Department of Emergency Medicine, New Haven, CT, United States of America.
Department of Internal Medicine (Section of Nephrology), New Haven, CT, United States of America.
Int J Cardiol. 2019 Mar 15;279:155-161. doi: 10.1016/j.ijcard.2018.12.061. Epub 2019 Jan 2.
We explored the relationship between inflammation, renalase an anti-inflammatory protein, and acute chest pain with coronary microvascular dysfunction (CMD).
We used cardiac Rb-82 PET/CT imaging to diagnose coronary artery disease (CAD/CALC) (defect or coronary calcification) and CMD (depressed coronary flow reserve without CAD) in patients with chest pain in an emergency department (ED). Blood samples were collected pre-imaging within 24 h of ED presentation and were analyzed for renalase and inflammatory markers including C-reactive protein, interleukins, interferon gamma, tumor necrosis factor, vascular endothelial growth factor, and metalloproteinases. Exclusions were age ≤30 years, myocardial infarction, hemodynamic instability, hypertensive crisis, heart failure or dialysis. Between 6/2014 and 11/2015, 80 patients undergoing PET/CT provided blood and were categorized as normal (18%), CAD/CALC (27%) and CMD (55%). Median renalase values were highest in patients with CMD (5503 ng/ml; IQR 3070) compared to patients with normal flows (4266 ng/ml; IQR 1503; p = 0.02) or CAD/CALC (4069 ng/ml IQR 1850; p = 0.004). CMD patients had similar median values for inflammatory markers as normal patients (p > 0.05). Renalase remained an independent predictor of CMD (OR 1.34; 95% CI = 1.1-1.7, per 1000 ng/ml) after adjustment for smoking, family history, obesity and Framingham risk score. In a model for CMD diagnosis with Framingham risk score, typical angina history and CRP, renalase improved discrimination from C-statistic = 0.60 (95% CI 0.47, 0.73) to 0.70 (95% CI, 0.59-0.82).
We found elevated renalase in response to ischemia from acute CMD. Its role as a biomarker needs validation in larger trials.
本研究旨在探讨炎症与肾酶(一种抗炎蛋白)和伴有冠状动脉微血管功能障碍(CMD)的急性胸痛之间的关系。
我们使用心脏放射性核素铷-82 PET/CT 成像来诊断急诊科(ED)胸痛患者的冠状动脉疾病(CAD/CALC)(存在缺损或冠状动脉钙化)和 CMD(无 CAD 的冠状动脉血流储备受损)。在 ED 就诊后 24 小时内采集血液样本进行成像前分析,并检测肾酶和炎症标志物,包括 C 反应蛋白、白细胞介素、干扰素 γ、肿瘤坏死因子、血管内皮生长因子和金属蛋白酶。排除标准为年龄≤30 岁、心肌梗死、血流动力学不稳定、高血压危象、心力衰竭或透析。2014 年 6 月至 2015 年 11 月,80 名接受 PET/CT 检查的患者提供了血液样本,并分为正常组(18%)、CAD/CALC 组(27%)和 CMD 组(55%)。CMD 患者的中位肾酶值最高(5503ng/ml;IQR 3070),明显高于正常血流患者(4266ng/ml;IQR 1503;p=0.02)或 CAD/CALC 患者(4069ng/ml;IQR 1850;p=0.004)。CMD 患者的炎症标志物中位数与正常患者相似(p>0.05)。在校正吸烟、家族史、肥胖和 Framingham 风险评分后,肾酶仍然是 CMD 的独立预测因子(每增加 1000ng/ml,OR 1.34;95%CI 1.1-1.7)。在Framingham 风险评分的 CMD 诊断模型中,加入典型心绞痛病史和 CRP 后,肾酶使 C 统计量从 0.60(95%CI 0.47, 0.73)提高到 0.70(95%CI 0.59-0.82)。
我们发现急性 CMD 时缺血反应中肾酶升高。其作为生物标志物的作用需要在更大的试验中验证。