ABSTRACT
Cardiovascular disease (CVD) is one of the main causes of death in Saudi Arabia. Cardiac remodeling plays a critical role in the pathophysiology of heart failure. Major focus of our study was to identify crucial genes involved in the pathological remodeling of the heart caused by pressure overload. We utilized various in-silico tools to analyze and interpret microarray data obtained from the Gene Expression Omnibus (GEO) database (GSE120739), including GEO2R analysis, Metascape analysis, WebGestalt analysis, and IPA (Ingenuity pathway analysis). Our findings indicate that certain genes, including Cartilage Oligomeric Matrix Protein (COMP), collagen type VIII alpha 1 chain (COL8A1) and Lysyl Oxidase (LOX) under the influence caused by knockdown of KDM3A, were down regulated by the extracellular matrix pathway. Moreover, genes, such as Acyl-CoA Thioesterase 1 (ACOT1) were up regulated by the fatty acid metabolism pathway. Overexpression of lysine-specific demethylase 3A (KDM3A) leads to the up regulation of fibrosis-related genes COMP, COL8A1, and LOX and the down regulation of ACOT1, result in enhanced fibrosis and heart failure. Our results suggest that COMP, COL8A1, LOX, and ACOT1 warrant further investigation in the development of cardiac fibrosis and as potential biomarkers for causing heart failure.
ABSTRACT
BACKGROUND: Atherosclerotic coronary plaque dissection (ACPD) is one cause of acute coronary syndrome (ACS) caused by underlying atherosclerosis. Spontaneous coronary artery dissection (SCAD) occurs outside the setting of atherosclerosis among young women and individuals with few or no conventional atherosclerotic risk factors, and has emerged as an important cause of ACS, and sudden death. A comparison between ACPD and SCAD has not been previously addressed in the literature. Our study will compare ACPD and SCAD. METHODS: Patients with confirmed diagnosis of SCAD and ACPD were retrospectively identified from 30 centers in 4 Arab Gulf countries between January 2011 and December 2017. In-hospital (ventricular tachycardia/ventricular fibrillation, myocardial infarction (MI), percutaneous coronary intervention, dissection extension, cardiogenic shock, death, implantable cardioverter-defibrillator placement) and follow-up (MI, de novo SCAD, spontaneous superior mesenteric artery dissection, death) events were compared between them. RESULTS: Eighty-three cases of SCAD and 48 ACPD were compared. ACPD patients were more frequently male (91.67% vs. 49.40%, P < 0.001) and older (58.5 vs. 44, P < 0.001). Cardiovascular risk factors were more prevalent in patients with ACPD, including diabetes mellitus (60.4% vs. 25.3%), dyslipidemia (62.5% vs. 38.5%), and hypertension (62.5% vs. 31.3%), P < 0.001. Hospital presentation of ST-elevation MI was diagnosed in 48% of SCAD versus 27% of ACPD patients (P = 0.012). SCAD patients received medical-only treatment in 40% of cases and ACPD in 21% (P = 0.042). In-hospital and follow-up events were comparable in both groups (P = 0.25). CONCLUSIONS: Despite a completely different pathophysiology of ACS between SCAD and ACPD, in-hospital and follow-up events were comparable.
Subject(s)
Coronary Vessel Anomalies , Coronary Angiography , Coronary Vessel Anomalies/complications , Coronary Vessel Anomalies/diagnosis , Coronary Vessel Anomalies/epidemiology , Dissection , Female , Humans , Male , Retrospective StudiesABSTRACT
The COVID-19 pandemic had significant impact on health care worldwide which has led to a reduction in all elective admissions and management of patients through virtual care. The purpose of this study is to assess changes in STEMI volumes, door to reperfusion, and the time from the onset of symptoms until reperfusion therapy, and in-hospital events between the pre-COVID-19 (PC) and after COVID-19 (AC) period. All acute ST-segment elevation myocardial infarction (STEMI) cases were retrospectively identified from 16 centers in the Kingdom of Saudi Arabia during the COVID-19 period from January 01 to April 30, 2020. These cases were compared to a pre-COVID period from January 01 to April 30, 2018 and 2019. One thousand seven hundred and eighty-five patients with a mean age 56.3 (SD ± 12.4) years, 88.3% were male. During COVID-19 Pandemic the total STEMI volumes was reduced (28%, nâ¯=â¯500), STEMI volumes for those treated with reperfusion therapy was reduced too (27.6%, n= 450). Door to balloon time < 90 minutes was achieved in (73.1%, noâ¯=â¯307) during 2020. Timing from the onset of symptoms to the balloon of more than 12 hours was higher during 2020 comparing to pre-COVID 19 years (17.2% vs <3%, respectively). There were no differences between the AC and PC period with respect to in-hospital events and the length of hospital stay. There was a reduction in the STEMI volumes during 2020. Our data reflected the standard of care for STEMI patients continued during the COVID-19 pandemic while demonstrating patients delayed presenting to the hospital.
Subject(s)
COVID-19 , Patient Acceptance of Health Care , Percutaneous Coronary Intervention , ST Elevation Myocardial Infarction , Time-to-Treatment/statistics & numerical data , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19/psychology , Disease Transmission, Infectious/prevention & control , Female , Humans , Length of Stay/statistics & numerical data , Male , Middle Aged , Outcome and Process Assessment, Health Care , Patient Acceptance of Health Care/psychology , Patient Acceptance of Health Care/statistics & numerical data , Percutaneous Coronary Intervention/methods , Percutaneous Coronary Intervention/statistics & numerical data , Retrospective Studies , SARS-CoV-2 , ST Elevation Myocardial Infarction/diagnosis , ST Elevation Myocardial Infarction/epidemiology , ST Elevation Myocardial Infarction/therapy , Saudi Arabia/epidemiology , Severity of Illness Index , Standard of Care/organization & administrationABSTRACT
Spontaneous coronary artery dissection (SCAD) has emerged as an important cause of acute coronary syndrome and sudden cardiac death. The triggers for SCAD often do not include traditional atherosclerotic risk factors. The most commonly reported triggers are extreme physical or emotional stress. The current study compared in-hospital and follow-up events in patients with SCAD with and without reported stress. Data from 83 patients with a confirmed diagnosis of SCAD were collected retrospectively from 30 centers in 4 Arab Gulf countries (KSA, UAE, Kuwait, and Bahrain) from January 2011 to December 2017. In-hospital myocardial infarction (MI), percutaneous coronary intervention (PCI), ventricular tachycardia/ventricular fibrillation, cardiogenic shock, death, ICD placement, dissection extension) and follow-up (MI, de novo SCAD, death, spontaneous superior mesenteric artery dissection) events were compared between those with and without reported stress. Emotional and physical stress was defined as new or unusually intense stress, within 1 week of their initial hospitalization. The median age of patients in the study was 44 (37-55) years. Foty-two (51%) were women. Stress (emotional, physical, and combined) was reported in 49 (59%) of all patients. Sixty-two percent of women with SCAD reported stress, and 51 % of men with SCAD reported stress. Men more commonly reported physical and combined stress. Women more commonly reported emotional stress (P < 0.001). The presence or absence of reported stress did not impact on overall adverse cardiovascular events (Pâ¯=â¯0.8). In-hospital and follow-up events were comparable in patients with SCAD in the presence or absence of reported stress as a trigger.
Subject(s)
Coronary Vessel Anomalies , Percutaneous Coronary Intervention , Psychological Distress , Stress, Physiological , Vascular Diseases , Arabs , Coronary Angiography , Coronary Vessel Anomalies/etiology , Coronary Vessel Anomalies/psychology , Coronary Vessels , Dissection , Humans , Retrospective Studies , Vascular Diseases/etiology , Vascular Diseases/psychologyABSTRACT
BACKGROUND: Apolipoprotein E (APOE) gene is a ligand protein in humans which mediates the metabolism of cholesterol by binding to the low-density lipoprotein receptor (LDLR). P.Leu167del mutation in APOE gene was recently connected with Familial Hypercholesterolemia, a condition associated with premature cardiovascular disease. The consequences of this mutation on the protein structure and its receptor binding capacity remain largely unknown. OBJECTIVE: The current study aims to further decipher the underlying mechanism of this mutation using advanced software-based algorithms. The consequences of disrupting the leucine zipper by this mutation was studied at the structural and functional level of the APOE protein. METHODS: 3D protein modeling for both APOE and LDLR (wild types), along with APOE (p.Leu167del) mutant type were generated using homology modeling template-based alignment. Structural deviation analysis was performed to evaluate the spatial orientation and the stability of the mutant APOE structure. Molecular docking analysis simulating APOE-LDLR protein interaction was carried out, in order to evaluate the impact of the mutation on the binding affinity. RESULT: Structural deviation analysis for APOE mutated model showed low degree of deviance scoring root-mean-square deviation, (RMSD) = 0.322 Å. Whereas Docking simulation revealed an enhanced molecular interaction towards the LDLR with an estimation of +171.03 kJ/mol difference in binding free energy. CONCLUSION: This in-silico study suggests that p.Leu167del is causing the protein APOE to associate strongly with its receptor, LDLR. This gain-of-function is likely hindering the ability of LDLR to be effectively recycled back to the surface of the hepatocytes to clear cholesterol from the circulation therefore leading to FH.
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OBJECTIVES: Data reflecting cardiopulmonary resuscitation (CPR) efforts in Saudi Arabia are limited. In this study, we analyzed the characteristics, and estimated the outcome, of in-hospital CPR in a teaching hospital in Saudi Arabia over 4 years. METHODS: A retrospective, observational study was conducted between January 2009 and December 2012 and included 4361 patients with sudden cardiopulmonary arrest. Resuscitation forms were reviewed. Demographic data, resuscitation characteristics, and survival outcomes were recorded. RESULTS: The mean ± standard deviation age of arrested patient was 40 ± 31 years. The immediate survival rate was 64%, 43% at 24 h, and 30% at discharge. The death rate was 70%. Respiratory type of arrest, time and place of arrest, short duration of arrest, witnessed arrest, the use of epinephrine and atropine boluses, and shockable arrhythmias were associated with higher 24-h survival rates. A low survival rate was found among patients with cardiac types of arrest, and those with a longer duration of arrest, pulseless electrical activity, and asystole. Comorbidities were present in 3786 patients with cardiac arrest and contributed to a poor survival rate (P < 0.001). CONCLUSIONS: The study confirms the findings of previously published studies in highly developed countries and provides some reflection on the practice of resuscitation in Saudi Arabia.
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BACKGROUND: Familial hypercholesterolemia (FH) is a life-threatening inherited condition. Untreated patients have the risk to develop raised plasma levels of cholesterol, atherosclerosis and cardiovascular disease (CVD). If diagnosed and treated early in life, the pathological consequences due to atherosclerosis could be avoided and patients with FH can have an anticipated normal life. Mounting evidence suggests that FH is underdiagnosed and undertreated in all populations. The underlying molecular basis of FH is the presence of mutations in one or more genes in the low-density lipoprotein receptor (LDLR), apolipoprotein B (APOB) or proprotein convertase subtilisin/kexin 9 (PCSK9). However, their prevalence is largely unknown in Saudi Arabia but given the high rates of consanguinity, the prevalence appears to be higher. Furthermore, the high prevalence of obesity and diabetes mellitus in Saudi Arabia increases the vascular disease burden in FH cases by adding additional CVD risk factors. OBJECTIVE: This article explores the spectrum of FH-causing mutations in the highly consanguineous Saudi community, the need for establishing the Saudi FH registry, the challenges in creating gene databases, and cascade screening. CONCLUSION: The establishment of FH registry and genetic testing should raise awareness not only among healthcare professionals, but the general population as well. It also helps to provide the best treatment regimen in a cost effective manner to this under-recognised population of FH patients.
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BACKGROUND AND OBJECTIVES: In practice, clinical and logistic hurdles may hamper performing transesophageal echocardiography in stroke patients. Cardiac computed tomography (CT) is a recently introduced noninvasive modality able to detect various embolic causes. Thus, we retrospectively assessed possible added values of applying cardiac CT in the real-world work-up of suspected cardioembolic stroke cases. METHODS: Forty-seven patients were neurology service referrals for suspected cardioembolic stroke. The CT images and clinical reports of our cardiac CT radiologists were retrospectively evaluated. Cardiac CT was assessed in terms of detecting major embolic potential findings, potentially significant stroke-unrelated findings, and coronary arterial disease (CAD). Computed tomography results were correlated with echocardiographic reports. RESULTS: Cardiac CT showed findings of major embolic potential in 10 patients (21%, 5 thrombi cases, 2 vasculitis cases, 1 case of metastasis invading the left superior pulmonary artery, 1 myocardial infarction case, and 1 pulmonary arteriovenous malformations case), none of which were documented in echocardiography reports. Two cases (4%) with findings of major embolic potential where identified on echocardiography but not on CT (1 left atrial appendage thrombus and 1 mitral valve vegetation). Computed tomography of 13 patients (28%) showed 16 potentially significant stroke-unrelated findings. Twenty-one patients (47%) had unexpected CAD on CT, 11 (52%) of which were obstructive. CONCLUSIONS: Implementing cardiac CT in assessing patients suspected of cardioembolic stroke added value to echocardiographic evaluation, by detecting major embolic potential findings. In addition, cardiac CT revealed additional potentially significant stroke-unrelated findings and CAD.