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Antiphospholipid antibodies and sub-clinical atherosclerosis in the Coronary Artery Risk Development in Young Adults (CARDIA) cohort

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Abstract

Objective and design

Antiphospholipid antibodies (APA) have been associated with clinical cardiovascular disease, but it remains unclear whether APA are associated with sub-clinical atherosclerosis. This study examined the relationship between APA and sub-clinical atherosclerosis, measured as coronary artery calcification (CAC), in participants from the prospective Coronary Artery Risk Development in Young Adults (CARDIA) Study.

Subjects and method

2,203 black and white participants with sera available from the CARDIA year 7 examination and CAC measured by computed tomography at years 15 or 20 were selected.

Results

Anti-β2-glycoprotein I (anti-β2-GPI) immunoglobulin (Ig) M, IgG, and IgA were positive in 7.0, 1.4, and 1.8 % of participants, respectively; anti-cardiolipin (aCL) IgM and IgG were positive in 1.5 and 1.0 %, respectively. 9.5 % of participants had CAC score >0 at year 15. Anti-β2-GPI IgM, IgG, IgA, and aCL IgG positivity were associated with CAC >0 at year 15 after adjustment for traditional cardiovascular risk factors; [odds ratios (95 % confidence intervals) were 1.7 (1.0, 3.1), 6.4 (2.4, 16.8), 5.6 (2.3, 13.2), and 5.1 (1.4, 18.6), respectively]. Anti-β2-GPI IgG was associated with year 20 CAC >0, and anti-β2-GPI IgA and aCL IgG were marginally associated.

Conclusions

These findings indicate that APA positivity during young adulthood is a risk factor for subsequent sub-clinical atherosclerosis and might play a role in the pathogenesis of atherosclerosis.

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References

  1. Greenland P, Smith SC Jr, Grundy SM. Improving coronary heart disease risk assessment in asymptomatic people: role of traditional risk factors and noninvasive cardiovascular tests. Circulation. 2001;104(15):1863–7.

    Article  PubMed  CAS  Google Scholar 

  2. Manzi S, Wasko MC. Inflammation-mediated rheumatic diseases and atherosclerosis. Ann Rheum Dis. 2000;59(5):321–5.

    Article  PubMed  CAS  Google Scholar 

  3. Van Doornum S, McColl G, Wicks IP. Accelerated atherosclerosis: an extraarticular feature of rheumatoid arthritis? Arthritis Rheum. 2002;46(4):862–73.

    Article  PubMed  Google Scholar 

  4. Grainger DJ, Bethell HW. High titres of serum antinuclear antibodies, mostly directed against nucleolar antigens, are associated with the presence of coronary atherosclerosis. Ann Rheum Dis. 2002;61(2):110–4.

    Article  PubMed  CAS  Google Scholar 

  5. Sherer Y, Tenenbaum A, Praprotnik S, Shemesh J, Blank M, Fisman EZ, Harats D, George J, Levy Y, Peter JB, et al. Coronary artery disease but not coronary calcification is associated with elevated levels of cardiolipin, beta-2-glycoprotein-I, and oxidized LDL antibodies. Cardiology. 2001;95(1):20–4.

    Article  PubMed  CAS  Google Scholar 

  6. Soltesz P, Szekanecz Z, Kiss E, Shoenfeld Y. Cardiac manifestations in antiphospholipid syndrome. Autoimmun Rev. 2007;6(6):379–86.

    Article  PubMed  CAS  Google Scholar 

  7. Liang KP, Kremers HM, Crowson CS, Snyder MR, Therneau TM, Roger VL, Gabriel SE. Autoantibodies and the risk of cardiovascular events. J Rheumatol. 2009;36(11):2462–9.

    Article  PubMed  Google Scholar 

  8. Shoenfeld Y, Sherer Y, George J, Harats D. Autoantibodies associated with atherosclerosis. Ann Med. 2000;32(Suppl 1):37–40.

    PubMed  CAS  Google Scholar 

  9. Brey RL, Abbott RD, Curb JD, Sharp DS, Ross GW, Stallworth CL, Kittner SJ. beta(2)-Glycoprotein 1-dependent anticardiolipin antibodies and risk of ischemic stroke and myocardial infarction: the Honolulu heart program. Stroke. 2001;32(8):1701–6.

    Article  PubMed  CAS  Google Scholar 

  10. Kobayashi K, Lopez LR, Matsuura E. Atherogenic antiphospholipid antibodies in antiphospholipid syndrome. Ann N Y Acad Sci. 2007;1108:489–96.

    Article  PubMed  CAS  Google Scholar 

  11. Hasunuma Y, Matsuura E, Makita Z, Katahira T, Nishi S, Koike T. Involvement of beta 2-glycoprotein I and anticardiolipin antibodies in oxidatively modified low-density lipoprotein uptake by macrophages. Clin Exp Immunol. 1997;107(3):569–73.

    Article  PubMed  CAS  Google Scholar 

  12. George J, Harats D, Gilburd B, Afek A, Shaish A, Kopolovic J, Shoenfeld Y. Adoptive transfer of beta(2)-glycoprotein I-reactive lymphocytes enhances early atherosclerosis in LDL receptor-deficient mice. Circulation. 2000;102(15):1822–7.

    Article  CAS  Google Scholar 

  13. George J, Afek A, Gilburd B, Blank M, Levy Y, Aron-Maor A, Levkovitz H, Shaish A, Goldberg I, Kopolovic J, et al. Induction of early atherosclerosis in LDL-receptor-deficient mice immunized with beta2-glycoprotein I. Circulation. 1998;98(11):1108–15.

    Article  CAS  Google Scholar 

  14. Matsuura E, Lopez LR. Are oxidized LDL/beta2-glycoprotein I complexes pathogenic antigens in autoimmune-mediated atherosclerosis? Clin Dev Immunol. 2004;11(2):103–11.

    Article  PubMed  CAS  Google Scholar 

  15. Ames PR, Margarita A, Delgado Alves J, Tommasino C, Iannaccone L, Brancaccio V. Anticardiolipin antibody titre and plasma homocysteine level independently predict intima media thickness of carotid arteries in subjects with idiopathic antiphospholipid antibodies. Lupus. 2002;11(4):208–14.

    Google Scholar 

  16. Dropinski J, Szczeklik W, Rubis P, Sydor WJ. Anti-phospholipid antibodies and carotid-artery intima-media thickness in young survivors of myocardial infarction. Med Sci Monit. 2003;9(4):BR105–9.

    Google Scholar 

  17. Margarita A, Batuca J, Scenna G, Alves JD, Lopez L, Iannaccone L, Matsuura E, Ames PR. Subclinical atherosclerosis in primary antiphospholipid syndrome. Ann N Y Acad Sci. 2007;1108:475–80.

    Article  PubMed  CAS  Google Scholar 

  18. Petri M. The lupus anticoagulant is a risk factor for myocardial infarction (but not atherosclerosis): Hopkins Lupus Cohort. Thromb Res. 2004;114(5–6):593–5.

    Article  PubMed  CAS  Google Scholar 

  19. Asanuma Y, Oeser A, Shintani AK, Turner E, Olsen N, Fazio S, Linton MF, Raggi P, Stein CM. Premature coronary-artery atherosclerosis in systemic lupus erythematosus. N Engl J Med. 2003;349(25):2407–15.

    Article  PubMed  CAS  Google Scholar 

  20. Plazak W, Pasowicz M, Kostkiewicz M, Podolec J, Tomkiewicz-Pajak L, Musial J, Podolec P. Influence of chronic inflammation and autoimmunity on coronary calcifications and myocardial perfusion defects in systemic lupus erythematosus patients. Inflamm Res. 2011;60(10):973–80.

    Article  PubMed  CAS  Google Scholar 

  21. Cutter GR, Burke GL, Dyer AR, Friedman GD, Hilner JE, Hughes GH, Hulley SB, Jacobs DR, Jr., Liu K, Manolio TA, et al. Cardiovascular risk factors in young adults. The CARDIA baseline monograph. Control Clin Trials. 1991;12(1 Suppl):1S–77S.

    Google Scholar 

  22. Fanopoulos D, Teodorescu MR, Varga J, Teodorescu M. High frequency of abnormal levels of IgA anti-beta2-glycoprotein I antibodies in patients with systemic lupus erythematosus: relationship with antiphospholipid syndrome. J Rheumatol. 1998;25(4):675–80.

    CAS  Google Scholar 

  23. Miyakis S, Lockshin MD, Atsumi T, Branch DW, Brey RL, Cervera R, Derksen RH, De Groot PG, Koike T, Meroni PL, et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost. 2006;4(2):295–306.

    Article  PubMed  CAS  Google Scholar 

  24. Budoff MJ, McClelland RL, Nasir K, Greenland P, Kronmal RA, Kondos GT, Shea S, Lima JA, Blumenthal RS. Cardiovascular events with absent or minimal coronary calcification: the Multi-Ethnic Study of Atherosclerosis (MESA). Am Heart J. 2009;158(4):554–61.

    Article  PubMed  Google Scholar 

  25. Lee CD, Jacobs DR Jr, Hankinson A, Iribarren C, Sidney S. Cardiorespiratory fitness and coronary artery calcification in young adults: The CARDIA Study. Atherosclerosis. 2009;203(1):263–8.

    Article  PubMed  CAS  Google Scholar 

  26. Loria CM, Liu K, Lewis CE, Hulley SB, Sidney S, Schreiner PJ, Williams OD, Bild DE, Detrano R. Early adult risk factor levels and subsequent coronary artery calcification: the CARDIA Study. J Am Coll Cardiol. 2007;49(20):2013–20.

    Article  PubMed  Google Scholar 

  27. Okwuosa TM, Greenland P, Ning H, Liu K, Lloyd-Jones DM. Yield of screening for coronary artery calcium in early middle-age adults based on the 10-year Framingham Risk Score: the CARDIA study. JACC Cardiovasc Imaging. 2012;5(9):923–30.

    Article  PubMed  Google Scholar 

  28. Pletcher MJ, Hulley BJ, Houston T, Kiefe CI, Benowitz N, Sidney S. Menthol cigarettes, smoking cessation, atherosclerosis, and pulmonary function: the Coronary Artery Risk Development in Young Adults (CARDIA) Study. Arch Intern Med. 2006;166(17):1915–22.

    Article  PubMed  Google Scholar 

  29. Wilkins JT, Gidding S, Liu K, Ning H, Polak JF, Lloyd-Jones DM. Associations between a parental history of premature cardiovascular disease and coronary artery calcium and carotid intima-media thickness: the Coronary Artery Risk Development In Young Adults (CARDIA) study. Eur J Prev Cardiol. 2012. doi:10.1177/2047487312462801.

  30. Karlson EW, Sanchez-Guerrero J, Wright EA, Lew RA, Daltroy LH, Katz JN, Liang MH. A connective tissue disease screening questionnaire for population studies. Ann Epidemiol. 1995;5(4):297–302.

    Article  PubMed  CAS  Google Scholar 

  31. Sherer Y, Gerli R, Gilburd B, Bartoloni Bocci E, Vaudo G, Mannarino E, Shoenfeld Y. Thickened carotid artery intima-media in rheumatoid arthritis is associated with elevated anticardiolipin antibodies. Lupus. 2007;16(4):259–64.

    Google Scholar 

  32. Vlachoyiannopoulos PG, Kanellopoulos PG, Ioannidis JP, Tektonidou MG, Mastorakou I, Moutsopoulos HM. Atherosclerosis in premenopausal women with antiphospholipid syndrome and systemic lupus erythematosus: a controlled study. Rheumatology (Oxford). 2003;42(5):645–51.

    Article  CAS  Google Scholar 

  33. Farzaneh-Far A, Roman MJ, Lockshin MD, Devereux RB, Paget SA, Crow MK, Davis A, Sammaritano L, Levine DM, Salmon JE. Relationship of antiphospholipid antibodies to cardiovascular manifestations of systemic lupus erythematosus. Arthritis Rheum. 2006;54(12):3918–25.

    Article  PubMed  CAS  Google Scholar 

  34. Arbuckle MR, McClain MT, Rubertone MV, Scofield RH, Dennis GJ, James JA, Harley JB. Development of autoantibodies before the clinical onset of systemic lupus erythematosus. N Engl J Med. 2003;349(16):1526–33.

    Article  PubMed  CAS  Google Scholar 

  35. Erkan D, Yazici Y, Peterson MG, Sammaritano L, Lockshin MD. A cross-sectional study of clinical thrombotic risk factors and preventive treatments in antiphospholipid syndrome. Rheumatology (Oxford). 2002;41(8):924–9.

    Article  CAS  Google Scholar 

  36. Alarcon-Segovia D, Boffa MC, Branch W, Cervera R, Gharavi A, Khamashta M, Shoenfeld Y, Wilson W, Roubey R. Prophylaxis of the antiphospholipid syndrome: a consensus report. Lupus. 2003;12(7):499–503.

    Article  PubMed  CAS  Google Scholar 

  37. Majka DS, Holers VM. Can we accurately predict the development of rheumatoid arthritis in the preclinical phase? Arthritis Rheum. 2003;48(10):2701–5.

    Article  PubMed  Google Scholar 

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Acknowledgments

This work was supported by the National Institutes of Health (Grant numbers R21 HL079057, K12 RR017707, K23 AI064397, P60 AR48098, AR048269, AR055240 and contracts N01-HC-48047 to N01-HC-48050 and N01-HC-95095) and the Arthritis Foundation.

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Authors and Affiliations

  1. Division of Rheumatology, Northwestern University Feinberg School of Medicine, 240 E. Huron, M300, Chicago, IL, 60611, USA

    Darcy S. Majka & Richard M. Pope

  2. Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, 680 N. Lake Shore Dr, Suite 1400, Chicago, IL, 60611, USA

    Darcy S. Majka, Kiang Liu, Thanh-Huyen T. Vu & Rowland W. Chang

  3. Section of Clinical Sciences, Division of Rheumatology, Immunology and Allergy, Brigham and Women’s Hospital, 75 Francis Street, Boston, MA, 02115, USA

    Elizabeth W. Karlson

  4. TheraTest Laboratories, 1111 North Main Street, Lombard, IL, 60148, USA

    Marius Teodorescu

  5. Section of Rheumatology, University of Illinois at Chicago, 840 South Wood Street (MC 718), Chicago, IL, 60612, USA

    Marius Teodorescu

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  1. Darcy S. Majka
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Correspondence to Darcy S. Majka.

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Responsible Editor: John Di Battista.

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Majka, D.S., Liu, K., Pope, R.M. et al. Antiphospholipid antibodies and sub-clinical atherosclerosis in the Coronary Artery Risk Development in Young Adults (CARDIA) cohort. Inflamm. Res. 62, 919–927 (2013). https://doi.org/10.1007/s00011-013-0652-x

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  • DOI: https://doi.org/10.1007/s00011-013-0652-x

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