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

• Published in: Hypertension (Dallas, Tex. 1979) Vol. 75; no. 1; pp. 246 - 256
• Main Authors: Chaudhary, Ninad S, Bridges, S Louis, Saag, Kenneth G, Rahn, Elizabeth J, Curtis, Jeffrey R, Gaffo, Angelo, Limdi, Nita A, Levitan, Emily B, Singh, Jasvinder A, Colantonio, Lisandro D, Howard, George, Cushman, Mary, Flaherty, Matthew L, Judd, Suzanne, Irvin, Marguerite R, Reynolds, Richard J
• Format: Journal Article
• Language: English
• Published: United States American Heart Association, Inc 01.01.2020
• Subjects: Aged; Blood Pressure - physiology; Cohort Studies; Female; Humans; Hypertension - complications; Hypertension - diagnosis; Hypertension - physiopathology; Hyperuricemia - blood; Hyperuricemia - complications; Hyperuricemia - physiopathology; Male; Middle Aged; Risk Factors; Severity of Illness Index; Stroke - blood; Stroke - complications; Stroke - physiopathology; Uric Acid - blood; blood pressure; hyperuricemia; comorbidity; hypertension; uric acid
• ISSN: 0194-911X; 1524-4563
• DOI: 10.1161/HYPERTENSIONAHA.119.13580

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.