Lipid-independent effects of statins on endothelial function and bioavailability of nitric oxide in hypercholesterolemic patients - 21/08/11
, Markus P. Schneider, MD, Christian Delles, MD, Johannes Jacobi, MD, Roland E. Schmieder, MD, FACCThis study was supported by a research grant of Bayer AG, Leverkusen, Germany and of the “Deutsche Forschungs Gemeinschaft” KFO 106 TP 3.
Riassunto |
Background |
Experimental evidence suggests a lipid-independent effect of statins on endothelial function and nitric oxide (NO) availability in humans. We investigated whether improvement in NO availability in hypercholesterolemia can be achieved rapidly with statins before lipid-lowering therapy is complete.
Methods |
We studied 41 patients (52 ± 11 years) with low-density lipoprotein (LDL) cholesterol ≥ 130 mg/dL (179 ± 45 mg/dL) randomly assigned to treatment either with atorvastatin (20 mg/day) or cerivastatin (0.4 mg/day). Endothelium-dependent vasodilation of the forearm vasculature was measured by plethysmography and intra-arterial infusion of acetylcholine (ACh) after 3 days (n = 18) and 14 days (n = 39) of treatment. NO availability and oxidative stress were assessed by coinfusion of l-NMMA and vitamin C.
Results |
After 3 days of treatment, LDL-cholesterol decreased by 11.9% with a further decrease to 29.6% after 14 days (P < .001). Endothelium-dependent vasodilation improved by +46.7% after 3 days of statin therapy compared with before therapy (ACh 48 μg/min: +15.7 ± 10.6 vs +10.7 ± 10.8 mL/min per 100 mL, P < .05). No further improvement in endothelium-dependent vasodilation (+42.7% compared with before therapy) could be demonstrated after 14 days of treatment (ACh 48 μg/min: +17.7 ± 10.3 vs +12.4 ± 9.3 mL/min per 100 mL before therapy, P < .001). Coinfusion of ACh plus vitamin C was able to improve endothelium-dependent vasodilation before but not after 3 or 14 days of statin therapy either. The improvement in endothelium-dependent vasodilation after therapy was no longer observed when the NO-synthase inhibitor l-NMMA was coinfused together with ACh.
Conclusions |
Short-term lipid-lowering therapy with statins is able to improve endothelial function and NO availability almost completely after 3 days in hypercholesterolemic patients probably by decreasing oxidative stress. This improvement seems to be more rapid than the accompanying decline in LDL-cholesterol and not related to these lipid changes. This finding can support the concept of lipid-independent effects of statins in humans.
Il testo completo di questo articolo è disponibile in PDF.Mappa
Vol 149 - N° 3
P. 473.e1-473.e10 - Marzo 2005 Ritorno al numero
Articolo precedente
- Dose-comparison study of the combination of ezetimibe and simvastatin (Vytorin) versus atorvastatin in patients with hypercholesterolemia: The Vytorin Versus Atorvastatin (VYVA) Study
- Christie M. Ballantyne, Nicola Abate, Zhong Yuan, Thomas R. King, Joanne Palmisano
- Influence of clinical trial enrollment on the quality of care and outcomes for patients with non–ST-segment elevation acute coronary syndromes
- David E. Kandzari, Matthew T. Roe, Anita Y. Chen, Barbara L. Lytle, Charles V. Pollack, Robert A. Harrington, E. Magnus Ohman, W. Brian Gibler, Eric D. Peterson
Benvenuto su EM|consulte, il riferimento dei professionisti della salute.
L'accesso al testo integrale di questo articolo richiede un abbonamento.
Già abbonato a @@106933@@ rivista ?