Type 2 diabetes increased the risk of cardiovascular death (HR 1.38; 95% CI 1.16-1.63; P<0.001), an effect that was significantly mediated by suPAR levels.
Cohort (n=4,324)
Do suPAR and hs-CRP levels mediate the risk of adverse cardiovascular outcomes associated with Type 2 diabetes in patients with coronary artery disease?
suPAR levels, but not hs-CRP, mediate more than half of the adverse cardiovascular risk associated with Type 2 diabetes in patients with coronary artery disease.
Hazard Ratio: 1.38 (95% CI 1.16–1.63)
p-value: p=<0.001
OBJECTIVE Type 2 diabetes (T2D) is a significant risk factor for adverse outcomes in coronary heart disease (CHD). We investigated whether inflammation and immune dysregulation, measured using soluble urokinase plasminogen activator receptor (suPAR) and high-sensitivity C-reactive protein (hs-CRP) levels, mediate this risk. RESEARCH DESIGN AND METHODS Patients with and without CHD enrolled in the Emory Cardiovascular Biobank had suPAR (ViroGates, Denmark) and hs-CRP levels measured and were followed for 1) cardiovascular death, 2) a composite of incident myocardial infarction and cardiovascular death, and 3) all-cause death. Fine and Gray or Cox proportional hazards models adjusted for demographic, clinical, and treatment variables were used. Regression-based causal mediation analyses were performed. RESULTS A total of 4,324 participants (mean SD age 64 11.9 years, 36% women, 31.8% with T2D) were followed for a median of 6.9 years. SuPAR levels were higher in those with T2D (median interquartile range 3,260 2,503–4,463 vs. 2,792 2,217–3,600 pg/mL). T2D was associated with a higher adjusted risk (hazard ratio HR 1.38; 95% CI 1.16, 1.63; P 0.001) of cardiovascular death that was greatly attenuated (HR 1.18; 95% CI 0.99, 1.40; P = 0.1) after adjustment for suPAR, but not hs-CRP, levels. Similar findings were observed for the other outcomes. SuPAR, but not hs-CRP, levels mediated 50% of the effect of T2D on adverse outcomes. CONCLUSIONS The impact of T2D on adverse outcomes is significantly mediated through chronic inflammation and immune dysregulation, estimated using suPAR levels. Whether novel therapies for reducing suPAR levels will impact CHD risk in T2D warrants further investigation.
Sakr et al. (Wed,) 在冠心病患者（n=4,324）中开展了一项队列研究。评估了 2 型糖尿病与无 2 型糖尿病对心血管死亡的影响（HR 1.38, 95% CI 1.16-1.63, p=<0.001）。2 型糖尿病增加了心血管死亡风险（HR 1.38; 95% CI 1.16-1.63; P<0.001），这一效应显著由 suPAR 水平介导。