高血压在糖尿病患者中很常见,其患病率取决于糖尿病的类型、病程、年龄、性别、种族/民族、BMI、血糖控制情况、肾脏病的存在情况以及其它因素(1-3)。此外,高血压是动脉粥样硬化性心血管疾病(ASCVD)、心衰、微血管并发症的一项强劲危险因素。ASCVD定义为由动脉粥样硬化导致的急性冠脉综合征(ACS)、心肌梗死(MI)、心绞痛、冠脉或其他动脉的血运重建、脑卒中、短暂性脑缺血发作(TIA)或外周动脉疾病(PAD);ASCVD是糖尿病患者死亡率和住院率的首要原因,构成了糖尿病直接或间接医疗费用最大的部分。大测量研究表明治疗高血压可以减少糖尿病患者的ASCVD事件,心衰和微血管并发症(4-8)。同时处理多重危险因素可有更大获益(9)。有证据表明自1990年以来,可能由于糖尿病患者的血压控制大部分得到改善,其ASCVD的发病率和死亡率已经下降。此立场声明旨在更新糖尿病患者高血压的评估和治疗,更新包括美国糖尿病学会(ADA)最近在2003年发表的立场声明以来的所有进展(3)。
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定义、筛查和诊断
推荐
每次常规临床接诊都要测量血压。有血压升高(140/90mmHg)的患者应该多次测量血压,包括在不同日测量血压来诊断高血压。
所有糖尿病伴高血压的患者应在家监测血压以检出白大衣高血压。
在初次评估高血压和在随访时应定期测量直立位血压,或在出现直立性低血压症状时和如果已经诊断了直立性低血压应常规测量直立位血压。
每次常规临床接诊都要测量血压(15)。在最初接诊时,需测量两臂血压,以便发现和解释可能因虚假血压如动脉狭窄所致的异常。对于未知有高血压的患者血压升高(≥140/90 mmHg),应当在1个月中的不同日测量血压,以便明确高血压的诊断。
基于诊室的半自动示波计血压 (常规或诊室血压)是诊断高血压和监测治疗反应的常规方法。血压应由受过训练的人来测量(15),受试者取坐位,双脚放在地板上,手臂支撑放置在心脏水平。袖带尺寸应与上臂围匹配(表1)。为了减少测量血压的变异性,应在休息5分钟后测量血压,测量2-3次血压,每次测量间隔1-2分钟,取测量值的平均值(16)。多次测量血压取平均值对于诊断高血压和调整降压治疗尤为重要。
表1 对于给定的上臂围血压测量袖带大小的推荐
自动化诊室血压(AOBP)是测量血压的另一种方法,它是完全自动的测量血压装置,能在几分钟内多次测量血压(3-5次)并取平均值,最好在患者静息时进行测量(17)。AOBP被用在两项大型、重要的临床试验中,即控制糖尿病患者的心血管风险行动(ACCORD)(18)和SBP干预试验(SPRINT)(19)。测量时如果患者独处,这种方法也用于诊断白大衣高血压。在患者单独一个人时测量血压仍可进行,这对诊断白大衣高血压很有用(20)。AOBP测值比常规测量血压数值平均低5-10mmHg。因此,使用AOBP的临床试验结果不能直接运用在使用常规测量血压的医疗实践中(17、21-23)。除了ACCORD(18),糖尿病患者高血压治疗获益的大多数证据是基于常规的诊室血压测量。
高血压定义为持续性的血压≥140/90mmHg。这个定义是基于明确的数据,即高于此域值水平的血压与ASCVD、死亡、残疾和微血管并发症密切相关(1、2、24-27),而基线血压高于此域值的人群降压治疗可减少ASCVD事件(4-6、28、29)。高血压定义中的“持续”很重要,因为血压有相当大的正常变异。诊断高血压的标准应与血压治疗目标相区别。
高血压的诊断和管理,可能因两种常见的情况即隐匿性高血压和白大衣高血压而变得复杂。隐匿性高血压的定义是:诊室血压正常,即<140/90mmHg,但家庭测量血压升高,即≥135/85mmHg(30);这个较低的家庭血压域值是基于几项预后研究(31),较低的家庭血压与较高的诊室血压相一致。白大衣高血压则是诊室血压升高,即≥140/90mmHg,而家庭血压正常,即(未治疗)<135/85mmHg(32)。通过家庭血压监测识别这2种情况,可能有助于防止对并不增高ASCVD风险的白大衣高血压进行过度治疗,而对于隐匿性高血压的情况,适当用药以减少在血压正常期间的副作用(33、34)。
家庭血压测量包括用动态血压监测所测得的白天血压,以及用家庭血压监测仪取得的血压测量。袖带规格很重要,因为袖带太小的测值会高于实际血压值,袖带太大的测值则会低于实际血压值。应当使用正确的袖带规格,即充气囊要围绕手臂的80%(表1)。袖带正中应置于患者的上臂,上臂放在右心房水平(胸骨中点),不应包在衣服上。
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直立性低血压
糖尿病自主神经病变或容量耗竭可导致直立性低血压(35),这可由降压药进一步加剧。直立性低血压的定义是,与坐位或仰卧血压相比,站立3分钟内SBP下降20mmHg或DBP下降10mmHg以上(36)。直立性高血压在2型糖尿病并高血压患者中是常见的,与死亡率和心衰风险增高相关(37)。
评估直立性低血压的症状是很重要的,以个体化地确定血压目标,选择最合适的降压药物,减少降压药的不良反应。另外,可能需要调整降压药类型和给药时间(转为夜间剂量)。特别是α受体阻滞剂和利尿剂可能需要停用。直立性低血压患者可从弹力袜和其他方法获益(38)。
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血压目标
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绝大多数糖尿病合并高血压的患者应当治疗到SBP目标<140mmHg和DBP目标<90mmHg。
对于存在心血管病高风险的个体,如果他们能够达到而没有过多的治疗负担,更低的SBP和DBP目标值,例如<130/80mmHg,可能是适宜的。
流行病学分析显示,血压≥115/75mmHg以逐级的形式与ASCVD(27)、心衰、视网膜病变、肾脏病变和死亡率风险增高相关,提供了控制血压对糖尿病临床预后是非常重要的证据(1、2、24、26、39)。然而,血压目标的观察研究易受到混杂因素的影响,且不是直接评估血压降低的效果。临床试验及其汇总分析提供了最强的处理血压的证据,并对血压目标,特别是2型糖尿病患者的血压目标,提供了根本的指导。
高血压治疗至血压<140/90mmHg得到了明确的证据支持,即对≥140/90mmHg的血压进行药物治疗,可降低心血管事件以及某些微血管并发症。在2型糖尿病患者中,英国前瞻性糖尿病研究(UKPDS)显示目标血压<150/85mmHg比180/105mmHg可减少糖尿病微血管和大血管并发症24%(28)。此外,临床试验的汇总分析显示,糖尿病伴有基线血压≥140/90mmHg人群的降压治疗,可降低ASCVD、心衰、视网膜病变、白蛋白尿的风险(4-8、40)。因此,大部分有高血压的1型或2型糖尿病患者至少应当治疗到血压目标值<140/90mmHg。
对于特定的糖尿病患者,强化降压到目标血压比<140/90mmHg更低(如<130/80mmHg或<120/80mmHg)可能是有益的。这样的强化血压控制已经在里程碑式的临床试验及其汇总分析中进行了评价。
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强化血压控制的随机临床试验
ACCORD 血压试验(ACCORD BP)检验了在2型糖尿病患者中强化血压控制(目标SBP<120/80mmHg)与标准血压控制(目标SBP<140/90mmHg)的效果。其它的试验,如高血压优化治疗(HOT)试验和SPRINT试验检验了强化降压与标准降压的潜在获益,尽管其结果与糖尿病患者的关联不太明朗。糖尿病和血管疾病行动:增哚普利和达美康缓释片有对照的评价–血压组 (ADVANCE BP)试验,在2型糖尿病患者中检验了固定剂量复方制剂降压干预与安慰剂的效果,也研究了降压目标(41)。试验的细节显示在表2。
表2 强化与标准降压治疗策略的随机对照试验
在ACCORD BP试验中,强化血压控制没有降低总体主要ASCVD事件,但的确减少了卒中风险,代价是增加了不良反应事件(18)。具体来说,相较目标SBP<140mmHg,目标SBP<120mmHg,MI、卒中、心血管死亡的一级复合终点,组间没有显著性差异(风险比(HR)0.88, 95% CI 0.73-1.06)。 卒中减少41% (HR 0.59, 95% CI 0.39 -0.89), 但归因为降压治疗导致的严重不良反应为3.3%对1.3%,低血压、电解质紊乱、血清肌酐增高的发生率显著升高。因此,ACCORD BP结果显示在经过选择、告知了其额外的治疗负担、副作用和花费增多的患者中,血压控制目标比<140/90mmHg更低可能是合理的(18、24)。ADVANCE试验中干预组所达到的血压(136/73mmHg)高于ACCORD试验强化组(119/64mmHg)所达到的血压,且与目标血压(<140/90mmHg)一致,但ADVANCE试验并不是明确地检验血压目标的(43)。需要注意的是,ACCORD BP试验和 SPRINT试验使用AOBP测量血压,测量值一般低于常规诊室血压约5-10mmHg(17),提示在典型的诊室中使用ACCORD BP试验和 SPRINT试验方案,SBP目标值可能要高于<120mmHg。
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试验的汇总分析
对使用多种降压药物的有安慰剂对照的临床试验进行汇总分析,明确地证明降压治疗一般都能降低糖尿病患者中的ASCVD、心衰、视网膜病变、白蛋白尿和死亡风险(4-8、40)。总的来说,与没有糖尿病的高血压患者相比,糖尿病合并高血压的患者,降压治疗相对获益相似,绝对获益可能更大(5、8、40)。为了明确糖尿病患者最佳的血压目标值,通过在干预或强化治疗组中所达到的平均基线血压或平均血压,汇总分析将临床试验进行了分层。根据这些分析,当平均基线血压≥140/90mmHg或平均达到的强化治疗血压≥130/80mmHg时,降压治疗似乎有益的(4、6-8)。在基线血压或达到的血压较低的试验中,降压治疗可降低卒中、视网膜病变和白尿蛋白的风险,但对其他ASCVD和心衰的影响不明显。关键是这些都是试验水平的汇总分析,与个体水平的汇总分析相反,易受到混杂因素的影响且其分层不精确,这是需要很好解决的问题(8)。此外,汇总分析主要关注治疗获益,而权衡潜在危害的另外的数据也是需要的。总之,这些汇总分析一致显示,对于基线血压≥140mmHg的患者,治疗到目标血压<140mmHg是有益的,虽然更强的目标可能提供额外却可能不太大的获益。
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治疗目标的个体化
患者和医生应当共同参与决策过程以确定个体化的血压目标,要充分认识到强化降压目标的获益与风险是不确定的,并且可能因人而异。根据ADA高糖血症的管理路径,影响治疗目标的因素包括治疗风险(如低血压、药物不良反应)、预期寿命、包括血管并发症在内的并存病、患者态度、期望治疗努力、资源和支持系统(44)。需要考虑的具体因素是心血管事件的绝对风险(40、45),由白蛋白尿反应出来的进行性肾病风险、不良反应、年龄和整体治疗负担。有较高心血管事件(特别是卒中)和白蛋白尿风险的患者,和能相对容易到达强化降压控制而没有显著不良反应的患者,最适合强化降压治疗。相反,具有在老年中常见的情况,如功能受限、使用多种药物和患有多种疾病的患者,可能更适合非强化的降压治疗。
值得注意的是,缺乏可用的高质量数据来指导1型糖尿病患者的降压目标。在1型糖尿病患者中, 血压水平与大血管和微血管预后的关系,与2型糖尿病和普通人群相似(1)。考虑到缺乏对1型糖尿病患者临床预后的随机试验,降压治疗的效果只能从针对其它人群的临床试验中,很可能可从ACCORD BP试验和SPRINT试验外推而来。值得注意的是,与SBP相反,在年龄50岁以下、没有糖尿病的人群中,DBP是预测心血管事件的关键变量,故在年轻成人中应优先考虑(46、47)。尽管缺乏令人信服的数据,年轻成人1型糖尿病患者可能更容易达到强化降压水平,并能从强化降压治疗中得到显著的长期获益。
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治疗
01
生活方式管理
推荐
SBP>120mmHg、DBP>80mmHgr的患者,生活方式干预应包括如果超重或肥胖应减轻体重;采用“预防高血压的饮食方法 (DASH)” 膳食模式包括减少钠而增加钾摄入、多吃水果和蔬菜、适量饮酒和增加体力活动。
生活方式管理是高血压治疗的重要组成部分,因为它能降低血压,加强某些降压药物的效果,促进代谢和血管健康,一般很少引起不良反应。此外,SBP>120mmHg、DBP>80mmHg的糖尿病患者存在发展为高血压及其并发症的风险(48、49),生活方式管理有助于预防和延缓需要药物治疗的高血压诊断。为了有利于长期保持行为改变,生活方式治疗应足以适应患者的需要,并作为糖尿病管理的一部分进行讨论。
尽管在糖尿病个体高血压的治疗中,对饮食和运动尚没有良好对照的研究,但DASH研究评估了健康饮食模式在没有糖尿病的个体中的影响,显示其降压效果与单药治疗的效果相似(50)。最近的一篇汇总分析发现,生活方式干预可降低2型糖尿病患者的血压(51)。中、高强度综合的生活方式建议,已经显示对于有包括糖尿病在内的心血管危险因素的患者,对血压、血脂、空腹血糖和体重的中间终点有益,特别是坚持了12到24月之后(52)。
生活方式治疗包括通过限制热量摄入减轻过多的体重、限制钠盐摄入(<2300mg/日)、多吃水果蔬菜(8-10份/日)和低脂奶制品(2-3份/日)、避免过量饮酒(男性<2份/日,女性<1份/日)(53)、戒烟、减少静坐时间(54)和增加体力活动(55)。这些生活方式策略还可能影响血糖和血脂控制,故对于即使血压轻度升高的人也应当鼓励进行。此外,应鼓励医生常规检查患者的用药清单,找出可能升高血压的药物,包括非处方药和草药。例如,一篇汇总分析显示,非甾体类抗炎药可平均升高血压5mmHg(56)。
02
钠盐
对于糖尿病患者,减少钠盐摄入还未在有对照的临床试验中进行检验。然而一些试验结果显示,原发性高血压患者,中等减少钠盐摄入(每日摄入量从200mmol[4600mg]减少至100mmol[2300mg]),可降低SBP5mmHg和DBP2-3mmHg(57)。随着钠盐摄入减少已观察到一种剂量反应关系。甚至在使用降压药时,如针对高血压的高容量同时限钠,可有更好的效果。
03
体育运动
中等强度体力活动,如1周中大多数日子进行30-45分钟快步走可降低血压(58)。规律的运动可以降低血压,使得需要调整降压药物的剂量(59)。β阻滞剂可降低最大运动能力,而利尿剂可增加脱水的风险。应鼓励所有患者包括身体受限的老年患者进行体力活动。体力活动的类型和强度应适应于患者的意愿和功能状态。
04
减轻体重
在血压管理中应考虑减轻体重。体重减轻1kg可使血压下降1mmHg(60)。一些减肥药可导致血压升高,故必须慎用。
05
睡眠呼吸暂停
对糖尿病患者的随机研究显示,治疗阻塞性睡眠呼吸暂停可降低血压(61)。
06
药物降压治疗
推荐
已证实诊室血压≥140/90mmHg的患者,除了生活方式治疗外,应及时滴定药物治疗以达到降压目标。
已证实诊室血压≥160/100mmHg的患者,除了生活方式治疗外,立即开始并及时滴定已经证实可降低糖尿病患者心血管事件的2种降压药或固定剂量单片复方制剂。
高血压的治疗应包括已证实可降低糖病患者心血管事件的药物类型:ACEI、ARB、噻嗪类利尿剂或二氢吡啶类钙拮抗剂(CCB)。为了达到降压目标一般需要多种药物联合治疗(但ACEI与ARB不能联用)。
ACEI或ARB,以适应于降压治疗的最大可耐受剂测量,推荐作为糖尿病伴尿白蛋白/肌酐比≥300mg/g的一线降压治疗(A);或作为伴尿白蛋白/肌酐比30-299mg/g的一线治疗(B)。如果其中1类不能耐受则用另1类。
对于用ACEI、ARB或利尿剂治疗的患者,应当监测血清肌酐/eGFR和血钾水平。
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初始降压药的数测量
糖尿病患者的初始降压治疗取决于高血压的严重程度(图1)。血压在140/90mmHg至159/99mmHg之间的患者可以用1种降压药开始治疗。对血压≥160/100mmHg患者,推荐初始治疗使用2种降压药物。糖尿病患者的高血压和氨氯地平效果 (SHIELD) 研究是最早的试验之一,旨在评估在平均血压超过160/100mmHg的患者,除了单药治疗外,给予单片复方制剂,是否达到血压目标值的患者比例更高。与单用ACEI组相比,214例患者了用ACEI加CCB初始治疗,在治疗3个月时,联合治疗的患者血压达标的比例增高(63% vs. 37%; P=0.002)(62)。简化治疗干预控制高血压(STITCH) 试验将超过2000名有或没有糖尿病、平均血压160/95mmHg的患者随机分配到单用ACEI组或ACEI联合噻嗪类利尿药组,在治疗6个月时,联合治疗组达到<140/90mmHg血压目标的比例更高(65% vs. 53%;P=0.026)(63)。单片复方制剂的依从性更好(64)。
糖尿病患者确诊了高血压的治疗推荐
图1.糖尿病患者中确诊了高血压的治疗推荐。
* 对于UACR30-299mg/g的患者,建议使用ACEI或ARB治疗高血压;对于UACR≥300mg/g的患者,强烈推荐使用ACEI或ARB治疗高血压。
** 利尿剂;长效药物如氯噻酮和吲达帕胺显示能降低心血管事件,可作为首选。
*** 二氢吡啶类。UACR=尿白蛋白/肌酐比
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降压药的种类
高血压的初始治疗应包括已证实可降低糖尿病患者心血管事件的药物:ACEI(65、66),ARB(65、66),噻嗪类利尿剂(67),二氢吡啶类CCB(68)。对于伴有白蛋白尿(尿白蛋白/肌酐比[UACR]≥30 mg/g)的患者,初始治疗应包括ACEI或ARB以降低进行性肾病的风险,以下详述。在没有白蛋白尿时,进行性肾病的风险是低的,与其它降压药相比,尚未发现ACEI和ARB可提供更好的心脏保护作用(69)。β阻滞剂可用于治疗冠心病或心衰,但在没有这些情况下作为降压药使用时,并不能降低死亡率(5、70)。
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多种药物治疗
为了达到降压目标,特别是并发糖尿病肾病时,通常需要多种药物治疗。然而,不推荐ACEI和ARB联用,因为缺乏额外的ASCVD获益,却增加不良事件即高钾血症、晕厥和急性肾损伤的发生率(71-73)。应及时滴定或/和加用降压药物,以克服降压达标的临床惰性。只有1项大型临床试验包括了随机分配到2种单片复方制剂和评估心血管和肾脏预后的糖尿病患者。通过联合治疗收缩期高血压的患者,避免心血管事件 (ACCOMPLISH) 试验纳入了存在心血管事件的高危风险患者(60%患糖尿病),显示ACEI(贝那普利)联用二氢吡啶类CCB(氨氯地平)组与ACEI(贝那普利)联用噻嗪类利尿剂(氢氯噻嗪)组相比,发病率和死亡率均降低(68、74)。还需要其他这样的试验来证实这些结果和评价其他的降压药物联合治疗。
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糖尿病肾病
糖尿病并发白蛋白尿(尿白蛋白肌酐比UACR ≥30 mg/g 特别是≥300 mg/g)的患者,存在进行性肾脏病增高的风险(24)。在这种情况下,ACEI和ARB治疗高血压有独特的肾脏保护优势。对有明确糖尿病肾病(包括尿白蛋白排泄率≥30 mg/g)的1型和2型糖尿病患者的预后试验已经证明,以最大的降压剂量使用ACEI和ARB,与安慰剂相比,可延缓肾脏病的进展(75-77)。因此,对尿白蛋白排泄率≥300 mg/g的患者,其降压治疗方案中应包括ACEI或ARB。对于存在任何尿白蛋白水平(尿白蛋白排泄率≥30 mg/g)的高血压患者,临床医生也应考虑使用ACEI或ARB(66)。
在没有白蛋白尿时, ACEI或ARB相较其它降压药在降低心血管事件上的优势并没有得到一致显示(66、69、78、66),尽管小型临床试验提示ACEI、ARB可减少复合的心血管事件并减慢肾脏疾病发展到严重阶段(80-82)。一般认为ACEI和ARB有类似的获益和风险,当1种药物不能耐受时,可用另1种药物(65、83)。
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高钾血症和急性肾损伤
在糖尿病肾病患者中,当估计的肾小球滤过率(eGFR)<45 mL/min/1.73 m2或肌酐>4.5 mEq/L时,虽然患者已经在用利尿剂,高钾血症风险也显著升高(84)。此外,在合并eGFR降低和血钾升高的特定患者中,如果螺内酯加用一种ACEI或ARB,可使发生高钾血症的风险升高8倍(85)。
噻嗪类利尿剂只有当eGFR在30mL/min/1.73 m2以上时,对维持容量和减少高钾血症风险才有效(86、87)。eGFR低于30mL/min/1.73 m2时,应当使用长效袢利尿剂如托拉塞米来代替。
为防止eGFR不经意的下降,用ACEI或ARB治疗的患者应注意容量状态并避免容量的耗竭以降低急性肾损伤的风险。而且,在容量耗竭状态时,高钾血症的风险增高(71、72、88)。
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睡前剂量
证据显示夜间血压下降消失和ASCVD事件存在着关联。一篇临床试验的汇总分析显示夜间比早晨服用降压药对血压控制有小的益处,但没有临床效果的数据(89)。在随后一项随机临床试验的2个亚组分析中,将至少1种降压药改为睡前服用可明显减少心血管事件,但结果是基于少量的事件(90、91)。
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监测
推荐
服用降压药物治疗的患者,应进行家庭血压监测,以提高患者的治疗参与度和依从性。
自我管理是糖尿病治疗并扩展到降压治疗中的关键部分。家庭血压监测可以改善患者药物依从性(92-94)并减少心血管事件风险(95)。此外,证据显示家庭血压监测与24小时动态血压监测的准确性一样(96、97),而且与ASCVD风险的相关性要比诊室血压测量更好(98、99)。
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与糖尿病药物的相互作用
高胰岛素血症和外源性胰岛素,理论上可通过血管收缩和水钠潴留导致高血压(100)。然而,胰岛素也能促进血管舒张,在2型糖尿病和糖尿病前期患者中进行的、用初始甘精胰岛素干预降低终点试验 (ORIGIN) 中,与标准治疗相比较,基础胰岛素与血压的变化无相关(101)。
钠-葡萄糖协同转运蛋白2(SGLT2)抑制剂与轻度利尿作用并降低SBP3-6mmHg、DBP1-2mmHg相关(102、103)。胰高血糖素样肽1受体拮抗剂也与SBP/DBP下降2-3/0-1mmHg相关(104)。
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难治性高血压
推荐
经过常规3种降压药物包括一种利尿剂治疗,不能达到降压目标的难治性高血压患者,应转诊给有资质的高血压专家。
经过常规3种降压药治疗不能达到降压目标的难治性高血压患者,应考虑用盐皮质激素受体拮抗剂(MRAs)治疗。
难治性高血压的定义是:尽管治疗策略包括了合适的生活方式管理加上一种利尿剂和2种其它不同类型的降压药,以足够的剂量使用,血压仍然≥140/90mmHg。在诊断难治性高血压之前,需要排除其它几种情况(表3)。
*高血压继发因素包括内分泌疾病、肾动脉疾病、进展期肾病过度水肿和激素如睾酮。能升高血压的药物包括NSAIDs、减充血剂和一些违禁药物。
因通常需要多种降压药物才能达到降压目标,故作为难治性高血压可能存在药物依从性问题。应常规评估药物依从性的潜在阻碍(如花费、药物数量和副作用)。如果确认依从性好,血压仍不能控制,临床医生应评估高血压的继发性原因。
在已用肾素-血管紧张素系统(RAS)抑制剂、利尿剂和CCB(105)治疗的基础上加用MRAs,对于治疗糖尿病患者的难治性高血压是有效的,部分原因是这些药能降低交感神经活性(106)。MRAs还可减轻白蛋白尿且有额外的心血管获益(107-110)。然而, MRAs与一种ACEI或ARB联用可能增加高钾血症发作的风险。高钾血症可通过饮食限钾、用排钾利尿剂和钾吸附剂(111)来处理,但还需要长期的预后试验来评估MRAs(有和没有辅助的钾管理)在血压管理中的作用。
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妊娠
推荐
糖尿病和原有高血压或并有轻度妊娠期高血压的孕妇,若SBP<160mmHg、DBP<105mmHg,无靶器官损害,无需降压药治疗。
对于糖尿病和原有高血压已行降压治疗的妊娠患者,为了母体健康和胎儿生长最好的长期利益,建议降压目标为120-160mmHg/80-105mmHg。
美国妇产科医师学会(ACOG)不推荐轻度妊娠期高血压(SBP<160mmHg或DBP<110mmHg)的妇女用降压药物治疗,因为没有明确治疗获益确是否超过治疗的潜在风险(112)。1篇Cochrane系统综述没有发现结论性的证据支持或反对治疗原有的轻中度高血压,以降低先兆子痫、早产、小胎龄儿和死胎的风险(113)。对于存在先兆子痫高风险的孕妇,推荐在妊娠12周时开始服用小剂量阿司匹林以降低先兆子痫风险(114)。
对于需要降压治疗的妇女,降压目标为SBP维持在120-160mmHg和DBP80-105mmHg之间,因为更低的血压水平可能与胎儿发育受损相关。高血压并发靶器官损害包括心血管病和肾病的孕妇,可以考虑更低的降压目标(即<140/90mmHg),以避免在妊娠期间这些疾病进展。
在妊娠期间,ACEI、ARB或螺内酯是禁忌的,因为其可导致胎儿损害。已知在妊娠期有效安全的降压药有甲基多巴、拉贝洛尔、肼苯哒嗪和长效硝苯地平。在妊娠后期如需容量控制时可使用利尿剂(115)。有妊娠高血压、先兆子痫、合并先兆子痫的患者,产后需在医院监测血压72小时,产后7-10天内应监测血压(112)。推荐长期随访这些妇女,因为其终生心血管风险增高。
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老年人(≥65岁)
在老化过程中,动脉僵硬可能发生并引起老年人的SBP升高和DBP降低(116、117)。糖尿病本身与动脉硬化加重相关(118)。与没有糖尿病的人相比,糖尿病本身可致动脉僵硬度增高(118),导致年龄相关的SBP升高程度更显著(119-121)。糖尿病伴高血压(主要是SBP)的老年人,通常存在心血管事件和其它年龄相关疾病的风险升高(122-124),因为动脉僵硬而难以达到降压目标,和医源性并发症包括低血糖、体位性低血压和容量耗竭风险增高。
在糖尿病伴高血压的老年患者中,在确定治疗策略和降压目标时,其机能状态、并存病和使用多种药物都是重要的考虑(125)。SBP应当是治疗的主要靶标。在合适的患者中,可以采用与年轻患者类似的治疗策略。在丧失自主能力和主要机能受限的亚组(如其基本日常活动需要帮助的患者)中,应考虑较高SBP目标(如145-160mmHg),在仰卧位SBP较低(<130mmHg)或存在直立性低血压时,治疗强度应当减弱(125、126)。
正如SBP与DBP之间>60mmHg(即脉压)所示,对于血管顺应性受损的老年患者,必须权衡要达到的SBP目标与降低DBP(<65-70mmHg)的风险。在老年人降低DBP低于此水平,可增高冠心病、死亡率和其他不良心血管事件的风险(127-130)。
当考虑老年糖病患者的药物降压治疗时,需注意β受体阻滞剂可掩盖低血糖症状,降压药可加重直立性低血压,利尿剂能加剧容量耗竭。认知功能障碍可能影响服药行为,特别在总体健康状况差、并存多种疾病、急性疾病、联合用药、营养不良时。应定期评估降压治疗的耐受性,特别是直立性低血压。
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在没有高血压时的降压治疗
对于没有治疗的血压<140/90mmHg的糖尿病患者,几乎没有证据表明降压治疗能改善健康预后。有人提出用ACEI或ARB治疗以预防或延缓糖尿病肾病,但数据并不支持这种方法。在1项针对2型糖尿病和正常尿白蛋白排泄率、有或没有高血压患者的试验中,ARB减少或阻滞白蛋白尿的发生,但增高心血管事件发生率(131)。在2项针对没有白蛋白尿或高血压患者的临床试验中,1项入选1型糖尿病患者(132),另1项入选2型糖尿病患者(133),肾活检显示RAS抑制剂并不能预防糖尿病患者肾小球病变的发展。因此,不推荐没有高血压的患者使用RAS抑制剂来预防糖尿病肾病的发生。
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结论
高血压是糖尿病大血管和微血管并发症的1项强劲而可改变的危险因素。大量文献证实了降压的临床效果,证实了多种类型的降压药物都有心血管和微血管获益。临床试验和汇总分析的强力证据支持对大多数成年糖尿病患者,目标血压至少要降到低于140/90mmHg。对于选定的存在心血管疾病高风险的患者,如果他们能够达到而没有过多的负担,更低的血压目标可能是有益的,根据个体基础情况可以考虑这样更低的目标。为了达到降压目标,除了生活方式改变外,通常需要多种类型的降压药物。已经证实ACEI、ARB、二氢吡啶类CCB和噻嗪类利尿剂可改善临床预后,并可作为血压控制的首选。对于有白蛋白尿的患者,ACEI或ARB应当作为降压方案的一部分。对于具体患者,基于其并存病、他们预期降低ASCVD、心衰、进行性糖尿病肾病和视网膜病变的获益和其不良事件风险,治疗应当个体化。这样的交流应当成为临床医生和各个患者之间共同决策过程的一部分。
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未来的更新
为了指导糖尿病患者中高血压的评估与治疗,当有更多的证据可用时,就将在每年的ADA“糖尿病医学诊疗标准”中发表更新的、重新定义的和新增的推荐,可从网址https://professional.diabetes.org/content/clinical- practice-recommendations上查阅。
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柳州市人民医院心内科黄山松教授翻译
柳州市人民医院心内科胡世红教授审校