S. Ilic

Circulating purine compounds, uric acid, and xanthine oxidase/dehydrogenase relationship in essential hypertension and end stage renal disease

Abstract Purine nucleotide liberation and their metabolic rate of interconversion may be important in the development of hypertension and its renal consequences. In the present study, blood triphosphate (ATP), adenosine diphosphate (ADP), and adenosine monophosphate (AMP) breakdown pathway was evaluated in relation to uric acid concentration and xanthine dehydrogenase/xanthine oxidase (XDH/XO) in patients with essential hypertension, patients with chronic renal diseases on dialysis, and control individuals. The pattern of nucleotide catabolism was significantly shifted toward catabolic compounds, including ADP, AMP, and uric acid in patients on dialysis program. A significant fall of ATP was more expressed in a group of patients on dialysis program, compared with the control value (p < 0.001), while ADP and AMP were significantly increased in both groups of patients compared with control healthy individuals (p < 0.001), together with their final degradation product, uric acid (p < 0.001). The index of ATP/ADP and ATP/uric acid showed gradual significant fall in both the groups, compared with the control value (p < 0.001), near five times in a group on dialysis. Total XOD was up-regulated significantly in a group with essential hypertension, more than in a group on dialysis. The activity of XO, which dominantly contributes reactive oxygen species (ROS) production, significantly increased in dialysis group, more than in a group with essential hypertension. In conclusion, the examination of the role of circulating purine nucleotides and uric acid in pathogenesis of hypertension and possible development of renal disease, together with XO role in ROS production, may help in modulating their liberation and ROS production in slowing progression from hypertension to renal failure.

Blood Pressure Variability and Left Ventricular Mass Index in Children

Clinical implications of blood pressure variability (BPV) on subclinical organ damage in children are unknown. The authors sought to explore the potential utility of two newly derived BPV indices: weighted standard deviation (wBPSD) and real average variability (ARV), as well as two standard ambulatory blood pressure indices: average 24‐hour systolic blood pressure (SBP) and 24‐hour SBP load, to identify children at high risk for left ventricular (LV) hypertrophy (LVH). The study group consisted of 67 consecutive children who were referred to our institution for evaluation of suspected hypertension. LV mass was estimated by M‐mode echocardiography using Devereuxs formula according to the Penn convention and indexed for height2.7. We found a statistically significant, positive correlation between 24‐hour wBPSD and LV mass index (LVMI) (ρ=0.389; P=.002) and no correlation between 24‐hour ARV and LVMI (P>.05). However, partial correlation analysis of 24‐hour wBPSD adjusted for body mass index (BMI) and LVMI showed only a weak correlation (ρ=0.3; P=.022). By using multiple linear regression analysis in a model with LVMI as a dependent variable and 24‐hour wBPSD, 24‐hour ARV, and BMI as independent variables, only BMI showed statistically significant independent positive associations with LVMI (P=.028). Results of our study showed that currently used BPV indices (24‐hour wBPSD and 24‐hour ARV) are not clinically reliable parameters to identify children at risk for LVH. Apparent contribution of the 24‐hour wBPSD parameter to LVMI is negligible and is secondary to its close correlation with BMI (ρ=0.335 P=.009).

Serum concentration of soluble adhesive molecules in patients with different forms of coronary artery disease

BACKGROUND/AIM Vascular cell adhesion molecules-1 (VCAM-1) and intercellular cell adhesive molecules-1 (ICAM-1) play an important role in developing and progression of coronary atherosderosis. The aim of the paper was to compare concentrations of soluble forms of VCAM-1 and ICAM-1 in patients with different clinical presentations of coronary artery disease (CAD) and patients without CAD. METHODS Blood samples were taken from 25 patients with acute myocardial infarction (AMI), 25 patients with unstable angina pectoris (UAP), 25 with stable angina pectoris (SAP) and from 15 control patients without CAD, and concentrations of solubile adhesive molecules (VCAM-1, ICAM-1) were determined. RESULTS Obesity was more prominent in the NAP than in the SAP and the control patients (p < 0.05). There were no significant differences in gender distribution, age, duration of the CAD and body mass index between the groups. Hypertension and diabetes mellitus type 2 were more frequent in the CAD patients than in the controls (p < 0.01). Family history of the CAD was more frequent in the AMI and the UAP group than in the controls (p < 0.05). Serum concentrations of VCAM-1 was similar in the patients with AMI (955.9 +/- 117.8 ng/mL), UAP (952.4 +/- 139.1 ng/mL) and SAP (931 +/- 169.8 ng/mL), and significantly higher in these groups compared with the controls (823.4 +/- 97.6; p < 0.05, p < 0.05 and p < 0.1 respectively). Serum concentration of ICAM-1 was similar in the patients with AMI (699.2 +/- 125.6 ng/mL), UAP (727.6 +/- 171.8 ng/mL) and SAP (697.5 +/- 165.6 ng/mL), and significantly higher in these groups compared with the controls (583.4 +/- 86.6; p < 0.1, p < 0.05 and p < 0.1 respectively). CONCLUSION Increased concentrations of VCAM-1 and ICAM-1, as markers of inflammation, showed the importance of inflammatory processes in development of atherosclerosis and clinical expresion of CAD. Measurement of soluble ICAM-1 and VCAM-1 concentrations is a usefull indicator of atherosclerosis presence but not severity of CAD clinical presentation.

Evaluation of myocardial function in the presence of left ventricular hypertrophy in athletes and hypertensive patients

INTRODUCTION Myocardial hypertrophy of the left ventricle may be of physiological or pathological nature. Distinction of these two types of hypertrophy is sometimes not easy and represents a diagnostic challenge. The aim of the study was to assess global diastolic and regional systolic and diastolic myocardial function in the presence of left ventricular hypertrophy in athletes and hypertensive patients. MATERIAL AND METHODS In 18 male hypertensive patients and 14 male athletes global diastolic left ventricular function and regional systolic and diastolic myocardial function of septum and posterior wall were investigated by pulsed wave tissue Doppler imaging. RESULTS Ejection fraction and left ventricle mass index did not differ significantly between two groups. Hypertensive patients were found to have diastolic dysfunction while athletes had normal left ventricular diastolic function (the difference between the groups was P < 0.00001). Index of regional diastolic function of septum as well as of the posterior wall was significantly less in hypertensive patients than in athletes (P < 0.00001 for both). In spite of the normal global systolic function the regional systolic function of septum and posterior wall was significantly less in hypertensive patients than in athletes (P < 0.02 for both). CONCLUSION The present results show significantly less global and regional diastolic function of hypertrophied myocardium in hypertensive patients than in athletes. In the presence of preserved left ventricular systolic function, the quantification of myocardial velocity revealed significantly lower regional systolic function of septum and posterior wall in hypertensive patients than in athletes.

Detrimental effects of a bout of physical exercise on circulating endogenous inhibitors of endothelial function in patients with coronary artery disease.

Background A bout of intense physical activity has been shown to transiently impair endothelial function; however, the underlying mechanisms are unclear. Aim The purpose of the review was to assess the impact of a bout of physical exercise induced by exercise stress echocardiography, on blood concentration of the endogenous inhibitors of nitric oxide synthase, asymmetric dimethylarginine (ADMA), and symmetric dimethylarginine (SDMA), in patients with atherosclerosis. Methods Overall, 83 study participants were enrolled, 25 coronary artery disease (CAD) patients, 20 age and sex-matched asymptomatic study participants with at least one risk factor for CAD, and 38 healthy controls. Results Patients with CAD developed symptoms and/or left ventricular wall motion abnormalities during exercise; no changes were seen in study participants with risk factors, or in healthy controls. At baseline, in CAD patients and in study participants with risk factors, both ADMA and SDMA were higher than healthy controls (P < 0.001). However, a further large increase occurred during exercise stress echocardiography in both groups, regardless of development of symptoms (P < 0.001). Conclusion Basal concentrations of ADMA and SDMA are high in CAD patients and in study participants with risk factors, consistent with impaired nitric oxide synthase activity in atherosclerosis. Large increase of these endogenous inhibitors of nitric oxide during intense exercise provide support to the hypothesis that in patients with atherosclerosis endothelial function may further deteriorate as a consequence of a bout of physical activity.

Prevalence and prognostic significance of silent myocardial ischemia in patients after myocardial infarction

BACKGROUND/AIM Silent myocardial ischemia (MI) can be detected in subjects with any symptoms, in patients after myocardial infarction and in coronary patients who have episodes of symptomatic, as well as of silent MI. This study was carried out to evaluate the frequency, characteristics and prognostic significance of silent MI detected in stress echocardiography test in patients after myocardial infarction. METHODS In 210 patients within three months after myocardial infarction exercise test was performed. In those patients with ischemic ST depression on exercise electrocardiogram, in order to confirm MI stress echocardiography was additionally performed. To assess the incidence of major cariovascular events, all the patients were followed at least five years after the first myocardial infraction. RESULTS Out of 210 patients 88 (42%) had ischemic response during stress echocardiography test. Out of 88 patients with MI 54 (61%) had anginal pain (patients with symptomatic MI), while 34 (39%) were free of symptoms (patients with silent MI). Level of exercise test, heart rate, time to the onset of ST segment depression, and the magnitude of ST segment depression were similar in both subgroups of the patients with MI. Duration of exercise test was longer in patients with silent MI (p < 0.05). Wall motion score index during stress echocardiography was higher in patients with symptomatic MI (p < 0.05). Coronary angiography findings were similar in patients with silent and those with symptomatic MI. During a five-yearsfollow-up period the occurrence of major cardic events (cardiac mortality and recurrent myocardial infarction) was similar in both subgroups of the patients with MI. CONCLUSION In more than one third of patients after myocardial infarction silent MI during stress echocardiography was detected. The patients with silent ischemia had longer duration of exercise test and smaller wall motion score index on stress echocardiography. There was no difference in coronary angiography finding between patients with silent and those with symptomatic MI. The incidence of major cardiac events during a five- years- follow-up was similar in the patients with silent and those with symptomatic MI.

EXERCISE TRAINING IMPROVES ENDOTHELIAL FUNCTION IN HYPERTENSIVE POSTMENOPAUSAL WOMEN: PP.6.252

Background: Various humoral systems have been proposed to play a role in postmenopausal hypertension and increased risk of coronary artery disease, such as changes in estrogen/androgen ratios, endothelium dysfunction, and activation of the renin-angiotensin system. It has been demonstrated that some interventions, known to reduce CV risk also, improve endothelial function. Aim: To examine the reaction of endothelium, assess through changes of circulating blood markers of endothelial function: the stable end products of nitric oxide (NOx) and S – nitrosothiols (RSNO – reservoir for bioavailable nitric oxide), that promote exercise training in hypertensive postmenopausal women. Methods: 31 hypertensive postmenopausal women after myocardial infarction, in the absence of hormone replacement therapy, were studied. At baseline and 3 weeks later, in all women values of NOx and RSNO were evaluated. After the initial study, women were randomized to trained (T,n = 19) and control (C,n = 12) group. Women in T group underwent a supervised 3 weeks aerobic exercise training at residential center, while women in C group received usual community care.To elucidate the dynamic of nitric oxide metabolism in the circulation, NOx and RSNO concentration were determined according to the modified Saville-Griess method. Results: After 3 weeks NOx increased significantly only in T group (from 24.9 ± 4.3 to 44.5 ± 12.2 μmol/l, P < 0.0001), as well as RSNO (from 3.2 ± 1.4 to 5.6 ± 2.2 μmol/l, P < 0,005), while in C group NOx and RSNO showed slightly changes (NOx increased from 26.6 ± 4.6 to 30.0 ± 4.8 μmol/l, NS, difference 12.8%; and RSNO from 3.0 ± 1.1 to 3.5 ± 1.3 μmol/l, NS, difference 16.6%). Baseline values of NOx and RSNO did not differ significantly between T and C group, but after 3 weeks, value of NOx was significantly higher in T than in C group (44.5 ± 12.2 vs 30.0 ± 4.8 μmol/l, P < 0,001), as well as value of RSNO (5.6 ± 2.2 vs 3.5 ± 1.3 μmol/l, P < 0.01). Conclusion: Residential short-term exercise training in hypertensive postmenopausal women after myocardial infarction, induced significant favorable modification of endothelial function, expressed through significant increased of NOx and RSNO.

The Association Between Obesity and Visit-to-visit Variability in Systolic Blood Pressure: A Prospective Study

Abstract With the prevalence of obesity and all accompanying health risks, both prevention and health education, as well as identifying predictors for the development of obesity-related diseases are primary. Th e pathophysiological relationship between obesity and visit-to-visit variability in systolic blood pressure (SBPV) has not been completely resolved. To investigate the association between obesity and SBPV in hypertensive patients. Th e prospective study comprised three visits was performed at the hypertension outpatient clinic during the follow up period of 22-months between March 2014 and January 2016. Th is study included 300 randomly selected hypertensive patients (average 67.76±9.84 years), who were divided in groups of obese/non-obese examinees. SBPV was defined as the standard deviation (SD) from three values of SBP. Th e values of SBP and SBP-SD were significantly higher in the group of obese hypertensive patients than in the group of non-obese patients (126.67±8.22 vs 120.45±7.79 mmHg, 11.00±5.64 vs 7.34±3.96; p<0.01). Th e highest SBPV was recorded in the 4th quartile in obese patients (43.13±7.50 mmHg). Th ere was statistically stronger correlation between SBPV and BMI/Waist cirumferences (WC) (ρο=0.425/ ρο=0.356, p<0.01). During 22-months follow up there was a significant decrease of SBPV for 8.2 mmHg, BP for 31/8 mmHg, BMI for 3.8 kg/m2, WC for 10 cm and body weight for 8.24 kg. During 22-months follow-up, reduction of body weight was associated with reduction of blood pressure variability in hypertensive patients. Persistently decrease both body weight and long term visit-to-visit variability may explain lower cardiovascular risk in obese-related disease.

Similarities and Differences in Epidemiology and Risk Factors of Cerebral and Myocardial Ischemic Disease

Abstract Ischemic heart disease and cerebral ischemia represent the leading causes of mortality worldwide. Both entities share risk factors, pathophisiology and etiologic aspects by means of a main common mechanism, atherosclerosis. The autors aimed to investigate differences and similarities in epidemiology and risk factors that could be found between both entities. In a retrospective sudy 403 patients were included and divided into two groups: group of 289 patients with history of myocardial infarction (AMI), and group of 114 patients with history of ischemic stroke (IS). All patients were evaluated for nonmodifiable risk faktors, which included age and sex, and modifiable, such as hypertension, dyslipidemia, diabetes, obesity, physical activity and smoking. Diff erences in some epidemiological aspects were also considered: occupation, marital status, alcohol consumption, exposure to stress. Patients with history of IS were significantly older then AMI patients (64.0 ± 9.9 vs 64.0 ± 9.9, p=0,028), with higher diastolic blood pressure (87,1 ± 10,2 vs 83,6 ± 10,4, p=0,003) and higher Sokolow-Lyon index in ECG, an also index of left ventricular hypertrophy (19,2 ± 9,1 vs 14,7 ± 6,5). Th ere were no significant differences between groups in the estimated body mass index and waist circumference. Differences between groups in stress exposure, occupation, alcohol consumption or physical activity were no significant. Patients in AMI group were more frequently male (199 (69%) vs 59 (52%), p=0,001), married (252 (87%) vs 88 (77%), p=0,037), smokers (162 (56%) vs 50 (44%), p=0,018) and with higher incidence od dyslipidemia (217 (75%) vs 73 (64%), p=0,019) compared with IS group. Incidence of arterial hypertension and diabetes was similar in both groups. Both entities share similar pathophysiological mechanisms and, consequently, main traditional risk factors. However, incidence of myocardial infarction increases with male sex, dyslipidemia, smoking and marital status, while incidense of ischemic stroke increases with age, higher diastolic blood pressure and also with ECG signs of left ventricular hypertrophy.

[PP.25.13] IMPACT OF EXERCISE TRAINING ON BIOMARKERS ON ENDOTHELIAL FUNCTION IN HYPERTENSIVE PATIENTS WITH METABOLIC SYNDROME

Objective: To evaluate the effects of exercise training on circulating blood markers of endothelial function: nitric oxide (NOx), Advanced Oxidation Protein Products (AOPP) and Xanthine Oxidase (XO) in hypertensive patients (pts) with metabolic syndrome. Design and method: 80 male hypertensive pts after myocardial infarction were studied. At baseline and after 3 weeks in all pts values of NOx, AOPP and XO were determined and exercise test was performed. After the initial study, pts were randomized to group with metabolic syndrome (MetS group, n = 40) and group without metabolic syndrome (no- MetS group, n = 40). All pts underwent a supervised 3 weeks aerobic exercise training at residential center. Results: Baseline value of NOx was lower (P = 0.018), and values of AOPP and XO were higher (ns for both) in MetS than in no- MetS group. After 3 weeks values of NOx increased in both groups: in MetS group from 39.09 ± 14.34 to 44.13 ± 13. 57 &mgr;mol/l (P = 0.025) and in no- MetS group from 47.11 ± 15.32 to 51.81 ± 16.48 &mgr;mol/l (P = 0.018), with mean difference higher in MetS than in no- MetS group 5.03 ± 13.71 vs 4.71 ± 12.01, ns. Compared to the baseline, value of XO at the end of the study was significantly lower in both groups (P < 0.0005, both) with mean difference higher in MetS than in no- MetS group (103.67 ± 27.57 vs 99.36 ± 28.11, ns) and with lower second value in MetS than in no- MetS group (P = 0.46).Value of AOPP significantly decreased in both groups (MetS group, P < 0.009; no- MetS group P = 0.002). After 3 weeks level (METs) and duration of exercise test significantly increased in both groups (P < 0.0005) with slightly higher mean increase of duration in MetS than in no- MetS group (ns). Conclusions: Regular residential exercise training induced improvement in endothelial function in hypertensive pts expressed through significant increase of NOx and decrease of XO and AOPP. Higher increase in NOx and reduction in XO in MetS than in no- MetS pts suggests that exercise training induces more pronounced benefit in pts with than in pts without metabolic syndrome.