張 薇,王瑞萍
阿托伐他汀對(duì)腦血管狹窄療效分析及TCD診斷作用研究
張 薇,王瑞萍*
目的探討阿托伐他汀對(duì)大腦中動(dòng)脈狹窄患者的治療效果以及TCD在診斷中的應(yīng)用價(jià)值。方法回顧性分析2015年12月至2017年1月我院神經(jīng)內(nèi)科因缺血性腦血管疾病收治的193例患者的臨床資料,其中經(jīng)CTA檢查及結(jié)合臨床癥狀確診的腦血管狹窄患者128例。依據(jù)腦血管狹窄治療用藥不同分為觀察組(57例)和對(duì)照組(71例)。對(duì)照組給予腦血管狹窄常規(guī)治療,觀察組在此基礎(chǔ)上給予阿托伐他汀鈣20 mg每晚1次。檢測(cè)治療前后患者血脂水平,TCD輔助檢查兩組患者M(jìn)CA狹窄情況及血流速度。結(jié)果治療后,兩組患者的TC、TG和LDL水平均明顯下降(P<0.05),且觀察組TC、TG和LDL顯著低于對(duì)照組(P<0.05)。觀察組MCA狹窄好轉(zhuǎn)率顯著高于對(duì)照組(χ2=4.174,P=0.041),病程進(jìn)展率顯著低于對(duì)照組(χ2=4.140,P=0.042),兩組患者病情穩(wěn)定率差異無(wú)統(tǒng)計(jì)學(xué)意義(χ2=0.543,P=0.461)。TCD檢查確診MCA狹窄的特異度為79.7%,敏感度為81.5%,尤其對(duì)于中、重度狹窄,敏感度更高,為94.5%。結(jié)論阿托伐他汀藥物在一定程度上可逆轉(zhuǎn)或穩(wěn)定MCA狹窄,減少缺血性腦卒中事件的發(fā)生;TCD可有效輔助診斷,判斷恢復(fù)情況。
腦血管狹窄;大腦中動(dòng)脈;阿托伐他??;經(jīng)顱多普勒超聲;血脂
動(dòng)脈粥樣硬化是引起腦動(dòng)脈狹窄或閉塞的重要病因[1],可繼發(fā)腦血供減少甚至中斷,腦部能量代謝異常,嚴(yán)重者可導(dǎo)致腦梗死。顱內(nèi)大血管因粥樣硬化產(chǎn)生狹窄是缺血性腦卒中的主要原因,研究顯示,血管狹窄超過50%的腦卒中患者,多在發(fā)病1年內(nèi)再次復(fù)發(fā)腦卒中[2]。臨床治療中,預(yù)防動(dòng)脈狹窄的進(jìn)展顯得尤為重要,作為甲基戊二酰輔酶A還原劑,他汀類藥物可改善動(dòng)脈粥樣硬化的進(jìn)展[3],因此,本研究觀察阿托伐他汀對(duì)腦動(dòng)脈狹窄的治療效果。
經(jīng)顱多普勒超聲(TCD)具有操作便利、無(wú)創(chuàng)、可重復(fù)等多項(xiàng)優(yōu)點(diǎn)[4],在臨床上常應(yīng)用于評(píng)估腦循環(huán),診斷腦血管狹窄及血流情況、血管畸形以及側(cè)支循環(huán),為檢驗(yàn)TCD對(duì)于腦血管狹窄診斷的可靠性,本研究以腦血管CTA檢查結(jié)果為對(duì)照,探討TCD對(duì)腦血管狹窄的診斷價(jià)值。
1.1 一般資料 回顧性分析2015年12月至2017年1月我院神經(jīng)內(nèi)科因缺血性腦血管疾病收治的193例患者的臨床資料,其中經(jīng)CTA檢查及結(jié)合臨床癥狀確診的腦血管狹窄患者128例。其中男88例,女40例,年齡45~74歲,平均年齡(60.25±8.1)歲。診斷依據(jù)全國(guó)第四屆腦血管病學(xué)術(shù)會(huì)議通過的診斷標(biāo)準(zhǔn)。納入標(biāo)準(zhǔn):①CTA診斷符合腦血管狹窄標(biāo)準(zhǔn);②TCD檢查通透窗口良好,血流頻譜顯示清晰;③患者可配合相關(guān)檢查及診療方案。所有受試對(duì)象均知情同意,研究經(jīng)醫(yī)院倫理委員會(huì)討論通過。排除標(biāo)準(zhǔn):①嚴(yán)重肝、腎、腦等器官功能損害及全身基礎(chǔ)狀況較差者;②動(dòng)脈炎、心源性栓塞等其他因素導(dǎo)致的腦血管狹窄者;③風(fēng)濕、自身免疫性疾病及神經(jīng)精神系統(tǒng)疾病患者;④既往患惡性腫瘤、先天心臟病及肺栓塞者;⑤無(wú)法耐受阿托伐他汀者。
1.2 分組情況 依據(jù)腦血管狹窄治療用藥不同分為觀察組(57例)和對(duì)照組(71例)。觀察組男45例,女12例;平均年齡(59.6±9.3)歲;收縮壓(128.6±10.2)mmHg,舒張壓(72.6±9.4)mmHg;有吸煙史23例,糖尿病史18例,高血壓病史15例,高脂血癥病史16例。對(duì)照組男43例,女28例;平均年齡(61.7±8.9)歲;收縮壓(126.9±11.3)mmHg,舒張壓(70.9±10.1)mmHg;有吸煙史25例,糖尿病史20例,高血壓病史17例,高脂血癥病史14例。組間基線資料比較差異無(wú)統(tǒng)計(jì)學(xué)意義,可比性良好。
1.3 治療方法 對(duì)照組給予腦血管狹窄常規(guī)治療,口服抗血小板聚集藥物,改善循環(huán),對(duì)癥治療高血壓和糖尿病,營(yíng)養(yǎng)腦神經(jīng)等;觀察組在對(duì)照組治療基礎(chǔ)上給予阿托伐他汀鈣(商品名:立普妥)20 mg每晚1次。兩組患者治療4~6個(gè)月。
1.4 觀測(cè)指標(biāo) 生化指標(biāo):所有患者治療前及療程結(jié)束后,抽取清晨空腹肘靜脈血3 mL,測(cè)定TC、TG、HDL和LDL等生化指標(biāo)。
TCD檢查:應(yīng)用Multi-Dop×2經(jīng)顱超聲多普勒檢測(cè)儀(德國(guó)DWL),用2 MHz探頭經(jīng)顳窗檢測(cè)大腦中動(dòng)脈,記錄頻譜形態(tài)及舒張期血流速度、收縮期血流速度、血流方向等參數(shù)。
1.5 MCA狹窄分級(jí)與治療轉(zhuǎn)歸 MCA收縮期血流超過220 cm/s為重度狹窄,180~220 cm/s為中度狹窄,160~180 cm/s提示輕度狹窄。治療后,收縮期血流速度下降超過30 cm/s,提示好轉(zhuǎn),復(fù)查顯示,MCA收縮期血流變化范圍小于30 cm/s,提示病情穩(wěn)定,若MCA收縮期血流速度增快超過30 cm/s,提示病情進(jìn)展。
2.1 兩組患者血脂水平比較 治療后,兩組患者TC、TG、LDL水平均明顯下降(P<0.05),且觀察組患者下降較對(duì)照組更為顯著。見表1。
表1 兩組患者血脂水平比較(mmol/L)
2.2 治療后MCA狹窄改善情況 療程結(jié)束后復(fù)查結(jié)果顯示,觀察組MCA狹窄好轉(zhuǎn)率顯著高于對(duì)照組(P<0.05),病程進(jìn)展率顯著低于對(duì)照組(P<0.05),兩組患者病情穩(wěn)定率差異無(wú)統(tǒng)計(jì)學(xué)意義(P>0.05)。見表2。
表2 治療后兩組患者M(jìn)CA狹窄治療情況(例)
2.3 MCA狹窄治療期間并發(fā)癥及隨訪結(jié)果 治療過程中,觀察組出現(xiàn)3例肝酶水平升高,AST和ALT升高低于2倍,繼續(xù)用藥1個(gè)月后復(fù)查,肝酶恢復(fù)正常水平,屬一過性改變。對(duì)照組出現(xiàn)2例肝酶水平升高,升高水平低于2倍,繼續(xù)觀察1個(gè)月后恢復(fù)正常。療程結(jié)束后隨訪1年,觀察組再發(fā)缺血性事件共計(jì)2例,對(duì)照組再發(fā)8例,組間對(duì)比差異無(wú)統(tǒng)計(jì)學(xué)意義(Fisher確切概率法,無(wú)統(tǒng)計(jì)值,P=0.183>0.05)。
2.4 TCD診斷價(jià)值 193例缺血性腦血管疾病患者中CTA確診為MCA狹窄128例,而經(jīng)TCD檢查確診MCA狹窄114例,特異度為79.7%,敏感度為81.5%,陽(yáng)性預(yù)測(cè)值為89.5%,陰性預(yù)測(cè)值為67.1%,尤其對(duì)于中、重度狹窄(87例),敏感度更高,為94.5%。治療前后的TCD檢查結(jié)果見圖1。
圖1 治療前后MCA狹窄情況TCD檢查結(jié)果
脂代謝異常在動(dòng)脈粥樣硬化發(fā)生發(fā)展過程中占據(jù)主導(dǎo)地位,顱內(nèi)大血管,尤其是MCA的粥樣硬化是引發(fā)缺血性腦卒中的主要病因[5]。研究顯示,顱內(nèi)段血管的粥樣硬化與頸動(dòng)脈的硬化存在相關(guān)性,高血壓及糖尿病影響顱內(nèi)段動(dòng)脈硬化,與顱外段動(dòng)脈硬化無(wú)相關(guān)性。另有研究表明,高脂血癥與顱內(nèi)段血管狹窄密切相關(guān)[6],MCA硬化與年齡和高血壓相關(guān),而基底動(dòng)脈硬化則與高血壓和糖尿病相關(guān),這提示不同血管狹窄發(fā)病的病理機(jī)制不盡相同[7],因人種差異,亞洲人群以顱內(nèi)大動(dòng)脈狹窄高發(fā)。研究發(fā)現(xiàn),近50%的急性腦梗死患者并發(fā)顱內(nèi)動(dòng)脈狹窄[8]。顱內(nèi)動(dòng)脈狹窄加重了中風(fēng)的發(fā)病程度,增加了中風(fēng)1年內(nèi)復(fù)發(fā)的風(fēng)險(xiǎn)。
他汀類藥物可能通過降低脂蛋白水平和減輕血管炎性反應(yīng)達(dá)到改善動(dòng)脈粥樣硬化的療效[9]。本研究發(fā)現(xiàn),通過中長(zhǎng)期聯(lián)合應(yīng)用阿托伐他汀治療MCA狹窄,MCA狹窄情況明顯好轉(zhuǎn),病例好轉(zhuǎn)率明顯高于對(duì)照組,病程進(jìn)展率顯著低于對(duì)照組。生化檢查提示,通過治療,觀察組膽固醇、低密度脂蛋白和三酰甘油水平顯著下降,且血脂改善程度明顯優(yōu)于對(duì)照組。這一結(jié)果在一定程度上闡釋了他汀類藥物改善顱內(nèi)動(dòng)脈狹窄的作用機(jī)制。
MCA是顱內(nèi)血管狹窄時(shí)最常受累的血管,是臨床診斷中監(jiān)測(cè)的首選動(dòng)脈[10]。以往研究發(fā)現(xiàn),與CTA對(duì)照分析,TCD檢測(cè)MCA狹窄結(jié)果的符合率約為80%,且狹窄程度高于50%的病例符合率更高,可達(dá)90%。本研究也得出了類似的結(jié)果,TCD檢測(cè)結(jié)果與CTA結(jié)果的符合率為80.3%,提示可進(jìn)一步擴(kuò)大TCD在顱腦血管狹窄中的應(yīng)用,利用其無(wú)創(chuàng)、價(jià)廉、方便隨診的特點(diǎn),作為腦血管狹窄的篩選手段。但臨床上單血管狹窄并不僅限于MCA,給TCD檢查帶來(lái)一定難度[11]。
經(jīng)顱多普勒超聲TCD以顳窗、枕窗和眼窗這三個(gè)公認(rèn)的顱骨薄弱部位作為檢查聲窗,應(yīng)用多普勒效應(yīng)檢查腦動(dòng)脈血流動(dòng)力學(xué)[12]。通過血流速度、頻譜形態(tài)改變等參數(shù),TCD可診斷待查血管是否存在狹窄或閉塞。MCA收縮期血流速度大于160~180 cm/s,提示MCA血管狹窄,狹窄近端血流速度正?;蛏缘停h(yuǎn)端血流明顯降低,頻譜顯示S1峰和S2峰融合,出現(xiàn)湍流或渦流。同時(shí),可測(cè)試同名血管雙側(cè)血流速度,若出現(xiàn)速度相差30%以上,則提示一側(cè)血管狹窄。血管閉塞表現(xiàn)為閉塞遠(yuǎn)端無(wú)血流信號(hào),常伴相鄰血管血流速度代償加快或側(cè)支循環(huán)建立。
綜上所述,長(zhǎng)期應(yīng)用阿托伐他汀可顯著降低患者血脂水平,并進(jìn)一步改善MCA狹窄情況,顱內(nèi)血管狹窄好轉(zhuǎn)情況顯著優(yōu)于對(duì)照組。診斷數(shù)據(jù)顯示,TCD可作為顱內(nèi)血管狹窄的重要篩查工具,可評(píng)估病情進(jìn)展及預(yù)后情況。
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CurativeeffectofatorvastatinoncerebralvascularstenosisanddiagnosisvalueofTCD
ZHANG Wei,WANG Rui-ping*
(Department of Neurology,Jinqiu Hospital of Liaoning Province,Shenyang 110016,China)
ObjectiveTo investigate the effect of atorvastatin in the treatment of patients with middle cerebral artery stenosis and the value of TCD in the diagnosis.MethodsFrom December 2015 to January 2017,193 patients with ischemic cerebrovascular disease were selected in Department of Neurology of our hospital,including 128 patients with middle cerebral artery stenosis.Patients were divided into 2 groups according to different drug treatments.Control group (n=71) was treated with conventional treatment and observation group (n=57) was also given atorvastatin calcium 20 mg,once a night.The blood lipid levels were detected before and after treatment.TCD was used to examine the MCA stenosis and blood flow velocity in the two groups.ResultsAfter treatment,the TC,TG and LDL levels of patients were significantly decreased (P<0.05),the TC,TG and LDL levels of observation group were lower than that of control group (P<0.05).TCD examination showed that the improvement rate of MCA stenosis in observation group was higher than that of control group (χ2=4.174,P=0.041);The rate of disease progression in observation group was lower than that of control group (χ2=4.140,P=0.042).There was no difference in disease stability rate between the two groups (χ2=0.543,P=0.461).The specificity of TCD in diagnosis of MCA stenesis was 79.7%,sensitivity 81.5%,which was even higher (94.5%) for moderate and severe stenosis.ConclusionAtorvastatin can reverse or stabilize MCA stenosis to a certain extent and reduce the occurrence of ischemic stroke events.TCD can effectively assist the diagnosis and judge the recovery.
Cerebral artery stenosis;MCA;Atorvastatin;TCD;Serum lipid
2017-01-28
遼寧省金秋醫(yī)院神經(jīng)內(nèi)科,沈陽(yáng) 110016
*通信作者
10.14053/j.cnki.ppcr.201710018