無(wú)癥狀冠心病頸動(dòng)脈內(nèi)膜中層厚度與血小板相關(guān)指標(biāo)和超敏C反應(yīng)蛋白的相關(guān)性

施根林, 腰利云,劉 華，祝 峰

無(wú)癥狀冠心病頸動(dòng)脈內(nèi)膜中層厚度與血小板相關(guān)指標(biāo)和超敏C反應(yīng)蛋白的相關(guān)性

施根林1, 腰利云2,劉 華3，祝 峰4

目的 探討無(wú)癥狀冠心病人群使用彩色多普勒超聲評(píng)估頸動(dòng)脈內(nèi)膜中層厚度(carotid intima-media thickness,IMT)與血小板平均體積(mean platelet volume,MPV)、血小板體積分布寬度(platelet volume distribution width，PDW)和超敏C反應(yīng)蛋白(hypersensitive c-reactive protein，Hs-CRP)之間的相關(guān)性。方法 選取符合無(wú)癥狀冠心病診斷標(biāo)準(zhǔn)的患者85例做為研究對(duì)象。根據(jù)頸動(dòng)脈IMT結(jié)果分為正常組(n=30例)和增厚組(n=55例)，比較兩組之間TG、UA、MPV、PDW、Hs-CRP的差別，然后再采用多元線性回歸分析頸動(dòng)脈IMT的相關(guān)因素。結(jié)果 IMT增厚組TG、UA、MPV、PDW、Hs-CRP水平明顯高于正常組,兩組之間的差異有統(tǒng)計(jì)學(xué)意義(均P<0.05),多元線性回歸分析表明頸動(dòng)脈IMT與MPV(β=0.215,P<0.001),PDW(β=-0.039,P=0.037),Hs-CRP(β=0.258,P=0.001)相關(guān)。結(jié)論 MPV、PDW、Hs-CRP與無(wú)癥狀頸動(dòng)脈粥樣硬化呈獨(dú)立相關(guān)，MPV升高可能是動(dòng)脈粥樣硬化初始階段關(guān)鍵的生物學(xué)標(biāo)記物。

頸動(dòng)脈內(nèi)膜中層厚度；血小板平均體積；血小板體積分布寬度；超敏C反應(yīng)蛋白；動(dòng)脈粥樣硬化

頸動(dòng)脈內(nèi)膜中層厚度(carotid intima-media thickness, IMT)增厚可反映早期動(dòng)脈粥樣硬化情況[1]。動(dòng)脈粥樣硬化過(guò)程中有血小板的黏附聚集釋放活化等過(guò)程，致使中層平滑肌細(xì)胞發(fā)生遷移增生和炎性細(xì)胞浸潤(rùn)等一系列連鎖反應(yīng)。近幾年，國(guó)外廣泛從血小板活化和炎性反應(yīng)角度出發(fā)，對(duì)動(dòng)脈硬化的相關(guān)機(jī)制進(jìn)行探討。筆者通過(guò)分析無(wú)癥狀冠心病人群IMT與血小板平均體積MPV、血小板體積分布寬度PDW和超敏C反應(yīng)蛋白Hs-CRP之間的相關(guān)性，為動(dòng)脈粥樣硬化疾病的預(yù)防和臨床治療工作提供幫助。

1 對(duì)象與方法

1.1 對(duì)象 選擇2014年2-11月在武警江蘇總隊(duì)醫(yī)院心臟內(nèi)科門(mén)診就醫(yī)，并符合無(wú)癥狀冠心病診斷標(biāo)準(zhǔn)[2]的患者85例。其中，男37例，女48例；年齡23～65歲，平均39歲。均進(jìn)行超聲心動(dòng)圖、彩色多普勒超聲檢測(cè)頸動(dòng)脈IMT及冠心病相關(guān)危險(xiǎn)因素檢測(cè)，如收縮壓(SBP)、舒張壓(DBP)、心率(HR)、血糖(GLU)、三酰甘油(TG)、總膽固醇(TC)、Hs-CRP、尿酸(UA)等。排除既往有冠心病者或心肌缺血的臨床癥狀，以及心力衰竭、周?chē)芗膊?、腎臟疾病、肝膽疾病、惡性腫瘤、高血壓或糖尿病等。

1.2 方法

1.2.1 血液指標(biāo)檢測(cè) 清晨空腹抽取靜脈血，MPV、PDW通過(guò)Sysmex XE-2100全自動(dòng)血液計(jì)數(shù)儀檢測(cè)；采用酶法檢測(cè)GLU、TG、TC、UA，采用免疫比濁法檢測(cè)Hs-CRP，儀器為羅氏P800全自動(dòng)生化分析儀。

1.2.2 頸動(dòng)脈IMT檢測(cè) 采用美國(guó)GE公司生產(chǎn)的VIVID7超聲多普勒檢測(cè)儀，先行常規(guī)二維的超聲心動(dòng)圖檢測(cè)左室射血分?jǐn)?shù)(EF%)。再讓受檢者取臥位，低枕，從頸根部逐漸向上探查頸總動(dòng)脈，頸內(nèi)外動(dòng)脈分叉處和頸內(nèi)動(dòng)脈顱外段頸動(dòng)脈IMT。頸動(dòng)脈IMT增厚判斷標(biāo)準(zhǔn)：頸動(dòng)脈管壁厚度≥1 mm為管壁增厚[3]，<1 mm為正常。根據(jù)頸動(dòng)脈IMT結(jié)果分為正常組(30例)和增厚組(55例)，兩組IMT水平分別為(0.70±0.14)mm和(1.49±0.21)mm。

2 結(jié) 果

2.1 單因素分析 頸動(dòng)脈IMT增厚組中TG、UA、MPV、PDW、Hs-CRP水平明顯高于正常組，且差異有統(tǒng)計(jì)學(xué)意義(P<0.05,表1)。

2.2 多因素分析 TG、UA、MPV、PDW 和Hs-CRP 5個(gè)因素中，只有MPV、PDW和 Hs-CRP 3個(gè)因素最終進(jìn)入了回歸方程，最佳的方程為IMT=-0.671 + 0.215MPV-0.039 PDW+0.258 Hs-CRP,回歸線性檢驗(yàn)F=32.505,P<0.001(表2)。

表1 頸動(dòng)脈IMT增厚組和正常組一般資料的比較 ±s;(n;%)]

表2 頸動(dòng)脈IMT與可能的影響因素的多元逐步性回歸分析

3 討 論

動(dòng)脈粥樣硬化進(jìn)展的研究已取得重要進(jìn)展，特別是頸動(dòng)脈IMT檢測(cè)已成為了解全身動(dòng)脈硬化的一種無(wú)創(chuàng)傷檢查方法。MPV作為反映巨核細(xì)胞增生和血小板生成的一項(xiàng)參數(shù)，近幾年越來(lái)越受到研究者較多關(guān)注。鑒于MPV臨床獲取較容易，費(fèi)用較低，且能夠直觀準(zhǔn)確地反映血小板的功能和活化程度等優(yōu)點(diǎn)，國(guó)外已廣泛報(bào)道MPV作為反映血小板活化程度的指標(biāo)，其在動(dòng)脈粥樣硬化的發(fā)生過(guò)程中起著重要的作用[4，5]。PDW反映血小板體積的異質(zhì)程度和分布趨向，當(dāng)骨髓造血功能正常時(shí)其與MPV呈正相關(guān)。動(dòng)脈粥樣硬化發(fā)生發(fā)展過(guò)程中需要血小板的活化，此時(shí)血液處于高凝狀態(tài)會(huì)反饋性激活骨髓中的巨核細(xì)胞產(chǎn)生體積更大的血小板,導(dǎo)致PDW增大。炎性反應(yīng)貫穿于動(dòng)脈粥樣硬化發(fā)生的全過(guò)程，而Hs-CRP是一種肝臟合成的急性炎性反應(yīng)蛋白，反映著炎性反應(yīng)的存在和活動(dòng)。

本研究頸動(dòng)脈IMT增厚組中TG、UA、Hs-CRP、MPV、PDW水平明顯高于正常組，提示與動(dòng)脈粥樣硬化的程度可能有關(guān)。國(guó)外有研究探討190例無(wú)癥狀冠心病者胸主動(dòng)脈動(dòng)脈內(nèi)膜中層厚度與MPV的相關(guān)性，并證實(shí)MPV與胸主動(dòng)脈粥樣硬化是獨(dú)立的相關(guān)，且MPV的增高是動(dòng)脈粥樣硬化的一個(gè)早期階段的標(biāo)志物[6]，與本研究的結(jié)果相似。既往有研究證實(shí)，體積較大的血小板含有致密小體的數(shù)量更多，質(zhì)膜糖蛋白表達(dá)增強(qiáng)，故那些較為活躍的、酶活性高的血小板通常都比較大[5,7]。儲(chǔ)存在血小板分泌顆粒中的P選擇素主要通過(guò)影響斑塊的穩(wěn)定，對(duì)動(dòng)脈粥樣硬化起著重要的作用。斑塊的穩(wěn)定多受內(nèi)皮細(xì)胞和血小板釋放顆粒-血小板P選擇素的作用[8]，表明作為血小板活化指標(biāo)MPV在無(wú)癥狀的動(dòng)脈粥樣硬化過(guò)程中發(fā)揮著作用。國(guó)外也有相似的研究證實(shí)，MPV和冠狀動(dòng)脈、頸動(dòng)脈粥樣硬化有相關(guān)性[9-12],與本研究的結(jié)論相同，證明了PDW與頸動(dòng)脈粥樣硬化程度成正相關(guān)。

有研究發(fā)現(xiàn)，血清CRP水平于急性心肌梗死或不穩(wěn)定心絞痛發(fā)病不久水平顯著增高，證實(shí)了炎性反應(yīng)機(jī)制的激活在急性冠脈綜合征或是急性心肌梗死發(fā)生發(fā)展中發(fā)揮著作用[13]。Gür等[14]對(duì)181例患者行食管超聲心動(dòng)圖檢測(cè)，根據(jù)胸主動(dòng)脈的IMT分為不同等級(jí)，結(jié)果發(fā)現(xiàn)胸主動(dòng)脈粥樣硬化與Hs-CRP成獨(dú)立相關(guān)。國(guó)外其他研究發(fā)現(xiàn)慢性炎性反應(yīng)推動(dòng)著動(dòng)脈粥樣硬化的發(fā)展[14-16]。本研究結(jié)果表明，Hs-CRP水平與頸動(dòng)脈IMT也呈獨(dú)立正相關(guān)，證實(shí)Hs-CRP水平升高可加速動(dòng)脈粥樣硬化的進(jìn)展。

國(guó)外有研究發(fā)現(xiàn)，血清UA水平與動(dòng)脈粥樣硬化的形成和發(fā)展存在獨(dú)立的相關(guān)性[14，17，18]。Tavil等[17]研究發(fā)現(xiàn)，頸動(dòng)脈IMT、血清尿酸水平和動(dòng)脈粥樣硬化的其他危險(xiǎn)因素之間存在著明顯的正相關(guān)。本研究結(jié)果與上述結(jié)論相一致，這可能與尿酸誘導(dǎo)血管內(nèi)皮功能障礙有關(guān)。通過(guò)細(xì)胞內(nèi)氧化應(yīng)激和炎性反應(yīng)等作用機(jī)制,誘發(fā)血管疾病和高血壓等[19，20],這為心血管疾病的預(yù)防治療提供了新的思路。

年齡、性別、高血脂、高血壓、吸煙史等作為冠狀動(dòng)脈粥樣硬化性心臟病公認(rèn)的危險(xiǎn)因素，而本研究的對(duì)象為無(wú)癥狀的冠心病者，都較年輕，而且是動(dòng)脈粥樣硬化疾病的早期階段，故研究結(jié)果與上述結(jié)果不太一致。本研究結(jié)果示頸動(dòng)脈IMT和高血脂成正相關(guān)，與Matsuzaki等[21]的研究結(jié)果相似。

筆者對(duì)頸動(dòng)脈IMT進(jìn)行多元線性回歸, 發(fā)現(xiàn)TG、UA、MPV、PDW 和Hs-CRP 5個(gè)因素中，只有MPV、PDW和 Hs-CRP 3個(gè)因素最終進(jìn)入了回歸方程，說(shuō)明MPV、PDW和 Hs-CRP與無(wú)癥狀的頸動(dòng)脈粥樣硬化成獨(dú)立的相關(guān)性，是反映頸動(dòng)脈粥樣硬化早期階段的重要的生物學(xué)指標(biāo)，可以更早更好地預(yù)測(cè)動(dòng)脈粥樣硬化疾病的發(fā)生發(fā)展，指導(dǎo)臨床的早期診斷及治療。

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(2015-03-20收稿 2015-04-12修回)

(責(zé)任編輯 武建虎)

Carotid intima-media thickness is associated with mean platelet volume, platelet volume distribution width and hypersensitive c-reactive protein in patients without clinical manifestation of atherosclerotic cardiovascular disease

SHI Genlin1, YAO Liyun2, LIU Hua3, and ZHU Feng4.

1. Department of Information, 3. B-ultrasound Center, 4. Department of Laboratory, Jiangsu Provincial Corps Hospital, Yangzhou 225003, China; 2. The First Hospital of Shanxi Medical University, Taiyuan 030001, China

Objective To study the relationship between carotid intima-media thickness (IMT) and mean platelet volume (MPV), platelet volume distribution width (PDW) and hypersensitive c-reactive protein (Hs-CRP) without clinical manifestation of atherosclerotic cardiovascular disease. Methods Retrospective analysis was performed. We studied the individuals who underwent the color Doppler ultrasound from February to November in 2014. The patients who had known atherosclerotic disease were excluded from study and 85 cases were finally admitted for the study. The patients were divided into IMT high group (55 cases) and IMT normal group (30 cases) according to the median carotid IMT values. A multiple linear regression analysis was performed to identify the independent associations of carotid IMT. Results The IMT high group had higher triglycerides (TG), uric acid (UA), MPV, PDW and Hs-CRP levels than those of the IMT normal group (P<0.05 for all). Multiple linear regression analysis showed that carotid IMT was independently related with MPV (β=0.215,P<0.001), PDW(β=-0.039,P=0.037)and Hs-CRP (β=0.258,P=0.001). Conclusions MPV、PDW or Hs-CRP is independently related to the extent of subclinical carotid atherosclerosis respectively. Increase in MPV may be a crucial biochemical marker for initial atherosclerosis.

carotid intima-media thickness; mean platelet volume; platelet volume distribution width; hypersensitive C-reactive protein; atherosclerotic disease

施根林，本科學(xué)歷，副主任技師，E-mail:2364613601@qq.com

225003 揚(yáng)州，武警江蘇總隊(duì)醫(yī)院:1.信息科，3.B超中心,4.檢驗(yàn)科；2.030001 太原,山西醫(yī)科大學(xué)第一臨床醫(yī)學(xué)院

R543.4