This is the first study showing that hyperuricemia is a risk factor for CAC progression in asymptomatic Japanese subjects. There are some published studies evaluating the risk factors for CAC progression. From the MESA study, standard coronary risk factors including age, sex, race, smoking, BMI, blood pressure, and diabetes mellitus correlated with both high CAC score and progression. Another studies showed that fatty liver  and metabolic syndrome  were associated with CAC progression. And recent study from China showed the association between uric acid and CAC progression in young adults with originally zero CAC . Considering about the relationship between uric acid and coronary artery disease, Sun et al studied about the relationship between uric acid and coronary atherosclerosis , and Lv et al showed it among young adults less than 35 years of age . But there are still limited number of studies which are evaluated the relationship between uric acid and CAC. Mostly many studies had not been analyzed the association with uric acid and CAC. In this study, we investigated risk factors including not only traditional coronary risk factors but also uric acid level. We found hyperuricemia to be associated with CAC progression.
Although it has been hypothesized that uric acid provides an antioxidant defense in humans, previous clinical and epidemiological studies suggested that elevated uric acid levels are associated with cardiovascular diseases. Several publications demonstrated the association between serum uric acid levels and cardiovascular disorders, including hypertension, [22–24] coronary artery disease, [25–27] and carotid artery atherosclerosis. The potential mechanisms of the association between hyperuricemia and cardiovascular diseases are related to xanthine oxidase and urate transporters. Higher concentration of uric acid may reflect high levels of xanthine oxidase activity and oxidative stress. The action of xanthine oxidase leads to generation of superoxide anions and is one of the principle sources of reactive oxygen species (ROS) in the human vasculature. [29, 30] Allopurinol is rapidly metabolized to ozypurinol, an analogue of xanthine that preferentially binds to xanthine oxidase, thereby inhibiting its activity. A recent study revealed that urate transporters, which have a major role in renal regulation of urate excretion, are expressed in smooth muscle cells. In case of hyperuricemia, urate transporters may allow uric acid to enter human vascular smooth muscle cells. [32, 33] As a result, the renin angiotensin system pathway is activated and NO synthesis is inhibited, causing endothelial dysfunction and cardiovascular diseases.
This study has several limitations. First, the study was retrospective and subjects were self-referred, which may have caused a selection bias compared to population-based participants. In addition, subjects were enrolled based on repeated participation in health screening examinations, and subjects who did not undergo a second CT scan were excluded. Second, use of lung cancer screening CT may also be a limitation, because the CAC score using this method tends to be lower than that that using ECG-gated CT. [11, 34, 35] The main reason for the lower score may be the radiation dose used in lung cancer screening CT, which is lower than that that used in ECG-gated CT. However, a recent meta-analysis by Xie et al.  showed that CAC score categories correlated well between ECG-gated CT and lung cancer screening CT, although the values were still slightly lower than in ECG gated CT. Third, the follow up duration may not be sufficient to evaluate CAC progression. More long-term follow up studies are warranted.