1、Clinical and Basic Research on Redegenerative Valvular Heart Disease and Vascular Calcification,20th GW-ICC Geriatric Cardiology symposium,Sponsored by Military “15th” key grant on medical science（No：01Z034）& NSFC foundation（No：39770869）,Wang Shiwen Institute of Geriatric Cardiology Chinese PLA Gene
2、ral Hospital,Background,Retrograde valvular heart disease in the elderly：A common valvular disease in the elderly that caused by calcification of heart valves with age. It is the most common reason of valve replacement and mortality Vascular calcification ：common lesion in the elderlyindicator of AS
3、 degreespathological foundation of many Vascular disease,Background,Mobility of RVHD increases in China along with advanced elderly population Compared with other diseases (CHD,DM, et al), research on RVHD remains largely insufficient,Study Contents,Follow-up study on RVHD Large scale epidemiologic
4、analysis on RVHD and vascular calcification in the elderly Further investigation on clinical and molecular etiology Statins intervention on RVHD and vascular calcification in the elderly,Follow-up Research on Clinical Epidemiology of RVHD,A 6-year follow to 95 cases of valvular calcification and 95
5、cases of normal patients Occurrence of murmur,ventricular enlargement,nodal lesion,A-V block and AF in the elderly patients with RVHD was shown much higher.（P 0.05） Occurrence of congestive heart failure,AMI,cerebral vascular disease and syncopy was also remarkably higher. （P 0.05）；,RVHD could lead
6、to hemodynamic change,worsen cardiac dysfunction,which turned to be one of the important cause of cardiocerebral disease as well as cardiac arrest. Recognizing the complication on time and early treatment might exert key role in prognosis.Yuzhen Zhang,Shiwen Wang, Bing Wu, et al. Chinese Gerontology
7、 Journal,1994; 13(4):9697,Large scale epidemiologic analysis on RVHD and vascular calcification in the elderly,Study was carried on in 8202 elderly retired veterans. 820 were randomized according to age. Mobility and proportions of RVHD in the elderlyRisk factors of RVHD in the elderlyCorrelation be
8、tween RVHD and carotid athrosclerosis (CAS),Mobility of RVHD and Relative Risk Factor,Age,hypertension,hyperlipidimia,stroke,cardiovascular family history consist of major risk factors of RVHD in the elderly. Lowering body weight,regular physical exercise as well as adjustment of relative unhealthy
9、life style would prevent and block the pathogenesis of RVHD in the elderly.,CAS：颈动脉粥样硬化； SDVHD：退行性心脏瓣膜病；IMT：颈动脉内膜中膜厚度,Relationship between Valvular Calcification and CAS,It was shown that valvular calcification was more popular in CAS patients.Doppler examination observing carotid inter-medial thick
10、ness would diagnose CAS early and guild the treatment,also effectively block the development of vulvalar calcification and improve the prognosis.,Alkaline phosphatase might be an initiator of vascular calcification. High homocystine level contributes to Ectopic calcipication MMP-3 protein level was
11、upregulated in aortic calcification,which might accelerate calcification by certain pathway. Many factors are involved in the aortic calcification, including SMC, TGF-、and IGF-1 et al. Human KARP-1 binding protein and KIAA0470 protein might play roles in aortic calcification.,Articles On RVHD and va
12、scular calcification in the elderly,clinical pathology of RVHD,瓣膜内皮下弹力层移位和碎片化。VvG染色 X 100,病变内钙盐沉积和胆固醇结晶。 茜素红染色X 400,纤维层内脂质沉积与胶原 纤维平行。油红O染色X100,病变瓣膜内单核细胞浸润。 CD68免疫组化染色X 400,病变瓣膜中新生毛细血管。 CD31免疫组化染色X 40,骨母细胞标志物表达阳性， OPN免疫组化染色X400,The study provide clinical pathology evidences of the hypothesis that RVH
13、D is a arts like pathology, also provide important theoretical foundation of statins interventions on RVHD.尹彤，王士雯，赵玉生等. 中华老年多器官疾病杂志,2004;4(4):277281 张玉珍，王士雯等.中华心血管病杂志,1991;19(6):372376 王从容，王士雯等.中华内科学杂志,1994; 33(10):690 王从容，王士雯等.中华老年医学杂志,1995;14(4):220223,Research of Potential prevention and treatmen
14、t of Statin on RVHD as well as Valvular Calcification,Backgroud： Epidemiology research showed hyperlipidemia is an independent risk factor of RVHD. Clinical pathological research showed RVHD possess similar pathohistological characteristics with AS. Basic research found RVHD possess similar influenc
15、e factors and mechanism with AS. Content： The beneficial role of statin on prevention and treatment of RVHD was proven by intervention in vivo and in vitro, as well as follow-up to RVHD patients.,Effect of Provastatin on Valvular Calcification and Possible Mechanism,Provastatin reduced calcium depos
16、ion dose-dependently.Also,despite ALP activity didnt change much, Osteocalcine in supernatant decreased obviously.,The present study proved for the first time provastatin could reduce calcium deposition,ameliorate in-vivo vascular calcification,suggesting the potency of provastatin on calcification
17、treatment.,50m 50m,500 nm 500 nm,高脂饮食组,高脂饮食及阿托伐他汀干预组,对照组,150 nm 150 nm,直径:1119 nm,In-situ observation on ultrastructure changes of arotic Valvular endothelium,In-situ observation shows that statins have protective effect on endothelium surface from hyperlidermia. The atom microscope revealed changes
18、 of nanometer channels and receptor like domains. This study suggested that hyperlidermia is a risk factot of RVHD and statins may be a prospective therapy.尹彤，王士雯，高磊, 纪小龙。临床与实验病理学杂志， 2005，21：713717.,Clinical Research of Statin in Early Prevention and HF mortality,Since 2000，1138 cases of RVHD was di
19、agnosed by UCG in IGC,including 417 cases of aortic valvular disease,310 of mitral valvular disease,385 cases of joint valvular disease.In 943 cases of HF in the elderly,about 24% were found to have RVHD. We realized the importance of lipid-lowering therapy from clinical and basic research, reinforc
20、ed the treating strategy to HF patients. Therefore, the efficiency of HF treatment was elevated to 93.5%.,Typical case 1：,male，71 years old，paroxysmal chest compression for 15 years,get severe for 1 day. Primary diagnosis：CHD,UAP,HP (2nd Grade),CAS,hyperlipidemia UCG：RVHD；Diminished left ventricular
21、 diastolic function. Anti-platelet,anti-inflammation treatment Follow-up in outpatient，strengthening lipid-lowering therapy、anti-platelet coagulation、coronary dilating,anti-hypertension, no cardiac end point event was found.,This is a typical case of multiple branches coronary disease.3 main branche
22、s was diffusingly invasive and stenosized. After lipid-lowering therapy, the AS and calcificating degree didnt get worse.,Typical case 2：,male，54 years old. Paroxysmal chest pain for 6 months,get strengthened for 1 month CTA：stenosis in left coronary artery,calcification. After strengthened lipid-lo
23、wering therapy and anti-platelet therapy for 4 years,the patients condition is still stable.,Innovations,This study is the first epidemical survey on RVHD in the elderly veterans。The first clinical pathology study on RVHD in the elderly in China. Revealed similarities between RVHD and arts。The first
24、 systemic study on mechanism of RVHD in ChinaThe first clinical study and observation about intervention of statins on RVHD and vascular calcification in China。,Application and social effect,The results of this study was published total 39 articles,international congress 23 times,3 books,was cited 5
25、7 times. Relative therapy and skills were applicated in 14 colleges and educated 2000 medical staff. Totally 12 doctors,as well as masters participated the study.,Future steps,A large scale epidemiologic study is needed to be done among citizens other than veterans to get more precise clinical dataA multi-center, prospective and larger scale study is needed to justify the statin intervention on RVHD in the elderly,谢谢！,
