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Relation between objective measures of atopy and myocardial infarction in the United States

Published:August 27, 2012DOI:https://doi.org/10.1016/j.jaci.2012.06.033

      Background

      Although rodent studies indicate that atherosclerosis is a TH1-mediated disease and that atopic TH2 immunity is atheroprotective, findings in humans are conflicting. Total IgE (tIgE) is associated with atherosclerotic disease but has limited specificity for atopy.

      Objective

      Our aim was to determine the relation between atopy, as indicated by a broad panel of serum allergen-specific IgE (sIgE), and past myocardial infarction (MI) in a sample representative of the US population.

      Methods

      Data were analyzed from 4002 participants aged ≥20 years from the 2005-2006 National Health and Nutrition Examination Survey.

      Results

      Subjects reporting a history of MI had lower summed sIgE (5.51 vs 7.71 kU/L; P < .001) and were less likely to have ≥1 positive sIgE test (29.9% vs 44.6%; P = .02) or current hay fever (3.3% vs 7.6%; P = .002). After adjustment for age, sex, race/ethnicity, diabetes mellitus, hypertension, family history of MI, smoking, total/high-density lipoprotein cholesterol, body mass index, and C-reactive protein, the odds ratio (OR) for MI was 0.91 (95% CI, 0.85-0.97) per positive sIgE; 0.70 (95% CI, 0.57-0.85) per 2-fold increase in sum[sIgE]; and 0.82 (95% CI, 0.69-0.98) per 10% increase in the ratio of sum[sIgE] to tIgE. Analysis with 7 data-driven, prespecified allergen clusters found that house dust mite is the only allergen cluster for which sIgE is associated with reduced odds for MI (fully adjusted OR, 0.36; 95% CI, 0.20-0.64).

      Conclusion

      Serum sIgE is inversely related to MI in the US population in a manner independent of multiple coronary risk factors.

      Key words

      Abbreviations used:

      ASCVD (Atherosclerotic cardiovascular disease), BMI (Body mass index), CRP (C-reactive protein), HDM (House dust mite), MI (Myocardial infarction), NHANES (National Health and Nutrition Examination Survey), OR (Odds ratio), sIgE (Allergen-specific IgE), tIgE (Total IgE), TC (Total cholesterol)
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      References

        • Hansson G.K.
        • Hermansson A.
        The immune system in atherosclerosis.
        Nat Immunol. 2011; 12: 204-212
        • Binder C.J.
        • Hartvigsen K.
        • Chang M.K.
        • Miller M.
        • Broide D.
        • Palinski W.
        • et al.
        IL-5 links adaptive and natural immunity specific for epitopes of oxidized LDL and protects from atherosclerosis.
        J Clin Invest. 2004; 114: 427-437
        • Schulte S.
        • Sukhova G.K.
        • Libby P.
        Genetically programmed biases in Th1 and Th2 immune responses modulate atherogenesis.
        Am J Pathol. 2008; 172: 1500-1508
        • Huber S.A.
        • Sakkinen P.
        • David C.
        • Newell M.K.
        • Tracy R.P.
        T helper-cell phenotype regulates atherosclerosis in mice under conditions of mild hypercholesterolemia.
        Circulation. 2001; 103: 2610-2616
        • Fredrikson G.N.
        • Andersson L.
        • Soderberg I.
        • Dimayuga P.
        • Chyu K.Y.
        • Shah P.K.
        • et al.
        Atheroprotective immunization with MDA-modified apo B-100 peptide sequences is associated with activation of Th2 specific antibody expression.
        Autoimmunity. 2005; 38: 171-179
        • Khallou-Laschet J.
        • Tupin E.
        • Caligiuri G.
        • Poirier B.
        • Thieblemont N.
        • Gaston A.T.
        • et al.
        Atheroprotective effect of adjuvants in apolipoprotein E knockout mice.
        Atherosclerosis. 2006; 184: 330-341
        • Laurat E.
        • Poirier B.
        • Tupin E.
        • Caligiuri G.
        • Hansson G.K.
        • Bariety J.
        • et al.
        In vivo downregulation of T helper cell 1 immune responses reduces atherogenesis in apolipoprotein E-knockout mice.
        Circulation. 2001; 104: 197-202
        • Miller A.M.
        • Xu D.
        • Asquith D.L.
        • Denby L.
        • Li Y.
        • Sattar N.
        • et al.
        IL-33 reduces the development of atherosclerosis.
        J Exp Med. 2008; 205: 339-346
        • Benagiano M.
        • Azzurri A.
        • Ciervo A.
        • Amedei A.
        • Tamburini C.
        • Ferrari M.
        • et al.
        T helper type 1 lymphocytes drive inflammation in human atherosclerotic lesions.
        Proc Natl Acad Sci U S A. 2003; 100: 6658-6663
        • Methe H.
        • Brunner S.
        • Wiegand D.
        • Nabauer M.
        • Koglin J.
        • Edelman E.R.
        Enhanced T-helper-1 lymphocyte activation patterns in acute coronary syndromes.
        J Am Coll Cardiol. 2005; 45: 1939-1945
        • Criqui M.H.
        • Lee E.R.
        • Hamburger R.N.
        • Klauber M.R.
        • Coughlin S.S.
        IgE and cardiovascular disease. Results from a population-based study.
        Am J Med. 1987; 82: 964-968
        • Langer R.D.
        • Criqui M.H.
        • Feigelson H.S.
        • McCann T.J.
        • Hamburger R.N.
        IgE predicts future nonfatal myocardial infarction in men.
        J Clin Epidemiol. 1996; 49: 203-209
        • Sinkiewicz W.
        • Blazejewski J.
        • Bujak R.
        • Kubica J.
        • Dudziak J.
        Immunoglobulin E in patients with ischemic heart disease.
        Cardiol J. 2008; 15: 122-128
        • Korkmaz M.E.
        • Oto A.
        • Saraclar Y.
        • Oram E.
        • Oram A.
        • Ugurlu S.
        • et al.
        Levels of IgE in the serum of patients with coronary arterial disease.
        Int J Cardiol. 1991; 31: 199-204
        • Gergen P.J.
        • Arbes Jr., S.J.
        • Calatroni A.
        • Mitchell H.E.
        • Zeldin D.C.
        Total IgE levels and asthma prevalence in the US population: results from the National Health and Nutrition Examination Survey 2005-2006.
        J Allergy Clin Immunol. 2009; 124: 447-453
        • Jackola D.R.
        • Blumenthal M.N.
        • Rosenberg A.
        Evidence for two independent distributions of serum immunoglobulin E in atopic families: cognate and non-cognate IgE.
        Hum Immunol. 2004; 65: 20-30
        • Joseph M.
        • Capron A.
        • Ameisen J.C.
        • Capron M.
        • Vorng H.
        • Pancre V.
        • et al.
        The receptor for IgE on blood platelets.
        Eur J Immunol. 1986; 16: 306-312
        • Ishizaka T.
        • Ishizaka K.
        Activation of mast cells for mediator release through IgE receptors.
        Prog Allergy. 1984; 34: 188-235
        • Kim J.
        • Purushottam B.
        • Chae Y.K.
        • Chebrolu L.
        • Amanullah A.
        Relation between common allergic symptoms and coronary heart disease among NHANES III participants.
        Am J Cardiol. 2010; 106: 984-987
        • Knoflach M.
        • Kiechl S.
        • Mayr A.
        • Willeit J.
        • Poewe W.
        • Wick G.
        Allergic rhinitis, asthma, and atherosclerosis in the Bruneck and ARMY studies.
        Arch Intern Med. 2005; 165: 2521-2526
        • Kounis N.G.
        Kounis syndrome (allergic angina and allergic myocardial infarction): a natural paradigm?.
        Int J Cardiol. 2006; 110: 7-14
        • Salo P.M.
        • Calatroni A.
        • Gergen P.J.
        • Hoppin J.A.
        • Sever M.L.
        • Jaramillo R.
        • et al.
        Allergy-related outcomes in relation to serum IgE: results from the National Health and Nutrition Examination Survey 2005-2006.
        J Allergy Clin Immunol. 2011; 127 (1226-35.e7)
        • Calatroni A.
        • Arbes Jr., S.
        • Gergen P.J.
        • Mitchell H.E.
        • Zeldin D.C.
        Classification of 19 allergen-specific IgE antibodies tested in NHANES 2005-2006.
        J Allergy Clin Immunol. 2009; 123: S193
        • Honda A.
        • Ametani A.
        • Matsumoto T.
        • Kaminogawa S.
        Suppression of collagen-induced arthritis in DBA/1J mice by preimmunization with house dust mite extract.
        Biosci Biotechnol Biochem. 2001; 65: 1063-1070
        • Eckman J.A.
        • Sterba P.M.
        • Kelly D.
        • Alexander V.
        • Liu M.C.
        • Bochner B.S.
        • et al.
        Effects of omalizumab on basophil and mast cell responses using an intranasal cat allergen challenge.
        J Allergy Clin Immunol. 2010; 125 (889-95.e7)
        • Di Lorenzo G.
        • Mansueto P.
        • Pacor M.L.
        • Rizzo M.
        • Castello F.
        • Martinelli N.
        • et al.
        Evaluation of serum s-IgE/total IgE ratio in predicting clinical response to allergen-specific immunotherapy.
        J Allergy Clin Immunol. 2009; 123 (1110.e1-4): 1103-1110
        • Falcone M.
        • Bloom B.R.
        A T helper cell 2 (Th2) immune response against non-self antigens modifies the cytokine profile of autoimmune T cells and protects against experimental allergic encephalomyelitis.
        J Exp Med. 1997; 185: 901-907
        • Hartung A.D.
        • Bohnert A.
        • Hackstein H.
        • Ohly A.
        • Schmidt K.L.
        • Bein G.
        Th2-mediated atopic disease protection in Th1-mediated rheumatoid arthritis.
        Clin Exp Rheumatol. 2003; 21: 481-484
        • Oro A.S.
        • Guarino T.J.
        • Driver R.
        • Steinman L.
        • Umetsu D.T.
        Regulation of disease susceptibility: decreased prevalence of IgE-mediated allergic disease in patients with multiple sclerosis.
        J Allergy Clin Immunol. 1996; 97: 1402-1408
        • Verhoef C.M.
        • van Roon J.A.
        • Vianen M.E.
        • Bruijnzeel-Koomen C.A.
        • Lafeber F.P.
        • Bijlsma J.W.
        Mutual antagonism of rheumatoid arthritis and hay fever; a role for type 1/type 2 T cell balance.
        Ann Rheum Dis. 1998; 57: 275-280
        • McQueen M.J.
        • Hawken S.
        • Wang X.
        • Ounpuu S.
        • Sniderman A.
        • Probstfield J.
        • et al.
        Lipids, lipoproteins, and apolipoproteins as risk markers of myocardial infarction in 52 countries (the INTERHEART study): a case-control study.
        Lancet. 2008; 372: 224-233
        • Wambre E.
        • Bonvalet M.
        • Bodo V.B.
        • Maillere B.
        • Leclert G.
        • Moussu H.
        • et al.
        Distinct characteristics of seasonal (Bet v 1) vs. perennial (Der p 1/Der p 2) allergen-specific CD4(+) T cell responses.
        Clin Exp Allergy. 2011; 41: 192-203
        • Ciprandi G.
        • De Amici M.
        • Tosca M.A.
        • Negrini S.
        • Puppo F.
        • Marseglia G.L.
        Immunoglobulin production pattern is allergen-specific in polysensitized patients.
        Int J Immunopathol Pharmacol. 2009; 22: 809-817
        • Ichikawa S.
        • Takai T.
        • Inoue T.
        • Yuuki T.
        • Okumura Y.
        • Ogura K.
        • et al.
        NMR study on the major mite allergen Der f 2: its refined tertiary structure, epitopes for monoclonal antibodies and characteristics shared by ML protein group members.
        J Biochem. 2005; 137: 255-263
        • Mueller G.A.
        • Edwards L.L.
        • Aloor J.J.
        • Fessler M.B.
        • Glesner J.
        • Pomes A.
        • et al.
        The structure of the dust mite allergen Der p 7 reveals similarities to innate immune proteins.
        J Allergy Clin Immunol. 2010; 125 (909-17.e4)
        • Okuyama K.
        • Wada K.
        • Chihara J.
        • Takayanagi M.
        • Ohno I.
        Sex-related splenocyte function in a murine model of allergic asthma.
        Clin Exp Allergy. 2008; 38: 1212-1219
        • Giron-Gonzalez J.A.
        • Moral F.J.
        • Elvira J.
        • Garcia-Gil D.
        • Guerrero F.
        • Gavilan I.
        • et al.
        Consistent production of a higher TH1:TH2 cytokine ratio by stimulated T cells in men compared with women.
        Eur J Endocrinol. 2000; 143: 31-36
        • Loza M.J.
        • Foster S.
        • Bleecker E.R.
        • Peters S.P.
        • Penn R.B.
        Asthma and gender impact accumulation of T cell subtypes.
        Respir Res. 2010; 11: 103
        • Melgert B.N.
        • Postma D.S.
        • Kuipers I.
        • Geerlings M.
        • Luinge M.A.
        • van der Strate B.W.
        • et al.
        Female mice are more susceptible to the development of allergic airway inflammation than male mice.
        Clin Exp Allergy. 2005; 35: 1496-1503
        • Zenovich A.G.
        • Panoskaltsis-Mortari A.
        • Caron G.J.
        • Kolb A.G.
        • Fremming R.
        • Nelson W.D.
        • et al.
        Sex-based differences in vascular repair with bone marrow cell therapy: relevance of regulatory and Th2-type cytokines.
        Transplant Proc. 2008; 40: 641-643
        • Gloria-Bottini F.
        • Bottini N.
        • Renzetti G.
        • Bottini E.
        ACP1 and Th class of immunological disease: evidence of interaction with gender.
        Int Arch Allergy Immunol. 2007; 143: 170-176
        • Hunninghake G.M.
        • Lasky-Su J.
        • Soto-Quiros M.E.
        • Avila L.
        • Liang C.
        • Lake S.L.
        • et al.
        Sex-stratified linkage analysis identifies a female-specific locus for IgE to cockroach in Costa Ricans.
        Am J Respir Crit Care Med. 2008; 177: 830-836
        • Yang K.D.
        • Liu C.A.
        • Chang J.C.
        • Chuang H.
        • Ou C.Y.
        • Hsu T.Y.
        • et al.
        Polymorphism of the immune-braking gene CTLA-4 (+49) involved in gender discrepancy of serum total IgE levels and allergic diseases.
        Clin Exp Allergy. 2004; 34: 32-37
        • Hunninghake G.M.
        • Chu J.H.
        • Sharma S.S.
        • Cho M.H.
        • Himes B.E.
        • Rogers A.J.
        • et al.
        The CD4+ T-cell transcriptome and serum IgE in asthma: IL17RB and the role of sex.
        BMC Pulm Med. 2011; 11: 17
        • Barrenas F.
        • Andersson B.
        • Cardell L.O.
        • Langston M.
        • Mobini R.
        • Perkins A.
        • et al.
        Gender differences in inflammatory proteins and pathways in seasonal allergic rhinitis.
        Cytokine. 2008; 42: 325-329
        • Shaw L.J.
        • Bugiardini R.
        • Merz C.N.
        Women and ischemic heart disease: evolving knowledge.
        J Am Coll Cardiol. 2009; 54: 1561-1575
        • Schlendorf K.H.
        • Nasir K.
        • Blumenthal R.S.
        Limitations of the Framingham risk score are now much clearer.
        Prev Med. 2009; 48: 115-116
        • Bairey Merz C.N.
        • Shaw L.J.
        • Reis S.E.
        • Bittner V.
        • Kelsey S.F.
        • Olson M.
        • et al.
        Insights from the NHLBI-Sponsored Women's Ischemia Syndrome Evaluation (WISE) study, part II: gender differences in presentation, diagnosis, and outcome with regard to gender-based pathophysiology of atherosclerosis and macrovascular and microvascular coronary disease.
        J Am Coll Cardiol. 2006; 47: S21-S29
        • Bergmann M.M.
        • Byers T.
        • Freedman D.S.
        • Mokdad A.
        Validity of self-reported diagnoses leading to hospitalization: a comparison of self-reports with hospital records in a prospective study of American adults.
        Am J Epidemiol. 1998; 147: 969-977
        • Okura Y.
        • Urban L.H.
        • Mahoney D.W.
        • Jacobsen S.J.
        • Rodeheffer R.J.
        Agreement between self-report questionnaires and medical record data was substantial for diabetes, hypertension, myocardial infarction and stroke but not for heart failure.
        J Clin Epidemiol. 2004; 57: 1096-1103
        • Eid R.E.
        • Rao D.A.
        • Zhou J.
        • Lo S.F.
        • Ranjbaran H.
        • Gallo A.
        • et al.
        Interleukin-17 and interferon-gamma are produced concomitantly by human coronary artery-infiltrating T cells and act synergistically on vascular smooth muscle cells.
        Circulation. 2009; 119: 1424-1432
        • Sampi M.
        • Ukkola O.
        • Paivansalo M.
        • Kesaniemi Y.A.
        • Binder C.J.
        • Horkko S.
        Plasma interleukin-5 levels are related to antibodies binding to oxidized low-density lipoprotein and to decreased subclinical atherosclerosis.
        J Am Coll Cardiol. 2008; 52: 1370-1378

      Linked Article

      • An alternative explanation for the inverse relationship between atopy and myocardial infarction
        Journal of Allergy and Clinical ImmunologyVol. 131Issue 6
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          I read with interest the recent report by Jaramillo et al1 regarding the inverse relationship between allergen-specific IgE and myocardial infarction and the proposed mechanism of TH1 versus TH2 inflammation in cardiovascular disease. Acute thrombosis in a coronary artery can cause myocardial infarction. Thus, anticlotting agents are used for prevention and treatment. Szczeklik et al2-4 have demonstrated that atopic individuals have a prolonged bleeding time.
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