The serum urate-lowering impact of weight loss among men with a high cardiovascular risk profile: the Multiple Risk Factor Intervention Trial.

OBJECTIVES To evaluate the person-level impact of weight loss on serum urate levels among men with a high cardiovascular risk profile. METHODS We analysed 12,379 men (mean serum urate level=407 μmol/l) from the Multiple Risk Factor Intervention Trial, using data prospectively collected at baseline and annually over a 7-year period (78,881 visits). Our endpoint was normouricaemia, defined by serum urate levels≤360 μmol/l, a widely accepted therapeutic target. Person-level effects were estimated using conditional logistic regression models to adjust for time-varying covariates (age, congestive heart failure, hypertension, diuretic use, renal function, alcohol intake and dietary factors). RESULTS There was a graded relation between weight loss and achieving normouricaemia (P-value for trend<0.001). Compared with no weight change (-0.9 to 0.9 kg), the multivariate odds ratios of achieving normouricaemia for a weight loss of 1-4.9, 5-9.9 and ≥10 kg were 1.43 (95% CI: 1.33, 1.54), 2.17 (1.95, 2.40) and 3.90 (3.31, 4.61), respectively. The corresponding serum urate level changes were -7, -19 and -37 μmol/l (-0.12, -0.31 and -0.62 mg/dl). Similar levels of associations persisted among subgroups stratified by demographics, presence of gout, hypertension, diuretic use, renal insufficiency, alcohol intake, trial group assignment and adiposity categories (all P-values for trend<0.001). CONCLUSIONS Weight reduction could help achieve a widely accepted therapeutic urate target level (≤360 μmol/l) among men with a high cardiovascular risk profile. Although the urate-lowering effect appeared weaker than that of urate-lowering drugs, other associated health benefits would make weight reduction important, particularly in this population.