Uric acid and thrombotic risk: an emerging link.

A large literature recently supports the role of uric acid (UA)—the end product of the urine nucleotide metabolism— as an emergent risk factor for the development of the cardiovascular diseases [1, 2]. Furthermore, serum UA seems to be a predictor of some pathological conditions associated with an increased risk of thrombotic events, such as arrhythmias [3, 4], heart failure [5], metabolic syndrome [6], type 2 diabetes [7] and chronic kidney disease [8]. To the question of whether serum UA can mediate an increased thrombotic risk, from a theoretical point of view, the answer is yes. In particular, elevated UA has been reported to promote vascular smooth muscle proliferation by increasing expression of the platelet-derived growth factor A-chain [9], up-regulating the expression of platelet-derived growth factor and monocyte chemo-attractant protein-1 and finally inducing cyclo-oxigenase-2, that links UA to inflammation [10] and potentially to platelet hyperreactivity. In the clinical practice, in gouty patients, the risk of venous thromboembolism, deep vein thrombosis, and pulmonary embolism increases gradually before the gout attack, peaking in the year prior to diagnosis and then progressively declines, following the typical serum UA trend [11, 12]. An interesting analysis from the ARIC (Atherosclerosis Risk in Communities) Study, which followed 14,126 subjects for venous thromboembolism occurrence from 1987 to 2011, has recently highlighted that high serum UA concentrations (≥ 8.8 mg/dL) are associated with an increased risk of venous thromboembolism after adjustment for the other risk factors [Hazard Ratio (HR): 2.13, 95% Confidence Interval (CI): 1.47–3.07] [13].