Hyperuricemia May Be a Risk Factor for Stroke Mediated by Severe Hypertension

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Hyperuricemia may represent a risk factor for stroke, and severe hypertension may mediate this association.

Hyperuricemia may represent a risk factor for stroke, and severe hypertension may mediate this association, according to a study published in Hypertension.

In this analysis, the data from the REGARDS (Reasons for Geographic and Racial Differences in Stroke) study, the largest prospective cohort study of white and black patients in the United States, were examined. A total of 30,239 community-dwelling individuals ≥45 years were recruited between 2003 and 2007 to participate in the REGARDS study. For the purposes of this study, researchers used a case-cohort design that included all incident adjudicated stroke cases and a randomly selected subcohort of the full population.

In the case-cohort sample, serum uric acid was measured and used to assess for the association between incident stroke and serum urate levels (≥6.8 mg/dL [hyperuricemia]; between 6.0 and 6.8 mg/dL; and <6.0 mg/dL [reference]). The effect of cardiovascular disease-related comorbidities on the association between serum urate and ischemic stroke was also evaluated.

After adjusting for systolic blood pressure (SBP), diastolic blood pressure (DBP), and demographic variables, hyperuricemia was found to be associated with ischemic stroke (hazard ratio [HR], 1.40; 95% CI, 1.10-1.78). In the fully adjusted model, the association between hyperuricemia and stroke was attenuated (HR, 1.06; 95% CI, 0.78-1.45).

The effect size of hyperuricemia on stroke was significantly reduced in a mediation analysis after adjusting for age, gender, race, the age-race interaction, SBP, DBP, and apparent treatment-resistant hypertension (change in β coefficient, 0.15; bootstrap 95% CI, 0.05-0.26). Apparent treatment-resistant hypertension was found to mediate 45% of the association between hyperuricemia and stroke, and the number of antihypertensive medications mediated 43% of the association. No effect size modification was found in the association between hyperuricemia and stroke by age, race, or sex.

Study limitations include the enrollment of only 2 ethnic groups, which may limit the generalizability of the findings across the broader population.

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“If further confirmed, the findings of the study will encourage clinicians to monitor hypertension severity while assessing the risk of stroke in individuals with high serum urate levels,” concluded the study authors.

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Chaudhary NS, Bridges SL Jr, Saag KG, et al. Severity of hypertension mediates the association of hyperuricemia with stroke in the REGARDS case cohort study. Hypertension. 2020;75(1):246-256.