Department of Clinical Laboratory, Wuhan Univ, Renmin Hospital, Wuhan, China.
Department of Cardiology, Wuhan Univ, Renmin Hospital, Wuhan, China.
Clin Chim Acta. 2019 Aug;495:630-636. doi: 10.1016/j.cca.2019.05.029. Epub 2019 May 31.
Current assessment tools for patients with acute chest pain are either traumatic (coronary angiography) or unreliable (measurement of cardiac troponin concentrations). We investigated whether the novel cardiovascular stress markers, serum growth differentiation factor-15 (GDF-15), Krüppel-like factor 4 (KLF4) and growth arrest-specific 6 (gas6) may be useful biomarkers of coronary artery disease (CAD).
A total of 350 male patients were enrolled, 198 with CAD and 152 controls, based on coronary angiography. GDF-15, KLF4 and gas6 concentrations were measured using commercial enzyme-linked immunosorbent assay kits. Multivariate logistic regression and multivariate linear regression were performed to evaluate potential associations of GDF-15, KLF4 and gas6 with risk of CAD or CAD severity.
Serum GDF-15, KLF4 and gas6 concentrations were significantly higher in male patients with CAD than in control subjects (P < .05), and they correlated significantly with involvement of coronary vessels (P < .05). After adjusting for confounding factors, we found that circulating GDF-15 concentrations remained positively associated with the presence of CAD (odds ratio [OR] per 1-standard deviation [SD] increase, 3.182; 95% confidence interval [CI] 1.586 to 6.382; P = .001), as did KLF4 concentrations (OR per 1-SD increase, 13.05; 95% CI 2.940 to 57.921, P = .001). Moreover, circulating GDF-15 concentrations were positively associated with the Gensini score (estimated SD change per 1-SD increase, 22.091; 95% CI 9.147 to 35.035, P = .001), as were KLF4 concentrations (estimated SD change per 1-SD increase, 27.996; 95% CI 10.082 to 45.910, P = .002). Gas6, in contrast, showed no relationship to presence of CAD or Gensini score.
, CONCLUSIONS: In this case-control study, increased concentrations of circulating GDF-15 and KLF4 were significantly associated with the presence and severity of CAD.
目前用于评估急性胸痛患者的评估工具要么具有创伤性（冠状动脉造影），要么不可靠（心肌肌钙蛋白浓度测量）。我们研究了新型心血管应激标志物，血清生长分化因子 15（GDF-15）、Krüppel 样因子 4（KLF4）和生长停滞特异性 6（gas6）是否可作为冠状动脉疾病（CAD）的有用生物标志物。
根据冠状动脉造影，共纳入 350 名男性患者，其中 198 名为 CAD 患者，152 名为对照组。使用商业酶联免疫吸附测定试剂盒测量 GDF-15、KLF4 和 gas6 浓度。采用多元逻辑回归和多元线性回归评估 GDF-15、KLF4 和 gas6 与 CAD 风险或 CAD 严重程度的潜在关联。
CAD 男性患者的血清 GDF-15、KLF4 和 gas6 浓度明显高于对照组（P <.05），且与冠状动脉受累呈显著正相关（P <.05）。调整混杂因素后，我们发现循环 GDF-15 浓度与 CAD 的存在仍呈正相关（每增加 1 个标准差的优势比[OR]，3.182；95%置信区间[CI]为 1.586 至 6.382；P =.001），KLF4 浓度也是如此（OR 每增加 1 个标准差，13.05；95%CI 为 2.940 至 57.921，P =.001）。此外，循环 GDF-15 浓度与 Gensini 评分呈正相关（每增加 1 个标准差估计的标准差变化，22.091；95%CI 为 9.147 至 35.035，P =.001），KLF4 浓度也是如此（每增加 1 个标准差估计的标准差变化，27.996；95%CI 为 10.082 至 45.910，P =.002）。相比之下，gas6 与 CAD 的存在或 Gensini 评分无关联。
在这项病例对照研究中，循环 GDF-15 和 KLF4 浓度升高与 CAD 的存在和严重程度显著相关。
