Elsevier

Atherosclerosis

Volume 202, Issue 1, January 2009, Pages 11-17
Atherosclerosis

Review
Uric acid: A marker of increased cardiovascular risk

https://doi.org/10.1016/j.atherosclerosis.2008.05.022Get rights and content

Abstract

The relationship between uric acid and cardiovascular disease has been known since the 19th century, after that many authors reported the classical association of gout, hypertension, obesity and cardiovascular disease. With the exception of specific genetic defects in purine metabolism, increased uric acid is generally associated with important risk factors for atherosclerosis like hypertension, abdominal obesity, insulin resistance, the metabolic syndrome and renal failure. Studies have clearly shown an association between increased uric acid concentrations with oxidative stress, endothelial dysfunction, inflammation, subclinical atherosclerosis and an increased risk of cardiovascular events. Increased uric acid levels are independent markers of cardiovascular disease risk. Prospective studies are necessary to show that reduction of uric acid levels prevent cardiovascular events.

Section snippets

Methods

Recent clinical data on this subject were collected by means of multiple EMBASE, PUBMED and SCIENCE DIRECT library searches, bibliography cross-referencing of all articles and previous review articles. Keywords including “uric acid”, “hyperuricemia”, “gout”, combined with “cardiovascular disease”, “stroke”, “metabolic syndrome”, “hypertension”, “risk factor”, “inflammation”, “subclinical atherosclerosis” were used in various combinations. Relevant study differences were included in this review.

Uric acid, the metabolic syndrome and risk factors for atherosclerosis

Due to their high prevalences, abdominal obesity and the metabolic syndrome are frequently associated with the prevalence of cardiovascular disease [15]. Plasma uric acid is often elevated in subjects with the metabolic syndrome and large epidemiological studies show that its prevalence increases according to uric acid levels [16], [17]. Onat et al. [18] have quantitatively estimated the assigned risk to uric acid concentrations and the clustering of metabolic syndrome components in adult and

Uric acid, endothelial dysfunction and inflammation

A correlation of C-reactive protein, a marker of subclinical inflammation related to atherosclerosis, and serum uric acid levels has been described [41], [42]. A significant independent association was found between uric acid and inflammatory markers, such as white blood cell count, blood neutrophil count, C-reactive protein, interleukin and tumor necrosis factor (TNF-α) levels [41], [43]. Moreover, there is a positive correlation between uric acid and inflammation in patients with systolic

Uric acid and subclinical coronary and carotid atherosclerosis

Coronary artery calcification (CAC) detected by computerized tomography is a surrogate marker of atherosclerosis and its severity correlates with coronary plaque burden [52]. CAC is also an independent marker of coronary heart disease risk [53], [54].

In a cross-sectional study with 559 Brazilian white men without known coronary disease, high uric acid levels (>7.1 mg/dL or 422 μmol/L) were independently associated with CAC presence and severity [55]. This relationship was especially strong in

Uric acid, gout and cardiovascular events

Fig. 1 depicts the hazard ratios and confidence intervals for cardiovascular events adjusted for cardiovascular disease risk factors for high versus low uric acid concentrations in prospective studies. In the MONICA Augsburg study [9] that included 1044 men, serum uric acid increase was an independent factor for all causes of death (hazard ratio 2.8; 95% CI, 1.6–5.0) and possibly mortality from cardiovascular disease (hazard ratio 2.2; 95% CI, 1.0–4.8). In the Losartan Intervention For Endpoint

Conclusions

So far there is strong evidence that for most subjects increased uric acid concentrations and gout are associated with subclinical atherosclerosis and an increased risk of cardiovascular events especially in the presence of the metabolic syndrome. It is our view that increased uric acid levels are independent markers of increased cardiovascular disease risk. Whether uric acid per se is atherogenic remains to be settled. Prospective randomized studies targeting uric acid reduction with

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