Uric Acid and Insulin Sensitivity and Risk of Incident Hypertension

Background: Uric acid, insulin sensitivity, and endothelial dysfunction may be important in the development of hypertension. Corresponding circulating biomarkers are associated with risk of hypertension, but because these factors may be interrelated, whether they independently affect risk is unknown. Methods: In 1496 women aged 32 to 52 years without hypertension at baseline, we prospectively analyzed the associations between fasting plasma levels of uric acid, insulin, triglycerides, the insulin sensitivity index, and 2 biomarkers associated with endothelial dysfunction ( homocysteine and soluble intercellular adhesion molecule-1) and the odds of incident hypertension. Odds ratios were adjusted for standard risk factors and then for all biomarkers plus estimated glomerular filtration rate and total cholesterol level. Population-attributable risk was estimated for biomarkers significantly associated with hypertension. Results: All the biomarkers were associated with incident hypertension after adjustment for standard hypertension risk factors. However, after simultaneously controlling for all the biomarkers, estimated glomerular filtration rate, and total cholesterol level, only uric acid and insulin levels were independently associated with incident hypertension. Comparing the highest and lowest quartiles of uric acid levels, the odds ratio was 1.89 (95% confidence interval, 1.26-2.82). A similar comparison yielded an odds ratio of 2.03 ( 95% confidence interval, 1.35-3.05) for insulin levels. Using an estimated basal incidence rate of 14.6 per 1000 annually, 30.8% of all hypertension occurring in young women annually is associated with uric acid levels of 3.4 mg/dL or greater ( to convert to micromoles per liter, multiply by 59.485). For insulin levels of 2.9 mu IU/mL or greater ( to convert to picomoles per liter, multiply by 6.945), this proportion is 24.2%. Conclusions: Differences in uric acid and insulin levels robustly and substantially affect the risk of hypertension in young women. Measuring these biomarkers in clinical practice may identify higher-risk individuals.