Clinical Implications of Uric Acid in Heart Failure: A Comprehensive Review

Abstract

Affecting more than 26 million people worldwide and with rising prevalence, heart failure (HF) represents a major global health problem. Hence, further research is needed in order to abate poor HF outcomes and mitigate significant expenses that burden health care systems. Based on available data, experts agree that there is an urgent need for a cost-effective prognostic biomarker in HF. Although a significant number of biomarkers have already been investigated in this setting, the clinical utility of adding biomarker evaluation to routine HF care still remains ambiguous. Specifically, in this review we focused on uric acid (UA), a purine metabolism detriment whose role as cardiovascular risk factor has been exhaustingly debated for decades. Multiple large population studies indicate that UA is an independent predictor of mortality in acute and chronic HF, making it a significant prognostic factor in both settings. High serum levels have been also associated with an increased incidence of HF, thus expanding the clinical utility of UA. Importantly, emerging data suggests that UA is also implicated in the pathogenesis of HF, which sheds light on UA as a feasible therapeutic target. Although to date clinical studies have not been able to prove the benefits of xanthine oxidase in HF patients, we discuss the putative role of UA and xanthine oxidase in the pathophysiology of HF as a therapeutic target.

Hyperuricemia as a Marker of Reduced Left Ventricular Ejection Fraction in Patients with Atrial Fibrillation: Results of the POL-AF Registry Study

“…Excessive XO activity stimulates oxidative stress, which in turn is also stimulated by tissue hypoperfusion. As a result, there is simultaneous overproduction of UA and a complex cardiotoxic effect [ 27 ]. On the other hand, excretion of UA in the urine is impaired.…”

“…On the other hand, excretion of UA in the urine is impaired. This is partly a consequence of an increased concentration of lactic acid (secondary to tissue hypoxia), partly caused by commonly used HF drugs such as renin–angiotensin–aldosterone inhibitors and diuretics, and also due to the effect of ischemia of the kidneys themselves (cardio-renal syndrome) [ 27 ].…”

How Are We Managing Patients with Hyperuricemia and Gout: A Cross Sectional Study Assessing Knowledge and Attitudes of Primary Care Physicians?

“…Hyperuricemia indicates an increased risk of diabetes mellitus or metabolic syndrome and it may lead to hypertension and cardiovascular disease [19,20], therefore it is essential to provide these patients with adequate care. Elevated serum uric acid has been associated not only with several cardiovascular risk factors but also with an increased cardiovascular mortality in the general population [21,22] and after acute myocardial infarction [23,24]. Moreover, in the setting of acute myocardial infarction, hyperuricemia has been linked with an increased inflammatory response [25].…”

Impact of SGLT2 Inhibitors on Heart Failure: From Pathophysiology to Clinical Effects

“…Inflammation has also been implied in a recently recognized pathologic process named endothelial-to-mesenchymal transition (endoMT). It seems that both TGF-β and the Slug signaling pathways are implied in the endoMT endothelial cell shift toward mesenchymal cells, thus leading to fibrosis and ventricular remodeling [ 49 ].…”