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考虑亚洲人特征,改善亚洲高血压患者管理的共识文件
作者:胡世红[1] 
单位:柳州市人民医院(广西医科大学第五附属医院)[1]  
文章号:W126141  
2018/1/22 19:54:54    
文字大小:

  高血压是全球死亡率的主要原因和心血管病(CVD)的首位原因。通过生活方式改善或药物,降低血压可降低心血管事件(CVE)。然而,在高血压的决定因素和高血压相关的CVD人口统计学风险方面,存在显著的种族差异。(1-4)在亚洲国家中,卒中特别是出血性卒中和非缺血性心力衰竭(HF)要比西方国家更常见。卒中和HF与高血压的关系要比冠心病(CAD)或肾病更密切。此外,亚太合作队列研究的数据显示血压与CVD的关系,在亚洲患者中要比澳大利亚和新西兰的白人患者更强。

  高血压是全球死亡率的主要原因和心血管病(CVD)的首位原因。通过生活方式改善或药物,降低血压可降低心血管事件(CVE)。然而,在高血压的决定因素和高血压相关的CVD人口统计学风险方面,存在显著的种族差异。(1-4)在亚洲国家中,卒中特别是出血性卒中和非缺血性心力衰竭(HF)要比西方国家更常见。卒中和HF与高血压的关系要比冠心病(CAD)或肾病更密切。此外,亚太合作队列研究的数据显示血压与CVD的关系,在亚洲患者中要比澳大利亚和新西兰的白人患者更强。(5,6)依据高血压决定因素的特征,亚洲人比西方人盐敏感性更高和盐摄入更多。在遗传上,亚洲人可能存在与盐敏感性肾素-血管紧张素系统(RAS)基因多态性相关的因素。(7)事实上,日本人的体重指数(BMI)即使轻微增加也更容易发生高血压前期和高血压,故与高血压前期相关的BMI低于西方国家。(8)

  既往一项对亚洲高年资医生的调查表明,需要考虑亚洲人CVD特征的亚洲指南。(9)考虑到种族特异的特征,为了优化东方亚洲人高血压的管理,在这里,我们制定了一份专家共识文件。

亚洲人高血压和心血管病的特征

共识声明

  1.卒中特别是出血性卒中和非缺血性HF是亚洲高血压相关性CVD常见的结局。

  2.血压与CVD之间的关系,亚洲人比西方人更强。

  3.即使轻度肥胖也有更高的盐敏感性,和盐摄入更多是亚洲人高血压的特征。

诊室外血压

共识声明


  1.为了识别白大衣高血压,推荐诊室外血压测量。

  2.准确地识别和管理隐匿性高血压(或隐匿性未控制的高血压)是很重要的。

  3.在亚洲人群中,最初的重点应放在清晨血压,其次是夜间血压。
测量诊室外血压最重要的作用之一是排除白大衣高血压。很多出版物报道,与真正正常的血压相比,白大衣高血压并不增高心血管风险。(10,11)此外,NICE(英国临床优化国家研究所)推荐使用动态血压监测(ABPM)以识别白大衣高血压(12)

   累积的证据表明,隐匿性高血压(或隐匿性未控制的高血压),定义为诊室血压正常而诊室外血压升高,具有等同于持续性高血压(定义为诊室血压和诊室外血压均升高)的CVE风险。来自ARTEMIS数据库(远程监测高血压与心血管风险的动态血压注册研究)的证据显示,在亚洲比任何其他地区有更多的人被诊为隐匿性高血压和隐匿性未控制的高血压。(13)这就强调了作为高血压治疗的一部分,识别和管理亚洲人中隐匿性高血压和隐匿性未控制的高血压的重要性。此外,由于如下原因:(1)在日本高血压病人中,经ABPM检出和在家测量的清晨血压升高是独立于诊室血压水平的心血管预后的预测因素;(15,16)(2)即使调整了年龄、诊室血压和24小时血压后,亚洲人群清晨血压升高也可能高于西方人群;(17 )(3)在日本的一般人群中,在家测量的清晨血压与傍晚血压相比,在调整了协变量包括诊室血压后,可提供识别卒中发生率的优越的模式;(18)(4)多中心HOMED-BP研究(基于电子血压装置测量的降压目标治疗)显示,在日本高血压患者中,调整降压药物治疗的可行性是根据在家测量的清晨血压,故清晨血压应当是亚洲人中诊室外血压管理最初的重点。(14)

  此外,即使在家控制了清晨血压(<135/85 mm Hg) 的情况下,通过家庭血压监测(HBPM),约1/4的患者仍有隐匿性夜间高血压(≥120/70 mm Hg)。(20)有些研究提示夜间高血压与高钠摄入和盐敏感性相关,这可能是亚洲人群高血压特异的特征。(21)国际流行病学数据证明夜间血压增高是一项强有力的心血管预后预测因素,特别是在治疗的高血压病人中。(22,23)此外,单纯夜间高血压在亚洲人中可能比欧洲人更多见。(23)因此,在亚洲人群中,清晨和夜间血压的管理是很重要的。

清晨血压

共识声明

  1.清晨血压升高,定义为从夜间睡眠时到清晨醒来几小时的血压变化,或清醒1-2小时内血压读数的平均水平,可带来独立于24小时动态血压的心血管风险。

  2.以适当的通常为充分的剂量和适当的联合使用长效降压药物就能控制和应当改善清晨血压。

  缺血性卒中和冠脉事件通常发生于早晨数小时内。(24,25)血压通常也在清晨达到峰值。(26)这类平行现象提示清晨高血压对CVE的发生也许是特别重要的。日本的前瞻性观察性研究首次证实,清晨血压升高,定义为从夜间睡眠时到早晨醒来几小时内的SBP升高,与卒中相关,独立于平均24小时动态SBP和其他心血管风险。(15)这一发现得到了IDACO(国际与心血管预后相关的ABP数据库)大型病例研究的证实。(27)

  清晨风险增高主要归因于清晨血压升高。(28)清晨血压水平,可通过ABPM或HBPM来评估,用于明确清晨高血压。即使在诊室血压已经控制的患者中,未控制的清晨血压也是很常见的,并与CVE风险增高相关。(29)

  清晨血压对亚洲高血压的管理也许特别有关联。一项最近的研究表明日本患者比欧洲患者清晨血压升高率高得多且升高幅度更大。(17)这种种族差异尚未完全了解,或许涉及到病理生理机制如交感神经系统的激活或饮食钠摄入的增多。(31)然而,降压药物使用不足例如使用短效或中效药物、药物剂量不够、或联合降压治疗使用不足,可能是亚洲清晨高血压未被控制的主要原因。(32)在2014年发表的专家推荐中,中国心脏病学会高血压委员会推荐以适当(通常充足)的剂量和适当联合使用长效药物来控制清晨血压。(33)如果经这些治疗方法还没有控制,可以考虑睡前用降压药物。最近,这一讨论扩大到亚洲,并且发表了一项亚洲专家小组的共识声明。(34)

血管老化

共识声明


  1.在很多国家中,特别是在亚洲,预期血管老化将成为高血压的主要表型。

  2.为了支持高血压血管老化的诊断和监测,最好用中心动脉血压策略来管理,将来需要进行随机对照试验。

  血管老化,以动脉僵硬度增高和脉搏波反射为特征,是高血压发生的主要风险因素,尤其是在老年人。(35)血管老化相关的高血压以中心主动脉的脉压增大为特征。(35)中心脉压由主动脉僵硬度和主动脉根部的几何结构所决定。(35)主动脉根部直径较小引起主动脉特征阻抗增高,反过来,又增高主动脉根部的脉压。(35-37)

  亚洲患者的主动脉根部直径通常小于白人患者,部分原因是个头较小。(38)然而,在调整了年龄、身高和体重后,亚洲患者比白人患者可能有更大的主动脉根部直径。(39)因此,亚洲人群与西方人群相比,由于调节心室射血和动脉负荷之间相互作用的主动脉近端直径较大和中层较薄,可能存在中心主动脉脉压增高的特别倾向。(40)亚洲人脉搏波反射往往短于西方人,这有助于增大来自外周动脉脉搏波反射的中心主动脉脉压,(41)这是一种易发生高血压的独立决定因素。(42)

  亚洲人口正在迅速老龄化。亚洲人一般身材也较小,其主动脉近端和管壁张力和僵硬度可能比白种人更大。将这3项因素放在血管老化的背景下表明血管老化对亚洲患者要比西方患者的高血压预后可能有更大的意义。

  为了准确地诊断单纯的中心动脉性高血压,理想的是应当对老龄的亚洲人群监测中心动脉血压。然而,关于中心动脉血压与肱动脉血压相比是否缺乏一致的高预测价值存在持续的争议,反映了一个真正的病理生理问题或由于中心主动脉血压测量使用的方法不足而有潜在偏倚。有必要研究比较中心动脉血压指导的治疗策略与经典指南指导的策略预防CVE的差异。

老年人

共识声明


  1.对老年高血压人群推荐的血压目标值是<140/90 mm Hg。

  2.然而,当患者存在低血压风险或肾脏副作用、或电解质异常风险增高时,可以考虑<150/90 mm Hg的目标。

  3.为了达到老年人群的血压目标和预防其卒中和HF,推荐用CCB、RAS抑制剂和利尿剂。

  在临床试验和各种高血压管理指南中,老年人的定义从>60 岁到>75岁不等。(43,47)大多数指南认为非常老的人应定义为>80岁,在这些病人中,药物治疗应谨慎滴定以避免不良反应和血压过度降低。

  老年人通常有交感神经系统活性增高、血压变异性增大、血压体内平衡受损如体位性低血压或餐后低血压、和盐敏感性增高。(48-50)老年人的高血压以单纯收缩期高血压优势为特征,而SBP是这个人群中的主要风险因素和药物治疗的目标。多种机制包括大动脉僵硬、内皮功能不全、心脏重构、自主神经调节障碍和肾功能不全,导致老年患者高血压患病率高并增高心血管发病率和死亡率。老年高血压患者经历的CVE率是相同血压水平的年轻患者的2-3倍。(51)

  因此,控制血压达到老年高血压人群的目标是很重要的。推荐正是根据已经证明老年患者的血压目标应至少<140/90 mm Hg的数据强度。(52,53) SPRINT(收缩压干预试验)中≥75岁患者的强化治疗,目标血压<120 mm Hg与<140 mm Hg相比,显著降低致命性和非致命性CVE34%和全因死亡率33%。(54,55)同时,HYVET研究(非常年迈老高血压试验)提示在年龄≥80岁的患者中,目标血压<150/90 mm Hg是合理的。(56)

  如果老年患者的SBP目标仍然<150 mm Hg,与SBP<140 mm Hg相比,卒中的相对风险将增高30%-40%。然而,对于存在低血压风险或肾脏副作用或电解质异常风险增高的老年患者,SBP目标<150 mm Hg可能是适合的。在2017ACC/AHA成人高血压预防、检测、评估和管理指南中,一般推荐对老年患者降压治疗的启动应当谨慎,并应监测体位性低血压和跌倒(57)

  在临床实践中,对老年高血压患者,可以推荐分阶段血压达标的方法。首先SBP目标<150 mm Hg;然后,如果可耐受和能达到, 则<140 mm Hg;理想的是,如果可耐受和能达到,<130 mm Hg。(58)最后这一目标与2017ACC/AHA指南对于平均SBP≥130 mm Hg、非集中照顾的、能走动的、在社区居住的老人(≥65岁)SBP治疗目标<130 mm Hg的推荐是一致的。(57)

  因为卒中是亚洲老年人群中心血管死亡最重要的原因,(59)故对这个人群需要更彻底的血压调节。这些人比普通人群往往还有更高的副作用发生率和血压变异性增高的风险,因此,推荐对老年人除了通常的诊室血压外,只要可行,要测量家庭血压。在老年高血压的治疗中,病理生理观念是很重要的:有血管老化和动脉僵硬的人如老年人,血压是高容量依赖的;因此,这些患者通常对小剂量利尿剂或钙拮抗剂反应良好。(60)大多数老年患者需要多种降压药物才能控制血压。对于糖尿病患者和如果有强制性适应证如慢性收缩性HF、心肌梗死后或CKD,可考虑用AECI或ARB。(61)

2型糖尿病(T2D)

共识声明

  1.在伴有T2D的亚洲高血压患者中,可以考虑血压的治疗目标<130/80 mm Hg。

  在ACCORD研究(控制糖尿病的心血管风险行动)中,严格的血压控制,定义为SBP目标<120 mm Hg,未能显示获益优于平常的血压控制(SBP目标<140 mm Hg)。(62)然而,在严格的降压组中,非致命性卒中显著降低37%,总体卒中降低41%。(62)最近在一篇纳入49项降压治疗临床试验涉及73 738例T2D患者的汇总分析中,降低SBP到<130 mm Hg,除了卒中降低外,没有获益的证据。(63)在亚洲人中,与高血压相关的主要CVE是卒中,而在白人中,缺血性心脏病是最常见的心血管结局。(64)因此,在有T2D的亚洲高血压患者中,可以考虑SBP目标130 mm Hg。(65)

慢性肾病(CKD)

共识声明

  1.高血压病人中的CKD患病率高于普通人群,而在亚洲人群中与高血压相关的CKD患病率正在升高。

  2.在CKD存在时,高血压病人需要更强的诊室外血压评估和综合的心血管评估。

  3.对于伴有CKD的患者,需要强化血压控制,以保护肾功能和预防CVE。

  在亚洲,高血压病人中的CKD患病率比总体人群高得多。(66-69)根据中国的全国性调查,CKD的患病率在高血压患者(n=16 691)中为18.9%,而在总体人群(n=47 204)中为10.8%。66此外,在亚洲CKD与高血压的共患率正在增高。日本分别在1974、1988和2002年进行的调查显示,CKD的患病率在已经治疗的高血压患者中(分别为18.8%, 23.8%和 36.1%)和未治疗的患者中(分别为16.6%, 17.5%28.8%)均增高。(70)

  当存在CKD时,高血压患者通常需要通过ABPM和HBPM进行更强的血压测量,因为他们有更大的血压变异性和更高的夜间血压。(71-74)在伴有CKD的患者中,为了准确评估血压和检出已经治疗的或未能控制的夜间高血压,必须进行ABPM。(75,76)HBPM对筛查夜间高血压或许有帮助。(2)因此,对于伴有CKD的亚洲患者,进行更多的诊室外血压测量是必不可少的。

  最新的高血压和CKD指南推荐对伴有CKD的高血压患者进行强化降压治疗。(43,77-85)在亚洲,高血压的主要并发症是卒中;因此,血压目标值可能与西方人群不同,尽管这需要进一步地研究。为了预防CKD进展和卒中,通常需要强化血压控制到130/80 mm Hg。

心房颤动(AF)

共识声明


  1.在伴有AF、拟行抗凝治疗的高血压患者中,可以考虑SBP目标值<130 mm Hg,以降低出血性卒中风险。

  AF患者中高血压的存在可使卒中和过多出血的风险显著增高,因此,需要严格的血压控制和抗凝治疗,以降低心血管风险。
  (86-88)伴有AF的高血压患者,有别于其他的高血压患者,在于大多数AF患者接受了抗凝治疗以降低栓塞并发症的风险。因此,这个亚组患者中的目标血压值也许与其他的高血压患者不同。来自注册研究的事后分析或分析表明,在接受了抗血小板或抗凝治疗的患者中,为了降低出血风险,可能需要较低的血压目标值。在PROGRESS(培哚普利防止复发性卒中研究)的事后分析中,对于有脑血管病史(伴或不伴AF)的患者,用培哚普利活性药治疗,无论是否联用吲哒帕胺,对于已经接受抗凝治疗的患者,可降低颅内出血风险46%,最低的出血风险与中位数SBP113 mm Hg相关。(89)同时,在7406例非瓣膜性AF患者的J-Rhythm注册研究,随访2年,SBP≥136 mm Hg是血栓栓塞和大出血的一项独立危险因素。(90)因此,在伴有AF已经接受了抗凝治疗的高血压患者中,为了降低颅内出血的风险,可以考虑目标血压值130 mm Hg。对于更易发生卒中和因抗凝治疗发生出血并发症的亚洲患者,这就增加了重要性。

卒中的二级预防

共识声明

  1.在东亚国家中,卒中是首要的死因,代表了很大的疾病负担,卒中或许与钠摄入量高相关。

  2.降低血压与复发性卒中风险之间的关系不如一级预防那么明显,但降低血压仍可使卒中事件幸存患者显著获益。

  3.对于卒中事件后卒中和血管事件的二级预防,RCT的证据支持使用基于利尿剂的治疗,尤其是与ACEI联用时。

  4.在卒中后患者中,血压高和血压变异性增大与不良预后相关。故在卒中后高血压的管理中,可以考虑使用对血压变异性控制有优越效果的CCB。

  2014年,在所有死因中,归因于脑血管病的死亡率,在日本排名第4,在中国大陆和台湾均排名第3。此外,调整了年龄和性别的卒中死亡率在亚洲国家最高。(91)钠摄入量高可升高血压,(92)是CVD的一项风险因素;因此,在亚洲的卒中高死亡率可能与这个地区钠摄入的饮食模式密切相关。(92,93)钠摄入减少能以线性方式有效地降低血压,钠摄入每减少2.3 g/d可使SBP降低3.82-mm Hg。(92)对于卒中幸存者,降低血压与复发性卒中之间的关系不如一级预防研究(95)中那么明显,但充分降压仍能使这些患者显著受益。(94,95)

  对于复发性卒中和血管事件的二级预防,来自RCT的证据支持使用基于利尿剂的治疗,尤其是与一种ACEI联用时。(94,96,97)这一发现意味着高钠摄入的不良影响可用基于利尿剂的策略来降低。此外,在卒中后的患者中,血压高和血压变异性增大与不良预后相关。(98-101)一篇研究各类降压药物对血压变异性影响的系统评价和汇总分析表明,个体间的SBP变异,其中50%是由于个体内一次次访视的SBP变异所致,可用CCB最大程度降低。(102)同样,对于管理卒中后的高血压,认为CCB可能是有用的。(102)

降压治疗

共识声明

  1.严格控制24小时血压是很重要的,尤其是在亚洲。

  2.对于个体层面血压的严格控制,家庭血压指导的方法是实践的第一步。

  3.为控制血压,最好使用长效和强效的CCB和RAS抑制剂,用或不用利尿剂。
严格控制24小时血压是很重要的,尤其是在亚洲。1SPRINT明确证明了对高风险或老年高血压患者严格控制血压的获益。

  (103)在亚洲患者中,降压的获益甚至比西方人群更大,因为降压对卒中和HF的影响大于对CAD的影响。(53)

  家庭血压指导的方法,尤其是针对清晨高血压,是个体控制24小时血压的第一步。(14,81,104)对于HBPM而言,清晨SBP目标值125 mm Hg可能是理想的。(105)根据HONEST研究(为确立标准目标血压,已用奥美沙坦的患者家庭血压测量)
(16,29)和HOMED-BP研究,(19)在降压治疗期间所达到的家庭血压是比诊室血压更好的预测指标,表明直到SBP<125 mm Hg,家庭血压越低,心血管预后越好。然而,为了证明这一点,尚需要有充分把握度的随机对照临床试验。当考虑亚洲高血压患者的特征如盐摄入多和高盐敏感性时,最好是使用长效和强效CCB和RAS抑制剂。(1,14,103)长效CCB可有效降低诊室、家庭清晨和24小时动态血压,降低增大的血压变异性,独立于盐摄入量和盐敏感性。(106-108) ARB单药治疗或与一种CCB或利尿剂联用也可有效地降低诊室血压和家庭清晨血压。(109-111)即使在同一类药物中,CCB和RAS抑制剂在其降低24小时血压的潜力方面相差很大。这些差异在盐敏感的、通常还有高盐摄入的亚洲人群中可能会增大。在RAS抑制剂加CCB的基础上加用小剂量利尿剂是一种有效的降压策略。(110,112)

  在特殊人群如心率增快的年轻高血压患者或CAD、AF、或HF患者中,β受体阻滞剂可能是有用的。(81)肾脏去神经治疗可有效治疗未控制的夜间或清晨高血压,(113)尤其是对亚洲患者,(114)因为耐药的亚洲高血压患者要比西方患者有更高的清晨和夜间血压变异性,即使诊室血压是可比的。(115)
  
  结论

  在亚洲国家中,考虑到亚洲人特征的高血压管理可能达到更有效的预防心血管事件和靶器官损害。然而,由于亚洲病人中的一般证据较少,故对于高血压的管理,要澄清亚洲人特异的特征,需要更多的临床研究。

 
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作者简介
胡世红
单位:柳州市人民医院(广西医科大学第五附属医院)
简介: 胡世红,男,出生于1951年9月。1988年7月毕业于广西医科大学,获医学硕士学位。曾在广西
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