Related Cardiovascular Disorders Research Articles

Coenzyme Q10: A Key Antioxidant in the Management of Diabetes-Induced Cardiovascular Complications-An Overview of Mechanisms and Clinical Evidence.

Diabetes mellitus (DM) presents a significant global health challenge with considerable cardiovascular implications. Coenzyme Q10 (CoQ10) has gained recognition for its potential as a natural antioxidant supplement in the management of diabetes and its associated cardiovascular complications. This comprehensive review systematically examines the scientific rationale underlying the therapeutic properties of CoQ10 in mitigating the impact of diabetes and its cardiovascular consequences. The analysis encompasses preclinical trials (in vitro and in vivo) and clinical studies evaluating the efficacy and mechanisms of action of CoQ10. Result & Discussion. Findings reveal that CoQ10, through its potent antioxidant and anti-inflammatory attributes, demonstrates significant potential in reducing oxidative stress, ameliorating lipid profiles, and regulating blood pressure, which are crucial aspects in managing diabetes-induced cardiovascular complications. CoQ10, chemically represented as C59H90O4, was administered in capsule form for human studies at doses of 50, 100, 150, 200, and 300 mg per day and at concentrations of 10 and 20 μM in sterile powder for experimental investigations and 10 mg/kg in powder for mouse studies, according to the published research. Clinical trials corroborate these preclinical findings, demonstrating improved glycemic control, lipid profiles, and blood pressure in patients supplemented with CoQ10. In conclusion, CoQ10 emerges as a promising natural therapeutic intervention for the comprehensive management of diabetes and its associated cardiovascular complications. Its multifaceted impacts on the Nrf2/Keap1/ARE pathway, oxidative stress, and metabolic regulation highlight its potential as an adjunct in the treatment of diabetes and related cardiovascular disorders. However, further extensive clinical investigations are necessary to fully establish its therapeutic potential and assess potential synergistic effects with other compounds.

Inhaled nitric oxide: can it serve as a savior for COVID-19 and related respiratory and cardiovascular diseases?

Nitric oxide (NO), as an important gaseous medium, plays a pivotal role in the human body, such as maintaining vascular homeostasis, regulating immune-inflammatory responses, inhibiting platelet aggregation, and inhibiting leukocyte adhesion. In recent years, the rapid prevalence of coronavirus disease 2019 (COVID-19) has greatly affected the daily lives and physical and mental health of people all over the world, and the therapeutic efficacy and resuscitation strategies for critically ill patients need to be further improved and perfected. Inhaled nitric oxide (iNO) is a selective pulmonary vasodilator, and some studies have demonstrated its potential therapeutic use for COVID-19, severe respiratory distress syndrome, pulmonary infections, and pulmonary hypertension. In this article, we describe the biochemistry and basic characteristics of NO and discuss whether iNO can act as a "savior" for COVID-19 and related respiratory and cardiovascular disorders to exert a potent clinical protective effect.

Effect of eucalyptol on matrix metalloproteinase-9 and its tissue inhibitor in hypertensive rats.

Effects of eucalyptol, a key component of eucalyptus globules, on matrix metalloproteinase-9 (MMP-9) and its tissue inhibitor (TIMP-1), compared with lisinopril, were investigated in a model of hypertension induced by chronic intraperitoneal (IP) injection of low dose nicotine in rats. The hypertensive rats were randomly allocated to 4 groups (n=8): Positive control (PC, untreated), eucalyptol-treated group (1.0 mg/kg, IP), lisinopril-treated group (10 mg/kg, IP), and eucalyptol+lisinopril-treated group. Systolic blood pressure and plasma levels of MMP-9 and TIMP-1 were measured. All treatments decreased the elevated blood pressure and plasma levels of MMP-9 and TIMP-1 most significantly with the combination group which showed non-significant differences from the normal control group. Lisinopril reduced plasma levels of MMP-9 and TIMP-1 more significantly than eucalyptol. In conclusion, eucalyptol significantly decreased the increased plasma levels of MMP-9 and TIMP-1 in nicotine-induced hypertension in rats. Moreover, its combination with lisinopril exerted more significant effects compared to each drug alone. This makes this combination particularly useful in hypertension and related cardiovascular disorders where suppression of MMP-9 and TIMP-1 activities decreases the related complications and improves the overall morbidity and mortality. To our knowledge, the current data are novel, and may open the way for development of a co-delivery system of both drugs which could be beneficial in treatment of hypertension in chronic smokers.

CXCL12 Inhibition Prevents Telomere Shortening and Repression of Telomerase Activity in Both Early and Late Post-menopausal Atherosclerosis via ABCA1 Upregulation

Vascular senescence is a key component in the initiation of atherosclerosis and its related cardiovascular disorders. C-X-C Motif Chemokine Ligand 12 (CXCL12), the CXC chemokine receptor 4 (CXCR4) ligand is a chemokine known to promote atherosclerosis. However, the role of telomeres in CXCL12-mediated senescence-induced atherosclerosis remains obscure. This study aimed to unravel the role of CXCL12 and its association with telomeres in the context of menopause-induced arterial senescence and atherosclerosis. Apoe–/– mice underwent bilateral ovariectomy (OVX) to simulate early and late postmenopausal (EPM) conditions (1 and 5 weeks post-OVX, respectively). POL5551, a selective CXCR4 antagonist, was administered as a continuous infusion (30 mg/kg/day in PBS) using a subcutaneously implanted osmotic minipump for two weeks. ATP binding cassette transporter A1 (ABCA1), a cholesterol efflux regulator was significantly downmodulated (p < 0.05), while NOD-, LRR- and pyrin domain-containing protein 3 (NLR) family pyrin domain containing 3 (NLRP3), inducible nitric oxide synthase (iNOS) and the inflammatory mediators were considerably enhanced (p < 0.05) in both EPM and LPM mice groups. Notably, atherosclerosis was more prominent in the EPM than in the LPM mice. However, POL5551 treatment effectively ameliorated the reduced ABCA1 expression and the increased inflammatory response. Hence, we propose that inhibition of CXCL12 proffers robust anti-senescent and anti-atherosclerotic effects.

Molecular Linkage under the Bicuspid Aortic Valve with Dyslipidemia.

Dyslipidemia is correlated with diverse cardiovascular problems, such as obesity, hypertension, and atherosclerosis, which are summarized as metabolic syndrome. Bicuspid aortic valve (BAV), as one of the congenital heart defects, is shown to influence approximately 2.2% of the general population worldwide, inducing the severe pathological development of aortic valve stenosis (AVS) or aortic valve regurgitation (AVR), and also to aortic dilatation. Notably, emerging evidence showed that BAV was correlated with not only the aortic valve and wall diseases but also the dyslipidemic related cardiovascular disorders. Recent results also proposed that multiple potential molecular mechanisms inducing the progression of dyslipidemia played important roles in BAV and the progression of AVS. Several altered serum biomarkers under dyslipidemic condition, including higher low-density lipoprotein cholesterol (LDL-C), higher lipoprotein (a) [Lp(a)], lower high-density lipoprotein cholesterol (HDL-C), and different pro-inflammatory signaling pathways, have proposed to embrace a vital function in the development of BAV correlated cardiovascular diseases. In this review, different molecular mechanisms which embrace an important role in personalized prognosis in the subjects with BAV was summarized. The illustration of those mechanisms might facilitate an accurate follow-up for patients with BAV and give new pharmacological strategies to improve development of dyslipidemia and BAV.

Non-Coding RNAs in Regulating Plaque Progression and Remodeling of Extracellular Matrix in Atherosclerosis.

Non-coding RNAs (ncRNAs) regulate cell proliferation, migration, differentiation, inflammation, metabolism of clinically important biomolecules, and other cellular processes. They do not encode proteins but are involved in the regulatory network of various proteins that are directly related to the pathogenesis of diseases. Little is known about the ncRNA-associated mechanisms of atherosclerosis and related cardiovascular disorders. Remodeling of the extracellular matrix (ECM) is critical in the pathogenesis of atherosclerosis and related disorders; however, its regulatory proteins are the potential subjects to explore with special emphasis on epigenetic regulatory components. The activity of regulatory proteins involved in ECM remodeling is regulated by various ncRNA molecules, as evident from recent research. Thus, it is important to critically evaluate the existing literature to enhance the understanding of nc-RNAs-regulated molecular mechanisms regulating ECM components, remodeling, and progression of atherosclerosis. This is crucial since deregulated ECM remodeling contributes to atherosclerosis. Thus, an in-depth understanding of ncRNA-associated ECM remodeling may identify novel targets for the treatment of atherosclerosis and other cardiovascular diseases.

A New Insight Into Pathophysiological Mechanism of Abdominal Aortic Aneurysm With Novel Parameters Salusin-β and Arterial Stiffness

Abdominal aortic aneurysm (AAA) has risk factors similar to those of atherosclerosis. Salusin-β and arterial stiffness are novel parameters that have been shown to predict atherosclerosis and related cardiovascular disorders. However, their predictive value for detecting AAA remains unclear. Forty-eight patients with AAA and 47 age- and sex-matched participants without AAA were enrolled in the study. Arterial stiffness parameters were obtained via an oscillometric Mobil-O-Graph PWA Monitor device (IEM GmbH) with integrated ARCSolver software (Australian Institute of Technology). Plasma salusin-β levels were analyzed using an enzyme-linked immunosorbent assay reagent kit (Abbkine, Inc). The measured salusin-β levels and arterial stiffness parameters of the AAA and control groups were compared. Salusin-β levels were significantly lower in patients with AAA (P = .014). There was a significant negative correlation between salusin-β levels and abdominal aorta diameter. No significant difference was detected between AAA and control groups in terms of arterial stiffness parameters (P > .05). In backward multiple regression analysis, the presence of AAA, platelet count, and augmentation index were found to be independent predictors of salusin-β levels (P = .006 and P = .023, respectively). Arterial stiffness parameters were not found to be associated with AAA. Contrary to previous results regarding atherosclerosis and related cardiovascular disorders, salusin-β levels were found to be lower in patients with AAA. Although AAA is thought to have similar risk factors as atherosclerosis, the exact pathophysiologic mechanism remains unclear.

Temporal fluctuations of cardiovascular parameters after intravitreal injections.

Despite the effectiveness of intravitreal injection (IVI) of anti-vascular endothelial growth factor in treating retinal diseases, there remains a paucity of evidence on potential systemic risks associated with this procedure. This study aims to investigate cardiovascular parameters and the risk of hypertensive urgency after IVIs. Patients who received IVIs for retinal/macular diseases were enrolled retrospectively. Patients who received cataract surgeries were enrolled as controls. Systolic and diastolic blood pressure (BP) and heart rate were measured 10 minutes before, immediately after, and more than 30 minutes after IVIs and cataract surgery. Multivariate analysis was performed to evaluate risk factors for hypertensive urgency. Seventy patients who received IVIs and 95 patients who received cataract surgeries were enrolled. A higher preoperative systolic BP was found in the IVI groups than in the control group (147.0 ± 22.9 vs 136.3 ± 21.8 mmHg, respectively). The patients who received IVIs had a higher increase in perioperative systolic BP immediately after the procedure than the controls (17.43 ± 20.53 mmHg vs 9.11 ± 18.92 mmHg, p = 0.009). The IVI procedure (odds ratio [OR] 4.84, p = 0.008), preoperative systolic BP ≥160 mmHg (OR 17.891, p = 0.001, compared to preoperative systolic BP <140 mmHg), and underlying hypertension (OR 3.305, p = 0.041) were risk factors for hypertensive urgency immediately after the IVIs. We found a transient increase in BP after IVIs, which may have been associated with hypertensive urgency and related cardiovascular disorders in older patients and in those with relevant comorbidities. Clinicians should pay more attention to these patients before performing IVIs.

Autonomic Testing Optimizes Therapy for Heart Failure and Related Cardiovascular Disorders.

Purpose of ReviewCardiovascular autonomic control is an intricately balanced dynamic process. Autonomic dysfunction, regardless of origin, promotes and sustains the disease processes, including in patients with heart failure (HF). Autonomic control is mediated through the two autonomic branches: parasympathetic and sympathetic (P&S). HF is arguably the disease that stands to most benefit from P&S manipulation to reduce mortality risk. This review article briefly summarizes some of the more common types of autonomic dysfunction (AD) that are found in heart failure, suggests a mechanism by which AD may contribute to HF, reviews AD involvement in common HF co-morbidities (e.g., ventricular arrhythmias, AFib, hypertension, and Cardiovascular Autonomic Neuropathy), and summarizes possible therapy options for treating AD in HF.Recent FindingsAutonomic assessment is important in diagnosing and treating CHF, and its possible co-morbidities. Autonomic assessment may also have importance in predicting which patients may be susceptible to sudden cardiac death. This is important since most CHF patients with sudden cardiac death have preserved left ventricular ejection fraction and better discriminators are needed.SummaryMany life-threatening cardiovascular disorders will require invasive testing for precise diagnoses and therapy planning when modulating the ANS is important. In cases of non-life-threatening disorders, non-invasive ANS testing techniques, especially those that individually assess both ANS branches simultaneously and independently, are sufficient to diagnose and treat serially.

Neonatal stress and loss of ovarian hormones: a novel multidisciplinary approach to understand the coincidence of cardiorespiratory and metabolic disorders in females

IntroductionIn women, the prevalence of sleep apnea (SA) rises 3‐fold at menopause and most patients also present hypertension and obesity. While the “protective effects” of ovarian hormones are well documented, we do not know why the loss of ovarian hormones leads to SA and related cardiovascular and metabolic disorders only in a subpopulation of women. Because neonatal stress is a major cause of adult diseases, we tested the hypothesis that loss of ovarian function reveals the latent effects of stress on cardiorespiratory and metabolic control. To do so, we subjected female rats to neonatal maternal separation (NMS), a translational model of early life stress.MethodologyRat pups subjected to NMS were placed in a temperature‐controlled incubator 3h/day from postnatal day 3 to 12; controls (CTRL) were undisturbed. The effects of loss of ovarian function were tested using a surgical approach (ovariectomy; OVX, animals with 8 weeks old) and aging (40 weeks old). Measurements of ventilation (by whole body plethysmography), blood pressure (by tail cuff plethysmography), and body composition (by nuclear magnetic resonance) were made. We also harvested brains from 8 weeks old females (SHAM versus OVX). Then, we compared the expression of FosB, a transcription factor that indicates neuronal activity. The number of FosB expressing neurons was counted in the paraventricular nucleus of the hypothalamus (PVH), the main structure regulating the hypothalamic pituitary adrenal (HPA) axis.ResultsNMS does not affect the incidence of apneic events in all groups. At 8 weeks, mean arterial pressure (MAP) of NMS females was 5% lower than CTRL. In addition, NMS females had 10% more body mass compared to CTRL. At 40 weeks, the MAP of NMS females was 15% higher than CTRL. In both ages, NMS presented 4% more fat, and 4% less lean tissue. OVX did not affect cardiorespiratory function but augmented the number of neurons expressing FosB in the PVH by 55% in NMS, not in CTRL females.DiscussionThe hypotension observed in young (8 weeks) NMS females was unexpected but is consistent with the fact that hypotension is a common comorbidity of depression. PVH dysfunction contributes to the increase of sympathetic vasomotor activity, characteristic of multiple forms of hypertension. Additionally, the chronic activation of the HPA axis can leads to obesity. The increased expression of FosB in OVX NMS animals indicate that ovarian hormones prevents the stress‐related rise of activity of the HPA axis. At 40 weeks old, the fact that NMS animals were obese and hypertensive indicates that those effects are age dependent. The emergence of dysregulation on the stress neuroaxis is a plausible mechanism to explain those results. Together, these data indicate that neonatal stress may explain why a subpopulation of women are at risk of developing cardiorespiratory and metabolic disturbance at menopause. Ongoing experiments will evaluate the incidence of SA in older animals (60 weeks old) and exploring the underlying mechanisms.

C-type natriuretic peptide is a pivotal regulator of metabolic homeostasis

Thermogenesis and adipogenesis are tightly regulated mechanisms that maintain lipid homeostasis and energy balance; dysfunction of these critical processes underpins obesity and contributes to cardiometabolic disease. C-type natriuretic peptide (CNP) fulfills a multimodal protective role in the cardiovascular system governing local blood flow, angiogenesis, cardiac function, and immune cell reactivity. Herein, we investigated a parallel, preservative function for CNP in coordinating metabolic homeostasis. Global inducible CNP knockout mice exhibited reduced body weight, higher temperature, lower adiposity, and greater energy expenditure in vivo. This thermogenic phenotype was associated with increased expression of uncoupling protein-1 and preferential lipid utilization by mitochondria, a switch corroborated by a corresponding diminution of insulin secretion and glucose clearance. Complementary studies in isolated murine and human adipocytes revealed that CNP exerts these metabolic regulatory actions by inhibiting sympathetic thermogenic programming via Gi-coupled natriuretic peptide receptor (NPR)-C and reducing peroxisome proliferator-activated receptor-γ coactivator-1α expression, while concomitantly driving adipogenesis via NPR-B/protein kinase-G. Finally, we identified an association between CNP/NPR-C expression and obesity in patient samples. These findings establish a pivotal physiological role for CNP as a metabolic switch to balance energy homeostasis. Pharmacological targeting of these receptors may offer therapeutic utility in the metabolic syndrome and related cardiovascular disorders.

Association of CYP24A1 gene, Vitamin D deficiency and heart diseases in Pakistani patients

To analyze the association of CYP24A1 gene polymorphism with vitamin D deficiency and its related cardiovascular disorders in the Pakistani population. The present prospective cohort study was carried out at KRL and Rawalpindi General Hospital from January 2017 to December 2018. A total of 110 subjects suffering from heart diseases like hypertension, myocardial infarction, or congestive cardiac failure (age range 12-90 years) were enrolled in this study with informed consent. Sampling was done by non-probability convenience sampling. Blood 24Hydroxyvitmin D levels were assessed in the participants by using an electrochemiluminescence system. Genetic polymorphism in the CYP24A1 gene was screened in selected patients (n=15) through PCR-RFLP, after genomic DNA extraction from the whole blood. Data were analyzed using SPSS version 24 for Mac. Fisher’s exact test and chi-square tests were applied for qualitative variables. The risk of polymorphism in CYP24A1(SNP rs6013897) genotypes TT, AT, and AA was determined by calculating the odds ratio and confidence interval. P-value &lt;0.05 was considered statistically significant. We observed the highest level of vitamin D deficiency in patients of age group 18-45 years and insufficiency in age group 50-60years. A greater percentage of female patients (34.19%) were deficient in Vitamin D as compared to males (25.72%). Vitamin D deficiency was found to be associated with cardiovascular diseases like hypertension (P=0.000*), myocardial infarction (P=0.334), and heart failure (0.001*). CYP24A1 (SNP rs6013897) was significantly associated (P=0.000*) with vitamin D deficiency and heart diseases (P=0.004*). Moreover, significant polymorphism of genotype AT was observed in our subjects. {P=0.007*, Cramer’s V =.003 and 95% CI (0.44-17.27)}. There is an association of CYP24A1 gene polymorphism with vitamin D deficiency and heart diseases. Prevention of low vitamin D levels in individuals with this known genetic marker may help to avert the development of heart diseases in Pakistan.

Targeting the microRNA-34a as a Novel Therapeutic Strategy for Cardiovascular Diseases

Cardiovascular diseases (CVDs) are still the main cause of morbidity and mortality worldwide and include a group of disorders varying from vasculature, myocardium, arrhythmias and cardiac development. MicroRNAs (miRs) are endogenous non-coding RNAs with 18–23 nucleotides that regulate gene expression. The miR-34 family, including miR-34a/b/c, plays a vital role in the regulation of myocardial physiology and pathophysiological processes. Recently, miR-34a has been implicated in cardiovascular fibrosis, dysfunction and related cardiovascular disorders as an essential regulator. Interestingly, there is a pivotal link among miR-34a, cardiovascular fibrosis, and Smad4/TGF-β1 signaling. Notably, both loss-of-function and gain-of-function approaches identified the critical roles of miR-34a in cardiovascular apoptosis, autophagy, inflammation, senescence and remodeling by modulating multifunctional signaling pathways. In this article, we focus on the current understanding of miR-34a in biogenesis, its biological effects and its implications for cardiac pathologies including myocardial infarction, heart failure, ischaemia reperfusion injury, cardiomyopathy, atherosclerosis, hypertension and atrial fibrillation. Thus, further understanding of the effects of miR-34a on cardiovascular diseases will aid the development of effective interventions. Targeting for miR-34a has emerged as a potential therapeutic target for cardiovascular dysfunction and related diseases.

Abstract MP32: Diaphanous 1 Regulates Actin Polymerization In Adipocytes: Potential Mechanism Regulating Obesity In Mice

The underlying pathophysiological mechanisms of obesity, a hallmark of metabolic and cardiovascular diseases, are not fully elucidated. Adipocyte hypertrophy contributes to insulin resistance, and is coupled to meaningful alterations in actin dynamics that favor actin polymerization. Diaphanous 1 (Diaph1) is a formin protein that associates with the fast-growing/barded end of actin filaments to regulate actin dynamics. We hypothesized that deletion of Diaph1 or pharmacological regulation of actin polymerization in the context of lipid surplus would prevent obesity, decrease adipocyte lipid load and protect from obesity-associated metabolic disease. We modeled obesity by feeding wild type (Wt) mice and mice globally or with adipocyte-specific deletion of Diaph1 a high fat diet (60%kcal from fat). Body composition was assessed by Dual-energy X-ray absorptiometry (DEXA) and dynamic glucose and insulin tolerance testing was performed to assess metabolic state. In-vitro studies were carried out in adipocytes differentiated from primary pre-adipocytes or 3T3-L1 fibroblasts. Lipid overload was modeled using a mixture of palmitate/oleate (P/O). Actin manipulations were achieved by pharmacologically preventing (Latrunculin B [LatB]) or promoting (Jasplakinolide [Jasp]) F-actin polymerization. Mice globally devoid of, or with adipocyte specific Diaph1 deletion were protected from obesity, glucose intolerance and insulin resistance. Wt adipocytes treated with P/O exhibited pronounced accumulation of triglycerides (Tg) which was absent in adipocytes differentiated from Diaph1 knock out mice. Pharmacological studies in 3T3-L1-derived adipocytes confirmed the P/O-induced Tg accumulation which was prevented by LatB and exacerbated by Jasp. We present the novel finding that adipocyte DIAPH1 is a major player in the pathophysiology of obesity and associated metabolic sequela which results, at least in part, from regulation of adipocyte hypertrophy by preventing actin polymerization. Thus, we propose that actin remodeling is an underlying mechanism for adipocyte hypertrophy in obesity and inhibition of DIAPH1 may represent a potential therapeutic target for the treatment of obesity and related metabolic and cardiovascular disorders.

Nitric-Oxide-Mediated Vasodilation of Bioactive Compounds Isolated from Hypericum revolutum in Rat Aorta.

Simple SummaryHypericum revolutum (HR) is reported to produce vasodilating activity in phenylephrine-precontracted aortae, where the chloroform fraction is the most potent. Chemical investigation of this fraction yielded two new compounds, revolutin (1) and hyperevolutin C (2), along with three known metabolites, β-sitosterol (3), euxanthone (4), and 2,3,4-tirmethoxy xanthone (5). Isolated compounds 1, 2, 3, and 5 produce vasodilation activities that are dependent on endothelial nitric oxide release.Vasodilators are an important class in the management of hypertension and related cardiovascular disorders. In this regard, the chloroform fraction of Hypericum revolutum (HR) has been reported to produce vasodilating activity in phenylephrine-precontracted aortae. The current work aims to identify the active metabolites in the chloroform fraction of HR and illustrate the possible mechanism of action. The vasodilation activities were investigated using the isolated artery technique. NO vascular release was assessed by utilizing the NO-sensitive fluorescent probe DAF-FM. Free radical scavenging capacity was assessed utilizing DPPH. Chemical investigation of this fraction yielded two new compounds, revolutin (1) and hyperevolutin C (2), along with three known metabolites, β-sitosterol (3), euxanthone (4), and 2,3,4-tirmethoxy xanthone (5). Compounds 1, 2, 3, and 5 showed significant vasodilation activities that were blocked by either endothelial denudation or L-NAME (nitric oxide synthase inhibitor), pointing towards a role of endothelial nitric oxide in their activities. In confirmation of this role, compounds 1–3 showed a significant release of NO from isolated vessels, as indicated by DAF-FM. On the other hand, only compound 5 showed free radical scavenging activities, as indicated by DPPH. In conclusion, isolated compounds 1, 2, 3, and 5 produce vasodilation activities that are dependent on endothelial nitric oxide release.

Association of human platelet alloantigens encoding gene polymorphisms with the risk of Coronary artery disease in Iranian patients

BackgroundCoronary artery disease (CAD) is characterized by narrowing/ blockade of coronary arteries that is mainly caused by atherosclerotic plaques. Considering the involvement of platelet abnormalities, such as defective aggregation and adhesion, in the cardiovascular-related disorders, genetic variations in human platelet alloantigens (HPA) have been implicated in the CAD susceptibility. Herein, we intended to determine the association of HPA-1 to -6, -9, and -15 biallelic polymorphisms with CAD in an Iranian population.MethodsIn this retrospective case–control study, 200 CAD subjects and 100 matched healthy individuals were enrolled. DNA samples were isolated from peripheral blood samples and genotyping of HPA polymorphisms was accomplished using polymerase chain reaction-sequence-specific primers.ResultsThe alleles and genotypes of studied HPA polymorphisms were equally distributed among cases and controls and therefore no statistically significant differences were detected. Univariate analysis identified no association of combined haplotypes with CAD risk. However, multivariate analysis showed a positive association of the‌ HPA1b/2a/3b haplotype with CAD after adjustment for some covariates (including BMI, TG, LDL, FBS and blood pressure) that conferred a CAD susceptibility haplotype (P = 0.015; OR = 2.792; 95% CI 1.45–8.59).ConclusionsAlthough alleles, genotypes, and haplotypes of HPA polymorphisms were not associated with CAD risk, HPA1b/2a/3b haplotype was found to be a dependent disease risk haplotype in Iranian population after correcting for confounding factors.

Cannabis cardiovascular related disorders

Cannabis use has increased in the past decade, becoming the most popular recreational drug abused. THC, have various effects modulating the immune function and the inflammatory response. Multiple pathophysiological mechanisms have been proposed to clarify cannabis cardiovascular-related disorders. Although the increasing therapeutic use of cannabis, its side effects remain important and has been reported to be the trigger of serious cardiovascular events up to cardiac arrest. The aim of this study is to report the impact of cannabis in order to aware the physicians about its potentially harmful health consequences. It is a transversal study conducted between May 2018 and June 2019 including all patients with notion of cannabis consumption admitted for acute cardiovascular events in the cardiology departments of IBN Rochd Hospital of Casablanca. The data were analyzed on Excel. Twelve patients were collected during this period. The mean age was 58 years old, with male predominance (80%). The main risk factors were chronic tobacco smoking (75%), hypertension (25%) and diabetes in 16.6%. 92% of the patients presented to the emergency room in the setting of acute chest pain, while 66.6% complained of dyspnea. Palpitations were reported in one case, and other presented with acute ischemia of the four limbs. After full investigations including electrocardiogram, echocardiography, coronary angiography, biological assessment and MRI, myocarditis was diagnosed in 58% of the cases, NSTEMI in 34%, and one patient with acute arteritis. Complete management of the patients included treatment of their cardiovascular affection associated with assisted smoking cessation. Marijuana is the most popular worldwide used drug. Vasospasm, peripheral arteritis and platelet aggregation are the main mechanisms leading to the reported disorders. Therefore, awareness of the adverse outcomes of this substance by the physicians is essential.

Cardiovascular disease among patients admitted to medicine intensive care unit (MICU) in tertiary care hospital

Introduction: Cardiovascular diseases (CVD’s) are rampantly increasing in the Indian population with an increasing trend in the younger patients. Overall cardiovascular diseases showed that almost one-fourth of all deaths in India in 2008. CVD’s were considered as the fastest growing chronic illness between 2005 and 2015, growing at an average of 9.2 % per year. Objectives: (i) To know cardiovascular diseases in patients admitted to MICU; (ii) Categorization of various CVD and associated conditions; (iii) To know the socio demographic profile of the patients. Materials and Methods: The study was retrospective of 3 months duration among patients of age group among 30-50 years admitted in KR Hospital Mysuru. All the patients admitted in the hospital for a minimum duration of 24 hours were included. Data were collected based on standard proforma from the available case record sheets. The analysis of data was based on descriptive statistical analysis. Results: The study found that majority of cases recorded in MICU was cardiovascular related disorders. In that Myocardial infraction (MI) was major cardiovascular disease (CVD) Keywords: Medicine intensive care unit (MICU), Myocardial infarction (MI), Cardiovascular diseases(CVD).

The Role of iRhom2 in Metabolic and Cardiovascular-Related Disorders.

Chronic obesity is associated with metabolic imbalance leading to diabetes, dyslipidemia, and cardiovascular diseases (CVDs), in which inflammation is caused by exposure to inflammatory stimuli, such as accumulating sphingolipid ceramides or intracellular stress. This inflammatory response is likely to be prolonged by the effects of dietary and blood cholesterol, thereby leading to chronic low-grade inflammation and endothelial dysfunction. Elevated levels of pro-inflammatory cytokines such as tumor necrosis factor (TNF) are predictive of CVDs and have been widely studied for potential therapeutic strategies. The release of TNF is controlled by a disintegrin and metalloprotease (ADAM) 17 and both are positively associated with CVDs. ADAM17 also cleaves most of the ligands of the epidermal growth factor receptor (EGFR) which have been associated with hypertension, atherogenesis, vascular dysfunction, and cardiac remodeling. The inactive rhomboid protein 2 (iRhom2) regulates the ADAM17-dependent shedding of TNF in immune cells. In addition, iRhom2 also regulates the ADAM17-mediated cleavage of EGFR ligands such as amphiregulin and heparin-binding EGF-like growth factor. Targeting iRhom2 has recently become a possible alternative therapeutic strategy in chronic inflammatory diseases such as lupus nephritis and rheumatoid arthritis. However, what role this intriguing interacting partner of ADAM17 plays in the vasculature and how it functions in the pathologies of obesity and associated CVDs, are exciting questions that are only beginning to be elucidated. In this review, we discuss the role of iRhom2 in cardiovascular-related pathologies such as atherogenesis and obesity by providing an evaluation of known iRhom2-dependent cellular and inflammatory pathways.

Abstract 15941: Derivation of Risk-Scores That Stratify Risk of Hospitalization and Death in SARS-CoV-2 Positive Patients

Introduction: It is well-documented that COVID-19 patients with pre-existing cardiovascular-related disorders are at higher risk of a complicated course. It would be valuable to integrate individual risk factors into overall risk scores for hospitalization and death from COVID-19. Methods: The Intermountain Healthcare medical record database was searched for all individuals tested for SARS-CoV-2 infection up to June 8, 2020. Data from test-positive patients (pts) was analyzed to determine the characteristics of pts requiring hospitalization. From these data, 2 risk scores for hospitalization were derived using multi-variable modeling: of only demographic and risk-factor data, or also including concurrent medications. The risk scores were also applied to predict the risk of dying from COVID-19. Results: Of 104,018 people tested at Intermountain Healthcare for SARS-CoV-2, 5505 (5.3%) were positive. Of test-positive pts, 451 (8.2%) were hospitalized, and 37 (0.7%) died. Using a demographic/risk factor only score, 1.4, 7.0, and 36.6% of low-, moderate-, and high-risk groups, respectively, were hospitalized (AUC=0.826). Using demographic risk-factors and medications, 1.4, 5.6, and 40.3% of low-, moderate-, and high-risk patients were hospitalized (AUC=0.854, Table 1). The demographic/risk factor-score was also predictive of the risk of dying, with 0%, 0.9% and 4.5% in low-, moderate-, and high-risk groups dying (AUC=0.918). Adding medications to the risk-factors model further improved the prediction of death with 0.1, 0.04, and 4.9% in the low-, moderate-, and high-risk groups dying (AUC=0.942, Table 2). Conclusions: We demonstrate the derivation of highly predictive risk scores for COVD-19 patients at low, moderate, and high risks of hospitalization or death. Pending appropriate validation in another cohort, application of these risk-scores may allow healthcare systems to risk-stratify COVID-19 patients requiring variable intensity of care.