Uric acid levels within the normal range predict increased risk of hypertension: a cohort study

• Serum uric acid within the normal range predicts hypertension in healthy adults.
• New SUA cutoffs are needed with regard to hypertension and the metabolic syndrome.
• Reverse causality is unlikely as higher SUA is not associated with declining GFR.

There are data describing that cardiovascular risks related to serum uric acid (SUA) levels may begin below the current diagnostic level for hyperuricemia. Values from 5.2 to 6.0 mg/dL were positively associated with higher cardiovascular risk. The risk associated with lower SUA levels has not been fully assessed in healthy adults. The purpose of this study was to evaluate whether normal SUA levels, even below 5–6 mg/dL, might be related to an increased risk of hypertension, compared with low–normal SUA. This cohort study was conducted in an outpatient setting: all clinics of the largest Health Maintenance Organization in Israel, in a national distribution. A total of 118,920 healthy adults (40–70 years old), who had SUA levels screened during 2002, were eligible for the study. They were stratified according to baseline SUA, and were followed for 10 years. The study endpoint was any new diagnosis of hypertension during the study period (until December 31, 2011). During 10 years of follow–up (2002–2011), 28,436 examinees developed hypertension (23.9%). Compared with the pre–defined SUA reference values (2–3 mg/dL), women with SUA within the normal range had a gradual, increased risk of developing new–onset hypertension, starting at values as low as 3–4 mg/dL (adjusted odds ratio, 1.15; 95% confidence interval, 1.01–1.30). Women with SUA 5–6 mg/dL, still accepted as normouricemia, had a 66% increased risk of developing hypertension. Younger women (ages 40–50 years at baseline) in a similar SUA subgroup (5–6 mg/dL) had an even higher risk (odds ratio, 2.25; 95% confidence interval, 1.96–2.60). Similar results were seen among men. The possibility of subtle confounders exists, despite extensive adjustment. SUA within the normal range is associated with new–onset hypertension among healthy adults, compared with once very common low–normal range values. Further study is warranted to determine new cutoffs of hypo–, normo–, and hyperuricemia, which might be far lower than current scales.