Severity of hypertension mediates the association of hyperuricemia with stroke in the REGARDS Case Cohort Study
Abstract
Previous studies do not widely support hyperuricemia as a risk factor for stroke and other cardiovascular diseases (CVD). We assessed the relationship between hyperuricemia and ischemic stroke (~ 900 cases) using a large dataset from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study. 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 (i.e., 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 (HR 1.40 [95%CI: 1.10–1.78]) after adjustment for demographic variables and systolic and diastolic blood pressure (SBP and DBP, respectively). This association was substantially attenuated (HR 1.17 [95%CI: 0.90–1.51]) by additional covariate adjustment. In particular, apparent treatment-resistant hypertension (aTRH: SBP≥140 mmHg or DBP≥90 mmHg on 3 antihypertensive medications, or use of ≥4 antihypertensive medications) and the count of antihypertensive medication classes (nAHT) significantly reduced the effect of hyperuricemia on ischemic stroke. Specifically, aTRH and nAHT, respectively, mediate 45% and 43% of the association. There was no effect modification in the association between…
How strong is the evidence?
Evidence Hub reads this as a cohort study, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence.
Read the paper
Related studies
- Noninvasive and Point-of-Care Surface-Enhanced Raman Scattering (SERS)-Based Breathalyzer for Mass Screening of Coronavirus Disease 2019 (COVID-19) under 5 min
- De Novo Transcriptome Analysis and Detection of Antimicrobial Peptides of the American Cockroach Periplaneta americana (Linnaeus)
- Molecular Characterization and Expression Profiling of Tomato GRF Transcription Factor Family Genes in Response to Abiotic Stresses and Phytohormones
- Assembly of Tight Junction Strands: Claudin-10b and Claudin-3 Form Homo Tetrameric Building Blocks that Polymerise in a Channel-Independent Manner
- Update of the Pompe variant database for the prediction of clinical phenotypes: Novel disease‐associated variants, common sequence variants, and results from newborn screening
- Machine Learning-Based SERS Chemical Space for Two-Way Prediction of Structures and Spectra of Untrained Molecules
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.