Asthma, asthma control and risk of acute myocardial infarction: HUNT study

  • Aivaras CepelisEmail author
  • Ben M. Brumpton
  • Lars E. Laugsand
  • Håvard Dalen
  • Arnulf Langhammer
  • Imre Janszky
  • Linn B. Strand


Asthma, a chronic inflammatory airway disease, shares several common pathophysiological mechanisms with acute myocardial infarction (AMI). Our aim was to assess the prospective associations between asthma, levels of asthma control and risk of AMI. We followed 57,104 adults without previous history of AMI at baseline from Nord-Trøndelag health study (HUNT) in Norway. Self-reported asthma was categorised as active asthma (i.e., using asthma medication) and non-active asthma (i.e., not using asthma medication). Levels of asthma control were defined as controlled, partly controlled, and uncontrolled based on the Global Initiative for Asthma guidelines. AMI was ascertained by linking HUNT data with hospital records. A total of 2868 AMI events (5.0%) occurred during a mean (SD) follow-up of 17.2 (5.4) years. Adults with active asthma had an estimated 29% higher risk of developing AMI [adjusted hazard ratio (HR) 1.29, 95% CI 1.08–1.54] compared with adults without asthma. There was a significant dose–response association between asthma control and AMI risk, with highest risk in adults with uncontrolled asthma (adjusted HR 1.73, 95% CI 1.13–2.66) compared to adults with controlled asthma (p for trend < 0.05). The associations were not explained by smoking status, physical activity and C-reactive protein levels. Our study suggests that active asthma and poor asthma control are associated with moderately increased risk of AMI. Further studies are needed to evaluate causal relationship and the underlying mechanisms and to clarify the role of asthma medications in the risk of AMI.


Myocardial infarction Heart attack Cardiovascular disease Asthma Asthma control 



The Nord-Trøndelag Health Study is a collaboration between HUNT Research Centre, Faculty of Medicine and Health Science, Norwegian University of Science and Technology (NTNU), Nord-Trøndelag County Council, Central Norway Health Authority and the Norwegian Institute of Public Health.


This work was supported by Nasjonalforeningen for folkehelsen (Norway National Association for Public Health) [Grant No. 10705]. BMB works in a research unit funded by Stiftelsen Kristian Gerhard Jebsen; Faculty of Medicine and Health Sciences, NTNU; The Liaison Committee for education, research and innovation in Central Norway; the Joint Research Committee between St. Olavs Hospital and the Faculty of Medicine and Health Sciences, NTNU; and the Medical Research Council Integrative Epidemiology Unit at the University of Bristol which is supported by the Medical Research Council and the University of Bristol [MC_UU_12013/1].

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

10654_2019_562_MOESM1_ESM.docx (200 kb)
Supplementary material 1 (DOCX 201 kb)


  1. 1.
    Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, et al. Heart disease and stroke statistics—2015 update: a report from the American Heart Association. Circulation. 2015;131(4):e29–322.Google Scholar
  2. 2.
    Canto JG, Kiefe CI, Rogers WJ, Peterson ED, Frederick PD, French WJ, et al. Number of coronary heart disease risk factors and mortality in patients with first myocardial infarction. JAMA. 2011;306(19):2120–7.CrossRefGoogle Scholar
  3. 3.
    Hing E, Rui P, Palso K (2013) National ambulatory medical care survey: 2013 state and national summary tables. Center for Disease Control and Prevention. Available from:
  4. 4.
    Naik SP, AM P, SJ B, Madhunapantula SV, Jahromi SR, Yadav MK. Evaluation of inflammatory markers interleukin-6 (IL-6) and matrix metalloproteinase-9 (MMP-9) in asthma. J Asthma: Off J Assoc Care Asthma. 2017;54(6):584–93.CrossRefGoogle Scholar
  5. 5.
    Macedo P, Hew M, Torrego A, Jouneau S, Oates T, Durham A, et al. Inflammatory biomarkers in airways of patients with severe asthma compared with non-severe asthma. Clin Exp Allergy. 2009;39(11):1668–76.CrossRefGoogle Scholar
  6. 6.
    Ruparelia N, Chai JT, Fisher EA, Choudhury RP. Inflammatory processes in cardiovascular disease: a route to targeted therapies. Nat Rev Cardiol. 2017;14(3):133–44.CrossRefGoogle Scholar
  7. 7.
    Salpeter SR, Ormiston TM, Salpeter EE. Cardiovascular effects of beta-agonists in patients with asthma and COPD: a meta-analysis. Chest. 2004;125(6):2309–21.CrossRefGoogle Scholar
  8. 8.
    de Miguel Díez J, Chancafe Morgan J, Jiménez García R. The association between COPD and heart failure risk: a review. Int J Chronic Obstr Pulm Dis. 2013;8:305–12.Google Scholar
  9. 9.
    Robinette CD, Fraumeni JF Jr. Asthma and subsequent mortality in world war II veterans. J Chronic Dis. 1978;31(9):619–24.CrossRefGoogle Scholar
  10. 10.
    Iribarren C, Tolstykh IV, Miller MK, Sobel E, Eisner MD. Adult asthma and risk of coronary heart disease, cerebrovascular disease, and heart failure: a prospective study of 2 matched cohorts. Am J Epidemiol. 2012;176(11):1014–24.CrossRefGoogle Scholar
  11. 11.
    Iribarren C, Tolstykh IV, Eisner MD. Are patients with asthma at increased risk of coronary heart disease? Int J Epidemiol. 2004;33(4):743–8.CrossRefGoogle Scholar
  12. 12.
    Schanen JG, Iribarren C, Shahar E, Punjabi NM, Rich SS, Sorlie PD, et al. Asthma and incident cardiovascular disease: the atherosclerosis risk in communities study. Thorax. 2005;60(8):633.CrossRefGoogle Scholar
  13. 13.
    Tattersall MC, Guo M, Korcarz CE, Gepner AD, Kaufman JD, Liu KJ, et al. Asthma predicts cardiovascular disease events: the multi-ethnic study of atherosclerosis. Arterioscler Thromb Vasc Biol. 2015;35(6):1520–5.CrossRefGoogle Scholar
  14. 14.
    Bang DW, Wi CI, Kim EN, Hagan J, Roger V, Manemann S, et al. Asthma status and risk of incident myocardial infarction: a population-based case-control study. J Allergy Clin Immunol Pract. 2016;4(5):917–23.CrossRefGoogle Scholar
  15. 15.
    Strand LB, Tsai MK, Wen CP, Chang S-S, Brumpton BM. Is having asthma associated with an increased risk of dying from cardiovascular disease? A prospective cohort study of 446 346 Taiwanese adults. BMJ Open. 2018;8(5):e019992.CrossRefGoogle Scholar
  16. 16.
    Krokstad S, Langhammer A, Hveem K, Holmen TL, Midthjell K, Stene TR, et al. Cohort profile: the HUNT study, Norway. Int J Epidemiol. 2013;42(4):968–77.CrossRefGoogle Scholar
  17. 17.
    Global Initiative for Asthma. Global strategy for asthma management and prevention. 2016. Available from:
  18. 18.
    Alpert JS, Thygesen K, Antman E, Bassand JP. Myocardial infarction redefined—a consensus document of The Joint European Society of Cardiology/American College of Cardiology Committee for the redefinition of myocardial infarction. J Am Coll Cardiol. 2000;36(3):959–69.CrossRefGoogle Scholar
  19. 19.
    Olson KA, Beatty AL, Heidecker B, Regan MC, Brody EN, Foreman T, et al. Association of growth differentiation factor 11/8, putative anti-ageing factor, with cardiovascular outcomes and overall mortality in humans: analysis of the Heart and Soul and HUNT3 cohorts. Eur Heart J. 2015;36(48):3426–34.CrossRefGoogle Scholar
  20. 20.
    Cepelis A, Brumpton BM, Malmo V, et al. Associations of asthma and asthma control with atrial fibrillation risk: results from the Nord-Trøndelag health study (hunt). JAMA Cardiol. 2018;3(8):721–8.CrossRefGoogle Scholar
  21. 21.
    Quanjer PH, Stanojevic S, Cole TJ, Baur X, Hall GL, Culver BH, et al. Multi-ethnic reference values for spirometry for the 3–95 year age range: the global lung function 2012 equations: Report of the Global Lung Function Initiative (GLI), ERS Task Force to establish improved lung function reference values. Eur Respir J. 2012;40(6):1324–43.CrossRefGoogle Scholar
  22. 22.
    Wolbers M, Koller MT, Stel VS, Schaer B, Jager KJ, Leffondre K, et al. Competing risks analyses: objectives and approaches. Eur Heart J. 2014;35(42):2936–41.CrossRefGoogle Scholar
  23. 23.
    O’brien R. A caution regarding rules of thumb for variance inflation factors. Qual Quant: Int J Methodol. 2007;41(5):673–90.CrossRefGoogle Scholar
  24. 24.
    Fujita M, Ueki S, Ito W, Chiba T, Takeda M, Saito N, et al. C-reactive protein levels in the serum of asthmatic patients. Ann Allergy Asthma Immunol: Off Publ Am Coll Allergy Asthma Immunol. 2007;99(1):48–53.CrossRefGoogle Scholar
  25. 25.
    Azur MJ, Stuart EA, Frangakis C, Leaf PJ. Multiple imputation by chained equations: what is it and how does it work? Int J Methods Psychiatr Res. 2011;20(1):40–9.CrossRefGoogle Scholar
  26. 26.
    Braido F, Brusselle G, Guastalla D, Ingrassia E, Nicolini G, Price D, et al. Determinants and impact of suboptimal asthma control in Europe: the international cross-sectional and longitudinal assessment on asthma control (liaison) study. Respir Res. 2016;17(1):51.CrossRefGoogle Scholar
  27. 27.
    Colak Y, Afzal S, Nordestgaard BG, Lange P. Characteristics and prognosis of never-smokers and smokers with asthma in the copenhagen general population study. A prospective cohort study. Am J Respir Crit Care Med. 2015;192(2):172–81.CrossRefGoogle Scholar
  28. 28.
    Global Initiative for Asthma (GINA) (2019) Global strategy for asthma management and prevention. Available from:
  29. 29.
    Macie C, Wooldrage K, Manfreda J, Anthonisen N. Cardiovascular morbidity and the use of inhaled bronchodilators. Int J Chronic Obstr Pulm Dis. 2008;3(1):163–9.Google Scholar
  30. 30.
    Suissa S, Assimes T, Brassard P, Ernst P. Inhaled corticosteroid use in asthma and the prevention of myocardial infarction. Am J Med. 2003;115(5):377–81.CrossRefGoogle Scholar
  31. 31.
    Engelkes M, Janssens HM, de Jongste JC, Sturkenboom MCJM, Verhamme KMC. Medication adherence and the risk of severe asthma exacerbations: a systematic review. Eur Respir J. 2015;45(2):396–407.CrossRefGoogle Scholar
  32. 32.
    Murdoch JR, Lloyd CM. Chronic inflammation and asthma. Mutat Res. 2010;690(1–2):24–39.CrossRefGoogle Scholar
  33. 33.
    Zimmerman GA, McIntyre TM, Prescott SM, Stafforini DM. The platelet-activating factor signaling system and its regulators in syndromes of inflammation and thrombosis. Crit Care Med. 2002;30(5 Suppl):S294–301.CrossRefGoogle Scholar
  34. 34.
    Held C, White HD, Stewart RAH, Budaj A, Cannon CP, Hochman JS, et al. Inflammatory biomarkers interleukin-6 and c-reactive protein and outcomes in stable coronary heart disease: experiences from the STABILITY (stabilization of atherosclerotic plaque by initiation of darapladib therapy) trial. J Am Heart Assoc. 2017;6(10):e005077.CrossRefGoogle Scholar
  35. 35.
    Ingelsson E, Yin L, Back M. Nationwide cohort study of the leukotriene receptor antagonist montelukast and incident or recurrent cardiovascular disease. J Allergy Clin Immunol. 2012;129(3):702–7.CrossRefGoogle Scholar
  36. 36.
    Henriksen AH, Langhammer A, Steinshamn S, Mai X-M, Brumpton BM. The prevalence and symptom profile of asthma–COPD overlap: the HUNT study. COPD: J Chronic Obstr Pulm Dis. 2018;15(1):27–35.CrossRefGoogle Scholar
  37. 37.
    Toren K, Brisman J, Jarvholm B. Asthma and asthma-like symptoms in adults assessed by questionnaires. A literature review. Chest. 1993;104(2):600–8.CrossRefGoogle Scholar
  38. 38.
    de Marco R, Cerveri I, Bugiani M, Ferrari M, Verlato G. An undetected burden of asthma in Italy: the relationship between clinical and epidemiological diagnosis of asthma. Eur Respir J. 1998;11(3):599–605.Google Scholar
  39. 39.
    To T, Stanojevic S, Moores G, Gershon AS, Bateman ED, Cruz AA, et al. Global asthma prevalence in adults: findings from the cross-sectional world health survey. BMC Public Health. 2012;12(1):204.CrossRefGoogle Scholar
  40. 40.
    Langhammer A, Krokstad S, Romundstad P, Heggland J, Holmen J. The HUNT study: participation is associated with survival and depends on socioeconomic status, diseases and symptoms. BMC Med Res Methodol. 2012;12:143.CrossRefGoogle Scholar
  41. 41.
    Rothman KJ, Greenland S, Lash TL. Modern epidemiology. 3rd ed. Philadelphia: Wolters Kluwer Health; 2008.Google Scholar
  42. 42.
    Hansen TE, Evjenth B, Holt J. Increasing prevalence of asthma, allergic rhinoconjunctivitis and eczema among schoolchildren: three surveys during the period 1985–2008. Acta Paediatr. 2013;102(1):47–52.CrossRefGoogle Scholar

Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  1. 1.Department of Public Health and Nursing, Faculty of Medicine and Health ScienceNTNU, Norwegian University of Science and TechnologyTrondheimNorway
  2. 2.Department of Thoracic and Occupational MedicineSt. Olavs Hospital, Trondheim University HospitalTrondheimNorway
  3. 3.K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and NursingNTNU, Norwegian University of Science and TechnologyTrondheimNorway
  4. 4.MRC Integrative Epidemiology Unit, School of Social and Community MedicineUniversity of BristolBristolUK
  5. 5.Department of Emergency MedicineSt. Olavs HospitalTrondheimNorway
  6. 6.Department of MedicineLevanger Hospital, Nord-Trøndelag Hospital TrustLevangerNorway
  7. 7.Department of Circulation and Medical ImagingNTNU, Norwegian University of Science and TechnologyTrondheimNorway
  8. 8.Cardiac ClinicSt. Olavs Hospital, Trondheim University HospitalTrondheimNorway
  9. 9.Department of Neurology, Medical SchoolUniversity of PécsPecsHungary

Personalised recommendations