EFFECT OF ALLOPURINOL TREATMENT ON CARDIAC FUNCTION AND LONG-TERM DISEASE PROGNOSIS IN PATIENTS WITH CHRONIC HEART FAILURE AND HYPERURICEMIA
Keywords:Serum uric acid, Hyperuricemia, Heart failure, Allopurinol
Hyperuricemia (HU) is important and common comorbidity that often coexist in patients with heart failure (HF). High values of serum uric acid are associated to severe heart failure. The purpose of the present study was to evaluate a UA-lowering and prognostic effects of allopurinol in patients with chronic HF and hyperuricemia.We studied 75 patients (50 men and 25 women) with HF and increased UA levels, who have been admitted to hospital since September 2019; All patients aged 18 years and older were eligible, provided a left ventricular ejection fraction of 45% or less was documented on echocardiography during the enrolment visit and signs and symptoms of chronic heart failure were present. Patient baseline assessment included a standardized HF history regarding HF aetiology (classified as ischemic or non-ischemic) and co-morbidities. All patients underwent a standardized clinical evaluation, including physical examination, determination of NYHA class, determination of body weight. Blood samples were drawn from an antecubital vein in the morning for the assessment of a full blood count and clinical chemistry. Echocardiographic parameters included interventricular septum thickness, left ventricular dimension, left ventricular diastolic function, posterior wall thickness, left ventricular mass index, LVEF. Hyperuricemia was defined according to World Health Organization criteria as uric acid level >5.7 mg/dl in women and >7 mg/dl in men. Patients were divided into two groups: 50 patients (group 1) received allopurinol. The initial dose of in most patients was 200 mg/day and it was reduced according to their renal function or UA level. 25 patients (group 2) – controlled group. Treatment duration was 6 and 12 months.Repeated studies after 12 months showed the following results: Uric acid treatment improved the echocardiographic parameters LVEF (38.5± 3.7 and 43.4± 2.4) LV mass index, IVS, PW, stroke volume), reduced NT-proBNP, improved renal function, Improved NYHA functional class; We studied the frequency of cardiovascular events 24-30 months after the start of treatment. Of the 50 patients treated with allopurinol, 11 patients (22%) required rehospitalisation and 9 patients (36%) in the control group;
Hamaguchi S, Furumoto T, Tsuchihash-Makaya M, Goto K, Goto D, Yokota T, Kinugawa S, Yokoshiki H, Takeshita A, Tsutsui H; JARE-CARD Investigators. Hyperuricemia predicts adverse outcomes in patients with heart failure. Int J Cardiol 2011; 151:143–147.
Huang H, Huang B, Li Y, Huang Y, Li J, Yao H, et al. Uric Acid and Risk of Heart Failure: A Systematic Review and Meta-Analysis. Eur J Heart Fail (2014), 16(1):15–24
Kobayashi Y, Omote K, Nagai T, Kamiya K, Konishi T, Sato T, et al. Prognostic Value of Serum Uric Acid in Hospitalized Heart Failure Patients With Preserved Ejection Fraction (From the Japanese Nationwide Multicenter Registry). Am J Cardiol (2020), 125(5):772–6.
Hare JM, Johnson JR. Uric acid predicts clinical outcomes in heart failure: insights regarding the role of xanthine oxidase and uric acid in disease pathophysiology. Circulation. (2003), 107:1951–3. doi: 10.1161/01.CIR.0000066420.36123.35
Ruggiero C, Cherubini A, Ble A, Bos AJ, Maggio M, Dixit VD, et al. Uric acid and inflammatory markers. Eur Heart J. 2006 May, 27(10):1174-81.
Cooper D, Stokes KY, Tailor A, Granger ND. Oxidative stress promotes blood cell-endothelial cell interactions in the microcirculation. Cardiovasc Toxicol. 2002, 2:165–80.
Jia N, Dong P, Ye Y, Qian C, Dai Q. Allopurinol Attenuates Oxidative Stress and Cardiac Fibrosis in Angiotensin II-Induced Cardiac Diastolic Dysfunction. Cardiovasc Ther, 2012, 30(2):117–23.
George J, Carr E, Davies J, Belch JJ, Struthers A. High-Dose Allopurinol Improves Endothelial Function by Profoundly Reducing Vascular Oxidative Stress and Not by Lowering Uric Acid. Circulation, 2007, 114(23):2508–16.
Wang Z, Ding J, Luo X et al. Effect of Allopurinol on Myocardial Energy Metabolism in Chronic Heart Failure Rats after Myocardial Infarct. Int Heart J, 2016; 57:753-9.
J.M. Hare, R.J. Johnson. Uric acid predicts clinical outcomes in heart failure: insights regarding the role of xanthine oxidase and uric acid in disease pathophysiology. Circulation, 2003, 107:1951-1953.
J.M. Zimmer, J.M. Hare. Nitroso-redox interactions in the cardiovascular system. Circulation, 2006, 114:1531-1544.
Y.Y. Sautin, T. Nakagawa, S. Zharikov, R.J. Johnson. Adverse effects of the classic antioxidant uric acid in adipocytes: NADPH oxidase-mediated oxidative/nitrosative stress. Am. J. Physiol. Cell Physiol., 2007, 293:C584-C596.
A.V. Naumova, V.P. Chacko, R. Ouwerkerk, L. Stull, E. Marban, R.G. Weiss. Xanthine oxidase inhibitors improve energetics and function after infarction in failing mouse hearts. Am. J. Physiol. Heart Circ. Physiol, 2006 Feb, 290(2):H837-H843.
M. Hare, B. Mangal, J. Brown, et al. OPT-CHF Investigators. Impact of oxypurinol in patients with symptomatic heart failure. Results of the OPT-CHF Study J. Am. Coll. Cardiol., 2008, 51:2301-2309.