Sex specific associations between serum uric acid levels and risk of hypertension for different reference values of high blood pressure

Abstract

Abstract Background Uric acid (UA) has been linked to the development of hypertension. However the sex specific associations between UA levels and different diagnostic blood pressure (BP) references is unknown. Purpose We aimed to ascertain the association between serum UA quartiles, hyperuricemia, and 5-year hypertension incidence and weather lower BP diagnostic references may alter these associations in men and women without cardiometabolic diseases. Methods This 5-year study used the check-up data from a hospital. We excluded participants with hypertension (defined as BP ≥140/90 mmHg in cohort 1 and BP ≥130/80 mmHg in cohort 2), diabetes, dyslipidemia, obesity, estimated glomerular filtration rate (eGFR) <60 ml/min/1.73m², metabolic syndrome, history of gout, and UA lowering medication. We categorized UA into quartiles as follows: men: 1st quartile UA≤4.8 mg/dL, 2nd quartile 4.9-5.6 mg/dL, 3rd quartile 5.7-6.4 mg/dL, and 4th quartile UA≥6.5 mg/dL; women: 1st quartile UA≤3.4 mg/dL, 2nd quartile 3.5-4.0 mg/dL, 3rd quartile 4.1-4.7 mg/dL, and 4th quartile UA≥4.8 mg/dL. Hyperuricemia was defined as UA>7 mg/dL in men and UA>6 mg/dL in women. To analyze the effects of UA on development of hypertension, we adjusted for age, body mass index, systolic BP, diastolic BP, tobacco smoking, alcohol consumption, exercise habit, serum triglyceride, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, fasting plasma glucose, and eGFR by sex in both cohorts. The outcome was 5-year hypertension incidence defined as BP ≥140/90 mmHg in cohort 1 and BP ≥130/80 mmHg in cohort 2. Results In total, 21,514 participants (age, 52.9±10.9 years; men, 39.8%), were enrolled in cohort 1, and 15,316 participants (age, 51.3±10.9 years; men, 36.5%), in cohort 2. The incidence of hypertension in cohort 1 and cohort 2 over a 5-year period was 16.3% and 29.7% in men and 10.9% and 21.4% in women, respectively. Using multivariable logistic regression, we found that when comparing the fourth to first UA quartile, there was an increased risk of hypertension in men in cohort 1, OR 1.36 (95% CI, 1.13-1.63, P<0.01) and cohort 2, OR 1.31 (95% CI, 1.09-1.57, P<0.01) but not in women, cohort 1, OR 1.14 (95% CI, 0.95-1.36, P=0.16) and cohort 2, OR 1.14 (95% CI, 0.98-1.34, P=0.10) respectively. In contrast, for hyperuricemia, we observed increased hypertension risk only in men in cohort 1, OR 1.23 (95% CI, 1.07-1.42, P=0.02) and women were associated with increased risk of hypertension in cohort 2, OR 1.57 (95% CI, 1.14-2.16, P<0.01) but not in men OR 1.15 (95% CI 0.95-1.40, P=0.15). Conclusion Uric acid effect on development of hypertension is affected by sex and incidence differs with the BP reference used. We emphasize on early UA screening to enhance hypertension prevention among cardiometabolic free population.Hypertension 5-Year Incidence Proportion