Abstract-The aim of this study was to investigate the effects of the vasodilating ␤-blocker nebivolol and the cardioselective ␤-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 (rϭ0.41; Pϭ0.001) and with central pulse pressure change (rϭ0.32; Pϭ0.01). No significant changes in augmentation index or carotid-femoral pulse wave velocity were detected in either treatment group. This proof-ofprinciple study provides evidence to suggest that ␤-blockers with vasodilating properties may offer advantages over conventional ␤-blockers in antihypertensive therapy; however, this remains to be tested in a larger trial. lood pressure (BP) varies throughout the arterial tree because of pulse wave amplification, a phenomenon of wave reflection and arterial stiffness. 1 Because of pulse wave amplification, reduction in brachial BP does not reflect changes in central BP, which may become a more important target in the treatment of hypertension. Recent data from the Strong Heart Study 2 confirm earlier results from smaller studies on high-risk patients 3,4 that central pulse pressure is superior to brachial pulse pressure in the prediction of further cardiovascular events. Moreover, several studies have demonstrated that brachial BP is not a good surrogate for the hemodynamic effects of drug therapies on central circulation. The recently published EX-PLOR Study 5 and the Conduit Artery Function Evaluation Study 6 clearly demonstrated that angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and calcium channel blockers have a more pronounced effect on reducing central BP compared with the cardioselective ␤-blocker (BB) atenolol. Different effects of BB on central BP can explain the findings of a recent meta-analysis published by Law et al, 7 which demonstrates a slight inferiority of BB in preventing stroke. The detrimental effect of BB on central BP has generated criticism regarding its use as first line therapy for essential hypertension. Dhakam et al 8 questioned the hypothesis that the inferiority of atenolol in reducing central BP is a class effect of BB. They demonstrated that the novel vasodilating BB nebivolol (NEB) reduces central BP si...

These results indicate that calcification of the aorta is independently associated with aortic stiffness and serum 25(OH)D level in patients with PAD and in healthy subjects. Aortic stiffness and abnormal vitamin D level may contribute to vascular calcification and are related to higher severity grade of atherosclerotic disease.

Safety of the probiotic Lactobacillus plantarum strain Tensia (DSM 21380) was tested in vitro, in semihard Edam-type cheese, in an animal model and after consumption of the probiotic cheese in double-blind randomized placebo-controlled human intervention studies with different age groups. The susceptibility of L. plantarum Tensia to 8 antibiotics, and the presence of tetracycline (tet M, S, O, K, L) genes and class 1 integron was assessed by applying epsilometer-test and PCR-based methods. Production of biogenic amines by the probiotic strain in decarboxylation medium containing 1% of l-histidine, l-glutamine, l-ornithine, l-arginine, or l-lysine and in cheese was tested by gas chromatography. The biosafety of L. plantarum Tensia was evaluated on National Institutes of Health-line mice fed cheese containing Tensia at a concentration of 9.6 log cfu/g for 30 consecutive days. In human intervention trials in adults and the elderly, the effects of different doses of Edam-type cheese and the probiotic bacterium on BW, gut functionality indices, and host metabolism were evaluated. The strain L. plantarum Tensia was susceptible to all tested antibiotics and did not possess the tetracycline resistance-determining genes tet(L), tet(S) and tet(O), nor did it contain the integron (Int1) gene. However, the strain was tet(K) and tet(M) positive. Lactobacillus plantarum Tensia did not produce potentially harmful biogenic amines, such as histamine or cadaverine. The amount of tyramine produced in the cheese environment during ripening and after 15 wk of storage was below the clinically significant content. In the animal model, no translocation of the administered strain or other microbes into the blood or organs of mice was detected. No harmful effect was observed on body mass index, inflammatory markers, or serum lipidograms during human intervention trials with different age groups at a daily dose of 10.3 or 8.17 log cfu/serving for 3 wk. No negative effect on gastrointestinal welfare was observed, but the consumption of 100g/d for 3 wk caused hard stools from the second week of the trial. The content of total lactobacilli increased in feces, and the presence of the ingested probiotic strain was confirmed after the consumption of cheese. Thus, L. plantarum strain Tensia is suitable for generally recognized as safe (GRAS) and qualified presumption of safety (QPS) criteria because it did not have any undesirable characteristics. The regular semihard Edam-type cheese (fat content of 26%) with the probiotic additive at a daily dose of 50 g or in excess (100g) and with a probiotic daily dose of 10 log cfu for 3 wk was safe.

Arterial stiffness is an independent determinant of cardiovascular risk and a marker of subclinical organ damage. Metabolomics may facilitate identification of novel low-molecular cardiovascular risk factors. The aim of the present study was to compare metabolic signatures and functional-biochemical characteristics of patients with peripheral arterial disease (PAD) and clinically healthy subjects. We studied 42 men with symptomatic PAD (aged 66±7 years) and 46 healthy men (aged 66±8 years). Aortic pulse wave velocity (aPWV) was assessed by applanation tonometry using the Sphygmocor device. Metabolic profiling was performed with high-performance liquid chromatography and mass spectrometry. Serum oxidized low-density lipoprotein (oxLDL) level was measured by enzyme-linked immunosorbent assay. The aPWV as well as serum levels of lactate, free carnitine and 11 amino acids including tyrosine were higher among the patients with PAD. In contrast, serum levels of pyruvate, citrate, α-ketoglutarate, aconitate and cysteine were higher in the control group. In multiple regression models, aPWV was independently determined by log-tyrosine and log-oxLDL in the patients (R(2)=0.61; P<0.001) and by age, log-pyruvate and log-oxLDL in the controls (R(2)=0.52; P<0.001). Our study describes for the first time significant differences in metabolomic signature of patients with advanced atherosclerosis compared with clinically healthy controls. The aPWV is independently associated with serum levels of tyrosine and oxLDL in the patients with PAD and is related to pyruvate and oxLDL levels in the control group. The measurement of low-molecular metabolites, which are related to changes in vascular phenotypes, may lead to identification of novel vascular risk markers.