Masato Matsushita , MD, PhD 1 , Akihiro Shirakabe , MD, PhD , 1 , Hirotake Okazaki , MD, PhD 1 , Yusaku Shibata , MD 1 , Hiroki Goda , MD 1 , Shota Shigihara , MD 1 , Kazuhiro Asano , MD 1 , Kenichi Tani , MD 1 , Kazutaka Kiuchi , MD 1 , Takayo Murase , PhD 3 , Takashi Nakamura , 4 , Tsutomu Takayasu , 5 , Miwako Asano , 6 , Fumitaka Okajima , MD, PhD 2 , Nobuaki Kobayashi , MD, PhD 1 , Noritake Hata , MD, PhD 1 , Kuniya Asai , MD, PhD 1 , Wataru Shimizu , MD, PhD 7
8 January 2020
10 February 2020
Background: The mechanisms of the increased plasma xanthine oxidoreductase (XOR) activity in outpatients with cardiovascular disease were unclear.
Methods and Results: A total of 372 outpatients were screened, and 301 outpatients with cardiovascular disease were prospectively analyzed. Blood samples were collected from patients who visited a daily cardiovascular outpatient clinic. Patients with diabetes mellitus (DM) were significantly more likely to be classified into the high-XOR group (≥100 pg/h/mL; 50%) than the low-XOR group (<100 pmol/h/mL; 28.7%). On multivariate logistic regression analysis, DM (OR, 2.683; 95% CI: 1.441–4.996) was independently associated with high plasma XOR activity in all cohorts. In the diabetic cardiovascular disease patients (n=100), median body mass index (BMI) in the high-XOR group (28.0 kg/m 2; IQR, 25.2–29.4 kg/m 2, n=32) was significantly higher than in the low-XOR group (23.6 kg/m 2; IQR, 21.2–25.7 kg/m 2, n=68), and BMI was independently associated with high plasma XOR activity (OR, 1.340; 95% CI: 1.149–1.540). Plasma hydrogen peroxide was significantly higher in DM patients with high plasma XOR activity and obesity (>22 kg/m 2) than in other patients.
Conclusions: DM with obesity is one of the mechanisms of XOR enhancement in cardiovascular disease. The increase of XOR is a possible pathway for the production of reactive oxygen species in obese cardiovascular disease patients with DM.