Background Hyperuricemia is known to be associated with metabolic syndrome and cardiovascular disease (CVD). It was reported that elevated level of homocysteine (Hcy) in patients with gout was related with decreased renal function. A high level of Hcy is regarded as a risk factor for CVD, since Hcy is related with endothelial cell damage, which can lead to inflammation in the blood vessels and atherosclerosis. However, there was no report about the relationship between Hcy and atherosclerosis in patients with hyperuricemia.
Objectives In this study, we investigated whether or not carotid intima-media thickness (IMT) was increased in patients with hyperuricemia. We also evaluated the correlation between serum Hcy level and carotid IMT in hyperuricemic patients.
Methods This study includes 1,228 patients who visited the Health Promotion Center of Chung-Ang University Hospital from January 2013 to August 2015. Serum Hcy, uric acid, fasting glucose, blood urea nitrogen (BUN) and creatinine (Cr), cholesterol profiles, C-reactive protein (CRP) and other laboratory findings were tested. Serum Hcy level was measured by a competitive immunoassay using direct chemiluminescent (Siemens Centaur Immunoassay Systems, USA). Carotid IMT was measured by B-mode carotid ultrasonography. Hyperuricemia was defined as the serum uric acid above 7.0 mg/dL, and hyperhomocysteinemia was defined as the serum Hcy above 15.0 μmol/L.
Results The mean ages of hyperuricemic and normouricemic patients were not significantly different (51.19 ± 15.08 vs. 51.57 ± 17.01, p=0.833), however, the male ratio in hyperuricemia group was higher than that in normouricemia group (160/167, 96% vs. 732/1,061, 69%, p <0.001). Patients with hyperuricemia showed significantly higher levels in serum Hcy than normouricemic individuals (13.65 ± 4.47 μmol/L vs 11.68 ± 3.65 μmol/L, p<0.001). Carotid IMT in hyperuricemia group was significantly thicker than that in normouricemia group (1.13 ± 0.66 mm vs 1.03 ± 0.53, p =0.029). In patients with hyperuricemia, carotid IMT was correlated with serum Hcy level (γ=0.209, p=0.007), estimated glomerular filtration rate (eGFR), serum BUN and Cr levels (γ= -0.318, p<0.001; γ=0.229, p=0.003; γ=0.311, p<0.001, respectively), however, it was not correlated with serum uric acid level, glucose level and cholesterol profiles. It was shown that serum Hcy level was correlated with eGFR, serum BUN and Cr levels in hyperuricemic patients (r= -0.490, p<0.001; r=0.369, p<0.001; r=0.487, p<0.001, respectively), whereas it was uncorrelated with cholesterol profiles. The patients with high serum Hcy showed higher level of IMT than the patients with low serum Hcy (1.18 ± 0.68 mm vs 1.02 ± 0.52 mm, p<0.001). In multiple linear analyses, carotid IMT was affected by eGFR (β= -0.289, p=0.001), however, it was not influenced by glucose level and cholesterol profiles in patients with hyperuricema.
Conclusions Carotid IMT was higher in patients with hyperuricemia than in those with normouricemia, and it was correlated with serum Hcy level in patients with hyperuricemia. This study suggests that decreased renal function in patients with hyperuricemia leads to elevated serum Hcy level, which in turn leads to atherosclerosis.
Disclosure of Interest None declared