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1、老年性瓣膜性心脏病 -主动脉瓣狭窄,卫生部北京医院 何青,内 容,老龄和瓣膜病 老年AS 的临床特点 老年AS 的治疗策略,内 容,老龄和瓣膜病 老年AS 的临床特点 老年AS 的治疗策略,1854 William Stokes 在他的教科书 “The diseases of the heart and the aorta”中描述钙化性主动脉瓣病的特征为： (1) permanent patency of the valve in which the diameter may be increased or diminished; (2) an extreme ossific growth a
2、long the valve surrounding the ventricle, at which the valves are often destroyed; (3) an atheromatous deposit on the ventricular surface of the valve which is often seen in the context of fatty degeneration of the heart. 1904年Monchkebery 首先发现人在自然衰老过程中会出现退行性变，引起主动脉瓣的钙化、狭窄。 1910年Dewisky首先描述了二尖瓣环的钙化。,
3、Nalini M Rajamannan et al, Heart 2003;89:801805,1997年美国B. FENDLEY STEWART等人报道了5201例65岁老年人的心血管健康研究，提示经心脏超声检查，主动脉瓣硬化发生率是26%，主动脉狭窄为2%。在75岁的人群中，硬化发生率是37%，狭窄为2.6%。与退行性瓣膜病相关的独立危险因子包括年龄（年龄每增长十年危险增长2倍）、性别（男性为女性两倍）、吸烟（仍然吸烟者增加危险35%）和高血压（有高血压病史者危险增加20%）。其他明确的危险因子有LP（a）和LDL-C的水平。作者认为与主动脉瓣硬化和狭窄相关的临床因素明确，且类似于动脉粥样
4、硬化的危险因素。,STEWART ET AL. AORTIC STENOSIS RISK FACTORS J Am Coll Cardiol 1997;29:6304,我国资料报道，301医院1986-1992年尸检心脏瓣膜病110例，中青年组未见钙化，50-60岁有轻度瓣膜钙化，而60岁以上者瓣膜钙化检出率随年龄增加而增高，且联合瓣膜病增多。老年瓣膜病与性别有关，主动脉钙化或硬化多见于男性，男女比例为2：1；二尖瓣环钙化多见于女性，1：2。,王从容、王士雯等 老年退行性心脏瓣膜钙化的病理学研究 中华老年医学杂志1995年8月第14卷第4期,AS 在老年人是最为常见的心脏瓣膜病变 年龄65岁人
5、群，钙化性AS为2%-7% 80%的症状性AS为男性,正常主动脉瓣膜,The normal aortic valve comprises 3 layers. The ventricularis, on the ventricular side of the leaflet, is composed of elastinrich fibers that are aligned in a radial direction, perpendicular to the leaflet margin. The fibrosa, on the aortic side of the leaflet, com
6、prises primarily fibroblasts and collagen fibers arranged circumferentially, parallel to the leaflet margin. The spongiosa is a layer of loose connective tissue at the base of the leaflet, between the fibrosa and ventricularis, composed of fibroblasts, mesenchymal cells, and a mucopolysaccharide-ric
7、h matrix. These layers work in concert to provide tensile strength and pliability for decades of repetitive motion.,Freeman and Otto Calcific Aortic Valve Disease Circulation June 21, 2005,早期病变：瓣膜主动脉侧内皮下细胞、脂质和细胞外基质的积聚，伴内皮下弹力层的移位。 晚期病变：更加明显的脂质、细胞、细胞外基质的聚集，弹力层移位、断裂。,钙化性主动脉瓣疾病组织学改变,Potential pathways d
8、epicting calcific aortic valve disease. T lymphocytes and macrophages infiltrate endothelium and release cytokines that act on valvular fibroblasts to promote cellular proliferation and extracellular matrix remodeling. A subset of valvular fibroblasts within fibrosa layer differentiate into myofibro
9、blasts that possess characteristics of smooth muscle cells. LDL that is taken into the subendothelial layer is oxidatively modified and taken up by macrophages to become foam cells. ACE is colocalized with apolipoprotein B (ApoB) and facilitates conversion of angiotensin II (AngII), which acts on an
10、giotensin 1 receptors (AT-1R), expressed on valvular myofibroblasts. A subset of valvular myofibroblasts differentiate into osteoblast phenotype that is capable of promoting calcium nodule and bone formation. IL indicates interleukin; TGF, transforming growth factor; and MMP, matrix metalloproteinas
11、es.,Freeman and Otto Calcific Aortic Valve Disease Circulation June 21, 2005,病变早期： 内皮损伤 机械作用 细胞外脂质聚集 炎症反应 细胞外液和ACE作用 病变晚期： 随着病变的进展，纤维膜层的纤维母细胞分化成具有平滑肌特点的成肌纤维细胞，瓣膜硬化。后者具有成骨作用，在炎症因子等的共同刺激下，钙盐沉积，瓣膜上进一步形成钙化结节。 瓣膜的骨化，可能和钙盐的代谢有关，有研究认为钙盐沉积是一个主动的过程，也可能和遗传有一定的关系。,病理机制,Freeman and Otto Calcific Aortic Valve Di
12、sease 3317,导致AS的主要原因： 正常三叶瓣的钙化和退行性变，随年龄而增加 和冠心病相关的多种危险因子 常于AS相伴 先天性主动脉瓣畸形，二叶瓣、单叶瓣 风湿,先天性主动脉二瓣畸形致狭窄,风湿性主动脉瓣狭窄,钙化的退行性主动脉瓣狭窄,内 容,老龄和瓣膜病 老年AS 的临床特点 老年AS 的治疗策略,Freeman and Otto Calcific Aortic Valve Disease Circulation June 21, 2005,瓣膜的钙化病变和形成动脉粥样硬化的临床因素类似,大部分主动脉瓣硬化的病人临床没有症状，或其心血管病危险因素已得到控制，但临床事件的发生率仍然是高
13、的。 有16%诊断为主动脉瓣硬化的病人在8年内进展为严重的主动脉瓣狭窄。,老年人主动脉瓣硬化和心血管发病率和死亡率的相关性 ASSOCIATION OF AORTIC-VALVE SCLEROSIS WITH CARDIOVASCULAR MORTALITY AND MORBIDITY IN THE ELDERLY,CATHERINE M. O TTO et al. N Engl J Med 1999;341:142-7,N=5621，年龄65岁，前瞻性研究，超声心动图检查，平均随访5年,Conclusions: Aortic sclerosis is common in the elderl
14、y and is associated with an increase of approximately 50% in the risk of death from cardiovascular causes and the risk of myocardial infarction, even in the absence of hemodynamically significant obstruction of left ventricular outflow.,CATHERINE M. O TTO et al. N Engl J Med 1999;341:142-7,伴有“良性”主动脉
15、瓣增厚病人发生主动脉瓣狭窄的危险性 The Risk of the Development of Aortic Stenosis in Patients With “Benign” Aortic Valve Thickening,John E. Cosmi,et al, Arch Intern Med. 2002;162:2345-2347,N=2131，回顾性研究，心脏超声诊断，,15.9%,伴有“良性”主动脉瓣增厚病人发生主动脉瓣狭窄的危险性 The Risk of the Development of Aortic Stenosis in Patients With “Benign” A
16、ortic Valve Thickening,John E. Cosmi,et al, Arch Intern Med. 2002;162:2345-2347,Conclusions: Aortic valve thickening without stenosis is common, and it may progress to significant AS. It is possible that this development of AS may be responsible for some of the increased morbidity and mortality in p
17、atients with AVT.,1973年中华医学杂志“老年人冠状动脉粥样硬化性心脏病临床与病理的对照分析”一文报道一例明显钙化性主动脉瓣狭窄的老年病人尸检提示多处不同发展阶段内膜下心梗，但没有明显的冠脉狭窄病变，认为AS可以引起MI，而且这种梗塞是反复发生的和范围较小的。,国内北京医院报道6例临床追随30年以上，又进行了尸解证实为严重钙化性主动脉瓣狭窄的老年病例，生前的临床特点均为逐渐出现并加重的心底部收缩期杂音，均有心电图的缺血改变和心脏超声的左室肥厚、瓣膜钙化表现，6例中5例生前有心肌梗死病史。尸检的病理特点是反复发生，不同时间，分散和灶性的非透壁性心梗，冠脉病变可以较轻甚至无明显病
18、变。6例中5例为猝死，其原因考虑与主动脉瓣狭窄患者的血液动力学障碍有关仍可有心梗的发生。,齐欣、王瑞萍、钱贻简等 中华内科杂志2000年2月第39卷第2期,内 容,老龄和瓣膜病 老年AS 的临床特点 老年AS 的治疗策略,Joint Recommendations ofAmerican Heart Association and American College of Cardiology for aortic valve replacement in patients with aortic stenosis Aortic valve replacement indicated In pat
19、ients with severe aortic stenosis with its classic “SAD” symptoms (syncope, angina, and/or dyspnoea In patients with severe aortic stenosis who are having coronary artery bypass grafting In patients with severe aortic stenosis having surgery on the aorta or other heart valves In patients with severe
20、 aortic stenosis with left ventricular systolic dysfunction (ejection fraction 60mmHg, or a jet velocity 5m/s) when the patients expected operative mortality is 1%,外科治疗,内科治疗,内科药物治疗？不确切。 相关的治疗： 他汀类药物 ACEI 对症治疗,目前研究尚未解决的问题,AS是否类似于动脉粥样硬化过程是不断进展的，可以通过药物来干预？ 通过生活方式的改善或他汀类药物是否可以延缓AS的进程？ 准备做心脏手术的无症状的轻度或中度A
21、S患者是否需换瓣？ 假设手术死亡率是低的，是否建议无症状的重度AS患者选择瓣膜置换术以减少以后的发病率和死亡率？,目前正在进行的关于主动脉瓣疾病的 他汀类药物作用的研究,STOP-ASStop aortic stenosis (Cleveland Clinic, Cleveland, Ohio, USA) SEASSimvastatin and the ezetimibe in aortic stenosis (Europe) ASTRONOMERAortic stenosis progression observation measuring effects of rosuvastatin (Canada),谢谢,