Abstract
The optimal range of serum uric acid (urate) associated with the lowest risk for developing cardiometabolic diseases is unknown in a generally healthy population. This 5-year cohort study is designed to identify the optimal range of serum urate. The data were collected from 13,070 Japanese between ages 30 and 85 at the baseline (2004) from the Center for Preventive Medicine, St. Luke’s International Hospital, Tokyo. We evaluated the number of subjects (and prevalence) of those free of the following conditions: hypertension, diabetes, dyslipidemia, and chronic kidney disease (CKD) over 5 years for each 1 mg/dL of serum urate stratified by sex. Furthermore, the odds ratios (ORs) for remaining free of these conditions were calculated with multiple adjustments. Except for truly hypouricemic subjects, having lower serum urate was an independent factor for predicting the absence of hypertension, dyslipidemia, and CKD, but not diabetes. The OR of each 1 mg/dL serum urate decrease as a protective factor for hypertension, dyslipidemia, and CKD was 1.153 (95% confidence interval, 1.068–1.245), 1.164 (1.077–1.258), and 1.226 (1.152–1.306) in men; 1.306 (1.169–1.459), 1.121 (1.022–1.230), and 1.424 (1.311–1.547) in women, respectively. Moreover, comparing serum urate of 3–5 mg/dL in men and 2–4 mg/dL in women, hypouricemia could be a higher risk for developing hypertension (OR: 4.532; 0.943–21.78) and CKD (OR: 4.052; 1.181–13.90) in women, but not in men. The optimal serum urate range associated with the lowest development of cardiometabolic diseases was less than 5 mg/dL for men and 2–4 mg/dL for women, respectively.
Highlights
Both epidemiologically and in animal models, hyperuricemia is strongly associated with the development and progression of cardiovascular disease [1,2]
Women were significantly older, and had lower body mass index (BMI), lower blood pressure, less smoking and drinking habits, lower prevalence of hypertension, diabetes, dyslipidemia, and chronic kidney disease (CKD), and lower serum urate compared to men
This study showed a positive association between serum urate and cardiometabolic diseases, but most Mendelian randomization studies or meta-analyses suggested that elevated serum urate was only associated with gout [25,26,27,28,29]
Summary
Both epidemiologically and in animal models, hyperuricemia is strongly associated with the development and progression of cardiovascular disease [1,2]. The variability in the findings from the cross-sectional studies and the evidence supporting a J-shaped cause-effect between urate and cardiovascular disease suggests the need to identify the proper level range for which urate could be relatively safe, or in contrast, could exert a substantial deleterious role in the pathogenesis of cardiovascular disease. In this regard, little information is known on the optimal serum urate range associated with the lowest risk of disease in a generally healthy population
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