Prevalence, Predictors, and Outcomes of Resistant Hypertension in Egyptian Population.

Background: Hypertension is a leading problem; it affects around thirty million adult Egyptians, according to the last national registry. The exact prevalence of resistant hypertension (RH) in Egypt wasn't spotted before. The purpose of this study was to determine the prevalence, predictors, and impact on adverse cardiovascular outcomes among adult Egyptians with RH. Methods: The present study examined a cohort of 990 hypertensive patients who were divided into two groups based on their blood pressure control; group I (n = 842) patients who achieved blood pressure control and group II (n = 148) patients who met the RH definition criteria. All patients underwent a close follow-up for one year to evaluate the major cardiovascular events. Results: The prevalence of RH was 14.9%. The main predictors impacting the cardiovascular outcomes of RH were advanced age (≥65 years), the presence of chronic kidney diseases, a BMI ≥ 30 kg/m2, and NSAID use. After one year of follow-up, the RH group displayed noticeably higher rates of major cardiovascular events, including new-onset atrial fibrillation (6.8% vs. 2.5%, P = 0.006), cerebral stroke (4.1% vs. 1.2%, P = 0.011), myocardial infarction (4.7% vs. 1.3%, P = 0.004), and acute heart failure (4.7% vs. 1.8%, P = 0.025). Conclusion: The prevalence of RH in Egypt is moderately high. Patients with RH have a far higher risk of cardiovascular events than those whose blood pressure is within control.

Predictors of Outcomes After Coronary Artery Bypass Grafting: The Effect of Concomitant Mitral Repair.

Background Ischemic mitral regurgitation (IMR) or functional MR intensity with or without repair increases the risk of coronary artery bypass grafting (CABG), and if the contaminant is undertaken, it doubles the risk of the surgery. This study aimed to characterize patients with concomitant CABG and mitral valve repair (MVR) and assess the surgical and long-term outcomes. Methods We conducted a cohort study from 2014 to 2020 on 364 patients who underwent CABG. A total of 364 patients were enrolled and divided into two groups. Group I (n= 349) included patients with isolated CABG, and Group II included patients who underwent CABG with concomitant mitral valve repair (MVR) (n= 15). Results Regarding preoperative presentation, most patients were male: 289 (79.40%), hypertensive 306 (84.07%), diabetic 281 (77.20%), dyslipidemic 246 (67.58%), presenting with NYHA classes III-IV: 200 (54.95%), and upon angiography, found to have the three-vessel disease: 265 (73%). Regarding their age mean± SD and Log EuroSCORE median (Q1-Q3), they had a mean age of 60.94± 10.60 years and a median score of 1.87 (1.13-3.19). The most prevalent postoperative complications were low cardiac output 75 (20.66%), acute kidney injury (AKI) 63 (17.45%), respiratory complications 55 (15.32%), and atrial fibrillation (AF) 55 (15.15%). Regarding long-term outcomes, most patients reported class I NYHA 271 (83.13%) and an echocardiographic decrease in MR severity. Patients with a CABG + MVR were significantly younger (53.93± 15.02 vs. 61.24± 10.29 years; P= 0.009), had a lower ejection fraction (33.6 [25-50] vs. 50 [43-55] %; p= 0.032), and had a higher prevalence of LV dilation (32 [9.17%]). EuroSCORE was significantly higher in patients with mitral repair (3.59 [1.54-8.63] vs. 1.78 (1.13-3.11); P= 0.022). The mortality percentage was higher with MVR but did not attain statistical significance. Intraoperative CPB and ischemic durations were longer in the CABG + MVR group. Furthermore, neurological complications were higher in patients with mitral repair (4 (28.57%) vs. 30 (8.65%), P= 0.012). The study's follow-up duration median was 24 (9-36) months. The composite endpoint occurred more frequently in older patients (HR: 1.05 [95% CI: 1.02-1.09]; 0.001), patients with low ejection fraction (HR: 0.96 [95% CI: 0.93-0.99]; P= 0.006) and in patients with preoperative myocardial infarction (MI) (HR: 2.3 [95%: 1.14- 4.68]; P= 0.021). Conclusion Most IMR patients benefited from CABG and CABG + MVR, as evident by NYHA class and echocardiographic follow-up. CABG + MVR had a higher Log EuroSCORE risk with increased intraoperative cardiopulmonary bypass (CPB) and ischemic durations, which may have played a role in increasing the incidence of postoperative neurological complications. On follow-up, no differences were reported between the two groups. However, age, ejection fraction, and a history of preoperative MI were identified as factors affecting the composite endpoint.

Incidence, predictors, and outcomes of new-onset atrial fibrillation in patients with ST-elevation myocardial infarction.

BACKGROUND: Atrial fibrillation (AF) is a common arrhythmia and one of the complications in the setting of ST-elevation myocardial infarction (STEMI). Our objective of the present study was to investigate the incidence, predictors, and outcomes of NOAF in patients with acute STEMI managed with pharmacoinvasive strategy (PIS) versus those managed with primary percutaneous coronary intervention (PPCI). METHODS: The study included 530 patients with STEMI divided into two groups according to the method of treatment. Group I: 269 patients subjected to pharmacoinvasive strategy (PIS), group II: 261 patients managed with primary percutaneous coronary intervention (PPCI). Incidence, predictors, and outcomes of NOAF were assessed in each group separately. RESULTS: The incidence of NOAF was 25 patients (9.3%) in group I and 24 patients (9.2%) in group II. Multivariate regression analysis identified the independent predictors of NOAF that were (advanced age ˃65 years, history of hypertension, left atrial volume index (LAVI) ˃34 ml/m2 , E/e' ratio ˃ 12, right coronary artery (RCA) as a culprit vessel and presence of heart failure). There was no statistically significant difference between both groups regarding the occurrence of MACE. CONCLUSION: New-onset AF represents one of the common complications in the setting of STEMI. Advanced age, hypertension, LAVI ˃34 ml/m2 , E/e' ratio ˃12, RCA culprit vessel, and heart failure were the independent predictors of NOAF.

Very Early Versus Early Percutaneous Coronary Intervention After Successful Fibrinolytic Therapy in Pharmacoinvasive Strategy.

BACKGROUND: The proper time for the use of percutaneous coronary intervention (PCI) following the successful fibrinolysis for ST-segment elevation myocardial infarction (STEMI) for maximum efficiency and minimum side effects has not been determined yet. The present study was designed to compare the outcome of myocardial infarction patients who received fibrinolytic therapy with successful results and underwent PCI very early (within 3-12 h) (group 1) versus early (within 12-24 h) (group 2). METHODS: The study compared the occurrence of major adverse cardiac events during PCI (no-reflow phenomenon, access site bleeding, cerebral hemorrhage, and cardiac death). Patients were followed for 6 months after PCI for the occurrence of unstable angina, recurrent angina, non-STEMI, recurrent STEMI, repeat revascularization, heart failure, and cardiac death. RESULTS: Group 1 (121 patients) with the mean age of 59.93 ± 10.43 years were compared with group 2 (144 patients) with the mean age of 62.84 ± 10.22 years. Except for age, the 2 groups were not significantly different regarding baseline characteristics. No-reflow phenomenon was less in group 1 with p value = 0.005, whereas incidence of access site bleeding and cerebral hemorrhage were more in this group with p value = 0.001 and 0.049, respectively. During the period of 6 months' follow-up, recurrent angina and recurrent non-STEMI occurred more in group 2 with p value = 0.049 and 0.035, respectively, with no other significant difference between the 2 groups. CONCLUSIONS: No-reflow phenomenon and the risk of recurrent ischemia is significantly lower in patients undergoing PCI very early after successful fibrinolytic therapy, but the risk of bleeding is increased in this time. So it is recommended that patients received successful fibrinolytic therapy to be subjected to very early PCI within 3 to 12 h from fibrinolysis.

Arterial stiffness in metabolic syndrome.

UNLABELLED: Arterial stiffness is increasingly recognized as an important determinant of cardiovascular risk and may be directly involved in the process of atherosclerosis. As atherosclerosis leads to increased arterial resistance and decrease the flow propagation speed within the arterial lumen, a similar decrease in aortic flow propagation with increased downstream resistance is detected, so aortic flow propagation velocity AVP was evaluated in many studies as a new parameter of aortic stiffness. AIM: To measure arterial stiffness using the new parameter AVP and compare it to flow mediated dilatation FMD as a parameter of endothelial dysfunction in patients with metabolic syndrome MS. METHODS: AVP (assessed by transthoracic echocardiography) and FMD (assessed by brachial artery reactivity test) were measured in 100 patients with MS (Group 1) and were compared to 14 normal subjects (Group 2). RESULTS: Patients with MS had significantly lower values of AVP as compared to the normal subjects; 36 ± 5 cm/s vs 57 ± 5, p < 0.05, and lower FMD; 6% ± 1 vs 17 ± 3 p < 0.05 as well, there was significant correlations between AVP and FMD (r = 0.89, p < 0.001). CONCLUSION: Transthoracic echocardiographic determination of AVP is a simple practical method and correlates well with FMD in patients with MS.

Characterization of the antigen specificity of T-cell clones from piperacillin-hypersensitive patients with cystic fibrosis.

ß-Lactam antibiotics provide the cornerstone of treatment and reduce the rate of decline in lung function in patients with cystic fibrosis, but their use is limited by a high frequency of delayed-type allergic reactions. The objective of this study was to use cloned T-cells expressing a single T-cell receptor from five piperacillin-hypersensitive patients to characterize both the cellular pathophysiology of the reaction and antigen specificity to define the mechanism of activation of T-cells by piperacillin. More than 400 piperacillin-responsive CD4+, CD4+CD8+, or CD8+ T-cell clones were generated from lymphocyte transformation test and ELIspot-positive patients. The T-cell response (proliferation, T helper 2 cytokine secretion, and cytotoxicity) to piperacillin was concentration-dependent and highly specific. Enzyme-linked immunosorbent assay, gel electrophoresis, and mass spectrometry revealed that piperacillin bound exclusively to albumin in T-cell culture. Irreversible piperacillin binding at Lys 190, 195, 199, 432, and 541 on albumin and the stimulation of T-cells depended on incubation time. A synthetic piperacillin albumin conjugate stimulated T-cell receptors via a major histocompatibility complex- and processing-dependent pathway. Flucloxacillin competes for the same Lys residues on albumin as piperacillin, but the resulting conjugate does not stimulate T-cells, indicating that binding of the ß-lactam hapten in peptide conjugates confers structural specificity on the activation of the T-cell receptors expressed on drug-specific clones. Collectively, these data describe the cellular processes that underlie the structural specificity of piperacillin antigen binding in hypersensitive patients with cystic fibrosis.

Enhanced antigenicity leads to altered immunogenicity in sulfamethoxazole-hypersensitive patients with cystic fibrosis.

BACKGROUND: Exposure of patients with cystic fibrosis to sulfonamides is associated with a high incidence of hypersensitivity reactions. OBJECTIVE: To compare mechanisms of antigen presentation and characterize the phenotype and function of T cells from sulfamethoxazole-hypersensitive patients with and without cystic fibrosis. METHODS: T cells were cloned from 6 patients and characterized in terms of phenotype and function. Antigen specificity and mechanisms of antigen presentation to specific clones were then explored. Antigen-presenting cell metabolism of sulfamethoxazole was quantified by ELISA. The involvement of metabolism in antigen presentation was evaluated by using enzyme inhibitors. RESULTS: Enzyme inhibitable sulfamethoxazole-derived protein adducts were detected in antigen-presenting cells from patients with and without cystic fibrosis. A significantly higher quantity of adducts were detected with cells from patients with cystic fibrosis. Over 500 CD4(+) or CD8(+) T-cell clones were generated and shown to proliferate and kill target cells. Three patterns of MHC-restricted reactivity (sulfamethoxazole-responsive, sulfamethoxazole metabolite-responsive, and cross-reactive) were observed with clones from patients without cystic fibrosis. From patients with cystic fibrosis, sulfamethoxazole metabolite-responsive and cross-reactive, but not sulfamethoxazole-responsive, clones were observed. The response of the cross-reactive clones to sulfamethoxazole was dependent on adduct formation and was blocked by glutathione and enzyme inhibitors. Antigen-stimulated clones from patients with cystic fibrosis secreted higher levels of IFN-γ, IL-6, and IL-10, but lower levels of IL-17. CONCLUSION: Sulfamethoxazole metabolism and protein adduct formation is critical for the stimulation of T cells from patients with cystic fibrosis. T cells from patients with cystic fibrosis secrete high levels of IFN-γ, IL-6, and IL-10.

Drug antigenicity, immunogenicity, and costimulatory signaling: evidence for formation of a functional antigen through immune cell metabolism.

Recognition of drugs by immune cells is usually explained by the hapten model, which states that endogenous metabolites bind irreversibly to protein to stimulate immune cells. Synthetic metabolites interact directly with protein-generating antigenic determinants for T cells; however, experimental evidence relating intracellular metabolism in immune cells and the generation of physiologically relevant Ags to functional immune responses is lacking. The aim of this study was to develop an integrated approach using animal and human experimental systems to characterize sulfamethoxazole (SMX) metabolism-derived antigenic protein adduct formation in immune cells and define the relationship among adduct formation, cell death, costimulatory signaling, and stimulation of a T cell response. Formation of SMX-derived adducts in APCs was dose and time dependent, detectable at nontoxic concentrations, and dependent on drug-metabolizing enzyme activity. Adduct formation above a threshold induced necrotic cell death, dendritic cell costimulatory molecule expression, and cytokine secretion. APCs cultured with SMX for 16 h, the time needed for drug metabolism, stimulated T cells from sensitized mice and lymphocytes and T cell clones from allergic patients. Enzyme inhibition decreased SMX-derived protein adduct formation and the T cell response. Dendritic cells cultured with SMX and adoptively transferred to recipient mice initiated an immune response; however, T cells were stimulated with adducts derived from SMX metabolism in APCs, not the parent drug. This study shows that APCs metabolize SMX; subsequent protein binding generates a functional T cell Ag. Adduct formation above a threshold stimulates cell death, which provides a maturation signal for dendritic cells.