Free estradiol index levels associated with high sensitivity CRP levels in male children.

Agirbasli M, Tanrikulu A, Azizy M. Free estradiol index levels associated with high sensitivitiy CRP levels in male children. Turk J Pediatr 2017; 59: 49-55. Biomarkers of inflammation such as high-sensitivity C-reactive protein (hs-CRP) associate with subclinical atherosclerosis. Atherosclerosis is an early onset disease in life. Sex hormones and puberty modulate metabolism in children. Studies indicate that low sex hormone binding globulin (SHBG) levels associate with insulin resistance and metabolic syndrome in children. The aim of this study is to study the correlation between sex hormones and hs-CRP levels in children and adolescents. The study sample was derived from a cross sectional survey on the prevalence of cardiovascular risk factors in a representative sample of school children (8-17 year-old) in Istanbul, Turkey. In addition to anthropometric and biochemical characteristics of cardiovascular risk, sex hormones such as free androgen index, free estradiol index (FEI), SHBG and hs-CRP levels were measured in all study participants: 91 boys (12.4 ± 3.4 years) and 77 girls (12.7 ± 3.4 years) were included in the study. Median (interquartile range) hs-CRP levels were similar among boys and girls [0.36 (0.9) versus 0.45 (0.7) mg/dl, p= 0.725]. Gender stratified analysis displayed that hs-CRP levels positively correlated with FEI levels (r=0.438, p < 0.001) in boys. Linear regression analysis was performed to determine the predictors of hs-CRP. Among covariates of FEI, homeostasis model assessment-estimated insulin resistance, body mass index, age, and SHBG; FEI was shown to significantly and independently predict hs-CRP levels in boys [ß=2.758, p < 0.001, 95% confidence interval (CI) for ß 1.471-4.045]. FEI levels associate with subclinical inflammation in boys. Future studies may elucidate the role of sex hormone levels in inflammation among children.

Metabolic Syndrome: Bridging the Gap from Childhood to Adulthood.

Childhood and adolescence are particularly vulnerable periods of life to the effects of cardiometabolic risk and later development of atherosclerosis, hypertension, and diabetes mellitus. Developing countries with limited resources suffer most heavily from the consequences of cardiometabolic risk in children and its future implications to the global health burden. A better understanding of mechanisms leading to cardiometabolic risk in early life may lead to more effective prevention and intervention strategies to reduce metabolic stress in children and later disease. Longitudinal "tracking" studies of cardiometabolic risk in children provide a tremendous global resource to direct prevention strategies for cardiovascular disease. In this review, we will summarize the pathophysiology, existing definitions for cardiometabolic risk components in children. Screening and identifying children and adolescents of high cardiometabolic risk and encouraging them and their families through healthy lifestyle changes should be implemented to as a global public health strategy.

Acute Exacerbation Impairs Right Ventricular Function in COPD Patients.

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) may impair right ventricular (RV) function. Tissue Doppler imaging (TDI) is helpful in the noninvasive evaluation of RV longitudinal function. The aim of this study was to assess the impact of acute COPD exacerbation on RV function assessed by TDI. METHODS: The study included 30 COPD patients who had acute exacerbation and 30 controls. RV function was assessed echocardiographically during acute exacerbation and after recovery. In addition to conventional echocardiographic parameters, tricuspid annular plane systolic excursion, tricuspid annulus peak systolic velocity (Sa), and TDI-derived isovolumic myocardial acceleration (IVA) were determined. RESULTS: During exacerbation, COPD patients had a significantly larger RV and higher pulmonary artery systolic pressure, with significantly lower IVA, Sa and tricuspid annular plane systolic excursion compared to controls. After recovery, IVA and Sa significantly increased, while RV diameter and pulmonary artery systolic pressure significantly decreased to levels similar to controls. There were statistically significant, but modest correlations between IVA and Sa (r=0.441, p=0.003), tricuspid annular plane systolic excursion (r=0.628, p<0.001), pulmonary artery systolic pressure (r=-0.391, p=0.002) and RV diameter (r=-0.309, p=0.018). Sa correlated with pulmonary artery systolic pressure (r=-0.350, p=0.007) and RV diameter (r=-0.344, p=0.008). CONCLUSIONS: COPD exacerbations have a negative impact on RV function. TDI-derived IVA and Sa may be used in the assessment of subclinical RV dysfunction in COPD patients with exacerbation.

Total cholesterol-to-high-density lipoprotein cholesterol ratio predicts high-sensitivity C-reactive protein levels in Turkish children.

BACKGROUND: High-sensitivity C-reactive protein (hs-CRP) is a biomarker of continued long-term systemic inflammation and cardiovascular (CV) risk. OBJECTIVE: To analyze the association of hs-CRP levels with CV risk factors in healthy school children. METHODS: The study sample was derived from a survey on the prevalence of CV risk factors (dyslipidemia, obesity, high blood pressure, and insulin resistance in school children. Along with anthropometry, hs-CRP levels, lipids, glucose levels, and insulin levels were measured. RESULTS: Ninety-one male (12.5 ± 3.4 years) and 77 female students (12.7 ± 3.4; P = .624) were included. Median (interquartile range) hs-CRP levels were similar among boys and girls (0.4 [1.2] vs 0.5 [0.7]; P = .928). Risk factors such as obesity (16%), high triglycerides (20%), low high-density lipoprotein cholesterol (HDL-C, 16%), and elevated blood pressure (25%) were commonly observed in study participants. Gender-stratified analysis displayed that insulin resistance (18 [19.8%] vs 3 [3.9%]; P = .002) and high triglycerides (26 [28.6%] vs 8 [10.4%]; P = .003) were more commonly observed among boys compared with girls. hs-CRP levels correlated positively with cardiometabolic risk factors such as waist circumference (boys) and total cholesterol (TC)-to-HDL-C ratio. Linear regression analysis displayed that among the covariates of age, body mass index, and glucose, TC-to-HDL-C ratio was the most significant determinant of hs-CRP levels (P = .004). CONCLUSION: Cardiometabolic risk factors such as TC-to-HDL-C ratio correlate with hs-CRP levels in children and adolescents. Long-term prospective studies are needed to confirm the association between hs-CRP and cardiometabolic risk in children.

Serum paraoxonase-1 activity in children: the effects of obesity and insulin resistance.

Oxidative stress (OS) is important in the pathogenesis of atherosclerosis. Paraoxonase-1 (PON1) is an enzyme found in the circulation associated with high-density lipoprotein (HDL). HDL-associated enzyme PON1 has an important role in the attenuation of atherogenic low-density lipoprotein (LDL) oxidation. The aim of this study was to determine PON1 and arylesterase (AREST) enzyme levels in relation to insulin resistance (IR) or obesity among children and adolescents. The study included healthy school children and adolescents. Blood was drawn for the determination of blood glucose, lipid, PON1 and AREST enzyme levels. Overall, we observed a positive correlation between PON1 enzyme activity and high-density lipoprotein cholesterol (HDL-C) levels (r = 0.189, P = 0.014). The correlation appeared to be more significant in boys (r = 0.271, P = 0.009). For subjects with IR and obesity, PON1 enzyme activity did not correlate with HDL-C levels (r = 0.038, P = 0.790), instead PON1 levels correlated negatively with BMI (r = -0.309 and P = 0.026). Multiple linear regression analysis was performed to find the predictors of log PON1 activity. HDL-C level was the strongest predictor of PON1 activity in the lean control group, while BMI appeared to be the strongest predictor in the subjects with obesity or IR. In conclusion, determinants of PON1 enzyme activity are variable in children and adolescents based on IR and obesity. Future studies will shed light on the underlying mechanisms and biomarkers of OS in children and may reveal possible targets for therapeutic intervention.

Triple therapy (aspirin, clopidogrel and oral anticoagulant) after percutaneous coronary intervention: another call for personalized medicine.

Studies indicate that 5-7% patients undergoing percutaneous coronary intervention (PCI) have an indication for anticoagulation therapy. Most commonly atrial fibrillation (AF) is the indication. These subjects require triple therapy with aspirin, clopidogrel, and an oral anticoagulant (OAC). Several questions, concerns and challenges exist regarding the duration, benefit, risks and alternatives related to triple therapy. These questions constitute a moving target with recently approved antiplatelet and anticoagulant agents. This brief review will summarize the current literature regarding triple therapy, potential solutions that can mitigate the formidable risk of bleeding. Arising from that discussion, a logical consensus can be developed that should be applicable to studies with novel agents that interfere with homeostasis. The ultimate goal is to enhance cardiovascular outcome and decrease thrombotic and bleeding complications.

Pleural fluid amino-terminal brain natriuretic peptide in patients with pleural effusions.

BACKGROUND: Definite diagnosis of transudative or exudative pleural fluids often presents a diagnostic dilemma. The aim of this study was to evaluate whether amino-terminal brain natriuretic peptide (NT-proBNP) levels in pleural fluid has a diagnostic value for discriminating heart-failure-related pleural effusions from non-heart-failure effusions. METHODS: Sixty-six subjects (40 male, mean age 61 ± 18 y) with pleural effusions were included. Samples of pleural fluid and serum were obtained simultaneously from each subject. Biochemical analysis, bacterial and fungal culture, acid-fast bacilli smear and culture, and cytology were performed on the pleural fluid. RESULTS: Subjects with heart-failure-related pleural effusion had significantly higher pleural NT-proBNP levels than other subjects (P < .001). Pleural and serum NT-proBNP measures were closely correlated (r = 0.90, P < .001). An NT-proBNP cutoff value of ≥ 2,300 pg/mL in pleural fluid had a sensitivity of 70.8%, a specificity of 97.6%, and positive and negative predictive values of 94.4% and 85.4%, respectively, for discriminating transudates caused by heart failure from exudates. Eight heart-failure subjects were misclassified as exudates by Light's criteria, 5 of whom received diuretics before thoracentesis. All misclassified subjects had pleural NT-proBNP levels higher than 1,165 pg/mL, which predicted heart-failure-associated transudates with 95.8% sensitivity and 85.7% specificity. CONCLUSIONS: Pleural fluid NT-proBNP measurement in the routine diagnostic panel may be useful in differentiation of heart-failure-related pleural effusions and exudative pleural fluids with reasonable accuracy, especially in heart-failure patients treated with diuretics.

Aspirin resistance in patients with acute ischemic stroke.

Aspirin is used in ischemic stroke therapy. However, some patients are not responsive to the antithrombotic action of aspirin. The aim of this study was to assess the prevalence of aspirin resistance in stroke patients and its association with mortality. One-hundred and six patients (mean age 64.9 ± 14.6 years, 53 male) with acute ischemic stroke were consecutively recruited. All subjects were taking aspirin regularly. Aspirin responsiveness was determined by Ultegra Rapid Platelet Function Assay-ASA (VerifyNow Aspirin). Aspirin resistance was defined as aspirin reaction unit (ARU) ≥ 550. Aspirin resistance was detected in 35 patients. There were not any significant differences in age, gender and comorbidities between aspirin-resistant and aspirin-sensitive patients. The mean National Institute of Health Stroke Scale (NIHSS) scores of the aspirin-resistant and aspirin-sensitive patients were 15 ± 3 and 12 ± 5, respectively (p = 0.006). Twenty-seven patients had a history of prior ischemic stroke and eight of them had aspirin resistance. Eleven patients died in-hospital and a total of 43 patients died during 2 years. Both the in-hospital and 2-year mortality rates were significantly higher in patients with aspirin resistance (20 vs. 5.6%, p = 0.038 and 60.0 vs. 31.0%, p = 0.004, respectively). Regression analysis revealed aspirin resistance [odds ratio (OR) 3.097, 95% confidence interval (CI) 1.070-8.959, p = 0.037] as an independent predictor of 2-year mortality, as well as age (OR 1.051, 95% CI 1.003-1.102, p = 0.038) and NIHSS scores (OR 1.208, 95% CI 1.016-1.437, p = 0.033). Aspirin resistance is not uncommon in patients with acute ischemic stroke and is associated with short and long term mortality in these patients.

Polymorphisms of the angiotensin-converting enzyme and angiotensinogen gene in patients with atrial fibrillation.

Activation of the renin-angiotensin system (RAS) is associated with atrial fibrillation (AF). The aim of this study was to investigate the relation between AF and polymorphisms in RAS. One hundred and fifty patients with AF, 100 patients with no documented episode of AF and 100 healthy subjects were consecutively recruited into the study. The angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism, and the M235T, A-20C, and G-6A polymorphisms of the angiotensinogen gene were genotyped. Patients with AF had significantly lower frequency of II genotype of ACE I/D and higher frequency of angiotensinogen M235T polymorphism T allele and TT genotype and G-6A polymorphism G allele and GG genotype compared with the controls. AF patients had significantly larger left atrium, higher left ventricular mass index (LVMI) and higher frequency of significant valvular pathology. ACE I/D polymorphism II genotype, angiotensinogen M235T polymorphism TT genotype and G allele and GG genotype of angiotensinogen G-6A polymorphism were still independently associated with AF when adjusted for left atrium, LVMI and presence of significant valvular pathology. Genetic predisposition might be underlying the prevalence of acquired AF. Patients with a specific genetic variation in the RAS genes may be more liable to develop AF.

Aspirin resistance in patients with chronic renal failure.

BACKGROUND: Chronic renal failure (CRF) is associated with increased risk of cardiovascular morbidity and mortality. Aspirin resistance worsens clinical prognosis. The aim of this study was to explore the prevalence of aspirin resistance in CRF. METHODS: Two hundred and forty-five CRF patients (115 patients undergoing chronic hemodialysis and 130 patients with stage 3-4 chronic kidney disease [CKD]) and 130 patients with normal renal functions (control group) were consecutively recruited. All subjects were taking aspirin regularly. Aspirin responsiveness was determined by Ultegra Rapid Platelet Function Assay-ASA (VerifyNow Aspirin). Aspirin resistance was defined as aspirin reaction unit (ARU) =550. RESULTS: Aspirin resistance was detected in 53 patients undergoing hemodialysis, 32 patients with stage 3-4 CKD and 22 controls. The frequency of aspirin resistance was significantly higher in the CRF group compared with controls (34.7% vs. 16.9%, p<0.001) and in hemodialysis patients (46.1%) compared with stage 3-4 CKD patients (24.6%, p<0.001) and controls (16.9%, p<0.001). Multivariate analysis revealed female sex (odds ratio [OR] = 2.201; 95% confidence interval [95% CI], 1.173-4.129; p=0.014), hemodialysis (OR=3.636; 95%CI, 1.313-10.066; p=0.013) and HDL cholesterol (OR=0.974; 95% CI, 0.950-0.999; p=0.043) as independent predictors of aspirin resistance in this cohort of patients. CONCLUSION: Patients with CRF have higher frequency of aspirin resistance. This might further increase the risk of cardiovascular morbidity and mortality in these patients.

Aspirin resistance in hypertensive patients.

Aspirin resistance is associated with poor clinical prognosis. The authors investigated aspirin resistance in 200 hypertensive patients (111 men, age: 68.3±11.4 years) by the Ultegra Rapid Platelet Function Assay-ASA (Accumetrics Inc., San Diego, CA). Aspirin resistance was defined as an aspirin reaction unit ≥550. Aspirin resistance was detected in 42 patients. Aspirin resistance was present in 25.6% of the patients with poor blood pressure control, while in 17.8% of the patients with controlled blood pressure (P=.182). Female gender and creatinine levels were significantly higher (P=.028 and P=.030, respectively), while platelet count was significantly lower (P=.007) in aspirin-resistant patients. Multivariate analysis revealed that female gender (odds ratio [OR], 2.445; P=.045), creatinine levels (OR, 1.297; P=.015) and platelet count (OR, 0.993; P=.005) were independent predictors of aspirin resistance. The frequency of aspirin resistance is not low in hypertensive patients. Female hypertensive patients, especially, with higher creatinine levels and lower platelet count are at higher risk for aspirin resistance.

Acute exacerbation impairs endothelial function in patients with chronic obstructive pulmonary disease.

OBJECTIVES: The effect of acute exacerbation of chronic obstructive pulmonary disease (COPD) on brachial artery flow-mediated dilation (FMD) has not been examined. The aim of this study was to assess the endothelial function of COPD patients during acute exacerbations. STUDY DESIGN: The study included 30 consecutive patients (8 women, 22 men; mean age 64.2+/-10.9 years) who experienced acute exacerbation of COPD, defined according to the Anthonisen criteria (increased dyspnea, sputum, and sputum purulence). All patients received the same antibiotic and bronchodilator treatment. Endothelial function was assessed by brachial artery ultrasonography within the first 48 hours and after complete resolution of exacerbation symptoms. Flow-mediated dilation was defined as both the maximum absolute and maximum percentage changes in the vessel diameter during reactive hyperemia. The results were compared with those of 20 age-and sex-matched controls without COPD. RESULTS: The patient and control groups were similar in terms of age, gender, hypertension, diabetes, hyperlipidemia, coronary artery disease, heart rate, and blood pressure. Parameters of FMD during acute exacerbation were significantly lower than those obtained after recovery (absolute change: 0.23+/-0.12 mm vs. 0.38+/-0.17 mm, p<0.001; percentage change: 6.44+/-3.99% vs. 10.42+/-4.86%, p<0.001) and than those of the control group (absolute change: 0.36+/-0.13 mm, p=0.001; percentage change: 9.77+/-3.83%, p=0.003). Flow-mediated dilation increased significantly after recovery, yielding similar values to those of the controls. Improvements in FMD were significant in both sexes. CONCLUSION: Acute COPD exacerbation is associated with worsening endothelial function, increasing the risk for cardiovascular morbidity.

Perindopril decreases P wave dispersion in patients with stage 1 hypertension.

INTRODUCTION: Angiotensin-converting enzyme inhibitors prevent atrial fibrillation episodes by effective control of blood pressure and improving electrical and structural remodelling in the atria. Increased P wave dispersion (PWD) is a non-invasive electrocardiographic marker for paroxysmal atrial fibrillation. The aim of the study was to evaluate the effect of perindopril treatment on PWD in hypertensive patients. METHODS: Forty-eight hypertensive patients (mean age 57.4+/-11.8 years, 18 men) were included. Blood pressure values were determined and 12-lead electrocardiograms were recorded at the beginning and at the first week, first month, third month and sixth month of the perindopril treatment.The difference between maximum and minimum P wave durations was calculated as PWD. RESULTS: PWDs were significantly shortened at the first, third and sixth months (41.7+/-8.8 ms, 39.1+/-6.9 ms and 38.3+/-7.1 ms, respectively) compared with baseline and first-week measurements (54.3+/-9.2 ms and 49.0+/-9.1 ms, respectively, p<0.001). Baseline PWD was correlated with body mass index (r=0.32, p=0.026), while PWD at the sixth month of treatment was significantly correlated with left atrial volume index (r=0.30, p=0.042). Multiple linear regression analysis revealed that PWD at the sixth month was related to baseline PWD (p=0.001). CONCLUSION: Perindopril treatment significantly reduced PWD in hypertensive patients.

P wave dispersion increases during hemodialysis sessions.

BACKGROUND/AIMS: Atrial fibrillation (AF) is common among hemodialysis (HD) patients and is associated with high mortality. P wave dispersion (PWD) is a noninvasive electrocardiographic marker of paroxysmal AF. Our aim was to evaluate the effect of HD session on PWD. METHODS: Twenty-five patients (mean age 63 years, 10 males) with sinus rhythm and undergoing chronic HD treatment were included. Blood samples were drawn and 12-lead electrocardiograms were recorded immediately before HD session, at the 2nd hour during HD and at the end of the HD session. The difference between maximum and minimum P wave durations was calculated as PWD. RESULTS: PWD significantly increased during HD sessions compared with predialysis values (41 +/- 12 vs. 21 +/- 10 ms, respectively, p < 0.001), then decreased to a value of 24 +/- 7 ms at the completion of HD, which was not significantly different from the predialysis values. PWD during HD was significantly correlated with predialysis systolic and diastolic blood pressure (r = 0.42, p = 0.037, and r = 0.59, p = 0.002, respectively) and predialysis serum potassium level (r = 0.44, p = 0.031). Linear regression model revealed that predialysis diastolic blood pressure (p = 0.002), predialysis serum potassium level (p = 0.037) and the amount of ultrafiltration (p = 0.048) were the significant predictors of prolonged PWD during HD. CONCLUSION: PWD increases significantly during HD sessions. This may increase the risk of AF episodes during HD. High diastolic blood pressure and serum potassium level before HD and ultrafiltration amount may predict prolonged PWD during HD.

Angiotensin-converting enzyme gene polymorphism in arrhythmogenic right ventricular dysplasia: is DD genotype helpful in predicting syncope risk?

INTRODUCTION: Arrhythmogenic right ventricular dysplasia (ARVD) is a heritable disorder characterised by fibrofatty replacement of right ventricular myocytes and increased risk of ventricular arrhythmias and sudden cardiac death. Angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism affects myocardial ACE levels. DD genotype favours myocardial fibrosis and is associated with malignant ventricular tachycardia. The aim of this study was to explore ACE gene polymorphism in ARVD patients. METHODS: Twenty-nine patients with ARVD and 24 controls were included. All ARVD patients had documented sustained ventricular tachycardia. Thirteen patients had syncopal episodes. Six patients were resuscitated from sudden cardiac death. ACE gene polymorphism was identified by polymerase chain reaction technique. RESULTS: There was no significant difference in DD genotype frequency between ARVD patients and controls (44.8% vs. 45.8%, p=0.94). However, DD genotype frequency was significantly higher in ARVD patients with syncopal episodes compared to those without syncope (69.2% vs. 25.0%, p=0.017, odds ratio:6.750, 95% confidence interval: 1.318-34.565). DD genotype was detected in higher frequency also in patients with a family history of sudden cardiac death (66.7% vs. 39.1%,p=0.36). CONCLUSION: High prevalence of DD genotype in ARVD patients with syncope suggests that ACE I/D polymorphism might be useful in identifying high-risk patients for syncope.