This cross-sectional study included 100 healthy males (aged41.9 +/- 6.4 years). Pulse wave velocity (PWV), beta-stiffness and intima-media thickness (IMT) of the carotid artery, and brachial artery flow-mediated dilation (FMD) were measured by a standardized ultrasound approach. In healthy middle-age males we found: i) absent or poor correlations among arterial stiffness, IMT and endothelial function; ii) a low impact of traditional risk factors on the studied variables, and iii) the presence of impaired arterial wall properties despite low calculated cardiovascular risk. These results provide a deepened understanding of arterial wall properties andcould help to improve cardiovascular risk stratification.
COBISS.SI-ID: 30085849
Our aim was to explore whether age-related arterial changes in middle-aged males could be reversed using short-term, low-dose fluvastatin/valsartan combination intervention. Forty apparently healthy, middle-aged males (43.3+/-5.8years) were recruited in a double-blind, randomised intervention. Individuals received either 10mg fluvastatin/20mg valsartan daily or placebo over 30days. The brachial artery flow mediated dilation (FMD), pulse wave velocity (PWV) and common carotid artery beta-stiffness were assessed at baseline and after 30days, and again 5-10months after therapy discontinuation. Arterial function variablessignificantly improved after 30days of intervention; FMD improved by 167.7% (P(0.001), PWV by 10.9% (P(0.05) and beta-stiffness by 18.8% (P(0.01), whereas no changes were obtained in the placebo group. The favourable outcomesin the intervention group were accompanied by a significant decrease of high sensitivity-C reactive protein levels (1.8-fold; P(0.05). In contrast,lipids and blood pressure remained unchanged. Surprisingly, the beneficial arterial effects were still present to a substantial degree 7months after completing intervention (remaining % of initial improvement: FMD 82.1%, PWV 69.5% and beta-stiffness 68.5%), but declined substantially after 10months. Our results indicate that age-related arterial changes, at least in middle-aged males, can be reversed. Short-term treatment with a low-dose fluvastatin/valsartan combination resulted in a large and longlasting improvement of arterial function.
COBISS.SI-ID: 29625561
We aimed to investigate whether low-dose atorvastatin and losartan, separately not possessing protective cardiovascular pleiotropic effects, express them when combined. Forty-five adultmale Wistar rats were anaesthetized and their thoracic aortas and hearts were isolated. Relaxation of aortic rings, coronary flow rate and the extent of myocardial ischaemic-reperfusion injury were measured. Different concentrations (0.01, 0.1, 1.0 microM) of atorvastatin and losartan added to a perfusion medium were first tested. The separate drugs, which were ineffective, were then combined at the same concentrations and the concentration was tested in the same model. Low concentrations of atorvastatin or losartan (0.1 and 1 microM, respectively) produced no effects in isolated aorta. However, surprisingly, when these drug concentrations were combined, a significantly improved endothelium-dependent relaxation of the thoracic aorta was observed. Similarly, when combining individually ineffective concentrations of atorvastatin or losartan (0.01 and 0.1 microM, respectively), significantly increased coronary flow and a decreased extent of myocardial injury were observed. By using a nitric oxide-synthase inhibitor, we demonstrated that the vasodilatory effects obtained were nitric oxide-dependent. The degree of effectiveness by the combination was comparable to that obtained by 10-fold (atorvastatin) or 100-fold (losartan) higher concentrations of the separate drugs. Our results revealed that remarkable additive/synergistic effectsexist between low-doses of a statin (atorvastatin) and an ARB (losartan), resulting in important cardiovascular protection. This new conceptcould be valuable in cardiovascular prevention.(br /)
COBISS.SI-ID: 30127577
The aim of this study was to investigate whether 30 days low-dose fluvastatin treatment could improve and reverse these arterial changes that are primarily associated with ageing, in otherwise healthy middle-aged males. In conclusion, we found that subtherapeutic low-dose fluvastatin (10mg daily; 30 days) considerably improves and reverses early functional and morphological arterial wall impairments that are present in apparently healthy, middle-aged males.
COBISS.SI-ID: 28582873
We aimed to explore whether these drugs at low doses induce the expression of vasoactive-related genes. Sixty adult Wistar rats were treated with low-dose atorvastatin (2 mg/kg), low-dose losartan (5 mg/kg), their combination or saline daily for 4, 6, or 8 weeks. Expression of the vasoactive-related genes endothelin receptor type A (EDNRA), endothelial nitric oxide synthase 3 (NOS3), inducible nitric oxide synthase 2 (NOS2), and angiotensin II receptor type 1 (AGTRL1a) was measured in isolated thoracic aortas. Expression of EDNRA gradually decreased, the lowest values being obtained after 8 weeks (low-dose atorvastatin, losartan [1.6- and 1-7-fold vs controls, respectively; both P ( .05], and the combination [2.3-fold vs control, P ( .001]). The highest values of NOS3 were obtained after 6 weeks (low-dose atorvastatin, losartan, and their combination, 3.1-fold, P ( .01; 3.4-fold, P ( .001; and 3.6-fold, P ( .001 vs controls, respectively) and then declined after 8 weeks. The combination was more effective in inducing total NOS3 expression when compared to the separate drugs (1.4-fold; P ( .05). Importantly, expression of NOS3 was associated with increased plasma NO levels and positively correlated with thoracic aorta relaxation. No changes in expression of NOS2 and AGTRL1a were observed. We showed that low-dose atorvastatin or losartan and especially their combination increases the expression of NOS3 and decreases the expression of EDNRA. These findings are valuable in explaining the effectiveness of the "low-dose pharmacological approach" for improvement in arterial function.