Vitamin D and Its Metabolites Deficiency in Acute Coronary Syndrome Patients Undergoing Coronary Angiography: A Case-Control Study.

BACKGROUND: Vitamin D deficiency is considered an emerging health problem that affects at least one billion patients worldwide. Calcitriol 1,25(OH)2D3 has several systemic effects, including anti-inflammatory, anti-thrombotic and anti-atherosclerotic impacts that explain its cardioprotective effects. The precise association between vitamin D and its metabolites and the value of supplements in acute coronary syndrome (ACS) is still controversial. This study aims to search the association between vitamin D2, D3, and metabolites and ACS in patients undergoing coronary angiography. MATERIALS AND METHODS: This was a case-control study on 73 consecutive adult patients with ACS undergoing coronary angiography compared to 50 controls without coronary artery disease and matched for age and sex from June 2019 till July 2019. Echocardiography and coronary angiography were done for all cases. Plasma vitamin D and its metabolites were measured at admission for all participants along with chemistry profiles. RESULTS: Vitamin D and its metabolites were statistically significantly lower in ACS patients than the controls. Multivariate regression analysis revealed that low levels of 25-hydroxyvitamin D (25(OH)D) and 1,25-dihydroxyvitamin D (1,25(OH)2D) significantly predicted ACS occurrence; the other significant predictors were high systolic blood pressure (BP), high total cholesterol, and low high-density lipoprotein-cholesterol. Interestingly, vitamin D2 and D3 did not significantly predict ACS (p>0.05). We did not find a statistically significant association between the number of affected coronary vessels and vitamin D metabolites. Moreover, there was no statistically significant correlation between vitamin D and its metabolites and left ventricular ejection fraction measured by echocardiography. CONCLUSION: There was a strong association between vitamin D and all its metabolites with ACS. Significantly, low 25(OH)D and 1,25(OH)2D predicted ACS, but vitamin D2 and D3 did not. Large randomized controlled trials are needed to verify the beneficial values of vitamin D supplementation in ACS patients.

Differential Effect of Three Macrolide Antibiotics on Cardiac Pathology and Electrophysiology in a Myocardial Infarction Rat Model: Influence on Sodium Nav1.5 Channel Expression.

Macrolides were reported to have cardiotoxic effects presented mainly by electrocardiogram (ECG) changes with increased risk in cardiac patients. We aimed to determine the impact of three macrolides, azithromycin, clarithromycin and erythromycin, on cardiac electrophysiology, cardiac enzyme activities, histopathological changes, and sodium voltage-gated alpha subunit 5 (Nav1.5) channel expression. We used eight experimental groups of male albino rats: vehicle, azithromycin (100 mg/kg), clarithromycin (100 mg/kg), erythromycin (100 mg/kg), MI + vehicle, MI + azithromycin (100 mg/kg), MI + clarithromycin (100 mg/kg) and MI + erythromycin (100 mg/kg); each group received chronic oral doses of the vehicle/drugs for seven weeks. ECG abnormalities and elevated serum cardiac enzymes were observed particularly in rats with AMI compared to healthy rats. Microscopic examination revealed elevated pathology scores for rats treated with clarithromycin in both experiments following treatment with erythromycin in healthy rats. Although rats with MI did not show further elevations in fibrosis score on treatment with macrolides, they produced significant fibrosis in healthy rats. Downregulation of cardiac Nav1.5 transcript was observed following macrolides treatment in both groups (healthy rats and rats with MI). In conclusion, the current findings suggested the potential cardiotoxic effects of chronic doses of macrolide antibiotics in rats with MI as manifested by abnormal ECG changes and pathological findings in addition to downregulation of Nav1.5 channels. Furthermore, in the current dose ranges, azithromycin produced the least toxicity compared to clarithromycin and erythromycin.

Association of MIR-499a expression and seed region variant (rs3746444) with cardiovascular disease in Egyptian patients.

BACKGROUND: Circulating microRNAs could be powerful markers of acute myocardial infarction (MI) and its functional genetic variants could increase susceptibility to cardiovascular disease (CVD). The current study aimed to quantify the microRNA (miR)-499a levels in serum of MI patients compared to hypertensive and healthy subjects and to investigate the association of its A/G variant rs3746444 with CVD in a sample of an Egyptian population. METHODS: Serum miR-499a relative expressions were measured in 110 acute MI patients, 76 hypertensive patients, and 121 healthy controls by Real-time quantitative polymerase chain reaction. MIR-499a genotyping was performed for an additional 107 coronary artery disease patients by Real-time allele discrimination assay. RESULTS: Acute MI patients showed high relative expression of miR-499a (> 105-fold, p < .001), and it was nearly undetectable in healthy controls and hypertensive patients. It showed an area under the curve of 0.953, with a sensitivity of 97.2% and a specificity of 75.0%. ST-elevation MI (STEMI) patients had higher miR-499a serum levels than patients with Non-STEMI. There was a significant association of MIR-499a variant with acute MI but not with hypertension under all genetic models tested. As a new finding, in overall and stratified analysis, the miR-499a variant was not correlated with its expression profile. CONCLUSIONS: Circulating miR-499a levels could be a useful biomarker, discriminating acute MI within 12 hours from healthy subjects. Its variant rs3746444 A/G is associated with increased susceptibility to acute MI and CAD in Egyptian population.

Association of MicroRNA-196a2 Variant with Response to Short-Acting ß2-Agonist in COPD: An Egyptian Pilot Study.

Chronic obstructive pulmonary disease (COPD) is a multifactorial chronic respiratory disease, characterized by an obstructive pattern. Understanding the genetic predisposition of COPD is essential to develop personalized treatment regimens. MicroRNAs (miRNAs) are small, endogenous, non-coding RNAs that modulate the expression levels of specific proteins based on sequence complementarity with their target mRNA molecules. Emerging evidences demonstrated the potential use of miRNAs as a disease biomarker. This pilot study aimed to investigate the association of the MIR-196a2 rs11614913 (C/T) polymorphism with COPD susceptibility, the clinical outcome and bronchodilator response to short-acting ß2-agonist. Genotyping of rs11614913 polymorphism was determined in 108 COPD male patients and 116 unrelated controls using real-time polymerase chain reaction technology. In silico target prediction and network core analysis were performed. COPD patients did not show significant differences in the genotype distribution (p = 0.415) and allele frequencies (p = 0.306) of the studied miRNA when compared with controls. There were also no associations with GOLD stage, dyspnea grade, disease exacerbations, COPD assessment test for estimating impact on health status score, or the frequency of intensive care unit admission. However, COPD patients with CC genotype corresponded to the smallest bronchodilator response after Salbutamol inhalation, the heterozygotes (CT) had an intermediate response, while those with the TT genotype showed the highest response (p < 0.001). In conclusion MIR-196a2 rs11614913 polymorphism is associated with the bronchodilator response of COPD in our sample of the Egyptian population, generating hypothesis of the potential use of MIR-196a2 variant as a pharmacogenetic marker for COPD.

Functional and Structural Impact of ATP-Binding Cassette Transporter A1 R219K and I883M Gene Polymorphisms in Obese Children and Adolescents.

INTRODUCTION: Obesity is a serious medical condition that affects children and adolescents. ATP-binding cassette transporter A1 (ABCA1) protein is known to mediate the transport of intracellular cholesterol and phospholipids across the cell membranes. Thus, we aimed to investigate the association between ABCA1 gene polymorphisms and overweight/obesity risk, and to evaluate their relation to the lipid profile. MATERIALS AND METHODS: The study included in silico analysis of ABCA1 gene and protein. Two genetic variants in ABCA1 gene-R219K (rs2230806; G/A) and I883M (rs2066714; A/G)-were genotyped in 128 normal weight and 128 overweight/obese subjects using polymerase chain reaction-restriction fragment length polymorphism technology. Anthropometric and biochemical assessments were performed. RESULTS: Our findings suggest that the heterozygote GA genotype of R219K polymorphism increased susceptibility to obesity under the heterozygous model (odds ratio 2.75, 95 % CI 1.01-6.12; p = 0.014) compared with the control group. This susceptibility could be gender-specific, with higher risk among females. In addition, the A variant was associated with a higher degree of obesity (p < 0.001). On the other hand, individuals with the G variant of I883M polymorphism showed lower susceptibility to obesity under all genetic models (allelic, homozygote, heterozygote, dominant, and recessive models; p < 0.05), with no observed association with body mass index or degree of obesity. However, both single nucleotide polymorphisms (SNPs) showed significant differences in lipid levels among patients with different genotypes. CONCLUSIONS: The study results suggest that R219K and I883M SNPs of the ABCA1 gene may play a role in susceptibility to obesity in our Egyptian population; the former increases susceptibility and phenotype severity, and the latter is protective. Larger epidemiological studies are needed for validation of the results.

Effectiveness of theophylline in preventing contrast-induced nephropathy after coronary angiographic procedures.

BACKGROUND: Contrast-induced nephropathy (CIN) is the third most common cause of hospital acquired acute renal failure and is associated with increased morbidity and mortality. The use of theophylline for prevention of CIN has yielded conflicting results. This study aimed at examining the effectiveness of theophylline in prevention of CIN when added to IV hydration and N-acetylcysteine (NAC). METHODS: Patients with stable serum creatinine and at least moderate risk for CIN according to Mehran's risk score were included in this parallel group, 1:1, single-blind, randomized controlled trial. All patients received IV hydration (1 mL/kg per hour for 24 hours) and NAC (600 mg bid for 2 days). Patients were randomized to placebo (group P) or theophylline (200 mg in 100 mL 0.9% saline, as IV infusion 30 minutes before contrast medium (CM) administration; group T). Patients underwent standard coronary angiography ± angioplasty. Serum creatinine (SCr) was assessed just before and 72 hours after contrast administration and estimated glomerular filtration rate (eGFR) was calculated. RESULTS: This study included 60 patients with mean SCr 1.44 ± 0.7 mg/dL and eGFR 60.2 ± 29.2 mL/min. Mean SCr among group T was 1.54 ± 0.7 mg/dL with eGFR 58.6 ± 28.6 mL/min, while group P showed mean SCr of 1.34 ± 0.7 mg/dL and eGFR of 61.8 ± 30.1 mL/min. Among group P, 6 (20%) patients developed CIN while none of the patients in group T developed CIN. In comparison to placebo, theophylline significantly decreased SCr (P = 0.0001) and increased eGFR (P = 0.001) at 72 hours. Multivariate regression analysis showed that receiving placebo instead of theophylline, anemia, congestive heart failure, chronic renal impairment, and high-contrast load are all independent predictors for deteriorating renal function after CM administration. CONCLUSION: Theophylline seems to be an effective prophylaxis against CIN for moderate- and high-risk patients undergoing coronary angiography or angioplasty. It offers additive protection when added to IV hydration and NAC.