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. 2003 Nov;62(11):1071–1077. doi: 10.1136/ard.62.11.1071

Risk factors for subclinical atherosclerosis in a prospective cohort of patients with systemic lupus erythematosus

A Doria 1, Y Shoenfeld 1, R Wu 1, P Gambari 1, M Puato 1, A Ghirardello 1, B Gilburd 1, S Corbanese 1, M Patnaik 1, S Zampieri 1, J Peter 1, E Favaretto 1, L Iaccarino 1, Y Sherer 1, S Todesco 1, P Pauletto 1
PMCID: PMC1754370  PMID: 14583570

Abstract

Objective: To evaluate traditional and non-traditional risk factors for subclinical atherosclerosis in systemic lupus erythematosus (SLE).

Methods: A prospective cohort of 78 patients with SLE without overt atherosclerotic disease was studied. SLE clinical and laboratory parameters, disease activity and damage, treatment and traditional risk factors for atherosclerosis were evaluated. At baseline (T1) and after five years' follow up (T2), the serum levels of anti-oxidised palmitoyl arachidonoyl phosphocholine (oxPAPC), anti-heat shock protein 65, and anti-ß2-glycoprotein I antibodies and C reactive protein were tested. At T2, intima-media thickness (IMT) was measured using duplex carotid sonography. Thickened intima, plaque, mean IMT (m-IMT), and maximum IMT (M-IMT) were assessed.

Results: A thickened intima was seen in 22/78 (28%) patients and plaque in 13/78 (17%). M-IMT and m-IMT were (mean (SD)) 0.77 (0.34) mm and 0.55 (0.15) mm, respectively. Patients with carotid abnormalities were significantly older, had higher blood pressure and total serum cholesterol levels, and had taken a higher prednisone cumulative dosage than those without any lesions. The carotid abnormalities were associated with renal disease and ECLAM >2 at T1, and with azathioprine treatment. In multivariate analysis, age and cumulative prednisone dose were associated with carotid abnormalities; age, hypertension, and anti-oxPAPC at T2 were correlated with higher M-IMT and m-IMT.

Conclusions: In patients with SLE some non-traditional risk factors for atherosclerosis were identified, the most important of which was the cumulative prednisone dose. The role of some traditional risk factors, such as age and hypertension, was also confirmed. The predictive value of the new immunological and inflammatory markers of atherosclerosis seems to be masked by some disease related features.

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Selected References

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  1. Birnie D. H., Holme E. R., McKay I. C., Hood S., McColl K. E., Hillis W. S. Association between antibodies to heat shock protein 65 and coronary atherosclerosis. Possible mechanism of action of Helicobacter pylori and other bacterial infections in increasing cardiovascular risk. Eur Heart J. 1998 Mar;19(3):387–394. doi: 10.1053/euhj.1997.0618. [DOI] [PubMed] [Google Scholar]
  2. Borhani N. O., Mercuri M., Borhani P. A., Buckalew V. M., Canossa-Terris M., Carr A. A., Kappagoda T., Rocco M. V., Schnaper H. W., Sowers J. R. Final outcome results of the Multicenter Isradipine Diuretic Atherosclerosis Study (MIDAS). A randomized controlled trial. JAMA. 1996 Sep 11;276(10):785–791. [PubMed] [Google Scholar]
  3. Bruce I. N., Gladman D. D., Urowitz M. B. Premature atherosclerosis in systemic lupus erythematosus. Rheum Dis Clin North Am. 2000 May;26(2):257–278. doi: 10.1016/s0889-857x(05)70138-1. [DOI] [PubMed] [Google Scholar]
  4. Bruce I. N., Urowitz M. B., Gladman D. D., Hallett D. C. Natural history of hypercholesterolemia in systemic lupus erythematosus. J Rheumatol. 1999 Oct;26(10):2137–2143. [PubMed] [Google Scholar]
  5. Bulkley B. H., Roberts W. C. The heart in systemic lupus erythematosus and the changes induced in it by corticosteroid therapy. A study of 36 necropsy patients. Am J Med. 1975 Feb;58(2):243–264. doi: 10.1016/0002-9343(75)90575-6. [DOI] [PubMed] [Google Scholar]
  6. Falaschi F., Ravelli A., Martignoni A., Migliavacca D., Sartori M., Pistorio A., Perani G., Martini A. Nephrotic-range proteinuria, the major risk factor for early atherosclerosis in juvenile-onset systemic lupus erythematosus. Arthritis Rheum. 2000 Jun;43(6):1405–1409. doi: 10.1002/1529-0131(200006)43:6<1405::AID-ANR26>3.0.CO;2-V. [DOI] [PubMed] [Google Scholar]
  7. George J., Afek A., Gilburd B., Harats D., Shoenfeld Y. Autoimmunity in atherosclerosis: lessons from experimental models. Lupus. 2000;9(3):223–227. doi: 10.1191/096120300678828190. [DOI] [PubMed] [Google Scholar]
  8. George J., Blank M., Levy Y., Meroni P., Damianovich M., Tincani A., Shoenfeld Y. Differential effects of anti-beta2-glycoprotein I antibodies on endothelial cells and on the manifestations of experimental antiphospholipid syndrome. Circulation. 1998 Mar 10;97(9):900–906. doi: 10.1161/01.cir.97.9.900. [DOI] [PubMed] [Google Scholar]
  9. Ghirardello A., Doria A., Ruffatti A., Rigoli A. M., Vesco P., Calligaro A., Gambari P. F. Antiphospholipid antibodies (aPL) in systemic lupus erythematosus. Are they specific tools for the diagnosis of aPL syndrome? Ann Rheum Dis. 1994 Feb;53(2):140–142. doi: 10.1136/ard.53.2.140. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Gladman D. D., Urowitz M. B. Morbidity in systemic lupus erythematosus. J Rheumatol Suppl. 1987 Jun;14 (Suppl 13):223–226. [PubMed] [Google Scholar]
  11. Gladman D., Ginzler E., Goldsmith C., Fortin P., Liang M., Urowitz M., Bacon P., Bombardieri S., Hanly J., Hay E. The development and initial validation of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index for systemic lupus erythematosus. Arthritis Rheum. 1996 Mar;39(3):363–369. doi: 10.1002/art.1780390303. [DOI] [PubMed] [Google Scholar]
  12. Harris E. N. Antiphospholipid antibodies. Br J Haematol. 1990 Jan;74(1):1–9. doi: 10.1111/j.1365-2141.1990.tb02530.x. [DOI] [PubMed] [Google Scholar]
  13. Hoppichler F., Lechleitner M., Traweger C., Schett G., Dzien A., Sturm W., Xu Q. Changes of serum antibodies to heat-shock protein 65 in coronary heart disease and acute myocardial infarction. Atherosclerosis. 1996 Oct 25;126(2):333–338. doi: 10.1016/0021-9150(96)05931-x. [DOI] [PubMed] [Google Scholar]
  14. Howard G., Sharrett A. R., Heiss G., Evans G. W., Chambless L. E., Riley W. A., Burke G. L. Carotid artery intimal-medial thickness distribution in general populations as evaluated by B-mode ultrasound. ARIC Investigators. Stroke. 1993 Sep;24(9):1297–1304. doi: 10.1161/01.str.24.9.1297. [DOI] [PubMed] [Google Scholar]
  15. Hughes G. R. Immunology, lupus and atheroma. Lupus. 2000;9(3):159–160. doi: 10.1191/096120300678828316. [DOI] [PubMed] [Google Scholar]
  16. Hörkkö S., Bird D. A., Miller E., Itabe H., Leitinger N., Subbanagounder G., Berliner J. A., Friedman P., Dennis E. A., Curtiss L. K. Monoclonal autoantibodies specific for oxidized phospholipids or oxidized phospholipid-protein adducts inhibit macrophage uptake of oxidized low-density lipoproteins. J Clin Invest. 1999 Jan;103(1):117–128. doi: 10.1172/JCI4533. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Hörkkö S., Olee T., Mo L., Branch D. W., Woods V. L., Jr, Palinski W., Chen P. P., Witztum J. L. Anticardiolipin antibodies from patients with the antiphospholipid antibody syndrome recognize epitopes in both beta(2)-glycoprotein 1 and oxidized low-density lipoprotein. Circulation. 2001 Feb 20;103(7):941–946. doi: 10.1161/01.cir.103.7.941. [DOI] [PubMed] [Google Scholar]
  18. Li R., Cai J., Tegeler C., Sorlie P., Metcalf P. A., Heiss G. Reproducibility of extracranial carotid atherosclerotic lesions assessed by B-mode ultrasound: the Atherosclerosis Risk in Communities Study. Ultrasound Med Biol. 1996;22(7):791–799. doi: 10.1016/0301-5629(96)00084-1. [DOI] [PubMed] [Google Scholar]
  19. Lockshin M. D., Salmon J. E., Roman M. J. Atherosclerosis and lupus: a work in progress. Arthritis Rheum. 2001 Oct;44(10):2215–2217. doi: 10.1002/1529-0131(200110)44:10<2215::aid-art381>3.0.co;2-o. [DOI] [PubMed] [Google Scholar]
  20. Manzi S., Meilahn E. N., Rairie J. E., Conte C. G., Medsger T. A., Jr, Jansen-McWilliams L., D'Agostino R. B., Kuller L. H. Age-specific incidence rates of myocardial infarction and angina in women with systemic lupus erythematosus: comparison with the Framingham Study. Am J Epidemiol. 1997 Mar 1;145(5):408–415. doi: 10.1093/oxfordjournals.aje.a009122. [DOI] [PubMed] [Google Scholar]
  21. Manzi S., Selzer F., Sutton-Tyrrell K., Fitzgerald S. G., Rairie J. E., Tracy R. P., Kuller L. H. Prevalence and risk factors of carotid plaque in women with systemic lupus erythematosus. Arthritis Rheum. 1999 Jan;42(1):51–60. doi: 10.1002/1529-0131(199901)42:1<51::AID-ANR7>3.0.CO;2-D. [DOI] [PubMed] [Google Scholar]
  22. O'Leary D. H., Polak J. F., Kronmal R. A., Manolio T. A., Burke G. L., Wolfson S. K., Jr Carotid-artery intima and media thickness as a risk factor for myocardial infarction and stroke in older adults. Cardiovascular Health Study Collaborative Research Group. N Engl J Med. 1999 Jan 7;340(1):14–22. doi: 10.1056/NEJM199901073400103. [DOI] [PubMed] [Google Scholar]
  23. Pauletto P., Palatini P., Da Ros S., Pagliara V., Santipolo N., Baccillieri S., Casiglia E., Mormino P., Pessina A. C. Factors underlying the increase in carotid intima-media thickness in borderline hypertensives. Arterioscler Thromb Vasc Biol. 1999 May;19(5):1231–1237. doi: 10.1161/01.atv.19.5.1231. [DOI] [PubMed] [Google Scholar]
  24. Petri M., Perez-Gutthann S., Spence D., Hochberg M. C. Risk factors for coronary artery disease in patients with systemic lupus erythematosus. Am J Med. 1992 Nov;93(5):513–519. doi: 10.1016/0002-9343(92)90578-y. [DOI] [PubMed] [Google Scholar]
  25. Phadke K. V., Phillips R. A., Clarke D. T., Jones M., Naish P., Carson P. Anticardiolipin antibodies in ischaemic heart disease: marker or myth? Br Heart J. 1993 May;69(5):391–394. doi: 10.1136/hrt.69.5.391. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Rahman P., Urowitz M. B., Gladman D. D., Bruce I. N., Genest J., Jr Contribution of traditional risk factors to coronary artery disease in patients with systemic lupus erythematosus. J Rheumatol. 1999 Nov;26(11):2363–2368. [PubMed] [Google Scholar]
  27. Ridker P. M. High-sensitivity C-reactive protein: potential adjunct for global risk assessment in the primary prevention of cardiovascular disease. Circulation. 2001 Apr 3;103(13):1813–1818. doi: 10.1161/01.cir.103.13.1813. [DOI] [PubMed] [Google Scholar]
  28. Roman M. J., Salmon J. E., Sobel R., Lockshin M. D., Sammaritano L., Schwartz J. E., Devereux R. B. Prevalence and relation to risk factors of carotid atherosclerosis and left ventricular hypertrophy in systemic lupus erythematosus and antiphospholipid antibody syndrome. Am J Cardiol. 2001 Mar 1;87(5):663-6, A11. doi: 10.1016/s0002-9149(00)01453-3. [DOI] [PubMed] [Google Scholar]
  29. Svenungsson E., Jensen-Urstad K., Heimbürger M., Silveira A., Hamsten A., de Faire U., Witztum J. L., Frostegård J. Risk factors for cardiovascular disease in systemic lupus erythematosus. Circulation. 2001 Oct 16;104(16):1887–1893. doi: 10.1161/hc4101.097518. [DOI] [PubMed] [Google Scholar]
  30. Tan E. M., Cohen A. S., Fries J. F., Masi A. T., McShane D. J., Rothfield N. F., Schaller J. G., Talal N., Winchester R. J. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1982 Nov;25(11):1271–1277. doi: 10.1002/art.1780251101. [DOI] [PubMed] [Google Scholar]
  31. Urowitz M. B., Bookman A. A., Koehler B. E., Gordon D. A., Smythe H. A., Ogryzlo M. A. The bimodal mortality pattern of systemic lupus erythematosus. Am J Med. 1976 Feb;60(2):221–225. doi: 10.1016/0002-9343(76)90431-9. [DOI] [PubMed] [Google Scholar]
  32. Vitali C., Bencivelli W., Isenberg D. A., Smolen J. S., Snaith M. L., Sciuto M., Neri R., Bombardieri S. Disease activity in systemic lupus erythematosus: report of the Consensus Study Group of the European Workshop for Rheumatology Research. II. Identification of the variables indicative of disease activity and their use in the development of an activity score. The European Consensus Study Group for Disease Activity in SLE. Clin Exp Rheumatol. 1992 Sep-Oct;10(5):541–547. [PubMed] [Google Scholar]
  33. Ward M. M. Premature morbidity from cardiovascular and cerebrovascular diseases in women with systemic lupus erythematosus. Arthritis Rheum. 1999 Feb;42(2):338–346. doi: 10.1002/1529-0131(199902)42:2<338::AID-ANR17>3.0.CO;2-U. [DOI] [PubMed] [Google Scholar]
  34. Watson A. D., Leitinger N., Navab M., Faull K. F., Hörkkö S., Witztum J. L., Palinski W., Schwenke D., Salomon R. G., Sha W. Structural identification by mass spectrometry of oxidized phospholipids in minimally oxidized low density lipoprotein that induce monocyte/endothelial interactions and evidence for their presence in vivo. J Biol Chem. 1997 May 23;272(21):13597–13607. doi: 10.1074/jbc.272.21.13597. [DOI] [PubMed] [Google Scholar]
  35. Xu Q., Willeit J., Marosi M., Kleindienst R., Oberhollenzer F., Kiechl S., Stulnig T., Luef G., Wick G. Association of serum antibodies to heat-shock protein 65 with carotid atherosclerosis. Lancet. 1993 Jan 30;341(8840):255–259. doi: 10.1016/0140-6736(93)92613-x. [DOI] [PubMed] [Google Scholar]
  36. ter Borg E. J., Horst G., Limburg P. C., van Rijswijk M. H., Kallenberg C. G. C-reactive protein levels during disease exacerbations and infections in systemic lupus erythematosus: a prospective longitudinal study. J Rheumatol. 1990 Dec;17(12):1642–1648. [PubMed] [Google Scholar]

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