The results of our study based on rural areas can be summarized as follows. In rural areas, an increase in UA was associated with incident hypertension. The risk of UA-related incident hypertension was significantly higher in non-elderly women. These results of this study were consistent with those of previous urban-based cohort study [4].
In previous meta-analyses, it has been reported that UA is associated with the risk of incident hypertension, regardless of traditional risk factors [2, 3]. However, in these analyses, the authors acknowledged that the statistical power to explain this relationship was weak in the elderly and that the statistical method, degree of adjustment, and residual confounding factors, which differed from study to study, were the limitations of the studies.
The weak statistical association in the elderly could be explained by a previous large cohort study based on urban areas [4], in which the association between UA and incident hypertension was age-dependent. In that study, the relative risk of incident hypertension according to UA levels differed between age groups, with the lower the age group, the higher the risk. In addition, they found that not only age but also sex play an important role in this association. They concluded that this association was age- and sex-dependent and strongest in younger women. However, in that study, as in previous studies [2, 3], residual confounders such as lifestyle remain a limitation.
UA is well known to be greatly affected by lifestyle [5,6,7,8,9,10,11]. However, since lifestyle such as dietary or behavioral patterns is difficult to objectively assess as well as difficult to categorize or quantify as a variable, it is impossible to completely adjust them in statistical analysis. Accordingly, we tried to determine whether age- and sex-dependent association between UA and incident hypertension is consistently observed in two different cohort groups, which are presumed to have different lifestyles. Because the lifestyles of urban and rural residents are inevitably different, the same analysis as in the previous urban-based cohort study was performed on CANVAS, a sub-study of KoGES targeting rural residents.
Although these two distinct cohorts cannot be directly compared, a numerical comparison of the study populations included in each study shows that the rural cohort had a higher mean age and more men, and higher rates of diabetes and hyperlipidemia and hyperuricemia, compared with the urban-based cohort (Supplementary Table 1). Despite these different baseline characteristics, the risk of UA-related incident hypertension was consistently high in both cohort studies, at least in non-elderly women.
Although the role of UA might be relatively high given the low prevalence of comorbidities such as chronic renal insufficiency and diabetes in non-elderly women, it is unclear why the risk of UA-associated hypertension is more pronounced in this group. Intriguingly, serum UA was more associated with metabolic syndrome [18], coronary heart disease [19], and renal insufficiency [20] in women than in men. Given these findings, it is conceivable that women tend to be more susceptible to UA-related cardiovascular disease.
Since most studies on the relationship between UA and the risk of incident hypertension have been conducted on relatively younger employed adults with an average age of 30–40 years, mainly men, few studies have focused on age and sex regarding this association [21,22,23,24,25,26]. As far as we know, one cross-sectional study reported that age and sex might be involved in the association between UA and hypertension [27], and one large-scale longitudinal study suggested that the risk of UA -related incident hypertension was age- and gender-dependent [4]. This study has clinical significance in confirming whether this association is still valid in populations with different characteristics.
This study also has some limitations. As with urban-based cohort study, age groups limited to 40–70 years and residual confounders undermine the value of this study. Also, considering that the concentration of UA can be affected and changed by various environmental factors, the significance of the value at the single point is inevitably limited. Unlike the urban-based cohort, the relatively small number of sample sizes and shorter follow-up duration made it impossible to analyze at a same level to the previous study, so direct comparison between urban and rural areas was not possible.