循环肝脏因子与高血压的关系

Association of circulating hepatokines with hypertension

目的探讨循环肝脏因子与高血压的相关性。方法选取2017年10月20日至2020年5月17日于西部战区总医院心内科住院的196例高血压患者(控制不良组114例和控制良好组82例),以及同期于西部战区总医院进行健康体检的正常血压者108名(正常血压组)。收集各组患者临床资料,并通过蛋白液态芯片检测法(Merck Millipore)测定血清肝脏因子,包括甲胎蛋白、血管生成素样蛋白3(ANGPTL3)、血管生成素样蛋白4(ANGPTL4)、血管生成素样蛋白6(ANGPTL6)、成纤维细胞生长因子19(FGF19)和成纤维细胞生长因子21(FGF21),比较各组患者基本临床资料和血清肝脏因子水平,并进行Pearson/Spearman相关分析和logistic回归分析。结果与正常血压组比较,控制不良组的ANGPTL4水平较低[114.08(89.63~143.45)比137.34(116.49~166.17)μg/L,P<0.001],FGF21水平较高[0.09(0.05~0.14)比0.07(0.03~0.10)μg/L,P=0.001];与控制良好组相比,控制不良组的ANGPTL4水平较低[114.08(89.63~143.45)比144.47(117.48~188.47)μg/L,P<0.001],而ANGPTL3水平较高[16.46(12.08~20.21)比12.79(9.65~17.38),P=0.001]。总人群中相关性分析显示,FGF21与收缩压(r=0.129)和舒张压(r=0.207)呈正相关,ANGPTL4与收缩压(r=-0.209)和舒张压(r=-0.157)呈负相关(均P<0.05)。多因素logistic回归分析显示,在校正了空腹血糖、甘油三酯和估算的肾小球滤过率等混杂因素后,ANGPTL4降低是血压升高(OR=0.780,95%CI 0.771~0.790)和控制不良(OR=0.785,95%CI 0.778~0.792)的独立危险因素;ANGPTL3降低是血压控制不良(OR=1.080,95%CI 1.023~1.141)的独立保护因素。结论血清ANGPTL4水平与血压升高和控制不良呈独立负相关;血清ANGPTL3水平与控制不良呈独立正相关。

Objective To investigate the correlation between circulating hepatokines and hypertension.Methods One hundred and ninety-six hypertensive patients[poorly controlled group(114 patients)and well-controlled group(82 patients)]hospitalized in the Cardiology Department of The General Hospital of Western Theater Command from October 20,2017 to May 17,2020,and 108 normotensive people who underwent health screening at the Cardiology Department of The General Hospital of Western Theater Command during the same period(normotensive group)were selected.Clinical data were collected from each group,and serum hepatokines were measured by protein liquid microarray assay(Merck Millipore),including alpha-fetoprotein(AFP),angiopoietin-like protein 3(ANGPTL3),angiopoietin-like protein 4(ANGPTL4),angiopoietin-like protein 6(ANGPTL6),fibroblast growth factor 19(FGF19)and fibroblast growth factor 21(FGF21),the basic clinical data and serum hapatokines levels were compared among the groups,and Pearson/Spearman correlation and logistic regression analyses were performed.Results Compared with the normotensive group,the poorly controlled group had lower levels of serum liver factor ANGPTL4[114.08(89.63-143.45)vs 137.34(116.49-166.17)μg/L,P<0.001]and higher levels of FGF21[0.09(0.05-0.14)vs 0.07(0.03-0.10)μg/L,P=0.001].ANGPTL4 levels were lower in the poorly controlled group compared with the well-controlled hypertension group[114.08(89.63-143.45)vs 144.47(117.48-188.47)μg/L,P<0.001],while ANGPTL3 levels were higher[16.46(12.08-20.21)vs 12.79(9.65-17.38)μg/L,P=0.001],with statistically significant differences.Correlation analysis showed that FGF21 was positively correlated with systolic blood pressure(r=0.129)and diastolic blood pressure(r=0.207,both P<0.05)and ANGPTL4 was negatively correlated with systolic blood pressure(r=-0.209)and diastolic blood pressure(r=-0.157,both P<0.05).Multivariate logistic regression analysis showed that after correcting for fasting glucose,triacylglycerol and estimated glomerular filtration rate(eGFR),lower ANGPTL4 was an independent risk factor for hypertension(OR=0.780,95%CI:0.771-0.790)and poorly controlled blood pressure(OR=0.785,95%CI:0.778-0.792),lower ANGPTL3 was an independent protective factor for poorly controlled blood pressure(OR=1.080,95%CI:1.023-1.141).Conclusions Serum ANGPTL4 levels are independently and negatively associated with hypertension and poorly controlled blood pressure.Serum ANGPTL3 levels are independently and positively associated with poorly controlled blood pressure.