1、老年性瓣膜性心臟病 -主動脈瓣狹窄,衛(wèi)生部北京醫(yī)院 何青,內(nèi) 容,老齡和瓣膜病 老年AS 的臨床特點(diǎn) 老年AS 的治療策略,內(nèi) 容,老齡和瓣膜病 老年AS 的臨床特點(diǎn) 老年AS 的治療策略,1854 William Stokes 在他的教科書 “The diseases of the heart and the aorta”中描述鈣化性主動脈瓣病的特征為： (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 首先發(fā)現(xiàn)人在自然衰老過程中會出現(xiàn)退行性變，引起主動脈瓣的鈣化、狹窄。 1910年Dewisky首先描述了二尖瓣環(huán)的鈣化。,

3、Nalini M Rajamannan et al, Heart 2003;89:801805,1997年美國B. FENDLEY STEWART等人報道了5201例65歲老年人的心血管健康研究，提示經(jīng)心臟超聲檢查，主動脈瓣硬化發(fā)生率是26%，主動脈狹窄為2%。在75歲的人群中，硬化發(fā)生率是37%，狹窄為2.6%。與退行性瓣膜病相關(guān)的獨(dú)立危險因子包括年齡（年齡每增長十年危險增長2倍）、性別（男性為女性兩倍）、吸煙（仍然吸煙者增加危險35%）和高血壓（有高血壓病史者危險增加20%）。其他明確的危險因子有LP（a）和LDL-C的水平。作者認(rèn)為與主動脈瓣硬化和狹窄相關(guān)的臨床因素明確，且類似于動脈粥樣

4、硬化的危險因素。,STEWART ET AL. AORTIC STENOSIS RISK FACTORS J Am Coll Cardiol 1997;29:6304,我國資料報道，301醫(yī)院1986-1992年尸檢心臟瓣膜病110例，中青年組未見鈣化，50-60歲有輕度瓣膜鈣化，而60歲以上者瓣膜鈣化檢出率隨年齡增加而增高，且聯(lián)合瓣膜病增多。老年瓣膜病與性別有關(guān)，主動脈鈣化或硬化多見于男性，男女比例為2：1；二尖瓣環(huán)鈣化多見于女性，1：2。,王從容、王士雯等 老年退行性心臟瓣膜鈣化的病理學(xué)研究 中華老年醫(yī)學(xué)雜志1995年8月第14卷第4期,AS 在老年人是最為常見的心臟瓣膜病變 年齡65歲人

5、群，鈣化性AS為2%-7% 80%的癥狀性AS為男性,正常主動脈瓣膜,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,早期病變：瓣膜主動脈側(cè)內(nèi)皮下細(xì)胞、脂質(zhì)和細(xì)胞外基質(zhì)的積聚，伴內(nèi)皮下彈力層的移位。 晚期病變：更加明顯的脂質(zhì)、細(xì)胞、細(xì)胞外基質(zhì)的聚集，彈力層移位、斷裂。,鈣化性主動脈瓣疾病組織學(xué)改變,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,病變早期： 內(nèi)皮損傷 機(jī)械作用 細(xì)胞外脂質(zhì)聚集 炎癥反應(yīng) 細(xì)胞外液和ACE作用 病變晚期： 隨著病變的進(jìn)展，纖維膜層的纖維母細(xì)胞分化成具有平滑肌特點(diǎn)的成肌纖維細(xì)胞，瓣膜硬化。后者具有成骨作用，在炎癥因子等的共同刺激下，鈣鹽沉積，瓣膜上進(jìn)一步形成鈣化結(jié)節(jié)。 瓣膜的骨化，可能和鈣鹽的代謝有關(guān)，有研究認(rèn)為鈣鹽沉積是一個主動的過程，也可能和遺傳有一定的關(guān)系。,病理機(jī)制,Freeman and Otto Calcific Aortic Valve Di

12、sease 3317,導(dǎo)致AS的主要原因： 正常三葉瓣的鈣化和退行性變，隨年齡而增加 和冠心病相關(guān)的多種危險因子 常于AS相伴 先天性主動脈瓣畸形，二葉瓣、單葉瓣 風(fēng)濕,先天性主動脈二瓣畸形致狹窄,風(fēng)濕性主動脈瓣狹窄,鈣化的退行性主動脈瓣狹窄,內(nèi) 容,老齡和瓣膜病 老年AS 的臨床特點(diǎn) 老年AS 的治療策略,Freeman and Otto Calcific Aortic Valve Disease Circulation June 21, 2005,瓣膜的鈣化病變和形成動脈粥樣硬化的臨床因素類似,大部分主動脈瓣硬化的病人臨床沒有癥狀，或其心血管病危險因素已得到控制，但臨床事件的發(fā)生率仍然是高

13、的。 有16%診斷為主動脈瓣硬化的病人在8年內(nèi)進(jìn)展為嚴(yán)重的主動脈瓣狹窄。,老年人主動脈瓣硬化和心血管發(fā)病率和死亡率的相關(guān)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，年齡65歲，前瞻性研究，超聲心動圖檢查，平均隨訪5年,Conclusions: Aortic sclerosis is common in the elderly

14、 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”主動脈瓣

15、增厚病人發(fā)生主動脈瓣狹窄的危險性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，回顧性研究，心臟超聲診斷，,15.9%,伴有“良性”主動脈瓣增厚病人發(fā)生主動脈瓣狹窄的危險性The Risk of the Development of Aortic Stenosis in Patients With “Benign” Aort

16、ic 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 pati

17、ents with AVT.,1973年中華醫(yī)學(xué)雜志“老年人冠狀動脈粥樣硬化性心臟病臨床與病理的對照分析”一文報道一例明顯鈣化性主動脈瓣狹窄的老年病人尸檢提示多處不同發(fā)展階段內(nèi)膜下心梗，但沒有明顯的冠脈狹窄病變，認(rèn)為AS可以引起MI，而且這種梗塞是反復(fù)發(fā)生的和范圍較小的。,國內(nèi)北京醫(yī)院報道6例臨床追隨30年以上，又進(jìn)行了尸解證實(shí)為嚴(yán)重鈣化性主動脈瓣狹窄的老年病例，生前的臨床特點(diǎn)均為逐漸出現(xiàn)并加重的心底部收縮期雜音，均有心電圖的缺血改變和心臟超聲的左室肥厚、瓣膜鈣化表現(xiàn)，6例中5例生前有心肌梗死病史。尸檢的病理特點(diǎn)是反復(fù)發(fā)生，不同時間，分散和灶性的非透壁性心梗，冠脈病變可以較輕甚至無明顯病變。6

18、例中5例為猝死，其原因考慮與主動脈瓣狹窄患者的血液動力學(xué)障礙有關(guān)仍可有心梗的發(fā)生。,齊欣、王瑞萍、錢貽簡等 中華內(nèi)科雜志2000年2月第39卷第2期,內(nèi) 容,老齡和瓣膜病 老年AS 的臨床特點(diǎn) 老年AS 的治療策略,Joint Recommendations ofAmerican Heart Association and American College of Cardiology for aortic valve replacement in patients with aortic stenosis Aortic valve replacement indicated In patients 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 p