In this cross-sectional study, we found that hyperuricemia is positively associated with BMI, drinking, hypertension, chronic kidney disease, and proteinuria, but negatively associated with old age (≧60 y/o), betel nut chewing, and diabetes mellitus.
To the best of our knowledge, this study was the first to investigate the association between betel nut chewing and hyperuricemia. Several mechanisms may provide potential explanations why betel nut chewers have a lower prevalence of hyperuricemia. The most important chemical components of betel nut are alkaloids . Kanbara and Seyama  found a lower serum uric acid level with an alkaline diet than with an acidic diet. Uric acid is more actively reabsorbed with acidic urine than with alkaline urine. They also found that alkalization of urine by eating alkaloid food was an effective way to excrete uric acid via the urine . Further research on uric acid excretion for betel nut chewers is warranted.
Our data showed that the relationship between hyperuricemia and diabetes mellitus is consistent with previous studies [23–26]. A possible mechanism for this inverse association may be related to the inhibition of uric acid reabsorption in the proximal tubules by high glucose levels [27, 28].
A recent research carried out with 14,362 Taiwanese showed that, for men, values of uric acid decreased as age increased . The finding is consistent with our result. Another longitudinal study for men showed that the incidence of hyperuricemia increased in parallel with the rise in BMI, with a correlation coefficient of 0.282 (p <0.0001) between serum uric acid levels and BMI . The results also support our finding of the positive association between hyperuricemia and BMI.
Our data also showed that drinking alcohol and hypertension were positively associated with hyperuricemia. A recent meta-analysis of 18 published prospective cohort studies with 55,607 subjects showed that hyperuricemia was associated with an increased risk for incidental hypertension (adjusted risk ratio 1.41, 95% CI 1.23-1.58) . The overall risk for incidental hypertension increases by 13% per 1 mg/dl increase in serum uric acid level. Several possible mechanisms for hyperuricemia in the development of hypertension have been proposed. Higher uric acid levels could lead to endothelial cell dysfunction via nitric oxide synthetase [32, 33] and stimulate vascular smooth muscle cell proliferation . Uric acid may directly stimulate the renin-angiotensin system [35, 36] and cause renal afferent arteriolopathy and tubulointerstitial nephritis, leading to higher blood pressure . Renal lesions and hypertension are prevented by lowering uric acid levels with a xanthine oxidase inhibitor or a uricosuric agent and reversed by an angiotensin-converting enzyme inhibitor .
Previous studies support our findings in associations between hyperuricemia and mixed hyperlipidemia, chronic kidney disease and proteinuria [38–43]. Uric acid can induce pre-glomerular arterial disease, vascular proliferation, renal inflammation, and hypertension via an activation of renin-angiotensin system and cyclooxygenase-2, which in turn aggravates renal disease, endothelial dysfunction, hypertension, and cardiovascular disease [44–47].
The stratified analyses shown in Table 4 support our main outcome. Irrespective of the status in overweight, diabetes and age, the odds ratios were still all less than one. In fact, according to Table 3, co-variables with age ≧ 60, BMI < 25 or presence of diabetes were already factors for lower hyperuricemia odds, which might thus keep their ORs less than one but fail to sustain statistical significance in the stratified analyses.
There are several limitations to this study. First, this study was a cross-sectional study and causality cannot be concluded. Further prospective cohort studies are necessary. Second, information about exposure to betel nut chewing was from self-reported questionnaires, and obtained from a fixed questionnaire, which included no status of ex-uses of betel nut, alcohol drinking and smoking. Potential misclassification of that exposure is possible without information on ex-uses of these substances. More detailed histories about the amount of betel nut chewed, duration, and previous abstinence are needed. Third, the participants who took the initiative to undergo the health check-up program in this hospital may not have represented the general population; they might have had higher socio-economic status or level of education, and might have been more alert to the status of their own health. These factors may have been sources of selection bias. However, the number of participants was large enough to enable us to examine associations between betel nut chewing and hyperuricemia after multivariate logistic regression modeling with comprehensive adjustments for confounders. The prevalence of betel nut chewing in our study was also consistent with two previous large studies in Taiwan [3, 4].