Uric Acid and Cardiovascular Disease: An Update From Molecular Mechanism to Clinical Perspective

Abstract

Uric acid (UA) is the end product of purine nucleotide metabolism in the human body. Hyperuricemia is an abnormally high level of UA in the blood and may result in arthritis and gout. The prevalence of hyperuricemia has been increasing globally. Epidemiological studies have shown that UA levels are positively correlated with cardiovascular diseases, including hypertension, atherosclerosis, atrial fibrillation (AF), and heart failure (HF). Hyperuricemia promotes the occurrence and development of cardiovascular diseases by regulating molecular signals, such as inflammatory response, oxidative stress, insulin resistance/diabetes, endoplasmic reticulum stress, and endothelial dysfunction. Despite extensive research, the underlying molecular mechanisms are still unclear. Allopurinol, a xanthine oxidase (XO) inhibitor, has been shown to improve cardiovascular outcomes in patients with HF, coronary heart disease (CHD), type 2 diabetes (T2D), and left ventricular hypertrophy (LVH). Whether febuxostat, another XO inhibitor, can improve cardiovascular outcomes as well as allopurinol remains controversial. Furthermore, it is also not clear whether UA-lowering treatment (ULT) can benefit patients with asymptomatic hyperuricemia. In this review, we focus on the latest cellular and molecular findings of cardiovascular disease associated with hyperuricemia and clinical data about the efficacy of ULT in patients with cardiovascular disease.

A study of the sequential treatment of acute heart failure with sacubitril/valsartan by recombinant human brain natriuretic peptide

“…[ 28 ] XO inhibitor, has been shown to improve cardiovascular outcomes in patients with heart failure and coronary heart disease. [ 29 ] In the present study, higher concentrations of MDA and XO were detected in the serum of patients with heart failure before treatment, and the concentration measured after treatment was significantly lower than the value detected before treatment. A significant increase in the efficacy of the rhBNP treatment was observed after 1 week and the efficacy of the sequential treatment was also significantly increased at 1 week of treatment and persisted to 36 weeks of treatment.…”

The Key Role of Uric Acid in Oxidative Stress, Inflammation, Fibrosis, Apoptosis, and Immunity in the Pathogenesis of Atrial Fibrillation

“…A recent review on the role of UA in cardiovascular diseases (CVD) has focused on summarizing the association between uric acid and various cardiovascular diseases, mainly from experimental evidence (13). Also, the review was shallow in the area of AF despite its well-organized content on the relationship between UA and CVD.…”

Carotid intima-media thickness in patients with hyperuricemia: a systematic review and meta-analysis

“…It is well known that hyperuricemia incidence is increasing and it has become the "fourth highest" risk factor after hyperlipidemia, hypertension and hyperglycemia [49], It is reported that there were 32.5 million patients with hyperuricemia in the United States [50] and 170 million in China [51]. There is strong epidemiological evidence that hyperuricemia is an important risk factor in several complications, such as chronic kidney disease, obesity, hypertension, and type 2 diabetes mellitus [52].…”