The association of atopy with incidence of ischemic heart disease, stroke, and diabetes

Abstract

Allergy is a systemic inflammatory disease that could theoretically affect the risk of cardiovascular disease (CVD) and diabetes through inflammatory pathways or mast cell-induced coronary spasm. Whether allergy is associated with an increased risk of CVD and diabetes is largely unknown. We investigated the association between atopy as assessed by IgE sensitization, a well-accepted biomarker of allergy, and incidence of ischemic heart disease, stroke, and diabetes in five Danish population-based cohorts. A total of 14,849 participants were included in the study. Atopy was defined as serum-specific IgE positivity to inhalant allergens. The Danish National Diabetes Register enabled identification of incident diabetes. Likewise, the Danish Registry of Causes of Death and the Danish National Patient Register provided information on fatal and non-fatal ischemic heart disease and stroke. Data were analyzed by Cox regression analyses with age as underlying time axis and adjusted for study cohort, gender, education, body mass index, alcohol intake, smoking habits, physical activity during leisure time, serum lipids, and blood pressure. The prevalence of atopy was 26.9 % (n = 3,994). There were 1,170, 817, and 1,063 incident cases of ischemic heart disease, stroke, and diabetes, respectively (median follow-up 11.2 years). The hazard ratios, HRs (95 % confidence intervals, CIs) for atopics versus non-atopics: for ischemic heart disease (HR 1.00, 95 % CI 0.86, 1.16), stroke (HR 1.18, 95 % CI 0.99, 1.41), and diabetes (HR 1.06, 95 % CI 0.91, 1.23). Our results did not support the hypothesis that atopy is associated with higher risk of ischemic heart disease, stroke, or diabetes. However, a small-moderately increased risk cannot be excluded from our data.

This is a preview of subscription content, log in to check access.

Fig. 1
Fig. 2
Fig. 3

References

  1. 1.

    S.G. Johansson, T. Bieber, R. Dahl, P.S. Friedmann, B.Q. Lanier et al., Revised nomenclature for allergy for global use: report of the Nomenclature Review Committee of the World Allergy Organization, October 2003. J. Allergy Clin. Immunol. 113, 832–836 (2004)

    Article  CAS  PubMed  Google Scholar 

  2. 2.

    A. Linneberg, Are we getting enough allergens? Int. Arch. Allergy Immunol. 147, 93–100 (2008)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  3. 3.

    R.R. Packard, A.H. Lichtman, P. Libby, Innate and adaptive immunity in atherosclerosis. Semin. Immunopathol. 31, 5–22 (2009)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  4. 4.

    B. Ozben, O. Erdogan, The role of inflammation and allergy in acute coronary syndromes. Inflamm. Allergy Drug Targets 7, 136–144 (2008)

    Article  CAS  PubMed  Google Scholar 

  5. 5.

    J. Liu, A. Divoux, J. Sun, J. Zhang, K. Clement et al., Genetic deficiency and pharmacological stabilization of mast cells reduce diet-induced obesity and diabetes in mice. Nat. Med. 15, 940–945 (2009)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  6. 6.

    T.C. Theoharides, D. Kalogeromitros, The critical role of mast cells in allergy and inflammation. Ann. NY Acad. Sci. 1088, 78–99 (2006)

    Article  CAS  PubMed  Google Scholar 

  7. 7.

    M.H. Criqui, E.R. Lee, R.N. Hamburger, M.R. Klauber, S.S. Coughlin, IgE and cardiovascular disease. Results from a population-based study. Am. J. Med. 82, 964–968 (1987)

    Article  CAS  PubMed  Google Scholar 

  8. 8.

    J.J. Hospers, B. Rijcken, J.P. Schouten, D.S. Postma, S.T. Weiss, Eosinophilia and positive skin tests predict cardiovascular mortality in a general population sample followed for 30 years. Am. J. Epidemiol. 150, 482–491 (1999)

    Article  CAS  PubMed  Google Scholar 

  9. 9.

    R. Jaramillo, R.D. Cohn, P.W. Crockett, K.M. Gowdy, D.C. Zeldin et al., Relation between objective measures of atopy and myocardial infarction in the United States. J. Allergy Clin. Immunol. 131, 405–411 (2013)

    Article  PubMed Central  PubMed  Google Scholar 

  10. 10.

    R.D. Langer, M.H. Criqui, H.S. Feigelson, T.J. McCann, R.N. Hamburger, IgE predicts future nonfatal myocardial infarction in men. J. Clin. Epidemiol. 49, 203–209 (1996)

    Article  CAS  PubMed  Google Scholar 

  11. 11.

    Z. Wang, H. Zhang, X.H. Shen, K.L. Jin, G.F. Ye et al., Immunoglobulin E and mast cell proteases are potential risk factors of human pre-diabetes and diabetes mellitus. PLoS One 6, e28962 (2011)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  12. 12.

    Z. Wang, H. Zhang, X.H. Shen, K.L. Jin, G.F. Ye et al., Immunoglobulin E and mast cell proteases are potential risk factors of impaired fasting glucose and impaired glucose tolerance in humans. Ann. Med. 45, 220–229 (2013)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  13. 13.

    L.L. Husemoen, M. Fenger, N. Friedrich, J.S. Tolstrup, F.S. Beenfeldt et al., The association of ADH and ALDH gene variants with alcohol drinking habits and cardiovascular disease risk factors. Alcohol. Clin. Exp. Res. 32, 1984–1991 (2008)

    CAS  PubMed  Google Scholar 

  14. 14.

    M. Osler, A. Linneberg, C. Glumer, T. Jorgensen, The cohorts at the Research Centre for Prevention and Health, formerly ‘The Glostrup Population Studies’. Int. J. Epidemiol. 40, 602–610 (2011)

    Article  PubMed  Google Scholar 

  15. 15.

    T. Drivsholm, L.F. Eplov, M. Davidsen, T. Jorgensen, H. Ibsen et al., Representativeness in population-based studies: a detailed description of non-response in a Danish cohort study. Scand. J. Public Health 34, 623–631 (2006)

    Article  PubMed  Google Scholar 

  16. 16.

    N.D. Berg, L.L. Husemoen, B.H. Thuesen, L.G. Hersoug, J. Elberling et al., Interaction between filaggrin null mutations and tobacco smoking in relation to asthma. J. Allergy Clin. Immunol. 129, 374–380 (2012)

    Article  CAS  PubMed  Google Scholar 

  17. 17.

    T. Jorgensen, K. Borch-Johnsen, T.F. Thomsen, H. Ibsen, C. Glumer et al., A randomized non-pharmacological intervention study for prevention of ischaemic heart disease: baseline results Inter99. Eur. J. Cardiovasc. Prev. Rehabil. 10, 377–386 (2003)

    Article  PubMed  Google Scholar 

  18. 18.

    B.H. Thuesen, L.L. Husemoen, L. Ovesen, T. Jorgensen, M. Fenger et al., Atopy, asthma, and lung function in relation to folate and vitamin B(12) in adults. Allergy 65, 1446–1454 (2010)

    Article  CAS  PubMed  Google Scholar 

  19. 19.

    A.B. Petersen, P. Gudmann, P. Milvang-Gronager, R. Morkeberg, S. Bogestrand et al., Performance evaluation of a specific IgE assay developed for the ADVIA centaur immunoassay system. Clin. Biochem. 37, 882–892 (2004)

    Article  CAS  PubMed  Google Scholar 

  20. 20.

    A. Linneberg, N. Friedrich, L.L. Husemoen, B. Thuesen, A. Gonzalez-Quintela et al., Incidence and remission of specific IgE aeroallergen sensitization from age of 40 to 60 years, and association with alcohol consumption. Int. Arch. Allergy Immunol. 151, 142–148 (2010)

    Article  CAS  PubMed  Google Scholar 

  21. 21.

    T.F. Andersen, M. Madsen, J. Jorgensen, L. Mellemkjoer, J.H. Olsen, The Danish National Hospital Register. A valuable source of data for modern health sciences. Dan. Med. Bull. 46, 263–268 (1999)

    CAS  PubMed  Google Scholar 

  22. 22.

    K. Juel, K. Helweg-Larsen, The Danish registers of causes of death. Dan. Med. Bull. 46, 354–357 (1999)

    CAS  PubMed  Google Scholar 

  23. 23.

    B. Carstensen, J.K. Kristensen, P. Ottosen, K. Borch-Johnsen, The Danish National Diabetes Register: trends in incidence, prevalence and mortality. Diabetologia 51, 2187–2196 (2008)

    Article  CAS  PubMed  Google Scholar 

  24. 24.

    A. Linneberg, N.H. Nielsen, F. Madsen, L. Frolund, A. Dirksen et al., Smoking and the development of allergic sensitization to aeroallergens in adults: a prospective population-based study. The Copenhagen Allergy Study. Allergy 56, 328–332 (2001)

    Article  CAS  PubMed  Google Scholar 

  25. 25.

    A. Linneberg, J. Petersen, N.H. Nielsen, F. Madsen, L. Frolund et al., The relationship of alcohol consumption to total immunoglobulin E and the development of immunoglobulin E sensitization: the Copenhagen Allergy Study. Clin. Exp. Allergy 33, 192–198 (2003)

    Article  CAS  PubMed  Google Scholar 

  26. 26.

    M. Knoflach, S. Kiechl, A. Mayr, J. Willeit, W. Poewe et al., Allergic rhinitis, asthma, and atherosclerosis in the Bruneck and ARMY studies. Arch. Intern. Med. 165, 2521–2526 (2005)

    Article  PubMed  Google Scholar 

  27. 27.

    H.R. Rodewald, T.B. Feyerabend, Widespread immunological functions of mast cells: fact or fiction? Immunity 37, 13–24 (2012)

    Article  CAS  PubMed  Google Scholar 

  28. 28.

    R. Ginsburg, M.R. Bristow, N. Kantrowitz, D.S. Baim, D.C. Harrison, Histamine provocation of clinical coronary artery spasm: implications concerning pathogenesis of variant angina pectoris. Am. Heart J. 102, 819–822 (1981)

    Article  CAS  PubMed  Google Scholar 

  29. 29.

    E.N. Deliargyris, B. Upadhya, D.C. Sane, G.J. Dehmer, J. Pye et al., Mast cell tryptase: a new biomarker in patients with stable coronary artery disease. Atherosclerosis 178, 381–386 (2005)

    Article  CAS  PubMed  Google Scholar 

  30. 30.

    A. Gonzalez-Quintela, L. Vizcaino, F. Gude, J. Rey, L. Meijide et al., Factors influencing serum total tryptase concentrations in a general adult population. Clin. Chem. Lab. Med. 48, 701–706 (2010)

    CAS  PubMed  Google Scholar 

  31. 31.

    M. Nastalek, A. Wojas-Pelc, A. Undas, Plasma fibrin clot properties in atopic dermatitis: links between thrombosis and atopy. J. Thromb. Thrombolysis 30, 121–126 (2010)

    Article  CAS  PubMed  Google Scholar 

  32. 32.

    A. Szczeklik, Atopy and sudden cardiac death. Lancet 355, 2254 (2000)

    Article  CAS  PubMed  Google Scholar 

  33. 33.

    A.B. Petersen, P. Gudmann, P. Milvang-Gronager, R. Morkeberg, S. Bogestrand et al., Performance evaluation of a specific IgE assay developed for the ADVIA centaur immunoassay system. Clin. Biochem. 37, 882–892 (2004)

    Article  CAS  PubMed  Google Scholar 

  34. 34.

    A. Linneberg, L.L. Husemoen, N.H. Nielsen, F. Madsen, L. Frolund et al., Screening for allergic respiratory disease in the general population with the ADVIA Centaur Allergy Screen Assay. Allergy 61, 344–348 (2006)

    Article  CAS  PubMed  Google Scholar 

  35. 35.

    A. Linneberg, M. Gislum, N. Johansen, L.L. Husemoen, T. Jorgensen, Temporal trends of aeroallergen sensitization over twenty-five years. Clin. Exp. Allergy 37, 1137–1142 (2007)

    Article  CAS  PubMed  Google Scholar 

Download references

Conflict of interest

The authors have no conflicts of interest.

Author information

Affiliations

Authors

Corresponding author

Correspondence to Tea Skaaby.

Electronic supplementary material

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Skaaby, T., Husemoen, L.L.N., Thuesen, B.H. et al. The association of atopy with incidence of ischemic heart disease, stroke, and diabetes. Endocrine 48, 541–550 (2015). https://doi.org/10.1007/s12020-014-0321-z

Download citation

Keywords

  • Atopy
  • Allergy
  • Diabetes
  • Stroke
  • Ischemic heart disease
  • Cardiovascular disease