Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Therapy Insight: systemic lupus erythematosus as a risk factor for cardiovascular disease

Nature Clinical Practice Cardiovascular Medicine volume 2, pages 423–430 (2005)Cite this article

Abstract

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease with a strong female predilection. Cardiovascular morbidity and mortality is a frequent complication, particularly in females aged 35–44 years, in whom the risk of myocardial infarction is raised 50-fold. The mechanisms underlying this increased risk are not fully understood. Certain traditional risk factors, such as hypertension and diabetes mellitus, are more common in SLE patients than in the general population. These factors do not, however, completely account for the increased cardiovascular risk; factors such as renal impairment, increased homocysteine levels and early menopause probably have a role. In addition, several factors more-specifically related to lupus are proposed to be of importance, including chronic inflammation, antiphospholipid antibodies and therapy, especially corticosteroid use. Thus, we need to be proactive in our approach to risk-factor management in SLE patients. Here, we propose that, like diabetes mellitus, SLE should be considered a coronary heart disease equivalent condition for baseline risk and that assessment of cardiovascular risk should be done routinely. In addition to lifestyle modifications, blood pressure and cholesterol levels should be stringently controlled, and administration of aspirin should be considered in selected patients. The increased use of certain interventions, such as statins, also needs to be more-widely investigated in this population.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Schematic summary of atherosclerosis development emphasizing the inflammatory nature of the process.

Similar content being viewed by others

References

  1. Johnson AE et al. (1995) The prevalence and incidence of systemic lupus erythematosus in Birmingham, England. Arthritis Rheum 38: 551–557

    Article  CAS  Google Scholar 

  2. McCarty DJ et al. (1995) Incidence of systemic lupus erythematosus: race and gender differences. Arthritis Rheum 38: 1260–1270

    Article  CAS  Google Scholar 

  3. Uromoto KM et al. (1999) Trends in the incidence and mortality of SLE, 1950–1992. Arthritis Rheum 42: 46–50

    Article  Google Scholar 

  4. Abu-Shakra M et al. (1995) Mortality studies in SLE. Results from a single centre II: predictor variables for mortality. J Rheumatol 22: 1256–1270

    Google Scholar 

  5. Urowitz MB et al. (1976) The bimodal mortality pattern of systemic lupus erythematosus. Am J Med 60: 221–225

    Article  CAS  Google Scholar 

  6. Ward MM (1999) Premature morbidity from cardiovascular and cerebrovascular diseases in women with systemic lupus erythematosus. Arthritis Rheum 42: 338–346

    Article  CAS  Google Scholar 

  7. Manzi S et al. (1997) Age-specific incidence rates of myocardial infarction and angina in women with systemic lupus erythematosus: comparison with the Framingham Study. Am J Epidemiol 145: 408–415

    Article  CAS  Google Scholar 

  8. Hosenpud JD et al. (1984) Myocardial perfusion abnormalities in asymptomatic patients with systemic lupus erythematosus. Am J Med 77: 286–292

    Article  CAS  Google Scholar 

  9. Sella EM et al. (2003) Myocardial perfusion scintigraphy and coronary disease risk factors in systemic lupus erythematosus. Ann Rheum Dis 62: 1066–1070

    Article  CAS  Google Scholar 

  10. Sella EM et al. (2003) Coronary artery angiography in systemic lupus erythematosus patients with abnormal myocardial perfusion scintigraphy. Arthritis Rheum 48: 3168–3175

    Article  CAS  Google Scholar 

  11. Roman MJ et al. (2003) Prevalence and correlates of accelerated atherosclerosis in systemic lupus erythematosus. N Engl J Med 349: 2399–2406

    Article  CAS  Google Scholar 

  12. Svenungsson E et al. (2001) Risk factors for cardiovascular disease in systemic lupus erythematosus. Circulation 104: 1887–1893

    Article  CAS  Google Scholar 

  13. Doria A et al. (2003) Risk factors for subclinical atherosclerosis in a prospective cohort of patients with systemic lupus erythematosus. Ann Rheum Dis 62: 1071–1077

    Article  CAS  Google Scholar 

  14. Leong KH et al. (1994) Lipid profiles in patients with systemic lupus erythematosus. J Rheumatol 21: 1264–1267

    CAS  PubMed  Google Scholar 

  15. Petri M et al. (1992) Coronary artery disease risk factors in the Johns Hopkins Lupus Cohort: prevalence, recognition by patients, and preventive practices. Medicine (Baltimore) 71: 291–302

    Article  CAS  Google Scholar 

  16. Bruce IN et al. (2003) Risk factors for coronary heart disease in women with systemic lupus erythematosus: the Toronto Risk Factor Study. Arthritis Rheum 48: 3159–3167

    Article  Google Scholar 

  17. Esdaile JM et al. (2001) Traditional Framingham risk factors fail to fully account for accelerated atherosclerosis in systemic lupus erythematosus. Arthritis Rheum 44: 2331–2337

    Article  CAS  Google Scholar 

  18. Bessant R et al. (2004) Risk of coronary heart disease and stroke in a large British cohort of patients with systemic lupus erythematosus. Rheumatol 43: 924–929

    Article  CAS  Google Scholar 

  19. Petri M et al. (1992) Risk factors for coronary heart disease in patients with SLE. Am J Med 93: 513–519

    Article  CAS  Google Scholar 

  20. Bulkley BH and Roberts WC (1975) The heart in systemic lupus erythematosus and the changes induced in it by corticosteroid therapy. A study of 36 necropsy patients. Am J Med 58: 243–264

    Article  CAS  Google Scholar 

  21. Ettinger WH et al. (1987) Dyslipoproteinemia in systemic lupus erythematosus. Effect of corticosteroids. Am J Med 83: 503–508

    Article  CAS  Google Scholar 

  22. MacGregor AJ et al. (1992) Fasting lipids and anticardiolipin antibodies as risk factors for vascular disease in systemic lupus erythematosus. Ann Rheum Dis 51: 152–155

    Article  CAS  Google Scholar 

  23. Hansson GK (2005) Inflammation, atherosclerosis and coronary artery disease. N Engl J Med 352: 1685–1695

    Article  CAS  Google Scholar 

  24. Spodlick DH et al. (1984) Association of acute respiratory symptoms with onset of acute myocardial infarction: prospective investigation of 150 consecutive patients and matched controls. Am J Cardiol 53: 481–482

    Article  Google Scholar 

  25. Grau AJ et al. (1995) Recent infections as a risk factor for cerebrovascular infarction. Stroke 26: 373–379

    Article  CAS  Google Scholar 

  26. Wick G et al. (1995) Is atherosclerosis an immunologically mediated disease? Immunol Today 16: 27–33

    Article  CAS  Google Scholar 

  27. Liuzzo G et al. (2000) Monoclonal T-cell proliferation and plaque instability in acute coronary syndromes. Circulation 101: 2883–2888

    Article  CAS  Google Scholar 

  28. Ridker PM et al. (2000) C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. N Engl J Med 342: 836–843

    Article  CAS  Google Scholar 

  29. Boey ML et al. (1983) Thrombosis in systemic lupus erythematosus: striking association with the presence of circulating lupus anticoagulant. BMJ (Clin Res Ed) 287: 1021–1023

    Article  CAS  Google Scholar 

  30. Harris EN et al. (1983) Anticardiolipin antibodies: detection by radioimmunoassay and association with thrombosis in SLE. Lancet 2: 1211–1214

    Article  CAS  Google Scholar 

  31. Ahmad Y et al. (2004) Antiphospholipid antibodies (APLA) contribute to atherogenesis in SLE. Arthritis Rheum 50 (Suppl 1): S191

    Google Scholar 

  32. Bilora F et al. (2002) Are antiphospholipid antibodies an independent risk factor for atherosclerosis? Clin Appl Thromb Hemost 8: 103–113

    Article  Google Scholar 

  33. Medina G et al. (2003) Increased carotid artery intima–media thickness may be associated with stroke in Primary Antiphospholipid Syndrome. Ann Rheum Dis 62: 607–610

    Article  CAS  Google Scholar 

  34. Vaarala O et al. (1995) Anti-cardiolipin antibodies and risk of myocardial infarction in a prospective cohort of middle-aged men. Circulation 91: 23–27

    Article  CAS  Google Scholar 

  35. Vaarala O et al. (1993) Cross-reaction between antibodies to oxidised low-density lipoprotein and to cardiolipin in systemic lupus erythematosus. Lancet 341: 923–925

    Article  CAS  Google Scholar 

  36. Witzum JL and Steinberg D (1991) Role of oxidised low-density lipoprotein in atherogenesis. J Clin Invest 88: 1785–1792

    Article  Google Scholar 

  37. Hasunuma Y et al. (1997) Involvement of beta 2-glycoprotein I and anticardiolipin antibodies in oxidatively modified low-density lipoprotein uptake by macrophages. Clin Exp Immunol 107: 569–573

    Article  CAS  Google Scholar 

  38. Kobayashi K et al. (2003) Circulating oxidized LDL forms complexes with beta 2-glycoprotein I: implication as an atherogenic autoantigen. J Lipid Res 44: 716–726

    Article  CAS  Google Scholar 

  39. Wu R et al. (1997) Antibodies against cardiolipin and oxidatively modified LDL in 50-year-old men predict myocardial infarction. Arterioscler Thromb Vasc Biol 17: 3159–3163

    Article  CAS  Google Scholar 

  40. Lahita RG et al. (1993). Low levels of total cholesterol, high-density lipoprotein, and apolipoprotein A1 in association with anticardiolipin antibodies in patients with systemic lupus erythematosus. Arthritis Rheum 36: 1566–1574

    Article  CAS  Google Scholar 

  41. Delgado AJ et al. (2003) Cross-reactivity between anti-cardiolipin, anti-high-density lipoprotein and anti-apolipoprotein A-I IgG antibodies in patients with systemic lupus erythematosus and primary antiphospholipid syndrome. Rheumatol 42: 893–899

    Article  Google Scholar 

  42. Nicolo D et al. (2003) Reduction of atherosclerosis in low-density lipoprotein receptor-deficient mice by passive administration of antiphospholipid antibody. Arthritis Rheum 48: 2974–2978

    Article  CAS  Google Scholar 

  43. Nickolas TL et al. (2003) Hyperlipidemia and thrombotic complications in patients with membranous nephropathy. Semin Nephrol 23: 406–411

    Article  Google Scholar 

  44. Manger K et al. (2003) Factors associated with coronary artery calcification in young female patients with SLE. Ann Rheum Dis 62: 846–850

    Article  CAS  Google Scholar 

  45. Petri M et al. (1996) Plasma homocysteine as a risk factor for atherothrombotic events in SLE. Lancet 348: 1120–1124

    Article  CAS  Google Scholar 

  46. Petri et al. (1992) Plasma homocysteine as a risk factor for patients with SLE. Am J Med 93: 513–519

    Article  CAS  Google Scholar 

  47. Takahashi R et al. (2005) Association of mannose binding lectin and serum mannose binding lectin concentration with characteristics and progression of SLE. Ann Rheum Dis 64: 311–314

    Article  CAS  Google Scholar 

  48. Ohlenschlaeger T et al. (2004) Mannose-binding lectin variant alleles and the risk of arterial thrombosis in systemic lupus erythematosus. N Engl J Med 351: 260–267

    Article  CAS  Google Scholar 

  49. Wajed J et al. (2004) Prevention of cardiovascular disease in systemic lupus erythematosus—proposed guidelines for risk factor management. Rheumatol 43: 7–12

    Article  CAS  Google Scholar 

  50. Sowers J (1998) Diabetes mellitus and cardiovascular disease in women. Arch Intern Med 158: 617–621

    Article  CAS  Google Scholar 

  51. Hearth-Holmes M et al. (1995) Dietary treatment of hyperlipidemia in patients with systemic lupus erythematosus. J Rheumatol 22: 450–454

    CAS  PubMed  Google Scholar 

  52. Borba EF and Bonfa E (2001) Longterm beneficial effect of chloroquine diphosphate on lipoprotein profile in lupus patients with and without steroid therapy. J Rheumatol 28: 780–785

    CAS  PubMed  Google Scholar 

  53. Leung BP et al. (2003) A novel anti-inflammatory role for simvastatin in inflammatory arthritis. J Immunol 170: 1524–1530

    Article  CAS  Google Scholar 

  54. Wahl DG et al. (2000) Prophylactic antithrombotic therapy for patients with systemic lupus erythematosus with or without antiphospholipid antibodies: do the benefits outweigh the risks? A decision analysis. Arch Int Med 160: 2042–2048

    Article  CAS  Google Scholar 

  55. Leung MH et al. (2002) Mortality and malignancy in the multi-ethnic Birmingham Lupus Cohort - aspirin use is beneficial and non-Caucasian origin is not associated with a poor outcome. Rheumatol 41 (Suppl 1): S17

    Google Scholar 

  56. Bruce IN et al. (1998). Detection and modification of risk factors for coronary artery disease in patients with systemic lupus erythematosus: a quality improvement study. Clin Exp Rheumatol 16: 435–440

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We acknowledge the support of the Ontario Lupus Association (Geoff Carr Lupus Fellowship), The Heart and Stroke Foundation of Ontario, The Arthritis Research Campaign (UK), Lupus UK, The Wellcome Trust and the charitable funds of Central Manchester and Manchester Children's University Hospital NHS Trust.

Author information

Authors and Affiliations

  1. North-West England Deanery Rheumatology Training Programme,

    Sahena Haque & Ian N Bruce

  2. Arthritis Research Campaign Epidemiology Unit and Rheumatism Research Centre, University of Manchester, and Central Manchester and Manchester Children's University Hospitals, UK

    Sahena Haque & Ian N Bruce

Authors
  1. Sahena Haque
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ian N Bruce
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ian N Bruce.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Glossary

SINGLE PHOTON EMISSION COMPUTED TOMOGRAPHY–DUAL ISOTOPE MYOCARDIAL PERFUSION IMAGING (SPECT-DIMPI)

A nuclear cardiac imaging technique where the resting and stress images are acquired using different isotopes (201Tl and 99mTc–sestamibi)

B-MODE DOPPLER ULTRASOUND

A vascular imaging technique used to examine the carotid and/or femoral artery: the ultrasound image is acquired using the Brightness (B) mode, and the Doppler technique allows examination of blood flow characteristics

ANTIPHOSPHOLIPID ANTIBODIES (aPL)

Antibodies directed against negatively charged phospholipids

ANTIPHOSPHOLIPID SYNDROME (APS)

A clinical syndrome of thrombosis (arterial or venous) and/or recurrent miscarriage in the presence of antiphospholipid antibodies and/or the lupus anticoagulant

β2 GLYCOPROTEIN I

Also known as apolipoprotein H, it is a cofactor in the binding of pathogenic antiphospholipid antibodies

MACROPHAGE SCAVENGER RECEPTORS

Membrane glycoproteins that mediate the uptake and endocytosis of a range of extracellular macromolecules including oxidatively modified LDL

FC RECEPTORS

Membrane receptors for the Fc portion of immunoglobulin molecules

PASSIVE ADMINISTRATION OF ANTIBODIES

Transfer of antibodies directly into an organism rather than generating them in the host by exposure to antigens

COMPLEMENT CASCADE

A constitutive, nonspecific protein cascade important in host defense, which makes bacteria susceptible to phagocytosis by lysing bacterial cell walls and activating other host defense systems

Rights and permissions

Reprints and permissions

About this article

Cite this article

Haque, S., Bruce, I. Therapy Insight: systemic lupus erythematosus as a risk factor for cardiovascular disease. Nat Rev Cardiol 2, 423–430 (2005). https://doi.org/10.1038/ncpcardio0270

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ncpcardio0270

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing