社区老年人群退行性心脏瓣膜病的五年纵向研究
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摘要
目的：
老年退行性心脏瓣膜病(Senile degenerated heart valvular disease, SDHVD)是心脏瓣膜纤维层的退行性病变及钙盐沉积的结果。近年来随着老龄化社会的到来,其发病率在全球及国内范围内均处于逐年上升趋势,并已成为老年心脏瓣膜病和瓣膜置换的首要原因之一。本研究在对5年前进行的一项退行性心脏瓣膜病流行病学研究的基础上,对原随机抽样人群进行了5年后纵向流行病学调查,以期明确该人群流行病学变化特点,包括加重、缓解、新增心脏瓣膜病以及心脑血管事件发生率,并探讨退行性瓣膜病与心血管事件,新发病例与相关危险因素和退行性瓣膜病与颈动脉粥样硬化的关系。
方法：
本次流行病学调查采取横向及纵向流行病学调查方法通过问卷调查及超声检查方式,对固定人群首先进行现况调查,再次研究发病率、致病危险因素以及心血管事件发生率等。然后与2005年第一次调查结果相比较,采用单因素方差及Cox比例风险回归模型分析,分析5年前后该人群退行性瓣膜病的流行病学变化特点、心血管事件发生情况及相关危险因素。
结果：
1、调查对象：原入选820例,此次回访人数739例,应答率为90.1%,心脏瓣膜钙化患病率15.6%。瓣膜钙化患者中主动脉瓣钙化比例42.6%,其中男性患病率高于女性；二尖瓣钙化比例40.0%,女性患病率高于男性。新增患者中,主动脉瓣钙化部位多位于无冠瓣和右冠瓣(75.0%,37.5%),二尖瓣钙化部位主要位于后叶瓣环(58.8%)。以上结果与5年前及国内外相关文献报道的结果较一致。
2、本研究发现5年期间新增瓣膜钙化21例,加重患者7例,平均年龄75.4±4.9岁。在739例随访人群中,新发心房颤动7例,新发心肌梗死7例,新发心绞痛47例,心力衰竭住院46例,血运重建26例,新发脑卒中49例,心源性死亡8例。单因素分析显示：(1)吸烟、高血压、脑卒中、冠心病、糖尿病中瓣膜钙化进展发生率高于对照人群。(2)饮酒、高血压、脑卒中、高脂血症是社区老年人群5年心血管事件的危险因素。(3)心脏瓣膜钙化是5年新发房颤的危险因素。通过Cox比例风险回归模型分析发现：(1)高血压、高脂血症是5年复合心血管事件的独立危险因素。(2)瓣膜钙化、增龄是5年新发房颤的独立危险因素。
3、本研究调查的698人中,颈动脉粥样硬化患病率为56.7%,患病率呈随年龄增长趋势,男性患病率显著高于女性(P<0.01),且患病程度高于女性。2005年颈动脉粥样硬化患者瓣膜钙化发生率为20.2%,而2005年瓣膜钙化患者颈动脉粥样硬化发病率为62.8%。结果表明,瓣膜钙化患者中颈动脉粥样硬化发生率高。
结论：
1、本研究首次在北京地区对820人进行了5年随访调查,失访81人,获得随访资料739人,其中死亡41人,应答率90.1%。心脏瓣膜钙化发生115例,患病率由2005年的13.4%增加至15.6%,其中新增瓣膜钙化21例,符合随龄增长趋势。
2、5年期间新增瓣膜钙化21例,加重患者7例,平均年龄75.4±4.9岁。瓣膜钙化、增龄是5年新发房颤的独立危险因素。高血压、高脂血症是5年复合心血管事件的独立危险因素。
3、瓣膜钙化与颈动脉粥样硬化之间存在某些一致性,心脏瓣膜钙化患者中颈动脉粥样硬化检出率高。瓣膜钙化可能与动脉粥样硬化存在某些相同的发病机制。
Objects:
Senile degenerated heart valvular disease (SDHVD) is the result of degeneration of calcium deposition in the fiber layer of the cardiac valve. In recent years, with the arriving of aging society the incident of SDHVD is increasing year by year domestically and abroad, SDHVD has become the primary reason of cardiac valve replacement in the elderly. This study was based on an epidemiological study on SDHVD 5 years ago. The same people were called back to investigate the epidemiology features of SDHVD, which include analysis of newly diagnosed patients' statistics; relationship between SDHVD and cardiovascular events, new case and correlation risk factor, SDHVD and carotid atherosclerosis.
Methods:
Firstly a prevalence survey was made in order to make morbidity rates, the risk of cardiovascular events and risk factor clear through questionnaire and echocardiography. Secondly the results were contrasted with that in 2005, and then analysed the characteristics of its changes and new phenomenons during the 5 years by using logistic regression analysis, Cox proportional hazard model and other normal statistical methods.
Results:
1. There were 739 people in this epidemiological survey, response rate is 90.1%, and morbidity of cardiac valve calcification is 15.6%. Aortic valve calcification took the proportion of 42.6% in all patients; the morbidity in male was higher than female. Mitral valve calcification proportion was 40.0%, female higher than male. In new patients, NCC, RCC(75.0%,37.5%) and PML(58.8%) were the most calcification sites in aortic valve and mitral valve. It was found that most consequences were the same as 5 years ago or other related reports in domestic and overseas.
2. SDHVD plays an important role in cardiovascular events, there were 21 new cardiac valve calcification and 7 aggravated patients. In 739 people of this study, there were 7 atrial fibrillation,47 angina,46 heart failure,26 revascularization,49 stroke. By Cox proportional hazard model, the study deemed that smoking, hypertension, stroke, coronary disease and diabetes mellitus were the major risk factor for SDHVD. And the atrial fibrillation is correlative with SDHVD explicitly. Analysed age, valve calcification and new atrial fibrillation by Cox model, it was found that the risk of atrial fibrillation was 3.685 times (P=0.091) greater for SDHVD compared to people without the disease.
3. Morbidity of carotid atherosclerosis was 56.7% in the study, increased with age, male higher than female (P<0.01) in amount and degree. The morbidity of valve calcification was 20.2% in the patients who suffer from carotid atherosclerosis in 2005, while the morbidity of carotid atherosclerosis was 62.8% in the patients who suffer from valve calcification in 2005. The result indicated that carotid atherosclerosis could be as predictor for valve calcification.
Conclusions:
1. There was first five-year longitudinal study in Beijing community.739 people were investigated,41 people were died, and response rate was 90.1%. SDHVD were 115 cases, the morbidity increased from 13.4% to 15.6%, and there were 21 new patients, according with the growth trend of age.
2. There were 21 new patients during this five years,7 aggravating patients, the average age was 75.4±4.9 years old. Valve calcification and age increasing were independent risk factors of new atrial fibrillation. Hypertension and hyperlipidemia were independent risk factors for cardiovascular events.
3. Carotid atherosclerosis could be as predictor for valve calcification, and Valve calcification may has the same pathogenesis with atherosclerosis.
老年退行性心脏瓣膜病(Senile degenerated heart valvular disease, SDHVD)是心脏瓣膜纤维层的退行性病变及钙盐沉积的结果。近年来随着老龄化社会的到来,其发病率在全球及国内范围内均处于逐年上升趋势,并已成为老年心脏瓣膜病和瓣膜置换的首要原因之一。本研究在对5年前进行的一项退行性心脏瓣膜病流行病学研究的基础上,对原随机抽样人群进行了5年后纵向流行病学调查,以期明确该人群流行病学变化特点,包括加重、缓解、新增心脏瓣膜病以及心脑血管事件发生率,并探讨退行性瓣膜病与心血管事件,新发病例与相关危险因素和退行性瓣膜病与颈动脉粥样硬化的关系。
方法：
本次流行病学调查采取横向及纵向流行病学调查方法通过问卷调查及超声检查方式,对固定人群首先进行现况调查,再次研究发病率、致病危险因素以及心血管事件发生率等。然后与2005年第一次调查结果相比较,采用单因素方差及Cox比例风险回归模型分析,分析5年前后该人群退行性瓣膜病的流行病学变化特点、心血管事件发生情况及相关危险因素。
结果：
1、调查对象：原入选820例,此次回访人数739例,应答率为90.1%,心脏瓣膜钙化患病率15.6%。瓣膜钙化患者中主动脉瓣钙化比例42.6%,其中男性患病率高于女性；二尖瓣钙化比例40.0%,女性患病率高于男性。新增患者中,主动脉瓣钙化部位多位于无冠瓣和右冠瓣(75.0%,37.5%),二尖瓣钙化部位主要位于后叶瓣环(58.8%)。以上结果与5年前及国内外相关文献报道的结果较一致。
2、本研究发现5年期间新增瓣膜钙化21例,加重患者7例,平均年龄75.4±4.9岁。在739例随访人群中,新发心房颤动7例,新发心肌梗死7例,新发心绞痛47例,心力衰竭住院46例,血运重建26例,新发脑卒中49例,心源性死亡8例。单因素分析显示：(1)吸烟、高血压、脑卒中、冠心病、糖尿病中瓣膜钙化进展发生率高于对照人群。(2)饮酒、高血压、脑卒中、高脂血症是社区老年人群5年心血管事件的危险因素。(3)心脏瓣膜钙化是5年新发房颤的危险因素。通过Cox比例风险回归模型分析发现：(1)高血压、高脂血症是5年复合心血管事件的独立危险因素。(2)瓣膜钙化、增龄是5年新发房颤的独立危险因素。
3、本研究调查的698人中,颈动脉粥样硬化患病率为56.7%,患病率呈随年龄增长趋势,男性患病率显著高于女性(P<0.01),且患病程度高于女性。2005年颈动脉粥样硬化患者瓣膜钙化发生率为20.2%,而2005年瓣膜钙化患者颈动脉粥样硬化发病率为62.8%。结果表明,瓣膜钙化患者中颈动脉粥样硬化发生率高。
结论：
1、本研究首次在北京地区对820人进行了5年随访调查,失访81人,获得随访资料739人,其中死亡41人,应答率90.1%。心脏瓣膜钙化发生115例,患病率由2005年的13.4%增加至15.6%,其中新增瓣膜钙化21例,符合随龄增长趋势。
2、5年期间新增瓣膜钙化21例,加重患者7例,平均年龄75.4±4.9岁。瓣膜钙化、增龄是5年新发房颤的独立危险因素。高血压、高脂血症是5年复合心血管事件的独立危险因素。
3、瓣膜钙化与颈动脉粥样硬化之间存在某些一致性,心脏瓣膜钙化患者中颈动脉粥样硬化检出率高。瓣膜钙化可能与动脉粥样硬化存在某些相同的发病机制。
Objects:
Senile degenerated heart valvular disease (SDHVD) is the result of degeneration of calcium deposition in the fiber layer of the cardiac valve. In recent years, with the arriving of aging society the incident of SDHVD is increasing year by year domestically and abroad, SDHVD has become the primary reason of cardiac valve replacement in the elderly. This study was based on an epidemiological study on SDHVD 5 years ago. The same people were called back to investigate the epidemiology features of SDHVD, which include analysis of newly diagnosed patients' statistics; relationship between SDHVD and cardiovascular events, new case and correlation risk factor, SDHVD and carotid atherosclerosis.
Methods:
Firstly a prevalence survey was made in order to make morbidity rates, the risk of cardiovascular events and risk factor clear through questionnaire and echocardiography. Secondly the results were contrasted with that in 2005, and then analysed the characteristics of its changes and new phenomenons during the 5 years by using logistic regression analysis, Cox proportional hazard model and other normal statistical methods.
Results:
1. There were 739 people in this epidemiological survey, response rate is 90.1%, and morbidity of cardiac valve calcification is 15.6%. Aortic valve calcification took the proportion of 42.6% in all patients; the morbidity in male was higher than female. Mitral valve calcification proportion was 40.0%, female higher than male. In new patients, NCC, RCC(75.0%,37.5%) and PML(58.8%) were the most calcification sites in aortic valve and mitral valve. It was found that most consequences were the same as 5 years ago or other related reports in domestic and overseas.
2. SDHVD plays an important role in cardiovascular events, there were 21 new cardiac valve calcification and 7 aggravated patients. In 739 people of this study, there were 7 atrial fibrillation,47 angina,46 heart failure,26 revascularization,49 stroke. By Cox proportional hazard model, the study deemed that smoking, hypertension, stroke, coronary disease and diabetes mellitus were the major risk factor for SDHVD. And the atrial fibrillation is correlative with SDHVD explicitly. Analysed age, valve calcification and new atrial fibrillation by Cox model, it was found that the risk of atrial fibrillation was 3.685 times (P=0.091) greater for SDHVD compared to people without the disease.
3. Morbidity of carotid atherosclerosis was 56.7% in the study, increased with age, male higher than female (P<0.01) in amount and degree. The morbidity of valve calcification was 20.2% in the patients who suffer from carotid atherosclerosis in 2005, while the morbidity of carotid atherosclerosis was 62.8% in the patients who suffer from valve calcification in 2005. The result indicated that carotid atherosclerosis could be as predictor for valve calcification.
Conclusions:
1. There was first five-year longitudinal study in Beijing community.739 people were investigated,41 people were died, and response rate was 90.1%. SDHVD were 115 cases, the morbidity increased from 13.4% to 15.6%, and there were 21 new patients, according with the growth trend of age.
2. There were 21 new patients during this five years,7 aggravating patients, the average age was 75.4±4.9 years old. Valve calcification and age increasing were independent risk factors of new atrial fibrillation. Hypertension and hyperlipidemia were independent risk factors for cardiovascular events.
3. Carotid atherosclerosis could be as predictor for valve calcification, and Valve calcification may has the same pathogenesis with atherosclerosis.
引文
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51. Kallikazaros I,Tsioufis C,Sideris S,et al.Carotid artery disease as a marker for the presence of severe coronary artery disease in patients evluated for chest pain. Stroke.1999,30(5):1002-1007.
52. Graven TE,Ryu JE,Espeland MA,et al.Evaluation of the associations between carotid artery atherosclerosis and coronary artery stenosis.Circulation.1990, 82(4):1230-1242.
53. Alaee A, Khademloo M. Evaluation of correlation between carotid artery intima media wall thickness and coronary artery stenosis in Sari, north of Iran. Pak J Biol Sci.2008,11(19):2360-2363.
54. Seo Y, Ishimitsu T, Ishizu T, et al. Relationship between mitral annular calcification and severity of carotid atherosclerosis in patients with symptomatic ischemic cerebrovascular disease. J Cardiol.2005,46(1):17-24.
55. Mazzone A, Epistolato MC, Gianetti J. Biological features (inflammation and neoangiogenesis) and atherosclerotic risk factors in carotid plaques and calcified aortic valve stenosis:two different sites of the same disease? Am J Clin Pathol. 2006,126(4):494-502.
56. Sgorbini L, Scuteri A, Leggio M, et al. Association of mitral annulus calcification, aortic valve calcification with carotid intima media thickness. Cardiovasc Ultrasound.2004,8(2):19-25.
57. Yamamoto H, shavelle D, Takasu J, et al. Valvular and thoracicaortic calcium as a marker of the extent and severity of angiographic coronary artery disease. Am Heart J,2003,146(1):153-159.
58. Sgorbini L, Scuteri A, Leggio M, et al. Carotid intima-media thickness, carotid distensibility and mitral, aortic valve calcification:a useful diagnostic parameter of systemic atherosclerotic disease. J Cardiovasc Med (Hagerstown).2007,8(5): 342-347.
59. Palmiero P, Maiello M, Passantino A, et al. Aortic valve sclerosis:is it a cardiovascular risk factor or a cardiac disease marker? Echocardiography.2007, 24(3):217-221.
60. Komorovsky R, Desideri A. Carotid ultrasound assessment of patients with coronary artery disease:a useful index for risk stratification. Vasc Health Risk Manag.2005,1(2):131-136.
61.易兴阳,陈存木,池丽芬等.颈动脉粥样硬化与进展性缺血性脑卒中关系.中华神经科杂志,2006,39(6)：388-391.
1. Comparative study of calcified changes in aortic valvular diseases. Togashi M, Tamura K, Masuda Y, Fukuda Y. J Nippon Med Sch.2008 Jun; 75(3):138-145.
2. 陈国伟,郑宗锷.现代心脏内科学.湖南科学技术出版社.1996：681-736.
3. Moura LM, Ramos S F, Zamorano J I, et al. Rosuvastatin affecting aortic valve endothelium to slow the p regression of aortic stenosis. J Am Coll Cardiol,2007, 49 (5):554-561.
4. 尹彤,王士雯,高磊,等.退行性钙化性主动脉瓣膜病的病理组织学分析.中华老年多器官疾病杂志,2005,4(4)：277-281.
5. Goldbarg S H, Elmariah S,MillerM A, et al. Insights into degenerative aortic valve disease. J Am Coll Cardiol,2007,50:1205-1213.
6. 万士荣,吴民,肖大鹄,等.退行性钙化性心瓣膜病的超声与临床研究.临床心血管病杂志,2000,16(7)：323-323.
7. Parker MW, Thompson PD.Exercise in valvular heart disease:risks and benefits. Prog Cardiovasc Dis.2011 May-Jun; 53(6):437-446.
8. Simmons C A, Grant G,Manduchi E, et al. Spatial heterogeneity of endothelial phenotypes correlates with side specific vulnerability to calcification in normal porcine aortic valves. Circ Res,2005,96 (7):792-799.
9. Emile R M, Francis G. Bone formation and inflammation in cardiac valves. Circulation,2001,103:1522-1528.
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13. Thomas S, Claudette A, Herbertf, et al. Cardiac abnormalities in patient s with primary hyperparathyroidism implications for follow-up. J Clinical Endocrinol Metab,1997,82:106-112.
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18. Novo G, Fazio G, Visconti C, et al. Atherosclerosis, degenerative aortic stenosis and statins. Curr Drug Targets.2011 Jan; 12(1):115-121.
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20. Shor A, Kuo C C, Patton D L. Detection of chlamydia pneumoniae in coronary arterial fatty st reaks and atheromatous plaques. S Af r Med J,1992,82:158-161.
1. Thom T, Haase N, Rosamond W, et al. Heart disease and stroke statistics-2006 update:a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation,2006,113:185-151.
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3. Goldbarg SH, Elmariah S, Miller MA, et al. Insights into degenerative aortic valve disease. J Am Coll Cardiol.2007,50(13):1205-1213.
4. Beckmann E, Grau JB, Sainger R, et al. Insights into the use of biomarkers in calcific aortic valve disease. J Heart Valve Dis.2010,19(4):441-452.
5. Yetkin E, Waltenberger J. Molecular and cellular mechanisms of aortic stenosis. Int J Cardiol.2009,135(1):4-13.
6. Hakuno D, Kimura N, Yoshioka M, et al. Periostin advances atherosclerotic and rheumatic cardiac valve degeneration by inducing angiogenesis and MMP production in humans and rodents. J Clin Invest.2010,120(7):2292-2306.
7. Nagase Jr H, Woessner JF. Matrix metalloproteinases. J Biol Chem.1999,274: 21491-21494.
8. Carson AE, Barker TH. Emerging concepts in engineering extracellular matrix variants for directing cell phenotype. Regen Med.2009,4(4):593-600.
9. Basu P, Sen U, Tyagi N, et al. Blood flow interplays with elastin:collagen and MMP:TIMP ratios to maintain healthy vascular structure and function. Vasc Health Risk Manag.2010,6:215-228.
10. Jiang L, Wei XF, Yi DH, et al. Synergistic effects of cyclic strain and Thl-like cytokines on tenascin-C production by rheumatic aortic valve interstitial cells. Clin Exp Immunol.2009,155(2):216-223.
11. O'brien K D, Kuusisto J, Reichenbach D D, et al. Osteopontin is expressed in human aortic valvular lesions. Circulation,1995,92:2163-2168.
12. Caira FC, Stock SR, Gleason TG, et al. Human degenerative valve disease is associated with up-regulation of low-density lipoprotein receptor-related protein 5 receptor-mediated bone formation. J Am Coll Cardiol.2006,47(8):1707-1712.
13. Shao JS, Cheng SL, Sadhu J, et al. Inflammation and the osteogenic regulation of vascular calcification:a review and perspective. Hypertension.2010,55(3): 579-592.
14. Yip CY, Chen JH, Zhao R, et al. Calcification by valve interstitial cells is regulated by the stiffness of the extracellular matrix. Arterioscler Thromb Vase Biol.2009,29(6):936-942.
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50. Lorenz MW, von Kegler S, Steinmetz H, et al. Carotid intima-media thickening indicates a higher vascular risk across a wide age range:prospective data from the Carotid Atherosclerosis Progression Study (CAPS). Stroke.2006,37(1):87-92.
51. Kallikazaros I,Tsioufis C,Sideris S,et al.Carotid artery disease as a marker for the presence of severe coronary artery disease in patients evluated for chest pain. Stroke.1999,30(5):1002-1007.
52. Graven TE,Ryu JE,Espeland MA,et al.Evaluation of the associations between carotid artery atherosclerosis and coronary artery stenosis.Circulation.1990, 82(4):1230-1242.
53. Alaee A, Khademloo M. Evaluation of correlation between carotid artery intima media wall thickness and coronary artery stenosis in Sari, north of Iran. Pak J Biol Sci.2008,11(19):2360-2363.
54. Seo Y, Ishimitsu T, Ishizu T, et al. Relationship between mitral annular calcification and severity of carotid atherosclerosis in patients with symptomatic ischemic cerebrovascular disease. J Cardiol.2005,46(1):17-24.
55. Mazzone A, Epistolato MC, Gianetti J. Biological features (inflammation and neoangiogenesis) and atherosclerotic risk factors in carotid plaques and calcified aortic valve stenosis:two different sites of the same disease? Am J Clin Pathol. 2006,126(4):494-502.
56. Sgorbini L, Scuteri A, Leggio M, et al. Association of mitral annulus calcification, aortic valve calcification with carotid intima media thickness. Cardiovasc Ultrasound.2004,8(2):19-25.
57. Yamamoto H, shavelle D, Takasu J, et al. Valvular and thoracicaortic calcium as a marker of the extent and severity of angiographic coronary artery disease. Am Heart J,2003,146(1):153-159.
58. Sgorbini L, Scuteri A, Leggio M, et al. Carotid intima-media thickness, carotid distensibility and mitral, aortic valve calcification:a useful diagnostic parameter of systemic atherosclerotic disease. J Cardiovasc Med (Hagerstown).2007,8(5): 342-347.
59. Palmiero P, Maiello M, Passantino A, et al. Aortic valve sclerosis:is it a cardiovascular risk factor or a cardiac disease marker? Echocardiography.2007, 24(3):217-221.
60. Komorovsky R, Desideri A. Carotid ultrasound assessment of patients with coronary artery disease:a useful index for risk stratification. Vasc Health Risk Manag.2005,1(2):131-136.
61.易兴阳,陈存木,池丽芬等.颈动脉粥样硬化与进展性缺血性脑卒中关系.中华神经科杂志,2006,39(6)：388-391.
1. Comparative study of calcified changes in aortic valvular diseases. Togashi M, Tamura K, Masuda Y, Fukuda Y. J Nippon Med Sch.2008 Jun; 75(3):138-145.
2. 陈国伟,郑宗锷.现代心脏内科学.湖南科学技术出版社.1996：681-736.
3. Moura LM, Ramos S F, Zamorano J I, et al. Rosuvastatin affecting aortic valve endothelium to slow the p regression of aortic stenosis. J Am Coll Cardiol,2007, 49 (5):554-561.
4. 尹彤,王士雯,高磊,等.退行性钙化性主动脉瓣膜病的病理组织学分析.中华老年多器官疾病杂志,2005,4(4)：277-281.
5. Goldbarg S H, Elmariah S,MillerM A, et al. Insights into degenerative aortic valve disease. J Am Coll Cardiol,2007,50:1205-1213.
6. 万士荣,吴民,肖大鹄,等.退行性钙化性心瓣膜病的超声与临床研究.临床心血管病杂志,2000,16(7)：323-323.
7. Parker MW, Thompson PD.Exercise in valvular heart disease:risks and benefits. Prog Cardiovasc Dis.2011 May-Jun; 53(6):437-446.
8. Simmons C A, Grant G,Manduchi E, et al. Spatial heterogeneity of endothelial phenotypes correlates with side specific vulnerability to calcification in normal porcine aortic valves. Circ Res,2005,96 (7):792-799.
9. Emile R M, Francis G. Bone formation and inflammation in cardiac valves. Circulation,2001,103:1522-1528.
10. Raggi P, Callister TQ, Lippolis NJ, et al. Is mitral valve prolapse due to cardiac entrapment in the chest Cavity? A CT view. Chest.2000 Mar; 117(3):636-642.
11. Nair CK, Sudhakaran C, Aronow WS, et al. Clinical characteristics of patients younger than 60 years with mitral anular calcium:comparison with age 2 and sex 2matched control subjects. Am J Cardiol,1984,54 (10):1286-1287.
12. El-Shehaby AM, Zakaria A, El-Khatib M, et al. Association of fetuin-A and cardiac calcification and inflammation levels in hemodialysis patients. Scand J Clin Lab Invest.2010,70(8):575-582.
13. Thomas S, Claudette A, Herbertf, et al. Cardiac abnormalities in patient s with primary hyperparathyroidism implications for follow-up. J Clinical Endocrinol Metab,1997,82:106-112.
14. Angela Y, Moon W. Cardiac valve calcification as an important predictor for all-cause mortality and cardiovascular mortality in longterm peritoneal dialysis patients:a prospective study. J Am Soc Nephrol,2003,13:159-168.
15. Segal B L. Valvular heart disease, Part 1. Diagnosis and surgical management of aortic valve disease in older adults. Geriatrics,2003,58 (9):31-35.
16. Benard L S. Dignosis and surgical management of aortic valve disease in old adult s. Geriat rics,2003.356-357.
17.王士雯,王琳,余颂涛.老年钙化性心瓣膜病的病理学研究.实用老年医学,2000,14(1)：45-47.
18. Novo G, Fazio G, Visconti C, et al. Atherosclerosis, degenerative aortic stenosis and statins. Curr Drug Targets.2011 Jan; 12(1):115-121.
19. Marcei P. Relation between cardiovascular risk factors and nonrheumatic severe calcific aortic stenosis among patient s with a three-cuspid aortic valve. Am J Cardiol,2003,91:245-250.
20. Shor A, Kuo C C, Patton D L. Detection of chlamydia pneumoniae in coronary arterial fatty st reaks and atheromatous plaques. S Af r Med J,1992,82:158-161.
1. Thom T, Haase N, Rosamond W, et al. Heart disease and stroke statistics-2006 update:a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation,2006,113:185-151.
2. 刘丽,赵玉生,王士雯等.北京地区军队老年人群退行性心脏瓣膜病流行病学研究.中华流行病学杂志,2006,26(10)：836-839.
3. Goldbarg SH, Elmariah S, Miller MA, et al. Insights into degenerative aortic valve disease. J Am Coll Cardiol.2007,50(13):1205-1213.
4. Beckmann E, Grau JB, Sainger R, et al. Insights into the use of biomarkers in calcific aortic valve disease. J Heart Valve Dis.2010,19(4):441-452.
5. Yetkin E, Waltenberger J. Molecular and cellular mechanisms of aortic stenosis. Int J Cardiol.2009,135(1):4-13.
6. Hakuno D, Kimura N, Yoshioka M, et al. Periostin advances atherosclerotic and rheumatic cardiac valve degeneration by inducing angiogenesis and MMP production in humans and rodents. J Clin Invest.2010,120(7):2292-2306.
7. Nagase Jr H, Woessner JF. Matrix metalloproteinases. J Biol Chem.1999,274: 21491-21494.
8. Carson AE, Barker TH. Emerging concepts in engineering extracellular matrix variants for directing cell phenotype. Regen Med.2009,4(4):593-600.
9. Basu P, Sen U, Tyagi N, et al. Blood flow interplays with elastin:collagen and MMP:TIMP ratios to maintain healthy vascular structure and function. Vasc Health Risk Manag.2010,6:215-228.
10. Jiang L, Wei XF, Yi DH, et al. Synergistic effects of cyclic strain and Thl-like cytokines on tenascin-C production by rheumatic aortic valve interstitial cells. Clin Exp Immunol.2009,155(2):216-223.
11. O'brien K D, Kuusisto J, Reichenbach D D, et al. Osteopontin is expressed in human aortic valvular lesions. Circulation,1995,92:2163-2168.
12. Caira FC, Stock SR, Gleason TG, et al. Human degenerative valve disease is associated with up-regulation of low-density lipoprotein receptor-related protein 5 receptor-mediated bone formation. J Am Coll Cardiol.2006,47(8):1707-1712.
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