Serum uric acid, diuretic treatment and risk of cardiovascular events in the Systolic Hypertension in the Elderly Program (SHEP)

Objective To assess longitudinally the association of serum uric acid and i ts change due to diuretic treatment with cardiovascular events in hypertens ive patients. Design Cohort study in a randomized trial. Setting Cohort of hypertensive patients. Participants A total of 4327 men and women, aged greater than or equal to 6 0 years, with isolated systolic hypertension, randomized to placebo or chlo rthalidone, with the addition of atenolol or reserpine if needed, were obse rved for 5 years. Main outcome measures Major cardiovascular events, coronary events, stroke and all-cause mortality. Results Cardiovascular event rates for quartiles of baseline serum uric aci d were: I, 32.7 per 1000 person-years; II, 34.5 per 1000 person-years; III, 38.1 per 1000 person-years; and IV, 41.4 per 1000 person-years (P for tren d = 0.02). The adjusted hazard ratio (HR), of cardiovascular events for the highest quartile of serum uric acid versus the lowest quartile was 1.32 (9 5% CI, 1.03-1.69). The benefit of active treatment was not affected by base line serum uric acid. After randomization, an increase of serum uric acid < 0.06 mmol/l (median change) in the active treatment group was associated w ith a HR of 0.58 (0.37-0.92) for coronary events compared with those with a serum uric acid increase greater than or equal to 0.06 mmol/l. This differ ence was not explained by blood pressure effects. Those with a serum uric a cid increase greater than or equal to 0.06 mmol/l in the active treatment g roup had a similar risk of coronary events as the placebo group. Conclusions Serum uric acid independently predicts cardiovascular events in older persons with isolated systolic hypertension. Monitoring serum uric a cid change during diuretic treatment may help to identify patients who will most benefit from treatment. J Hypertens 2000, 18:1149-1154 (C) Lippincott Williams & Wilkins.