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John P. Forman, MD, MSc; Hyon Choi, MD, DrPH; Gary C. Curhan, MD, ScD

Arch Intern Med. 2009;169(2):155-162.

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 µIU/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.

Author Affiliations: Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School (Drs Forman, Choi, and Curhan), and Renal Division, Department of Medicine, Brigham and Women's Hospital (Drs Forman and Curhan), Boston, Massachusetts; Division of Rheumatology, Vancouver General Hospital, University of British Columbia, Vancouver, British Columbia, Canada (Dr Choi); and Department of Epidemiology, Harvard School of Public Health, Boston (Dr Curhan).

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