Aortic sclerosis and mitral annulus calcification: a window to vascular atherosclerosis?

Several similarities exist between atherosclerosis in the vasculature and chronic degenerative changes in valvular structures. It has been suggested that aortic valve sclerosis (AVS) and mitral annulus calcification (MAC) are manifestations of a generalized atherosclerosis, have similar pathogenesis, share common risk factors and are observed with higher prevalence in patients with different forms of atherosclerotic vascular disease. Moreover, recent studies have shown a close relation of MAC and AVS with adverse cardiovascular and cerebrovascular outcomes. However, many patients with AVS or MAC do not have coexisting peripheral vascular atherosclerosis and vice versa. Lipid-reducing therapy has been uniformly unsuccessful in slowing valvular calcification. Thus, whether valve calcifications are the result of a more generalized atherosclerosis, or reflect a primary degenerative process, progressing with advancing age, still remains. From a clinical point of view, it is of great importance to identify common links between valve calcification and vascular atherosclerosis with a view to assess whether the detection of AVS, MAC or both are indicative of subclinical atherosclerosis and predicts cardiovascular or cerebrovascular events. Thus, in this article, the authors review current evidence regarding the association between AVS and MAC with vascular atherosclerosis.

[1]  C. Lang,et al.  Aortic valvular heart disease: is there a place for angiotensin-converting-enzyme inhibitors? , 2013, Expert review of cardiovascular therapy.

[2]  H. Uzun,et al.  Association of serum fetuin-A levels with heart valve calcification and other biomarkers of inflammation among persons with acute coronary syndrome. , 2012, Clinical and investigative medicine. Medecine clinique et experimentale.

[3]  B. Gersh,et al.  Determinants of aortic sclerosis progression: implications regarding impairment of nitric oxide signalling and potential therapeutics. , 2012, European heart journal.

[4]  J. Horowitz,et al.  Prevention of aortic valve stenosis: a realistic therapeutic target? , 2012, Pharmacology & therapeutics.

[5]  N. Rajamannan Oxidative‐mechanical stress signals stem cell niche mediated Lrp5 osteogenesis in eNOS−/− null mice , 2012, Journal of cellular biochemistry.

[6]  Nikolaos Kavantzas,et al.  First in vivo application of microwave radiometry in human carotids: a new noninvasive method for detection of local inflammatory activation. , 2012, Journal of the American College of Cardiology.

[7]  N. Rajamannan Calcific aortic valve disease: cellular origins of valve calcification. , 2011, Arteriosclerosis, thrombosis, and vascular biology.

[8]  J. Krzysiek,et al.  One-year observation of inflammatory markers in patients with aortic valve stenosis. , 2011, The Journal of heart valve disease.

[9]  K. J. Grande-Allen,et al.  Calcific Aortic Valve Disease : Not Simply a Degenerative Process A Review and Agenda for Research from the National Heart and Lung and Blood Institute Aortic Stenosis Working Group , 2012 .

[10]  G. Lip,et al.  Mitral annular calcification predicts cardiovascular morbidity and mortality in middle-aged patients with atrial fibrillation: the Belgrade Atrial Fibrillation Study. , 2011, Chest.

[11]  N. Rajamannan The role of Lrp5/6 in cardiac valve disease: Experimental hypercholesterolemia in the ApoE−/−/Lrp5−/− mice , 2011, Journal of cellular biochemistry.

[12]  N. Rajamannan The role of Lrp5/6 in cardiac valve disease: LDL‐density‐pressure theory , 2011, Journal of cellular biochemistry.

[13]  P. Pibarot,et al.  Clinical and Echocardiographic Correlates of Plasma B‐type Natriuretic Peptide Levels in Patients with Aortic Valve Stenosis and Normal Left Ventricular Ejection Fraction , 2011, Echocardiography.

[14]  N. Rajamannan Serum phosphate concentrations: a novel pre-clinical biomarker for cardiovascular calcification. , 2011, Journal of the American College of Cardiology.

[15]  R. Kronmal,et al.  Relation of mitral annular calcium and coronary calcium (from the Multi-Ethnic Study of Atherosclerosis [MESA]). , 2011, The American journal of cardiology.

[16]  C. Stefanadis,et al.  A new non-invasive method for detection of local inflammation in atherosclerotic plaques: experimental application of microwave radiometry. , 2011, Atherosclerosis.

[17]  Yuan Zhang,et al.  Ramipril retards development of aortic valve stenosis in a rabbit model: mechanistic considerations , 2011, British journal of pharmacology.

[18]  F. Veglia,et al.  Do statins improve outcomes and delay the progression of non-rheumatic calcific aortic stenosis? , 2011, Heart.

[19]  V. Figueredo,et al.  Can total cardiac calcium predict the coronary calcium score? , 2011, International journal of cardiology.

[20]  J. Blacher,et al.  Cardiac and arterial calcifications and all-cause mortality in the elderly: the PROTEGER Study. , 2010, Atherosclerosis.

[21]  Y. Kihara,et al.  Combined presence of aortic valve calcification and mitral annular calcification as a marker of the extent and vulnerable characteristics of coronary artery plaque assessed by 64-multidetector computed tomography. , 2010, Atherosclerosis.

[22]  E. Picano,et al.  Cardiac calcification by transthoracic echocardiography in patients with known or suspected coronary artery disease. , 2010, International journal of cardiology.

[23]  R. Sainger,et al.  Insights into the use of biomarkers in calcific aortic valve disease. , 2010, The Journal of heart valve disease.

[24]  R. Cury,et al.  Associations of long-term and early adult atherosclerosis risk factors with aortic and mitral valve calcium. , 2010, Journal of the American College of Cardiology.

[25]  U. John,et al.  Heart valve sclerosis predicts all-cause and cardiovascular mortality. , 2010, Atherosclerosis.

[26]  J. J. Rivera,et al.  Relationships of mitral annular calcification to cardiovascular risk factors: the Multi-Ethnic Study of Atherosclerosis (MESA). , 2010, Atherosclerosis.

[27]  B. Carabello The SEAS Trial , 2010, Current cardiology reports.

[28]  K. Teo,et al.  Effect of Lipid Lowering With Rosuvastatin on Progression of Aortic Stenosis: Results of the Aortic Stenosis Progression Observation: Measuring Effects of Rosuvastatin (ASTRONOMER) Trial , 2010, Circulation.

[29]  H. Hense,et al.  Association between degenerative aortic valve disease and long-term exposure to cardiovascular risk factors: results of the longitudinal population-based KORA/MONICA survey. , 2009, European heart journal.

[30]  S. Sawada,et al.  Does diabetes accelerate progression of calcific aortic stenosis? , 2009, European journal of echocardiography : the journal of the Working Group on Echocardiography of the European Society of Cardiology.

[31]  J. McNeil,et al.  Determinants of occurrence of aortic sclerosis in an aging population. , 2009, JACC. Cardiovascular imaging.

[32]  J. Waltenberger,et al.  Molecular and cellular mechanisms of aortic stenosis. , 2009, International journal of cardiology.

[33]  Craig A Simmons,et al.  Calcification by Valve Interstitial Cells Is Regulated by the Stiffness of the Extracellular Matrix , 2009, Arteriosclerosis, thrombosis, and vascular biology.

[34]  Ajit P Yoganathan,et al.  Endothelium-dependent regulation of the mechanical properties of aortic valve cusps. , 2009, Journal of the American College of Cardiology.

[35]  Jeroen J. Bax,et al.  Usefulness of echocardiographic assessment of cardiac and ascending aorta calcific deposits to predict coronary artery calcium and presence and severity of obstructive coronary artery disease. , 2009, The American journal of cardiology.

[36]  S. Abbasi,et al.  Aortic and mitral valve atherosclerosis: Predictive factors and associations with coronary atherosclerosis using Gensini score. , 2009, Archives of medical research.

[37]  N. Rajamannan Calcific aortic stenosis: lessons learned from experimental and clinical studies. , 2009, Arteriosclerosis, thrombosis, and vascular biology.

[38]  R. Sacco,et al.  Impact of mitral annular calcification on cardiovascular events in a multiethnic community: the Northern Manhattan Study. , 2008, JACC. Cardiovascular imaging.

[39]  M. Yacoub,et al.  In vivo aortic valve thermal heterogeneity in patients with nonrheumatic aortic valve stenosis the: first in vivo experience in humans. , 2008, Journal of the American College of Cardiology.

[40]  J. Horowitz,et al.  Vitamin D(2) supplementation induces the development of aortic stenosis in rabbits: interactions with endothelial function and thioredoxin-interacting protein. , 2008, European journal of pharmacology.

[41]  J. Després,et al.  Association between circulating oxidised low-density lipoprotein and fibrocalcific remodelling of the aortic valve in aortic stenosis , 2007, Heart.

[42]  A. Arboix,et al.  Mitral Annular Calcification as a Marker of Complex Aortic Atheroma in Patients with Stroke of Uncertain Etiology , 2007, Echocardiography.

[43]  G. Borgulya,et al.  Intracardiac Calcification Is a Marker of Generalized Atherosclerosis , 2007, Angiology.

[44]  C. Tsioufis,et al.  Correlation of systemic inflammation with local inflammatory activity in non-culprit lesions: beneficial effect of statins. , 2007, International journal of cardiology.

[45]  C. Stefanadis,et al.  Correlation between morphologic characteristics and local temperature differences in culprit lesions of patients with symptomatic coronary artery disease. , 2007, Journal of the American College of Cardiology.

[46]  M. Cicoira,et al.  Aortic valve sclerosis: a marker of significant obstructive coronary artery disease in patients with chest pain? , 2007, Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography.

[47]  M. Shlipak,et al.  Association of Fetuin-A With Mitral Annular Calcification and Aortic Stenosis Among Persons With Coronary Heart Disease: Data From the Heart and Soul Study , 2007, Circulation.

[48]  R. Bonow,et al.  Calcific aortic stenosis: an update , 2007, Nature Clinical Practice Cardiovascular Medicine.

[49]  W. Gianni,et al.  Carotid intima–media thickness, carotid distensibility and mitral, aortic valve calcification: a useful diagnostic parameter of systemic atherosclerotic disease , 2007, Journal of cardiovascular medicine.

[50]  P. Collinson,et al.  Mitral annular calcification predicts mortality and coronary artery disease in end stage renal disease. , 2007, Atherosclerosis.

[51]  N. Rajamannan Reassessment of statins to retard the progression of aortic stenosis , 2007, Current cardiology reports.

[52]  T. Marwick,et al.  Aortic stenosis is associated with elevated plasma levels of asymmetric dimethylarginine (ADMA). , 2007, Nitric oxide : biology and chemistry.

[53]  Yun Zhang,et al.  A High Association of Aortic Valve Sclerosis Detected by Transthoracic Echocardiography with Coronary Arteriosclerosis , 2007, Cardiology.

[54]  J. Zamorano,et al.  Rosuvastatin affecting aortic valve endothelium to slow the progression of aortic stenosis. , 2007, Journal of the American College of Cardiology.

[55]  F. Ruschitzka,et al.  Persistent endothelial dysfunction in calcified aortic stenosis beyond valve replacement surgery , 2006, Heart.

[56]  M. Aksoy,et al.  Relationship between Aortic Valve Sclerosis and the Extent of Coronary Artery Disease in Patients Undergoing Diagnostic Coronary Angiography , 2006, Cardiology.

[57]  M. C. Epistolato,et al.  Biological features (inflammation and neoangiogenesis) and atherosclerotic risk factors in carotid plaques and calcified aortic valve stenosis: two different sites of the same disease? , 2006, American journal of clinical pathology.

[58]  N. Rajamannan Role of statins in aortic valve disease. , 2006, Heart failure clinics.

[59]  T. Zapolski,et al.  Relationship between aortic valve calcification and aortic atherosclerosis: a transoesophageal echocardiography study. , 2006, Kardiologia polska.

[60]  R. D'Agostino,et al.  Relations of inflammation and novel risk factors to valvular calcification. , 2006, The American journal of cardiology.

[61]  V. Ribeiro,et al.  Calcific aortic stenosis: another face of atherosclerosis? , 2006 .

[62]  P. Chaves,et al.  Cardiovascular morbidity and mortality in community-dwelling elderly individuals with calcification of the fibrous skeleton of the base of the heart and aortosclerosis (The Cardiovascular Health Study). , 2006, The American journal of cardiology.

[63]  R. Bonow,et al.  Human degenerative valve disease is associated with up-regulation of low-density lipoprotein receptor-related protein 5 receptor-mediated bone formation. , 2006, Journal of the American College of Cardiology.

[64]  F. Schoen,et al.  Human Semilunar Cardiac Valve Remodeling by Activated Cells From Fetus to Adult: Implications for Postnatal Adaptation, Pathology, and Tissue Engineering , 2006, Circulation.

[65]  R. Langer,et al.  Mitral and Aortic Annular Calcification Are Highly Associated With Systemic Calcified Atherosclerosis , 2006, Circulation.

[66]  C. Stefanadis,et al.  Elevated plaque temperature in non-culprit de novo atheromatous lesions of patients with acute coronary syndromes. , 2006, Journal of the American College of Cardiology.

[67]  N. Rajamannan Calcific aortic stenosis: Medical and surgical management in the elderly , 2005, Current treatment options in cardiovascular medicine.

[68]  D. Wiebers,et al.  Mitral Annular Calcification, Aortic Valve Sclerosis, and Incident Stroke in Adults Free of Clinical Cardiovascular Disease: The Strong Heart Study , 2005, Stroke.

[69]  C. Stefanadis,et al.  Increased heat generation from atherosclerotic plaques in patients with type 2 diabetes: an increased local inflammatory activation. , 2005, Diabetes care.

[70]  C. Stefanadis,et al.  Patients with type two diabetes mellitus: increased local inflammatory activation in culprit atheromatous plaques. , 2005, Hellenic journal of cardiology : HJC = Hellenike kardiologike epitheorese.

[71]  W. Edwards,et al.  Calcified Rheumatic Valve Neoangiogenesis Is Associated With Vascular Endothelial Growth Factor Expression and Osteoblast-Like Bone Formation , 2005, Circulation.

[72]  R. Prescott,et al.  A randomized trial of intensive lipid-lowering therapy in calcific aortic stenosis. , 2005, The New England journal of medicine.

[73]  R. Bonow,et al.  Atorvastatin decreases cellular proliferation and bone matrix expression in the hypercholesterolemic mitral valve. , 2005, Journal of the American College of Cardiology.

[74]  R. Garrison,et al.  Relation of aortic valve sclerosis to risk of coronary heart disease in African-Americans. , 2005, American Journal of Cardiology.

[75]  C. Stefanadis,et al.  Detection of increased temperature of the culprit lesion after recent myocardial infarction: the favorable effect of statins. , 2004, American heart journal.

[76]  M. Wen,et al.  Aortic valve sclerosis is an echocardiographic indicator of significant coronary disease in patients undergoing diagnostic coronary angiography , 2004, International journal of clinical practice.

[77]  T. Akasaka,et al.  Relation of aortic valve sclerosis to carotid artery intima-media thickening in healthy subjects. , 2004, The American journal of cardiology.

[78]  C. Otto,et al.  Targeted therapy to prevent progression of calcific aortic stenosis. , 2004, Circulation.

[79]  H. Reichenspurner,et al.  Angiogenic activation of valvular endothelial cells in aortic valve stenosis. , 2004, Experimental cell research.

[80]  K. Aytemir,et al.  Is carotid atherosclerosis more important in patients with mitral annular calcification than in those without? , 2004, Japanese heart journal.

[81]  K. J. Grande-Allen,et al.  Glycosaminoglycans and proteoglycans in normal mitral valve leaflets and chordae: association with regions of tensile and compressive loading. , 2004, Glycobiology.

[82]  C. Stefanadis,et al.  Coronary artery plaque temperature: what do we measure? , 2004, European heart journal.

[83]  R. de Caterina,et al.  Neoangiogenesis, T-lymphocyte infiltration, and heat shock protein-60 are biological hallmarks of an immunomediated inflammatory process in end-stage calcified aortic valve stenosis. , 2004, Journal of the American College of Cardiology.

[84]  D. Levy,et al.  Mitral annular calcification is a predictor for incident atrial fibrillation. , 2004, Atherosclerosis.

[85]  W. O’Neill,et al.  Adverse outcome in aortic sclerosis is associated with coronary artery disease and inflammation. , 2004, Journal of the American College of Cardiology.

[86]  C. Otto Why is aortic sclerosis associated with adverse clinical outcomes? , 2004, Journal of the American College of Cardiology.

[87]  M. Schemper,et al.  Mild and moderate aortic stenosis. Natural history and risk stratification by echocardiography. , 2003, European heart journal.

[88]  M. Demir,et al.  Mitral Annular Calcification and Aortic Valve Calcification May Help in Predicting Significant Coronary Artery Disease , 2003, Angiology.

[89]  W. Edwards,et al.  Hypercholesterolemic aortic-valve disease. , 2003, The New England journal of medicine.

[90]  B. Gersh,et al.  CALCIFIC AORTIC STENOSIS: FROM BENCH TO THE BEDSIDE—EMERGING CLINICAL AND CELLULAR CONCEPTS , 2003, Heart.

[91]  A. Tajik,et al.  Human Aortic Valve Calcification Is Associated With an Osteoblast Phenotype , 2003, Circulation.

[92]  D. Levy,et al.  Mitral Annular Calcification Predicts Cardiovascular Morbidity and Mortality: The Framingham Heart Study , 2003, Circulation.

[93]  Huai Luo,et al.  Mitral annular calcification: a marker of severe coronary artery disease in patients under 65 years old , 2003, Heart.

[94]  M. Crawford,et al.  Aortic valve sclerosis, mitral annular calcium, and aortic root sclerosis as markers of atherosclerosis in men. , 2002, The American journal of cardiology.

[95]  Y. Adler,et al.  Nonobstructive aortic valve calcification: a window to significant coronary artery disease. , 2002, Atherosclerosis.

[96]  M. Lauer,et al.  Effect of Hydroxymethylglutaryl Coenzyme A Reductase Inhibitors on the Progression of Calcific Aortic Stenosis , 2001, Circulation.

[97]  K. Chan,et al.  Case-controlled study to assess risk factors for aortic stenosis in congenitally bicuspid aortic valve. , 2001, The American journal of cardiology.

[98]  A. Tajik,et al.  Experimental hypercholesterolemia induces apoptosis in the aortic valve. , 2001, The Journal of heart valve disease.

[99]  Emile R. Mohler,et al.  Bone Formation and Inflammation in Cardiac Valves , 2001, Circulation.

[100]  Y. Adler,et al.  Mitral annulus calcification--a window to diffuse atherosclerosis of the vascular system. , 2001, Atherosclerosis.

[101]  P. Weissberg,et al.  Vascular and valvar calcification: recent advances , 2001, Heart.

[102]  I. Kallikazaros,et al.  Closed Relation Between Carotid and Ascending Aortic Atherosclerosis in Cardiac Patients , 2000, Circulation.

[103]  W. O'Fallon,et al.  Predictors of Cerebrovascular Events and Death Among Patients With Valvular Heart Disease: A Population-Based Study , 2000, Stroke.

[104]  A. Zelikovski,et al.  Association between mitral annulus calcification and peripheral arterial atherosclerotic disease. , 2000, Angiology.

[105]  A. Tenenbaum,et al.  Advanced mitral annular calcification is associated with severe coronary calcification on fast dual spiral computed tomography. , 2000, Investigative radiology.

[106]  C. Stefanadis,et al.  Mitral valve prolapse: the merchant of venice or much ado about nothing? , 2000, European heart journal.

[107]  Bonnie K. Lind,et al.  Association of aortic-valve sclerosis with cardiovascular mortality and morbidity in the elderly. , 1999, The New England journal of medicine.

[108]  P Toutouzas,et al.  Thermal heterogeneity within human atherosclerotic coronary arteries detected in vivo: A new method of detection by application of a special thermography catheter. , 1999, Circulation.

[109]  Jagmeet P. Singh,et al.  Prevalence and clinical determinants of mitral, tricuspid, and aortic regurgitation (the Framingham Heart Study) , 1999, The American journal of cardiology.

[110]  W. Aronow,et al.  Comparison of frequency of new coronary events in older subjects with and without valvular aortic sclerosis. , 1999, The American journal of cardiology.

[111]  Y. Adler,et al.  Mitral annular calcium detected by transthoracic echocardiography is a marker for high prevalence and severity of coronary artery disease in patients undergoing coronary angiography. , 1998, The American journal of cardiology.

[112]  P. Toutouzas,et al.  Left atrial energy in normal subjects, in patients with symptomatic mitral stenosis, and in patients with advanced heart failure. , 1998, The American journal of cardiology.

[113]  C. Tsioufis,et al.  Retrograde nontransseptal balloon mitral valvuloplasty: immediate results and intermediate long-term outcome in 441 cases--a multicenter experience. , 1998, Journal of the American College of Cardiology.

[114]  C. Vlachopoulos,et al.  Effects of balloon mitral valvuloplasty on left atrial function in mitral stenosis as assessed by pressure-area relation. , 1998, Journal of the American College of Cardiology.

[115]  Y. Adler,et al.  Association between mitral annular calcium and aortic atheroma as detected by transesophageal echocardiographic study. , 1998, The American journal of cardiology.

[116]  W. Aronow,et al.  Comparison of frequency of new coronary events in older persons with mild, moderate, and severe valvular aortic stenosis with those without aortic stenosis. , 1998, The American journal of cardiology.

[117]  J. Lodder,et al.  Cardiac valve calcification: characteristics of patients with calcification of the mitral annulus or aortic valve , 1997, Heart.

[118]  J. Lodder,et al.  Mitral annulus calcification is not an independent risk factor for stroke: a cohort study of 657 patients , 1997, Journal of Neurology.

[119]  E. Mohler,et al.  Detection of osteopontin in calcified human aortic valves. , 1997, Arteriosclerosis, thrombosis, and vascular biology.

[120]  Bonnie K. Lind,et al.  Clinical factors associated with calcific aortic valve disease. Cardiovascular Health Study. , 1997, Journal of the American College of Cardiology.

[121]  Catherine M. Otto,et al.  Clinical Factors Associated With Calcific Aortic Valve Disease , 1997 .

[122]  J. Lodder,et al.  Risk of stroke in a cohort of 815 patients with calcification of the aortic valve with or without stenosis. , 1996, Stroke.

[123]  C. Stefanadis,et al.  Percutaneous mitral valvuloplasty: a decade of experience. , 1995, European heart journal.

[124]  C. Vlachopoulos,et al.  Retrograde nontransseptal balloon mitral valvuloplasty using a modified Inoue balloon catheter. , 1994, Catheterization and cardiovascular diagnosis.

[125]  A. Gown,et al.  Characterization of the Early Lesion of ‘Degenerative’ Valvular Aortic Stenosis: Histological and Immunohistochemical Studies , 1994, Circulation.

[126]  T. Strandberg,et al.  Factors associated with calcific aortic valve degeneration in the elderly. , 1994, European heart journal.

[127]  M. Rosenqvist,et al.  Accumulation of T lymphocytes and expression of interleukin-2 receptors in nonrheumatic stenotic aortic valves. , 1994, Journal of the American College of Cardiology.

[128]  D. Levy,et al.  Mitral annular calcification and the risk of stroke in an elderly cohort. , 1992, The New England journal of medicine.

[129]  W. Aronow,et al.  Frequency of thromboembolic stroke in persons ≥60 years of age with extracranial carotid arterial disease and/or mitral annular calcium , 1992 .

[130]  C. Vlachopoulos,et al.  Retrograde Nontransseptal Balloon Mitral Valvuloplast: Immediate Results and Long‐term Follow‐up , 1992, Circulation.

[131]  Predictors of Thromboembolism in Atrial Fibrillation: II. Echocardiographic Features of Patients at Risk , 1992, Annals of Internal Medicine.

[132]  Bernard Rosner,et al.  The effect of low-dose warfarin on the risk of stroke in patients with nonrheumatic atrial fibrillation. , 1990, The New England journal of medicine.

[133]  W. Aronow,et al.  Association of mitral anular calcium with new thromboembolic stroke and cardiac events at 39-month follow-up in elderly patients. , 1990, The American journal of cardiology.

[134]  C. Nair,et al.  Long-term follow-up of patients with echocardiographically detected mitral anular calcium and comparison with age- and sex-matched control subjects. , 1989, The American journal of cardiology.

[135]  W. Aronow,et al.  Correlation of serum lipids, calcium, and phosphorus, diabetes mellitus and history of systemic hypertension with presence or absence of calcified or thickened aortic cusps or root in elderly patients. , 1987, The American journal of cardiology.

[136]  W. Roberts The senile cardiac calcification syndrome. , 1986, The American journal of cardiology.

[137]  W. Aronow,et al.  Clinical characteristics of patients younger than 60 years with mitral anular calcium: comparison with age- and sex-matched control subjects. , 1984, The American journal of cardiology.

[138]  W. Roberts,et al.  Morphologic features of the normal and abnormal mitral valve. , 1983, The American journal of cardiology.

[139]  K. Walton,et al.  The pathogenesis of atherosclerosis of the mitral and aortic valves , 1970, The Journal of pathology.

[140]  J. Bavaria,et al.  Analysis of osteopontin levels for the identification of asymptomatic patients with calcific aortic valve disease. , 2012, The Annals of thoracic surgery.

[141]  J. Horowitz,et al.  Pathogenesis of aortic stenosis: not just a matter of wear and tear. , 2011, American journal of cardiovascular disease.

[142]  N. Rajamannan Mechanisms of aortic valve calcification: the LDL-density-radius theory: a translation from cell signaling to physiology. , 2010, American journal of physiology. Heart and circulatory physiology.

[143]  P. Kovanen,et al.  Complement system is activated in stenotic aortic valves. , 2008, Atherosclerosis.

[144]  K. Fukuda,et al.  Molecular mechanisms underlying the onset of degenerative aortic valve disease , 2008, Journal of Molecular Medicine.

[145]  M. Nieminen,et al.  Aortic valve sclerosis relates to cardiovascular events in patients with hypertension (a LIFE substudy). , 2005, The American journal of cardiology.

[146]  C. Tribouilloy,et al.  Relation between cardiovascular risk factors and nonrheumatic severe calcific aortic stenosis among patients with a three-cuspid aortic valve. , 2003, The American journal of cardiology.

[147]  W. Aronow,et al.  Frequency of thromboembolic stroke in persons greater than or equal to 60 years of age with extracranial carotid arterial disease and/or mitral annular calcium. , 1992, American Journal of Cardiology.