林祖近等
[摘要]目的探討冠心病患者血漿腦鈉肽(BNP)與冠狀動(dòng)脈病變嚴(yán)重程度及心臟變時(shí)性的相關(guān)性。方法記錄冠心病患者血漿BNP水平及心臟變時(shí)性指標(biāo),包括rHR和HRR,并記錄冠狀動(dòng)脈造影(CAG)結(jié)果,計(jì)算Gensini評(píng)分,對(duì)比分析無癥狀性心肌缺血、穩(wěn)定型心絞痛及不穩(wěn)定型心絞痛3組患者血漿BNP水平及心臟變時(shí)性指標(biāo)差異。評(píng)價(jià)血漿BNP水平與冠狀動(dòng)脈病變嚴(yán)重程度及心臟變時(shí)性指標(biāo)相關(guān)性。結(jié)果本研究共納入462例冠心病患者,單因素方差分析結(jié)果顯示各組間BNP水平差異均有統(tǒng)計(jì)學(xué)意義(均P<0.05);無癥狀性心肌缺血與不穩(wěn)定型心絞痛心臟變時(shí)性指標(biāo)rHR比較差異有統(tǒng)計(jì)學(xué)意義(P<0.05)。Person相關(guān)分析顯示,冠心病患者血漿BNP水平與冠狀動(dòng)脈病變Gensini評(píng)分呈正相關(guān)(r=0.43,P<0.05),與心臟變時(shí)性指標(biāo)rHR及HRR均呈負(fù)相關(guān)(r=-0.34,-0.40,均P<0.05)。結(jié)論冠心病患者血漿BNP與冠狀動(dòng)脈病變程度及心臟變時(shí)性指標(biāo)rHR和HRR密切相關(guān),對(duì)于評(píng)價(jià)冠心病心臟功能的改變有重要的臨床價(jià)值。
[關(guān)鍵詞]冠心??;腦鈉肽;心臟變時(shí)性
中圖分類號(hào):R541.4文獻(xiàn)標(biāo)識(shí)碼:A文章編號(hào):1009_816X(2014)06_0470_04
[Abstract] Objective To investigate the correlation of degree of coronary artery lesion and chronotropic response in patients with coronary heart disease. Methods BNP and chronotropic response including rHR and HRR were recorded of patients with coronary heart disease, outcomes of coronary angiography (CAG) and the score of Gensini were also recorded. Contrastive analysis of BNP and chronotropic response of three groups, myocardial ischemia, stable angina pectoris (SAP) and unstable angina pectoris (UAP), were taken and the correlation of degree of coronary artery lesion and chronotropic response was evaluated. Results A total of 462 patients with coronary heart disease were enrolled. Analysis of Variance showed there were significant differences of the level of BNP among the three groups (all P<0.05). There were significant differences of rHR between the group of myocardial ischemia and UAP (P<0.05). There was positive correlation between BNP and the score of Gensini (r=0.43,P<0.05). There was negative correlations between BNP and rHR, so did BNP and HRR (r=-0.34,-0.40, all P<0.05). Conclusions BNP, rHR, HRR, and degree of coronary artery lesion are closely related and valuable for the evaluation of cardiac function in patients with coronary heart disease.
[Key words] Coronary disease; Brain natriuretic peptide; Chronotropic response
腦鈉肽(brain natriuretic peptide,BNP)又稱B型利鈉肽(B_type natriuretic peptide),是利尿肽家族中最為重要的一員。早期已有研究提示血漿BNP水平可為心力衰竭、急性心肌梗死(acute myocardial infarction,AMI)及急性冠狀動(dòng)脈綜合征(acute coronary syndromes,ACS)的診斷及評(píng)估提供很大的幫助[1]。心臟變時(shí)性與心肌缺血程度密切相關(guān),可反映心臟自主神經(jīng)功能狀態(tài),亦可用于評(píng)價(jià)冠心病患者心臟功能的改變。臨床中關(guān)于冠心病患者血漿BNP水平、冠狀動(dòng)脈病變嚴(yán)重程度及心臟變時(shí)性相關(guān)性研究近年來開展較少。本文旨在分析冠心病患者血漿BNP水平與冠狀動(dòng)脈病變嚴(yán)重程度及心臟變時(shí)性的相關(guān)性,為冠心病臨床診斷提供一定的臨床參考。
1資料與方法
1.1一般資料:2008年1月至2013年12月間就診于臺(tái)州市中心醫(yī)院心內(nèi)科并接受冠狀動(dòng)脈造影檢查(coronary angiogram,CAG)的462例冠心病患者被納入本研究,診斷標(biāo)準(zhǔn)參照我國(guó)《冠狀動(dòng)脈粥樣硬化性心臟病診斷標(biāo)準(zhǔn)》2010版。其中男327例,女135例,年齡39~73歲,平均(54.91±14.24)歲,病程2~64個(gè)月,平均(38.23±12.07)月,合并高血壓299例,陳舊性心肌梗死33例,高脂血癥59例,2型糖尿病43例;有吸煙史315例。排除標(biāo)準(zhǔn):合并肺動(dòng)脈高壓,肺源性心臟病,嚴(yán)重肝腎功能不全,血液病,嚴(yán)重感染,惡性腫瘤,或因心功能不全或急性心肌梗死不能耐受檢查者均未納入本研究。所有患者納入研究前均簽署知情同意書。endprint
1.2方法:所有患者于首次發(fā)病后24h內(nèi)未使用或停用β受體阻滯劑、阿托品、硝酸酯類藥物48小時(shí)后抽取肘靜脈血3ml,置入含乙二胺四乙酸抗凝劑的試管中,離心機(jī)中離心10min,離心速率為3000轉(zhuǎn)/min,采用酶聯(lián)免疫吸附測(cè)定法(enzyme_linked immunosorbent assay,ELISA)測(cè)定血漿BNP水平。試驗(yàn)所需試劑由Biomerieux.S.A公司生產(chǎn)。本研究血漿BNP正常參考范圍為0~125ng/L?;顒?dòng)平板設(shè)備為TM_200(北泠通用電氣公司),采用Bruce分級(jí)方案。運(yùn)動(dòng)終止目標(biāo):(1)達(dá)到亞極量心率[(220-年齡)×85%];(2)出現(xiàn)典型心絞痛癥狀或明顯的癥狀和體征;(3)以R波為主的導(dǎo)聯(lián)出現(xiàn)缺血性ST段改變(ST段水平或下斜型壓低≥0.1mV,且持續(xù)2min以上);(4)血壓改變(血壓下降≥10mmHg,或血壓升高>220/120mmHg);(5)出現(xiàn)嚴(yán)重心律失常;(6)不能耐受運(yùn)動(dòng)量,要求終止。禁忌證:(1)高度危險(xiǎn)的不穩(wěn)定性心絞痛;(2)引起癥狀或影響血流動(dòng)力學(xué)的未控制的心律失常;(3)軀體障礙影響安全性或運(yùn)動(dòng)量等。記錄所有患者運(yùn)動(dòng)時(shí)間、運(yùn)動(dòng)后最高心率及靜息心率等數(shù)值,并計(jì)算心臟變時(shí)性指標(biāo)、運(yùn)動(dòng)最高心率與預(yù)測(cè)最大心率值之比(ratio of heart rate,rHR)。預(yù)測(cè)最大心率值=(220-年齡)次/分,心率儲(chǔ)備率(heart rate reserve,HRR)=(最大心率-靜息心率)/(220-年齡-靜息心率)×100%。使用德國(guó)西門子公司血管造影機(jī),采用Judkins法行常規(guī)冠狀動(dòng)脈造影檢查,對(duì)左主干、回旋支、前降支、右冠狀動(dòng)脈及其主要分支的狹窄程度進(jìn)行定量評(píng)價(jià),以主要冠狀動(dòng)脈管腔直徑狹窄≥50%定義為冠狀動(dòng)脈造影陽(yáng)性。冠狀動(dòng)脈病變嚴(yán)重程度以Gensini評(píng)分[2]進(jìn)行評(píng)價(jià),見表1,根據(jù)評(píng)分將冠狀動(dòng)脈病變程度分為≤20分組、21~39分組及≥40分組3組。
表1冠狀動(dòng)脈病變Gensini評(píng)分
冠狀動(dòng)脈腔徑狹窄程度Gensini評(píng)分(分)無腔徑狹窄0≤25%1≤50%2≤75%4≤90%8≤99%16100%321.3統(tǒng)計(jì)學(xué)處理:采用SPSS11.5版統(tǒng)計(jì)軟件進(jìn)行數(shù)據(jù)分析,計(jì)量資料以(x-±s)表示。3組間比較采用單因素方差分析,兩組間比較采用LSD檢驗(yàn)。血漿BNP水平與冠狀動(dòng)脈病變嚴(yán)重程度及心臟變時(shí)性相關(guān)性采用Person相關(guān)分析。P<0.05為差異有統(tǒng)計(jì)學(xué)意義。
3討論目前臨床中已有研究提出冠心病患者血漿BNP水平與冠狀動(dòng)脈病變程度存在一定的相關(guān)性。CAG作為臨床應(yīng)用中診斷冠心病的“金標(biāo)準(zhǔn)”,可提供冠狀動(dòng)脈病變的量化指標(biāo),早在1983年由美國(guó)學(xué)者提出冠狀動(dòng)脈病變嚴(yán)重程度的Gensini評(píng)分標(biāo)準(zhǔn)[3]。冠狀動(dòng)脈病變的量化評(píng)價(jià),為冠心病的診斷和介入治療提供了直觀的臨床數(shù)據(jù)支持。Goyal等[1]的研究結(jié)果提示,隨著冠狀動(dòng)脈病變支數(shù)的增加,冠心病患者血漿BNP水平顯著增高,血漿BNP水平與冠狀動(dòng)脈病變Gensini評(píng)分呈正相關(guān)(r=0.68,P<0.01)。Palazzuoli等[4]的研究探討了冠心病患者血漿BNP水平與冠狀動(dòng)脈病變程度的相關(guān)性,結(jié)果提示隨著病變嚴(yán)重程度的增加,血漿BNP水平呈遞增趨勢(shì);隨著冠狀動(dòng)脈病變數(shù)量的增加,血漿BNP水平亦呈遞增趨勢(shì),血漿BNP水平與冠狀動(dòng)脈病變Gensini評(píng)分呈正相關(guān)(r=0.38,P<0.01)。本文結(jié)果提示,隨著冠狀動(dòng)脈病變Gensini評(píng)分的增加,冠心病患者血漿BNP水平顯著增加,兩者呈正相關(guān)。但本文結(jié)果血漿BNP水平與上述研究結(jié)果存在一些差異,這可能與入選患者存在不同合并癥及前期治療或處理不同有關(guān)。臨床中需要進(jìn)一步大樣本研究,通過ROC曲線界定不同分型、不同冠狀動(dòng)脈病變程度的血漿BNP水平。正常情況下,心率隨機(jī)體代謝需要的增加而增加,基本呈線性關(guān)系,當(dāng)心率不能隨著機(jī)體代謝需要的增加而增加時(shí)稱為心臟變時(shí)性功能不全。心臟變時(shí)性是心臟電活動(dòng)和心臟節(jié)律方面的一個(gè)重要功能。早期已有大量的研究證明心臟變時(shí)功能不全是冠心病死亡率升高的強(qiáng)烈預(yù)測(cè)因子[5]。Lee等[6]進(jìn)行了105例臨床表現(xiàn)為胸痛的疑似冠心病患者血漿BNP與心臟變時(shí)性指標(biāo)HRR相關(guān)性研究,結(jié)果顯示冠心病患者治療前血漿BNP與心臟變時(shí)性指標(biāo)HRR呈負(fù)相關(guān)(r=-0.28,P<0.01)。而Benes等[7]的研究則以心力衰竭患者為研究對(duì)象,結(jié)果提示心力衰竭患者HRR與血漿BNP水平間無顯著相關(guān)性。本文納入研究者均為冠心病患者,而心力衰竭患者因未能耐受相關(guān)檢查而納入排除范圍。研究結(jié)果提示冠心病血漿BNP與心臟變時(shí)性指標(biāo)HRR呈負(fù)相關(guān),與Lee等[6]的研究結(jié)果相似。rHR作為評(píng)價(jià)心率儲(chǔ)備的另一指標(biāo),近年來相關(guān)研究較少,臨床中尚無與血漿BNP水平的相關(guān)研究。本研究結(jié)果亦提示冠心病患者血漿BNP水平與心臟變時(shí)性指標(biāo)rHR呈負(fù)相關(guān),揭示了心臟變時(shí)性指標(biāo)與血漿BNP水平相關(guān)性,以期為冠心病的診斷及預(yù)后提供更大的幫助。本文提示血漿BNP水平與心臟變時(shí)性指標(biāo)相關(guān)性較好,對(duì)冠狀動(dòng)脈病變程度及病變支數(shù)可做定量評(píng)價(jià)。然而,冠心病患者合并癥種類繁多、血漿BNP水平可受藥物或運(yùn)動(dòng)影響[8]、心臟變時(shí)性指標(biāo)易受多種因素影響等,因此,不同病變程度的冠心病血漿BNP水平臨床參考范圍的確定,仍需大樣本的臨床研究,這為我們的進(jìn)一步研究提供了更廣泛的空間。
參考文獻(xiàn)
[1]Goyal BM, Sharma SM, Walia M. B_Type natriuretic peptide levels predict extent and severity of coronary artery disease in non_ST elevation acute coronary syndrome and normal left ventricular function [J]. Indian Heart J,2014,66(2):183-187.endprint
[2]Choi EY, Kwon HM, Yoon YW, et al. Assessment of extent of myocardial ischemia in patients with non_ST elevation acute coronary syndrome using serum B_type natriuretic peptide level[J]. Yonsei Med J,2004,45(2):255-262.
[3]Gensini GG. A more meaningful scoring system for determining the severity of coronary heart disease[J]. Am J Cardiol,1983,51(3):606.
[4]Palazzuoli A, Maisel A, Caputo M, et al. B_type natriuretic peptide levels predict extent and severity of coronary disease in non_ST elevation coronary syndromes and normal left ventricular systolic function[J]. Regul Pept,2011,167(1):129-133.
[5]Lauer MS, Okin PM, Larson MG, et al. Impaired heart rate response to graded exercise. Prognostic implications of chronotropic incompetence in the Framingham Heart Study[J]. Circulation,1996,93(8):1520-1526.
[6]Lee JE, Kim BS, Park W, et al. The relationship between heart rate recovery and brain natruretic Peptide in patients with chest discomfort: a study for relationship between heart rate recovery and pre_exercise, post_exercise levels of brain natruretic Peptide in patients with normal systolic function and chest discomfort[J]. Korean Circ J,2010,40(4):172-178.
[7]Benes J, Kotrc M, Borlaug BA, et al. Resting heart rate and heart rate reserve in advanced heart failure have distinct pathophysiologic correlates and prognostic impact: a prospective pilot study[J]. JACC Heart Fail,2013,1(3):259-266.
[8]Lu W, Fu C, Chen Y, et al. Multiplex detection of B_type natriuretic peptide, cardiac troponin I and C_reactive protein with photonic suspension array[J]. PLoS One,2012,7(7):e41448.
(收稿日期:2014_6_20)endprint
[2]Choi EY, Kwon HM, Yoon YW, et al. Assessment of extent of myocardial ischemia in patients with non_ST elevation acute coronary syndrome using serum B_type natriuretic peptide level[J]. Yonsei Med J,2004,45(2):255-262.
[3]Gensini GG. A more meaningful scoring system for determining the severity of coronary heart disease[J]. Am J Cardiol,1983,51(3):606.
[4]Palazzuoli A, Maisel A, Caputo M, et al. B_type natriuretic peptide levels predict extent and severity of coronary disease in non_ST elevation coronary syndromes and normal left ventricular systolic function[J]. Regul Pept,2011,167(1):129-133.
[5]Lauer MS, Okin PM, Larson MG, et al. Impaired heart rate response to graded exercise. Prognostic implications of chronotropic incompetence in the Framingham Heart Study[J]. Circulation,1996,93(8):1520-1526.
[6]Lee JE, Kim BS, Park W, et al. The relationship between heart rate recovery and brain natruretic Peptide in patients with chest discomfort: a study for relationship between heart rate recovery and pre_exercise, post_exercise levels of brain natruretic Peptide in patients with normal systolic function and chest discomfort[J]. Korean Circ J,2010,40(4):172-178.
[7]Benes J, Kotrc M, Borlaug BA, et al. Resting heart rate and heart rate reserve in advanced heart failure have distinct pathophysiologic correlates and prognostic impact: a prospective pilot study[J]. JACC Heart Fail,2013,1(3):259-266.
[8]Lu W, Fu C, Chen Y, et al. Multiplex detection of B_type natriuretic peptide, cardiac troponin I and C_reactive protein with photonic suspension array[J]. PLoS One,2012,7(7):e41448.
(收稿日期:2014_6_20)endprint
[2]Choi EY, Kwon HM, Yoon YW, et al. Assessment of extent of myocardial ischemia in patients with non_ST elevation acute coronary syndrome using serum B_type natriuretic peptide level[J]. Yonsei Med J,2004,45(2):255-262.
[3]Gensini GG. A more meaningful scoring system for determining the severity of coronary heart disease[J]. Am J Cardiol,1983,51(3):606.
[4]Palazzuoli A, Maisel A, Caputo M, et al. B_type natriuretic peptide levels predict extent and severity of coronary disease in non_ST elevation coronary syndromes and normal left ventricular systolic function[J]. Regul Pept,2011,167(1):129-133.
[5]Lauer MS, Okin PM, Larson MG, et al. Impaired heart rate response to graded exercise. Prognostic implications of chronotropic incompetence in the Framingham Heart Study[J]. Circulation,1996,93(8):1520-1526.
[6]Lee JE, Kim BS, Park W, et al. The relationship between heart rate recovery and brain natruretic Peptide in patients with chest discomfort: a study for relationship between heart rate recovery and pre_exercise, post_exercise levels of brain natruretic Peptide in patients with normal systolic function and chest discomfort[J]. Korean Circ J,2010,40(4):172-178.
[7]Benes J, Kotrc M, Borlaug BA, et al. Resting heart rate and heart rate reserve in advanced heart failure have distinct pathophysiologic correlates and prognostic impact: a prospective pilot study[J]. JACC Heart Fail,2013,1(3):259-266.
[8]Lu W, Fu C, Chen Y, et al. Multiplex detection of B_type natriuretic peptide, cardiac troponin I and C_reactive protein with photonic suspension array[J]. PLoS One,2012,7(7):e41448.
(收稿日期:2014_6_20)endprint