先麗紅 李娟 薛超 趙雪姣 盧婷 顏歡
【摘要】 背景 腦微出血(CMBs)是嚴(yán)重危害我國(guó)國(guó)民健康的重要疾病,其發(fā)病率與年齡呈正相關(guān)。同時(shí),CMBs也是卒中復(fù)發(fā)及誘發(fā)出血性腦卒中的獨(dú)立危險(xiǎn)因素。了解CMBs的患病現(xiàn)狀對(duì)于推動(dòng)我國(guó)健康老齡化進(jìn)程及加強(qiáng)腦卒中防治工作具有重大現(xiàn)實(shí)意義。目的 系統(tǒng)評(píng)價(jià)我國(guó)CMBs發(fā)生的現(xiàn)況,為推進(jìn)我國(guó)健康老齡化進(jìn)程及加強(qiáng)腦卒中防治工作提供數(shù)據(jù)支撐。方法 系統(tǒng)檢索中國(guó)生物醫(yī)學(xué)文獻(xiàn)數(shù)據(jù)庫(kù)(CBM)、中國(guó)知網(wǎng)(CNKI)、萬(wàn)方數(shù)據(jù)知識(shí)服務(wù)平臺(tái)(Wanfang Data)、維普網(wǎng)(VIP)、PubMed、Embase、Web of Science等數(shù)據(jù)庫(kù)中有關(guān)我國(guó)CMBs患病率的橫斷面研究,檢索時(shí)限為建庫(kù)至2023年11月。2名研究者分別對(duì)文獻(xiàn)進(jìn)行篩選、資料提取及納入文獻(xiàn)的偏倚風(fēng)險(xiǎn)評(píng)估,并采用Stata 16.0軟件進(jìn)行Meta分析。結(jié)果 共納入39項(xiàng)研究,25 877例研究對(duì)象。Meta分析結(jié)果顯示:我國(guó)CMBs的總體患病率為25.0%(95%CI=21.0%~29.0%)。亞組分析結(jié)果顯示,51~60、61~70、71~80歲CMBs患病率分別為27.0%(95%CI=12.0%~44.0%)、23.0%(95%CI=16.0%~30.0%)、27.0%(95%CI=20.0%~35.0%);男、女性CMBs患病率分別為14.0%(95%CI=11.0%~18.0%)、10.0%(95%CI=8.0%~12.0%);華北、華東、華南、華中、西南、西北地區(qū)CMBs患病率分別為21.0%(95%CI=15.0%~28.0%)、26.0%(95%CI=21.0%~33.0%)、21.0%(95%CI=8.0%~39.0%)、21.0%(95%CI=16.0%~27.0%)、24.0%(95%CI=21.0%~27.0%)、46.0%(95%CI=41.0%~51.0%);有、無(wú)高血壓病史CMBs患病率分別為19.0%(95%CI=13.0%~26.0%)、8.0%(95%CI=6.0%~11.0%);有、無(wú)吸煙史CMBs患病率分別為9.0%(95%CI=5.0%~14.0%)、16.0%(95%CI=12.0%~21.0%)。結(jié)論 我國(guó)CMBs總體患病率較高,不同年齡分段、地域及省份之間存在明顯差異。高齡、男性、西北地區(qū)以及有高血壓病史的人群發(fā)病率較高。受納入研究數(shù)量和質(zhì)量限制,該結(jié)論亟待更多高質(zhì)量研究證實(shí)。
【關(guān)鍵詞】 腦微出血;患病率;中國(guó);系統(tǒng)評(píng)價(jià);Meta分析
【中圖分類號(hào)】 R 743.34 【文獻(xiàn)標(biāo)識(shí)碼】 A DOI:10.12114/j.issn.1007-9572.2023.0908
Prevalence for Cerebral Microbleeds in China:a Meta-analysis
XIAN Lihong1,LI Juan2*,XUE Chao3,ZHAO Xuejiao3,LU Ting3,YAN Huan1
1.Zunyi Medical University,Zunyi 563003,China
2.Nursing Department,Guizhou Provincial People's Hospital,Guiyang 550002,China
3.Nursing School of Guizhou University of TCM,Guiyang 550002,China
*Corresponding author:LI Juan,Professor/Chief superintendent nurse;E-mail:694807055@qq.com
【Abstract】 Background Cerebral microbleeds(CMBs)are important diseases that seriously endanger our national health,and their incidence is positively correlated with age. Meanwhile,CMBs are also an independent risk factor for stroke recurrence and induced hemorrhagic stroke. Understanding the current prevalence of CMBs is of great practical significance for promoting healthy aging and strengthening stroke prevention and treatment in China. Objective To systematically evaluate the current status of the occurrence of CMBs in China and to provide data support for promoting the process of healthy aging and strengthening the prevention and treatment of stroke in China. Methods Literature related to the occurrence of the disease of CMBs in our national population was systematically searched through Chinese and English databases such as CBM,CNKI,Wanfang Data,VIP,PubMed,Embase,and Web of Science,with a timeframe of the establishment of the database until November 2023 for all searches. Two researchers separately performed literature screening,data extraction,and evaluation of the risk of bias in the included literature,and meta-analysis was performed using Stata 16.0 software. Results A total of 39 studies were included,with a total of 25 877 study subjects. Meta-analysis showed that the overall incidence of CMBs in China was 25.0%(95%CI=21.0%-29.0%). The results of subgroup analysis showed that the prevalence was 27.0%(95%CI=12.0%-44.0%)for those aged 51-60 years,23.0%(95%CI=16.0%-30.0%)for those aged 61-70 years,and 27.0%(95%CI=20.0%-35.0%)for those aged 71-80 years;the prevalence was 21.0%(95%CI=15.0%-28.0%)in North China,26.0%(95%CI=21.0%-33.0%)in East China,21.0%(95%CI=8.0%-39.0%)in South China,21.0%(95%CI=16.0%-27.0%)in Central China,24.0%(95%CI=21.0%-27.0%)in Southwest China and 46.0%(95%CI=41.0%-51.0%)in Northwest China by geographic area;the prevalence of CMBs with a history of hypertension was 19.0%(95%CI=13.0%-26.0%)and without a history of hypertension was 8.0%(95%CI=6.0%-11.0%);the prevalence of CMBs with a history of smoking was 9.0%(95%CI=5.0%-14.0%) and without a history of smoking was 16.0%(95%CI=12.0%-21.0%). Conclusion The overall prevalence of CMBs in China is high,with significant differences between different age segments,regions,and provinces. Its prevalence was higher in people of advanced age,males,Northwest China,and nationals with a history of hypertension. Due to the limitations in both quantity and quality of the included studies,further confirmation of this conclusion through additional high-quality research is required.
【Key words】 Cerebral microbleeds;Prevalence rate;China;Systematic evaluation;Meta-analysis
腦微出血(cerebral microbleeds,CMBs)是腦小血管病(cerebral small vessel disease,CSVD)中的一個(gè)特殊亞型,是由多種因素導(dǎo)致的腦內(nèi)小血管滲漏出血引起的腦實(shí)質(zhì)亞臨床損傷,其病變的腦小血管周圍含有鐵血黃素沉積是主要的病理特征[1]。CMBs發(fā)生時(shí)會(huì)引發(fā)血液分解和壞死物質(zhì)的釋放,進(jìn)而引起老年急性腦梗死患者周圍腦組織的水腫程度加重、顱內(nèi)壓升高,最終導(dǎo)致患者出現(xiàn)頭暈、頭痛和惡心等癥狀,嚴(yán)重時(shí)還會(huì)引發(fā)呼吸循環(huán)衰竭,威脅患者生命[2]。AKOUDAD等[3]對(duì)2008—2015年45歲以上的4 759名社區(qū)常住健康人群進(jìn)行MRI篩查時(shí)發(fā)現(xiàn),CMBs患病率為11.1%~18.7%。HAN等[4]研究顯示,50~59歲人群CMBs患病率為7.6%,60~69歲上升至18.4%,70~80歲人群患病率高達(dá)24.8%。此外,有研究發(fā)現(xiàn),CMBs被視為缺血性腦卒中再發(fā)和出血性腦卒中的獨(dú)立危險(xiǎn)因素,也是觸發(fā)卒中后血管性認(rèn)知功能障礙和情感障礙的關(guān)鍵因素[5]。由此可見(jiàn),CMBs好發(fā)于老年人群中,對(duì)我國(guó)健康老齡化造成嚴(yán)重威脅。然而,國(guó)內(nèi)尚缺乏有關(guān)CMBs患病率及發(fā)展趨勢(shì)的綜合報(bào)道。因此,本研究通過(guò)Meta分析的方法系統(tǒng)評(píng)價(jià)我國(guó)成年人CMBs發(fā)生情況,以期為我國(guó)CMBs的相關(guān)研究提供更加全面的數(shù)據(jù)支撐和參考依據(jù),對(duì)推進(jìn)我國(guó)健康老齡化和卒中防治工作也具有重大意義。
1 資料與方法
1.1 納入與排除標(biāo)準(zhǔn)
1.1.1 研究類型:橫斷面研究。
1.1.2 研究對(duì)象:(1)在中國(guó)長(zhǎng)期居住的人群(長(zhǎng)期居?。撼钟谐W艨诨蚓幼〕^(guò)半年的人);(2)年齡≥18歲。
1.1.3 結(jié)局指標(biāo):CMBs患病率,CMBs為經(jīng)影像學(xué)檢查確診后明確診斷。
1.1.4 排除指標(biāo):(1)研究數(shù)據(jù)重復(fù)或原始數(shù)據(jù)雷同;(2)非中、英文文獻(xiàn);(3)綜述、會(huì)議及評(píng)論;(4)文獻(xiàn)中的研究方案設(shè)計(jì)存在不合理之處或文獻(xiàn)質(zhì)量較低;(5)原始研究數(shù)據(jù)不全或無(wú)法獲??;(6)樣本量不少于200例。
1.2 文獻(xiàn)檢索策略
系統(tǒng)檢索中國(guó)生物醫(yī)學(xué)文獻(xiàn)數(shù)據(jù)庫(kù)(CBM)、中國(guó)知網(wǎng)(CNKI)、萬(wàn)方數(shù)據(jù)知識(shí)服務(wù)平臺(tái)(Wanfang Data)、維普網(wǎng)(VIP)、PubMed、Embase、Web of Science等數(shù)據(jù)庫(kù)中有關(guān)我國(guó)CMBs患病率的文獻(xiàn),文獻(xiàn)檢索時(shí)限均為建庫(kù)至2023年11月。結(jié)合各數(shù)據(jù)庫(kù)特點(diǎn),使用主題詞與自由詞相結(jié)合的方式檢索文獻(xiàn),并結(jié)合文獻(xiàn)追蹤技術(shù)獲取具有研究意義的文獻(xiàn)。英文檢索詞包括:Cerebral microbleeds,Cerebral microbleed,Cerebral microhemorrhages,Microbleed,microhemorrhage,CMBs,prevalence,Incidence,Occurrence,epidemi*,Chinese,China等。中文檢索詞包括:腦微出血、腦微出血灶、腦微出血病變、腦內(nèi)微出血、患病率、現(xiàn)況調(diào)查、流行病學(xué)、調(diào)查等。以PubMed為例,具體檢索策略見(jiàn)表1。
1.3 文獻(xiàn)篩選和資料提取
由2名研究人員分別負(fù)責(zé)文獻(xiàn)篩選和資料提取工作,并進(jìn)行交叉驗(yàn)證以確保結(jié)果的準(zhǔn)確性。若有分歧,可采取雙方商議或邀請(qǐng)第三方介入進(jìn)行討論解決。文獻(xiàn)篩選時(shí),研究者先閱讀文題剔除無(wú)關(guān)文獻(xiàn),再閱讀摘要和全文,以確定是否采用。若有需要,可采取電子郵件和/或電話等方式與原始作者取得聯(lián)系,征得作者同意后獲取對(duì)本次研究至關(guān)重要但未報(bào)告的資料。提取資料包括:第一作者、發(fā)表時(shí)間、研究地點(diǎn)、確診方式、總樣本量、患病例數(shù)、年齡及相關(guān)數(shù)據(jù)等。
1.4 納入研究的偏倚風(fēng)險(xiǎn)評(píng)價(jià)
納入文獻(xiàn)由2名研究者分別進(jìn)行偏倚風(fēng)險(xiǎn)評(píng)價(jià),在評(píng)價(jià)完成后進(jìn)行交叉核對(duì),旨在確保評(píng)估結(jié)果的準(zhǔn)確性。若遇分歧,可采取雙方商議或邀請(qǐng)第三方介入進(jìn)行討論解決。偏倚風(fēng)險(xiǎn)的評(píng)估是基于美國(guó)衛(wèi)生保健質(zhì)量和研究機(jī)構(gòu)(Agency for Healthcare Research and Quality,AHRQ)所推薦的橫斷面研究偏倚風(fēng)險(xiǎn)評(píng)價(jià)準(zhǔn)則而進(jìn)行[6]。該工具共計(jì)11個(gè)條目,若每個(gè)條目評(píng)定為“是”則計(jì)1分,“否”或“不清楚”則計(jì)0分,其評(píng)定總分8~11分為高質(zhì)量,4~7分為中等質(zhì)量,0~3分為低質(zhì)量[7]。
1.5 統(tǒng)計(jì)學(xué)方法
使用統(tǒng)計(jì)學(xué)軟件Stata 16.0對(duì)我國(guó)CMBs患病率進(jìn)行統(tǒng)計(jì)分析,采取雙反正弦轉(zhuǎn)換法對(duì)患病率進(jìn)行轉(zhuǎn)換合并計(jì)算,并提供其95%可信區(qū)間(CI)。使用χ2檢驗(yàn)(檢驗(yàn)水準(zhǔn)α=0.1)和I2檢驗(yàn)對(duì)研究的結(jié)果進(jìn)行異質(zhì)性分析。倘若研究結(jié)果間無(wú)統(tǒng)計(jì)學(xué)異質(zhì)性,則選用固定效應(yīng)模型進(jìn)行Meta分析;倘若研究結(jié)果間有統(tǒng)計(jì)學(xué)異質(zhì)性,則進(jìn)一步分析異質(zhì)性來(lái)源。在排除明顯臨床異質(zhì)性影響后,采用隨機(jī)效應(yīng)模型進(jìn)行Meta分析。Meta分析設(shè)定的水準(zhǔn)為α=0.05。明顯的臨床異質(zhì)性采用亞組分析進(jìn)行處理,旨在進(jìn)一步探討影響CMBs發(fā)生的可能因素。
2 結(jié)果
2.1 文獻(xiàn)篩選流程及結(jié)果
經(jīng)初步篩選,共獲得相關(guān)文獻(xiàn)2 281篇。通過(guò)逐層篩選,最終納入39篇文獻(xiàn)[4,8-45],總樣本量為25 877例。文獻(xiàn)篩選流程圖及結(jié)果見(jiàn)圖1。
2.2 納入研究的基本特征與偏倚風(fēng)險(xiǎn)評(píng)價(jià)結(jié)果
本研究納入39項(xiàng)研究的基本特征與偏倚風(fēng)險(xiǎn)評(píng)價(jià)結(jié)果見(jiàn)表2。
2.3 Meta分析結(jié)果
2.3.1 總患病率:本研究納入39項(xiàng)研究采取隨機(jī)效應(yīng)模型進(jìn)行Meta分析,結(jié)果顯示我國(guó)CMBs總患病率為25.0%(95%CI=21.0%~29.0%)(圖2)。
2.3.2 亞組分析:按年齡、性別、地理區(qū)域、發(fā)表年份、有無(wú)高血壓病史及吸煙史等類別進(jìn)行亞組分析(表3)。
(1)按年齡分組,51~60歲CMBs患病率為27.0%(95%CI=12.0%~44.0%),61~70歲為23.0%(95%CI=16.0%~30.0%),71~80歲為27.0%(95%CI=20.0%~35.0%)。
(2)按性別分組,男性CMBs患病率為14.0%(95%CI=11.0%~18.0%),女性為10.0%(95%CI=8.0%~12.0%)。
(3)按地理區(qū)域分組,華北地區(qū)CBMs患病率為21.0%(95%CI=15.0%~28.0%),華東地區(qū)為26.0%(95%CI=21.0%~33.0%),華南地區(qū)為21.0%(95%CI=8.0%~39.0%),華中地區(qū)為21.0%(95%CI=16.0%~27.0%),西南地區(qū)為24.0%(95%CI=21.0%~27.0%),西北地區(qū)為46.0%(95%CI=41.0%~51.0%)。
(4)按發(fā)表年份分組,2009—2013年CMBs患病率為34.0%(95%CI=24.0%~44.0%),2014—2018年為26.0%(95%CI=19.0%~34.0%),2019—2023年為22.0%(95%CI=16.0%~27.0%)。
(5)按有無(wú)高血壓病史分組,有高血壓病史CMBs患病率為19.0%(95%CI=13.0%~26.0%),無(wú)高血壓病史為8.0%(95%CI=6.0%~11.0%)。
(6)按有無(wú)吸煙史分組,有吸煙史CMBs患病率為9.0%(95%CI=5.0%~14.0%),無(wú)吸煙史為16.0%(95%CI=12.0%~21.0%)。
2.4 敏感性分析與發(fā)表偏倚檢驗(yàn)
本研究采取逐一剔除研究法進(jìn)行敏感性分析。結(jié)果表明效應(yīng)量無(wú)顯著變化,提示研究結(jié)果較穩(wěn)定。
3 討論
CMBs是一種亞臨床性腦實(shí)質(zhì)改變,源于正?;蚪咏5哪X組織中慢性血液產(chǎn)物的小病灶,因出血量較少,在臨床上通常不伴有明顯的癥狀和體征[46-47],易被忽視。有研究報(bào)道,CMBs發(fā)病率呈現(xiàn)顯著的年齡依賴性增長(zhǎng)趨勢(shì)[48]。然而,目前尚無(wú)明確的CMBs治療手段[49],這對(duì)我國(guó)健康老齡化來(lái)說(shuō)是一個(gè)亟待關(guān)注的挑戰(zhàn)。因此,本研究旨在對(duì)我國(guó)國(guó)人CMBs患病率進(jìn)行系統(tǒng)評(píng)價(jià),以明確CMBs在我國(guó)的流行狀況,為我國(guó)CMBs的防治策略提供科學(xué)依據(jù)。
本研究匯總分析了39項(xiàng)橫斷面研究。其文獻(xiàn)質(zhì)量評(píng)價(jià)結(jié)果顯示AHRQ評(píng)分為7~10分,其中高質(zhì)量研究37項(xiàng),中等質(zhì)量研究2項(xiàng),研究結(jié)果的可靠性得以保證。本研究Meta分析結(jié)果顯示:我國(guó)CMBs總體患病率為25.0%,略低于CORICA等[50]的Meta分析結(jié)果28.3%,其原因可能與納入研究的研究對(duì)象、地域環(huán)境、樣本量和文化背景不同等因素有關(guān)。
本研究亞組分析結(jié)果顯示:(1)從年齡分段來(lái)看,CMBs發(fā)病率會(huì)隨著60歲以上人群的年齡增長(zhǎng)而呈現(xiàn)上升趨勢(shì)。QIN等[51]一項(xiàng)為期5年的隊(duì)列研究發(fā)現(xiàn),相較于青年人群,大腦萎縮的老年患者大腦腦葉性微出血的風(fēng)險(xiǎn)會(huì)增加2.6倍,表明年齡是CMBs的一個(gè)重要危險(xiǎn)因素。LEE等[52]也證實(shí)高齡是CMBs的危險(xiǎn)因素,可能與高齡相關(guān)的血管內(nèi)皮功能紊亂有關(guān)[53]。(2)從患病史來(lái)看,有高血壓病史人群的CMBs患病率遠(yuǎn)高于無(wú)高血壓病史人群,與徐大飛等[54]研究結(jié)果一致。其原因可能是:①血管的自我調(diào)節(jié)功能隨年齡增長(zhǎng)及高血壓的長(zhǎng)期影響而逐漸衰退。顱內(nèi)眾多深穿支動(dòng)脈對(duì)血壓波動(dòng)更為敏感,加之高齡導(dǎo)致胰島素樣生長(zhǎng)因子分泌減少、羥基二十碳四烯酸介導(dǎo)通路受抑制,進(jìn)而使血管平滑肌收縮功能減弱,誘發(fā)CMBs[55];②高血壓可引發(fā)小動(dòng)脈玻璃樣變性,使血管平滑肌遭受纖維組織或壞死組織的替代。此外,隨著年齡的增長(zhǎng),腦小動(dòng)脈會(huì)出現(xiàn)萎縮,導(dǎo)致血管平滑肌細(xì)胞減少,腦小動(dòng)脈更容易發(fā)生破裂,進(jìn)而導(dǎo)致CMBs的發(fā)生[56]。(3)從有無(wú)吸煙史來(lái)看,有吸煙史人群的CMBs患病率比無(wú)吸煙史人群低。但相關(guān)研究認(rèn)為吸煙是CMBs的獨(dú)立危險(xiǎn)因素[50,54],原因是吸煙會(huì)對(duì)人體的血管內(nèi)皮細(xì)胞產(chǎn)生危害,而煙霧中的一氧化碳會(huì)與血液中的血紅蛋白相結(jié)合形成碳氧血紅蛋白,進(jìn)而影響紅細(xì)胞的攜氧能力,導(dǎo)致組織缺氧,引起血管痙攣。此外,吸煙會(huì)增加血漿纖維蛋白原,引起凝血系統(tǒng)功能紊亂,從而誘發(fā)CMBs[57]。本研究的結(jié)果與既往研究結(jié)果存在爭(zhēng)議,其原因可能與納入研究的數(shù)量、質(zhì)量和對(duì)吸煙的定義以及樣本量等因素有關(guān)。(4)從性別分組來(lái)看,男性CMBs患病率高于女性,原因可能是男性的高血壓患病率高于女性,而高血壓對(duì)CMBs發(fā)病機(jī)制起著一定的作用。因此,性別差異對(duì)CMBs的患病率也有一定的影響[56]。(5)從地理區(qū)域來(lái)看,西北地區(qū)患病率顯著高于其他地區(qū),這可能與地區(qū)醫(yī)療政策和發(fā)展情況、不同地區(qū)之間的生活習(xí)慣和文化差異等密切相關(guān)。因此,建議相關(guān)區(qū)域的衛(wèi)生管理部門(mén)人員要重視該地人群CMBs的篩查及預(yù)防,這對(duì)我國(guó)卒中防治工作起著關(guān)鍵作用。
本次研究的樣本量涵蓋了中國(guó)大部分省份,能在一定程度上揭示我國(guó)CMBs患病率的分布狀況。但該研究仍存在一定的局限性:(1)納入的研究均為橫斷面研究,受研究設(shè)計(jì)、樣本來(lái)源及大小等因素影響;(2)各研究間存在一定的異質(zhì)性,雖在性別、年齡、地區(qū)等方面采取了亞組分析也未發(fā)現(xiàn)異質(zhì)性來(lái)源;(3)部分亞組納入的研究數(shù)量有限,其結(jié)果可靠性在一定程度上會(huì)有所降低;(4)個(gè)別分組在進(jìn)行亞組分析時(shí)由于缺乏原始數(shù)據(jù),其結(jié)果可能會(huì)存在偏倚。
綜上所述,當(dāng)前研究結(jié)果顯示我國(guó)CMBs總體患病率較高,其患病率在男性、高齡、有高血壓史及西北地區(qū)間表現(xiàn)得更為明顯。因此,建議各級(jí)醫(yī)療機(jī)構(gòu)應(yīng)重點(diǎn)關(guān)注以上人群,發(fā)病率較高的地區(qū)醫(yī)療衛(wèi)生機(jī)構(gòu)要加強(qiáng)CMBs的篩查力度和政策關(guān)注,以降低我國(guó)CMBs的患病率,減輕我國(guó)醫(yī)療負(fù)擔(dān)的同時(shí)也能減輕我國(guó)卒中防治工作負(fù)擔(dān)。
作者貢獻(xiàn):先麗紅負(fù)責(zé)文章構(gòu)思與設(shè)計(jì)、數(shù)據(jù)收集與整理、論文撰寫(xiě)及修訂;先麗紅、薛超、趙雪姣負(fù)責(zé)文獻(xiàn)檢索、數(shù)據(jù)提取、質(zhì)量評(píng)價(jià)及數(shù)據(jù)分析;先麗紅、盧婷、顏歡負(fù)責(zé)結(jié)果的分析與解釋;李娟負(fù)責(zé)文章審校及質(zhì)量控制,并對(duì)文章整體負(fù)責(zé)。
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(收稿日期:2023-12-06;修回日期:2024-03-02)
(本文編輯:賈萌萌)