Effects of Nebivolol on Artery Hypertension-Multicentre Study Bosnia And Herzegovina

Hypertension is a major risk factor for cardiovascular diseases; drugs that reduce blood pressure and simultaneously improve or reverse endothelian dysfunction, as nebivolol, may be advantageous in terms of cardiovascular protection. Th e objective of this study is to show the anti-hypertensive effi cacy and safety of nebivolol ( mg once a day) given to patients with arterial hypertension for  months. It should also provide information about drug’s infl uence on laboratory tests fasting blood glucose and serum cholesterol, triglyceride and creatinine concentrations. Six centers Tuzla, Sarajevo, Mostar, Bihać, Zenica and Banja Luka participated in this prospective study with follow-up period of  months that included  visits. Th e study group consisted of  hypertensic patients. Results showed a signifi cant decrease in both systolic and diastolic blood pressure and heart rate at the end of the study. Fasting blood glucose level and serum cholesterol, triglyceride and creatinine changed signifi cantly during the study, with lower levels of all the tests. Nebivolol seems to be free from some of the problems that generally accompany not only the classical betablockers but sometimes also newer classes of antihypertensive drugs. With its high anti-hypertensive effi ciency and safety, and presence of statically signifi cant diff erence in laboratory tests and benefi cial eff ects, absence of adverse interaction with glucose and lipid metabolism, patients treated with Nebivolol may show an optimal adherence to therapy.

ZUMRETA KUŠLJUGIĆ ET AL.: EFFECTS OF NEBIVOLOL ON ARTERY HYPERTENSION -MULTICENTRE STUDY BOSNIA AND HERZEGOVINA

Introduction
Arterial hypertension is a major modifi able risk factor for cardiovascular diseases that can, if untreated, result in serious morbidity and mortality from cardiac, cerebrovascular, vascular and renal diseases ().Th e treatment of hypertension has evolved over the last years as we accumulated knowledge of the natural history, pathophysiology, and risk factors for hypertension as well as the eff ects of therapy and interactions of this factors.Th e goal of treating high blood pressure is to reduce blood pressure and prevent or reverse end-organe damage.Beta-adrenoreceptor blockers have long been established for the treatment of hypertension and much of the evidence that they reduce the risk of developing serious cardiovascular complications is based on clinical trials that used this class of drugs (,).Th ey were recommended as one of the initial medications for the treatment of hypertension by the fifth and sixth National Committees on Detection, Evaluation and Treatment of High Blood Pressure and the World Health Organization-International Society of Hypertension ( -).Eff ective antihypertensive therapy should reduce vascular resistance without impairment of cardiac output, a measure of both systolic and diastolic function.Nebivolol, a highly selective ß-adrenoreceptors blocker, actually decreases arterial blood pressure by reducing systemic vascular resistance without depressing left ventricular function (,), inducing an endothelium-dependent vasodilatation, which arises from the release of nitric oxide (NO).In hypertensic patients the basal and stimulated production of nitric oxide is reduced and the normal balance between vasodilating and vasoconstricting factors is modifi ed with a decrease in vasodilation and an increase in vasoconstriction, so endothelial dysfunction may be considered as a target for the treatment of hypertension.Th e most common cause of death in patients with high blood pressure are complications from atherosclerosis.Nitric oxide plays a protective role as it prevents monocyte adhesion, platelet aggregation, vascular smooth-cell proliferation and migration, events known to be associated with arteriosclerosis and thrombosis development.Beta adrenergic blockers have been shown to reduce hypertension-related cardiovascular and cerebrovascular morbidity and mortality in long-term clinical trials (,).Antihypertensive therapy should be directed toward controlling all the patient' s cardiovascular risk factors.Fasting blood glucose, serum cholesterol and triglycerides and serum creatinine provide information on potential cardiovascular risk factors and also establish a baseline for the eff ects of drug therapy.

Materials and Methods
Th e study was designed as a prospective study with follow-up period of  months including  visits for each patient.Th e study population consisted of  patients,  female and  male, mean age ,±,, mean weight ,±, and mean body mass index (BMI) ,±,.We included patients with blood pressure > / who were recruited from centers in Tuzla, Sarajevo, Mostar, Bihać, Zenica and Banja Luka.Patients were classifi ed according to JNC classifi cation in three groups: (Table 

Results
Th e study was completed by  patients (,), while  patients (,) withdrew.Considering these results, in this study nebivolol is demonstrated to be suitable for therapy in arterial hypertension.Th e results provide evidence of good tolerability profi le and lower incidence of adverse eff ects on glucose and lipids metabolism.Diff erent studies compared the effi cacy of Nebivolol with other antihypertensive drugs.Th e percentage of patients with fully normalized blood pressure was significantly higher with nebivolol than with nifedipine ( vs ) ().In the studies comparing nebivolol with nifedipine or amlodipine heart rate was decreased by nebivolol and slightly increased with the two dihydropiridines: the lower heart rate is a potential advantage of nebivolol, due to the epidemiological relation between heart rate and cardiovascular morbidity (,).Nebivolol was also compared with other beta-blockers, such as atenolol (,) and metoprolol ().Th erefore, the antihypertensive effi cacy of nebivolol was superior or similar to that of other beta-blocking drugs.Antihypertensive drug must have not only blood pressure -lowering properties, but also infl uence other critical cardiovascular, metabolic, and renal end points.
The impairment of nitric oxide (NO) bioactivity, the main feature of endothelial dysfunction, is a key factor in the pathogenesis of many common cardiovascular diseases.High levels of blood glucose can impair not only vascular tone but also blood flow, both depending on NO controlled endothelial function ().High blood glucose level or dislipidaemia can aff ect by several mechanisms-such as oxidative stress-endothelial function thus leading to vascular damage, so opportunities of treatment can arise from nebivolol, some eff ects of which were shown to be just mediated by NO.In most of the studies nebivolol did not signifi cantly alter blood glucose or plasma lipid levels ().Nebivolol seems to be free from some of the problems that generally aff ect not only the classical beta-blockers but sometimes also the newer classes of antihypertensive drugs.With its high anti-hypertensive effi ciency and safety, and fi nding of signifi cant diff erence in laboratory tests and cial eff ects, without adverse interaction with glucose and lipids metabolism, patients treated with Nebivolol may show an optimal adherence to therapy.

Conclusions
Nebivolol administered in a single daily dose of  mg lowers both systolic and diastolic blood pressure in patients with arterial hypertension.It is simple one daily dosage, that can be given to patients of all groups.Th e major objective of our study is to provide an adequate cardiovascular protection by appropriate reduction of blood pressure values.Results data of our study provide evidence of antihypertensive effects, good tolerability profile and lower incidence of adverse effects on glucose and lipids metabolism of Nebivolol, which is in relationship with that obtained by other authors.

Table 
. andTable .show results of descriptive statisticmean and standard deviation for systolic blood pressure, diastolic blood pressure, mean arterial pressure and heart rate at the start and at the end of study.ZUMRETA KUŠLJUGIĆ ET AL.: EFFECTS OF NEBIVOLOL ON ARTERY HYPERTENSION -MULTICENTRE STUDY BOSNIA AND HERZEGOVINA KRUSKAL-WALLIS ONE WAY ANALYSIS OF VARIANCE ON RANKS We used ANOVA test -Kruskal Wallis to analyze one group of results, there we repeat measurement in some patients-four measurements of blood pressure and heart rate and table  shows descriptive statistic for subgroup of patients called GroupHYP , n=.Table.showresults of t-test and signifi cance level for fasting blood glucose, serum creatinine, cholesterol and triglyceride at the start and the end of the study.Th ere was a signifi cant diff erence (p< ,) in fasting blood glucose, serum creatinine and triglyceride at the end of the study, with signifi cant decrease, and statistical signifi cant difference (p< ,) in serum cholesterol level at the end of the study, which is shown in Table.and.BOSNIANJOURNALOFBASIC MEDICAL SCIENCES 2005; 5 (1): 42-51 ZUMRETA KUŠLJUGIĆ ET AL.: EFFECTS OF NEBIVOLOL ON ARTERY HYPERTENSION -MULTICENTRE STUDY BOSNIA AND HERZEGOVINA  BOSNIAN JOURNAL OF BASIC MEDICAL SCIENCES 2005; 5 (1): 42-51 ZUMRETA KUŠLJUGIĆ ET AL.: EFFECTS OF NEBIVOLOL ON ARTERY HYPERTENSION -MULTICENTRE STUDY BOSNIA AND HERZEGOVINA (Table , ; Figure -) We used (Kruskal Wallis One Way ANOVA on Ranks) for  sub-groups of patients, where we used repeated measurement.The results showed statistically significant diff erence in blood pressure level on the fi rst control (P<,) in  patients (,).(Table,;Figure -) Results of our study show improvement of serum parameters-fasting blood glucose, creatinine, cholesterol and trygliceride, with statistical significant difference (p<,) at the end of study.(Table-)