慢性心衰患者血清GDF-15与PⅠCP、PⅢNP的相关性分析
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摘要
目的检测心力衰竭(心衰)患者血清生长分化因子15(GDF-15)与Ⅰ型前胶原羧基端肽(PⅠCP)、Ⅲ型前胶原氨基端肽(PⅢNP)的变化并分析其相关性,探究GDF-15对心衰患者心室重构的指导作用。方法纳入219例心衰患者,按照美国纽约心脏病协会(NYHA)心功能分级分为NYHAⅠ级组58例、Ⅱ级组39例、Ⅲ级组47例、Ⅳ级组75例;按左室射血分数(LVEF)分为射血分数减低的心衰组(LVEF<0.45,HFrEF组,69例)和射血分数保留的心衰组(LVEF≥0.45,HFpEF组,150例);选取32例同期健康体检者作为对照组。采用ELISA法检测血清GDF-15、PⅠCP、PⅢNP水平,超声心动图测量左室舒张末期内径(LVEDD)、左心房内径(LA)、室间隔厚度(IVST)、左室后壁厚度(LVPWT)以及LVEF,计算左室质量指数(LVMI),并分析心衰患者血清GDF-15与PⅠCP、PⅢNP、NT-proBNP、LVEDD、LA、LVMI及LVEF的相关性。结果心衰患者血清NT-proBNP、GDF-15、PⅠCP、PⅢNP水平随NYHA分级增加而升高(P<0.05)。对照组、HFpEF组和HFrEF组LA、LVEDD、LVMI、NT-proBNP、GDF-15、PⅠCP及PⅢNP依次升高(P<0.05)。心衰患者血清GDF-15水平与PⅠCP、PⅢNP、NT-proBNP、LA、LVEDD、LVMI呈正相关(r_s分别为0.549、0.533、0.539、0.393、0.403、0.485,均P<0.01),与LVEF呈负相关(r_s=-0.568,P<0.01)。结论心衰患者血清GDF-15与心衰严重程度相关,并可反映心衰患者心室重构情况。
Objective To detect the changes of serum growth differentiation factor 15(GDF-15) and type Ⅰ procollagen carboxy terminal peptide(P Ⅱ CP) and type Ⅲ procollagen amino terminal peptide(P Ⅲ NP) in patients with heart failure, and to analyze the correlation between GDF-15, P I CP and P Ⅲ NP, and to explore the guiding role of GDF-15 in ventricular remodeling in patients with heart failure. Methods A total of 219 patients with heart failure were enrolled. Patients were divided into heart function Ⅰ grade(n=58), Ⅱ grade(n=39), Ⅲ grade(n=47), and Ⅳ grade(n=75) groups in accordance with New York Heart Association(NYHA). According to left ventricular ejection fraction(LVEF), the heart failure patients were divided into heart failure with reduced LVEF group(LVEF <0.45, n=69) and heart failure with preserved LVEF group(LVEF≥0.45, n=150). And 32 healthy subjects were chosen as the control group. Serum levels of GDF-15, P Ⅰ CP, and PⅢNP were measured by ELISA. Left ventricular end-diastolic diameter(LVEDD), left atrial(LA), interventricular septal thickness(IVST), left ventricular posterior wall thickness(LVPWT), and left ventricular ejection fraction(LVEF) were measured by echocardiography. The left ventricular mass index(LVMI) was calculated. And also the correlation between serum GDF-15 and P Ⅰ CP, PⅢNP, NT-proBNP, LVEDD, LA, LVMI and LVEF were analyzed in patients with heart failure.Results Serum levels of GDF-15, P Ⅰ CP, P Ⅲ NP and NT-proBNP were significantly elevated in patients with heart failure(P <0.05), and increased with the increasing NYHA classification. The serum levels of LA, LVEDD, LVMI, NT-proBNP, GDF-15, P Ⅰ CP and P Ⅲ NP were increased in turn in control group, HFpEF group and HFrEF group(P < 0.05). Serum GDF-15 levels were positively correlated with P Ⅰ CP, P Ⅲ NP, NT-proBNP, LA, LVEDD, and LVMI in patients with heart failure(r_s=0.549, 0.533, 0.539, 0.393,0.403, 0.485,P < 0.01),and negatively correlated with LVEF(r_s=-0.568, P < 0.01). Conclusion Serum GDF-15 is associated with the severity of heart failure and may reflect ventricular remodeling in patients with heart failure.
Objective To detect the changes of serum growth differentiation factor 15(GDF-15) and type Ⅰ procollagen carboxy terminal peptide(P Ⅱ CP) and type Ⅲ procollagen amino terminal peptide(P Ⅲ NP) in patients with heart failure, and to analyze the correlation between GDF-15, P I CP and P Ⅲ NP, and to explore the guiding role of GDF-15 in ventricular remodeling in patients with heart failure. Methods A total of 219 patients with heart failure were enrolled. Patients were divided into heart function Ⅰ grade(n=58), Ⅱ grade(n=39), Ⅲ grade(n=47), and Ⅳ grade(n=75) groups in accordance with New York Heart Association(NYHA). According to left ventricular ejection fraction(LVEF), the heart failure patients were divided into heart failure with reduced LVEF group(LVEF <0.45, n=69) and heart failure with preserved LVEF group(LVEF≥0.45, n=150). And 32 healthy subjects were chosen as the control group. Serum levels of GDF-15, P Ⅰ CP, and PⅢNP were measured by ELISA. Left ventricular end-diastolic diameter(LVEDD), left atrial(LA), interventricular septal thickness(IVST), left ventricular posterior wall thickness(LVPWT), and left ventricular ejection fraction(LVEF) were measured by echocardiography. The left ventricular mass index(LVMI) was calculated. And also the correlation between serum GDF-15 and P Ⅰ CP, PⅢNP, NT-proBNP, LVEDD, LA, LVMI and LVEF were analyzed in patients with heart failure.Results Serum levels of GDF-15, P Ⅰ CP, P Ⅲ NP and NT-proBNP were significantly elevated in patients with heart failure(P <0.05), and increased with the increasing NYHA classification. The serum levels of LA, LVEDD, LVMI, NT-proBNP, GDF-15, P Ⅰ CP and P Ⅲ NP were increased in turn in control group, HFpEF group and HFrEF group(P < 0.05). Serum GDF-15 levels were positively correlated with P Ⅰ CP, P Ⅲ NP, NT-proBNP, LA, LVEDD, and LVMI in patients with heart failure(r_s=0.549, 0.533, 0.539, 0.393,0.403, 0.485,P < 0.01),and negatively correlated with LVEF(r_s=-0.568, P < 0.01). Conclusion Serum GDF-15 is associated with the severity of heart failure and may reflect ventricular remodeling in patients with heart failure.
引文
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[14]马萍,徐环,徐烨华,等.充血性心力衰竭患者血浆生长分化因子-15水平变化及临床意义[J].天津医药,2016,44(6):736-739. Ma P,Xu H,Xu YH,et al. Changes and clinical significanceof the plasma growth differentiation factor-15 in patients withchronic congestive heart failure[J]. Tianjin Med J,2016,44(6):736-739. doi:10.11958/58776.
[15]Zannad F,Rossignol P,Iraqi W. Extracellular matrix fibroticmarkers in heart failure[J]. Heart Fail Rev,2010,15(4):319-329.doi:10.1007/s10741-009-9143-0.
[16]Florea VG,Anand IS. Troponin T and plasma collagen peptides inheart failure[J]. Circ Heart Fail,2012,5(4):394-397. doi:10.1161/circheartfailure.112.969279.
[17]Radovan J,Vaclav P,Petr W,et al. Changes of collagen metabolismpredict the left ventricular remodeling after myocardial infarction[J]. Mol Cell Biochem,2006,293(1/2):71-78. doi:10.1007/s11010-006-2955-5.
[18]Prockop DJ,Kivirikko KI. Collagens:molecular biology,diseases,and potentials for therapy[J]. Annu Rev Biochem,1995,64:403-434. doi:10.1146/annurev.bi.64.070195.002155.
[19]Lind L,Sundstrom J. Change in left ventricular geometry over 10years in the elderly and risk of incident cardiovascular disease[J]. JHypertens,2018. doi:10.1097/hjh. 0000000000001897.[Epubahead of print].
[20]Lind L,Wallentin L,Kempf T,et al. Growth-differentiation factor-15 is an independent marker of cardiovascular dysfunction anddisease in the elderly:results from the Prospective Investigation ofthe Vasculature in Uppsala Seniors(PIVUS)Study[J]. Eur HeartJ,2009,30(19):2346-2353. doi:10.1093/eurheartj/ehp261.
[2] Konstam MA,Kramer DG,Patel AR,et al. Left ventricularremodeling in heart failure:current concepts in clinical significanceand assessment[J]. JACC Cardiovasc Imaging,2011,4(1):98-108. doi:10.1016/j.jcmg.2010.10.008.
[3] Wollert KC,Kempf T. Growth differentiation factor 15 in heartfailure:an update[J]. Curr Heart Fail Rep,2012,9(4):337-345.doi:10.1007/s11897-012-0113-9.
[4] Kou H,Jin X,Gao D,et al. Association between growthdifferentiation factor 15 and left ventricular hypertrophy inhypertensive patients and healthy adults[J]. Clin Exp Hypertens,2018,40(1):8-15. doi:10.1080/10641963.2016.1273948.
[5] Lok SI,Winkens B,Goldschmeding R,et al. Circulating growthdifferentiation factor-15 correlates with myocardial fibrosis inpatients with non-ischaemic dilated cardiomyopathy and decreasesrapidly after left ventricular assist device support[J]. Eur J HeartFail,2012,14(11):1249-1256. doi:10.1093/eurjhf/hfs120.
[6]中华医学会心血管病学分会,中华心血管病杂志编辑委员会.中国心力衰竭诊断和治疗指南2014[J].中华心血管病杂志,2014,42(2):98-122. Chinese Society of Cardiaology of ChineseMedical Association,Editorial Board of Chinese Journal ofCardiology. Chinese heart failure diagnosis and treatmentguidelines 2014[J]. Chin J Cardiol,2014,42(2):98-122. doi:10.3760/cma.j.issn.0253-3758.2014.02.004.
[7] Madahar P,Duprez DA,Podolanczuk AJ,et al. Collagenbiomarkers and subclinical interstitial lung disease:The Multi-Ethnic Study of Atherosclerosis[J]. Respir Med,2018,140:108-114. doi:10.1016/j.rmed.2018.06.001.
[8] Santhanakrishnan R,Chong JP,Ng TP,et al. Growth differentiationfactor 15,ST2,high-sensitivity troponin T,and N-terminal probrain natriuretic peptide in heart failure with preserved vs. reducedejection fraction[J]. Eur J Heart Fail,2012,14(12):1338-1347.doi:10.1093/eurjhf/hfs130.
[9] Kempf T,Eden M,Strelau J,et al. The transforming growth factor-beta superfamily member growth-differentiation factor-15 protectsthe heart from ischemia/reperfusion injury[J]. Circ Res,2006,98(3):351-360. doi:10.1161/01.res.0000202805.73038.48.
[10]Xu J,Kimball TR,Lorenz JN,et al. GDF15/MIC-1 functions as a protective and antihypertrophic factor released from the myocardiumin association with SMAD protein activation[J]. Circ Res,2006,98(3):342-350. doi:10.1161/01.RES.0000202804.84885.d0.
[11]Wollert KC,Kempf T,Peter T,et al. Prognostic value of growth-differentiation factor-15 in patients with non-ST-elevation acutecoronary syndrome[J]. Circulation,2007,115(8):962-971. doi:10.1161/circulationaha.106.650846.
[12]Kempf T,von Haehling S,Peter T,et al. Prognostic utility of growthdifferentiation factor-15 in patients with chronic heart failure[J]. JAm Coll Cardiol,2007,50(11):1054-1060. doi:10.1016/j.jacc.2007.04.091.
[13]Li J,Cui Y,Huang A,et al. Additional diagnostic value of growthdifferentiation factor-15(GDF-15)to N-Terminal B-typenatriuretic peptide(NT-proBNP)in patients with different stagesof heart failure[J]. Med Sci Monit,2018,24:4992-4999. doi:10.12659/msm.910671.
[14]马萍,徐环,徐烨华,等.充血性心力衰竭患者血浆生长分化因子-15水平变化及临床意义[J].天津医药,2016,44(6):736-739. Ma P,Xu H,Xu YH,et al. Changes and clinical significanceof the plasma growth differentiation factor-15 in patients withchronic congestive heart failure[J]. Tianjin Med J,2016,44(6):736-739. doi:10.11958/58776.
[15]Zannad F,Rossignol P,Iraqi W. Extracellular matrix fibroticmarkers in heart failure[J]. Heart Fail Rev,2010,15(4):319-329.doi:10.1007/s10741-009-9143-0.
[16]Florea VG,Anand IS. Troponin T and plasma collagen peptides inheart failure[J]. Circ Heart Fail,2012,5(4):394-397. doi:10.1161/circheartfailure.112.969279.
[17]Radovan J,Vaclav P,Petr W,et al. Changes of collagen metabolismpredict the left ventricular remodeling after myocardial infarction[J]. Mol Cell Biochem,2006,293(1/2):71-78. doi:10.1007/s11010-006-2955-5.
[18]Prockop DJ,Kivirikko KI. Collagens:molecular biology,diseases,and potentials for therapy[J]. Annu Rev Biochem,1995,64:403-434. doi:10.1146/annurev.bi.64.070195.002155.
[19]Lind L,Sundstrom J. Change in left ventricular geometry over 10years in the elderly and risk of incident cardiovascular disease[J]. JHypertens,2018. doi:10.1097/hjh. 0000000000001897.[Epubahead of print].
[20]Lind L,Wallentin L,Kempf T,et al. Growth-differentiation factor-15 is an independent marker of cardiovascular dysfunction anddisease in the elderly:results from the Prospective Investigation ofthe Vasculature in Uppsala Seniors(PIVUS)Study[J]. Eur HeartJ,2009,30(19):2346-2353. doi:10.1093/eurheartj/ehp261.