Soluble urokinase Plasminogen Activator Receptor (suPAR) mediates the effect of a lower education level on adverse outcomes in patients with coronary artery disease.
Soluble urokinase Plasminogen Activator Receptor (suPAR) mediates the effect of a lower education level on adverse outcomes in patients with coronary artery disease.
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可溶性尿激酶纤溶酶原激活剂受体 (suPAR) 介导较低教育水平对冠状动脉疾病患者不良结局的影响。
DOI：
10.1093/eurjpc/zwad311
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发表时间：
2024
影响因子：
8.3
通讯作者：
Quyyumi,ArshedA
中科院分区：
文献类型：
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作者：
Füller,David;Liu,Chang;Ko,Yi-An;Alkhoder,AymanA;Desai,ShivangR;Almuwaqqat,Zakaria;Patel,ShivaniA;Ejaz,Kiran;Kauser,Tanveer;Martini,MohamedAfif;Alvi,Zain;Mehta,PujaK;Sperling,LaurenceS;Quyyumi,ArshedA
目的探讨低教育程度对冠心病（CAD）患者死亡风险的不利影响是否由炎症和免疫途径的激活介导，估计为可溶性尿激酶纤溶酶原激活物受体水平升高。方法和结果在3164例接受冠状动脉造影的患者中，我们调查了suPAR与受教育程度之间的多变量关联，并使用Cox比例风险模型和Fine and Gray亚分布竞争风险模型评估了受教育程度较低（定义为高中或以下学历为最高学历）与预后之间的关系。通过中介分析评估suPAR和高敏c反应蛋白（hs-CRP）的潜在中介作用。高学历（≥大学）患者1814例（57.3%），低学历（≤高中）患者1350例（42.7%）。协变量调整后，学历低的患者可溶性尿激酶纤溶酶原激活剂受体水平比学历高的患者高9.0%[95%可信区间（CI） 6.3 ~ 11.8,P≤0.0001]。在调整人口统计学、临床和行为协变量（包括CAD严重程度和心力衰竭史、药物使用和hs-CRP水平）后，较低的受教育程度与较高的心血管死亡风险相关[危险比1.26 (95% CI 1.02-1.55，P= 0.03)]。然而，在调整suPAR水平后，较低的教育水平对心血管死亡的影响变得不显著。全因死亡的数值相似。可溶性尿激酶纤溶酶原激活物受体水平和hs-CRP水平分别介导了受教育程度较低的心血管死亡风险的49%和17%。结论循环suPAR水平在低受教育程度对死亡率的影响中起重要作用，表明全身炎症和免疫失调作为不利健康社会决定因素的生物介质的重要性。
AimsTo investigate whether the adverse impact of lower educational attainment on mortality risk in patients with coronary artery disease (CAD) is mediated by the activation of inflammatory and immune pathways, estimated as elevated soluble urokinase plasminogen activator receptor levels.Methods and resultsIn 3164 patients undergoing coronary angiography, we investigated multivariable associations between suPAR and educational attainment and assessed the relationship between a lower educational level (defined as a high-school degree or less as the highest educational qualification) and outcomes using Cox proportional hazard and Fine and Gray’s subdistribution competing risk models. The potential mediating effect through suPAR and high-sensitivity C-reactive protein (hs-CRP) was assessed using mediation analysis. A total of 1814 patients (57.3%) had achieved a higher (≥college) education level and 1350 patients (42.7%) a lower (≤high school) education level. Soluble urokinase plasminogen activator receptor levels were 9.0% [95% confidence interval (CI) 6.3–11.8,P≤ 0.0001] higher in patients with lower educational qualifications than in those with higher educational qualifications after covariate adjustment. Lower educational attainment was associated with a higher risk of cardiovascular death after adjustment for demographic, clinical, and behavioural covariates, including CAD severity and heart failure history, medication use, and hs-CRP levels [hazard ratio 1.26 (95% CI 1.02–1.55,P= 0.03)]. However, after adjustment for suPAR levels, the effect of a lower educational level on cardiovascular death became insignificant. Values were similar for all-cause death. Soluble urokinase plasminogen activator receptor levels mediated 49% and hs-CRP levels 17% of the cardiovascular death risk attributable to lower educational attainment.ConclusionCirculating suPAR levels importantly mediate the effects of lower educational attainment on mortality, indicating the importance of systemic inflammation and immune dysregulation as biologic mediators of adverse social determinants of health.