Uric acid in cachectic and noncachectic patients with chronic heart failure: Relationship to leg vascular resistance

Wolfram Doehner, Mathias Rauchhaus, Viorel G. Florea, Rakesh Sharma, Aidan P. Bolger, Constantinos H. Davos, Andrew J.S. Coats, Stefan D. Anker

Research output: Contribution to journalArticlepeer-review

75 Scopus citations

Abstract

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 μmol/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), peakV̇o2 (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, peakV̇o2, 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.

Original languageEnglish (US)
Pages (from-to)792-799
Number of pages8
JournalAmerican Heart Journal
Volume141
Issue number5
DOIs
StatePublished - 2001

Bibliographical note

Funding Information:
Supported by grants of the “Verein der Freunde und Förderer der Berliner Charité” and the NHLI London (Dr Doehner) and by the Ernst- und Bertha-Grimmke-Stiftung and the Max Delbrück Centrum (Dr Anker).

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