Plasma uric acid concentrations and risk of ischaemic stroke in women

Abstract

Background Elevated plasma uric acid has been inconsistently associated with a increased risk of total stroke; however, data are sparse among women. We examined the association between plasma uric acid concentrations and ischemic stroke among women and evaluate effect modification by key cardiovascular risk factors. Methods A nested case-control design with matching by age, race/ethnicity, smoking status, menopausal status, postmenopausal hormone therapy use, date of blood draw and fasting status was utilized among female participants of the Nurses' Health Study who provided blood samples between 1989-1990. Plasma uric acid was measured on stored blood samples. The National Survey of Stroke criteria were utilized to confirm 460 incident cases of ischemic stroke by medical records from 1990-2006. Multivariable conditional logistic regression models were estimated. Results In matched analysis, risk of ischemic stroke increased by 15% for each 1 mg/dL increase in plasma uric acid (95% CI: 3%-28%), but was no longer significant after adjustment for cardiovascular risk factors, particularly history of hypertension. The highest quartile of uric acid was significantly associated with greater risk of ischemic stroke (OR=1.56; 95% CI: 1.06-2.29, extreme quartiles) in matched analysis, but estimates were no longer significant after adjustment for cardiovascular risk factors (OR=1.43; 95% CI: 0.93-2.18). Significant effect modification by key cardiovascular risk factors was not observed. Conclusions Plasma uric acid levels were not independently associated with increased risk of ischemic stroke in this cohort of women. While plasma uric acid was associated with stroke risk factors, it was not independently associated with stroke risk.

Sex‐Specific Relationship Between Serum Uric Acid and Risk of Stroke: A Dose‐Response Meta‐Analysis of Prospective Studies

“…Six studies were conducted in Asia, 5 in Europe, and 2 in the United States . Of the included studies, 12 were prospective cohorts, whereas only 1 was a prospective, nested case‐control study . Study quality was assessed by using the NOS (Table ).…”

“…A recent prospective study in the Japanese population showed no significant association between serum UA levels and stroke mortality in both men and women . Also, another recent nested case‐control study by Jimenez et al found that UA levels were associated with stroke risk factors, but not independently associated with stroke, among generally healthy women . Although Storhaug et al analyzed the data from The Tromsø Study and suggested a sex‐specific finding of the association between serum UA and ischemic stroke, they found that serum UA is an independent marker of ischemic stroke only in men .…”

“…On the other hand, UA is a potent endogenous antioxidant that effectively scavenges reactive nitrogen and oxygen radicals . During the past decades, epidemiological studies investigating the association between serum UA levels and risk of stroke have yielded inconsistent findings . Some studies, but not all, demonstrated significant and positive correlations.…”

“…During the past decades, epidemiological studies investigating the association between serum UA levels and risk of stroke have yielded inconsistent findings . Some studies, but not all, demonstrated significant and positive correlations. Two previous meta‐analyses indicated that hyperuricemia could modestly increase the risks of both stroke incidence and mortality; several prospective studies with conflicting results have been published since then .…”

Response to comment on plasma uric acid and risk of ischaemic stroke in women

“…We appreciate Dr. Kawada’s interest [1] in our study[2] and careful consideration of the design. Kawada suggests that design considerations may limit the precision of our estimates and causal interpretation.…”