Dysregulation of long non-coding RNA gene expression pathways in monocytes of type 2 diabetes patients with cardiovascular disease.

BACKGROUND: Monocytes play a central role in the pathophysiology of cardiovascular complications in type 2 diabetes (T2D) patients through different mechanisms. We investigated diabetes-induced changes in lncRNA genes from T2D patients with cardiovascular disease (CVD), long-duration diabetes, and poor glycemic control. METHODS: We performed paired-end RNA sequencing of monocytes from 37 non-diabetes controls and 120 patients with T2D, of whom 86 had either macro or microvascular disease or both. Monocytes were sorted from peripheral blood using flow cytometry; their RNA was purified and sequenced. Alignments and gene counts were obtained with STAR to reference GRCh38 using Gencode (v41) annotations followed by batch correction with CombatSeq. Differential expression analysis was performed with EdgeR and pathway analysis with IPA software focusing on differentially expressed genes (DEGs) with a p-value < 0.05. Additionally, differential co-expression analysis was done with csdR to identify lncRNAs highly associated with diabetes-related expression networks with network centrality scores computed with Igraph and network visualization with Cytoscape. RESULTS: Comparing T2D vs. non-T2D, we found two significantly upregulated lncRNAs (ENSG00000287255, FDR = 0.017 and ENSG00000289424, FDR = 0.048) and one significantly downregulated lncRNA (ENSG00000276603, FDR = 0.017). Pathway analysis on DEGs revealed networks affecting cellular movement, growth, and development. Co-expression analysis revealed ENSG00000225822 (UBXN7-AS1) as the highest-scoring diabetes network-associated lncRNA. Analysis within T2D patients and CVD revealed one lncRNA upregulated in monocytes from patients with microvascular disease without clinically documented macrovascular disease. (ENSG00000261654, FDR = 0.046). Pathway analysis revealed DEGs involved in networks affecting metabolic and cardiovascular pathologies. Co-expression analysis identified lncRNAs strongly associated with diabetes networks, including ENSG0000028654, ENSG00000261326 (LINC01355), ENSG00000260135 (MMP2-AS1), ENSG00000262097, and ENSG00000241560 (ZBTB20-AS1) when we combined the results from all patients with CVD. Similarly, we identified from co-expression analysis of diabetes patients with a duration ≥ 10 years vs. <10 years two lncRNAs: ENSG00000269019 (HOMER3-AS10) and ENSG00000212719 (LINC02693). The comparison of patients with good vs. poor glycemic control also identified two lncRNAs: ENSG00000245164 (LINC00861) and ENSG00000286313. CONCLUSION: We identified dysregulated diabetes-related genes and pathways in monocytes of diabetes patients with cardiovascular complications, including lncRNA genes of unknown function strongly associated with networks of known diabetes genes.

Angiogenic content of microparticles in patients with diabetes and coronary artery disease predicts networks of endothelial dysfunction.

BACKGROUND: Elevated endothelial microparticles (EMPs) levels are surrogate markers of vascular dysfunction. We analyzed EMPs with apoptotic characteristics and assessed the angiogenic contents of microparticles in the blood of patients with type 2 diabetes (T2D) according to the presence of coronary artery disease (CAD). METHODS: A total of 80 participants were recruited and equally classified as (1) healthy without T2D, (2) T2D without cardiovascular complications, (3) T2D and chronic coronary artery disease (CAD), and (4) T2D and acute coronary syndrome (ACS). MPs were isolated from the peripheral circulation, and EMPs were characterized using flow cytometry of CD42 and CD31. CD62E was used to determine EMPs' apoptotic/activation state. MPs content was extracted and profiled using an angiogenesis array. RESULTS: Levels of CD42- CD31 + EMPs were significantly increased in T2D with ACS (257.5 ± 35.58) when compared to healthy subjects (105.7 ± 12.96, p < 0.01). There was no significant difference when comparing T2D with and without chronic CAD. The ratio of CD42-CD62 +/CD42-CD31 + EMPs was reduced in all T2D patients, with further reduction in ACS when compared to chronic CAD, reflecting a release by apoptotic endothelial cells. The angiogenic content of the full population of MPs was analyzed. It revealed a significant differential expression of 5 factors in patients with ACS and diabetes, including TGF-ß1, PD-ECGF, platelet factor 4, serpin E1, and thrombospondin 1. Ingenuity Pathway Analysis revealed that those five differentially expressed molecules, mainly TGF-ß1, inhibit key pathways involved in normal endothelial function. Further comparison of the three diabetes groups to healthy controls and diabetes without cardiovascular disease to diabetes with CAD identified networks that inhibit normal endothelial cell function. Interestingly, DDP-IV was the only differentially expressed protein between chronic CAD and ACS in patients with diabetes. CONCLUSION: Our data showed that the release of apoptosis-induced EMPs is increased in diabetes, irrespective of CAD, ACS patients having the highest levels. The protein contents of MPs interact in networks that indicate vascular dysfunction.

Soluble ACE2 and angiotensin II levels are modulated in hypertensive COVID-19 patients treated with different antihypertension drugs.

PURPOSE: This study examines the effect of antihypertensive drugs on ACE2 and Angiotensin II levels in hypertensive COVID-19 patients. INTRODUCTION: Hypertension is a common comorbidity among severe COVID-19 patients. ACE2 expression can be modulated by antihypertensive drugs such as ACEis and ARBs, which may affect COVID-19's prognosis. BB and CCB reduce mortality, according to some evidence. Their effect on circulating levels of ACE2 and angiotensin II, as well as the severity of COVID-19, is less well studied. MATERIALS AND METHODS: The clinical data were collected from 200 patients in four different antihypertensive medication classes (ACEi, ARB, BB, and CCB). Angiotensin II and ACE2 levels were determined using standard ELISA kits. ACE2, angiotensin II, and other clinical indices were evaluated by linear regression models. RESULTS: Patients on ACEi (n = 57), ARB (n = 68), BB (n = 15), or CCB (n = 30) in this study had mild (n = 76), moderate (n = 76), or severe (n = 52) COVID-19. ACE2 levels were higher in COVID-19 patients with severe disease (p = 0.04) than mild (p = 0.07) and moderate (p = 0.007). The length of hospital stay is correlated with ACE2 levels (r = 0.3, p = 0.003). Angiotensin II levels decreased with severity (p = 0.04). Higher ACE2 levels are associated with higher CRP and D-dimer levels. Elevated Angiotensin II was associated with low levels of CRP, D-dimer, and troponin. ACE2 levels increase with disease severity in patients taking an ARB (p = 0.01), patients taking ACEi, the degree of disease severity was associated with a decrease in angiotensin II. BB patients had the lowest disease severity. CONCLUSION: We found different levels of soluble ACE2, and angiotensin II are observed among COVID-19 patients taking different antihypertensive medications and exhibiting varying levels of disease severity. COVID-19 severity increases with elevated ACE2 levels and lower angiotensin II levels indicating that BB treatment reduces severity regardless of levels of ACE2 and angiotensin II.

Diabetes-related cardiovascular and economic burden in patients hospitalized for heart failure in the US: a recent temporal trend analysis from the National Inpatient Sample.

We aimed to study the cardiovascular and economic burden of diabetes mellitus (DM) in patients hospitalized for heart failure (HF) in the US and to assess the recent temporal trend. Data from the National Inpatient Sample were analyzed between 2005 and 2014. The prevalence of DM increased from 40.4 to 46.5% in patients hospitalized for HF. In patients with HF and DM, mean (SD) age slightly decreased from 71 (13) to 70 (13) years, in which 47.5% were males in 2005 as compared with 52% in 2014 (p trend < 0.001 for both). Surprisingly, the presence of DM was associated with lower in-hospital mortality risk, even after adjustment for confounders (adjusted OR = 0.844 (95% CI [0.828-0.860]). Crude mortality gradually decreased from 2.7% in 2005 to 2.4% in 2014 but was still lower than that of non-diabetes patients' mortality on a yearly comparison basis. Hospitalization for HF also decreased from 211 to 188/100,000 hospitalizations. However, median (IQR) LoS slightly increased from 4 (2-6) to 4 (3-7) days, so did total charges/stay that jumped from 15,704 to 26,858 USD (adjusted for inflation, p trend < 0.001 for both). In total, the prevalence of DM is gradually increasing in HF. However, the temporal trend shows that hospitalization and in-hospital mortality are on a descending slope at a cost of an increasing yearly expenditure and length of stay, even to a larger extent than in patient without DM.

Medications adherence post-primary percutaneous coronary intervention in acute myocardial infarction: A population-based cohort study.

WHAT IS KNOWN AND OBJECTIVE: The use of medications for secondary prevention is the cornerstone in the treatment of coronary artery disease (CAD). However, adherence to these medications is still suboptimal worldwide. This retrospective observational study aimed to assess the adherence to post-percutaneous coronary intervention (PCI) medications, along with predictors of non-adherence. METHODS: We conducted a retrospective observational cohort study to assess the adherence to post-PCI medications by determining the rate of prescription refills for 12 months after discharge among STEMI patients, as well as predictors of non-adherence. Adherence was assessed by medication availability 80% of the time monitored by the prescription refills rate for 1 year post-discharge. RESULTS AND DISCUSSION: A total of 1334 patients who presented with STEMI and underwent primary PCI were included in our retrospective analysis. The majority of patients included were male (96%) with a mean age of 51 ± 10.2 years. The overall adherence rate for all medications was only 28.4%, with an individual adherence rate of 50.5% for aspirin, 49.9% for P2 Y12 inhibitors, 48.1% for statins, 39.6% for beta-blockers and 42.9% for angiotensin-converting enzyme (ACE) inhibitors/angiotensin II receptor blockers (ARB). Factors that increased the likelihood of non-adherence were prolonged hospital length of stay and getting the medications with charge (aOR = 1.94, 95% CI 1.1-3.3; p-value = 0.017, aOR = 1.87, 95% CI 1.1-3.3; p-value = 0.029, respectively), while having a regular follow-up after discharge and attending the first clinic appointment were significantly associated with decreased likelihood of non-adherence (aOR = 0.01, 95% CI 0.004-0.04; p-value < 0.001, aOR = 0.06, 95% CI 0.03-0.1; p-value < 0.001, respectively). WHAT IS NEW AND CONCLUSION: The adherence rate to post-PCI medications among patients with STEMI was relatively low; however, attending the first outpatient clinic appointment and having a regular follow-up reduced the likelihood of non-adherence.

Association of vitamin D2 and D3 with type 2 diabetes complications.

AIMS: Vitamin D measurement is a composite of vitamin D2 (25(OH)D2) and D3 (25(OH)D3) levels, and its deficiency is associated with the development of type 2 diabetes (T2DM) and diabetic complications; vitamin D deficiency may be treated with vitamin D2 supplements. This study was undertaken to determine if vitamin D2 and D3 levels differed between those with and without T2DM in this Middle Eastern population, and the relationship between diabetic microvascular complications and vitamin D2 and vitamin D3 levels in subjects with T2DM. METHODS: Four hundred ninety-six Qatari subjects, 274 with and 222 without T2DM participated in the study. Plasma levels of total vitamin D2 and D3 were measured by LC-MS/MS analysis. RESULTS: All subjects were taking vitamin D2 and none were taking D3 supplements. Vitamin D2 levels were higher in diabetics, particularly in females, and higher levels were associated with hypertension and dyslipidemia in the diabetic subjects (p < 0.001), but were not related to diabetic retinopathy or nephropathy. Vitamin D3 levels measured in the same subjects were lower in diabetics, particularly in females (p < 0.001), were unrelated to dyslipidemia or hypertension, but were associated with retinopathy (p < 0.014). Neither vitamin D2 nor vitamin D3 were associated with neuropathy. For those subjects with hypertension, dyslipidemia, retinopathy or neuropathy, comparison of highest with lowest tertiles for vitamin D2 and vitamin D3 showed no difference. CONCLUSIONS: In this Qatari cohort, vitamin D2 was associated with hypertension and dyslipidemia, whilst vitamin D3 levels were associated with diabetic retinopathy. Vitamin D2 levels were higher, whilst vitamin D3 were lower in diabetics and females, likely due to ingestion of vitamin D2 supplements.

Low dose combined oral contraceptives induced thrombotic anterior wall myocardial infarction: a case report.

BACKGROUND: Combined oral contraceptive pills are associated with an established risk for venous thrombosis; however, their risk for arterial thrombosis remains uncertain, especially with the development of low dose new generations of combined oral contraceptive. Arterial thrombosis is less likely to occur with the use of oral contraceptive pills in the absence of cardiovascular risk factors. CASE PRESENTATION: We report a 35-year old female with no cardiovascular risk factors who presented with thrombotic anterior wall myocardial infarction 6 months after using a third generation low dose combined oral contraceptive pills (Marvelon; ethinylestradiol 30 mcg and desogestrel 150 mcg). CONCLUSION: Third generation low dose combined oral contraceptives may lead to myocardial infarction in young women, even in the absence of other cardiovascular risk factors.

Precipitating Factors for Hospitalization with Heart Failure: Prevalence and Clinical Impact Observations from the Gulf CARE (Gulf aCute heArt failuRe rEgistry).

OBJECTIVE: Despite the expanding burden of heart failure (HF) worldwide, data on HF precipitating factors (PFs) in developing countries, particularly the Middle East, are very limited. We examined PFs in patients hospitalized with acute HF in a prospective multicenter HF registry from 7 countries in the Middle East. METHOD: Data were derived from the Gulf CARE (Gulf aCute heArt failuRe rEgistry) for a prospective, multinational, multicenter study of consecutive patients hospitalized with HF in 47 hospitals in 7 Middle Eastern countries between February 2012 and November 2012. PFs were determined by the treating physician from a predefined list at the time of hospitalization. RESULTS: The study included 5,005 patients hospitalized with acute HF, 2,276 of whom (45.5%) were hospitalized with acute new-onset HF (NOHF) and 2,729 of whom (54.5%) had acute decompensated chronic HF (DCHF). PFs were identified in 4,319 patients (86.3%). The most common PF in the NOHF group was acute coronary syndromes (ACS) (39.2%). In the DCHF group, it was noncompliance with medications (27.8%). Overall, noncompliance with medications was associated with a lower inhospital mortality (OR 0.47; 95% CI 0.28-0.80; p = 0.005) but a higher 1-year mortality (OR 1.43; 95% CI 1.1-1.85; p = 0.007). ACS was associated with higher inhospital mortality (OR 1.84; 95% CI 1.26-2.68; p = 0.002) and higher 1-year mortality (OR 1.62; 95% CI 1.27-2.06; p = 0.001). CONCLUSION: Preventive and therapeutic interventions specifically directed at noncompliance with medications and ACS are warranted in our region.

The influence of Elixhauser comorbidity index on percutaneous coronary intervention outcomes.

BACKGROUND: Clinical outcomes with respect to the evolution of comorbidity burden in national cohorts of patients undergoing PCI have not been reported. OBJECTIVES: We sought to explore the association between comorbidity burden and periprocedural outcomes in patients treated with PCI in the National Inpatient Sample. METHODS: 6,601,526 PCI procedures were identified between 2004 and 2014 and comorbidities were defined by the Elixhauser classification system (ECS) consisting of 30 comorbidity measures. Endpoints included in-hospital mortality, periprocedural complications, length of stay and cost. Patients were classified based on their ECS in five categories (ECS I < 0, ECS II = 0, ECS III = 1-5, ECS IV = 6-13, and ECS V ≥ 14). RESULTS: Patients with a score over 13 had a fivefold increase in the odds of mortality (OR: 5.13, 95% CI: 4.76-5.54), major bleeding (OR: 11.46, 95% CI: 10.66-12.33) and doubled the hospitalization costs ($31,452 vs $17.566). CONCLUSIONS: Our study of over six million PCI procedures demonstrates that patients with the greatest comorbid burden (as defined by an ECS of >13) have a fivefold increase risk of in-hospital mortality, a fourfold increase in in-hospital periprocedural complications and an 11-fold increase in major bleeding events once differences in baseline patient characteristics are adjusted for. In addition, ECS significantly impacts the length of stay and doubles the healthcare costs. Comorbid burden is an important predictor of poor outcomes after PCI and should be considered as part of the decision-making processes in patients undergoing PCI.

Inotropic agents use in patients hospitalized with acute decompensated heart failure: a retrospective analysis from a 22-year registry in a Middle-Eastern Country (1991-2013).

BACKGROUND: Data about the use of positive inotropic agents in patients hospitalized with acute decompensated heart failure (ADHF) is limited. METHODS: The records of 8066 patients with ADHF who were hospitalized at Hamad Medical Corporation, Qatar from 1991 to 2013 were analyzed to explore demographics and clinical characteristics of the patients according to inotropic agents use. RESULTS: Eight hundred fifty eight patients [10.6%, 95% CI (10 to 11.3%)] received intravenous inotropic support. Patients receiving inotropes were more likely to be female and have preserved ejection fraction when compared to those not receiving inotropic agents. Comorbidities associated with higher likelihood of receiving inotropic treatment included acute myocardial infarction, chronic renal impairment, dyslipidemia, hypertension, obesity and hyperglycemia. Patient on inotropes were more likely to undergone percutaneous coronary intervention (PCI), intra-aortic balloon pump support and intubation. There were no differences in the mean plasma BNP and CK-MB levels between the 2 groups. Heart failure patients receiving inotropes also were more likely to have complications including ventricular tachycardia (2.0% vs. 0.9%, p = 0.003), prolonged hospital stay (8.0 vs. 5.0 days, p = 0.001), cardiac arrest (14.6% vs. 3.2%, p = 0.001) and in-hospital mortality (30.8% vs. 9.1 %, p = 0.001). Over the study period there was an increase use of inotropic agents and decreased mortality rates. CONCLUSION: Inotropic use increased over the period whereas; female gender and conventional cardiac risk factors were predictors of inotropic agents use in the study.

Diabetes Is Associated with Worse Postoperative Mortality and Morbidity in Bariatric Surgery, Regardless of the Procedure.

Background/Objectives: Bariatric surgery is a central cornerstone in obesity treatment. We aimed to assess the impact of diabetes on the postoperative outcomes of bariatric surgery and compare three techniques: sleeve gastrectomy, Roux-en-Y, and gastric banding. Methods: We extracted data from the National Inpatient Sample (2015-2019) using ICD codes. The primary outcome was postoperative mortality. Secondary outcomes were major bleeding, atrial fibrillation, and acute renal failure. Results: Among patients who underwent sleeve gastrectomy, diabetes was associated with a higher adjusted risk of mortality (aOR 2.07 [1.36-3.16]), atrial fibrillation, and acute renal failure, but a similar risk of bleeding. Among patients who underwent Roux-en-Y, diabetes did not increase mortality and bleeding risk. Still, it was associated with a higher risk of atrial fibrillation and acute renal failure. Among patients who underwent gastric banding, diabetes was only associated with a higher risk of bleeding. When comparing the three techniques in diabetes patients, Roux-en-Y was significantly associated with higher mortality and acute renal failure risk when compared to the other procedures. Bleeding was more common in Roux-en-Y than in Sleeve. Conclusions: In total, diabetes is associated with worse postoperative outcomes in bariatric surgery, regardless of the technique. Among diabetes patients, Roux-en-Y was associated with the highest mortality and morbidity.

Acute Triple Coronary Artery Occlusion Leading to Cardiogenic Shock and Cardiac Arrest Emphasizing the Role of Mechanical Circulatory Support (Escalate before It's Too Late).

We report a case of cardiac arrest in a 38-year-old male with no past medical history who presented as a case of ST-segment elevation myocardial infarction, and coronary angiography showed triple coronary artery thrombosis complicated with cardiogenic shock (CS) that warrants starting on inotropic support and insertion of intra-aortic balloon pump. CS diagnosis with a high likelihood of deterioration was established based on hemodynamics assessment; hence, an early prompt decision for escalation of mechanical circulatory support to Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) was made, which helped to prevent the patient's further deterioration and organ damage. The patient had uneventful VA-ECMO decannulation and was transferred to the ward and discharged after 28 days in stable condition on oral medical therapy and was following up regularly in the cardiology clinic. Therefore, early hemodynamics assessment in acute myocardial infarction CS cases will help predict rapid worsening, which may require prompt escalation of mechanical circulatory support and perhaps improve the outcome.

Correlations between Resting Electrocardiogram Findings and Disease Profiles: Insights from the Qatar Biobank Cohort.

BACKGROUND: Resting electrocardiogram (ECG) is a valuable non-invasive diagnostic tool used in clinical medicine to assess the electrical activity of the heart while the patient is resting. Abnormalities in ECG may be associated with clinical biomarkers and can predict early stages of diseases. In this study, we evaluated the association between ECG traits, clinical biomarkers, and diseases and developed risk scores to predict the risk of developing coronary artery disease (CAD) in the Qatar Biobank. METHODS: This study used 12-lead ECG data from 13,827 participants. The ECG traits used for association analysis were RR, PR, QRS, QTc, PW, and JT. Association analysis using regression models was conducted between ECG variables and serum electrolytes, sugars, lipids, blood pressure (BP), blood and inflammatory biomarkers, and diseases (e.g., type 2 diabetes, CAD, and stroke). ECG-based and clinical risk scores were developed, and their performance was assessed to predict CAD. Classical regression and machine-learning models were used for risk score development. RESULTS: Significant associations were observed with ECG traits. RR showed the largest number of associations: e.g., positive associations with bicarbonate, chloride, HDL-C, and monocytes, and negative associations with glucose, insulin, neutrophil, calcium, and risk of T2D. QRS was positively associated with phosphorus, bicarbonate, and risk of CAD. Elevated QTc was observed in CAD patients, whereas decreased QTc was correlated with decreased levels of calcium and potassium. Risk scores developed using regression models were outperformed by machine-learning models. The area under the receiver operating curve reached 0.84 using a machine-learning model that contains ECG traits, sugars, lipids, serum electrolytes, and cardiovascular disease risk factors. The odds ratio for the top decile of CAD risk score compared to the remaining deciles was 13.99. CONCLUSIONS: ECG abnormalities were associated with serum electrolytes, sugars, lipids, and blood and inflammatory biomarkers. These abnormalities were also observed in T2D and CAD patients. Risk scores showed great predictive performance in predicting CAD.

The Effect of Beta-Blocker Post-Myocardial Infarction With Ejection Fraction >40% Pooled Analysis From Seven Arabian Gulf Acute Coronary Syndrome Registries.

The use of beta-blockers (BB) in reduced left ventricular ejection fraction (LVEF) post-myocardial infarction (MI) is associated with reduced 1-year mortality, while their role in patients with mid-range and preserved LVEF post-MI remains controversial. We studied 31,620 patients who presented with acute coronary syndrome (ACS) enrolled in seven Arabian Gulf registries between 2005 and 2017. Patients with LVEF ≤40% were excluded. The remaining cohort was divided into two groups: BB group (n = 15,541) and non-BB group (n = 2,798), based on discharge medications. Patients in the non-BB group were relatively younger (55.3 vs. 57.4, P = .004) but higher risk at presentation; with higher Global Registry of Acute Coronary Events (GRACE) score (119.2 vs 109.2, P < .001), higher percentage of cardiogenic shock (3.5 vs 1.4%, P < .001), despite lower prevalence of comorbidities, such as hypertension and hyperlipidemia. BB use was associated with lower 1-year mortality in a multivariate logistic regression analysis, adjusting for major confounders [adjusted odds ratio (OR): 0.71 (95% CI 0.51-0.99)]. This remained the case in a sensitivity analysis using propensity score matching [adjusted OR: 0.34 (95% CI 0.16-0.73)]. In this study, using Arabian Gulf countries registries, the use of BB after ACS with LVEF >40% was independently associated with lower 1-year mortality.

Genetic Susceptibility to Arrhythmia Phenotypes in a Middle Eastern Cohort of 14,259 Whole-Genome Sequenced Individuals.

Background: The current study explores the genetic underpinnings of cardiac arrhythmia phenotypes within Middle Eastern populations, which are under-represented in genomic medicine research. Methods: Whole-genome sequencing data from 14,259 individuals from the Qatar Biobank were used and contained 47.8% of Arab ancestry, 18.4% of South Asian ancestry, and 4.6% of African ancestry. The frequency of rare functional variants within a set of 410 candidate genes for cardiac arrhythmias was assessed. Polygenic risk score (PRS) performance for atrial fibrillation (AF) prediction was evaluated. Results: This study identified 1196 rare functional variants, including 162 previously linked to arrhythmia phenotypes, with varying frequencies across Arab, South Asian, and African ancestries. Of these, 137 variants met the pathogenic or likely pathogenic (P/LP) criteria according to ACMG guidelines. Of these, 91 were in ACMG actionable genes and were present in 1030 individuals (~7%). Ten P/LP variants showed significant associations with atrial fibrillation p < 2.4 × 10-10. Five out of ten existing PRSs were significantly associated with AF (e.g., PGS000727, p = 0.03, OR = 1.43 [1.03, 1.97]). Conclusions: Our study is the largest to study the genetic predisposition to arrhythmia phenotypes in the Middle East using whole-genome sequence data. It underscores the importance of including diverse populations in genomic investigations to elucidate the genetic landscape of cardiac arrhythmias and mitigate health disparities in genomic medicine.

QPGx-CARES: Qatar pharmacogenetics clinical applications and research enhancement strategies.

Pharmacogenetic (PGx)-informed medication prescription is a cutting-edge genomic application in contemporary medicine, offering the potential to overcome the conventional "trial-and-error" approach in drug prescription. The ability to use an individual's genetic profile to predict drug responses allows for personalized drug and dosage selection, thereby enhancing the safety and efficacy of treatments. However, despite significant scientific and clinical advancements in PGx, its integration into routine healthcare practices remains limited. To address this gap, the Qatar Genome Program (QGP) has embarked on an ambitious initiative known as QPGx-CARES (Qatar Pharmacogenetics Clinical Applications and Research Enhancement Strategies), which aims to set a roadmap for optimizing PGx research and clinical implementation on a national scale. The goal of QPGx-CARES initiative is to integrate PGx testing into clinical settings with the aim of improving patient health outcomes. In 2022, QGP initiated several implementation projects in various clinical settings. These projects aimed to evaluate the clinical utility of PGx testing, gather valuable insights into the effective dissemination of PGx data to healthcare professionals and patients, and identify the gaps and the challenges for wider adoption. QPGx-CARES strategy aimed to integrate evidence-based PGx findings into clinical practice, focusing on implementing PGx testing for cardiovascular medications, supported by robust scientific evidence. The current initiative sets a precedent for the nationwide implementation of precision medicine across diverse clinical domains.

Primary hyperaldosteronism is associated with increased mortality and morbidity in patients with hypertension and diabetes.

Aims: Primary hyperaldosteronism (PA) is a common cause of hypertension. It is more prevalent in patients with diabetes. We assessed the cardiovascular impact of PA in patients with established hypertension and diabetes. Methods: Data from the National Inpatient Sample (2008-2016) was used to identify adults with PA with hypertension and diabetes comorbidities and then compared to non-PA patients. The primary outcome was in-hospital death. Secondary outcomes included ischemic stroke, hemorrhagic stroke, acute renal failure, atrial fibrillation, and acute heart failure. Results: A total of 48,434,503 patients with hypertension and diabetes were included in the analysis, of whom 12,850 (0.03%) were diagnosed with primary hyperaldosteronism (PA). Compared to patients with hypertension and diabetes but no PA, those with PA were more likely to be younger [63(13) vs. 67 (14), male (57.1% vs. 48.3%), and African-Americans (32% vs. 18.5%) (p<0.001 for all). PA was associated with a higher risk of mortality (adjusted OR 1.076 [1.076-1.077]), ischemic stroke [adjusted OR 1.049 (1.049-1.05)], hemorrhagic stroke [adjusted OR 1.05 (1.05-1.051)], acute renal failure [adjusted OR 1.058 (1.058-1.058)], acute heart failure [OR 1.104 (1.104-1.104)], and atrial fibrillation [adjusted OR 1.034 (1.033-1.034)]. As expected, older age and underlying cardiovascular disease were the strongest predictors of mortality. However, the female gender conferred protection [OR 0.889 (0.886-0.892]. Conclusion: Primary hyperaldosteronism in patients with hypertension and diabetes is associated with increased mortality and morbidity.

Type 2 diabetes and in-hospital sudden cardiac arrest in ST-elevation myocardial infarction in the US.

Aims: We aimed to assess the impact of diabetes on sudden cardiac arrest (SCA) in US patients hospitalized for ST-elevation myocardial infarction (STEMI). Methods: We used the National Inpatient Sample (2005-2017) data to identify adult patients with STEMI. The primary outcome was in-hospital SCA. Secondary outcomes included in-hospital mortality, ventricular tachycardia (VT), ventricular fibrillation (VF), cardiogenic shock (CS), acute renal failure (ARF), and the revascularization strategy in SCA patients. Results: SCA significantly increased from 4% in 2005 to 7.6% in 2018 in diabetes patients and from 3% in 2005 to 4.6% in 2018 in non-diabetes ones (p < 0.001 for both). Further, diabetes was associated with an increased risk of SCA [aOR = 1.432 (1.336-1.707)]. In SCA patients with diabetes, the mean age (SD) decreased from 68 (13) to 66 (11) years old, and mortality decreased from 65.7% to 49.3% during the observation period (p < 0.001). Compared to non-diabetes patients, those with T2DM had a higher adjusted risk of mortality, ARF, and CS [aOR = 1.72 (1.62-1.83), 1.52 (1.43-1.63), 1.25 (1.17-1.33); respectively] but not VF or VT. Those patients were more likely to undergo revascularization with CABG [aOR = 1.197 (1.065-1.345)] but less likely to undergo PCI [aOR = 0.708 (0.664-0.754)]. Conclusion: Diabetes is associated with an increased risk of sudden cardiac arrest in ST-elevation myocardial infarction. It is also associated with a higher mortality risk in SCA patients. However, the recent temporal mortality trend in SCA patients shows a steady decline, irrespective of diabetes.

Overweight and obesity are associated with better survival in STEMI patients with diabetes.

OBJECTIVE: The relationship between obesity and in-hospital outcomes in individuals with type 2 diabetes mellitus (T2DM) who develop an ST-elevation myocardial infarction (STEMI) was assessed. METHODS: Data from the National Inpatient Sample (NIS) from 2008 to 2017 were analyzed. Patients with STEMI and T2DM were classified as being underweight or having normal weight, overweight, obesity, and severe obesity. The temporal trend of those BMI ranges and in-hospital outcomes among different obesity groups were assessed. RESULTS: A total of 74,099 patients with T2DM and STEMI were included in this analysis. In 2008, 35.8% of patients had obesity, and 37.3% had severe obesity. However, patients with obesity accounted for most of the study population in 2017 (57.8%). During the observation period, mortality decreased in underweight patients from 18.1% to 13.2% (p < 0.001). Still, it gradually increased in all other BMI ranges, along with cardiogenic shock, atrial fibrillation, and ventricular fibrillation (p < 0.001 for all). After the combination of all patients during the observation period, mortality was lower in patients with overweight and obesity (adjusted odds ratio = 0.625 [95% CI 0.499-0.784]; 0.606 [95% CI 0.502-0.733], respectively). CONCLUSIONS: A U-shaped association governs the relationship between BMI and mortality in STEMI patients with diabetes, with those having overweight and obesity experiencing better survival.

Predictors of 30-Day Re-admission in Cardiac Patients at Heart Hospital, Qatar.

Background: Cardiovascular disease patients are more likely to be readmitted within 30 days of being discharged alive. This causes an enormous burden on health-care systems in terms of poor care of patients and misutilization of resources. Aims and Objective: This study aims to find out the risk factors associated with 30-day readmission in cardiac patients at Heart Hospital, Qatar. Methods: A total of 10,550 cardiac patients who were discharged alive within 30 days at the heart hospital in Doha, Qatar, from January 2015 and December 2019 were analyzed. The bootstrap method, an internal validation statistical technique, was applied to present representative estimates for the population. Results: Out of the 10,550 cardiac patients, there were 8418 (79.8%) index admissions and 2132 (20.2%) re-admitted at least once within 30 days after the index admission. The re-admissions group was older than the index admission group (65.6 ± 13.2 vs. 56.0 ± 13.5, P = 0.001). Multinomial regression analysis showed that females were 30% more likely to be re-admitted than males (adjusted odds ratio [aOR] 1.30, 95% confidence interval [CI]: 1.11-1.50, P = 0.001). Diabetes (aOR 1.36, 95% CI: 1.20-1.53, P = 0.001), chronic renal failure (aOR 1.93, 95% CI: 1.66-2.24, P = 0.001), previous MI (aOR 3.22, 95% CI: 2.85-3.64, P = 0.001), atrial fibrillation (aOR 2.17, 95% C.I. : 1.10-2.67, P = 0.01), cardiomyopathy (aOR 1.72, 95% CI 1.47-2.02, P = 0.001), and chronic heart failure (aOR 1.56, 95% C.I.: 1.33-1.82, P = 0.001) were also independent predictors for re-admission in the regression model. C-statistics showed these variables could predict 82% accurately hospital readmissions within 30 days after being discharged alive. Conclusion: The model was more than 80% accurate in predicting 30-day readmission after being discharged alive. The presence of five or more risk factors was found to be crucial for readmissions within 30 days. The study may help design interventions that may result in better outcomes with fewer resources in the population.