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失眠对心血管疾病的影响

2016-01-24罗鸿宇华琦

中国心血管杂志 2016年2期
关键词:心血管障碍人群

罗鸿宇 华琦

100053 北京,首都医科大学宣武医院老年病(综合)科(罗鸿宇),心脏中心(华琦)



·综述·

失眠对心血管疾病的影响

罗鸿宇华琦

100053 北京,首都医科大学宣武医院老年病(综合)科(罗鸿宇),心脏中心(华琦)

【摘要】失眠是临床工作中最常见的睡眠障碍之一,因其可影响代谢、内分泌、免疫等,甚至引发或加重多种内科疾病,近年来受到广泛关注。目前许多研究显示,失眠与高血压、冠心病、心力衰竭、心律失常等多种心血管疾病密切相关。因此,本文就失眠对上述心血管疾病的影响及其可能机制进行综述,以期提高临床医师对心血管疾病患者睡眠质量的关注。

【关键词】入睡和睡眠障碍;心血管疾病

睡眠是人和高等动物普遍存在的生理节律现象,以维护机体健康及中枢神经系统正常功能。人类的正常睡眠对于生物修复十分重要。尽管睡眠被机体内多系统共同调节,但睡眠障碍仍普遍存在。睡眠障碍是睡眠-觉醒过程中表现出的各种功能障碍的总称,包括睡眠的数量、质量、时间或节律紊乱。由于目前睡眠障碍影响着全世界45%以上的人口,因此该问题已成为重要的全球性公共卫生问题[1]。失眠是最常见的睡眠障碍,因其可能影响代谢、内分泌、免疫等,甚至引发或加重多种内科疾病,近年来受到广泛关注。目前许多研究显示,失眠与高血压、冠心病、心力衰竭、心律失常等心血管疾病密切相关[2-5],并指出失眠可作为心血管疾病的危险因素之一[6]。因此,本文就失眠对心血管疾病的影响进行综述,以期提高临床医师对心血管疾病患者睡眠质量的关注。

1失眠的定义及流行病学

失眠指由于各种原因引起的主观上的睡眠不足,包括入睡困难、睡眠维持困难、过早觉醒以及不能恢复体力的睡眠[7]。由于失眠的诊断受患者主观因素影响,不同研究对于失眠流行病学的统计差异较大。

2失眠对心血管疾病的影响

2.1失眠与高血压

国内外很多研究显示,失眠为高血压发生的危险因素之一[8-9]。Meng等[8]采用荟萃分析方法对11项研究进行汇总,指出短睡眠时间以及失眠相关症状与高血压患病风险的增加相关。美国一项研究对4 810例32~59岁的研究对象进行了为期8~10年的随访,结果显示每晚睡眠≤5 h者,在调整肥胖、糖尿病等因素后,发生高血压的危险仍可增加2.1倍(HR:2.10,95%CI:1.58~2.79)[9]。针对亚裔人群的研究也获得了相似结果[10-11]。此外,失眠亦可影响血压。Sherwood等[12]在校正人种差别后发现,睡眠质量差可导致睡眠期收缩压下落不足。Huang等[13]则提出,睡眠质量可作为非杓型高血压的独立预测因子。

上述研究均提示,失眠可显著影响健康人群及高血压人群的血压状况,但其作用机制目前仍不明确。有研究认为睡眠不足可能导致胰岛素敏感性降低,瘦素分泌减少,胃饥饿素分泌增加[14],引发2型糖尿病或肥胖,从而增加高血压发病风险。另一些研究指出,血压和交感神经活性在睡眠剥夺后可显著升高[15-16],这可能与长期睡眠障碍引起反复紧张、焦虑、抑郁等情绪,兴奋大脑皮层,使皮层下中枢活动的调节发生异常,交感神经活性增强,周围动脉血管收缩,外周阻力增加有关。Ogawa等[17]利用微神经成像技术对成年男性进行睡眠剥夺的相关研究发现,在完全睡眠剥夺后,动脉压力感受器的敏感性降低,自主神经对动脉压力感受器进行调节,导致血压升高。另有学者认为,失眠可引起肾素-血管紧张素-醛固酮系统异常激活,导致体液调节失衡,进而影响血压[18-19]。血管紧张素Ⅱ是强有力的缩血管物质,可使全身微动脉收缩,血压升高;同时,促进醛固酮分泌,引起水钠潴留,加重血压升高。正常情况下,醛固酮的分泌节律为清醒时多,睡眠时少[20],而长期的失眠使机体处于清醒状态的时间延长,醛固酮分泌节律紊乱,分泌增加,进一步使血压升高。

2.2失眠与冠心病

目前认为,失眠可增加人群罹患冠心病的风险[21-22],甚至促发心肌梗死(myocardial infarction,MI)[23]、急性心力衰竭、心原性休克[24]等心血管事件,间接或直接影响心脏功能。Hoevenaar-Blom等[21]通过对20 432名健康受试者进行10~15年的随访研究发现,在校正混杂因素后,睡眠时间≤6 h者较睡眠时间正常者冠心病发病率提高19%(HR:1.19,95%CI:1.00~1.40);而合并睡眠质量差的短睡者比睡眠质量好的健康人冠心病发病率提高79%。Cappuccio等[22]的研究也获得了近似的结果。Cole等[23]对1 270例女性初发MI患者进行回顾性分析,发现睡眠障碍的主诉可能与MI的发生有一定相关性。Laugsand等[25]对52 610例研究对象进行了长达11.4年的随访,发现失眠发生的频率越高,症状越明显,MI发病风险越高。

失眠可通过改变交感神经活性,诱发内分泌或代谢紊乱,促进炎症反应等多方面影响心血管系统,促进冠心病的发生发展。长期失眠引起交感活性增强[15-16],儿茶酚胺释放,使心率增快,心肌耗氧量增加,冠状动脉收缩,氧自由基释放,导致心脏损伤[26]。而具有心脏保护作用的褪黑素在失眠患者中分泌水平降低[27],同样促进冠心病的发生。有研究显示,失眠可导致血管内皮功能受损,进而使血管内皮细胞释放的一氧化氮活性下降,引起血管收缩、血小板聚集及血栓形成,在冠心病的发生发展中也起到了重要作用[28]。此外,近年来失眠所致炎症反应对心血管事件的影响也已受到广泛重视。Frey等[29]的睡眠剥夺研究发现,健康青年人在睡眠剥夺48 h后,机体E-选择蛋白、细胞间黏附分子-1、白细胞介素-1β等炎症因子水平显著升高;而Irwin等[30]则发现,睡眠缺失可引起单核细胞促炎细胞因子反应,驱动细胞免疫激活和炎性细胞因子释放;这些炎性因子共同作用,增加心血管事件危险性。

2.3失眠与心力衰竭

心力衰竭是多种心血管疾病的终末状态。在心力衰竭患者中,有23%~73%伴发失眠症状[31]。由于心力衰竭和失眠可互相影响,目前对于二者相关性的研究较少。但现有研究显示,失眠可增加人群未来发生心力衰竭的风险,同时可严重影响慢性心力衰竭患者的生活质量。Ingelsson等[32]对2 314名中年男性进行了长达30年的随访,发现睡眠障碍可作为心力衰竭发生的独立危险因素,但仅限于超重(体质指数>25 kg/m2)的中年男性。Laugsand等[33]对54 279名基线无心力衰竭的研究对象进行了平均时长11.3年的随访研究,发现在校正其他心血管危险因素及急性MI后,失眠仍可增加人群心力衰竭的患病风险,且与无失眠的健康人群比较,合并失眠症状越多,患病风险越高,当合并3种失眠症状时,心力衰竭的患病风险可增至正常睡眠者的4.53倍(95%CI:1.99~10.31)。目前的研究对上述情况发生的原因尚无明确解释,但许多学者认为,这一过程类似失眠对冠心病的促进过程。

2.4失眠与心律失常

健康人群在睡眠过程中可出现窦性心动过缓等生理性心律失常,但睡眠时间不足以及睡眠质量下降则可能诱发心律失常。Sgoifo等[34]发现,在48 h睡眠剥夺后大鼠心率变异性降低,迷走神经活性明显受到抑制,自主神经系统活动失衡;当继续给予大鼠急性束缚应激时,大鼠迷走神经抑制进一步加深,并出现室性期前收缩。Ewing等[35]则证实,健康人群在发生睡眠剥夺后,其心率变异性的昼夜变化节律同样消失。另有研究指出,当健康人群发生急性睡眠不足时,其体表心电图P波时限以及P波离散度均较正常睡眠时增加[36],心房电机械延迟也明显增加[37],而这些指标变化均被认为与心房颤动的发生密切相关[38]。但目前的研究尚未能完全解释失眠如何影响心电活动,很多学者认为,神经-体液调节在这一过程中发挥了重要作用。

3小结与展望

根据目前国内外现有的研究成果,失眠可通过增加交感神经活性,调节内分泌或代谢情况,促进炎症反应等方式,促进高血压、冠心病、心力衰竭及心律失常等心血管疾病的发生与发展,并增加相关疾病心血管事件发生率。因此,对于失眠患者,应早期予以临床干预,以减少其对机体的损害及各种心血管事件的发生。

利益冲突:无

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(本文编辑:谭潇)

Influence of insomnia on cardiovascular diseases

LuoHongyu,HuaQi

DepartmentofGeriatricMedicine,XuanwuHospital,CapitalMedicalUniversity,Beijing100053,China(LuoHY);DepartmentofCardiology,XuanwuHospital,CapitalMedicalUniversity,Beijing100053,China(HuaQ)

【Abstract】Insomnia is one of the most common sleep disorders in clinical practice. Because insomnia can affect the metabolic,endocrine and immune system,and even cause a variety of internal diseases,it attracted more and more attention in recent years. At present,many studies have suggested that insomnia was closely related to many cardiovascular diseases. Therefore,the influences and mechanisms of insomnia on cardiovascular disease were reviewed in this article,in order to raise the clinician attention of sleep quality in patients with cardiovascular disease.

【Key words】Sleep initiation and maintenance disorders;Cardiovascular diseases

(收稿日期:2015-06-11)

Corresponding author:Hua Qi,Email:huaqi5371@medmail.com.cn

DOI:10.3969/j.issn.1007-5410.2016.02.020

通讯作者:华琦,电子信箱:huaqi5371@medmail.com.cn

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