The relation between serum uric acid level and cardiovascular risk factors is complex and has been investigated mainly in men. We examined the correlation between serum uric acid level and obesity, hypertension, dyslipidemia, and diabetes mellitus (DM) in both men and women of a screened cohort in Okinawa, Japan. A total of 9,914 individuals (6,163 men and 3,751 women ranging in age from 18 to 89 years) who were screened at Okinawa General Health Maintenance Association were subjects in this study. Hyperuricemia tality in individuals with ischemic heart disease (7), the specific role of serum uric acid in relation to cardiovascular disease remains unclear.The association between serum uric acid and other cardiovascular risk factors complicates the issue. Increased serum uric acid levels are often accompanied by obesity, dyslipidemia, and hypertension (8-11), all of which are associated with increased risk for cardiovascular disease. In Japan, there are reports suggesting a significant correlation between increased serum uric acid level and cardiovascular risk factors in large members of men, but not women (12). Okada et al. (13) showed a significant correlation between serum uric acid and cardiovascular risk factors, but the number of indi-

Several epidemiological studies have shown a positive association between serum uric acid levels and the risk of hypertension. However, subjects in these studies were mostly men, or were incompletely examined for lifestyle-related variables. We prospectively examined the relation between hyperuricemia and the risk of sociations between the serum uric acid levels and the risk of development of hypertension (5-10). Selby et al. (5) indicated that serum uric acid was closely linked to the development of hypertension and that it might be a marker of susceptibility or an intermediate step in the pathway leading to hypertension. In the Olivetti heart study (6), serum uric acid levels were positively associated with increased risk of hypertension, but analyses were adjusted only for age, body mass index (BMI), serum total cholesterol, and serum triglyceride. Control for confounders such as lifestyle factors was incomplete.In Japan, Nakanishi et al. (7) reported that the risk for development of hypertension over a 6-year period increased progressively as serum uric acid levels increased, even after

Uric acid (UA) can induce renal arteriolopathy in animal models. Whether there is an association between UA and renal arteriolopathy in patients with chronic kidney disease (CKD) is unknown. Here, we examined the cross-sectional association of serum UA levels with renal arteriolar hyalinosis and wall thickening. Arteriolar parameters were assessed by semiquantitative grading (max: grade 3) of arterioles in 167 patients with CKD (mean age, 42.4 years; 86 men and 81 women) who underwent renal biopsy. The mean serum UA level was 6.4 mg dl(-1). We observed hyalinosis in 94 patients (56%) and wall thickening in 119 patients (71%). As the UA level tertile increased, the proportion of higher-grade (grade 2 and 3) hyalinosis and wall thickening increased (hyalinosis, P<0.0001 and wall thickening, P=0.0002, for trend). Multiple logistic analysis adjusted for age ≥40 years, sex, hypertension status, diabetes mellitus status and estimated glomerular filtration rate <60 ml min(-1) per 1.73 m(2) showed that hyperuricemia (UA ≥7 mg dl(-1)) was significantly associated with a higher risk of hyalinosis (adjusted odds ratio: 3.13; 95% confidence interval: 1.23-7.94; P=0.02) and higher-grade (equal to or higher than the mean value) wall thickening (adjusted odds ratio: 2.66; 95% confidence interval: 1.11-6.38; P=0.03). Hence, these results suggest that hyperuricemia may be related to renal arteriolar damage in patients with CKD.

The aim of this study was to determine whether hyperuricemia could predict future metabolic syndrome (MetS) in a large screened cohort of Japanese male and female subjects. We evaluated 5936 subjects (3144 male subjects, 2792 female subjects; mean age 48.7 years) who underwent health checkup programs in 2006 and 2010, who were MetS free in 2006. At baseline, hyperuricemia was detected in 927 male subjects (29.5%) and 276 female subjects (9.9%). Subjects with baseline hyperuricemia had significantly higher MetS prevalence in 2010 than those without (male subjects: 34.8 vs. 20.6%, P<0.0001; female subjects: 15.6 vs. 4.8%, P<0.0001). Compared with subjects in the first quintile of uric acid levels at baseline, the age-adjusted odds ratios (ORs) for MetS cumulative incidence among subjects in the third, fourth and fifth quintiles were, 1.8 (95% confidence interval (CI): 1.4-2.4: P<0.0001), 2.1 (95% CI: 1.6-2.8: P<0.0001) and 3.2 (95% CI: 2.4-4.1: P<0.0001), respectively, for male subjects and 2.4 (95% CI: 1.3-4.7: P=0.0075), 3.0 (95% CI: 1.6-5.7: P=0.0010) and 4.8 (95% CI: 2.6-8.8: P<0.0001), respectively for female subjects. Multivariable logistic analysis revealed that hyperuricemia was significantly associated with MetS cumulative incidence in male subjects (OR 1.5: 95% CI: 1.3-1.8, P<0.0001) and female (OR 2.0, 95% CI: 1.3-3.0, P<0.0001). In conclusion, hyperuricemia is a significant and independent predictor of MetS in Japanese male and female subjects. For both genders, MetS risk increases with increased serum uric acid levels.

The purpose of this study was to examine the associations between serum uric acid (SUA) levels and the incidences of hypertension and metabolic syndrome (MetS) in a large screened cohort of Japanese men and women. We evaluated 4812 subjects (males, 2528; females, 2284; mean age, 47.5 years) who underwent health checkups between 2006 and 2010 and were free of hypertension and MetS in 2006. After 4 years, 618 (13%), 764 (16%) and 158 (3%) subjects developed hypertension, MetS and hypertension with MetS, respectively. Increased SUA levels were significantly and positively associated with the incidences of hypertension, MetS and hypertension with MetS. Compared with the first quartile of SUA levels, the odds ratios (95% confidence intervals) for the third and fourth quartiles, respectively, were as follows: 1.5 (1.1-2.1; P = 0.0128) and 1.8 (1.2-2.5; P = 0.0022) for hypertension, 1.3 (0.9-1.9; P = 0.1910) and 1.8 (1.2-2.7; P = 0.0039) for MetS and 2.7 (1.1-6.6; P = 0.0276) and 3.2 (1.3-8.0; P = 0.0115) for hypertension with MetS. In conclusion, increased SUA levels were significantly and independently associated with the incidences of hypertension and MetS in subjects without hypertension or MetS at baseline. Increased SUA levels might also be correlated with the incidence of hypertension with MetS.