Abstract
Serum uric acid (SUA) at high levels and bilirubin at low levels were potent antioxidant but it was uncertain that whether SUA and total bilirubin (TBIL) had additive interaction for the risk of CVD in type 2 diabetes mellitus (T2DM). We conducted a cross-sectional survey of 6713 inpatients with T2DM and admitted to 81 tertiary care hospitals. CVD was defined as having either prior coronary heart disease or stroke or peripheral arterial disease. Binary logistic regression was used to estimate odds ratios of SUA and TBIL for CVD. The effect size of additive interaction was estimated by three measures, i.e., relative excess risk due to interaction, attributable proportion due to interaction and synergy index. Among 6713 patients with T2DM, 561 (8.36%) suffered from CVD. Using ≥283 umol/L (median) to define high SUA and <11.5 umol/L (n = 2290 or 34.11%) to define low TBIL, copresence of both factors (n = 621 or 9.25%) was associated with 5.18-fold (95% CI, 4.00–6.72) risk of CVD with significant additive interactions in multivariable analysis as compared to absence of both risk factors. The copresence of both high SUA and low TBIL was associated with a large increased risk of CVD in high-risk Chinese patients with type 2 diabetes.
Highlights
SUA and the severity of metabolic syndrome and cardiovascular diseases were in a linear manner[14,16], J-shaped and U-shaped associations with cardiovascular mortality were reported in two cohort studies[17,18]
low-density lipoprotein cholesterol (LDL-C) and TG were higher but high-density lipoprotein cholesterol (HDL-C) and albumin to creatinine ratio (ACR) were lower in patients with Cardiovascular disease (CVD) than in those without CVD
The detected associations between SUA, total serum bilirubin (TBIL) and their interactive effect with CVD were mainly driven by CHD, and to a lesser extent, by Peripheral arterial disease (PAD) (Supplementary Table 5 and Supplementary Table 6). In this cross-sectional study of inpatients with type 2 diabetes, we used non-linear approach to define cutoff points for SUA and TBIL and found that presence of isolated high SUA, i.e., ≥283 umol/l and isolated low TBIL, i.e.,
Summary
SUA and the severity of metabolic syndrome and cardiovascular diseases were in a linear manner[14,16], J-shaped and U-shaped associations with cardiovascular mortality were reported in two cohort studies[17,18]. In a recent statin-treated cohort of 130,052 patients, total serum bilirubin (TBIL) was associated with the risk of CVD in a L-shaped manner[9]. Another prospective epidemiological study reported a U-shaped relationship between bilirubin levels and the risk of coronary heart disease[26]. The current study used the data from a cross sectional survey of inpatients with T2DM from 81 top tertiary care hospitals in China to test 1) full-range associations of SUA and TBIL with CVD; and 2) interactive effects of both factors towards increasing the risk of CVD in Chinese patients with T2DM
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