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李贺 三甲
李贺 主任医师
平津医院 老年病科

老年人群心、脑血管病的特殊性及防治(武警医学.2010;21(2):163-167)

李  明,郭喜朝,李金升,钟士江,代二庆,吕新亮,审校:李贺

武警部队老年医学专业委员会

 

   人口老龄化是目前世界人口变化的主要特征。欧美国家率先进入老龄化社会, 1999年欧洲≥65岁人口已达总人口14%[1],随后2004年美国老年人口达总人口13% [2]。与世界人口变化趋势同步,我国2004年也开始进入“老龄社会”,老龄人口达1.42亿,约占总人口11%。由于人口基数大,老龄人口增加迅速,截至2006年6月1日,我国60岁及以上老年人口总数为14657万人,其中城市3856万,农村10801万,80岁及以上高龄人口1619万。与2000年第一次抽样调查相比,老年人口占总人口比重由10.2%提高到11.3%,高龄老人占老年人口比例从9.2%增至10.7%。2007年12月发布的统计结果,我国老龄人口1.47亿。联合国人口司预测至2050年不发达国家老龄人口将占全球老龄人口约4/5[3]。随社会老龄化进程加速,老龄人口,特别是≥80岁高龄老年人群健康、医疗问题日益凸显,得到世界各国的重视。平津医院老年病科李贺

    60%以上老年人常并存多种慢性疾病[4],由于年龄相关的机体组织、器官功能变化[5],老年人群发生疾病有其特定的规律和特点,即使老龄后不同年龄段疾病的发生、发展特点也不完全相同,美国心脏病协会(American Heart Association,AHA)和老年心脏病学会(Society of Geriatric Cardiology)按年龄将老年人进一步分为老年65~74岁,中老75~85岁,高龄≥85岁三个年龄段[6]。我国流行病学研究表明,肿瘤、心、脑血管病为导致国人死亡的主要原因[7]。除少数老年特有疾病外,主要年龄相关疾病为高血压、冠心病、脑血管病、代谢综合征(Metabolic Syndrome,MetS)、糖尿病、外周血管病等[5,8-12]

    Framingham研究显示,60~69岁老年人1/2以上发生高血压,70岁以上增加至3/4。55~65岁血压正常者,80~85岁时90%将发生高血压[8]。随年龄增加收缩期高血压(systolic hypertension)发生率升高,50岁以上人群单纯收缩期高血压(Isolated Systolic Hypertension,ISH)最常见。老年人不同年龄段、不同性别对血压水平也有重要影响[13-15]

    年龄是最强的冠心病(Coronary heart disease,CHD)危险因素[16]。人群调查≥75岁,男性CHD发生率2.2%,女性1.3%。尸检研究显示,50%老年女性,70~80%老年男性患阻塞性冠心病(obstructive coronary artery disease)。>80岁老年人占美国人口5%,但占全部心肌梗死(myocardial infarction,MI)住院患者20%,全部住院MI患者死亡30%。冠脉造影检查表明老年人冠心病血管病变更广泛、累及血管更多、钙化更严重、陈旧性MI更常见[17]

    流行病学研究显示,50岁后随年龄增加心力衰竭(heart failure,HF)发生率显著增高。最近美国人群调查结果,HF总发生率为2.2%(95%CI 1.6%~2.8%),45~54岁发病率为0.7%,≥75岁老年人为8.4%;欧洲Rotterdam研究与之相近,55~64岁HF发生率1%,65~74岁3%,75~84岁7%,>85岁为10% [18,19]。老年HF,特别是女性,从收缩性HF主要转向舒张性HF。近来有学者推荐将舒张性HF称为射血分数正常的HF(Heart failure with a normal ejection fraction,HF NEF)[20-22]

     55岁以上人群,年龄每增加10岁,脑血管病发生率增加2倍。美国人群调查资料显示,无症状脑梗塞(silent cerebral infarction)发生率随年龄显著增加,55~64岁人群约11%,65~69岁22%,70~74岁28%,75~79岁32%,80~85岁40%,≥85岁达43%[9]

    代谢异常也随年龄显著增加。已证明糖尿病、糖耐量异常(Impaired glucose tolerance,IGT)和空腹血糖异常(impaired fasting glucose,IFG)与动脉粥样硬化(Atherosclerosis,AS)关系密切,增加心、脑血管病(cardiovascular disease,CVD)、外周血管病危险性和早期死亡率(premature mortality)。第三次美国国家健康、营养调查( third National Health and Nutrition Examination survey,NHANES III)显示,代谢综合征(metablic syndorme,MetS)人群发生率20~29岁为6.7%,60~69岁43.5%,70以上人群42.0%。NHANES 1999~2000年资料显示,美国20岁以上成人糖尿病发生率8.3%,包括诊断和未诊断糖尿病(Undiagnosed diabetes),60岁以上人群发生率增加到19.2%;成人IFG发生率6.1%,60岁人群增加到14.4%。美国20岁以上人群糖尿病和IFG发生率估计为14.4%,60岁以上人群增加到33.6%[23-26]

    近年来,逐渐增多的流行病学证据还显示,与AS、血管病变关系密切的促炎细胞因子(pro-inflammatory cytokines)、血脂水平变化对老年人心脑血管病发生的影响与成人不同。心血管病发生危险预测因子血浆C反应蛋白(C-reactive protein,CRP)水平随年龄增加,然而对心脑血管病危险的预测作用下降[27,28],最近发表的大规模前瞻性PROSPER试验(the Prospective Study of Pravastatin in the Elderly at Risk),入选对象5804人,70~82岁,结果显示,CRP对老年人群心血管病事件发生的预测作用有限[29]。另一最近发表的MDC研究(The Malmö Diet and Cancer study),对5067名无心血管病挪威马尔默市(Malmö)居民(平均年龄58岁)平均随访12.8年,未观察到CRP水平对心血管病和冠心病事件发生较传统危险因素(性别、高血压、糖尿病、吸烟、血脂水平等)预测作用更显著[28];即将发表的ELSA试验(The English Longitudinal Study of Ageing)未发现老年人群中(年龄66.5±10.1岁)不同CRP水平与心血管病发生率升高相关[30]

    挪威DOIT试验(Diet and Omega-3 Intervention Trial)研究中老年男性563名(MetS 221名,非MetS 342名,年龄64~76岁),Trøseid等分析研究结果表明,经相关协变量校正后,MetS组炎症标志物中仅白介素-18(IL-18)为心血管病事件独立预测因素,IL-6和CRP无预测作用,相反在非MetS组中CRP与心血管病事件显著相关,IL-18、白介素-6(IL-6)无预测作用[31]。最近一项大规模英国老年人群研究(年龄60~79岁,平均随访7年)未观察到肿瘤坏死因子α(Tumour necrosis factor,TNFα)水平对发生MI和脑卒中危险有明显预测作用[32]

   越来越多的证据显示,成年人心血管病发生主要危险因素高胆固醇,在老年人心血管病发生中的作用减弱至消失,甚至80岁以上高胆固醇老年人长寿[33-35]。最近发表的一项前瞻性心血管病人群研究(The Copenhagen City Heart Study),随机观察19,329名20~93岁哥本哈根登记市民不同血浆总胆固醇(total plasma-cholesterol,TC)水平(正常水平<5 mmol/L、5~6 mmol/L、6~8 mmol/L及≥8mmol/L)对不同年龄(<60、60~70、70~80、≥80岁)健康人群发生冠心病危险的影响,结果表明,60岁以上人群高TC对发生冠心病危险影响逐渐下降,80岁以上人群TC与冠心病危险性无相关[36]。最近的一些研究表明,具有血管保护作用的高密度脂蛋白胆固醇水平降低对老年人群心血管病的发生可能发挥重要作用[33-35]。这些结果将促使对无明显动脉硬化性心血管病老年人群的治疗对策和调脂药物的应用重新考虑。

   除上述心血管病危险因素变化外, 老年人冠心病病变血管形态特征与年轻成人比较显著不同。根据冠状动脉重塑指数(remodeling index,RI,RI=罪犯病变部位外弹力膜横截面积/近端参考血管外弹力膜横截面积)将冠脉重塑分为缩窄型重塑(constrictive remodeling)-负性重塑(negative remodeling)(RI<0.95)、中间型重塑(intermediate remodeling)(RI:0.95~1.05)、扩张型重塑(expansive remodeling)-正性重塑(positive remodeling)(RI>1.05)三种类型。不同年龄急性冠脉综合征(acute coronary syndrome,ACS)患者冠脉罪犯血管重塑特征不同,冠脉内超声(intravascular ultrasound,IVUS)研究显示<55、56~69、≥70岁AMI患者罪犯血管冠脉重塑特征(RI)差异显著,缩窄型、中间型及扩张型重塑<55岁组分别为53%、26%和 21% ,56~69岁组25%、17%、58%,≥70岁组为15%、21%和65%,年轻组以缩窄型重塑为主,中、老年组则以扩张型为主[37]。最近一项亚洲单中心回顾性研究,观察<50岁、51~60岁、61~70岁、71~80岁及≥80岁年组冠心病患者各年龄组靶血管重塑特征,冠脉PCI术前行IVUS检查,显示老年组冠脉钙化型病变最重,伴有缩窄和弥漫性冠脉重塑,而年轻组重塑主要特征为不稳定斑块(正性重塑,多伴斑块破裂、血栓),年龄增加是斑块钙化、负性重塑、弥漫性动脉硬化的独立预测因素[38]

   随年龄增加老年人机体组织、功能出现一系列重要变化,使老年人群疾病的治疗有别于成年人[5]。高血压与发生脑卒中、冠心病、HF、心源性死亡关系密切,虽然血压升高对所有年龄人群均增加上述危险性,但随年龄增加高血压与这些危险的相关程度减弱[39,40]。目前老年人高血压的治疗,特别是≥80岁高龄老年人的降压治疗临床试验资料缺乏。最近,有我国参加的大规模HYVET试验(The Hypertension in the Very Elderly Trial)结果支持给予高龄高血压老年人降压治疗,观察到降压治疗可显著减低全因死亡(21%)、HF(64%)、卒中相对危险性(30%),但总死亡率无下降[41]。然而,也有许多试验,包括较早发布的前期HYVET试验研究(the pilot study of the Hypertension in the Very Elderly Trial)结果显示,老年高血压降压治疗减少心血管病事件危险性的同时,全因死亡率/总死亡率升高[39,42],最近报告的日本JATOS试验(the Japanese trial to assess optimal systolic blood pressure in elderly hypertensive patients)(试验入选年龄65~85岁)结果与之相近[42]。目前仍不清楚,老年人,特别是高龄老年人高血压降压治疗血压的控制靶目标水平,因为许多证据表明,老年人严格降压治疗血压达标,反而不良事件发生率升高、生存率降低,有流行病学研究结果显示,高龄老年人血压越高,总死亡率越低[39,40,42,43]

    与成年人高血压降压治疗结果比较,不同年龄段的老年人降压治疗获益不同。依据现有循证医学资料,基本观点多倾向对已患有心脑血管病、糖尿病的老年高血压,降压治疗获益较大[44,45],对老年轻、中度高血压,特别是高龄老年人降压治疗是否有益,血压控制在何种水平合适,还需要取得进一步循证医学研究证据。

  面对迅速增多的老年人口,特别是高龄老年人所占比例日益增加,老年人健康和疾病治疗、康复问题凸显。老年人群代谢异常、AS、高血压、冠心病、脑卒中、外周血管疾病发病率高,这些疾病之间互相影响有密切关系,目前对这些疾病规律的认识中许多问题尚不清楚。加之老年人机体多方面功能变化增加了预防和治疗的复杂性。老年高血压、冠心病、脑卒中的预防、治疗对策,老年代谢异常与这些疾病关系及其如何发挥影响等都是亟需解决的重要问题。因此加强对老年人群疾病规律特殊性的研究,是目前应该着力开展的重要工作。近10年来世界各国开始高度重视老年人群疾病,特别是老年心脑血管病的防治,随着研究的开展对老年人疾病规律的认识逐渐深入。对疾病新认识的增加,将对人类延长寿命、老年人健康、疾病的治疗、康复发挥越来越大的作用。

 

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李贺
李贺 主任医师
平津医院 老年病科
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