Correlation between serum FGF21, CHOP levels, and acute coronary syndrome and its clinical prognosis
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摘要: 目的 探讨血浆成纤维生长因子21(FGF21)、内质网应激标志蛋白CHOP水平与急性冠状动脉综合征(ACS)及其临床预后之间的关系。方法 纳入2018年10月—2019年7月就诊的400例患者，根据临床表现及冠状动脉(冠脉)造影结果分为ACS组(304例)和对照组(96例)。检测患者术前血浆FGF21、CHOP水平，对ACS组患者进行平均15个月的随访，其中失访12例。根据主要不良心脑血管事件(MACCE)的发生情况，将ACS组进一步分为MACCE组(38例)和非MACCE组(254例)，分析ACS患者发生MACCE的危险因素。依据ACS患者FGF21测得数值的中位数361.98 pg/mL，将ACS组分为FGF21≥361.98 pg/mL组(152例)和FGF21 < 361.98 pg/mL组(152例)，利用Kaplan-Meier法绘制累计终点事件发生曲线。结果 ACS组患者血浆FGF21、CHOP水平明显高于对照组(P< 0.05)，且血浆FGF21水平与CHOP水平呈正相关(r=0.580，P< 0.05)，但FGF21、CHOP水平与糖尿病及高血压无明显相关性。对ACS组患者随访平均15个月后，发现MACCE组患者血浆FGF21、CHOP水平明显高于非MACCE组(P< 0.05)。Cox回归分析显示血浆FGF21(HR：1.022，95%CI：1.014~1.031，P< 0.001)、肌钙蛋白I(HR：1.028，95%CI：1.003~1.052，P=0.025)、糖尿病史(HR：2.542，95%CI：1.274~5.070，P=0.008)和Gensini评分(HR：1.007，95%CI：1.000~1.014，P=0.038)是ACS患者MACCE发生的危险因素；FGF21≥361.98 pg/mL组中患者发生终点事件的平均时间早于FGF21 < 361.98 pg/mL组。结论 ACS患者血浆FGF21和CHOP水平明显上升；血浆FGF21水平是ACS患者发生远期MACCE的独立危险因素，对ACS患者发生远期MACCE有一定预测价值。Abstract: Objective To investigate the correlation between serum fibroblast growth factor 21(FGF21), endoplasmic reticulum stress marker protein CHOP levels, and acute coronary syndrome(ACS) and its clinical prognosis.Methods A total of 400 patients who were admitted to our hospital from October 2018 to July 2019 were enrolled. According to clinical manifestations and coronary angiography results, they were divided into the ACS group(n=304) and the control group(n=96). The preoperative serum FGF21 and CHOP levels were measured. Patients in the ACS group were followed up for an average of 15 months. Among them, 12 patients were lost to follow-up. According to the occurrence of major adverse cardiovascular and cerebrovascular events(MACCE), patients in the ACS group were divided into the MACCE group(n=38) and non-MACCE group(n=254), and the risk factors of MACCE were analyzed. According to the median value of FGF21 measured in ACS patients, subjects in ACS group were divided into FGF21≥361.98 pg/mL group(n=152) and FGF21 < 361.98 pg/mL group(n=152), Kaplan-Meier method was used to draw the cumulative end-point event occurrence curves.Results The serum FGF21 and CHOP levels in the ACS group were significantly higher than those in the control group(P< 0.05), and the serum FGF21 level was positively correlated with the CHOP level(r=0.580,P< 0.05). However, there was no significant relationship between diabetes or hypertension and FGF21 or CHOP levels. After an average of 15 months follow-up in the ACS group, serum FGF21 and CHOP levels in the MACCE group were significantly higher than those in the non-MACCE group(P< 0.05). Cox regression analysis showed that plasma FGF21(HR: 1.022, 95%CI: 1.014-1.031,P< 0.001), cTnI(HR: 1.028, 95%CI: 1.003-1.052,P=0.025), diabetes history(HR: 2.542, 95%CI: 1.274-5.070,P=0.008), and Gensini score(HR: 1.007, 95%CI: 1.000-1.014,P=0.038) were risk factors for MACCE in ACS patients; the average time of endpoint events in the FGF21≥361.98 pg/mL group was earlier than that in the FGF21 < 361.9 8 pg/mL.Conclusion Serum FGF21 and CHOP levels are significantly increased in patients with ACS; Serum FGF21 level is an independent risk factor for the occurrence of long-term MACCE and has a certain predictive value for the occurrence of long-term MACCE in ACS patients.
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图 2 不同水平FGF21患者Kaplan-Meier曲线
Figure 2. Kaplan-Meier curves of patients with different levels of FGF21
表 1 对照组和ACS组的基线资料比较
Table 1. Baseline clinical data in control and ACS group
X±S, M(P25, P75) 项目 ACS组(304例) 对照组(96例) t/Z/χ2 P 年龄/岁 64.54±10.29 55.75±8.27 8.532 < 0.001 男性/例(%) 201(66.1) 37(38.5) 23.025 < 0.001 吸烟/例(%) 24(7.9) 5(5.2) 0.783 0.500 高血压/例(%) 199(65.5) 44(45.8) 11.787 0.001 糖尿病/例(%) 86(28.3) 10(10.4) 12.777 < 0.001 UA/(μmol·L-1) 315.00(251.00，379.00) 285.50(251.00，358.00) -1.658 0.097 Scr/(μmol·L-1) 68.00(63.00，77.00) 65.00(57.00，69.00) -4.262 < 0.001 TC/(mmol·L-1) 3.80(3.18，4.81) 3.88(3.17，4.64) -0.156 0.876 TG/(mmol·L-1) 1.53(1.12，2.07) 1.29(0.97，1.79) -3.148 0.002 HDL-C/(mmol·L-1) 0.87(0.74，1.02) 0.95(0.82，1.18) -3.334 0.001 LDL-C/(mmol·L-1) 2.08(1.63，2.70) 2.13(1.70，2.72) -0.204 0.838 cTnI/(mg·L-1) 0.22(0.01，0.84) 0.13(0.00，0.37) -3.469 0.001 FGF21/(pg·mL-1) 361.98(346.45，381.02) 269.85(257.92，326.58) -11.543 < 0.001 CHOP/(ng·mL-1) 19.05(16.36，21.60) 15.18(12.18，18.15) -7.410 < 0.001 
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表 2 糖尿病与高血压亚组血浆FGF21、CHOP水平比较
Table 2. FGF21 and CHOP levels in diabetes and hypertension subgroups
M(P25, P75) 组别 例数 FGF21 Z P CHOP Z P 糖尿病组 85 358.17(343.76，388.29) 0.653 0.513 18.91(15.38，21.96) -0.972 0.331 非糖尿病组 219 362.58(348.03，378.11) 19.14(16.77，21.46) 高血压组 199 359.97(345.12，382.77) -0.123 0.902 19.06(16.41，21.59) -0.068 0.946 非高血压组 105 363.00(348.26，378.44) 19.00(16.18，21.62)
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表 3 MACCE组及非MACCE组基线资料比较
Table 3. Baseline data in MACCE and non-MACCE groups
X±S, M(P25, P75) 项目 MACCE组(38例) non-MACCE组(254例) t/Z/x2 P 年龄/岁 62.08±9.61 64.84±10.40 1.541 0.124 男性/例(%) 27(71.1) 169(66.5) 0.306 0.580 吸烟/例(%) 4(10.5) 20(7.9) 0.308 0.579 高血压/例(%) 23(60.5) 169(66.5) 0.530 0.467 糖尿病/例(%) 16(42.1) 64(25.2) 4.751 0.029 PCI /例(%) 22(57.9) 146(57.5) 0.002 0.962 UA/(μmol·L-1) 308.00(237.25，371.25) 316.00(254.00，380.50) -0.571 0.568 Scr/(μmol·L-1) 68.00(61.00，81.50) 68.00(63.00，77.00) -0.096 0.923 TC/(mmol·L-1) 4.04(2.88，5.00) 3.80(3.20，4.80) -0.001 0.999 TG/(mmol·L-1) 1.35(1.07，1.96) 1.53(1.12，2.08) -0.523 0.601 HDL-C/(mmol·L-1) 0.87(0.73，1.00) 0.87(0.74，1.03) -0.678 0.498 LDL-C/(mmol·L-1) 2.15(1.54，2.84) 2.07(1.66，2.72) -0.329 0.742 cTnI/(mg·L-1) 2.05(0.73，5.53) 0.16(0.01，0.48) -6.945 < 0.001 Gensini评分 50.00(30.50，84.00) 30.00(12.00，50.00) -3.458 0.001 FGF21/(pg·mL-1) 415.56(368.87，487.33) 357.86(345.03，372.93) -6.144 < 0.001 CHOP/(ng·mL-1) 21.61(20.12，23.96) 18.78(16.07，21.00) -5.757 < 0.001
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表 4 MACCE发生的多因素Cox回归分析
Table 4. Multivariate Cox regression analysis of MACCE
自变量 B SE Wald P HR(95% CI) 糖尿病 0.933 0.352 7.010 0.008 2.542(1.274~5.070) cTnI 0.027 0.012 5.023 0.025 1.028(1.003~1.052) Gensini评分 0.007 0.004 4.293 0.038 1.007(1.000~1.014) FGF21 0.022 0.004 29.526 < 0.001 1.022(1.014~1.031) CHOP 0.092 0.071 1.654 0.198 1.096(0.953~1.260)
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