Cardiovascular risk stratification and appropriate use of statins in patients with systemic lupus erythematosus according to different strategies

  • Walter MassonEmail author
  • Emiliano Rossi
  • Lorena M. Mora-Crespo
  • Guillermo Cornejo-Peña
  • Carla Pessio
  • Mariela Gago
  • Rodolfo N. Alvarado
  • Marina Scolnik
Original Article



Cardiovascular risk management of patients with systemic lupus erythematosus (SLE) is medically relevant. The objectives were to estimate the cardiovascular risk by different strategies in patients with SLE, analyzing which proportion of patients would be candidates to receive statin therapy, and identify how many patients with statin indication received such drugs.


A cross-sectional study was performed from a secondary database. Following the recommendations of National Institute for Health and Care Excellence (NICE) guidelines and the Argentine Consensus, the QRISK-3 and the adjusted Framingham (multiplying factor × 2) scores were calculated in primary prevention subjects. The indications for statin therapy according to these recommendations were analyzed.


In total, 110 patients were included. Regarding patients without previous cardiovascular history, the median adjusted Framingham score was 12.8% (4.1–21.9), and 45.2%, 22.6%, and 32.2% of them were classified at low, moderate, or high risk. The median QRISK-3 score was 6.0% (2.1–14.1) and 42.1% of subjects were classified “at risk”. Only 60% of subjects in secondary prevention received statins, although no patient received the recommended doses. Analyzing patients in primary prevention who did not receive statins (87%), 43.4% and 45.2% of the patients were eligible for statin therapy according to NICE guidelines and Argentine Consensus, respectively.


Our findings showed that a large proportion of patients with SLE have a considerable cardiovascular risk and many of them would be eligible for statin therapy. However, the statin use observed was low.

Key Points

• A large proportion of patients with lupus have a considerable cardiovascular risk, explained in part by dyslipidemia.

• Many patients with SLE would be eligible for statin therapy according to risk stratification based on conventional risk factors.

• The use of statins in this population is inadequate.


Cardiovascular risk scores Statins Systemic lupus erythematosus 


Ethical approval

The study was conducted in compliance with the recommendations for medical research contained in the Declaration of Helsinki, Good Clinical Practice standards, and the applicable ethical regulations. The protocol was reviewed and approved by the Ethical Board of the Institution.

Author contributions

All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by Lorena M Mora-Crespo, Guillermo Cornejo-Peña, Carla Pessio, Mariela Gago, and Rodolfo N Alvarado. The first draft of the manuscript was written by Walter Masson and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Compliance with ethical standards




  1. 1.
    Andrades C, Fuego C, Manrique-Arija S, Fernández-Nebro A (2017) Management of cardiovascular risk in systemic lupus erythematosus: a systematic review. Lupus 26:1407–1419CrossRefGoogle Scholar
  2. 2.
    Esdaile JM, Abrahamowicz M, Grodzicky T, Li Y, Panaritis C, du Berger R, Côte R, Grover SA, Fortin PR, Clarke AE, Senécal JL (2001) Traditional Framingham risk factors fail to fully account for accelerated atherosclerosis in systemic lupus erythematosus. Arthritis Rheum 44:2331–2337CrossRefGoogle Scholar
  3. 3.
    Manzi S, Meilahn EN, Rairie JE, Conte CG, Medsger TA Jr, McWilliams LJ 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 145:408–415CrossRefGoogle Scholar
  4. 4.
    Fernández-Nebro A, Rúa-Figueroa Í, López-Longo FJ, Galindo-Izquierdo M, Calvo-Alén J, Olivé-Marqués A et al (2015) Cardiovascular events in systemic lupus erythematosus: a nationwide study in Spain from the RELESSER registry. Medicine (Baltimore) 94:e1183CrossRefGoogle Scholar
  5. 5.
    Borchers AT, Keen CL, Shoenfeld Y, Gershwin ME (2004) Surviving the butterfly and the wolf: mortality trends in systemic lupus erythematosus. Autoimmun Rev 3:423–453CrossRefGoogle Scholar
  6. 6.
    Gu MM, Wang XP, Cheng QY, Zhao YL, Zhang TP, Li BZ, Ye DQ (2019) A meta-analysis of cardiovascular events in systemic lupus erythematosus. Immunol Investig 48:505–520CrossRefGoogle Scholar
  7. 7.
    Croca S, Rahman A (2017) Atherosclerosis in systemic lupus erythematosus. Best Pract Res Clin Rheumatol 31:364–372CrossRefGoogle Scholar
  8. 8.
    Boulos D, Koelmeyer RL, Morand EF, Hoi Y (2017) Cardiovascular risk profiles in a lupus cohort: what do different calculators tell us? Lupus Sci Med 4(1):e000212CrossRefGoogle Scholar
  9. 9.
    Artola RT, Mihos CG, Santana O (2016) Effects of statin therapy in patients with systemic lupus erythematosus. South Med J 109:705–711PubMedGoogle Scholar
  10. 10.
    Yu HH, Chen PC, Yang YH, Wang LC, Lee JH, Lin YT, Chiang BL (2015) Statin reduces mortality and morbidity in systemic lupus erythematosus patients with hyperlipidemia: a nationwide population-based cohort study. Atherosclerosis 243:11–18CrossRefGoogle Scholar
  11. 11.
    Hippisley-Cox J, Coupland C, Brindle P (2017) Development and validation of QRISK3 risk prediction algorithms to estimate future risk of cardiovascular disease: prospective cohort study. BMJ 357:j2099CrossRefGoogle Scholar
  12. 12.
    Sociedad Argentina de Cardiología. Área de normas y consensos (2019) Riesgo cardiovascular en las enfermedades inflamatorias crónicas. Rev Arg Cardiol 87(Supl. 2)Google Scholar
  13. 13.
    Hochberg M (1997) Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 40:1725CrossRefGoogle Scholar
  14. 14.
    Petri M, Orbai AM, Alarcon GS, Gordon C, Merrill JT, Fortin PR et al (2012) Derivation and validation of the systemic lupus international collaborating clinics classification criteria for systemic lupus erythematosus. Arthritis Rheum 64:2677–2686CrossRefGoogle Scholar
  15. 15.
  16. 16.
    D’Agostino RB, Vasan RS, Pencina MJ, Wolf PA, Cobain M, Massaro JM et al (2008) General cardiovascular risk profile for use in primary care: the Framingham heart study. Circulation 117:743–753CrossRefGoogle Scholar
  17. 17.
    Sociedad Argentina de Cardiología. Área de normas y consensos (2018) Uso apropiado de las estatinas en la Argentina. Documento de posición. Rev Arg Cardiol 86(Supl. 1):1–13Google Scholar
  18. 18.
    Hermansen ML, Lindhardsen J, Torp-Pedersen C, Faurschou M, Jacobsen S (2017) The risk of cardiovascular morbidity and cardiovascular mortality in systemic lupus erythematosus and lupus nephritis: a Danish nationwide population-based cohort study. Rheumatology (Oxford) 56:709–715Google Scholar
  19. 19.
    Bessant R, Duncan R, Ambler G, Swanton J, Isenberg DA, Gordon C, Rahman A (2006) Prevalence of conventional and lupus-specific risk factors for cardiovascular disease in patients with systemic lupus erythematosus: a case-control study. Arthritis Rheum 55:892–899CrossRefGoogle Scholar
  20. 20.
    Medeiros MM, Xavier de Oliveira ÍM, Ribeiro ÁT (2016) Prevalence of metabolic syndrome in a cohort of systemic lupus erythematosus patients from Northeastern Brazil: association with disease activity, nephritis, smoking, and age. Rheumatol Int 36:117–124CrossRefGoogle Scholar
  21. 21.
    Yang L, Tao J, Tang X, Wang Y, He X, Xu G et al (2012) Prevalence and correlation of conventional and lupus-specific risk factors for cardiovascular disease in Chinese systemic lupus erythematosus patients. J Eur Acad Dermatol Venereol 26:95–101CrossRefGoogle Scholar
  22. 22.
    Westerweel PE, Luyten RK, Koomans HA, Derksen RH, Verhaar MC (2007) Premature atherosclerotic cardiovascular disease in systemic lupus erythematosus. Arthritis Rheum 56:1384–1396CrossRefGoogle Scholar
  23. 23.
    Fasano S, Margiotta DPE, Pierro L, Navarini L, Riccardi A, Afeltra A, Valentini G (2019) Prolonged remission is associated with a reduced risk of cardiovascular disease in patients with systemic lupus erythematosus: a GIRRCS (Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale) study. Clin Rheumatol 38:457–463CrossRefGoogle Scholar
  24. 24.
    Goldberg RJ, Urowitz MB, Ibanez D, Nikpour M, Gladman DD (2009) Risk factors for development of coronary artery disease in women with systemic lupus erythematosus. J Rheumatol 36:2454–2461CrossRefGoogle Scholar
  25. 25.
    Urowitz MB, Ibáñez D, Su J, Gladman DD (2016) Modified Framingham risk factor score for systemic lupus erythematosus. J Rheumatol 43:875–879CrossRefGoogle Scholar
  26. 26.
    Edwards N, Langford-Smith AWW, Parker BJ, Bruce IN, Reynolds JA, Alexander MY et al (2018) QRISK3 improves detection of cardiovascular disease risk in patients with systemic lupus erythematosus. Lupus Sci Med 5(1):e000272CrossRefGoogle Scholar
  27. 27.
    Plazak W, Gryga K, Dziedzic H, Tomkiewicz-Pajak L, Konieczynska M, Podolec P et al (2011) Influence of atorvastatin on coronary calcifications and myocardial perfusion defects in systemic lupus erythematosus patients: a prospective, randomized, double-masked, placebo-controlled study. Arthritis Res Ther 13:R117CrossRefGoogle Scholar
  28. 28.
    Mok CC, Wong CK, To CH, Lai JP, Lam CS (2011) Effects of rosuvastatin on vascular biomarkers and carotid atherosclerosis in lupus: a randomized, double-blind, placebo-controlled trial. Arthritis Care Res (Hoboken) 63:875–883CrossRefGoogle Scholar
  29. 29.
    Ruiz-Limon P, Barbarroja N, Perez-Sanchez C, Aguirre MA, Bertolaccini ML, Khamashta MA, Rodriguez-Ariza A, Almadén Y, Segui P, Khraiwesh H, Gonzalez-Reyes JA, Villalba JM, Collantes-Estevez E, Cuadrado MJ, Lopez-Pedrera C (2015) Atherosclerosis and cardiovascular disease in systemic lupus erythematosus: effects of in vivo statin treatment. Ann Rheum Dis 74:1450–1458CrossRefGoogle Scholar
  30. 30.
    Tan MKX, Heng TYJ, Mak A (2019) The potential use of metformin, dipyridamole, n-acetylcysteine and statins as adjunctive therapy for systemic lupus erythematosus. Cells Apr 6;8(4). Pii: E323Google Scholar
  31. 31.
    Rozo C, Chinenov Y, Maharaj RK, Gupta S, Leuenberger L, Kirou KA, Bykerk VP, Goodman SM, Salmon JE, Pernis AB (2017) Targeting the RHOA-ROCK pathway to reverse t-cell dysfunction in SLE. Ann Rheum Dis 76:740–747CrossRefGoogle Scholar
  32. 32.
    Jury EC, Isenberg DA, Mauri C, Ehrenstein MR (2006) Atorvastatin restores LCK expression and lipid raft-associated signaling in t cells from patients with systemic lupus erythematosus. J Immunol 177:7416–7422CrossRefGoogle Scholar
  33. 33.
    Janes PW, Ley SC, Magee AI, Kabouridis PS (2000) The role of lipid rafts in t cell antigen receptor (TCR) signalling. Semin Immunol 12:23–34CrossRefGoogle Scholar
  34. 34.
    Ferreira GA, Teixeira AL, Sato EI (2010) Atorvastatin therapy reduces interferon-regulated chemokine CXCL9 plasma levels in patients with systemic lupus erythematosus. Lupus 19:927–934CrossRefGoogle Scholar
  35. 35.
    Mach F, Sauty A, Iarossi AS, Sukhova GK, Neote K, Libby P, Luster AD (1999) Differential expression of three t lymphocyte-activating CXC chemokines by human atheroma-associated cells. J Clin Investig 104:1041–1050CrossRefGoogle Scholar
  36. 36.
    Sheikh AM, Ochi H, Manabe A, Masuda J (2005) Lysophosphatidylcholine posttranscriptionally inhibits interferon-gamma-induced IP-10, Mig and I-Tac expression in endothelial cells. Cardiovasc Res 65:263–271CrossRefGoogle Scholar
  37. 37.
    Amuro H, Ito T, Miyamoto R, Sugimoto H, Torii Y, Son Y, Nakamichi N, Yamazaki C, Hoshino K, Kaisho T, Ozaki Y, Inaba M, Amakawa R, Fukuhara S (2010) Statins, inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, function as inhibitors of cellular and molecular components involved in type I interferon production. Arthritis Rheum 62:2073–2085PubMedGoogle Scholar
  38. 38.
    Ferreira GA, Teixeira AL, Calderaro DC, Sato EI (2016) Atorvastatin reduced soluble receptors of TNF-α in systemic lupus erythematosus. Clin Exp Rheumatol 34:42–48PubMedGoogle Scholar
  39. 39.
    Parameswaran N, Patial S (2010) Tumor necrosis factor-α signaling in macrophages. Crit rev Eukaryot. Gene Expr 20:87–103CrossRefGoogle Scholar
  40. 40.
    De Backer G, Jankowski P, Kotseva K, Mirrakhimov E, Reiner Ž, Rydén L et al (2019) Management of dyslipidaemia in patients with coronary heart disease: results from the ESC-EORP EUROASPIRE V survey in 27 countries. Atherosclerosis 285:135–146CrossRefGoogle Scholar
  41. 41.
    Nikpour M, Urowitz MB, Ibanez D, Harvey PJ, Gladman DD (2011) Importance of cumulative exposure to elevated cholesterol and blood pressure in development of atherosclerotic coronary artery disease in systemic lupus erythematosus: a prospective proof-of-concept cohort study. Arthritis Res Ther 13(5):R156CrossRefGoogle Scholar

Copyright information

© International League of Associations for Rheumatology (ILAR) 2019

Authors and Affiliations

  1. 1.Hospital Italiano de Buenos AiresCiudad Autónoma de Buenos AiresArgentina

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