Study on the relationship between plasma soluble semaphorin 4D protein, galectin 3 and ventricular remodeling and mortality in patients with ischemic cardiomyopathy heart failure after myocardial infarction
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摘要: 目的 探讨血浆可溶性信号素4D(sSema4D)蛋白、半乳糖凝集素3(Gal-3)与心梗后缺血性心肌病(ICM)心衰患者心室重构、病死率的关系。方法 纳入2018年8月-2020年8月收治的心梗后ICM心衰患者68例作为心梗组，选取同期收治的非心梗后ICM心衰患者60例作为对照组。比较2组的血浆sSema4D、Gal-3水平，采用超声心动图检测2组的心室重构指标，包括左心房内径(LAD)、左心室射血分数(LVEF)、左心室舒张末期内径(LVEDd)、左心室收缩末期容积(LVESV)、左心室短轴缩短率(LVFS)。分析心梗后ICM心衰患者血浆sSema4D、Gal-3水平与心室重构指标的相关性。根据患者3个月的生存、死亡情况分成生存组、死亡组，分析影响预后的危险因素。结果 心梗组血浆sSema4D、Gal-3水平高于对照组，LAD、LVEDd长于对照组，LVEF、LVFS低于对照组(P＜0.001)。Pearson线性相关分析提示，血浆sSema4D、Gal-3水平与LAD、LVEDd呈正相关，与LVEF、LVFS呈负相关(P＜0.05)。COX多元回归分析提示，年龄≥65岁(95%CI 1.044~5.924，RR=2.487)、N-末端B型利钠肽原≥952.39 pg/mL(95%CI 1.344~11.580，RR=3.945)、sSema4D≥916.82 ng/L(95%CI 1.481~8.328，RR=3.512)、Gal-3≥6.78 ng/mL(95%CI 1.994~5.890，RR=3.427)是预后的危险因素，而LVEF≥54.23%(95%CI 0.895~0.977，RR=0.935)是预后的保护性因素(P＜0.05)。结论 心梗后ICM心衰患者的血浆sSema4D、Gal-3水平明显增高，且与心室重构指标有相关性，二者增高可增加患者的死亡风险，临床有望通过对二者进行检测来判断患者预后。Abstract: Objective To explore the relationship between plasma soluble semaphorin 4D(sSema4D) protein, galectin 3(Gal-3) and ventricular remodeling and mortality in patients with ischemic cardiomyopathy(ICM) heart failure after myocardial infarction.Methods Patients with ICM heart failure who were admitted to our hospital from August 2018 to August 2020 were included.Sixty-eight patients with ICM heart failure after myocardial infarction were taken as the myocardial infarction group, and 60 patients with ICM heart failure without myocardial infarction were taken as the control group. The levels of plasma sSema4D and Gal-3 were compared between the two groups, and echocardiography was used to detect the indicators of ventricular remodeling in the two groups, including left atrial diameter(LAD), left ventricular ejection fraction(LVEF), left ventricular end diastolic diameter(LVEDd), left ventricular end systolic volume(LVESV), left ventricular fractional shortening(LVFS). Analyzed the correlation between plasma sSema4D, Gal-3 levels and ventricular remodeling indexes in patients with ICM heart failure after myocardial infarction. According to the 3-month prognosis, the patients were divided into survival group and death group, and the risk factors of prognosis were analyzed.Results The plasma levels of sSema4D and Gal-3 in the infarct group were higher than those in the control group, LAD and LVEDd were longer than those in the control group, and LVEF and LVFS were lower than those in the control group(P < 0.001). Pearson linear correlation analysis showed that plasma sSema4D and Gal-3 levels were positively correlated with LAD and LVEDd, and negatively correlated with LVEF and LVFS(P < 0.05).COX multiple regression analysis indicated that age ≥ 65 years old(95%CI 1.044-5.924, RR=2.487), NT-proBNP ≥ 952.39 pg/mL(95%CI 1.344-11.580, RR=3.945), sSema4D ≥ 916.82 ng /L(95%CI 1.481-8.328, RR=3.512), Gal-3 ≥ 6.78 ng/mL(95%CI 1.994-5.890, RR=3.427) were prognostic risk factors, while LVEF ≥54.23%(95 %CI 0.895-0.977, RR=0.935) was a protective factor for prognosis(P < 0.05).Conclusion Plasma sSema4D and Gal-3 levels in patients with ICM heart failure after myocardial infarction were significantly increased, and they were correlated with ventricular remodeling indicators. The increase in both levels could increase the risk of death. The prognosis of ICM patients with heart failure after myocardial infarction could be judged clinically by detecting the sSema4D and Gal-3 levels.
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表 1 2组临床资料比较
例，X±S 组别 例数 性别 年龄/岁 BMI 心功能分级 吸烟史 饮酒史 高血压史 糖尿病史 NT-proBNP/(pg·mL-1) 男 女 Ⅱ级 Ⅲ级 心梗组 68 38 30 58.85±10.27 21.64±2.12 32 36 21 13 23 17 952.39±323.14 对照组 60 33 27 59.39±9.76 21.53±2.26 31 29 16 10 18 20 545.32±212.65 χ2/t 0.010 0.304 0.284 0.271 0.276 0.130 0.214 1.077 8.298 P 0.920 0.762 0.777 0.603 0.600 0.719 0.644 0.299 ＜0.001 
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表 2 2组血浆sSema4D、Gal-3水平及心室重构指标比较
X±S 指标 心梗组(n=68) 对照组(n=60) t P sSema4D/(ng·L-1) 916.82±108.85 576.34±91.46 19.017 ＜0.001 Gal-3/(ng·mL-1) 6.78±1.37 4.95±1.75 6.625 ＜0.001 LAD/mm 36.74±3.31 33.15±4.37 5.274 ＜0.001 LVEF/% 54.23±6.52 61.29±4.87 6.865 ＜0.001 LVEDd/mm 51.58±5.37 47.42±5.61 4.283 ＜0.001 LVESV/mL 58.53±4.82 57.45±4.99 1.244 ＞0.05 LVFS/% 17.41±2.47 22.51±2.68 11.202 ＜0.001
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表 3 心梗后ICM心衰患者血浆sSema4D、Gal-3水平与心室重构指标的相关性
指标 sSema4D Gal-3 r P r P LAD 0.658 ＜0.001 0.712 ＜0.001 LVEF -0.471 0.023 -0.504 0.014 LVEDd 0.811 ＜0.001 0.542 0.005 LVESV 0.184 0.076 0.270 0.062 LVFS -0.656 ＜0.001 -0.643 ＜0.001
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表 4 心梗后ICM心衰患者预后情况及预后单因素分析
例(%)，X±S 指标 例数 生存组(n=47) 死亡组(n=21) χ2/t P 性别 男 38 25(53.19) 13(61.90) 0.447 0.504 女 30 22(46.81) 8(38.10) 年龄/岁 57.34±6.74 62.22±4.29 3.047 0.003 BMI 21.51±1.27 21.93±1.24 1.269 0.209 心功能分级 Ⅱ级 32 26(55.32) 6(28.57) 4.168 0.041 Ⅲ级 36 21(44.68) 15(71.43) 吸烟史 有 21 14(29.79) 7(33.33) 0.086 0.770 无 47 33(70.21) 14(66.67) 饮酒史 有 13 10(21.28) 3(14.29) 0.118a) 0.731 无 55 37(78.72) 18(85.71) 高血压史 有 23 18(38.30) 5(23.81) 1.361 0.243 无 45 29(61.70) 16(76.19) 糖尿病史 有 17 10(21.28) 7(33.33) 1.125 0.289 无 51 37(78.72) 14(66.67) NT-proBNP/(pg·mL-1) 878.54±158.95 1 117.67±164.65 5.669 ＜0.001 sSema4D/(ng·L-1) 890.84±45.23 974.35±29.41 7.744 ＜0.001 Gal-3/(ng·mL-1) 6.32±0.34 7.80±0.22 18.271 ＜0.001 LAD/mm 36.54±1.75 37.19±1.12 1.562 0.123 LVEF/% 56.34±4.12 49.51±2.01 7.202 ＜0.001 LVEDd/mm 51.27±3.56 52.27±3.15 1.107 0.272 LVESV/mL 58.41±2.74 58.80±2.76 0.541 0.590 LVFS/% 17.47±1.22 17.27±1.65 0.558 0.579 注：a)行连续性校正χ2检验。
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表 5 心梗后ICM心衰患者预后的COX多元回归分析
变量 量化赋值 β SE χ2 P RR 95%CI 年龄 ＜65岁=0，≥65岁=1 0.911 0.443 4.232 0.040 2.487 1.044~5.924 心功能分级 Ⅱ级=0，Ⅲ级=1 1.096 0.582 3.545 0.060 2.993 0.956~9.370 NT-proBNP ＜952.39 pg/mL=0，≥952.39 pg/mL=1 1.372 0.549 6.241 0.012 3.945 1.344~11.580 sSema4D ＜916.82 ng/L=0，≥916.82 ng/L=1 1.256 0.441 8.131 0.004 3.512 1.481~8.328 Gal-3 ＜6.78 ng/mL=0，≥6.78 ng/mL=1 1.232 0.276 19.872 ＜0.001 3.427 1.994~5.890 LVEF ＜54.23%=0，≥54.23%=1 -0.067 0.022 9.077 0.003 0.935 0.895~0.977
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