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. 2020 Jan;75(1):246-256.
doi: 10.1161/HYPERTENSIONAHA.119.13580. Epub 2019 Dec 2.

Severity of Hypertension Mediates the Association of Hyperuricemia With Stroke in the REGARDS Case Cohort Study

Ninad S Chaudhary  1 , S Louis Bridges Jr  2 , Kenneth G Saag  2 , Elizabeth J Rahn  2 , Jeffrey R Curtis  2 , Angelo Gaffo  2   3 , Nita A Limdi  4 , Emily B Levitan  1 , Jasvinder A Singh  2   3 , Lisandro D Colantonio  1 , George Howard  5 , Mary Cushman  6 , Matthew L Flaherty  7 , Suzanne Judd  5 , Marguerite R Irvin  1 , Richard J Reynolds  2
Affiliations

Severity of Hypertension Mediates the Association of Hyperuricemia With Stroke in the REGARDS Case Cohort Study

Ninad S Chaudhary et al. Hypertension. 2020 Jan.

Abstract

Previous studies do not widely support hyperuricemia as a risk factor for stroke and other cardiovascular diseases. We assessed the relationship between hyperuricemia and ischemic stroke (≈900 cases) using a large data set from the REGARDS study (Reasons for Geographic and Racial Differences in Stroke). We employed a case-cohort design (incident stroke cases and randomly selected cohort participants) and weighted Cox-proportional hazard models to estimate the association of serum urate level ≥6.8 mg/dL (ie, hyperuricemia) and 6.0 to <6.8 mg/dL versus <6.0 mg/dL (reference) with incident stroke. Analyses were stratified by race, gender, and age. Mediation of cardiovascular disease comorbidities on the serum urate-stroke association was tested. Hyperuricemia was associated with stroke (hazard ratio, 1.40 [95% CI, 1.10-1.78]) after adjustment for demographic variables and systolic and diastolic blood pressure. This association was substantially attenuated (hazard ratio, 1.17 [95% CI, 0.90-1.51]) by additional covariate adjustment. In particular, apparent treatment-resistant hypertension (systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg on 3 antihypertensive medications or use of ≥4 antihypertensive medications) and the count of antihypertensive medication classes significantly reduced the effect of hyperuricemia on ischemic stroke. Specifically, apparent treatment-resistant hypertension and number of antihypertensive, respectively, mediate 45% and 43% of the association. There was no effect modification in the association between hyperuricemia and stroke by age, race, or gender. We conclude that hyperuricemia may be a risk factor for stroke. The substantial attenuation of this association by apparent treatment-resistant hypertension and number of antihypertensive suggests that severe hypertension may be a mediator.

Keywords: blood pressure; comorbidity; hypertension; hyperuricemia; uric acid.

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References

    1. Zhu Y, Pandya BJ, Choi HK. Prevalence of gout and hyperuricemia in the us general population: The national health and nutrition examination survey 2007–2008. Arthritis Rheum. 2011;63:3136–3141 - PubMed
    1. Borghi C, Rosei EA, Bardin T, Dawson J, Dominiczak A, Kielstein JT, Manolis AJ, Perez-Ruiz F, Mancia G. Serum uric acid and the risk of cardiovascular and renal disease. J Hypertens. 2015;33:1729–1741; discussion 1741 - PubMed
    1. Abeles AM. Hyperuricemia, gout, and cardiovascular disease: An update. Curr Rheumatol Rep. 2015;17:13. - PubMed
    1. Culleton BF, Larson MG, Kannel WB, Levy DJAoim. Serum uric acid and risk for cardiovascular disease and death: The framingham heart study. 1999;131:7–13 - PubMed
    1. Feig DI, Kang DH, Johnson RJ. Uric acid and cardiovascular risk. N Engl J Med. 2008;359:1811–1821 - PMC - PubMed

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