BACKGROUND: Chronic heart failure (CHF) is a hyperuricemic state, and capillary endothelium is the predominant site of xanthine oxidase in the vasculature. Upregulated xanthine oxidase activity (through production of toxic free radicals) may contribute to impaired regulation of vascular tone in CHF. We aimed to study the relationship between serum uric acid levels and leg vascular resistance in patients with CHF with and without cachexia and in healthy control subjects. METHODS: In 23 cachectic and 44 noncachectic patients with CHF (age, 62 +/- 1 years, mean +/- SEM) and 10 healthy control subjects (age, 68 +/- 1 years), we assessed leg resting and postischemic peak vascular resistance (calculated from mean blood pressure and leg blood flow by venous occlusion plethysmography). RESULTS: Cachectic patients, compared with noncachectic patients and control subjects, had the highest uric acid levels (612 +/- 36 vs 459 +/- 18 and 346 +/- 21 micromol/L, respectively, both P <.0001) and the lowest peak leg blood flow and vascular reactivity (reduction of leg vascular resistance from resting to postischemic conditions: 83% vs 88% and 90%, both P <.005). In all patients, postischemic vascular resistance correlated significantly and independently of age with uric acid (r = 0.61), creatinine (r = 0.47, both P <.0001), peak VO2 (r = 0.34), and New York Heart Association class (r = 0.33, both P <.01). This correlation was not present in healthy control subjects (r = -0.04, P =.9). In multivariate and stepwise regression analyses, serum uric acid emerged as the strongest predictor of peak leg vascular resistance (standardized coefficient = 0.61, P <.0001) independent of age, peak VO2, creatinine, New York Heart Association class, and diuretic dose. CONCLUSIONS: Hyperuricemia and postischemic leg vascular resistance are highest in cachectic patients with CHF, and both are directly related independent of diuretic dose and kidney function. The xanthine oxidase metabolic pathway may contribute to impaired vasodilator capacity in CHF.
BACKGROUND:Chronic heart failure (CHF) is a hyperuricemic state, and capillary endothelium is the predominant site of xanthine oxidase in the vasculature. Upregulated xanthine oxidase activity (through production of toxic free radicals) may contribute to impaired regulation of vascular tone in CHF. We aimed to study the relationship between serum uric acid levels and leg vascular resistance in patients with CHF with and without cachexia and in healthy control subjects. METHODS: In 23 cachectic and 44 noncachectic patients with CHF (age, 62 +/- 1 years, mean +/- SEM) and 10 healthy control subjects (age, 68 +/- 1 years), we assessed leg resting and postischemic peak vascular resistance (calculated from mean blood pressure and leg blood flow by venous occlusion plethysmography). RESULTS: Cachectic patients, compared with noncachectic patients and control subjects, had the highest uric acid levels (612 +/- 36 vs 459 +/- 18 and 346 +/- 21 micromol/L, respectively, both P <.0001) and the lowest peak leg blood flow and vascular reactivity (reduction of leg vascular resistance from resting to postischemic conditions: 83% vs 88% and 90%, both P <.005). In all patients, postischemic vascular resistance correlated significantly and independently of age with uric acid (r = 0.61), creatinine (r = 0.47, both P <.0001), peak VO2 (r = 0.34), and New York Heart Association class (r = 0.33, both P <.01). This correlation was not present in healthy control subjects (r = -0.04, P =.9). In multivariate and stepwise regression analyses, serum uric acid emerged as the strongest predictor of peak leg vascular resistance (standardized coefficient = 0.61, P <.0001) independent of age, peak VO2, creatinine, New York Heart Association class, and diuretic dose. CONCLUSIONS:Hyperuricemia and postischemic leg vascular resistance are highest in cachectic patients with CHF, and both are directly related independent of diuretic dose and kidney function. The xanthine oxidase metabolic pathway may contribute to impaired vasodilator capacity in CHF.
Authors: Michelle M Kittleson; Marcus E St John; Valeriani Bead; Hunter C Champion; Edward K Kasper; Stuart D Russell; Ilan S Wittstein; Joshua M Hare Journal: Heart Date: 2007-03 Impact factor: 5.994
Authors: Gerasimos S Filippatos; Mustafa I Ahmed; James D Gladden; Marjan Mujib; Inmaculada B Aban; Thomas E Love; Paul W Sanders; Bertram Pitt; Stefan D Anker; Ali Ahmed Journal: Eur Heart J Date: 2011-01-03 Impact factor: 29.983
Authors: Carmelinda Ruggiero; Antonio Cherubini; Jack Guralnik; Richard D Semba; Marcello Maggio; Shari M Ling; Fulvio Lauretani; Stefania Bandinelli; Umberto Senin; Luigi Ferrucci Journal: J Am Geriatr Soc Date: 2007-08 Impact factor: 5.562
Authors: Simon Reinke; Tim Karhausen; Wolfram Doehner; William Taylor; Kuno Hottenrott; Georg N Duda; Petra Reinke; Hans-Dieter Volk; Stefan D Anker Journal: PLoS One Date: 2009-03-18 Impact factor: 3.240