LAUSR

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]. In this context, Wang et al. have published in this issue of Internal and Emergency Medicine the results of an interesting investigation showing that high serum UA significantly predicts future thromboembolism in patients with hypertrophic cardiomyopathy, especially when atrial fibrillation and non-obstructive hypertrophic cardiomyopathy coexist [14]. The main limitations of this study are the small number of the observed thromboembolic events and the relative high prevalence of atrial fibrillation, that reduces the possibility of quantifying the weight of UA per se on thromboembolism occurence. As a matter of fact, high serum UA is a well-known risk factor for atrial fibrillation that is itself a very strong predictor of thromboembolic events [15]. Even if there is a growing evidence suggesting that decreasing serum UA levels is associated to a cardiovascular disease risk reduction [16], it is not yet clear whether this is equally true for the thromboembolic risk. Recently, some authors have also supposed that high serum UA might modify the antiplatelet activity of drugs largely used in high-risk patients [17]. On the other side, Zhang et al. have showed that serum UA is a weak predictor of high on-aspirin platelet reactivity with increasing thrombotic risks in hospitalized elderly patients with coronary artery disease [Odd Ratio (OR): 1.004, 95% Confidence Interval (CI): 1.000–1.007, P = 0.048] [18], and Barbieri et al. have found that serum UA levels are not able to influence the response to aspirin, clopidogrel or ticagrelor in patients on dual antiplatelet treatment [19]. Actually, this finding is potentially of great interest, because hyperuricemia is a very frequent metabolic disorder, particularly in patients affected by prothrombotic condition such as arrhythmias, metabolic syndrome, type 2 diabetes and or chronic kidney disease, that are frequently treated with dual antiplatelet treatment when incur in a thromboembolic complication. Based on a recent analysis, serum UA levels are also an independent predictor of short-term mortality in acute pulmonary thromboembolism subjects (OR: 1.2, 95% CI: 1.1–1.4, P < 0.001), suggesting that serum UA might be a potential biomarker for outcome prediction [20]. Anyway, the available evidence is limited by the small sample size and the high heterogeneity degree of the patients involved in the published clinical studies. Consequently, further research is needed to clarify the potential relationship between high * Arrigo Francesco Giuseppe Cicero [email protected]