血清视黄醇结合蛋白、N末端脑钠肽前体及铜蓝蛋白水平对高血压并射血分数保留的心力衰竭的诊断价值研究
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摘要
背景射血分数保留的心力衰竭(HFpEF)是慢性心力衰竭的一种常见类型,目前尚无明确的诊断指标及特效药物,而早期诊断HFpEF可有效减轻患者负担及挽救患者生命。目的分析血清视黄醇结合蛋白(RBP)、N末端脑钠肽前体(NT-proBNP)及铜蓝蛋白(CP)水平对高血压并HFpEF的诊断价值。方法选取2016—2017年复旦大学附属中山医院青浦分院收治的高血压并HFpEF患者115例作为观察组,另选取同期单纯高血压患者35例作为对照组。比较两组患者血清RBP、NT-proBNP、CP水平及心功能指标[包括左心室射血分数(LVEF)和左心房容积指数(LAVI)],比较观察组中不同高血压分级及纽约心脏病协会(NYHA)分级患者血清RBP、NT-proBNP、CP水平及心功能指标;绘制ROC曲线以评价血清RBP、NT-proBNP及CP水平对高血压患者HFpEF的诊断价值。结果(1)两组患者LVEF比较,差异无统计学意义(P>0.05);观察组患者血清RBP、NT-proBNP、CP水平及LAVI高于对照组(P<0.01)。(2)观察组中不同高血压分级患者LVEF比较,差异无统计学意义(P>0.05);观察组中高血压2级、3级患者血清RBP、NT-proBNP、CP水平及LAVI高于高血压1级患者,高血压3级患者血清RBP、NT-proBNP、CP水平及LAVI高于高血压2级患者(P<0.05)。(3)观察组中不同NYHA分级患者LVEF比较,差异无统计学意义(P>0.05);观察组中NYHA分级Ⅲ级、Ⅳ级患者血清RBP、NT-proBNP、CP水平及LAVI高于NYHA分级Ⅱ级患者,NYHA分级Ⅳ级患者血清RBP、NT-proBNP、CP水平及LAVI高于NYHA分级Ⅲ级患者(P<0.05)。(4)绘制ROC曲线显示,血清RBP水平诊断高血压患者HFpEF的曲线下面积(AUC)为0.888,血清NT-proBNP水平为0.913,血清CP水平为0.835,三者联合检测为0.978;三者联合检测诊断高血压患者HFpEF的AUC大于血清RBP、NT-proBNP、CP水平(P<0.05);血清RBP、NT-proBNP、CP水平诊断高血压患者HFpEF的AUC比较,差异均无统计学意义(P>0.05)。结论血清RBP、NT-proBNP、CP水平随着高血压分级及NYHA分级增加而升高,可能参与高血压并HFpEF的发生发展过程,且三者联合检测能有效提高高血压患者HFpEF的诊断价值。
Background Heart failure with preserved ejection fraction(HFpEF)is a common type of chronic heart failure,but There are no clear diagnostic indicators and specific drugs,so early diagnosis has important clinical value for reducing patients' burden and saving their lives. Objective To observe the diagnostic value of serum levels of retinol binding protein(RBP),NT-proBNP and ceruloplasmin(CP)in hypertension patients complicated with HFpEF. Methods A total of 115 hypertension patients complicated with HFpEF were enrolled as observation group in Qingpu Branch of Zhongshan Hospital Affiliated to Fudan University from 2016 to 2017,meanwhile 35 patients with hypertension but no heart failure were selected as control group. Serum levels of RBP,NT-proBNP and CP,and cardiac function indicators(including LVEF and LAVI)were compared between the two groups,in patients with different hypertension grades and different NYHA grades in observation group. ROC curve was drawn to evaluate the diagnostic value of serum levels of RBP,NT-proBNP and CP for HFpEF in patients with hypertension. Results(1)There was no statistically significant difference in LVEF between the two groups(P>0.05);serum levels of RBP,NT-proBNP and CP,and LAVI in observation group were statistically significantly higher than those in control group(P<0.01).(2)There was no statistically significant difference in LVEF in patients with different hypertension grades in observation group(P>0.05);serum levels of RBP,NT-proBNP and CP,and LAVI in patients with hypertension grade 2 and 3 in observation group were statistically significantly higher than those in patients with hypertension grade 1,meanwhile serum levels of RBP,NT-proBNP and CP,and LAVI in patients with hypertension grade 3 in observation group were statistically significantly higher than those in patients with hypertension grade 2(P<0.05).(3)There was no statistically significant difference in LVEF in patients with different NYHA grades in observation group(P>0.05);serum levels of RBP,NT-proBNP and CP,and LAVI in patients with NYHA grade Ⅲ and Ⅳ were statistically significantly higher than those in patients with NYHA grade Ⅱ,meanwhile serum levels of RBP,NT-proBNP and CP,and LAVI in patients with NYHA grade Ⅳ were statistically significantly higher than those in patients with NYHA grade Ⅲ(P<0.05).(4)ROC curve showed that,AUC of serum RBP level in the diagnosis of HFpEF in patients with hypertension was 0.888,of serum NT-proBNP level was 0.913,of serum CP level was 0.835,and combined detection of the above three was 0.978;AUC of combined detection of serum levels of RBP,NT-proBNP and CP in the diagnosis of HFpEF in patients with hypertension was statistically significantly higher than that of serum level of RBP,NT-proBNP and CP individually(P<0.05);there was no statistically significant difference in AUC of serum level of RBP,NT-proBNP and CP individually in the diagnosis of HFpEF in patients with hypertension(P>0.05). Conclusion Serum levels of RBP,NT-proBNP and CP raise with increase of hypertension grade and NYHA grade,which may be involved in the occurrence and development of HFpEF in patients with hypertension,and combined detection of the above three can effectively improve the diagnostic value of HFpEF in patients with hypertension.
Background Heart failure with preserved ejection fraction(HFpEF)is a common type of chronic heart failure,but There are no clear diagnostic indicators and specific drugs,so early diagnosis has important clinical value for reducing patients' burden and saving their lives. Objective To observe the diagnostic value of serum levels of retinol binding protein(RBP),NT-proBNP and ceruloplasmin(CP)in hypertension patients complicated with HFpEF. Methods A total of 115 hypertension patients complicated with HFpEF were enrolled as observation group in Qingpu Branch of Zhongshan Hospital Affiliated to Fudan University from 2016 to 2017,meanwhile 35 patients with hypertension but no heart failure were selected as control group. Serum levels of RBP,NT-proBNP and CP,and cardiac function indicators(including LVEF and LAVI)were compared between the two groups,in patients with different hypertension grades and different NYHA grades in observation group. ROC curve was drawn to evaluate the diagnostic value of serum levels of RBP,NT-proBNP and CP for HFpEF in patients with hypertension. Results(1)There was no statistically significant difference in LVEF between the two groups(P>0.05);serum levels of RBP,NT-proBNP and CP,and LAVI in observation group were statistically significantly higher than those in control group(P<0.01).(2)There was no statistically significant difference in LVEF in patients with different hypertension grades in observation group(P>0.05);serum levels of RBP,NT-proBNP and CP,and LAVI in patients with hypertension grade 2 and 3 in observation group were statistically significantly higher than those in patients with hypertension grade 1,meanwhile serum levels of RBP,NT-proBNP and CP,and LAVI in patients with hypertension grade 3 in observation group were statistically significantly higher than those in patients with hypertension grade 2(P<0.05).(3)There was no statistically significant difference in LVEF in patients with different NYHA grades in observation group(P>0.05);serum levels of RBP,NT-proBNP and CP,and LAVI in patients with NYHA grade Ⅲ and Ⅳ were statistically significantly higher than those in patients with NYHA grade Ⅱ,meanwhile serum levels of RBP,NT-proBNP and CP,and LAVI in patients with NYHA grade Ⅳ were statistically significantly higher than those in patients with NYHA grade Ⅲ(P<0.05).(4)ROC curve showed that,AUC of serum RBP level in the diagnosis of HFpEF in patients with hypertension was 0.888,of serum NT-proBNP level was 0.913,of serum CP level was 0.835,and combined detection of the above three was 0.978;AUC of combined detection of serum levels of RBP,NT-proBNP and CP in the diagnosis of HFpEF in patients with hypertension was statistically significantly higher than that of serum level of RBP,NT-proBNP and CP individually(P<0.05);there was no statistically significant difference in AUC of serum level of RBP,NT-proBNP and CP individually in the diagnosis of HFpEF in patients with hypertension(P>0.05). Conclusion Serum levels of RBP,NT-proBNP and CP raise with increase of hypertension grade and NYHA grade,which may be involved in the occurrence and development of HFpEF in patients with hypertension,and combined detection of the above three can effectively improve the diagnostic value of HFpEF in patients with hypertension.
引文
[1]BORLAUG B A,ANSTROM K J,LEWIS G D,et al.Effect of Inorganic Nitrite vs Placebo on Exercise Capacity Among Patients With Heart Failure With Preserved Ejection Fraction:The INDIEHFpEF Randomized Clinical Trial[J].JAMA,2018,320(17):1764-1773.DOI:10.1001/jama.2018.14852.
[2]RICH J D,BURNS J,FREED B H,et al.Meta-Analysis Global Group in Chronic(MAGGIC)Heart Failure Risk Score:Validation of a Simple Tool for the Prediction of Morbidity and Mortality in Heart Failure With Preserved Ejection Fraction[J].J Am Heart Assoc,2018,7(20):e9594.DOI:10.1161/JAHA.118.009594.
[3]贾冬霞,彭君臣,刘思泰,等.老年高血压病患者与血浆视黄醇结合蛋白4水平相关性研究[J].心肺血管病杂志,2017,36(7):511-513,533.DOI:10.3969/j.issn.1007-5062.2017.07.002.
[4]宋婷婷,贾红丹,国强华,等.高血压合并射血分数保留心衰老年患者N末端脑钠肽前体水平与心脏超声改变的相关性[J].中国老年学杂志,2018,38(6):1307-1309.DOI:10.3969/j.issn.1005-9202.2018.06.012.
[5]宋婷婷,崔蕊,国强华,等.老年高血压合并射血分数保留的心衰患者血浆BNP、同型半胱氨酸、C反应蛋白水平变化的关系及意义[J].标记免疫分析与临床,2017,24(2):200-203.DOI:10.11748/bjmy.issn.1006-1703.2017.02.019.
[6]DADU R T,DODGE R,NAMBI V,et al.Ceruloplasmin and heart failure in the Atherosclerosis Risk in Communities study[J].Circ Heart Fail,2013,6(5):936-943.DOI:10.1161/CIRCHEARTFAILURE.113.000270.
[7]XU Y,LIN H,ZHOU Y,et al.Ceruloplasmin and the extent of heart failure in ischemic and nonischemic cardoimyopathy patients[J].Mediators Inflamm,2013:348145.DOI:10.1155/2013/348145.
[8]射血分数正常心力衰竭诊治的中国专家共识[J].中国医刊,2010,45(11):63-67.DOI:10.3969/j.issn.1008-1070.2010.11.027.
[9]XANTHOPOULOS A,TRIPOSKIADIS F,STARLING R C.Heart failure with preserved ejection fraction:Classification based upon phenotype is essential for diagnosis and treatment[J].Trends Cardoivasc Med,2018,28(6):392-400.DOI:10.1016/j.tcm.2018.01.001.
[10]BEKFANI T,PELLICORI P,MORRIS D,et al.Iron deficiency in patients with heart failure with preserved ejection fraction and its association with reduced exercise capacity,muscle strength and quality of life[J].Clin Res Cardoil,2019,108(2):203-211.DOI:10.1007/s00392-018-1344-x.
[11]方宗信,黄瑞茹,夏昕,等.原发性高血压肾病患者血清胱抑素C和视黄醇结合蛋白检测的临床意义[J].海南医学,2013,24(6):853-855.DOI:10.3969/j.issn.1003-6350.2013.06.0364.
[12]马睿,刘洁,成佳景,等.尿视黄醇结合蛋白、转化生长因子β1和转铁蛋白对妊娠期高血压疾病肾损害的诊断意义[J].同济大学学报(医学版),2017,38(6):97-101.DOI:10.16118/j.1008-0392.2017.06.020.
[13]KAMANO C,OSAWA H,HASHIMOTO K,et al.N-Terminal pro-brain natriuretic peptide as a predictor of heart failure with preserved ejection fraction in hemodialysis patients without fluid overload[J].Blood Purif,2012,33(1/3):37-43.DOI:10.1159/000333841.
[14]CARLSEN C M,BAY M,KIRK V,et al.Prevalence and prognosis of heart failure with preserved ejection fraction and elevated N-terminal pro brain natriuretic peptide:a 10-year analysis from the Copenhagen Hospital Heart Failure Study[J].Eur J Heart Fail,2012,14(3):240-247.DOI:10.1093/eurjhf/hfs003.
[15]MASUTANI S,SAIKI H,KURISHIMA C,et al.Heart failure with preserved ejection fraction in children:hormonal imbalance between aldosterone and brain natriuretic peptide[J].Circ J,2013,77(9):2375-2382.
[16]SAVIC-RADOJEVIC A,PLJESA-ERCEGOVAC M,MATIC M,et al.Novel Biomarkers of Heart Failure[J].Adv Clin Chem,2017,79:93-152.DOI:10.1016/bs.acc.2016.09.002.
[17]HAMMADAH M,FAN Y,WU Y,et al.Prognostic value of elevated serum ceruloplasmin levels in patients with heart failure[J]. J Card Fail,2014,20(12):946-952.DOI:10.1016/j.cardfail.2014.08.001.
[18]CABASSI A,BINNO S M,TEDESCHI S,et al.MyeloperoxidaseRelated Chlorination Activity Is Positively Associated with Circulating Ceruloplasmin in Chronic Heart Failure Patients:Relationship with Neurohormonal,Inflammatory,and Nutritional Parameters[J].BiomedResInt,2015:691693.DOI:10.1155/2015/691693.
[2]RICH J D,BURNS J,FREED B H,et al.Meta-Analysis Global Group in Chronic(MAGGIC)Heart Failure Risk Score:Validation of a Simple Tool for the Prediction of Morbidity and Mortality in Heart Failure With Preserved Ejection Fraction[J].J Am Heart Assoc,2018,7(20):e9594.DOI:10.1161/JAHA.118.009594.
[3]贾冬霞,彭君臣,刘思泰,等.老年高血压病患者与血浆视黄醇结合蛋白4水平相关性研究[J].心肺血管病杂志,2017,36(7):511-513,533.DOI:10.3969/j.issn.1007-5062.2017.07.002.
[4]宋婷婷,贾红丹,国强华,等.高血压合并射血分数保留心衰老年患者N末端脑钠肽前体水平与心脏超声改变的相关性[J].中国老年学杂志,2018,38(6):1307-1309.DOI:10.3969/j.issn.1005-9202.2018.06.012.
[5]宋婷婷,崔蕊,国强华,等.老年高血压合并射血分数保留的心衰患者血浆BNP、同型半胱氨酸、C反应蛋白水平变化的关系及意义[J].标记免疫分析与临床,2017,24(2):200-203.DOI:10.11748/bjmy.issn.1006-1703.2017.02.019.
[6]DADU R T,DODGE R,NAMBI V,et al.Ceruloplasmin and heart failure in the Atherosclerosis Risk in Communities study[J].Circ Heart Fail,2013,6(5):936-943.DOI:10.1161/CIRCHEARTFAILURE.113.000270.
[7]XU Y,LIN H,ZHOU Y,et al.Ceruloplasmin and the extent of heart failure in ischemic and nonischemic cardoimyopathy patients[J].Mediators Inflamm,2013:348145.DOI:10.1155/2013/348145.
[8]射血分数正常心力衰竭诊治的中国专家共识[J].中国医刊,2010,45(11):63-67.DOI:10.3969/j.issn.1008-1070.2010.11.027.
[9]XANTHOPOULOS A,TRIPOSKIADIS F,STARLING R C.Heart failure with preserved ejection fraction:Classification based upon phenotype is essential for diagnosis and treatment[J].Trends Cardoivasc Med,2018,28(6):392-400.DOI:10.1016/j.tcm.2018.01.001.
[10]BEKFANI T,PELLICORI P,MORRIS D,et al.Iron deficiency in patients with heart failure with preserved ejection fraction and its association with reduced exercise capacity,muscle strength and quality of life[J].Clin Res Cardoil,2019,108(2):203-211.DOI:10.1007/s00392-018-1344-x.
[11]方宗信,黄瑞茹,夏昕,等.原发性高血压肾病患者血清胱抑素C和视黄醇结合蛋白检测的临床意义[J].海南医学,2013,24(6):853-855.DOI:10.3969/j.issn.1003-6350.2013.06.0364.
[12]马睿,刘洁,成佳景,等.尿视黄醇结合蛋白、转化生长因子β1和转铁蛋白对妊娠期高血压疾病肾损害的诊断意义[J].同济大学学报(医学版),2017,38(6):97-101.DOI:10.16118/j.1008-0392.2017.06.020.
[13]KAMANO C,OSAWA H,HASHIMOTO K,et al.N-Terminal pro-brain natriuretic peptide as a predictor of heart failure with preserved ejection fraction in hemodialysis patients without fluid overload[J].Blood Purif,2012,33(1/3):37-43.DOI:10.1159/000333841.
[14]CARLSEN C M,BAY M,KIRK V,et al.Prevalence and prognosis of heart failure with preserved ejection fraction and elevated N-terminal pro brain natriuretic peptide:a 10-year analysis from the Copenhagen Hospital Heart Failure Study[J].Eur J Heart Fail,2012,14(3):240-247.DOI:10.1093/eurjhf/hfs003.
[15]MASUTANI S,SAIKI H,KURISHIMA C,et al.Heart failure with preserved ejection fraction in children:hormonal imbalance between aldosterone and brain natriuretic peptide[J].Circ J,2013,77(9):2375-2382.
[16]SAVIC-RADOJEVIC A,PLJESA-ERCEGOVAC M,MATIC M,et al.Novel Biomarkers of Heart Failure[J].Adv Clin Chem,2017,79:93-152.DOI:10.1016/bs.acc.2016.09.002.
[17]HAMMADAH M,FAN Y,WU Y,et al.Prognostic value of elevated serum ceruloplasmin levels in patients with heart failure[J]. J Card Fail,2014,20(12):946-952.DOI:10.1016/j.cardfail.2014.08.001.
[18]CABASSI A,BINNO S M,TEDESCHI S,et al.MyeloperoxidaseRelated Chlorination Activity Is Positively Associated with Circulating Ceruloplasmin in Chronic Heart Failure Patients:Relationship with Neurohormonal,Inflammatory,and Nutritional Parameters[J].BiomedResInt,2015:691693.DOI:10.1155/2015/691693.