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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[1] 胡盛寿, 高润霖, 刘力生, 等. 《中国心血管病报告2018》概要[J]. 中国循环杂志, 2019, 34(3): 209-220. doi: 10.3969/j.issn.1000-3614.2019.03.001
[2] 林子祥, 刘丹, 薛雅芝, 等. 血清膜联蛋白A2在冠心病患者血清中明显升高[J]. 南方医科大学学报, 2020, 40(3): 382-387. https://www.cnki.com.cn/Article/CJFDTOTAL-DYJD202003017.htm
[3] Su X, Kong Y, Peng D. Fibroblast growth factor 21 in lipid metabolism and non-alcoholic fatty liver disease[J]. Clin Chim Acta, 2019, 498: 30-37. doi: 10.1016/j.cca.2019.08.005
[4] Luo Y, Ye S, Chen X, et al. Rush to the fire: FGF21 extinguishes metabolic stress, metaflammation and tissue damage[J]. Cytokine Growth Factor Rev, 2017, 38: 59-65. doi: 10.1016/j.cytogfr.2017.08.001
[5] Shen Y, Zhang X, Pan X, et al. Contribution of serum FGF21 level to the identification of left ventricular systolic dysfunction and cardiac death[J]. Cardiovasc Diabetol, 2017, 16(1): 106. doi: 10.1186/s12933-017-0588-5
[6] 靳海斌, 刘丽君, 高波. 内质网应激在成纤维细胞生长因子21抑制大鼠血管钙化过程中的作用[J]. 中国动脉硬化杂志, 2019, 27(12): 1032-1036, 1093. doi: 10.3969/j.issn.1007-3949.2019.12.005
[7] Guo X, Ren F, Zhang X, et al. Endoplasmic reticulum stress collaborates with lipopolysaccharide to promote the inflammatory response in macrophages[J]. Zhonghua Gan Zang Bing Za Zhi, 2015, 23(8): 604-608.
[8] 高宏, 文楠, 徐雪松, 等. 内质网应激介导的Kupffer细胞源性TNF-α经TNFR/caspase 8途径诱导肝星状细胞凋亡[J]. 南方医科大学学报, 2020, 40(5): 632-639. https://www.cnki.com.cn/Article/CJFDTOTAL-DYJD202005005.htm
[9] 梁平平, 仲琳, 龚磊, 等. 成纤维细胞生长因子21对内质网应激诱导心肌细胞凋亡的影响及其机制研究[J]. 中国循环杂志, 2017, 32(3): 279-283. doi: 10.3969/j.issn.1000-3614.2017.03.017
[10] 张新超, 于学忠, 陈凤英, 等. 急性冠脉综合征急诊快速诊治指南(2019)[J]. 临床急诊杂志, 2019, 20(4): 253-262. doi: 10.13201/j.issn.1009-5918.2019.04.001
[11] Gensini GG. A more meaningful scoring system for determining the severity of coronary heart disease[J]. Am J Cardiol, 1983, 51(3): 606. doi: 10.1016/S0002-9149(83)80105-2
[12] 宋莉, 邓士兵, 管常东, 等. ST段抬高型心肌梗死患者早期和晚期延迟PCI并置入药物洗脱支架的远期预后比较[J]. 中华心血管病杂志, 2020, 48(2): 118-122. doi: 10.3760/cma.j.issn.0253-3758.2020.02.006
[13] 曹保江, 李晓召, 曹向波, 等. 急性冠状动脉综合征患者血清促肾上腺皮质激素和肾上腺皮质醇水平及其与短期预后的相关性分析[J]. 中国循环杂志, 2020, 35(2): 149-155. doi: 10.3969/j.issn.1000-3614.2020.02.007
[14] 石艳璞, 曹晔萱, 靳景璐, 等. 血浆脂蛋白(a)浓度与青年人群冠心病关系的横断面研究[J]. 中国循环杂志, 2020, 35(4): 343-348. doi: 10.3969/j.issn.1000-3614.2020.04.005
[15] Poh KK, Ambegaonkar B, Baxter CA, et al. Low-density lipoprotein cholesterol target attainment in patients with stable or acute coronary heart disease in the Asia-Pacific region: results from the Dyslipidemia International Study Ⅱ[J]. Eur J Prev Cardiol, 2018, 25(18): 1950-1963. doi: 10.1177/2047487318798927
[16] Bailey KA, Moreno E, Haj FG, et al. Mechanoregulation of p38 activity enhances endoplasmic reticulum stress-mediated inflammation by arterial endothelium[J]. FASEB J, 2019, 33(11): 12888-12899. doi: 10.1096/fj.201900236R
[17] Guan H, Lin Y, Bai L, et al. Dietary Cocoa Powder Improves Hyperlipidemia and Reduces Atherosclerosis in apoE Deficient Mice through the Inhibition of Hepatic Endoplasmic Reticulum Stress[J]. Mediators Inflamm, 2016, 2016: 1937572.
[18] Wang M, Kaufman RJ. Protein misfolding in the endoplasmic reticulum as a conduit to human disease[J]. Nature, 2016, 529(7586): 326-335. doi: 10.1038/nature17041
[19] Tabari FS, Karimian A, Parsian H, et al. The roles of FGF21 in atherosclerosis pathogenesis[J]. Rev Endocr Metab Disord, 2019, 20(1): 103-114.
[20] Anuwatmatee S, Allison MA, Shlipak MG, et al. Relationship of fibroblast growth factor 21 with kidney function and albuminuria: multi-ethnic study of atherosclerosis[J]. Nephrol Dial Transplant, 2019, 34(6): 1009-1016. doi: 10.1093/ndt/gfy120
[21] Kokkinos J, Tang S, Rye KA, et al. The role of fibroblast growth factor 21 in atherosclerosis[J]. Atherosclerosis, 2017, 257: 259-265. doi: 10.1016/j.atherosclerosis.2016.11.033
[22] Cao F, Wang S, Cao X, et al. Fibroblast growth factor 21 attenuates calcification of vascular smooth muscle cells in vitro[J]. J Pharm Pharmacol, 2017, 69(12): 1802-1816. doi: 10.1111/jphp.12826
[23] Zeng Z, Zheng Q, Chen J, et al. FGF21 mitigates atherosclerosis via inhibition of NLRP3 inflammasome-mediated vascular endothelial cells pyroptosis[J]. Exp Cell Res, 2020, 393(2): 112108. doi: 10.1016/j.yexcr.2020.112108
[24] Shi Y, Wang S, Peng H, et al. Fibroblast growth factor21 attenuates vascular cal cification by alleviating endoplasmic reticulum stress mediated apoptosis in rats[J]. Int J Biol Sci, 2019, 15(1): 138-147. doi: 10.7150/ijbs.28873
[25] Xiaolong L, Dongmin G, Liu M, et al. FGF21 induces autophagy-mediated cholesterol efflux to inhibit atherogenesis via RACK1 up-regulation[J]. J Cell Mol Med, 2020, 24(9): 4992-5006. doi: 10.1111/jcmm.15118
[26] Lee CH, Woo YC, Chow WS, et al. Role of circulating fibroblast growth factor 21 measurement in primary prevention of coronary heart disease among chinese patients with type 2 diabetes mellitus[J]. J Am Heart Assoc, 2017, 6(6).
[27] Kim WJ, Kim SS, Lee HC, et al. Association between Serum Fibroblast Growth Factor 21 and Coronary Artery Disease in Patients with Type 2 Diabetes[J]. J Korean Med Sci, 2015, 30(5): 586-590. doi: 10.3346/jkms.2015.30.5.586
[28] 陈海峰, 吴峰, 卢楠, 等. 血清成纤维细胞生长因子21、脂联素与冠状动脉性心脏病的相关性[J]. 中华高血压杂志, 2016, 24(8): 758-762, 773. https://www.cnki.com.cn/Article/CJFDTOTAL-ZGGZ201608014.htm
[29] 曾玉玲, 占德进, 刘婷, 等. 肿瘤坏死因子相关蛋白3、成纤维细胞生长因子21与冠心病合并糖尿病经皮冠状动脉介入术后支架内再狭窄的相关性[J]. 实用医学杂志, 2020, 36(11): 1494-1498. https://www.cnki.com.cn/Article/CJFDTOTAL-SYYZ202011019.htm
[30] 高国峰, 周林丽, 张冬, 等. ACEF评分在中国经皮冠状动脉介入治疗患者中的预测价值研究[J]. 中国循环杂志, 2019, 34(11): 1047-1054. https://www.cnki.com.cn/Article/CJFDTOTAL-ZGXH201911002.htm
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