Yadalam Adithya K, Liu Chang, Sun Yan V, Mandawat Anant, Quyyumi Arshed A, Hayek Salim S
Division of Cardiology Emory University School of Medicine Atlanta GA USA.
Department of Epidemiology Emory University, Rollins School of Public Health Atlanta GA USA.
J Am Heart Assoc. 2025 May 6;14(9):e039728. doi: 10.1161/JAHA.124.039728. Epub 2025 May 2.
Breast cancer is associated with increased risk for cardiovascular disease. suPAR (soluble urokinase plasminogen activator receptor) is an immune-derived signaling glycoprotein implicated in the pathogenesis of atherosclerosis, as well as cancer, representing a shared risk factor for these conditions. We sought to examine whether elevated proteomics-based suPAR levels are associated with cardiovascular death or incident coronary artery disease in survivors of breast cancer.
We leveraged Olink proteomics-based measurement of suPAR levels in 845 female survivors of breast cancer without cardiovascular disease enrolled in the UK Biobank. We examined the association between suPAR levels and the primary composite end point of cardiovascular death or incident coronary artery disease with Fine and Gray competing-risk regression, while accounting for the competing risk of noncardiovascular death and adjusted for clinical variables and C-reactive protein levels.
The median age was 61.0 years, and 96% were of White race. Over a median follow-up of 13.4 years, 84 (9.9%) events of cardiovascular death or incident coronary artery disease occurred. After adjustment for demographics, traditional cardiovascular risk factors, and C-reactive protein levels, proteomics-based suPAR levels (per 1 SD) were independently associated with adverse cardiovascular outcome risk (subdistribution hazard ratio [sHR], 1.48 [95% CI, 1.16-1.88], =0.002). When compared with participants in the lowest quartile of suPAR levels, those in the highest quartile had a 3-fold increase in the risk of cardiovascular death or incident coronary artery disease (sHR, 3.08 [95% CI, 1.03-6.78], =0.005).
In this cohort study of survivors of breast cancer, proteomics-based suPAR levels were associated with an increased risk for adverse cardiovascular outcomes, highlighting the potential role of suPAR as a shared risk factor for cancer and cardiovascular disease.
乳腺癌与心血管疾病风险增加相关。可溶性尿激酶型纤溶酶原激活物受体（suPAR）是一种免疫源性信号糖蛋白，参与动脉粥样硬化以及癌症的发病机制，是这些疾病的共同危险因素。我们旨在研究基于蛋白质组学的suPAR水平升高是否与乳腺癌幸存者的心血管死亡或冠心病事件相关。
我们利用Olink蛋白质组学方法测量了英国生物银行中845名无心血管疾病的乳腺癌女性幸存者的suPAR水平。我们采用Fine和Gray竞争风险回归分析suPAR水平与心血管死亡或冠心病事件这一主要复合终点之间的关联，同时考虑非心血管死亡的竞争风险，并对临床变量和C反应蛋白水平进行了调整。
中位年龄为61.0岁，96%为白人。在中位随访13.4年期间，发生了84例（9.9%）心血管死亡或冠心病事件。在对人口统计学、传统心血管危险因素和C反应蛋白水平进行调整后，基于蛋白质组学的suPAR水平（每增加1个标准差）与不良心血管结局风险独立相关（亚分布风险比[sHR]为1.48[95%CI，1.16 - 1.88]，P = 0.002）。与suPAR水平处于最低四分位数的参与者相比，处于最高四分位数的参与者发生心血管死亡或冠心病事件的风险增加了3倍（sHR为3.08[95%CI，1.03 - 6.78]，P = 0.005）。
在这项乳腺癌幸存者队列研究中，基于蛋白质组学的suPAR水平与不良心血管结局风险增加相关，凸显了suPAR作为癌症和心血管疾病共同危险因素的潜在作用。
