Serum Uric Acid – Risk Factor for Acute Ischemic Stroke and Poor Outcomes

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Abstract

Over the last decades several studies among the adult population have attempted to establish a correlation between the risk of stroke incidence and serum uric acid (SUA) concentration, and how these levels influence the patient’s neurological outcome after a stroke. But, to date, the results are conflicting. In this review, an extensive literature search was performed through PubMed for articles published until May 2019 to review the association. The study selection was narrowed by searching PubMed database using the Medical Subject Headings (MesH) and associated keywords. Only articles conducted in English and on human subjects were included. We considered an article for this review if it had statistics on either the incidence, stroke mortality or post-stroke functional outcomes along with serum uric acid levels in adults.

This review includes 21 articles with data of 33,580 cases of stroke and 1,100,888 participants. We can divide the articles reviewed into two separate cohorts of studies. One relates serum uric acid levels to stroke frequency and mortality, while the other is associated with serum uric acid and outcomes for stroke survivors. Based on our review, no significant relationship is observed with uric acid exhibiting protective effects on stroke outcome. Large clinical trials are advised to provide well-defined solutions to further assess the benefits of uric acid level lowering treatment in patients of vascular events, such as a stroke. However, we confidently report that increasing uric acid levels poses a higher risk for incidence of stroke.

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Most cited references 44

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Uric acid provides an antioxidant defense in humans against oxidant- and radical-caused aging and cancer: a hypothesis.

B. N. Ames, R Cathcart, E Schwiers … (1981)

During primate evolution, a major factor in lengthening life-span and decreasing age-specific cancer rates may have been improved protective mechanisms against oxygen radicals. We propose that one of these protective systems is plasma uric acid, the level of which increased markedly during primate evolution as a consequence of a series of mutations. Uric acid is a powerful antioxidant and is a scavenger of singlet oxygen and radicals. We show that, at physiological concentrations, urate reduces the oxo-heme oxidant formed by peroxide reaction with hemoglobin, protects erythrocyte ghosts against lipid peroxidation, and protects erythrocytes from peroxidative damage leading to lysis. Urate is about as effective an antioxidant as ascorbate in these experiments. Urate is much more easily oxidized than deoxynucleosides by singlet oxygen and is destroyed by hydroxyl radicals at a comparable rate. The plasma urate levels in humans (about 300 microM) is considerably higher than the ascorbate level, making it one of the major antioxidants in humans. Previous work on urate reported in the literature supports our experiments and interpretations, although the findings were not discussed in a physiological context.

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Febuxostat compared with allopurinol in patients with hyperuricemia and gout.

Michael A Becker, H Schumacher, Robert Wortmann … (2005)

Febuxostat, a novel nonpurine selective inhibitor of xanthine oxidase, is a potential alternative to allopurinol for patients with hyperuricemia and gout. We randomly assigned 762 patients with gout and with serum urate concentrations of at least 8.0 mg per deciliter (480 micromol per liter) to receive either febuxostat (80 mg or 120 mg) or allopurinol (300 mg) once daily for 52 weeks; 760 received the study drug. Prophylaxis against gout flares with naproxen or colchicine was provided during weeks 1 through 8. The primary end point was a serum urate concentration of less than 6.0 mg per deciliter (360 micromol per liter) at the last three monthly measurements. The secondary end points included reduction in the incidence of gout flares and in tophus area. The primary end point was reached in 53 percent of patients receiving 80 mg of febuxostat, 62 percent of those receiving 120 mg of febuxostat, and 21 percent of those receiving allopurinol (P<0.001 for the comparison of each febuxostat group with the allopurinol group). Although the incidence of gout flares diminished with continued treatment, the overall incidence during weeks 9 through 52 was similar in all groups: 64 percent of patients receiving 80 mg of febuxostat, 70 percent of those receiving 120 mg of febuxostat, and 64 percent of those receiving allopurinol (P=0.99 for 80 mg of febuxostat vs. allopurinol; P=0.23 for 120 mg of febuxostat vs. allopurinol). The median reduction in tophus area was 83 percent in patients receiving 80 mg of febuxostat and 66 percent in those receiving 120 mg of febuxostat, as compared with 50 percent in those receiving allopurinol (P=0.08 for 80 mg of febuxostat vs. allopurinol; P=0.16 for 120 mg of febuxostat vs. allopurinol). More patients in the high-dose febuxostat group than in the allopurinol group (P=0.003) or the low-dose febuxostat group discontinued the study. Four of the 507 patients in the two febuxostat groups (0.8 percent) and none of the 253 patients in the allopurinol group died; all deaths were from causes that the investigators (while still blinded to treatment) judged to be unrelated to the study drugs (P=0.31 for the comparison between the combined febuxostat groups and the allopurinol group). Febuxostat, at a daily dose of 80 mg or 120 mg, was more effective than allopurinol at the commonly used fixed daily dose of 300 mg in lowering serum urate. Similar reductions in gout flares and tophus area occurred in all treatment groups. Copyright 2005 Massachusetts Medical Society.

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Uric acid is a risk factor for myocardial infarction and stroke: the Rotterdam study.

Michiel Bos, Peter J Koudstaal, Albert Hofman … (2006)

The role of uric acid as a risk factor for myocardial infarction is controversial, and little is known about its role as a risk factor for stroke. Recent evidence suggests that uric acid may be an important causal agent in cardiovascular disease, for example, by inducing renal disease and hence hypertension. We investigated the association between serum uric acid and coronary heart disease and stroke in a large prospective population-based study. The study was based on 4385 participants of the Rotterdam Study who, at baseline (1990 to 1993), were > or =55 years of age, free from stroke and coronary heart disease, and had blood taken. Follow-up for incident stroke and myocardial infarction was complete until January 1, 2002. Data were analyzed with Cox proportional hazards models with adjustment for relevant confounders. Average follow-up was 8.4 years. High serum uric acid levels were associated with risk of myocardial infarction and stroke; age- and sex-adjusted hazard ratios (95% CIs) for highest versus lowest quintile of uric acid were 1.68 (1.24 to 2.27) for cardiovascular disease (515 cases), 1.87 (1.12 to 3.13) for myocardial infarction (194 cases), 1.57 (1.11 to 2.22) for stroke (381 cases), 1.77 (1.10 to 2.83) for ischemic stroke (205 cases), and 1.68 (0.68 to 4.15) for hemorrhagic stroke (46 cases). Adjustment for other vascular risk factors only slightly attenuated these associations. Associations were stronger in persons without hypertension than in those with hypertension. Uric acid is a strong risk factor for myocardial infarction and stroke.

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Author and article information

Journal

Journal ID (nlm-ta): Cureus

Journal ID (iso-abbrev): Cureus

Journal ID (issn): 2168-8184

Title: Cureus

Publisher: Cureus (Palo Alto (CA) )

ISSN (Electronic): 2168-8184

Publication date (Electronic, pub): 28 October 2019

Publication date (Electronic, collection): October 2019

Volume: 11

Issue: 10

Electronic Location Identifier: e6007

Affiliations

[1 ] Internal Medicine, California Institute of Behavioral Neurosciences and Psychology, Fairfield, USA

[2 ] Neurology, California Institute of Behavioral Neurosciences and Psychology, Fairfield, USA

[3 ] Family Medicine, California Institute of Behavioral Neurosciences and Psychology, Fairfield, USA

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Muhammad Ali Tariq m.alitariqpk@ 123456gmail.com

Article

DOI: 10.7759/cureus.6007

PMC ID: 6881082

PubMed ID: 31815071

SO-VID: b7bb2313-b59d-47b4-a8b9-eb9202089fb6

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This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Serum Uric Acid – Risk Factor for Acute Ischemic Stroke and Poor Outcomes

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Most cited references 44

Uric acid provides an antioxidant defense in humans against oxidant- and radical-caused aging and cancer: a hypothesis.

Febuxostat compared with allopurinol in patients with hyperuricemia and gout.

Uric acid is a risk factor for myocardial infarction and stroke: the Rotterdam study.

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