丁曉宇 錢宗杰
[摘要] 高血壓病引起患者靶器官損傷證據(jù)充分,特別是與心血管系統(tǒng)有關(guān)聯(lián)的靶器官。血壓變異性因與靶器官損傷也有一定正相關(guān)關(guān)系,關(guān)注度明顯增高。越來越多的證據(jù)表明,高血壓病患者的血壓變異性越大,靶器官損傷的程度越明顯。所以,降低血壓的變異性能夠一定程度地降低靶器官損傷的風(fēng)險。本文就血壓變異的監(jiān)測方法及血壓變異性與靶器官損傷關(guān)系進(jìn)行綜述,以期最終通過降低血壓變異性來降低高血壓病患者的靶器官損傷率及臨床伴隨疾病的發(fā)生率。
[關(guān)鍵詞] 高血壓病;血壓變異性;動態(tài)血壓監(jiān)測;靶器官損傷
[中圖分類號] R544.1 [文獻(xiàn)標(biāo)識碼] A [文章編號] 1673-7210(2017)05(c)-0035-04
[Abstract] There is sufficient evidence that hypertension caused target organ damage, especially in the cardiovascular system. The damage degree of target organs is positively correlated with BP variability (BPV). A growing body of evidences show that the more hypertension patient's BPV increased, the more serious target organ damaged, so it can reduce the risk of target organ damage in some degree by reducing the BPV. This article reviews the literature about the methods of BPV monitoring and relationship between BPV and target organ damage, looks forward to reduce the target organ damage rate of the hypertension patients and the incidence of clinical diseases by reducing the BPV.
[Key words] Hypertension; Blood pressure variability; Ambulatory blood pressure monitoring; Target-organ damage
高血壓病引起靶器官損傷的證據(jù)已十分充足,高血壓病已經(jīng)不是單純的血壓升高,而是一種心血管綜合征,是以血壓升高為主要特征的全身代謝性疾病和生活方式相關(guān)性疾病[1]。大量的研究表明,降低高血壓病患者的血壓可以降低心血管疾病的風(fēng)險[2]。同時,一些研究發(fā)現(xiàn),發(fā)生心血管疾病的風(fēng)險程度不只取決于血壓升高的水平,還與血壓變異性(blood pressure variability,BPV)有關(guān)。血壓在人體是不斷變化的,我們把這種變化稱為BPV。這種變異是為了讓機(jī)體更好地適應(yīng)外界變化,是人體的正常生理現(xiàn)象,但是如果高血壓病患者血壓控制不平穩(wěn),處于波動狀態(tài),將給機(jī)體帶來嚴(yán)重靶器官損傷。證據(jù)表明,短時的BPV與發(fā)生嚴(yán)重的腎臟、心臟及血管損傷密切相關(guān),同樣也增加了心血管疾病的死亡率[3-5]。新近研究表明,對伴有24 h尿微量白蛋白升高、左心室質(zhì)量增加的高血壓病患者的動態(tài)血壓監(jiān)測結(jié)果發(fā)現(xiàn)其長時BPV明顯增加[6-7]。
1 血壓的變異性
BPV即每一個獨(dú)立個體在單位時間內(nèi)血壓波動的程度,根據(jù)時間的長短可分為短時變異及長時變異。短時變異主要以24 h動態(tài)血壓監(jiān)測為主,長時變異主要包括家庭自測血壓變異和隨診間血壓變異。BPV是一個復(fù)雜的現(xiàn)象,是由所處環(huán)境、自身的體液、神經(jīng)中樞、反射等影響因素決定的。鑒于這種復(fù)雜性,BPV可以在不同的時間段被記錄下來。目前臨床上對于高血壓病患者BPV的評估使用24 h動態(tài)血壓監(jiān)測較為普遍,對于門診隨診患者則較多使用長時BPV的監(jiān)測方法[8]。通常用動態(tài)血壓標(biāo)準(zhǔn)差(standard deviation,SD)、變異系數(shù)(coefficient of variability,CV)、動態(tài)血壓標(biāo)準(zhǔn)差與平均值的比值(SD/mean)來表示BPV。通過對高血壓病患者的血壓監(jiān)測,可以更好地了解血壓的控制情況以及血壓變異程度。血壓變異及血壓晝夜模式均與高血壓病患者靶器官損傷程度有關(guān)。調(diào)整血壓的晝夜模式,控制血壓的變異程度能有效地降低靶器官損傷事件的發(fā)生率。同時應(yīng)定期檢測患者靶器官的功能狀態(tài),了解高血壓病是否給自身帶來靶器官的損傷。
2 血壓的變異性和靶器官損傷
2.1 血壓的變異性和慢性腎臟疾病
終末期腎?。╡nd stage renal disease,ESRD)的高血壓病患者通常都伴有明顯的BPV和生理血壓節(jié)奏的改變。然而,在過去的研究中,幾乎所有關(guān)于短時BPV的研究均沒有發(fā)現(xiàn)圍繞平均血壓水平的BPV在預(yù)測腎功能障礙形成或惡化方面具有普遍性的作用。少量研究已經(jīng)表明,短時BPV加劇可能與通過尿微量白蛋白及腎小球濾過率評估的腎功能障礙存在正向相關(guān)性[8],但與血肌酐、血尿素氮關(guān)系不密切。短時BPV越大,尿微量白蛋白升高越明顯。同時,尿微量白蛋白是反映高血壓病患者早期腎損傷的敏感指標(biāo)。尿常規(guī)中尿蛋白的出現(xiàn)要遠(yuǎn)遠(yuǎn)遲于尿微量白蛋白的出現(xiàn)。所以尿微量白蛋白的監(jiān)測是一種比眼底檢查更敏感的高血壓所致血管損傷指標(biāo)。然而,縱向研究發(fā)現(xiàn),夜間血壓的非杓型或反向杓型模式是腎功能不佳預(yù)后的獨(dú)立預(yù)測因子。夜間血壓主要是根據(jù)24 h動態(tài)血壓監(jiān)測進(jìn)行評估的。這個結(jié)果與通過多種腎功能臨床指標(biāo)評估的結(jié)果是一致的[9-10]。家庭自測血壓具有預(yù)測腎功能受損的作用[11-13]。隨診間BPV可能在預(yù)測腎病和慢性腎臟疾病形成和惡化風(fēng)險方面具有顯著作用[14]。所以密切監(jiān)測血壓,使血壓控制在一個相對穩(wěn)定的水平,能降低高血壓病患者腎臟的損害,防止慢性腎衰竭的發(fā)生。同時完善監(jiān)測BPV的方式,劃分好BPV的等級,對于降低靶器官損傷及預(yù)測該事件發(fā)生率有著至關(guān)重要的作用。
2.2 血壓的變異性和心肌肥厚
BPV主要反映自主神經(jīng)功能的完整性以及交感神經(jīng)和迷走神經(jīng)對血管調(diào)節(jié)的動態(tài)平衡。大量研究表明,高血壓病患者夜間交感神經(jīng)功能活躍,BPV增加,結(jié)果使腎素-血管緊張素-醛固酮系統(tǒng)激活。醛固酮能使心臟間質(zhì)細(xì)胞增生成纖維細(xì)胞,膠原量增多,同時血管緊張素Ⅱ能直接刺激心肌細(xì)胞,最終導(dǎo)致心肌肥厚,心室質(zhì)量增加。相關(guān)研究已經(jīng)證明,正常人群左心室質(zhì)量與BPV獨(dú)立相關(guān),而且有證據(jù)顯示左心室質(zhì)量與心率值無關(guān)。同時,也發(fā)現(xiàn)主動脈增厚明顯與BPV呈正相關(guān),甚至主動脈對BPV增高的反應(yīng)性比心臟更敏感。早期部分研究數(shù)據(jù)表明,24 h血壓監(jiān)測獲得的血壓平均值在預(yù)測左心室肥厚方面比簡單的血壓測量更加準(zhǔn)確。動態(tài)血壓監(jiān)測記錄了24 h BPV。24 h BPV幅度升高提示高血壓病患者發(fā)生心血管并發(fā)癥的風(fēng)險較高,例如左心室收縮功能不全[15]。在調(diào)查了BPV和左心室肥厚之間關(guān)系的研究中,大部分考察的都是短時變化[16-17]。在夜間血壓的非杓型模型和動態(tài)血壓評估的晨峰血壓升高及普通人群的左心室質(zhì)量增加均與心血管疾病發(fā)病率增加有一定關(guān)系,并且與高血壓病患者的心室重構(gòu)也有關(guān)系。然而,最近的一項薈萃分析研究了短期血壓變異性和左室質(zhì)量指數(shù)之間的相關(guān)性。結(jié)果表明,BPV和左心室質(zhì)量存在微弱的正相關(guān)性[17]。然而另外一項研究表明,頻率較高的隨診間BPV監(jiān)測能夠預(yù)測高血壓病患者發(fā)生左心室肥厚的概率[18]。通過監(jiān)測高血壓病患者BPV,能早期預(yù)測高血壓病患者發(fā)生心肌肥厚的風(fēng)險,同時預(yù)防心血管事件的發(fā)生。
2.3 血壓的變異性和動脈粥樣硬化
BPV是頸動脈粥樣硬化和腦小血管病變形成的最主要的危險因素。頸動脈粥樣硬化和腦小血管病變會增加中老年人中風(fēng)風(fēng)險或?qū)е抡J(rèn)知能力下降。近年來,對于BPV引起的頸動脈粥樣硬化合并腦血管的病變繼而引發(fā)高血壓病患者中風(fēng)及認(rèn)知功能障礙的關(guān)注度明顯增高。因此,在臨床癥狀出現(xiàn)之前,盡早對這些頸動脈及腦小血管進(jìn)行檢測,可能能夠降低動脈粥樣硬化及腦損傷的發(fā)生率[19]。
短期和長期的血容量脈沖增加即BPV已經(jīng)被認(rèn)為是引起老年高血壓病患者中風(fēng)的一個獨(dú)立危險因素[20]。夜間血壓下降與腦梗死有關(guān),而晨峰血壓上升或血壓在夜間大幅下降都與腦出血有關(guān)。近日,對大量高血壓病患者的研究表明,隨診間BPV被認(rèn)為是日常生活中中風(fēng)的預(yù)測指標(biāo)[21]。
對于認(rèn)知功能障礙,BPV與老年受試者在認(rèn)知測試中得到低分?jǐn)?shù)存在關(guān)聯(lián),而且也是中年受試者認(rèn)知能力下降高風(fēng)險預(yù)測指標(biāo)[22]。此外,在年輕受試者中,長期BPV與其25年后精神反應(yīng)速度和言語記憶下降有關(guān),而與血壓水平的高低無關(guān)[23-24]。最新的研究也證實了短期BPV和動脈損傷早期階段的關(guān)聯(lián),并且近10年來,這種關(guān)聯(lián)性的發(fā)現(xiàn)越來越多[25]。非杓型模型和晨峰血壓的增加,不僅與具有高風(fēng)險心血管疾病的老年受試者和患有高血壓病的中年受試者的頸動脈內(nèi)膜-中層厚度(carotid intima media thickness,cIMT)的增加有關(guān),而且也與其血清炎癥標(biāo)志物的水平升高有關(guān)[26]。頸總動脈位置表淺,形態(tài)直,測量的可重復(fù)性好,是超聲觀察動脈IMT的理想窗口。同時大量研究表明,24 h收縮壓或脈壓的標(biāo)準(zhǔn)差與IMT值呈正相關(guān)關(guān)系[27]。此外,24 h BPV不僅與頸動脈粥樣硬化有關(guān),而且也與頸動脈硬度有關(guān),同時BPV也與血壓正常的人和中度高血壓病患者的內(nèi)皮功能障礙有關(guān)[28]。近期研究證明,短期BPV與高血壓病患者受試者的頸動脈粥樣硬化及亞臨床腦小血管疾病有關(guān),而與血壓水平和其他臨床協(xié)變量無關(guān)[29-30]。
3 小結(jié)
本文旨在闡明BPV與靶器官損傷的關(guān)系,其中最新證據(jù)表明對于降低靶器官的損傷,相比降低血壓水平來說,嚴(yán)格控制BPV也至關(guān)重要。此外,通過對血壓的密切監(jiān)測發(fā)現(xiàn)血壓變異程度及血壓的晝夜模式,可更清楚地了解BPV與腎、心、頸動脈等靶器官損傷之間的關(guān)系。然而,目前對BPV還沒有標(biāo)準(zhǔn)化的測量方式以及明確的劃分。同時也發(fā)現(xiàn)24 h SBP相對于24 h DBP和CV值來說對靶器官的影響更大。進(jìn)一步研究顯示,使用不同的降壓藥物對降低血壓水平及BPV有不同效果,比起其他降壓藥,鈣離子拮抗劑的單一療法或者配合利尿劑的使用可以更好地降低BPV。而腎素-血管緊張素轉(zhuǎn)化酶抑制劑在控制BPV方面并沒有相關(guān)證據(jù)可以證明。所以在降壓過程中,應(yīng)正確評價藥物療效,根據(jù)患者異常血壓的分布,全面指導(dǎo)臨床醫(yī)生調(diào)整降壓藥物的劑量、種類及給藥時間等。近年幾項研究表明,高血壓患者BPV引起靶器官損傷事件中可能存在炎癥標(biāo)志物作為介質(zhì),應(yīng)進(jìn)一步探索炎癥標(biāo)志物的種類及導(dǎo)致靶器官損傷的機(jī)制,從而降低炎癥介質(zhì)水平,達(dá)到降低靶器官損傷率的目的。鑒于BPV程度的劃分及最佳控制藥物沒有明確規(guī)定,所以在未來研究中,需要更深入研究,以明確BPV的安全范圍及最佳用藥,早期預(yù)測及避免靶器官損傷事件的發(fā)生,以降低靶器官損傷發(fā)生率及心血管事件死亡率。
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(收稿日期:2017-01-20 本文編輯:程 銘)