Uncovering myocardial infarction genetic signatures using GWAS exploration in Saudi and European cohorts.

Genome-wide association studies (GWAS) have yielded significant insights into the genetic architecture of myocardial infarction (MI), although studies in non-European populations are still lacking. Saudi Arabian cohorts offer an opportunity to discover novel genetic variants impacting disease risk due to a high rate of consanguinity. Genome-wide genotyping (GWG), imputation and GWAS followed by meta-analysis were performed based on two independent Saudi Arabian studies comprising 3950 MI patients and 2324 non-MI controls. Meta-analyses were then performed with these two Saudi MI studies and the CardioGRAMplusC4D and UK BioBank GWAS as controls. Meta-analyses of the two Saudi MI studies resulted in 17 SNPs with genome-wide significance. Meta-analyses of all 4 studies revealed 66 loci with genome-wide significance levels of p < 5 × 10-8. All of these variants, except rs2764203, have previously been reported as MI-associated loci or to have high linkage disequilibrium with known loci. One SNP association in Shisa family member 5 (SHISA5) (rs11707229) was evident at a much higher frequency in the Saudi MI populations (> 12% MAF). In conclusion, our results replicated many MI associations, whereas in Saudi-only GWAS (meta-analyses), several new loci were implicated that require future validation and functional analyses.

Coffee Staining and Simulated Brushing Induced Color Changes and Surface Roughness of 3D-Printed Orthodontic Retainer Material.

This in vitro study evaluated the influence of combined coffee staining and simulated brushing-induced color changes and surface roughness on 3D-printed orthodontic retainers. Specimens measuring 10 × 10 × 0.75 mm3 were obtained either by conventional vacuum forming or 3D printing at four print angulations (0°, 15°, 30°, and 45°) (n = 10). The prepared specimens were immersed in a coffee beverage and then mechanically brushed using a simulating device. The specimen's color difference (ΔE) and surface roughness (Ra) were quantified using a spectrophotometer and a non-contact profilometer, respectively. The highest and lowest mean ΔE values were recorded for the 3D-printed-45° (4.68 ± 2.07) and conventional (2.18 ± 0.87) groups, respectively. The overall mean comparison of ΔE between the conventional and 3D-printed groups was statistically significant (p < 0.01). After simulated brushing, all groups showed a statistically significant increase in the Ra values (p < 0.01). The highest Ra was in the 3D-printed-45° (1.009 ± 0.13 µm) and conventional (0.743 ± 0.12 µm) groups, respectively. The overall ΔE of 3D-printed orthodontic retainers was not comparable to conventional VFRs. Among the different angulations used to print the retainers, 15° angulations were the most efficient in terms of color changes and surface roughness and were comparable to conventional VFRs.

The impact of SELP gene Thr715Pro polymorphism on sP-selectin level and association with cardiovascular disease in Saudi diabetic patients: A cross-sectional case-control study.

Background: Cardiovascular diseases (CVD) are leading cause of mortality in patients with type 2 diabetes mellitus (T2DM). Increased soluble sP-selectin and 715Thr > Pro polymorphism were studied in CVD and T2DM, but association between them hasn't been explored in Saudi Arabia. We aimed to assess sP-selectin levels in T2DM and T2DM-associated CVD patients in comparison to healthy control cohort. Also, we sought to investigate relationship between Thr715Pro polymorphism and sP-selectin levels and disease state. Methods: This is a cross-sectional case-control study. sP-selectin level (measured by Enzyme-linked immunosorbent assay) and prevalence of Thr715Pro polymorphism (assessed by Sanger sequencing) were investigated in 136 Saudi participants. The study comprised 3 groups: group1 included 41 T2DM patients; group 2 (48 T2DM patients with CVD), and group 3 (47 healthy controls). Results: sP-selectin levels were significantly higher in diabetics and diabetics + CVD groups as compared to the corresponding control. In addition, results showed that the prevalence of 715Thr > Pro polymorphism is 11.75 % in the study population amongst the three study groups (9.55 % Thr/Pro, and 2.2 % Pro/Pro). No statistical difference was found between sP-selectin levels in subject carrying the wildtype genotype of this polymorphism and these who carry the mutant gene. There could be an association between this polymorphism and T2DM, whilst the polymorphism may protect diabetic patients from having CVD. However, odds ratio is not statistically significant in both cases. Conclusion: Our study supports the previous researches' results that Thr715Pro is neither influencing the sP-selectin level nor the risk of CVD in T2DM patients.

Effect of COVID-19 on Glycemic Control, Insulin Resistance, and pH in Elderly Patients With Type 2 Diabetes.

Background The coronavirus disease of 2019 (COVID-19) was spread all over the world, while diabetes mellitus (DM) remains the most prevalent chronic disease worldwide. Aims This study aims to investigate the effect of COVID-19 on glycemic control, insulin resistance (IR), and pH in elderly patients with type 2 diabetes. Methods  A retrospective study was conducted on patients with type 2 DM who were diagnosed with COVID-19 infection in the central hospitals of the Tabuk region. Patient data were collected from September 2021 to August 2022. Four non-insulin-based insulin resistance indexes were calculated for patients: the triglyceride-glucose (TyG) index, the triglyceride glucose-body mass index (TyG-BMI) index, the triglyceride to high-density lipoprotein cholesterol (TG/HDL) ratio, and the metabolic score for insulin resistance (METS-IR). Results Patients showed increased serum fasting glucose and blood HbA1c associated with a high TyG index, TyG-BMI index, TG/HDL ratio, and METS-IR as compared with results before COVID-19. Moreover, during COVID-19, patients revealed a reduction in pH, associated with a reduction in cBase and bicarbonate, and an elevation in PaCO2 as compared with their results before COVID-19. After complete remission, all patients' results turn back to their level before COVID-19. Conclusions Patients with type 2 DM who catch the COVID-19 infection suffer from dysregulation of glycemic control and elevated insulin resistance associated with a significant reduction in their pH.

The Overriding of Computerized Physician Order Entry (CPOE) Drug Safety Alerts Fired by the Clinical Decision Support (CDS) Tool: Evaluation of Appropriate Responses and Alert Fatigue Solutions.

Introduction Most computerized physician order entry (CPOE) software come with clinical decision-support components (CDS) that provide prescribers assistance and notify them about adverse drug reactions. An excessive number of alerts in a repeated and non-relevant manner leads to alert fatigue and enforces physicians and pharmacists to alert overrides. King Abdulaziz Medical City (KAMC) in Jeddah still reports a higher percentage of drug alerts overridden by clinicians and pharmacists. Thus, this study was conducted to evaluate CDS alerts overriding and to determine which alerts are clinically irrelevant and need modifications. Methods The study was carried out in the inpatient setting at KAMC in Jeddah, from September 1, 2020, to December 31, 2020. It was designed as a retrospective chart review study that included all red alerts that required comments and were overridden by a physician and pharmacist. Results Among 11350 red alerts, potential drug-drug interaction (pDDI), dose, and allergy alerts represent 57%, 41%, and 2%, respectively, of the total alerts. The most common drug-drug interactions (DDIs) in category X were proton pump inhibitors and clopidogrel (9.9%). The appropriate response by prescribers and pharmacists toward allergy alerts was associated with the highest odds compared with the other alerts (p < 0.05) while there is a significant decrease in the odds of appropriate action being taken by both prescribers and pharmacists in the dose screen alerts (p < 0.05). Among all clinical specialties, there is an increased odds of appropriate action being taken by residents and fellows for allergy and dose alerts, respectively, compared to other groups (p < 0.05). For diminishing the unnecessary alerts, we provided 14 alert refinements strategies and advised turning off four alerts. Applying this will terminate 32% of irrelevant alerts. Conclusion Our study's findings indicated that a substantial number of alerts are ignored, and the rate of appropriateness varies significantly by alert type and prescriber level.

Advances in Fungal Phenaloenones-Natural Metabolites with Great Promise: Biosynthesis, Bioactivities, and an In Silico Evaluation of Their Potential as Human Glucose Transporter 1 Inhibitors.

Phenaloenones are structurally unique aromatic polyketides that have been reported in both microbial and plant sources. They possess a hydroxy perinaphthenone three-fused-ring system and exhibit diverse bioactivities, such as cytotoxic, antimicrobial, antioxidant, and anti-HIV properties, and tyrosinase, α-glucosidase, lipase, AchE (acetylcholinesterase), indoleamine 2,3-dioxygenase 1, angiotensin-I-converting enzyme, and tyrosine phosphatase inhibition. Moreover, they have a rich nucleophilic nucleus that has inspired many chemists and biologists to synthesize more of these related derivatives. The current review provides an overview of the reported phenalenones with a fungal origin, including their structures, sources, biosynthesis, and bioactivities. Moreover, more than 135 metabolites have been listed, and 71 references have been cited. SuperPred, an artificial intelligence (AI) webserver, was used to predict the potential targets for selected phenalenones. Among these targets, we chose human glucose transporter 1 (hGLUT1) for an extensive in silico study, as it shows high probability and model accuracy. Among them, aspergillussanones C (60) and G (60) possessed the highest negative docking scores of -15.082 and -14.829 kcal/mol, respectively, compared to the native inhibitor of 5RE (score: -11.206 kcal/mol). The MD (molecular dynamics) simulation revealed their stability in complexes with GLUT1 at 100 ns. The virtual screening study results open up a new therapeutic approach by using some phenalenones as hGLUT1 inhibitors, which might be a potential target for cancer therapy.

Bedside testing of CYP2C19 vs. conventional clopidogrel treatment to guide antiplatelet therapy in ST-segment elevation myocardial infarction patients.

BACKGROUND: ST-segment elevation myocardial infarction (STEMI) patients are treated with dual antiplatelet therapy comprising aspirin and a P2Y12 inhibitor. Clopidogrel is widely used in these patients in several areas worldwide, such as Middle East, but is associated to sub-optimal platelet inhibition in up to 1/3 of treated patients. We investigated a CYP2C19 genotype-guided strategy to select the optimal P2Y12 inhibitor. METHODS: This prospective randomized clinical trial included STEMI patients. The standard-treatment group received clopidogrel, while the genotype-guided group were genotyped for CYP2C19 loss-of-function alleles and carriers were prescribed ticagrelor and noncarriers were prescribed clopidogrel. Primary outcome was a combined ischemic and bleeding outcome, comprising myocardial infarction, non-fatal stroke, cardiovascular death, or Platelet Inhibition and Patient Outcomes major bleeding one year after STEMI. RESULTS: STEMI patients (755) were randomized into a genotype-guided- (383) and standard-treatment group (372). In the genotype-guided group, 31 patients carrying a loss-of-function allele were treated with ticagrelor, while all other patients in both groups were treated with clopidogrel. Patients in the genotype-guided group had a significantly lower risk of primary outcome (odds ratio (OR) 0.34, 95% confidence interval (CI) 0.20-0.59,), recurrent myocardial infarction (OR 0.25, 95%CI 0.11-0.53), cardiovascular death (OR 0.16, 95%CI0.06-0.42) and major bleeding (OR 0.49, 95%CI 0.32-0.74). There was no significant difference in the rate of stent thrombosis (OR 0.85, 95%CI 0.43-1.71). CONCLUSION: A genotype-guided escalation of P2Y12 inhibitor strategy is feasible in STEMI patients treated with clopidogrel and undergoing PCI and is associated with a reduction of primary outcomes compared to conventional antiplatelet therapy.

Prevalence of CYP2C19*2 carriers in Saudi ischemic stroke patients and the suitability of using genotyping to guide antiplatelet therapy in a university hospital setup.

OBJECTIVES: To mitigate the incidence of recurrent stroke in patients, dual antiplatelet therapy comprising aspirin and clopidogrel is usually administered. Clopidogrel is a prodrug and its bioactivation is catalyzed by cytochrome P450 (CYP)2C19. The main objective of this work was to determine the prevalence of CYP2C19*2 carriers in Saudi ischemic stroke patients and assess the suitability of using genotyping to guide antiplatelet therapy in a university hospital setup. METHODS: This prospective (2018-2019) study was conducted on 256 patients (age 61 ± 12.5) clinically diagnosed with ischemic stroke who were genotyped using Spartan RX CYP2C19 assay. RESULTS: From the total patient group (256), upon admission, 210 patients were prescribed either aspirin, clopidogrel or dual antiplatelet therapy. Of the 27 patients with the CYP2C19*2 allele who were prescribed clopidogrel (18) or dual antiplatelet therapy (9), only 21 patients could be followed up for a period of six months post stroke event, in addition to 21 age- and sex-matched patients with the normal allele. The CYP2C19*2 allele carriers had a statistically significant increased risk of recurrent stroke compared to patients carrying the normal allele. CONCLUSIONS: This study shows the suitability of using genotyping to guide antiplatelet therapy in ischemic stroke patients in a clinical setting.

Prevalence of CYP2C19*2 carriers in Saudi ischemic stroke patients and the suitability of using genotyping to guide antiplatelet therapy in a university hospital setup.

OBJECTIVES: To mitigate the incidence of recurrent stroke in patients, dual antiplatelet therapy comprising aspirin and clopidogrel is usually administered. Clopidogrel is a prodrug and its bioactivation is catalyzed by cytochrome P450 (CYP)2C19. The main objective of this work was to determine the prevalence of CYP2C19*2 carriers in Saudi ischemic stroke patients and assess the suitability of using genotyping to guide antiplatelet therapy in a university hospital setup. METHODS: This prospective (2018-2019) study was conducted on 256 patients (age 61 ± 12.5) clinically diagnosed with ischemic stroke who were genotyped using Spartan RX CYP2C19 assay. RESULTS: From the total patient group (256), upon admission, 210 patients were prescribed either aspirin, clopidogrel or dual antiplatelet therapy. Of the 27 patients with the CYP2C19*2 allele who were prescribed clopidogrel (18) or dual antiplatelet therapy (9), only 21 patients could be followed up for a period of six months post stroke event, in addition to 21 age- and sex-matched patients with the normal allele. The CYP2C19*2 allele carriers had a statistically significant increased risk of recurrent stroke compared to patients carrying the normal allele. CONCLUSIONS: This study shows the suitability of using genotyping to guide antiplatelet therapy in ischemic stroke patients in a clinical setting.

Coronavirus disease 2019 pandemic stress and its effects on irritable bowel syndrome patients in Saudi Arabia.

ABSTRACT: Coronavirus disease 2019 (COVID-19 pandemic has affected the psychological health of people, causing a higher level of stress. Stress can exaggerate the symptoms of irritable bowel syndrome (IBS).To assess the effect of the COVID-19 pandemic stress on patients with IBS in Saudi Arabia.A descriptive cross-sectional approach was used, which targeted accessible subjects with IBS from different regions of Saudi Arabia. Data were collected from participants using a structured electronic questionnaire, which captured the participants' socio-demographic data, medical history, IBS clinical data, self-reported stress due to COVID-19, and its effect on IBS symptoms.A total of 1255 IBS patients completed the questionnaire. About 63.4% of them reported stress due to the pandemic. The most frequently reported causes of stress were fear of infection occurring in the family, followed by fear of self-infection (43.5%), and death due to COVID-19 infection (17.2%). Most of the stressed participants (56.6%) reported that stress usually exaggerated IBS symptoms. Almost 22% of them consulted a physician for stress aggravation of the symptoms, 18.1% used sedatives due to stress, 9.2% modified IBS medications due to the stress, and 75.5% of the participants reported impaired daily activities due to symptoms exacerbation. Coexisting chronic morbidities and inability to differentiate between COVID-19 gastrointestinal symptoms and IBS symptoms were significantly associated with COVID-19 related stress (P = .039 and .001, respectively).Two-thirds of IBS patients were stressed during the first few months of COVID-19 pandemic. Patients unable to differentiate between COVID-19 gastrointestinal tract symptoms and IBS symptoms, and patients suffering from chronic morbidities were more vulnerable. Pandemic stress exacerbated patients' symptoms and impacted their activities of daily life.

Schoolteachers' Knowledge of Attention-Deficit/Hyperactivity Disorder-Current Status and Effectiveness of Knowledge Improvement Program: A Randomized Controlled Trial.

BACKGROUND: Adequately knowledgeable schoolteachers can play an essential role in early detection and proper treatment of children with attention-deficit/hyperactivity disorder (ADHD) at school. OBJECTIVES: To assess the schoolteachers' knowledge of ADHD and to evaluate the effectiveness of the ADHD knowledge improvement program. METHODS: A randomized controlled trial study design was followed on 100 primary school teachers from Abha City, Saudi Arabia. Teachers were randomly selected and allocated into trial and control groups. A self-administered questionnaire was used to evaluate teachers' knowledge about ADHD. After the baseline assessment, participants in the trial group received a two-day ADHD knowledge improvement program. Teachers' knowledge about ADHD was reassessed using the same questionnaire immediately after finishing the intervention program and after three months in both groups. RESULTS: Only 16% and 22% of trial and control groups, respectively, showed adequate baseline knowledge about ADHD. Teachers' main sources of information about ADHD were the internet (67%), friends (47%), TV (34%), and reading books (23%). Knowledge of teachers in the trial group significantly improved immediately after the intervention. After three months, these knowledge benefits slightly declined but remained more adequate than those of teachers in the control group. The logistic regression model revealed that being a participant in the trial group and of higher qualification were associated with significant improvement in teachers' retained knowledge on ADHD (p < 0.001 and p = 0.050, respectively). CONCLUSIONS: The majority of male primary school teachers in Abha City, Saudi Arabia, have inadequate knowledge about ADHD. Applying a knowledge improvement program can substantially improve their knowledge of ADHD. Consideration should be given to the integration of ADHD knowledge improvement program into teachers' educational programs.

Bedside testing of CYP2C19 gene for treatment of patients with PCI with antiplatelet therapy.

BACKGROUND: To mitigate the risk of stent thrombosis, patients treated by percutaneous coronary intervention (PCI) are administered dual anti-platelet therapy comprising aspirin and a platelet P2Y12 receptor inhibitor. Clopidogrel is a prodrug requiring activation by the cytochrome P450 enzyme, CYP2C19. In Saudi Arabia, it has been reported that approximately 26% of the population carries CYP2C19*2 and/or *3 loss-of-function polymorphisms in addition to a high prevalence of CVD. METHODS: This prospective (April 2013-December 2020) parallel assignment clinical trial focuses on ST-Elevation Myocardial Infarction (STEMI) patient outcomes. The clinical trial includes 1500 STEMI patients from two hospitals in the Eastern Province of Saudi Arabia. Patients are assigned to one of two groups; the control arm receives conventional therapy with clopidogrel, while in the active arm the Spartan RX CYP2C19 assay is used to determine the *2 genotype. Carriers of a CYP2C19*2 loss-of-function allele receive prasugrel or ticagrelor, while non-carriers are treated with clopidogrel. Follow-up is one year after primary PCI. The primary end point is the number of patients who develop an adverse major cardiovascular event, including recurrent MI, non-fatal stroke, cardiovascular death, or major bleeding one year after PCI. DISCUSSION: The risk of stent thrombosis in PCI patients is usually reduced by dual anti-platelet therapy, comprising aspirin and a P2Y12 inhibitor, such as clopidogrel. However, clopidogrel requires activation by the cytochrome P450 enzyme, CYP2C19. Approximately 20% of the population are unable to activate clopidogrel as they possess the CYP2C19*2 loss-of function (LoF) allele. The primary goal of this trial is to study the benefits of treating only those patients that cannot activate clopidogrel with an alternative that has shown to be a more effective platelet inhibitor and does not require bioactivation by the cytochrome P450 enzyme. We expect an improvement in net clinical benefit outcome in the active arm patients, thus supporting pharmacogenetic testing in PCI patients post STEMI. TRIAL REGISTRATION: Trial registration name is "Bedside Testing of CYP2C19 Gene for Treatment of Patients with PCI with Antiplatelet Therapy" (number NCT01823185) retrospectively registered with clinicaltrials.gov on April 4, 2013. This trial is currently at the patient recruitment stage.

Patient-Ventilator Asynchrony in Critical Care Settings: National Outcomes of Ventilator Waveform Analysis.

BACKGROUND: Patient-ventilator asynchrony (PVA) is a prevalent and often underrecognized problem in mechanically ventilated patients. Ventilator waveform analysis is a noninvasive and reliable means of detecting PVAs, but the use of this tool has not been broadly studied. METHODS: Our observational analysis leveraged a validated evaluation tool to assess the ability of critical care practitioners (CCPs) to detect different PVA types as presented in three videos. This tool consisted of three videos of common PVAs (i.e., double-triggering, auto-triggering, and ineffective triggering). Data were collected via an evaluation sheet distributed to 39 hospitals among the various CCPs, including respiratory therapists (RTs), nurses, and physicians. RESULTS: A total of 411 CCPs were assessed; of these, only 41 (10.2%) correctly identified the three PVA types, while 92 (22.4%) correctly detected two types and 174 (42.3%) correctly detected one; 25.3% did not recognize any PVA. There were statistically significant differences between trained and untrained CCPs in terms of recognition (three PVAs, p < 0.001; two PVAs, p = 0.001). The majority of CCPs who identified one or zero PVAs were untrained, and such differences among groups were statistically significant (one PVA, p = 0.001; zero PVAs, p = 0.004). Female gender and prior training on ventilator waveforms were found to increase the odds of identifying more than two PVAs correctly, with odds ratios (ORs) (95% confidence intervals [CIs]) of 1.93 (1.07-3.49) and 5.41 (3.26-8.98), respectively. Profession, experience, and hospital characteristics were not found to correlate with increased odds of detecting PVAs; this association generally held after applying a regression model on the RT profession, with the ORs (95% CIs) of prior training (2.89 [1.28-6.51]) and female gender (2.49 [1.15-5.39]) showing the increased odds of detecting two or more PVAs. CONCLUSION: Common PVAs detection were found low in critical care settings, with about 25% of PVA going undetected by CCPs. Female gender and prior training on ventilator graphics were the only significant predictive factors among CCPs and RTs in correctly identifying PVAs. There is an urgent need to establish teaching and training programs, policies, and guidelines vis-à-vis the early detection and management of PVAs in mechanically ventilated patients, so as to improve their outcomes.

Large Aneurysm of the Left Main Coronary Artery: A Case Report.

Left main coronary artery aneurysms are very rare and are incidentally encountered in about 0.1% of patients undergoing angiography. Atherosclerosis represents the main cause of this aneurysm in adult patients. Here, the author presents a case of a 58-year-old female with a history of hypertension and diabetes who had a Canadian Cardiovascular Society Grade II-III angina for the past 6 months. Selective coronary angiography revealed a large aneurysm involving the left main coronary artery (measuring 2 cm × 3 cm) with extensive coronary calcifications, ectatic proximal left circumflex followed by 80% stenotic lesion with normal left anterior descending and right coronary artery. The patient was managed with coronary artery bypass grafting along with ligation of the aneurysm. At the 3-month follow-up, the patient was asymptomatic. Therefore, distal coronary artery bypass surgery represents one of the therapeutic options and was safe and effective in our case.

Stroke in atrial fibrillation: Review of risk stratification and preventive therapy.

Atrial fibrillation (AF) is a leading preventable cause of ischemic stroke for which early detection and treatment are critical. The risk of stroke in people with AF can be stratified by the use of such validated prediction instruments such as CHADS2 or CHA2 DS2-VASc. The CHA2 DS2-VASc adds to the evaluation of the risk of stroke by reliably identifying patients at very low risk. Additional points are assigned for an additional age category of 65-74 years (1 point), female sex (1 point), and vascular disease other than cerebrovascular disease (1 point). Two points are awarded for age ≥75 years. The risk of stroke increases according to point score: 0.5% per year (0 points), 1.5% per year (1 point), 2.5% per year (2 points), 5% per year (3 points), 6% per year (4 points), and 7% per year (5-6 points). For decades, Vitamin K antagonists were the only class of oral anticoagulants available to clinicians for the prevention of stroke in AF. However, new oral anticoagulants (NOACs), such as apixaban, dabigatran, and rivaroxaban, are currently available and have proved to be safe and effective in preventing stroke in patients with nonvalvular AF. In addition, a nonpharmacologic procedure like left atrial appendage occlusion is a possible option in selected patients. In this article, we have reviewed the stratification of stroke risk in AF, prevention of stroke in nonvalvular AF, warfarin versus NOACs, weighting risk of bleeding versus stroke risk when deciding on the anticoagulation protocol in patients with AF, and the use of nonpharmacologic therapy for stroke prevention.

Effect of Xanthine Oxidase Inhibition on Arterial Stiffness in Patients With Chronic Heart Failure.

BACKGROUND: The xanthine oxidase inhibitor allopurinol improves endothelial function in different populations, including patients with chronic heart failure (CHF). Its effect on arterial stiffness parameters is less clear. We investigated the effect of short-term low-dose allopurinol therapy on arterial stiffness in Saudi patients with stable mild-moderate CHF. METHODS: A prospective, randomized, double-blind, placebo-controlled study was performed on 73 patients with mild-moderate CHF. In all, 36 patients were randomized to allopurinol 300 mg daily for 3 months, while 37 patients were randomized to placebo. Arterial stiffness parameters, aortic pulse wave velocity (Ao-PWV) and heart rate corrected augmentation index (c-AIx), were assessed before and after treatment along with serum uric acid. RESULTS: A total of 66 patients completed the study. Both groups were matched for age, sex, severity of heart failure, and arterial stiffness. Compared with placebo, allopurinol recipients had a significant fall in uric acid concentration from 6.31 ± 1.4 (SD) mg/dL to 3.81 ± 1.2 (P < .001). Despite that, there was no significant change in arterial stiffness parameters between allopurinol and placebo groups. Post-treatment Ao-PWV was 9.79 ± 2.6 m/s in the allopurinol group and 10.07 ± 3.4 m/s in the placebo group, P = .723. Post-treatment c-AIx was 24.0% ± 9.1% and 22.0% ± 9.9%, respectively, P = .403. CONCLUSIONS: We have shown that allopurinol significantly reduced uric acid concentration in Saudi patients with CHF but was not associated with a change in arterial stiffness. Our cohort of patients had worse arterial stiffness values at baseline, which might make them more resistant to change using our study regimen.The study has been registered with the International Standard Randomized Controlled Trial Number registry with an identifier number of ISRCTN58980230.

Morning Blood Pressure Surge as a Predictor of Outcome in Patients with Essential Hypertension.

OBJECTIVE: To determine the usefulness of monitoring morning blood pressure surge (MBPS) to predict cardiovascular events in patients with essential hypertension. MATERIALS AND METHODS: A total of 81 patients (43 males and 38 females) with a mean age of 55.9 ± 9.8 years with essential hypertension were included in the study. Twenty-four hour ambulatory blood pressure (BP) monitoring was carried out to record MBPS. All patients were followed up for 36 months for cardiovascular events. RESULTS: Mean MBPS was 26.23 ± 10.17 mmHg. Nineteen patients (23%) who experienced a cardiovascular event during the follow-up period had higher MBPS than patients who did not experience a cardiovascular event (P < 0.0001). MBPS was positively correlated with interventricular septum thickness (r = +0.38 and P = 0.000), left atrial size (r = +0.39 and P = 0.000), 24-h mean systolic BP (r = +0.36 and P = 0.001) and total cholesterol level (r = +0.23 and P = 0.003). MBPS was negatively correlated with high-density lipoprotein-cholesterol (r = -0.37 and P = 0.001). CONCLUSION: MBPS can be used as a biomarker for a cardiovascular disease event in hypertensive patients.

Exome-Wide Association Analysis of Coronary Artery Disease in the Kingdom of Saudi Arabia Population.

Coronary Artery Disease (CAD) remains the leading cause of mortality worldwide. Mortality rates associated with CAD have shown an exceptional increase particularly in fast developing economies like the Kingdom of Saudi Arabia (KSA). Over the past twenty years, CAD has become the leading cause of death in KSA and has reached epidemic proportions. This rise is undoubtedly caused by fast urbanization that is associated with a life-style that promotes CAD. However, the question remains whether genetics play a significant role and whether genetic susceptibility is increased in KSA compared to the well-studied Western European populations. Therefore, we performed an Exome-wide association study (EWAS) in 832 patients and 1,076 controls of Saudi Arabian origin to test whether population specific, strong genetic risk factors for CAD exist, or whether the polygenic risk score for known genetic risk factors for CAD, lipids, and Type 2 Diabetes show evidence for an enriched genetic burden. Our results do not show significant associations for a single genetic locus. However, the heritability estimate for CAD for this population was high (h(2) = 0.53, S.E. = 0.1, p = 4e(-12)) and we observed a significant association of the polygenic risk score for CAD that demonstrates that the population of KSA, at least in part, shares the genetic risk associated to CAD in Western populations.