Gout Pharmacotherapy in Cardiovascular Diseases

A Review of Utility and Outcomes

Subuhi Kaul; Manasvi Gupta; Dhrubajyoti Bandyopadhyay; Adrija Hajra; Prakash Deedwania; Edward Roddy; Mamas Mamas; Allan Klein; Carl J. Lavie; Gregg C. Fonarow; Raktim K. Ghosh

Disclosures

Am J Cardiovasc Drugs. 2021;21(5):499-512. 

In This Article

Inflammation and Uric Acid in Atherosclerosis

Initially thought to be primarily cholesterol-induced, the atherosclerotic process is now known to be the result of a complex interplay between endothelial injury, inflammation, and conventional metabolic risk factors such as dyslipidemia, hypertension, and diabetes (Figure 1).

Figure 1.

A brief outline of inflammation in atherosclerosis. IFN interferon, IL interleukin, LDL low-density lipoprotein, ROS reactive oxygen species, Th1 T-helper 1, VCAM-1 vascular cell adhesion molecule 1, NLRP3 nucleotide oligomerization domain-, leucine-rich repeat-, pyrin domain-containing protein

Hyperuricemia is prevalent in CV diseases such as hypertension, ischemic heart disease (IHD) and HF. However, it is unclear whether hyperuricemia is responsible for CV morbidity or is a marker of a more advanced disease. Uric acid itself has antioxidant and oxidizing properties, and its production from purines is catalyzed by xanthine oxidase (XO), which generates reactive oxygen species during the reaction, as shown in Figure 2.[8] Uric acid also promotes oxidation of low-density lipoprotein (LDL), which has an important role in plaque initiation and propagation. Additionally, decreased nitric oxide (which effects vasodilation, platelet aggregation inhibition, and intimal proliferation) levels have been demonstrated with elevated uric acid, possibly due to uric acid-mediated inhibition of insulin-induced nitric oxide synthase.[9]

Figure 2.

A simplified representation of the role of uric acid in atherogenesis and cardiovascular disease. Other proposed mechanisms, not represented here, are activation of the renin–angiotensin–aldosterone system and insulin resistance. LDL low-density lipoprotein, ROS reactive oxygen species, VCAM-1 vascular cell adhesion molecule 1, XO xanthine oxidase

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