IFIH1 loss of function predisposes to inflammatory and SARS-CoV-2-related infectious diseases.

The IFIH1 gene, encoding melanoma differentiation-associated protein 5 (MDA5), is an indispensable innate immune regulator involved in the early detection of viral infections. Previous studies described MDA5 dysregulation in weakened immunological responses, and increased susceptibility to microbial infections and autoimmune disorders. Monoallelic gain-of-function of the IFIH1 gene has been associated with multisystem disorders, namely Aicardi-Goutieres and Singleton-Merten syndromes, while biallelic loss causes immunodeficiency. In this study, nine patients suffering from recurrent infections, inflammatory diseases, severe COVID-19 or multisystem inflammatory syndrome in children (MIS-C) were identified with putative loss-of-function IFIH1 variants by whole-exome sequencing. All patients revealed signs of lymphopaenia and an increase in inflammatory markers, including CRP, amyloid A, ferritin and IL-6. One patient with a pathogenic homozygous variant c.2807+1G>A was the most severe case showing immunodeficiency and glomerulonephritis. The c.1641+1G>C variant was identified in the heterozygous state in patients suffering from periodic fever, COVID-19 or MIS-C, while the c.2016delA variant was identified in two patients with inflammatory bowel disease or MIS-C. There was a significant association between IFIH1 monoallelic loss of function and susceptibility to infections in males. Expression analysis showed that PBMCs of one patient with a c.2016delA variant had a significant decrease in ISG15, IFNA and IFNG transcript levels, compared to normal PBMCs, upon stimulation with Poly(I:C), suggesting that MDA5 receptor truncation disrupts the immune response. Our findings accentuate the implication of rare monogenic IFIH1 loss-of-function variants in altering the immune response, and severely predisposing patients to inflammatory and infectious diseases, including SARS-CoV-2-related disorders.

Rapid whole genome sequencing of critically ill pediatric patients from genetically underrepresented populations.

We describe a case series of five infants (age range: 1-90 days; 4 females and 1 male) who presented to Al Jalila Children's intensive care units (ICU) with complex multisystem disorders. Patients were Emirati, Kenyan, Jordanian, Filipino, or Pakistani. Trio rapid whole genome sequencing (rWGS) was performed on all five patients and their parents within the hospital's genomics facility. Results were returned within ~37 h from blood sample draws and were diagnostic in 3 out of 5 patients. Positive findings were a homozygous pathogenic variant in POMT1 gene causing muscular dystrophydystroglycanopathy, a mosaic tetrasomy of the short arm of chromosome 12 (12p13.33p11.1) causing Pallister-Killian syndrome, and compound heterozygous pathogenic variants in the LIPA gene causing lysosomal acid lipase deficiency and Wolman disease. The rWGS analysis provided fast and precise diagnostic findings in those 3 patients and also aided in devising better management plans for them in the intensive care setting. For example, the 3-month-old infant with pathogenic variants in the LIPA gene is now a candidate for an FDA-approved, potentially lifesaving enzyme replacement therapy (sebelipase alfa). Our case series emphasize the feasibility and utility of rWGS in pediatric intensive care setting, in a diverse population that has long been underserved in genomic services. Significant investments in local healthcare infrastructure are needed, globally, for more equitable access of genomic medicine among vulnerable patients.

Risk Factors for Premature Myocardial Infarction: A Systematic Review and Meta-analysis of 77 Studies.

OBJECTIVE: To evaluate the magnitude of the association between risk factors and premature myocardial infarction (MI) (men aged 18-55 years; women aged 18-65 years). PATIENTS AND METHODS: We searched MEDLINE and other databases from inception through April 30, 2020, as well as bibliography of articles selected for data extraction. We selected observational studies reporting the magnitude of the association of at least 1 risk factor (demographic characteristics, lifestyle factors, clinical risk factors, or biomarkers) with premature MI and a control group. Pooled risk estimates (random effects) from all studies unadjusted and adjusted for risk factors were reported as summary odds ratios (ORs) with 95% CIs. RESULTS: From 35,320 articles of 12.7 million participants, we extracted data on 19 risk factors from 77 studies across 58 countries. Men had a higher risk of premature MI (OR, 2.39; 95% CI, 1.71 to 3.35) than did women. Family history of cardiac disease was associated with a higher risk of premature MI (OR, 2.67; 95% CI, 2.29 to 3.27). Major modifiable risk factors associated with higher risk were current smoking (OR, 4.34; 95% CI, 3.68 to 5.12 vs no/former), diabetes mellitus (OR, 3.54; 95% CI, 2.69 to 4.65), dyslipidemia (OR, 2.94; 95% CI, 1.76 to 4.91), and hypertension (OR, 2.85; 95% CI, 2.48 to 3.27). Higher body mass index carried higher risk (OR, 1.46; 95% CI, 1.24 to 1.71 for ≥25 kg/m2 vs <25 kg/m2). Biomarkers associated with 2- to 3-fold higher risk were total cholesterol levels greater than 200 mg/dL, triglyceride levels higher than 150 mg/dL, and high-density lipoprotein cholesterol levels less than 60 mg/dL (to convert to mmol/L, multiply by 0.0259). CONCLUSION: Major risk factors for premature MI are mostly amenable to patient, population, and policy level interventions. Mild elevations in body mass index and triglyceride levels were associated with higher risk, which has implications for the growing worldwide epidemic of cardiometabolic diseases.

Association of Lipid, Inflammatory, and Metabolic Biomarkers With Age at Onset for Incident Coronary Heart Disease in Women.

Importance: Risk profiles for premature coronary heart disease (CHD) are unclear. Objective: To examine baseline risk profiles for incident CHD in women by age at onset. Design, Setting, and Participants: A prospective cohort of US female health professionals participating in the Women's Health Study was conducted; median follow-up was 21.4 years. Participants included 28 024 women aged 45 years or older without known cardiovascular disease. Baseline profiles were obtained from April 30, 1993, to January 24, 1996, and analyses were conducted from October 1, 2017, to October 1, 2020. Exposures: More than 50 clinical, lipid, inflammatory, and metabolic risk factors and biomarkers. Main Outcomes and Measures: Four age groups were examined (<55, 55 to <65, 65 to <75, and ≥75 years) for CHD onset, and adjusted hazard ratios (aHRs) were calculated using stratified Cox proportional hazard regression models with age as the time scale and adjusting for clinical factors. Women contributed to different age groups over time. Results: Of the clinical factors in the women, diabetes had the highest aHR for CHD onset at any age, ranging from 10.71 (95% CI, 5.57-20.60) at CHD onset in those younger than 55 years to 3.47 (95% CI, 2.47-4.87) at CHD onset in those 75 years or older. Risks that were also noted for CHD onset in participants younger than 55 years included metabolic syndrome (aHR, 6.09; 95% CI, 3.60-10.29), hypertension (aHR, 4.58; 95% CI, 2.76-7.60), obesity (aHR, 4.33; 95% CI, 2.31-8.11), and smoking (aHR, 3.92; 95% CI, 2.32-6.63). Myocardial infarction in a parent before age 60 years was associated with 1.5- to 2-fold risk of CHD in participants up to age 75 years. From approximately 50 biomarkers, lipoprotein insulin resistance had the highest standardized aHR: 6.40 (95% CI, 3.14-13.06) for CHD onset in women younger than 55 years, attenuating with age. In comparison, weaker but significant associations with CHD in women younger than 55 years were noted (per SD increment) for low-density lipoprotein cholesterol (aHR, 1.38; 95% CI, 1.10-1.74), non-high-density lipoprotein cholesterol (aHR, 1.67; 95% CI, 1.36-2.04), apolipoprotein B (aHR, 1.89; 95% CI, 1.52-2.35), triglycerides (aHR, 2.14; 95% CI, 1.72-2.67), and inflammatory biomarkers (1.2- to 1.8-fold)-all attenuating with age. Some biomarkers had similar CHD age associations (eg, physical inactivity, lipoprotein[a], total high-density lipoprotein particles), while a few had no association with CHD onset at any age. Most risk factors and biomarkers had associations that attenuated with increasing age at onset. Conclusions and Relevance: In this cohort study, diabetes and insulin resistance, in addition to hypertension, obesity, and smoking, appeared to be the strongest risk factors for premature onset of CHD. Most risk factors had attenuated relative rates at older ages.

Incidence of Contrast-Induced Nephropathy after Coronary Procedures in the United Arab Emirates: A Single-Center Study.

Contrast-induced nephropathy (CIN) is a major cause of morbidity and mortality in patients undergoing coronary procedures. The reported incidence of CIN ranges from ~3% to 30%. The profile of patients undergoing coronary procedures in the United Arab Emirates (UAE) differs from those included in published reports of CIN, and the incidence of CIN after coronary procedures in the UAE remains unknown. We conducted a retrospective analysis of all adult patients who underwent coronary procedures at a large tertiary care facility in the UAE in 2013-2014. Patients on dialysis or missing creatinine values were excluded. CIN was defined as an increase of creatinine of ≥44 µmol/L within 48-72 h after coronary procedures. Most patients (84.8%) underwent coronary procedures for urgent/emergent indications. The incidence of CIN was 44 out of 1010 (4.35%), with 17 out of 44 (38%) of CIN patients requiring dialysis. After adjusting for baseline differences, older patients, use of angiotensin-converting enzyme inhibitors, and oxygen use during the procedure were associated with a 20.6% increased risk of development of CIN. The risk of in-hospital mortality was significantly higher in the CIN group (29.5% vs. 1.8%).

Regulation of Angiotensin- Converting Enzyme 2 in Obesity: Implications for COVID-19.

The ongoing COVID-19 pandemic is caused by the novel coronavirus SARS-CoV-2. Age, smoking, obesity, and chronic diseases such as cardiovascular disease and diabetes have been described as risk factors for severe complications and mortality in COVID-19. Obesity and diabetes are usually associated with dysregulated lipid synthesis and clearance, which can initiate or aggravate pulmonary inflammation and injury. It has been shown that for viral entry into the host cell, SARS-CoV-2 utilizes the angiotensin-converting enzyme 2 (ACE2) receptors present on the cells. We aimed to characterize how SARS-CoV-2 dysregulates lipid metabolism pathways in the host and the effect of dysregulated lipogenesis on the regulation of ACE2, specifically in obesity. In our study, through the re-analysis of publicly available transcriptomic data, we first found that lung epithelial cells infected with SARS-CoV-2 showed upregulation of genes associated with lipid metabolism, including the SOC3 gene, which is involved in the regulation of inflammation and inhibition of leptin signaling. This is of interest as viruses may hijack host lipid metabolism to allow the completion of their viral replication cycles. Furthermore, a dataset using a mouse model of diet-induced obesity showed a significant increase in Ace2 expression in the lungs, which negatively correlated with the expression of genes that code for sterol response element-binding proteins 1 and 2 (SREBP). Suppression of Srebp1 showed a significant increase in Ace2 expression in the lung. Moreover, ACE2 expression in human subcutaneous adipose tissue can be regulated through changes in diet. Validation of the in silico data revealed a higher expression of ACE2, TMPRSS2 and SREBP1 in vitro in lung epithelial cells from obese subjects compared to non-obese subjects. To our knowledge this is the first study to show upregulation of ACE2 and TMPRSS2 in obesity. In silico and in vitro results suggest that the dysregulated lipogenesis and the subsequently high ACE2 expression in obese patients might be the mechanism underlying the increased risk for severe complications in those patients when infected by SARS-CoV-2.

Beta-Blockers and Cardiovascular Outcomes in Acute Heart Failure with a History of Coronary Artery Disease and an Ejection Fraction ≥ 40.

The prognostic impact of beta-blockers (BB) in coronary artery disease (CAD) is controversial, especially in the post-reperfusion era. We studied in-hospital cardiovascular events in patients hospitalized for acute HF, a previous history of CAD and a left ventricular ejection fraction (LVEF) ≥40%, in relation to BB on admission; and 1-year outcome in relation to BB on discharge, in the GULF aCute heArt failuRe (GULF-CARE) registry. From a total of 5005 patients included in the GULF-CARE registry, 303 patients with a previous history of CAD and a LVEF ≥40% on BB were propensity-matched to 303 patients without BB on admission. In-hospital mortality (OR= 0.82; 95% CI [0.35-1.94]), stroke and cardiogenic shock were not reduced by BB. On discharge, 306 patients on BB, including the ones newly diagnosed with myocardial infarction as a precipitating cause of HF, were propensity-scored matched with 306 patients without BB. Mortality (OR= 0.86; 95%CI [0.51-1.45], hospitalization for HF or PCI/CABG at 1 year were also not reduced by BB at discharge. In summary, our data show that BB have a neutral effect on in-hospital and 1-year outcomes in acute heart failure patients with a previous history of CAD and a LVEF ≥40%.

Premature Myocardial Infarction in the Middle East and North Africa: Rationale for the Gulf PREVENT Study.

The Middle East and North Africa (MENA) region has a high burden of morbidity and mortality due to premature (≤55 years in men; ≤65 years in women) myocardial infarction (MI) and acute coronary syndrome (ACS). Despite this, the prevalence of risk factors in patients presenting with premature MI or ACS is incompletely described. We compared lifestyle, clinical risk factors, and biomarkers associated with premature MI/ACS in the MENA region with selected non-MENA high-income countries. We identified English-language, peer-reviewed publications through PubMed (up to March 2018). We used the World Bank classification system to categorize countries. Patients with premature MI/ACS in the MENA region had a higher prevalence of smoking than older patients with MI/ACS but a lower prevalence of diabetes, hypertension, and dyslipidemia. Men with premature MI/ACS had a higher prevalence of smoking than women but a lower prevalence of diabetes and hypertension. The MENA region had sparse data on lifestyle, diet, psychological stress, and physical activity. To address these knowledge gaps, we initiated the ongoing Gulf Population Risks and Epidemiology of Vascular Events and Treatment (Gulf PREVENT) case-control study to improve primary and secondary prevention of premature MI in the United Arab Emirates, a high-income country in the MENA region.

Demystifying Smoker's Paradox: A Propensity Score-Weighted Analysis in Patients Hospitalized With Acute Heart Failure.

Background Smoker's paradox has been observed with several vascular disorders, yet there are limited data in patients with acute heart failure (HF). We examined the effects of smoking in patients with acute HF using data from a large multicenter registry. The objective was to determine if the design and analytic approach could explain the smoker's paradox in acute HF mortality. Methods and Results The data were sourced from the acute HF registry (Gulf CARE [Gulf Acute Heart Failure Registry]), a multicenter registry that recruited patients over 10 months admitted with a diagnosis of acute HF from 47 hospitals in 7 Middle Eastern countries. The association between smoking and mortality (in hospital) was examined using covariate adjustment, making use of mortality risk factors. A parallel analysis was performed using covariate balancing through propensity scores. Of 5005 patients hospitalized with acute HF, 1103 (22%) were current smokers. The in-hospital mortality rates were significantly lower in current smoker's before (odds ratio, 0.71; 95% CI, 0.52-0.96) and more so after (odds ratio, 0.47; 95% CI, 0.31-0.70) covariate adjustment. With the propensity score-derived covariate balance, the smoking effect became much less certain (odds ratio, 0.63; 95% CI, 0.36-1.11). Conclusions The current study illustrates the fact that the smoker's paradox is likely to be a result of residual confounding as covariate adjustment may not resolve this if there are many competing prognostic confounders. In this situation, propensity score methods for covariate balancing seem preferable. Clinical Trial Registration URL: https://www.clinicaltrials.gov/. Unique identifier: NCT01467973.

Investigating the Relationship Between Resilience, Stress-Coping Strategies, and Learning Approaches to Predict Academic Performance in Undergraduate Medical Students: Protocol for a Proof-of-Concept Study.

BACKGROUND: The evolution of an undergraduate medical student into an adept physician is perpetual, demanding, and stressful. Several studies have indicated medical students have a higher predominance of mental health problems than other student groups of the same age, where medical education acts as a stressor and may lead to unfavorable consequences such as depression, burnout, somatic complaints, decrease in empathy, dismal thoughts about quitting medical school, self harm and suicidal ideation, and poor academic performance. It is imperative to determine the association between important psychoeducational variables and academic performance in the context of medical education to comprehend the response to academic stress. OBJECTIVE: The aim of this proof-of-concept study is to determine the relationship between resilience, learning approaches, and stress-coping strategies and how they can collectively predict achievement in undergraduate medical students. The following research questions will be addressed: What is the correlation between the psychoeducational variables resilience, learning approaches, and stress-coping strategies? Can academic performance of undergraduate medical students be predicted through the construction of linear relationships between defined variables employing the principles of empirical modeling? METHODS: Study population will consist of 234 students registered for the MBBS (Bachelor of Medicine, Bachelor of Surgery) at Mohammed Bin Rashid University of Medicine and Health Sciences distributed over 4 cohorts. Newly registered MBBS students will be excluded from the study. Various psychoeducational variables will be assessed using prevalidated questionnaires. For learning approaches assessment, the Approaches and Study Skills Inventory for Students questionnaire will be employed. Resilience and stress-coping strategies will be evaluated using the Wagnild-Young resilience scale and a coping strategies scale derived from Holahan and Moos's Coping Strategies Scale, respectively. Independent variables (resilience, stress-coping strategies, and learning approaches) will be calculated. Scores will be tested for normality by using the Shapiro-Wilk test. An interitem correlational matrix of the dependent and independent variables to test pairwise correlation will be formed using Pearson bivariate correlation coefficients. Regression models will be used to answer our questions with type II analyses of variance in tests involving multiple predictors. Regression analyses will be checked for homogeneity of variance (Levine test) and normality of residuals and multicollinearity (variance inflation factor). Statistical significance will be set at 5% (alpha=.05). Effect sizes will be estimated with 95% CIs. RESULTS: Psychoeducational instruments in the form of validated questionnaire have been identified in relation to the objectives. These questionnaires have been formatted for integration into Google forms such that they can be electronically distributed to the consenting participants. We submitted the proposal to MBRU institutional review board (IRB) for which exemption has been awarded (application ID: MBRU-IRB-2019-013). There is no funding in place for this study and no anticipated start date. Total duration of the proposed research is 12 months. CONCLUSIONS: Psychoeducational instruments used in this study will correlate resilience, stress-coping strategies, and learning approaches to academic performance of undergradudate medical students. To the best of our knowledge, no study exploring the multidimensional association of key psychoeducational variables and academic performance in undergraduate medical students has been pursued. Investigated variables, resilience, learning approaches, and stress-coping strategies, are individual traits, however; students' learning history before they joined MBRU is unknown, so our research will not be able to address this specific aspect. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/14677.

Incidence and impact of cardiorenal anaemia syndrome on all-cause mortality in acute heart failure patients stratified by left ventricular ejection fraction in the Middle East.

AIMS: This study aims to evaluate the incidence and impact of cardiorenal anaemia syndrome (CRAS) on all-cause mortality in acute heart failure (AHF) patients stratified by left ventricular ejection fraction (LVEF) status in the Middle East. METHODS AND RESULTS: Data were analysed from 4934 consecutive patients admitted to 47 hospitals in seven Middle Eastern countries (Saudi Arabia, Oman, Yemen, Kuwait, United Arab Emirates, Qatar, and Bahrain) with AHF from February to November 2012. CRAS was defined as AHF with estimated glomerular filtration rate of <60 mL/min and low haemoglobin (<13 g/dL for men or <12 g/dL for women). Analyses were performed using univariate and multivariate statistical techniques. The overall mean age of the cohort was 59 ± 15 years, 62% (n = 3081) were men, and 27% (n = 1319) had CRAS. Co-morbid conditions were common including hypertension (n = 3014; 61%), coronary artery disease (n = 2971; 60%), and diabetes mellitus (n = 2449; 50%). A total of 79% (n = 3576) of the patients had AHF with reduced ejection fraction (HFrEF) (LVEF < 50%). CRAS patients were associated with major bleeding (1.29% vs. 0.6%; P = 0.017), blood transfusion (10.1% vs. 3.0%; P < 0.001), higher re-admission rate for AHF at 3 months' follow-up (27.6% vs. 18.8%; P < 0.001) and at 12 months' follow-up (34.3% vs. 26.2%; P < 0.001). Multivariate logistic regression demonstrated that patients with CRAS were associated with higher odds of all-cause mortality during hospital admission [adjusted odds ratio (aOR), 2.10; 95% confidence interval (CI): 1.34-3.31; P = 0.001], at 3 months' follow-up (aOR, 1.48; 95% CI: 1.07-2.06; P = 0.018), and at 12 months' follow-up (aOR, 1.45; 95% CI: 1.12-1.87; P = 0.004). Stratified analyses showed that CRAS patients with HFrEF were associated with higher odds of all-cause mortality during hospital admission (aOR, 2.03; 95% CI: 1.20-3.45; P = 0.009) and at 12 months' follow-up (aOR, 1.42; 95% CI: 1.06-1.89; P = 0.019) but not at 3 months' follow-up (aOR, 1.43; 95% CI: 0.98-2.09; P = 0.063). However, in AHF patients with preserved ejection fraction (LVEF ≥ 50%), CRAS was not associated with higher odds of all-cause mortality not only during hospital admission (aOR, 2.15; 95% CI: 0.84-5.55; P = 0.113) but also at 3 months' follow-up (aOR, 1.87; 95% CI: 0.93-3.76; P = 0.078) and at 12 months' follow-up (aOR, 1.59; 95% CI: 0.91-2.76; P = 0.101). CONCLUSIONS: The incidence of CRAS was 27%. CRAS was associated with higher odds of all-cause mortality in AHF patients in the Middle East, especially in those with HFrEF.

Prevalence, management, and outcomes of familial hypercholesterolemia in patients with acute coronary syndromes in the Arabian Gulf.

BACKGROUND: Information on the epidemiology of familial hypercholesterolemia (FH) in the Arabian Gulf region, which has an elevated rate of consanguinity and type II diabetes, is scarce. OBJECTIVES: To assess the prevalence of FH, its management, and impact on atherosclerotic cardiovascular disease (ASCVD) outcomes in a multicenter cohort of Arabian Gulf patients with acute coronary syndrome (ACS). METHODS: Patients (N = 3224) hospitalized with ACS were studied. FH was diagnosed using the Dutch Lipid Clinic Network criteria. A composite endpoint of nonfatal myocardial infarction, stroke, transient ischemic attack, and mortality between the "probable/definite" and the "unlikely" FH patients was assessed after 1 year. Analyses were performed using univariate and multivariate statistical techniques. RESULTS: At admission, the proportion of "probable/definite", "possible", and "unlikely" FH in ACS patients was 3.7% (n = 119), 28% (n = 911), and 68% (n = 2194), respectively. Overall, 54% (n = 1730) of patients had diabetes, whereas 24% (n = 783) were current smokers. The "probable/definite" FH group was younger (50 vs 63 years; P < .001), had a greater prevalence of early coronary disease (38% vs 8.8%; P < .001), and previous statin use (87% vs 57%; P < .001) when compared with the "unlikely" FH group. After 1 year, the "probable/definite" FH cohort had worse lipid control (13% vs 23%; P < .001) and presented with a greater association with the composite ASCVD endpoint when compared with the "unlikely" FH group (odds ratio: 1.85; 95% confidence interval: 1.01-3.38; P = .047) after multivariable adjustment. CONCLUSIONS: In Arabian Gulf citizens, FH was common in ACS patients, was undertreated, and was associated with a worse 1-year prognosis.

Cardiovascular risk factor burden in Africa and the Middle East across country income categories: a post hoc analysis of the cross-sectional Africa Middle East Cardiovascular Epidemiological (ACE) study.

BACKGROUND: A significant number of cardiovascular disease (CVD)-related deaths occur in developing countries. An increasing prevalence of CVD is associated with a change in the macro-economy of these countries. In this post hoc analysis, CVD risk factor (CVDRF) prevalence is evaluated across countries based on national income in the Africa and Middle East Region (AfME). METHODS: Data from the Africa Middle East Cardiovascular Epidemiological (ACE) study were used; a cross-sectional study in 14 AfME countries (94 clinics) from July 2011-April 2012, which evaluated CVDRF prevalence in stable adult outpatients. World Bank definitions were used to classify countries as low-income (LI), lower-middle-income (LMI), upper-middle-income (UMI) or high-income (HI) countries. Four thousand three hundred seventy-eight subjects were recruited where 260 (6%), 1324 (30%), 1509 (35%) and 1285 (29%) were from LI, LMI, UMI, and HI countries, respectively. RESULTS: Of all the CVDRFs evaluated, almost two-thirds of the study population across the national income groups had abdominal obesity and dyslipidemia. Countries in the HI category were associated with a higher prevalence of diabetes (32%), obesity (44%) and smoking (16%). UMI and HI countries were associated with higher clustering of CVDRFs where at least one-third of subjects having four or more CVDRFs. Lower income countries had lower blood pressure control rates and lower percentages of outpatients achieving LDL-cholesterol targets. CONCLUSION: The burden of CVDRFs in stable outpatients is high across the national income categories in the AfME region, with HI countries showing a higher prevalence of CVDRFs. The high burden in lower income countries is associated with sub-optimal control of dyslipidemia and hypertension. Lowering the CVDRF burden would need specific public health actions in line with positive changes in the macro-economy of these countries. TRIAL REGISTRATION: The ACE trial is registered under NCT01243138.

Analysis of risk factors, presentation, and in-hospital events of very young patients presenting with ST-elevation myocardial infarction.

INTRODUCTION: In the Indian subcontinent and Arab Gulf, coronary artery disease is affecting younger persons at greater rates. Few studies have focused on young ST-elevation myocardial infarction (STEMI) patients in these regions. We examine the clinical profile and treatment of STEMI patients aged <40 years. METHODS: Participants consisted of 77 STEMI patients, aged <40 years, admitted to hospitals in Abu Dhabi. Data were collected using electronic medical records. Descriptive statistics were calculated for STEMI profile, medical history, risk factors, in-hospital events, and treatment. RESULTS: Smoking was prevalent (61.0%). Beta blockers were frequently prescribed (90.7%); aspirin infrequently (12%). Of patients without history of each condition, 36.7% were diagnosed in-hospital with hypertension, 28.6% with elevated low-density lipoprotein, and 18.8% with lowered high-density lipoprotein. CONCLUSIONS: Among young adults who use tobacco, there is a need for improved screening for risk factors. Earlier detection and treatment of dyslipidemia and hypertension could prevent acute cardiac events among individuals aged <40 years with multiple risk factors.

Sex differences in management and outcomes of patients with atrial fibrillation in the Middle East: Gulf survey of atrial fibrillation events (Gulf SAFE).

Differences in the management of atrial fibrillation (AF) between men and women were investigated by using Gulf SAFE data in the Middle East. The study included 2,043 patients presenting with AF to emergency room (ER) were prospectively enrolled and followed for one-year. Women were older, have higher body mass index (BMI), comorbidities, and health complications than men. With regard to management of AF, cardioversion was recommended more often for men (16.7% vs. 9.3%), and underwent electrical cardioversion (2.2% vs. 1.1%). Women were prescribed digoxin more frequently than men (25.6% vs. 17.4%) and a significant number women received warfarin alone (31.1% vs. 8.7%). No difference between the sexes was noticed in One-year rates of stroke/transient ischemic attacks (TIA) and all-cause of mortality after one-year follow-up (3.1% men vs. 3.3% women, and 7.5% vs. 7.4%). Older age (≥ 65 years), smoking, alcohol use, CHADS2 scores ≥5 were some of the significant risk factors in men with AF. Suboptimal use of anticoagulants, higher mortality and stroke/TIA events at one year are high but similar between the sexes. ER management revealed high use of rate control strategy and high rate of hospital admission was noticed in women.

Widowhood and severity of coronary artery disease: a multicenter study.

OBJECTIVES: The aim of this study was to assess the association of widowhood with the severity and extent of coronary artery disease (CAD), and whether it is modified by sex or socioeconomic status. PATIENTS AND METHODS: A total of 1068 patients undergoing coronary angiography at five centers in Saudi Arabia and the United Arab Emirates were included in the study. CAD was defined as more than 70% lumen stenosis in a major epicardial vessel or more than 50% in the left main coronary artery. Multivessel disease was defined as more than one diseased vessel. RESULTS: Of 1068 patients, 65 (6%) were widowed. Widowed patients were older (65±15 vs. 59±12), more likely to be female (75 vs. 25%), less likely to be smokers (18 vs. 47%), of lower economic and education status, and more likely to have undergone coronary angiography for urgent/emergent indications (75 vs. 61%) (P<0.05 for all). There was a significant association between widowhood and the number of coronary arteries with more than 70% lumen stenosis. Consequently, such a high degree of lumen stenosis in those who were widowed was more likely to require coronary artery bypass graft surgery (38 vs. 16%; P<0.01). After adjusting for baseline differences, widowhood was associated with a significantly higher odds of CAD [adjusted odds ratio (OR) 3.6; 95% confidence interval (CI) 1.2-10.5] and multivessel disease (adjusted OR 4.6; 95% CI 2.2-9.6), but not left main disease (adjusted OR 1.3; 95% CI 0.5-3.1). All associations were consistent in men and women and not modified by age, community setting (urban vs. rural), employment, income, or educational levels (Pinteraction>0.1 for all). CONCLUSION: Widowhood is associated with the severity and extent of CAD. The association is not modified by sex or socioeconomic status.

Physician perceptions and recommendations about pre-hospital emergency medical services for patients with ST-elevation acute myocardial infarction in Abu Dhabi.

INTRODUCTION: Physician perceptions about emergency medical services (EMS) are important determinants of improving pre-hospital care for cardiac emergencies. No data exist on physician attitudes towards EMS care of patients with ST-Elevation Myocardial Infarction (STEMI) in the Emirate of Abu Dhabi. OBJECTIVES: To describe the perceptions towards EMS among physicians caring for patients with STEMI in Abu Dhabi. METHODS: We surveyed a convenience sample of physicians involved in the care of patients with STEMI (emergency medicine, cardiology, cardiothoracic surgery and intensive care) in four government facilities with 24/7 Primary PCI in the Emirate of Abu Dhabi. Surveys were distributed using dedicated email links, and used 5-point Likert scales to assess perceptions and attitudes to EMS. RESULTS: Of 106 physician respondents, most were male (82%), practicing in emergency medicine (47%) or cardiology (44%) and the majority (63%) had been in practice for >10 years. Less than half of the responders (42%) were "Somewhat Satisfied" (35%) or "Very Satisfied" (7%) with current EMS level of care for STEMI patients. Most respondents were "Very Likely" (67%) to advise a patient with a cardiac emergency to use EMS, but only 39% felt the same for themselves or their family. Most responders were supportive (i.e. "Strongly Agree") of the following steps to improve EMS care: 12-lead ECG and telemetry to ED by EMS (69%), EMS triage of STEMI to PCI facilities (65%), and activation of PCI teams by EMS (58%). Only 19% were supportive of pre-hospital fibrinolytics by EMS. There were no significant differences in the responses among the specialties. CONCLUSIONS: Most physicians involved in STEMI care in Abu Dhabi are very likely to advise patients to use EMS for a cardiac emergency, but less likely to do so for themselves or their families. Different specialties had concordant opinions regarding steps to improve pre-hospital EMS care for STEMI.

Sleep apnea and severe bradyarrhythmia--an alternative treatment option: a case report.

INTRODUCTION: Sinus arrest, atrio-ventricular block, supraventricular, and ventricular arrhythmias have been reported in patients with sleep apnea syndrome. The arrhythmias usually occur during sleep and contribute to the cardiovascular morbidity and mortality, and the treatment of sleep apnea usually results in the resolution of the brady- arrhythmias. Weight loss, continuous positive airway pressure (CPAP), oral appliances, and upper airway surgery are the recommended treatments, however, compliance and efficacy are issues. CASE PRESENTATION: A 58-year-old Arab man presented with recurrent presyncope. He was subsequently diagnosed with sleep apnea associated with frequent and significant sinus pauses. He presented a treatment challenge because he refused continuous positive airway pressure and pacemaker, however, he was successfully treated with theophylline. CONCLUSION: Frequent and significant sinus pause associated with sleep apnea was successfully treated with theophylline in our patient when the standard treatment of care was refused.

Clinical characteristics, precipitating factors, management and outcome of patients with prior stroke hospitalised with heart failure: an observational report from the Middle East.

OBJECTIVES: The purpose of this study is to report the prevalence, clinical characteristics, precipitating factors, management and outcome of patients with prior stroke hospitalised with acute heart failure (HF). DESIGN: Retrospective analysis of prospectively collected data. SETTING: Data were derived from Gulf CARE (Gulf aCute heArt failuRe rEgistry), a prospective multicentre study of consecutive patients hospitalised with acute HF in 2012 in seven Middle Eastern countries and analysed according to the presence or absence of prior stroke; demographics, management and outcomes were compared. PARTICIPANTS: A total of 5005 patients with HF. OUTCOME MEASURES: In-hospital and 1-year outcome. RESULTS: The prevalence of prior stroke in patients with HF was 8.1%. Patients with stroke with HF were more likely to be admitted under the care of internists rather than cardiologists. When compared with patients without stroke, patients with stroke were more likely to be older and to have diabetes mellitus, hypertension, atrial fibrillation, hyperlipidaemia, chronic kidney disease, ischaemic heart disease, peripheral arterial disease and left ventricular dysfunction (p=0.001 for all). Patients with stroke were less likely to be smokers (0.003). There were no significant differences in terms of precipitating risk factors for HF hospitalisation between the two groups. Patients with stroke with HF had a longer hospital stay (mean±SD days; 11±14 vs 9±13, p=0.03), higher risk of recurrent strokes and 1-year mortality rates (32.7% vs 23.2%, p=0.001). Multivariate logistic regression analysis showed that stroke is an independent predictor of in-hospital and 1-year mortality. CONCLUSIONS: This observational study reports high prevalence of prior stroke in patients hospitalised with HF. Internists rather than cardiologists were the predominant caregivers in this high-risk group. Patients with stroke had higher risk of in-hospital recurrent strokes and long-term mortality rates. TRIAL REGISTRATION NUMBER: NCT01467973.

Design and Rationale of Gulf locals with Acute Coronary Syndrome Events (Gulf Coast) Registry.

OBJECTIVES: To describe the risk profile, management and one-year outcomes of patients hospitalized with acute coronary syndrome (ACS) in the Gulf region of the Middle East. SUBJECTS AND METHODS: The Gulf locals with acute coronary syndrome events (Gulf COAST) registry is a prospective, multinational, longitudinal, observational, cohort-based registry of consecutive citizens, from the Gulf region of the Middle East, admitted from January 2012 to January 2013 to 29 hospitals with a diagnosis of ACS. Data entered online included patient demographics, cardiovascular risk profiles, past medical history, physical findings on admission, in-hospital diagnostic tests and therapeutic management, as well as one year outcomes. RESULTS: 3188 patients were recruited. The mean age was 60.4 ± 12.6years (range: 22-112), 2104 (66%) were males and 1084 (34%) females. The discharge diagnosis was ST-segment elevation myocardial infarction (STEMI) in 741 (23.2%), new-onset left bundle branch block myocardial infarction (LBBBMI) in 30 (0.9%), non-ST-segment elevation myocardial infarction (NSTEMI) in 1486 (46.6%) and unstable angina in 931 (29.2%). At hospital presentation, 2105 (66%), 1779 (55.8%), 1703 (53.4%) and 740 (23.2%) had history of hypertension, dyslipidemia, diabetes mellitus and active smoking, respectively. CONCLUSION: Patients with ACS in our region are young with very high risk profile. The Gulf COAST registry is an example of successful regional collaboration and will provide information on contemporary management of ACS in the region.