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European Journal of Epidemiology

, Volume 29, Issue 8, pp 567–575 | Cite as

Assessment of risk factors for developing incident aortic stenosis: the Tromsø Study

  • Gry Wisthus EvebornEmail author
  • Henrik Schirmer
  • Per Lunde
  • Geir Heggelund
  • John-Bjarne Hansen
  • Knut Rasmussen
CARDIOVASCULAR DISEASE

Abstract

To disclose risk factors of incident aortic stenosis (AS) and progression of established AS. A prospective cohort study. The Tromsø Study, a population based health survey. Over a 14 years span we performed three repeated echocardiographic examinations (1994, 2001 and 2008) of a random sample of initially 3,243 participants. Data from the only hospital serving this population were included in the follow up. Throughout the study 132 participants were diagnosed with incident AS, defined as mean aortic valve gradient ≥15 mmHg. Cox proportional hazards regression disclosed age (HR 1.11, 95 %CI 1.08–1.14), systolic blood pressure (BP) (HR 1.01, 95 % CI 1.00–1.02), active smoking (HR 1.71, 95 % CI 1.09–2.67), and waist circumference (HR 1.02, 95 % CI 1.00–1.03) as independent predictors of incident AS. Analysis of risk factors for progression of AS disclosed a higher mean aortic gradient at first measurement (p = 0.015), weight (p = 0.015), a low haemoglobin (Hgb) (p = 0.030) and high density lipoprotein (HDL) (p = 0.032) as significant independent predictors. Age, systolic BP, smoking and waist circumference were independent predictors of incident AS, whereas cholesterol was not. Mean aortic gradient at first measurement, weight, an elevated HDL and low Hgb increase the progression rate of the disease. Our data indicate that calcific aortic valve disease is a distinct pathophysiological process, with age, smoking and “wear and tear” of the valve being major contributors to the disease development.

Keywords

Calcific aortic valve disease Degenerative aortic stenosis Epidemiology Risk factor Echocardiography 

Notes

Acknowledgments

Tom Wilsgård for statistical support. This study was supported by the Northern Norway Regional Health Authorities (PhD Grant Number SFP-727-08).

Conflict of interest

None declared.

References

  1. 1.
    Freeman RV, Otto CM. Spectrum of calcific aortic valve disease: pathogenesis, disease progression, and treatment strategies. Circulation. 2005;111(24):3316–26.PubMedCrossRefGoogle Scholar
  2. 2.
    Nkomo VT, Gardin JM, Skelton TN, Gottdiener JS, Scott CG, Enriquez-Sarano M. Burden of valvular heart diseases: a population-based study. Lancet. 2006;368(9540):1005–11.PubMedCrossRefGoogle Scholar
  3. 3.
    Stewart BF, Siscovick D, Lind BK, et al. Clinical factors associated with calcific aortic valve disease. cardiovascular health study. J Am Coll Cardiol. 1997;29(3):630–4.PubMedCrossRefGoogle Scholar
  4. 4.
    Lindroos M, Kupari M, Heikkila J, Tilvis R. Prevalence of aortic valve abnormalities in the elderly: an echocardiographic study of a random population sample. J Am Coll Cardiol. 1993;21(5):1220–5.PubMedCrossRefGoogle Scholar
  5. 5.
    Eveborn GW, Schirmer H, Heggelund G, Lunde P, Rasmussen K. The evolving epidemiology of valvular aortic stenosis. The Tromso study. Heart. 2012;. doi: 10.1136/heartjnl-2012-302265.PubMedGoogle Scholar
  6. 6.
    Kurtz CE, Otto CM. Aortic stenosis: clinical aspects of diagnosis and management, with 10 illustrative case reports from a 25-year experience. Medicine. 2010;89(6):349–79. doi: 10.1097/MD.0b013e3181fe5648.PubMedCrossRefGoogle Scholar
  7. 7.
    Chan KL. Is aortic stenosis a preventable disease? J Am Coll Cardiol. 2003;42(4):593–9.PubMedCrossRefGoogle Scholar
  8. 8.
    Jacobsen BK, Eggen AE, Mathiesen EB, Wilsgaard T, Njolstad I. Cohort profile: the Tromso study. Int J Epidemiol. 2011;. doi: 10.1093/ije/dyr049.Google Scholar
  9. 9.
    Ix JH, Shlipak MG, Katz R, et al. Kidney function and aortic valve and mitral annular calcification in the Multi-Ethnic Study of Atherosclerosis (MESA). Am J Kidney Dis. 2007;50(3):412–20. doi: 10.1053/j.ajkd.2007.05.020.PubMedCrossRefGoogle Scholar
  10. 10.
    Katz R, Wong ND, Kronmal R, et al. Features of the metabolic syndrome and diabetes mellitus as predictors of aortic valve calcification in the multi-ethnic study of atherosclerosis. Circulation. 2006;113(17):2113–9.PubMedCrossRefGoogle Scholar
  11. 11.
    Stritzke J, Linsel-Nitschke P, Markus MR, 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. Eur Heart J. 2009;30(16):2044–53. doi: 10.1093/eurheartj/ehp287.PubMedCrossRefGoogle Scholar
  12. 12.
    Perkovic V, Hunt D, Griffin SV, du Plessis M, Becker GJ. Accelerated progression of calcific aortic stenosis in dialysis patients. Nephron Clin Prac. 2003;94(2):c40–5. doi: 10.1159/000071280.CrossRefGoogle Scholar
  13. 13.
    Bahler RC, Desser DR, Finkelhor RS, Brener SJ, Youssefi M. Factors leading to progression of valvular aortic stenosis. Am J Cardiol. 1999;84(9):1044–8.PubMedCrossRefGoogle Scholar
  14. 14.
    Palta S, Pai AM, Gill KS, Pai RG. New insights into the progression of aortic stenosis: implications for secondary prevention. Circulation. 2000;101(21):2497–502.PubMedCrossRefGoogle Scholar
  15. 15.
    Rosenhek R, Binder T, Porenta G, et al. Predictors of outcome in severe, asymptomatic aortic stenosis. N Engl J Med. 2000;343(9):611–7. doi: 10.1056/nejm200008313430903.PubMedCrossRefGoogle Scholar
  16. 16.
    Nassimiha D, Aronow WS, Ahn C, Goldman ME. Association of coronary risk factors with progression of valvular aortic stenosis in older persons. Am J Cardiol. 2001;87(11):1313–4.PubMedCrossRefGoogle Scholar
  17. 17.
    Yamamoto K, Yamamoto H, Yoshida K, et al. Prognostic factors for progression of early- and late-stage calcific aortic valve disease in Japanese: the Japanese Aortic Stenosis Study (JASS) Retrospective Analysis. Hypertens Res. 2010;33(3):269–74. doi: 10.1038/hr.2009.225.PubMedCrossRefGoogle Scholar
  18. 18.
    Rossebo AB, Pedersen TR, Boman K, et al. Intensive lipid lowering with simvastatin and ezetimibe in aortic stenosis. N Engl J Med. 2008;359(13):1343–56.PubMedCrossRefGoogle Scholar
  19. 19.
    Cowell SJ, Newby DE, Prescott RJ, et al. A randomized trial of intensive lipid-lowering therapy in calcific aortic stenosis. N Engl J Med. 2005;352(23):2389–97. doi: 10.1056/NEJMoa043876.PubMedCrossRefGoogle Scholar
  20. 20.
    Rosenhek R, Rader F, Loho N, et al. Statins but not angiotensin-converting enzyme inhibitors delay progression of aortic stenosis. Circulation. 2004;110(10):1291–5. doi: 10.1161/01.CIR.0000140723.15274.53.PubMedCrossRefGoogle Scholar
  21. 21.
    Antonini-Canterin F, Hirsu M, Popescu BA, et al. Stage-related effect of statin treatment on the progression of aortic valve sclerosis and stenosis. Am J Cardiol. 2008;102(6):738–42. doi: 10.1016/j.amjcard.2008.04.056.PubMedCrossRefGoogle Scholar
  22. 22.
    Kamstrup PR, Tybjaerg-Hansen A, Nordestgaard BG. Elevated lipoprotein(a) and risk of aortic valve stenosis in the general population. J Am Coll Cardiol. 2014;63(5):470–7. doi: 10.1016/j.jacc.2013.09.038.PubMedCrossRefGoogle Scholar
  23. 23.
    Thanassoulis G, Campbell CY, Owens DS, et al. Genetic associations with valvular calcification and aortic stenosis. N Engl J Med. 2013;368(6):503–12. doi: 10.1056/NEJMoa1109034.PubMedCentralPubMedCrossRefGoogle Scholar
  24. 24.
    Otto CM, Kuusisto J, Reichenbach DD, Gown AM, O’Brien KD. Characterization of the early lesion of ‘degenerative’ valvular aortic stenosis. Histological and immunohistochemical studies. Circulation. 1994;90(2):844–53.PubMedCrossRefGoogle Scholar
  25. 25.
    Hermans H, Herijgers P, Holvoet P, et al. Statins for calcific aortic valve stenosis: into oblivion after SALTIRE and SEAS? An extensive review from bench to bedside. Curre Probl Cardiol. 2010;35(6):284–306. doi: 10.1016/j.cpcardiol.2010.02.002.CrossRefGoogle Scholar
  26. 26.
    Otto CM, Burwash IG, Legget ME, et al. Prospective study of asymptomatic valvular aortic stenosis. clinical, echocardiographic, and exercise predictors of outcome. Circulation. 1997;95(9):2262–70.PubMedCrossRefGoogle Scholar
  27. 27.
    Yetkin E, Waltenberger J. Molecular and cellular mechanisms of aortic stenosis. Int J Cardiol. 2009;135(1):4–13. doi: 10.1016/j.ijcard.2009.03.108.PubMedCrossRefGoogle Scholar
  28. 28.
    Ortlepp JR, Hoffmann R, Ohme F, Lauscher J, Bleckmann F, Hanrath P. The vitamin D receptor genotype predisposes to the development of calcific aortic valve stenosis. Heart. 2001;85(6):635–8.PubMedCentralPubMedCrossRefGoogle Scholar
  29. 29.
    Dweck MR, Khaw HJ, Sng GK, et al. Aortic stenosis, atherosclerosis, and skeletal bone: is there a common link with calcification and inflammation? Eur Heart J. 2013;34(21):1567–74. doi: 10.1093/eurheartj/eht034.PubMedCrossRefGoogle Scholar
  30. 30.
    Roberts WC, Ko JM. Frequency by decades of unicuspid, bicuspid, and tricuspid aortic valves in adults having isolated aortic valve replacement for aortic stenosis, with or without associated aortic regurgitation. Circulation. 2005;111(7):920–5. doi: 10.1161/01.cir.0000155623.48408.c5.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2014

Authors and Affiliations

  • Gry Wisthus Eveborn
    • 1
    Email author
  • Henrik Schirmer
    • 1
    • 2
  • Per Lunde
    • 1
  • Geir Heggelund
    • 1
  • John-Bjarne Hansen
    • 3
  • Knut Rasmussen
    • 2
  1. 1.Division of Cardiothoracic and Respiratory Medicine, Department of Heart DiseaseUniversity Hospital of Northern NorwayTromsöNorway
  2. 2.Department of Clinical Medicine, Faculty of Health SciencesUniversity of TromsøTromsöNorway
  3. 3.Department of Medicine, Center for Atherothrombotic Research in Tromsø (CART), Institute of Clinical MedicineUniversity of TromsøTromsöNorway

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