Associations Between Inflammation, Cardiovascular Regenerative Capacity, and Cardiovascular Events: A Cohort Study.
Associations Between Inflammation, Cardiovascular Regenerative Capacity, and Cardiovascular Events: A Cohort Study.
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DOI：
10.1161/atvbaha.121.316574
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发表时间：
2021-11
期刊：
影响因子：
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通讯作者：
Quyyumi AA
中科院分区：
文献类型：
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作者：
Almuwaqqat Z;Hwan Kim J;Garcia M;Ko YA;Moazzami K;Lima B;Sullivan S;Alkhalaf J;Mehta A;Shah AJ;Hussain MS;Pearce BD;Bremner JD;Waller EK;Vaccarino V;Quyyumi AA
循环祖细胞具有免疫调节特性，可能减轻CAD患者特有的炎症。我们假设CPC较少的患者将具有较高的炎症标志物和较差的结局。稳定型CAD患者入组前瞻性研究，CPC计数为表达CD 34的单核细胞（CD 34+），炎症计数为白细胞介素-6（IL-6）和高敏C反应蛋白（hsCRP）水平。患者随访5年，终点为死亡和心肌梗死，中位时间为2年后重复测量炎症生物标志物。在392例患者的整个队列中，IL-6和hsCRP水平在2年后保持不变（0.3 ± 2.4 pg/mL和0.1 ± 1.0 mg/L，p=0.45）。CPC计数（对数转换）与IL-6水平的变化呈负相关（r=-0.17，P <0.001）。使用线性回归，在调整人口统计学和临床变量以及药物后，CPC计数每增加1个对数，IL-6和hsCRP水平分别下降− 0.59（（95%CI），−0.90，−0.20）pg/mL和−0.13（−0.28，0.01）mg/L。使用校正了这些危险因素的考克斯模型，IL-6升高1 pg/mL与死亡/MI风险增加11%（95%CI，9，13）相关。我们发现，IL 6水平的变化部分（40%）介导了低CPC计数患者不良事件的高风险。心血管再生能力降低与CAD患者的进行性炎症独立相关，而炎症反过来又与不良结局相关。
Circulating progenitor cells possess immune modulatory properties and might mitigate inflammation that is characteristic of patients with CAD. We hypothesized that patients with fewer CPC will have higher inflammatory markers and worse outcomes. Patients with stable CAD were enrolled in a prospective study enumerating CPCs as CD34-expressing mononuclear cells (CD34+), and inflammation as levels of interleukin-6 (IL-6) and high sensitivity C-reactive protein (hsCRP) levels. Patients were followed for 5 years for the endpoints of death and myocardial infarction with repeat inflammatory biomarkers measured after a median of 2 years. In the entire cohort of 392 patients, IL-6 and hsCRP levels remained unchanged (0.3 ± 2.4 pg/mL and 0.1 ± 1.0 mg/L, p=0.45) after 2 years. CPC counts (log-transformed) were inversely correlated with the change in IL-6 levels (r=− 0.17, P <0.001). Using linear regression, IL-6 and hsCRP levels declined by − 0.59 ((95%CI), −0.90, −0.20) pg/mL and −0.13 (−0.28, 0.01) mg/L per 1 log higher CPC counts after adjustment for the demographic and clinical variables as well as medications. Using Cox models adjusted for these risk factors, a rise in 1 pg/mL of IL-6 was associated with a 11% (95%CI, 9, 13) greater risk of death/MI. We found that the change in IL6 level partly (by 40%) mediated the higher risk of adverse events among those with low CPC counts. Reduced cardiovascular regenerative capacity is independently associated with progressive inflammation in patients with CAD, that in turn is associated with poor outcomes.