Abdullah M. Alshehri

Metabolic syndrome and cardiovascular risk

The constellation of dyslipidemia (hypertriglyceridemia and low levels of high-density lipoprotein cholesterol), elevated blood pressure, impaired glucose tolerance, and central obesity is now classified as metabolic syndrome, also called syndrome X. In the past few years, several expert groups have attempted to set forth simple diagnostic criteria for use in clinical practice to identify patients who manifest the multiple components of the metabolic syndrome. These criteria have varied somewhat in specific elements, but in general, they include a combination of multiple and metabolic risk factors. The most widely recognized of the metabolic risk factors are atherogenic dyslipidemia, elevated blood pressure, and elevated plasma glucose. Individuals with these characteristics, commonly manifest a prothrombotic state as well as and a proinflammatory state. Atherogenic dyslipidemia consists of an aggregation of lipoprotein abnormalities including elevated serum triglyceride and apolipoprotein B (apoB), increased small LDL particles, and a reduced level of HDL cholesterol (HDL-C). The metabolic syndrome is often referred to as if it were a discrete entity with a single cause. Available data suggest that it truly is a syndrome, ie, a grouping of atherosclerotic cardiovascular disease (ASCVD) risk factors, that probably has more than one cause. Regardless of cause, the syndrome identifies individuals at an elevated risk for ASCVD. The magnitude of the increased risk can vary according to the components of the syndrome present as well as the other, non–metabolic syndrome risk factors in a particular person.

Can the duration of vomiting predict postoperative outcomes in hypertrophic pyloric stenosis

Background and Objectives: Hypertrophic pyloric stenosis (HPS) is a common cause of gastric outlet obstruction (GOO) in infants. Prolonged GOO is believed to result in acid and electrolyte disturbances, gastric atony, and delayed postoperative recovery. We studied the impact of prolonged vomiting as an indicator of GOO symptoms on the post-operative outcomes in HPS. Design and Setting: A retrospective chart review of all patients who underwent pyloromyotomy at a tertiary care center between February 1997 and February 2009. Patients and Methods: The duration of pre-operative vomiting was correlated with presenting electrolytes and acid-base balances, postoperative time to full feed, postoperative morbidity and duration of hospitalization. Results : Forty-seven patients were identified. At presentation, the median (range) for duration of symptoms was 14 (3-60) days, and surgeries were performed at 2 (0-6) days after admission. Apart from one case of postoperative wound infection, all patients had an unremarkable recovery. The unusually prolonged duration of vomiting in our cohort did not correlate with the mean (SD) preoperative chloride level of 93.9 (8.8) mEq/L, mean (SD) pH level of 7.5 (0.9), mean postoperative time to full feeding of 31 (15.1) hours, or mean duration of hospitalization of 5.1 (2.2) days. Conclusion : Duration of vomiting in HPS at presentation does not seem to have a significant impact on the postoperative outcomes.

Intronic Polymorphisms in the CDKN2B-AS1 Gene Are Strongly Associated with the Risk of Myocardial Infarction and Coronary Artery Disease in the Saudi Population

Recent genome-wide association studies identified single nucleotide polymorphisms (SNPs) on the chromosome 9p21.3 conferring the risk for CAD (coronary artery disease) in individuals of Caucasian ancestry. We performed a genetic association study to investigate the effect of 12 candidate SNPs within 9p21.3 locus on the risk of CAD in the Saudi population of the Eastern Province of Saudi Arabia. A total of 250 Saudi CAD patients who had experienced an myocardial infarction (MI) and 252 Saudi age-matched healthy controls were genotyped using TaqMan assay. Controls with evidenced lack of CAD provided 90% of statistical power at the type I error rate of 0.05. Five percent of the results were rechecked for quality control using Sanger sequencing, the results of which concurred with the TaqMan genotyping results. Association analysis of 12 SNPs indicated a significant difference in the genotype distribution for four SNPs between cases and controls (rs564398 p = 0.0315, χ2 = 4.6, odds ratio (OD) = 1.5; rs4977574 p = 0.0336, χ2 = 4.5, OD = 1.4; rs2891168 p = 1.85 × 10 − 10, χ2 = 40.6, OD = 2.1 and rs1333042 p = 5.14 × 10 − 9, χ2 = 34.1, OD = 2.2). The study identified three protective haplotypes (TAAG p = 1.00 × 10 − 4; AGTA p = 0.022 and GGGCC p = 0.0175) and a risk haplotype (TGGA p = 2.86 × 10 − 10) for the development of CAD. This study is in line with others that indicated that the SNPs located in the intronic region of the CDKN2B-AS1 gene are associated with CAD.

The impact of common polymorphisms in CETP and ABCA1 genes with the risk of coronary artery disease in Saudi Arabians

BackgroundCoronary artery disease (CAD) is a leading cause of morbidity and mortality worldwide. Many genetic and environmental risk factors including atherogenic dyslipidemia contribute towards the development of CAD. Functionally relevant mutations in the dyslipidemia-related genes and enzymes involved in the reverse cholesterol transport system are associated with CAD and contribute to increased susceptibility of myocardial infarction (MI).MethodBlood samples from 990 angiographically confirmed Saudi CAD patients with at least one event of myocardial infarction were collected between 2012 and 2014. A total of 618 Saudi controls with no history or family history of CAD participated in the study. Four polymorphisms, rs2230806, rs2066715 (ABCA1), rs5882, and rs708272 (CETP), were genotyped using TaqMan Assay.ResultsCETP rs5882 (OR = 1.45, P < 0.005) and ABCA1 rs2230806 (OR = 1.42, P = 0.017) polymorphisms were associated with increased risk of CAD. However, rs708272 polymorphism showed protective effect (B1 vs. B2: OR = 0.80, P = 0.003 and B2B2 vs. B1B1: OR = 0.68, P = 0.012) while the ABCA1 variant rs2066715 was not associated.ConclusionThis study is the first to report the association of these polymorphisms with CAD in the population of the Eastern Province of Saudi Arabia. The rs5882 polymorphism (CETP) showed a significant association and therefore could be a promising marker for CAD risk estimation while the rs708272 polymorphism had a protective effect from CAD.

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 (h2 = 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.

Investigation of KIF6 Trp719Arg gene polymorphism in a case-control study of coronary artery disease and non-fatal myocardial infarction in the Eastern Province of Saudi Arabia.

BACKGROUND Kinesin-like protein 6 (KIF6), a member of the kinesin superfamily, is involved in intracellular transport. A few prospective studies have shown the KIF6 variant Trp719Arg (rs20455) to be associated with coronary artery disease (CAD) in Caucasian populations. However, recent genome-wide association studies on CAD have not proven these associations. OBJECTIVES Since the role of KIF6 719Arg allele in other ethnic populations is largely unknown, we sought to determine whether the KIF6 719Arg allele is associated with CAD in an ethnic population of Saudi Arabia. DESIGN Case-control study. SETTING CAD patients and control subjects from King Fahd Hospital of the University, Al-Khobar, Saudi Arabia. PATIENTS AND METHODS The study population included angiographically defined CAD patients (n=1002) and controls (n=984) with a normal electrocardiogram. MAIN OUTCOME MEASURE(S) Association of KIF6 Trp719Arg mutation with CAD. RESULTS The KIF6 Trp719Arg polymorphism was not associated with CAD (OR 0.976, 95% CI 0.861–1.105; P=.704). In addition, KIF6 Trp719Arg polymorphism showed a lack of association even in stratified myocardial infarction patients (n=802) (OR 1.006, 95% CI 0.881–1.148; P=.929) in comparison to controls. CONCLUSIONS The absence of Trp719Arg polymorphism association with CAD and CAD in stratified myocardial infarction cases indicates that the polymorphism is not associated with an increased risk among CAD patients from the Eastern Province of Saudi Arabia. Further studies in different provinces are required to unravel biological mechanisms underlying CAD in patients from Saudi Arabia. LIMITATIONS Unavailability of data on statin usage among the patient population.

β 2 -adrenergic receptor gene polymorphisms in normal and in patients with myocardial infarction in the eastern province of Saudi Arabia

Introduction: Single nucleotide polymorphisms (SNPs) of the β2 -adrenergic receptor (β2 -AR) gene have been implicated in the pathogenesis of cardiovascular diseases. This study evaluated two β2 -AR SNPs in association with myocardial infarction (MI), namely arginine-glycine (G16R) substitution at codon 16 and glutamine-glutamic (Q27E) substitution at condon 27. Objectives: Therefore, our main objective was to determine the association of these two SNPs among patients with MI with and without type 2 diabetes (T2D). Materials and Methods: Blood samples were collected from 201 MI patients with and without diabetes and from 115 controls and the β2 -AR gene polymorphisms at codon 16 and codon 27 were assessed by restriction fragment length polymorphism. The χ2 test was used to compare differences between groups. Results: The SNPs did not deviate significantly from Hardy-Weinberg equilibrium in the control population. The allele and genotype frequencies of the β2 -AR gene polymorphism at codon 16 (G16R) was significantly different between MI cases and controls (χ2 = 10.495, P < 0.05 and χ2 = 8.849, P < 0.05, respectively). No significant difference in genotype and allele frequencies at codon 27 was shown between these two groups (χ2 = 2.661, P ≥ 0.05 and χ2 = 1.587, P ≥ 0.05, respectively). When the MI patients with and without T2D were pooled together, genotype distribution was different between cases and controls at codon 16 (χ2 = 4.631, P = 0.099) and codon 27 (χ2 = 7.247, P = 0.027). However, no significant differences were found in allele frequencies for codon 16 and codon 27 between the two groups (χ2 = 0.628, P = 0.428; χ2 = 0.33, P = 0.565, respectively). Conclusion: Our findings indicate a moderate association of the β2 -AR G16R gene polymorphism with MI suggesting that this gene plays a universal role in the development of MI across ethnicities. However, there was no association of β2 -AR G16R gene polymorphism with diabetic patients with MI.

Correlation between ST segment shift and cardiac diastolic function in patients with acute myocardial infarction

BACKGROUND Diastolic dysfunction is the early sign of myocardial ischemia that usually occurs earlier than ECG changes. AIM OF THE STUDY To determine the existence of a correlation between ST segment shift and diastolic dysfunction among patients with AMI. METHODS Fourty six patients with significant ST segment elevation or depression and having symptoms of acute myocardial infarction for <12 h were enrolled in this study. Patients were examined for serial ECG, cardiac enzymes, and echocardiography. RESULTS There was no significant correlation between ST segment elevation or depression and majority of the diastolic indices. Few diastolic parameters; such as, E/A ratio of the mitral valve and deceleration time of the tricuspid valve showed a direct correlation with the ECG changes. Whereas, the Tei Index of the LV function showed a borderline correlation to the ST segment elevation at discharge. CONCLUSION Overall, there was no correlation between either ST segment elevation or depression and the LV or RV diastolic function in patients with acute coronary syndrome (ACS). Improvement of the ST segment total score was associated with improvement of the diastolic function grades at discharge. Moreover, this association has shown an evidence of dose response relationship, the more improvement in total score at discharge the more improvement in diastolic function grade level.

Functional and structural changes in soccer players' heart and the risk for sudden cardiac death

Background: Regular exercise in athletes is associated with cardiac acclimation in the form of functional and structural changes. Its effect on the cardiac functions still debated. Objective: The objective was to detect the impact of long-term regular physical exercise on the cardiac systolic and diastolic function of soccer players. Materials and Methods: Thirty professional soccer players were examined twice, the first examination was made during the passive resting period before the beginning of the season (measurement I) and the second during the peak of the season (measurement II). At both examinations, players underwent electrocardiogram (ECG), conventional Echo-Doppler, pulsed tissue Doppler imaging on both septal and lateral sides of the mitral annulus and lateral tricuspid annulus. The (propagation velocity [Vp]) values were measured. Paired t-test was used for comparison. Results: The following changes between measurement I and measurement II were found: ECG Changes; 80% of the entire group showed early repolarization, 93% had left ventricular hypertrophy (LVH) by voltage criteria, 20% showed right atrial abnormalities, 20% left atrial abnormalities, 40% showed inverted T-wave in leads V1-V4, 5% showed mobitz type I second degree heart block, and 5% showed incomplete right bundle branch block. Echo changes; The mitral E/E` ratio increased from 6.18 ± 1.27 to 6.91 ± 1.18; the Vp decreased from 56.3 ± 9.23 to 50.67 ± 8.6; the tricuspid valve Ratio between the early and late peak pulsed Doppler velocities on tricuspid valve decreased from 1.67 ± 0.23 to 1.54 ± 0.23 while the E`/A` ratio decreased from 1.67 ± 0.53 to 1.28 ± 0.49; the (isovolumetric relaxation time) of the right ventricle increased from 52.4 ± 11.33 to 58.17 ± 10.73; the (isovolumetric contraction time) decreased from 70.47 ± 9.9 to 65.2 ± 7.9. All changes were statistically significant at P < 0.001. Conclusions: Long-term regular exercise in soccer players is associated with cardiac alterations in the form of bradycardia, early repolarization, inverted T-wave, concentric LVH, and a tendency toward diastolic impairment of both ventricles.

Comparison of Angioseal and Manual Compression in Patients Undergoing Transfemoral Coronary and Peripheral Vascular Interventional Procedures.

Vascular closure devices (VCDs) were introduced in the early 1990s with the goal of limiting the time, labor, bed rest, and patient discomfort associated with manual compression (MC) for hemostasis after cardiovascular interventions. However, its advantage over MC has not been extensively studied after interventional procedures. The aim of this study was to do prospective, randomized study comparing the safety and efficacy of the Angio-Seal (AS) to that of MC in patients undergoing transfemoral coronary and peripheral vascular interventional procedure. A prospective, randomized trial was undertaken on consecutive series of patients admitted to King Fahd Hospital of the University for transfemoral coronary and peripheral vascular interventional procedures over 1 year. The study was designed to compare the hemostasis time in minutes and the incidence of vascular complications in patients receiving AS with those undergoing MC. All patients were on antiplatelets and received heparin during the procedure. During the study period, 160 patients were included, 80 in each group. There was a significant difference in mean time to hemostasis in minutes (15.83 ± 1.63 minutes for MC and 0.42 ± 0.04 minutes for the AS; p < 0.001), time to ambulation in minutes (280 ± 15 for MC and 120 for AS; p = 0.04) and in minor complications (33.8% in MC vs. AS 5%; p < 0.001). However, the major complication rate did not significantly differ between the two groups (0% in AS vs. 2.5% in MC; p = 0.15). AS was found to achieve rapid closure of the femoral access site safely in patients undergoing coronary and peripheral vascular interventional procedures under antiplatelets and systemic heparinization.