Aortic sclerosis natural history, complications and prognosis: Difference between revisions

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==Overview==
==Overview==
Calcification of the aortic valve is common among the elderly population and shares epidemiologic and histopathologic similarities to [[atherosclerosis]].<ref name="pmid20185020">{{cite journal |author=Owens DS, Katz R, Takasu J, Kronmal R, Budoff MJ, O'Brien KD |title=Incidence and progression of aortic valve calcium in the Multi-ethnic Study of Atherosclerosis (MESA) |journal=[[The American Journal of Cardiology]] |volume=105 |issue=5 |pages=701–8 |year=2010 |month=March |pmid=20185020 |pmc=2829478 |doi=10.1016/j.amjcard.2009.10.071 |url=http://linkinghub.elsevier.com/retrieve/pii/S0002-9149(09)02766-0 |accessdate=2012-04-11}}</ref> Progressive thickening and calcification of the aortic valve subsequently causes left ventricular stiffness resulting in [[left ventricular outflow tract obstruction]], thereby leading to [[aortic stenosis]].<ref name="pmid10403851">{{cite journal |author=Otto CM, Lind BK, Kitzman DW, Gersh BJ, Siscovick DS |title=Association of aortic-valve sclerosis with cardiovascular mortality and morbidity in the elderly |journal=[[The New England Journal of Medicine]] |volume=341 |issue=3 |pages=142–7 |year=1999 |month=July |pmid=10403851 |doi=10.1056/NEJM199907153410302 |url=http://dx.doi.org/10.1056/NEJM199907153410302 |accessdate=2012-04-11}}</ref> Prognostically, it is known that [[aortic stenosis]] is clearly associated with adverse cardiovascular outcomes; however, it is unclear whether [[aortic sclerosis]] independently increases the risk of cardiovascular events or progression of [[aortic sclerosis]] to [[aortic stenosis]] increases the risk, including mortality.<ref name="pmid10403851">{{cite journal |author=Otto CM, Lind BK, Kitzman DW, Gersh BJ, Siscovick DS |title=Association of aortic-valve sclerosis with cardiovascular mortality and morbidity in the elderly |journal=[[The New England Journal of Medicine]] |volume=341 |issue=3 |pages=142–7 |year=1999 |month=July |pmid=10403851 |doi=10.1056/NEJM199907153410302 |url=http://dx.doi.org/10.1056/NEJM199907153410302 |accessdate=2012-04-11}}</ref>
[[Calcification of the aortic valve]] is common among the elderly population and shares epidemiologic and histopathologic similarities to [[atherosclerosis]].<ref name="pmid20185020">{{cite journal |author=Owens DS, Katz R, Takasu J, Kronmal R, Budoff MJ, O'Brien KD |title=Incidence and progression of aortic valve calcium in the Multi-ethnic Study of Atherosclerosis (MESA) |journal=[[The American Journal of Cardiology]] |volume=105 |issue=5 |pages=701–8 |year=2010 |month=March |pmid=20185020 |pmc=2829478 |doi=10.1016/j.amjcard.2009.10.071 |url=http://linkinghub.elsevier.com/retrieve/pii/S0002-9149(09)02766-0 |accessdate=2012-04-11}}</ref> Progressive thickening and calcification of the aortic valve subsequently causes left ventricular stiffness resulting in [[left ventricular outflow tract obstruction]], thereby leading to [[aortic stenosis]].<ref name="pmid10403851">{{cite journal |author=Otto CM, Lind BK, Kitzman DW, Gersh BJ, Siscovick DS |title=Association of aortic-valve sclerosis with cardiovascular mortality and morbidity in the elderly |journal=[[The New England Journal of Medicine]] |volume=341 |issue=3 |pages=142–7 |year=1999 |month=July |pmid=10403851 |doi=10.1056/NEJM199907153410302 |url=http://dx.doi.org/10.1056/NEJM199907153410302 |accessdate=2012-04-11}}</ref> Prognostically, it is known that [[aortic stenosis]] is clearly associated with adverse cardiovascular outcomes; however, it is unclear whether [[aortic sclerosis]] independently increases the risk of cardiovascular events or progression of [[aortic sclerosis]] to [[aortic stenosis]] increases the risk, including mortality.<ref name="pmid10403851">{{cite journal |author=Otto CM, Lind BK, Kitzman DW, Gersh BJ, Siscovick DS |title=Association of aortic-valve sclerosis with cardiovascular mortality and morbidity in the elderly |journal=[[The New England Journal of Medicine]] |volume=341 |issue=3 |pages=142–7 |year=1999 |month=July |pmid=10403851 |doi=10.1056/NEJM199907153410302 |url=http://dx.doi.org/10.1056/NEJM199907153410302 |accessdate=2012-04-11}}</ref>


==Natural History & Disease Progression==
==Natural History & Disease Progression==
===Progression to Aortic Stenosis===
===Progression to Aortic Stenosis===
*Echocardiographic indicators of progression of aortic sclerosis to aortic stenosis include:
*Echocardiographic indicators of progression of [[aortic sclerosis]] to [[aortic stenosis]] include:
:* Restricted leaflet mobility
:* Restricted leaflet mobility
:* Increased echogenicity suggestive of increase leaflet calcification
:* Increased echogenicity suggestive of increase leaflet calcification
:* Increase in jet flow velocity across the valve
:* Increase in jet flow velocity across the valve


*Based on a '''''database study''''' from 1987 to 1993, that evaluated 2131 cases of aortic valve thickening with minimum 1-year echocardiographic follow-up, reported the development of [[aortic stenosis]] in 15.9% cases, of which 10.5% developed [[mild AS]], 2.9% had [[moderate AS]] and 2.5% had [[severe AS]]. Thus, this study demonstrates the prevalence of benign aortic valve thickening with the progression to significant [[aortic stenosis]].<ref name="pmid12418948">{{cite journal |author=Cosmi JE, Kort S, Tunick PA, Rosenzweig BP, Freedberg RS, Katz ES, Applebaum RM, Kronzon I |title=The risk of the development of aortic stenosis in patients with "benign" aortic valve thickening |journal=[[Archives of Internal Medicine]] |volume=162 |issue=20 |pages=2345–7 |year=2002 |month=November |pmid=12418948 |doi= |url=http://archinte.ama-assn.org/cgi/pmidlookup?view=long&pmid=12418948 |accessdate=2012-04-11}}</ref><ref name="pmid12505585">{{cite journal |author=Faggiano P, Antonini-Canterin F, Erlicher A, Romeo C, Cervesato E, Pavan D, Piazza R, Huang G, Nicolosi GL |title=Progression of aortic valve sclerosis to aortic stenosis |journal=[[The American Journal of Cardiology]] |volume=91 |issue=1 |pages=99–101 |year=2003 |month=January |pmid=12505585 |doi= |url=http://linkinghub.elsevier.com/retrieve/pii/S0002914902030114 |accessdate=2012-04-11}}</ref>
*Based on a '''''database study''''' from 1987 to 1993, that evaluated 2131 cases of aortic valve thickening with minimum 1-year echocardiographic follow-up, reported the development of [[aortic stenosis]] in '''15.9%''' cases, of which 10.5% developed [[mild AS]], 2.9% had [[moderate AS]] and 2.5% had [[severe AS]]. Thus, this study demonstrated the prevalence of benign aortic valve thickening with the progression to significant [[aortic stenosis]].<ref name="pmid12418948">{{cite journal |author=Cosmi JE, Kort S, Tunick PA, Rosenzweig BP, Freedberg RS, Katz ES, Applebaum RM, Kronzon I |title=The risk of the development of aortic stenosis in patients with "benign" aortic valve thickening |journal=[[Archives of Internal Medicine]] |volume=162 |issue=20 |pages=2345–7 |year=2002 |month=November |pmid=12418948 |doi= |url=http://archinte.ama-assn.org/cgi/pmidlookup?view=long&pmid=12418948 |accessdate=2012-04-11}}</ref><ref name="pmid12505585">{{cite journal |author=Faggiano P, Antonini-Canterin F, Erlicher A, Romeo C, Cervesato E, Pavan D, Piazza R, Huang G, Nicolosi GL |title=Progression of aortic valve sclerosis to aortic stenosis |journal=[[The American Journal of Cardiology]] |volume=91 |issue=1 |pages=99–101 |year=2003 |month=January |pmid=12505585 |doi= |url=http://linkinghub.elsevier.com/retrieve/pii/S0002914902030114 |accessdate=2012-04-11}}</ref>
 
*Another '''''large population-based cohort''''' reported an '''~9%''' of subjects with [[aortic sclerosis]] progressed to [[aortic stenosis]] over a 5-year echocardiographic follow-up. Additionally, no association was observed between [[C-reactive protein]] levels and the presence of calcific aortic-valve disease or incidental [[aortic stenosis]]. However, if [[C-reactive protein]] was present it was a poor predictor of subclinical calcific aortic-valve disease.<ref name="pmid17996566">{{cite journal |author=Novaro GM, Katz R, Aviles RJ, Gottdiener JS, Cushman M, Psaty BM, Otto CM, Griffin BP |title=Clinical factors, but not C-reactive protein, predict progression of calcific aortic-valve disease: the Cardiovascular Health Study |journal=[[Journal of the American College of Cardiology]] |volume=50 |issue=20 |pages=1992–8 |year=2007 |month=November |pmid=17996566 |doi=10.1016/j.jacc.2007.07.064 |url=http://linkinghub.elsevier.com/retrieve/pii/S0735-1097(07)02703-9 |accessdate=2012-04-11}}</ref>
 
==Complication==
===Risk of Microembolism===
Spontaneous calcific embolization has been associated with [[calcific aortic valve disease]];<ref name="pmid14173487">{{cite journal |author=HOLLEY KE, BAHN RC, MCGOON DC, MANKIN HT |title=SPONTANEOUS CALCIFIC EMBOLIZATION ASSOCIATED WITH CALCIFIC AORTIC STENOSIS |journal=[[Circulation]] |volume=27 |issue= |pages=197–202 |year=1963 |month=February |pmid=14173487 |doi= |url= |accessdate=2012-04-11}}</ref> however, Boon et al<ref name="pmid8623104">{{cite journal |author=Boon A, Lodder J, Cheriex E, Kessels F |title=Risk of stroke in a cohort of 815 patients with calcification of the aortic valve with or without stenosis |journal=[[Stroke; a Journal of Cerebral Circulation]] |volume=27 |issue=5 |pages=847–51 |year=1996 |month=May |pmid=8623104 |doi= |url=http://stroke.ahajournals.org/cgi/pmidlookup?view=long&pmid=8623104 |accessdate=2012-04-11}}</ref> and Kizer et al<ref name="pmid16254219">{{cite journal |author=Kizer JR, Wiebers DO, Whisnant JP, Galloway JM, Welty TK, Lee ET, Best LG, Resnick HE, Roman MJ, Devereux RB |title=Mitral annular calcification, aortic valve sclerosis, and incident stroke in adults free of clinical cardiovascular disease: the Strong Heart Study |journal=[[Stroke; a Journal of Cerebral Circulation]] |volume=36 |issue=12 |pages=2533–7 |year=2005 |month=December |pmid=16254219 |doi=10.1161/01.STR.0000190005.09442.ad |url=http://stroke.ahajournals.org/cgi/pmidlookup?view=long&pmid=16254219 |accessdate=2012-04-11}}</ref>, demonstrated no significant increase in the risk of [[stroke]] in [[aortic sclerosis]] patients with or without [[aortic stenosis]].<ref name="pmid10403851">{{cite journal |author=Otto CM, Lind BK, Kitzman DW, Gersh BJ, Siscovick DS |title=Association of aortic-valve sclerosis with cardiovascular mortality and morbidity in the elderly |journal=[[The New England Journal of Medicine]] |volume=341 |issue=3 |pages=142–7 |year=1999 |month=July |pmid=10403851 |doi=10.1056/NEJM199907153410302 |url=http://dx.doi.org/10.1056/NEJM199907153410302 |accessdate=2012-04-11}}</ref>


==Prognosis==
==Prognosis==
*Prognostically, it is known that [[aortic stenosis]] is clearly associated with adverse cardiovascular outcomes; however, it is unclear whether [[aortic sclerosis]] independently increases the risk of cardiovascular events or progression of [[aortic sclerosis]] to [[aortic stenosis]] increases the risk, including mortality.<ref name="pmid10403851">{{cite journal |author=Otto CM, Lind BK, Kitzman DW, Gersh BJ, Siscovick DS |title=Association of aortic-valve sclerosis with cardiovascular mortality and morbidity in the elderly |journal=[[The New England Journal of Medicine]] |volume=341 |issue=3 |pages=142–7 |year=1999 |month=July |pmid=10403851 |doi=10.1056/NEJM199907153410302 |url=http://dx.doi.org/10.1056/NEJM199907153410302 |accessdate=2012-04-11}}</ref>
*Prognostically, it is known that [[aortic stenosis]] is clearly associated with adverse cardiovascular outcomes; however, it is unclear whether [[aortic sclerosis]] independently increases the risk of cardiovascular events or progression of [[aortic sclerosis]] to [[aortic stenosis]] increases the risk, including mortality.<ref name="pmid10403851">{{cite journal |author=Otto CM, Lind BK, Kitzman DW, Gersh BJ, Siscovick DS |title=Association of aortic-valve sclerosis with cardiovascular mortality and morbidity in the elderly |journal=[[The New England Journal of Medicine]] |volume=341 |issue=3 |pages=142–7 |year=1999 |month=July |pmid=10403851 |doi=10.1056/NEJM199907153410302 |url=http://dx.doi.org/10.1056/NEJM199907153410302 |accessdate=2012-04-11}}</ref> One of the possible explanation, could be that [[aortic sclerosis]] serves as a inflammatory marker for [[coronary artery disease]];<ref name="pmid14736432">{{cite journal |author=Chandra HR, Goldstein JA, Choudhary N, O'Neill CS, George PB, Gangasani SR, Cronin L, Marcovitz PA, Hauser AM, O'Neill WW |title=Adverse outcome in aortic sclerosis is associated with coronary artery disease and inflammation |journal=[[Journal of the American College of Cardiology]] |volume=43 |issue=2 |pages=169–75 |year=2004 |month=January |pmid=14736432 |doi= |url=http://linkinghub.elsevier.com/retrieve/pii/S0735109703014104 |accessdate=2012-04-11}}</ref><ref name="pmid14736433">{{cite journal |author=Otto CM |title=Why is aortic sclerosis associated with adverse clinical outcomes? |journal=[[Journal of the American College of Cardiology]] |volume=43 |issue=2 |pages=176–8 |year=2004 |month=January |pmid=14736433 |doi= |url=http://linkinghub.elsevier.com/retrieve/pii/S0735109703014098 |accessdate=2012-04-11}}</ref><ref name="pmid21679852">{{cite journal |author=Marincheva-Savcheva G, Subramanian S, Qadir S, Figueroa A, Truong Q, Vijayakumar J, Brady TJ, Hoffmann U, Tawakol A |title=Imaging of the aortic valve using fluorodeoxyglucose positron emission tomography increased valvular fluorodeoxyglucose uptake in aortic stenosis |journal=[[Journal of the American College of Cardiology]] |volume=57 |issue=25 |pages=2507–15 |year=2011 |month=June |pmid=21679852 |doi=10.1016/j.jacc.2010.12.046 |url=http://linkinghub.elsevier.com/retrieve/pii/S0735-1097(11)01263-0 |accessdate=2012-04-11}}</ref><ref name="pmid16679093">{{cite journal |author=Fox CS, Guo CY, Larson MG, Vasan RS, Parise H, O'Donnell CJ, D'Agostino RB, Keaney JF, Benjamin EJ |title=Relations of inflammation and novel risk factors to valvular calcification |journal=[[The American Journal of Cardiology]] |volume=97 |issue=10 |pages=1502–5 |year=2006 |month=May |pmid=16679093 |doi=10.1016/j.amjcard.2005.11.086 |url=http://linkinghub.elsevier.com/retrieve/pii/S0002-9149(06)00290-6 |accessdate=2012-04-11}}</ref> however, Novaro et al demonstrated no association between [[C-reactive protein]] levels and the presence of calcific aortic-valve disease or incidental [[aortic stenosis]].<ref name="pmid17996566">{{cite journal |author=Novaro GM, Katz R, Aviles RJ, Gottdiener JS, Cushman M, Psaty BM, Otto CM, Griffin BP |title=Clinical factors, but not C-reactive protein, predict progression of calcific aortic-valve disease: the Cardiovascular Health Study |journal=[[Journal of the American College of Cardiology]] |volume=50 |issue=20 |pages=1992–8 |year=2007 |month=November |pmid=17996566 |doi=10.1016/j.jacc.2007.07.064 |url=http://linkinghub.elsevier.com/retrieve/pii/S0735-1097(07)02703-9 |accessdate=2012-04-11}}</ref>
 
*'''''Population-based prospective study''''', evaluated baseline [[transthoracic echocardiography|echocardiograms]] obtained from 5621 men and women 65 years of age or older, off which 70% had normal aortic valve, 29% had [[aortic sclerosis]] without [[Left ventricular outflow tract obstruction|outflow obstruction]] and only 2% had [[aortic stenosis]]. During a mean 5-year follow-up, a stepwise significant increase in mortality was observed in patients with increasing aortic-valve abnormality. Thus, the study concluded an '''~50% increase in the risk''' of death from cardiovascular causes and the risk of [[myocardial infarction]] in patients with [[aortic sclerosis]], even in the absence of hemodynamically significant [[LVOT|obstruction of left ventricular outflow]].<ref name="pmid10403851">{{cite journal |author=Otto CM, Lind BK, Kitzman DW, Gersh BJ, Siscovick DS |title=Association of aortic-valve sclerosis with cardiovascular mortality and morbidity in the elderly |journal=[[The New England Journal of Medicine]] |volume=341 |issue=3 |pages=142–7 |year=1999 |month=July |pmid=10403851 |doi=10.1056/NEJM199907153410302 |url=http://dx.doi.org/10.1056/NEJM199907153410302 |accessdate=2012-04-11}}</ref>


*'''''Population-based prospective study''''', evaluated baseline [[transthoracic echocardiography|echocardiograms]] obtained from 5621 men and women 65 years of age or older, off which 70% had normal aortic valve, 29% had [[aortic sclerosis]] without [[Left ventricular outflow tract obstruction|outflow obstruction]] and only 2% had [[aortic stenosis]]. During a mean 5-year follow-up, a stepwise significant increase in mortality was observed in patients with increasing aortic-valve abnormality. Thus, the study concluded an ~50% increase in the risk of death from cardiovascular causes and the risk of [[myocardial infarction]] in patients with [[aortic sclerosis]], even in the absence of hemodynamically significant [[LVOT|obstruction of left ventricular outflow]].<ref name="pmid10403851">{{cite journal |author=Otto CM, Lind BK, Kitzman DW, Gersh BJ, Siscovick DS |title=Association of aortic-valve sclerosis with cardiovascular mortality and morbidity in the elderly |journal=[[The New England Journal of Medicine]] |volume=341 |issue=3 |pages=142–7 |year=1999 |month=July |pmid=10403851 |doi=10.1056/NEJM199907153410302 |url=http://dx.doi.org/10.1056/NEJM199907153410302 |accessdate=2012-04-11}}</ref>
*Similar association between [[aortic sclerosis]] and the incidence of new coronary events were reported in multiple prospective studies<ref name="pmid10073870">{{cite journal |author=Aronow WS, Ahn C, Shirani J, Kronzon I |title=Comparison of frequency of new coronary events in older subjects with and without valvular aortic sclerosis |journal=[[The American Journal of Cardiology]] |volume=83 |issue=4 |pages=599–600, A8 |year=1999 |month=February |pmid=10073870 |doi= |url=http://linkinghub.elsevier.com/retrieve/pii/S0002-9149(98)00922-9 |accessdate=2012-04-11}}</ref><ref name="pmid15670554">{{cite journal |author=Taylor HA, Clark BL, Garrison RJ, Andrew ME, Han H, Fox ER, Arnett DK, Samdarshi T, Jones DW |title=Relation of aortic valve sclerosis to risk of coronary heart disease in African-Americans |journal=[[The American Journal of Cardiology]] |volume=95 |issue=3 |pages=401–4 |year=2005 |month=February |pmid=15670554 |doi=10.1016/j.amjcard.2004.09.043 |url=http://linkinghub.elsevier.com/retrieve/pii/S0002-9149(04)01611-X |accessdate=2012-04-11}}</ref> and was independent of co-existing cardiovascular disease or traditional cardiovascular risk factors.<ref name="pmid15619412">{{cite journal |author=Olsen MH, Wachtell K, Bella JN, Gerdts E, Palmieri V, Nieminen MS, Smith G, Ibsen H, Devereux RB |title=Aortic valve sclerosis relates to cardiovascular events in patients with hypertension (a LIFE substudy) |journal=[[The American Journal of Cardiology]] |volume=95 |issue=1 |pages=132–6 |year=2005 |month=January |pmid=15619412 |doi=10.1016/j.amjcard.2004.08.080 |url=http://linkinghub.elsevier.com/retrieve/pii/S0002-9149(04)01464-X |accessdate=2012-04-11}}</ref>


==References==
==References==

Latest revision as of 20:15, 10 April 2019

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: Lakshmi Gopalakrishnan, M.B.B.S. [2]

Overview

Calcification of the aortic valve is common among the elderly population and shares epidemiologic and histopathologic similarities to atherosclerosis.[1] Progressive thickening and calcification of the aortic valve subsequently causes left ventricular stiffness resulting in left ventricular outflow tract obstruction, thereby leading to aortic stenosis.[2] Prognostically, it is known that aortic stenosis is clearly associated with adverse cardiovascular outcomes; however, it is unclear whether aortic sclerosis independently increases the risk of cardiovascular events or progression of aortic sclerosis to aortic stenosis increases the risk, including mortality.[2]

Natural History & Disease Progression

Progression to Aortic Stenosis

  • Restricted leaflet mobility
  • Increased echogenicity suggestive of increase leaflet calcification
  • Increase in jet flow velocity across the valve
  • Based on a database study from 1987 to 1993, that evaluated 2131 cases of aortic valve thickening with minimum 1-year echocardiographic follow-up, reported the development of aortic stenosis in 15.9% cases, of which 10.5% developed mild AS, 2.9% had moderate AS and 2.5% had severe AS. Thus, this study demonstrated the prevalence of benign aortic valve thickening with the progression to significant aortic stenosis.[3][4]
  • Another large population-based cohort reported an ~9% of subjects with aortic sclerosis progressed to aortic stenosis over a 5-year echocardiographic follow-up. Additionally, no association was observed between C-reactive protein levels and the presence of calcific aortic-valve disease or incidental aortic stenosis. However, if C-reactive protein was present it was a poor predictor of subclinical calcific aortic-valve disease.[5]

Complication

Risk of Microembolism

Spontaneous calcific embolization has been associated with calcific aortic valve disease;[6] however, Boon et al[7] and Kizer et al[8], demonstrated no significant increase in the risk of stroke in aortic sclerosis patients with or without aortic stenosis.[2]

Prognosis

  • Similar association between aortic sclerosis and the incidence of new coronary events were reported in multiple prospective studies[13][14] and was independent of co-existing cardiovascular disease or traditional cardiovascular risk factors.[15]

References

  1. ↑ Owens DS, Katz R, Takasu J, Kronmal R, Budoff MJ, O'Brien KD (2010). "Incidence and progression of aortic valve calcium in the Multi-ethnic Study of Atherosclerosis (MESA)". The American Journal of Cardiology. 105 (5): 701–8. doi:10.1016/j.amjcard.2009.10.071. PMC 2829478. PMID 20185020. Retrieved 2012-04-11. Unknown parameter |month= ignored (help)
  2. ↑ 2.0 2.1 2.2 2.3 2.4 Otto CM, Lind BK, Kitzman DW, Gersh BJ, Siscovick DS (1999). "Association of aortic-valve sclerosis with cardiovascular mortality and morbidity in the elderly". The New England Journal of Medicine. 341 (3): 142–7. doi:10.1056/NEJM199907153410302. PMID 10403851. Retrieved 2012-04-11. Unknown parameter |month= ignored (help)
  3. ↑ Cosmi JE, Kort S, Tunick PA, Rosenzweig BP, Freedberg RS, Katz ES, Applebaum RM, Kronzon I (2002). "The risk of the development of aortic stenosis in patients with "benign" aortic valve thickening". Archives of Internal Medicine. 162 (20): 2345–7. PMID 12418948. Retrieved 2012-04-11. Unknown parameter |month= ignored (help)
  4. ↑ Faggiano P, Antonini-Canterin F, Erlicher A, Romeo C, Cervesato E, Pavan D, Piazza R, Huang G, Nicolosi GL (2003). "Progression of aortic valve sclerosis to aortic stenosis". The American Journal of Cardiology. 91 (1): 99–101. PMID 12505585. Retrieved 2012-04-11. Unknown parameter |month= ignored (help)
  5. ↑ 5.0 5.1 Novaro GM, Katz R, Aviles RJ, Gottdiener JS, Cushman M, Psaty BM, Otto CM, Griffin BP (2007). "Clinical factors, but not C-reactive protein, predict progression of calcific aortic-valve disease: the Cardiovascular Health Study". Journal of the American College of Cardiology. 50 (20): 1992–8. doi:10.1016/j.jacc.2007.07.064. PMID 17996566. Retrieved 2012-04-11. Unknown parameter |month= ignored (help)
  6. ↑ HOLLEY KE, BAHN RC, MCGOON DC, MANKIN HT (1963). "SPONTANEOUS CALCIFIC EMBOLIZATION ASSOCIATED WITH CALCIFIC AORTIC STENOSIS". Circulation. 27: 197–202. PMID 14173487. Unknown parameter |month= ignored (help); |access-date= requires |url= (help)
  7. ↑ Boon A, Lodder J, Cheriex E, Kessels F (1996). "Risk of stroke in a cohort of 815 patients with calcification of the aortic valve with or without stenosis". Stroke; a Journal of Cerebral Circulation. 27 (5): 847–51. PMID 8623104. Retrieved 2012-04-11. Unknown parameter |month= ignored (help)
  8. ↑ Kizer JR, Wiebers DO, Whisnant JP, Galloway JM, Welty TK, Lee ET, Best LG, Resnick HE, Roman MJ, Devereux RB (2005). "Mitral annular calcification, aortic valve sclerosis, and incident stroke in adults free of clinical cardiovascular disease: the Strong Heart Study". Stroke; a Journal of Cerebral Circulation. 36 (12): 2533–7. doi:10.1161/01.STR.0000190005.09442.ad. PMID 16254219. Retrieved 2012-04-11. Unknown parameter |month= ignored (help)
  9. ↑ Chandra HR, Goldstein JA, Choudhary N, O'Neill CS, George PB, Gangasani SR, Cronin L, Marcovitz PA, Hauser AM, O'Neill WW (2004). "Adverse outcome in aortic sclerosis is associated with coronary artery disease and inflammation". Journal of the American College of Cardiology. 43 (2): 169–75. PMID 14736432. Retrieved 2012-04-11. Unknown parameter |month= ignored (help)
  10. ↑ Otto CM (2004). "Why is aortic sclerosis associated with adverse clinical outcomes?". Journal of the American College of Cardiology. 43 (2): 176–8. PMID 14736433. Retrieved 2012-04-11. Unknown parameter |month= ignored (help)
  11. ↑ Marincheva-Savcheva G, Subramanian S, Qadir S, Figueroa A, Truong Q, Vijayakumar J, Brady TJ, Hoffmann U, Tawakol A (2011). "Imaging of the aortic valve using fluorodeoxyglucose positron emission tomography increased valvular fluorodeoxyglucose uptake in aortic stenosis". Journal of the American College of Cardiology. 57 (25): 2507–15. doi:10.1016/j.jacc.2010.12.046. PMID 21679852. Retrieved 2012-04-11. Unknown parameter |month= ignored (help)
  12. ↑ Fox CS, Guo CY, Larson MG, Vasan RS, Parise H, O'Donnell CJ, D'Agostino RB, Keaney JF, Benjamin EJ (2006). "Relations of inflammation and novel risk factors to valvular calcification". The American Journal of Cardiology. 97 (10): 1502–5. doi:10.1016/j.amjcard.2005.11.086. PMID 16679093. Retrieved 2012-04-11. Unknown parameter |month= ignored (help)
  13. ↑ Aronow WS, Ahn C, Shirani J, Kronzon I (1999). "Comparison of frequency of new coronary events in older subjects with and without valvular aortic sclerosis". The American Journal of Cardiology. 83 (4): 599–600, A8. PMID 10073870. Retrieved 2012-04-11. Unknown parameter |month= ignored (help)
  14. ↑ Taylor HA, Clark BL, Garrison RJ, Andrew ME, Han H, Fox ER, Arnett DK, Samdarshi T, Jones DW (2005). "Relation of aortic valve sclerosis to risk of coronary heart disease in African-Americans". The American Journal of Cardiology. 95 (3): 401–4. doi:10.1016/j.amjcard.2004.09.043. PMID 15670554. Retrieved 2012-04-11. Unknown parameter |month= ignored (help)
  15. ↑ Olsen MH, Wachtell K, Bella JN, Gerdts E, Palmieri V, Nieminen MS, Smith G, Ibsen H, Devereux RB (2005). "Aortic valve sclerosis relates to cardiovascular events in patients with hypertension (a LIFE substudy)". The American Journal of Cardiology. 95 (1): 132–6. doi:10.1016/j.amjcard.2004.08.080. PMID 15619412. Retrieved 2012-04-11. Unknown parameter |month= ignored (help)

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