in the top quartile of HVO tended to have 68% greater risk for myocardial infarction compared with those in the first quartile (95% CI: 1.02, 2.78; P = 0.058). No association was found for other dietary fat sources with ischaemic heart disease, stroke, all-cause and CVD mortality after adjustment for all potential confounders. Higher consumption of HVO was associated with increased risk of myocardial infarction.

Shen-Yuan-Dan Capsule Attenuates Verapamil-Induced Zebrafish Heart Failure and Exerts Antiapoptotic and Anti-Inflammatory Effects via Reactive Oxygen Species-Induced NF-κB Pathway.

Background: Heart failure (HF) is the end stage of ischemic cardiovascular diseases; nonetheless, safe and effective therapeutic agents for HF are still lacking, and their discovery remains challenging. Our previous studies demonstrated that Shen-Yuan-Dan Capsule (SYDC), a hospital preparation of traditional Chinese herbal, effectively protected ischemic injury in cardiovascular diseases. However, its therapeutic effects and possible mechanisms on HF remain unclear. Methods: A zebrafish HF model treated with verapamil was developed to assess the therapeutic effect of SYDC on HF zebrafish. Zebrafish were administered with SYDC and digoxin (positive control) by direct soaking. After drug treatment, zebrafish were randomly assigned to the visual observation and image acquisition using a Zebralab Blood Flow System. The reactive oxygen species (ROS), MDA, and SOD levels were determined by fluorescence signal detection, TBA, and WST-8 methods. RT-PCR determined the mRNA expressions of Caspase-3, Caspase-1, Bcl-2, Bax, IL-1β, NF-κB, and TNF-α. Results: SYDC significantly inhibited the levels of heart dilatation and venous congestion and markedly increased the levels of cardiac output, blood flow dynamics, and heart rates in HF zebrafish (p < 0.05, p < 0.01, and p < 0.001). Moreover, SYDC also significantly decreased the levels of MDA and ROS and increased the level of SOD in HF zebrafish. The RT-PCR results revealed that SYDC decreased the expression of Caspase-1, Caspase-3, Bax, IL-1β, NF-κB, and TNF-α but increased the expression of Bcl-2 in HF zebrafish (p < 0.05, p < 0.01, and p < 0.001). Conclusions: SYDC improved the heart function in verapamil-induced HF zebrafish and alleviated inflammation and apoptosis by inhibiting the ROS-mediated NF-κB pathway.

Strategies to Overcome the Barrier of Ischemic Microenvironment in Cell Therapy of Cardiovascular Disease.

The transplantation of various immune cell types are promising approaches for the treatment of ischemic cardiovascular disease including myocardial infarction (MI) and peripheral arterial disease (PAD). Major limitation of these so-called Advanced Therapy Medicinal Products (ATMPs) is the ischemic microenvironment affecting cell homeostasis and limiting the demanded effect of the transplanted cell products. Accordingly, different clinical and experimental strategies have been evolved to overcome these obstacles. Here, we give a short review of the different experimental and clinical strategies to solve these issues due to ischemic cardiovascular disease.

ShengMai-San Attenuates Cardiac Remodeling in Diabetic Rats by Inhibiting NOX-Mediated Oxidative Stress.

Background and PurposeShengMai-San (SMS) is traditionally used to treat ischemic cardiovascular and cerebrovascular diseases. Recently, several studies have reported the cardioprotective effects of SMS in diabetic animals. However, the potential mechanisms have not yet been fully elucidated. In this study, we investigated whether SMS exerts a beneficial effect in diabetic cardiomyopathy (DCM) by alleviating NADPH oxidase (NOX)-mediated oxidative stress.MethodsSD rats were randomly divided into a negative control group (NC), diabetes mellitus group (DM) and SMS-treated group (SMS). The myocardial structure alterations, apoptosis and biomarkers of oxidative stress were observed. Moreover, to explore the protective mechanism of SMS, the activation of AMPKα, expression and translocation of NOX-related proteins were assessed.ResultsDiabetes led to excessive collagen content, fibrosis, and apoptosis in the myocardium. Oxidative stress in diabetic hearts was indicated by low levels of T-AOC, high levels of 8-iso-PGF2α and 8-OHdG, inactivation of AMPKα, elevated expression of NOX2 and NOX4 and translocation of NOX isoforms p47phox and p67phox. Treatment with SMS for 10 weeks resulted in the alleviation of diabetes-associated myocardial structure abnormalities and apoptosis. Additionally, SMS attenuated the accumulation of oxidative stress markers in myocardial tissue. Further investigation showed that SMS was able to reverse the levels of oxidative stress-associated proteins NOX2 and NOX4 in the DM rats. Moreover, SMS treatment blunted the translocation of NADPH oxidase isoforms p47phox and p67phox as well. Furthermore, SMS promoted the activation of AMPK in the cardiac tissue of diabetic rats.ConclusionThese findings indicate that SMS exhibits therapeutic properties against diabetic cardiomyopathy by attenuating myocardial oxidative damage via activation of AMPKα and inhibition of NOX signaling.

Efficacy and safety of traditional Chinese patent medicine on carotid artery atherosclerosis in adults: A network meta-analysis protocol.

Background:Atherosclerosis (AS), the predominant pathological basis of ischemic cardiovascular and cerebrovascular diseases, remains a common and severe clinical problem. The experiments in vitro and in vivo indicate that Traditional Chinese patent medicine (TCPM) shows beneficial efficacy against AS through a variety of mechanisms. However, the existing therapeutic TCPM for the treatment of AS are diverse, and it is still significant to evaluate the pros and cons of a certain TCPM. Therefore, the study aims to compare the efficacy and outcomes of different anti-atherosclerotic TCPM in adults with the hope of providing references for clinical decision making.Methods:Cochrane Library, PubMed, Embase, Web of Science, China National Knowledge Infrastructure Database, Wanfang Database, Chinese BioMedical Literature Database, and China Science and Technology Journal Database will be searched. Randomized controlled trials (RCTs) of TCPM for aortic AS in adults will be included in this study if they meet the Population/Intervention/Comparison/Outcomes/Study Design (PICOS) criteria. Two reviewers will independently perform citations screening, data extraction and risk of bias assessment. STATA 15.0 and WinBUGS 1.4.3 will be employed to conduct statistical analyses under the Bayesian framework.Results:The efficacy and safety of various TCPM strategies on aortic AS in adults will be compared.Conclusion:The study will expand the range of options for anti-atherosclerotic therapeutic strategies and encourages further clinical research in traditional Chinese medicine.INPLASY registration number:INPLASY2020120036.

Hypoxia-induced amniotic fluid stem cell secretome augments cardiomyocyte proliferation and enhances cardioprotective effects under hypoxic-ischemic conditions

Secretome derived from human amniotic fluid stem cells (AFSC-S) is rich in soluble bioactive factors (SBF) and offers untapped therapeutic potential for regenerative medicine while avoiding putative cell-related complications. Characterization and optimal generation of AFSC-S remains challenging. We hypothesized that modulation of oxygen conditions during AFSC-S generation enriches SBF and confers enhanced regenerative and cardioprotective effects on cardiovascular cells. We collected secretome at 6-hourly intervals up to 30 h following incubation of AFSC in normoxic (21%O2, nAFSC-S) and hypoxic (1%O2, hAFSC-S) conditions. Proliferation of human adult cardiomyocytes (hCM) and umbilical cord endothelial cells (HUVEC) incubated with nAFSC-S or hAFSC-S were examined following culture in normoxia or hypoxia. Lower AFSC counts and richer protein content in AFSC-S were observed in hypoxia. Characterization of AFSC-S by multiplex immunoassay showed higher concentrations of pro-angiogenic and anti-inflammatory SBF. hCM demonstrated highest proliferation with 30h-hAFSC-S in hypoxic culture. The cardioprotective potential of concentrated 30h-hAFSC-S treatment was demonstrated in a myocardial ischemia–reperfusion injury mouse model by infarct size and cell apoptosis reduction and cell proliferation increase when compared to saline treatment controls. Thus, we project that hypoxic-generated AFSC-S, with higher pro-angiogenic and anti-inflammatory SBF, can be harnessed and refined for tailored regenerative applications in ischemic cardiovascular disease.

Remifentanil protects against myocardial ischemia/reperfusion injury via miR-205-mediated regulation of PINK1.

Myocardial ischemia/reperfusion (I/R) injury could lead to severe cardiovascular ischemic disease, including myocardial infarction and contractile dysfunction. Remifentanil demonstrated protective effect on myocardial I/R injury. The underlying pathophysiological mechanism was then investigated in this study. In the current study, primary cardiomyocytes were isolated from rats, and then preconditioned with remifentanil. Rats, tail vein injected with miR-205 antagomir, were subjected to infusion of remifentanil, and then subjected to regional ischemia followed by reperfusion. The results demonstrated that cell viability of hypoxia/reoxygenation-induced cardiomyocytes was increased post remifentanil, while the apoptosis was decreased accompanied with reduced cleaved caspase-3 expression. Hypoxia/reoxygenation treatment increased miR-205 and decreased PINK1 (PTEN induced putative kinase 1) expression. However, preconditioning with remifentanil reduced miR-205 and enhanced PINK1. Moreover, over-expression of miR-205 decreased PINK1 expression and counteracted the effects of remifentanil-induced increase of cell viability and decrease of cell apoptosis in hypoxia/reoxygenation-induced cardiomyocytes. Injection with miR-205 antagomir improved remifentanil-induced decrease of infarct size and LDH (lactic acid dehydrogenase) activity in rat model with I/R injury. In conclusion, miR-205 might participate in the protective effect of remifentanil in rat myocardial I/R injury via regulation of PINK1, providing a potential target for amelioration of cardiovascular ischemic disease.

Routine Serial Myocardial Perfusion Scanning in Type 1 Diabetics Pre- and Post-Islet Cell Transplantation is Expensive and Associated With Excessive Radiation Exposure

Type 1 diabetes (T1DM) is a risk factor for cardiovascular disease (CVD) and is associated with increased cardiovascular mortality, heart failure and ischaemic heart disease (IHD). CVD is the leading cause of death in those with T1DM over 40 years of age. At our institution, patients undergoing islet cell transplantation (ICT) for T1DM are subject to routine serial myocardial perfusion scanning (MIBI) pre- and post-transplant to evaluate for IHD.

Melatonin and healthy aging.

Preservation of a robust circadian rhythmicity (particulsarly of the sleep/wake cycle), a proper nutrition and adequate physical exercise are key elements for healthy aging. Aging comes along with circadian alteration, e.g. a disrupted sleep and inflammation, that leads to metabolic disorders. In turn, sleep cycle disturbances cause numerous pathophysiological changes that accelerates the aging process. In the central nervous system, sleep disruption impairs several functions, among them, the clearance of waste molecules. The decrease of plasma melatonin, a molecule of unusual phylogenetic conservation present in all known aerobic organisms, plays a particular role as far as the endocrine sequels of aging. Every day, the late afternoon/nocturnal increase of melatonin synchronizes both the central circadian pacemaker located in the hypothalamic suprachiasmatic nuclei as well as myriads of peripheral cellular circadian clocks. This is called the "chronobiotic effect" of melatonin, the methoxyindole being the prototype of the endogenous family of chronobiotic agents. In addition, melatonin exerts a significant cytoprotective action by buffering free radicals and reversing inflammation via down regulation of proinflammatory cytokines, suppression of low degree inflammation and prevention of insulin resistance. Because of these properties melatonin has been advocated to be a potential therapeutic tool in COVID 19 pandemic. Melatonin administration to aged animals counteracts a significant number of senescence-related changes. In humans, melatonin is effective both as a chronobiotic and a cytoprotective agent to maintain a healthy aging. Circulating melatonin levels are consistently reduced in the metabolic syndrome, ischemic and non-ischemic cardiovascular diseases and neurodegenerative disorders like the Alzheimer's and Parkinson's diseases. The potential therapeutic value of melatonin has been suggested by a limited number of clinical trials generally employing melatonin in the 2-10mg/day range. However, from animal studies the cytoprotective effects of melatonin need higher doses to become apparent (i.e. in the 100mg/day range). Hence, controlled studies employing melatonin doses in this range are urgently needed.

A ten-year comparative study of cardiovascular disease publications, health and socioeconomic indicators between European countries

The aim of this study was to investigate and compare gross domestic product (GDP) per capita, the number of physicians per one million inhabitants, the number of cardiovascular disease (CVD) publications, standardized death rate (SDR) from ischemic heart disease (IHD) and CVD per 100 000 inhabitants per year between European countries. GDP per capita from the Eurostat database served as the socioeconomic indicator, whereas human resources in medicine were reported as the number of physicians per million inhabitants. PubMed was searched for CVD publications published between 2005 and 2014 for each country. The rate per million inhabitants and proportions of CVD publications in the MEDLINE database were calculated. Results showed that although Croatia was the only country with stagnation in GDP per capita and with a lower rate of physicians than Austria (P = 0.007) and the Czech Republic (P = 0.005), Croatia had a lower SDR from IHD and CVD than the European region (P = 0.05, P = 0.021; respectively), and had a continuous decrease in the average annual growth rate of IHD and CVD (-2.36%, -3.81%; respectively). In conclusion our study showed that Croatia, despite being the only country with the stagnation of GDP per capita and a relatively low rate of physicians, had a SDR from IHD and CVD that was lower than in the European region which continuously decreased during the study period.

ABO Blood Group: A Risk Factor for a Cardiovascular Disease in Adults in Morocco

BACKGROUND The association between antigens A and B and cardiovascular disease is still unclear. Several reports have suggested an important involvement of the ABO blood group system in the susceptibility to thrombosis. Assessing that non-O blood groups in particular A blood group confer a higher risk of venous and arterial thrombosis than group O. Epidemiologic data are typically not available for all racial and ethnics groups. The purpose of this observational study was to identify a probable link between ABO blood group and ischemic and non-ischemic disease in subjects from the province of Casablanca, Morocco and to analyze whether A blood group individuals were at higher risk of ischemic disease or not. METHOD An observational study had been conducted from the beginning of 2017 until the end of 2019 in the Department of Cardiology, University Hospital Centre, Ibn Rochd, Casablanca, Morocco. We recruited consecutive subjects (549 men and 544 woman) at our center between 2017 and 2019. We studied data on age, gender, past history of hypertension, diabetes, smoking, sedentarism, obesity, hyperlipidemia, use of estrogen-progestin contraceptives and blood group distribution. Their ABO blood groups were determined using standard agglutination techniques. In each blood group type, we evaluated the prevalence of ischemic and non-ischemic cardiovascular disease. RESULT Of the 1093 patients whose medical records were reviewed, 482 (44.1%) were carrying blood group A. Of the remaining 611 patients, 353 (32.3%) had blood group O, 212 (19.4%) blood group B, and 46 (4.3%) blood group AB. The diagnosis of ischemic disease (ID) was higher in patients with blood group O (63.3%) than in other blood groups, and the diagnosis of valvular disease was higher in patients with blood group A (48.7%) compared to other groups. In patients with blood group B or AB compared to non-B or non-AB, respectively there was no statistically significant difference in ID incidence. The incidence of ID in men was significantly higher in blood group O (63.2%, p = 0.015) compared with women, while there valvular disease was a statistically higher in women (54.5%, p = 0.035). This difference remains statistically significant after adjustment for common cardiovascular risk factors. CONCLUSION Our study suggests an association between ABO blood group and Ischemic disease and non-ischemic disease in Moroccan population. In African countries, where most of health facilities are understaffed, more rigorous studies with a larger population are needed to give high level of evidence to confirm this association in order to establish the need to be more aggressive in risk factor control in these individuals.

Postpartum haemorrhage requiring transfusion and risk of cardiovascular disease later in life: a retrospective cohort study.

To determine whether postpartum haemorrhage (PPH) is associated with cardiovascular disease (CVD), including cerebrovascular and ischaemic heart disease beyond the peripartum period. Population-based cohort study. Merged databases of the Korea National Health Insurance (KNHI) claims, National Health Screening Examination and National Health Screening Program for Infants and Children. Women who gave birth in 2007 in the Republic of Korea and who were tracked through to 2015 for the occurrence of CVD. Patients were identified and the occurrences of PPH and transfusion were determined using the KNHI claims database. The occurrence of CVD was tracked through 2015 using codes from the International Classification of Diseases, tenth revision (ICD-10). The risk of CVD after PPH. Among 150381 women who gave birth during the study period, 9107 were diagnosed with PPH and 899 were treated with transfusion. The risk of CVD in women with PPH was no different than in women without PPH, after adjustment (HR1.03, 95%CI 0.93-1.13). The risk of CVD in women with PPH requiring transfusion was significantly increased compared with women without PPH, after adjustment (HR1.60, 95%CI 1.25-2.06). The risk of CVD in women with PPH without transfusion was not significantly different compared with women without PPH (HR0.96, 95%CI 0.86-1.07). Postpartum haemorrhage (PPH) requiring transfusion is associated with an increased risk of CVD. Guidelines for management should be established, and further studies on the mechanisms involved should be conducted. PPH requiring transfusion is associated with an increased risk of CVD.