Differential effects of nebivolol and metoprolol on central aortic pressure and left ventricular wall thickness.

The aim of this study was to investigate the effects of the vasodilating ß-blocker nebivolol and the cardioselective ß-blocker metoprolol succinate on aortic blood pressure and left ventricular wall thickness. We conducted a randomized, double-blind study on 80 hypertensive patients. The patients received either 5 mg of nebivolol or 50 to 100 mg of metoprolol succinate daily for 1 year. Their heart rate, central and brachial blood pressures, mean arterial pressure, augmentation index, carotid-femoral pulse wave velocity, and left ventricular wall thickness were measured at baseline and at the end of the study. Nebivolol and metoprolol significantly reduced heart rate, brachial blood pressure, and mean arterial pressure to the same degree. However, reductions in central systolic and diastolic blood pressures, central pulse pressure, and left ventricular wall thickness were significant only in the nebivolol group. The change in left ventricular septal wall thickness was significantly correlated with central systolic blood pressure change (r=0.41; P=0.001) and with central pulse pressure change (r=0.32; P=0.01). No significant changes in augmentation index or carotid-femoral pulse wave velocity were detected in either treatment group. This proof-of-principle study provides evidence to suggest that ß-blockers with vasodilating properties may offer advantages over conventional ß-blockers in antihypertensive therapy; however, this remains to be tested in a larger trial.

Association between asymmetric dimethylarginine and indices of vascular function in patients with essential hypertension.

Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase and is associated with endothelial dysfunction. The aim of the present study was to investigate the relationship between ADMA, indices of arterial stiffness, endothelial function and carotid artery intima-media thickness (IMT) in hypertension patients. Eighty middle-aged (47 ± 10 years) untreated patients with mild to moderate essential hypertension underwent routine physical examination, pulse wave analysis (PWA), measurement of aortic pulse wave velocity (PWV) and IMT. In PWA, administration of salbutamol and nitroglycerine was used to assess endothelium-dependent (EDV) and endothelium-independent vasodilation, respectively. In univariate analysis, ADMA was correlated with EDV (r = -0.26; p = 0.02) and IMT (r = 0.32; p = 0.007). In multiple regression analysis, ADMA was independently associated with the female gender, EDV, IMT and total cholesterol (R(2) = 0.30; p < 0.001). No correlation was detected between ADMA and augmentation index, central/brachial blood pressure or aortic PWV. In hypertension patients, ADMA is independently correlated with IMT and EDV. Thus, ADMA is a marker of endothelial dysfunction and intima-media thickening in patients with hypertension.

Acute phase proteins and oxidised low-density lipoprotein in association with ischemic stroke subtype, severity and outcome.

OBJECTIVES: The goal of our study was to investigate the associations of oxidized LDL (apoB100 aldehyde-modified form) and acute phase proteins (fibrinogen, CRP) with acute ischemic stroke severity and outcome. MATERIALS AND METHODS: The study included 61 ischemic stroke patients and 64 controls. Strokes were subtyped according to TOAST criteria, the severity and outcome of stroke (at 1 year) were measured. RESULTS: The mean triglyceride, fibrinogen, CRP and glucose values were significantly higher among cases. The median oxLDL value for patients with large artery atherosclerosis (LAA) type of stroke was significantly higher than for other subtypes. The oxLDL values did not correlate with age, stroke severity and outcome. CONCLUSIONS: Inflammatory markers (fibrinogen and CRP) predicted the stroke severity and outcome whereas elevation of oxLDL levels did not. Our data refer to possibility that there may exist some links between the LAA subtype of stroke and elevated oxLDL (apoB100 aldehyde-modified form).

Augmentation index and carotid intima-media thickness are differently related to age, C-reactive protein and oxidized low-density lipoprotein.

OBJECTIVE: Ageing, plasma circulating C-reactive protein (CRP), oxidized low-density lipoprotein (OxLDL) and homocysteine (Hcy) are associated with atherosclerosis. The aim of this study was to evaluate the relationship between age, inflammatory and oxidative stress-related markers with functional and structural changes of the arteries in asymptomatic persons. METHODS: CRP, OxLDL and Hcy were measured in 175 clinically healthy subjects, aged 40-70 years. Ultrasonography and pulse wave analysis were used to measure carotid intima-media thickness (IMT) and augmentation index (AIx). RESULTS: OxLDL was correlated with IMT (r = 0.24, P = 0.003), whereas CRP was correlated with AIx (r = 0.21, P = 0.005). No correlation was detected between Hcy and AIx or age-adjusted IMT. There was a significant association between AIx and age 50 years (r = 0.40; P = 0.001). In stepwise regression analysis age, weight, white blood cell count, OxLDL, heart rate and timing of the reflected waveform adjusted for height were significantly and independently associated with IMT (R = 0.41; P < 0.001). At the same time, AIx as the dependent variable correlated positively with age, gender, CRP and mean arterial pressure, and negatively with heart rate, weight and height, in stepwise regression analysis (R = 0.63; P < 0.001). CONCLUSION: The results of the present study showed that CRP, OxLDL, Hcy and age are not similarly related to AIx and IMT in asymptomatic persons. The results suggest that CRP and younger age are related to arterial stiffness, whereas OxLDL and older age become more important determinants of structural changes of the arteries in asymptomatic persons.

Effects of amlodipine and candesartan on oxidized LDL level in patients with mild to moderate essential hypertension.

OBJECTIVE: To compare the effects of amlodipine and candesartan on oxidized low-density lipoprotein (OxLDL), conjugated dienes (CD) and baseline diene conjugation in circulating low-density lipoproteins (LDL-BDC) level during antihypertensive treatment. METHODS: Forty-nine patients with untreated mild to moderate essential hypertension were recruited in a randomized double-blind study to receive a daily dose either of 8 mg candesartan or 5 mg amlodipine for 16 weeks. Blood pressure, OxLDL, CD, LDL-BDC, triglycerides (TG), total cholesterol and lipoprotein cholesterol were measured at baseline, at week 2 and at week 16. RESULTS: During treatment, in addition to a significant decrease in systolic and diastolic blood pressure, high level of OxLDL decreased significantly reaching practically upper kit reference values. Both treatment groups were similar with regard to the studied parameters at all time points. At the same time serum TG, lipoprotein and total cholesterol levels as well as LDL-BDC did not change and CD levels did not exceed endemic normal. Decrease in both systolic and diastolic blood pressure was associated with decrease in LDL-BDC/LDL. CONCLUSIONS: Besides their antihypertensive effects, both candesartan and amlodipine are efficient drugs for reducing OxLDL level, being neutral with regard to serum lipids.

The relationship between inflammation and arterial stiffness in patients with essential hypertension.

BACKGROUND: Data about the correlation between augmentation index (AIx), timing of the reflected waveform (T(r)) and inflammatory markers in patients with essential hypertension are not yet well established. The aim of this study was to compare plasma high-sensitivity C-reactive protein (hsCRP), white blood cell count and fibrinogen in hypertensive patients and in normotensive controls and to assess the relationship between inflammatory markers and arterial stiffness. METHODS: Forty-two healthy middle-aged patients with untreated stage I-II essential hypertension and 42 sex- and age-matched controls were recruited in the study. Pulse wave analysis was used to assess AIx and T(r). RESULTS: Plasma hsCRP, white blood cell count, AIx and T(r) were significantly higher in the patients with essential hypertension. In multiple regression analysis, AIx correlated positively with age, female gender, mean arterial pressure and log(hsCRP), and negatively with heart rate and height (R(2)=0.75, p<0.001). T(r) correlated negatively with log(hsCRP) (r=-0.34, p=0.002) for the whole study group. However, after adjusting for mean arterial pressure, age, height, heart rate and sex to the regression model, no correlation was revealed between log(hsCRP) and T(r) (p=0.35) as the dependent variable (R(2)=0.48, p<0.001). CONCLUSIONS: Untreated hypertensive patients with low or moderate total cardiovascular risk had significantly increased blood hsCRP and white blood cell count and arterial stiffness, expressed as AIx and T(r). AIx correlated independently with hsCRP in multiple regression analysis. Measurement of arterial stiffness and inflammation can be suggested as an additional tool to assess cardiovascular risk in hypertensive patients with low or moderate total cardiovascular risk as estimated by traditional risk factors.

Effect of antihypertensive treatment with candesartan or amlodipine on glutathione and its redox status, homocysteine and vitamin concentrations in patients with essential hypertension.

OBJECTIVE: To compare the effect of candesartan or amlodipine on concentrations of cellular markers of oxidative stress, plasma homocysteine and vitamins in hypertensive patients. METHODS: Forty-nine middle-aged patients with untreated stage I-II essential hypertension were recruited in a randomized double-blind double-dummy study to receive a daily dose either of 8 mg candesartan (n = 25) or 5 mg amlodipine (n = 24) for 16 weeks. Blood pressure, reduced glutathione (GSH) and oxidized glutathione (GSSG), glutathione redox ratio (GSSG : GSH) in red blood cells, plasma homocysteine, vitamin B12 and folic acid status were measured at baseline, at week 2 and at week 16. The same parameters were measured in 32 healthy age- and sex-matched controls. An increase in homocysteine of at least 2 micromol/l was considered significant. RESULTS: Hypertensive patients had significantly greater oxidative stress and homocysteine concentrations than controls. In addition to a significant decrease in blood pressure, in both treatment groups GSSG decreased (P < 0.03), GSSG : GSH had a tendency to decrease (P = 0.054), but homocysteine did not change. An increase in homocysteine concentration of at least 2 micromol/l was found in 12 patients (five in the candesartan group, seven in the amlodipine group), with a significant decrease in folic acid concentration and no changes in cellular oxidative stress. In patients with no increase in homocysteine concentration, both GSSG (P < 0.02) and GSSG : GSH (P = 0.051) decreased. GSH and vitamin B12 did not change in any of the groups studied. CONCLUSION: Untreated hypertension is associated with disturbed glutathione redox status and increased plasma homocysteine concentrations. Both candesartan and amlodipine had favourable effects on cellular oxidative stress, but the oxidative stress status did not decrease in patients with adverse changes in homocysteine.

Homocysteine and red blood cell glutathione as indices for middle-aged untreated essential hypertension patients.

OBJECTIVE: Intracellular glutathione in its reduced state is a principal cellular biomolecule with antioxidant activity. Glutathione and homocysteine metabolism are closely associated. As both oxidative stress and hyperhomocystinemia are associated with hypertension, we assessed the relationships between these variables. DESIGN AND SETTING: An observation-based case-control study, performed at a university teaching hospital. PATIENTS: Middle-aged male patients with untreated uncomplicated essential hypertension (mean +/- standard deviation age 53.0 +/- 7.2 years, n = 48) before any treatment and controls with similar age distributions (age 51.6 +/- 5.5 years, n = 28) were evaluated. METHODS: In all subjects, the plasma levels of homocysteine, lipids, creatinine, protein, and glucose were measured. Reduced and oxidized glutathione and folic acid were measured from red blood cells (RBC). RESULTS: The hypertensive patients had decreased levels of red blood cell reduced glutathione (RBC-GSH) and increased levels of oxidized glutathione, which resulted in elevated ratio of oxidized/reduced glutathione as compared to controls (P < 0.001). Plasma homocysteine levels were significantly higher in the hypertensive patients versus the age-matched controls (P < 0.004). In the hypertensive patients, RBC-GSH correlated inversely with systolic blood pressure, serum creatinine, protein and RBC folic acid. No correlation was detected between RBC-GSH and homocysteine. In the controls, RBC-GSH correlated inversely with homocysteine, RBC folic acid and creatinine. According to multiple regression, in the hypertensive patients RBC-GSH was related to systolic blood pressure, hemoglobin, plasma homocysteine, creatinine and protein. Such a relationship was not detected for the controls. CONCLUSION: In untreated hypertensive patients both homocysteine and systolic blood pressure are associated with intracellular oxidative stress as determined by RBC-GSH.