Stroke Risk and Serum Uric Acid Levels: Does Gender Play a Role?
Risk of stroke is associated with high serum UA levels in both genders.
Results of a meta-analysis published in the Journal of the American Heart Association1 found no indication of gender-specific effects of elevated serum uric acid (UA) levels on stroke risk. The investigators did find a moderately increased risk of stroke in association with high serum UA levels, but it was equally distributed between men and women.
Previous studies have produced contradictory evidence of a link between serum UA and stroke risk,2-6 and 2 studies specifically pointed to greater risks in women compared with men.3,7 Chongke Zhong, MD, from the Medical College of Soochow University, Suzhou, China, and colleagues undertook the current study to provide a systematic analysis to evaluate a gender bias.
The investigators conducted a literature search of 3 main medical databases of all relevant studies reported by September, 2016, starting in 1965 for PubMed and Embase and in 1986 for Web of Science, specifically looking for trials that reported gender-specific results of serum UA levels associated with stroke.
The main analysis evaluated a total of 13 studies,2-14 including 11 prospective cohort studies that reported an increased risk of serum UA tied to stroke outcomes in men and 10 that supported increased risk in women. The total number of patients in the cohorts was 12,494 and 10,229, respectively.
The relative risk (RR) of ischemic stroke associated with every 1 mg/dL increase of serum UA was slightly higher in men than in women (1.13 [CI 95%,1.08-1.17] vs 1.12 [CI 95%, 1.06-1.18]). Conversely, RR of hemorrhagic stroke was marginally increased in women compared with men (1.07 CI 95% 1.01-1.14 vs 1.05, CI 95% 0.97-1.14, respectively).
Moderate heterogeneity was observed in the men and none in the women. For both types of stroke, a significant nonlinear trend toward higher stroke risk was seen with men but not women with elevated serum UA levels.
The risk of future stroke was similar in both groups, with no significant difference attributed to gender. Overall, the investigators found a 10% increase in stroke risk for men (RR = 1.10 [1.05-1.14]) and an 11% increase for women (RR = 1.11 [1.09-1.13]) associated with each 1 mg/dL increase in serum UA, consistent with 2 previous meta-analyses suggesting a potential effect of hyperurecemia on mortality.15,16 The nonlinear association observed only in men became most significant at serum UA levels above 6 mg/dL, increasing more sharply at higher levels.
- Sex-specific relationship between serum uric acid and risk of stroke: a dose-response meta-analysis of prospective studies. J Am Heart Assoc. 2017;6:e005042.
- Kamei K, Konta T, Hirayama A, et al. Associations between serum uric acid levels and the incidence of nonfatal stroke: a nationwide community-based cohort study [published online July 12, 2016]. Clin Exp Nephrol. doi:10.1007/s10157-016-1311-7
- Zhang W, Iso H, Murakami Y, et al. Serum uric acid and mortality form cardiovascular disease:EPOCH-JAPAN Study. J Atheroscler Thromb. 2016;23:692-703.
- Strasak AM, Kelleher CC, Brant LJ, et al. Serum uric acid is an independent predictor for all major forms of cardiovascular death in 28,613 elderly women: a prospective 21-year follow-up study. Int J Cardiol. 2008;125:232-239.
- Strasak A, Ruttmann E, Brant L, et al. Serum uric acid and risk of cardiovascular mortality: a prospective long-term study of 83,683 Austrian men. Clin Chem 2008;54:273-284.
- Jimenez MC, Curhan GC, Choi HK, et al. Plasma uric acid concentrations and risk of ischaemic stroke in women. Eur J Neurol. 2016;23:1158-1164.
- Bos MJ, Koudstaal PJ, Hofman A, et al. Uric acid is a risk factor for myocardial infarction and stroke: the Rotterdam Study. Stroke. 2006;37:1503-1507.
- Chien KL, Hsu HC, Sung FC, et al. Hyperuricemia as a risk factor on cardiovascular events in Taiwan: the Chin-Shan Community Cardiovascular Cohort Study. Atherosclerosis. 2005;183:147-155.
- Gerber Y, Tanne D, Medalie JH, et al. Serum uric acid and long-term mortality from stroke, coronary heart disease and all causes. Eur J Cardiovasc Prev Rehabil. 2006;13:193-198.
- Jee SH, Lee SY, Kim MT. Serum uric acid and risk of death from cancer, cardiovascular disease or all causes in men. Eur J Cardiovasc Prev Rehabil. 2004;11:185-191.
- Sakata K, Hashimoto T, Ueshima H, et al. Absence of an association between serum uric acid and mortality from cardiovascular disease: NIPPON DATA 80, 1980–1994. National Integrated Projects for Prospective Observation of Non-communicable Diseases and its Trend in the Aged. Eur J Epidemiol. 2001;17:461-468.
- Storhaug HM, Norvik JV, Toft I, et al. Uric acid is a risk factor for ischemic stroke and all-cause mortality in the general population: a gender specific analysis from The Tromso Study. BMC Cardiovasc Disord. 2013;13:115.
- Holme I, Aastveit AH, Hammar N, et al. Uric acid and risk of myocardial infarction, stroke and congestive heart failure in 417,734 men and women in the Apolipoprotein MOrtality RISk study. (AMORIS). J Intern Med 2009;266:558-570.
- Hozawa A, Folsom AR, Ibrahim H, et al. Serum uric acid and risk of ischemic stroke: the ARIC Study. Atherosclerosis. 2006;187:401-407.
- Li M, Hou W, Zhang X, et al. Hyperuricemia and risk of stroke: a systematic review and meta-analysis of prospective studies. Atherosclerosis. 2014;232:265-270.
- Kim SY, Guevara JP, Kim KM, et al. Hyperuricemia and risk of stroke: a systematic review and meta-analysis. Arthritis Rheum. 2009;61:885-892.