The online version of this article (doi:10.1186/ar3402) contains supplementary material, which is available to authorized users.
The authors declare that they have no competing interests.
WP was responsible for the study concept and design, acquisition, analysis and interpretation of the data, and manuscript preparation. KG, HD, LTP, and MK acquired and analyzed the data. PP and JM were responsible for data interpretation and manuscript preparation. All authors read and approved the final version of the manuscript.
Mortality in systemic lupus erythematosus (SLE) patients is influenced by an increased occurrence of severe cardiovascular complications. Statins have been proven to protect a wide spectrum of SLE patients from these complications. This study was conducted to determine the possible efficacy of atorvastatin in SLE patients as assessed by multi-detector computed tomography (MDCT)-based coronary calcium scoring and single photon emission computed tomography (SPECT) of the myocardium.
Sixty SLE patients in stable clinical conditions were randomized to receive either atorvastatin (40 mg daily; n = 28) or placebo (n = 32). Clinical and biochemical evaluation together with MDCT-based coronary calcium scoring and SPECT studies (Tc-99 m sestamibi) were performed at the time of randomization and after 1 year of treatment.
At randomization, SPECT revealed perfusion defects at rest in 22 (36.7%) patients and exercise-induced defects in 8 (13.3%), whereas MDCT revealed coronary calcifications in 15 subjects (25%). Coronary calcium deposits increased after 1 year in the placebo group (plaque volume change from 35.2 ± 44.9 to 62.9 ± 72.4, P < 0.05; calcium score from 32.1 ± 39.1 to 59.5 ± 64.4; P < 0.05), but not in the atorvastatin group (plaque volume 54.5 ± 62.4 vs. 51.0 ± 47.6, P not significant; calcium score 44.8 ± 50.6 vs. 54.9 ± 62.5, P not significant). The atorvastatin group showed a decrease in total serum cholesterol (from 5.1 ± 1.2 to 4.4 ± 0.7 mmol/L, P < 0.05), LDL cholesterol (2.9 ± 1.0 to 2.3 ± 0.6 mmol/L, P < 0.05), triglycerides (1.6 ± 0.6 to 1.2 ± 0.5 mmol/L, P < 0.05), and C-reactive protein (CRP) (4.4 ± 4.1 to 2.7 ± 1.7 mg/L, P < 0.05). There was no change in the mean Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score in patients from both groups. Perfusion defects observed at randomization showed no change after one year treatment with atorvastatin.
In SLE patients 40 mg of atorvastatin daily for 1 year led to a decrease in serum lipids and CRP levels. Additionally the progression of atherosclerosis, as assessed by MDCT-based coronary calcium scoring, is restrained by atorvastatin treatment. The value of statin treatment in patients with SLE free from cardiovascular disease clinical symptoms should be addressed in large, prospective clinical trials.
Lopez-Pedrera Ch, Aguirre MA, Barbarroja N, Cuadrado MJ: Accelerated atherosclerosis in systemic lupus erythematosus: role of proinflammatory cytokines and therapeutic approaches. J Biomed Biotechnol. 2010, pii: 607084-
Pons-Estel GJ, Gonzales LA, Zhang J, Burgos Pl, Reveille JD, Vila LM, Alarcon GS: Predictors of cardiovascular damage in patients with systemic lupus erythematosus: data from LUMINA (LXVIII), a multicenter US cohort. Rheumatology. 2009, 48: 817-822. 10.1093/rheumatology/kep102. PubMedCentralCrossRefPubMed
ALLHAT-LLT Officers and Coordinators: Major outcomes in moderately-hypercholesterolemic, hypertensive patients randomized to pravastatin vs. usual care: the antihypertensive and lipid-lowering treatment to prevent heart attack trial (ALLHAT-LLT). JAMA. 2002, 288: 2998-3007. 10.1001/jama.288.23.2998. CrossRef
Shepherd J, Cobbe SM, Ford I, Isles CG, Lorimer AR, MacFarlane PW, McKillop JH, Packard CJ: Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. West of Scotland Coronary Prevention Study Group. N Engl J Med. 1995, 333: 1301-1307. 10.1056/NEJM199511163332001. CrossRefPubMed
Schwartz G, Olsson A, Ezekowitz M, Ganz P, Oliver M, Waters D, Zeiher A, Chaitman B, Leslie S, Stern T: Effect of atorvastatin on early recurrent ischaemic events in acute coronary syndromes. The MIRACL study: a randomized controlled trial. JAMA. 2001, 285: 1711-1718. 10.1001/jama.285.13.1711. CrossRefPubMed
Nissen SE, Nicholls SJ, Sipahi I, Libby P, Raichlen JS, Ballantyne CM, Davignon J, Erbel R, Fruchart JC, Tardif JC, Schoenhagen P, Crowe T, Cain V, Wolski K, Goormastic M, Tuzcu EM: Effect of very high-intensity statin therapy on regression of coronary atherosclerosis: the ASTEROID trial. JAMA. 2006, 295: 1556-1565. 10.1001/jama.295.13.jpc60002. CrossRefPubMed
Giri S, Parke AL, Waters DD: Controlling cardiovascular risk factors in systemic lupus erythematosus. J Musculoskel Med. 1998, 15: 42-52.
Urowitz MB, Gladman DD: How to improve morbidity and mortality in systemic lupus erythematosus. Rheumatology (Oxford). 2000, 39: 238-244. 10.1093/rheumatology/39.3.238. CrossRef
Samon JE, Roman MJ: Accelerated atherosclerosis in systemic lupus erythematosus: implications for patient management. Curr Opin Rheumatol. 2001, 13: 341-344. 10.1097/00002281-200109000-00001. CrossRef
Smolen J, Weisman M: Connective tissue disorders. Rheumatology. Edited by: Hochberg M, Silman A, Smolen J, Weinblatt M, Weisman M. 2008, Philadelphia, Mosby Elsevier, 1205-1485.
Smilde TJ, van Wissen S, Wollersheim H, Trip MD, Kastelein JJ, Stalenhoef AF: Effect of aggressive versus conventional lipid lowering on atherosclerosis progression in familial hypercholesterolaemia (ASAP): a prospective, randomized, double-blind study. Lancet. 2001, 357: 577-581. 10.1016/S0140-6736(00)04053-8. CrossRefPubMed
Taylor AJ, Kent SM, Flaherty PJ, Coyle LC, Markwood TT, Vemalis MN: ARBITER: arterial biology for the investigation of the treatment effects of reducing cholesterol. A randomized trial comparing the effects of atorvastatin and pravastatin on carotid intima media thickness. Circulation. 2002, 106: 2055-2060. 10.1161/01.CIR.0000034508.55617.65. CrossRefPubMed
Agatson AS, Janowitz WR, Hildner FJ, Zusmer NR, Viamonte M, Detrano R: Quantification of coronary artery calcium using ultrafast computed tomography. J Am Coll Cardiol. 1990, 15: 827-832. 10.1016/0735-1097(90)90282-T. CrossRef
Swadzba J, de Clerck LS, Stevens WJ, Bridts CH, van Cotthem KA, Musial J, Jankowski M, Szczeklik A: Anticardiolipin antibodies, anti-β2-glycoprotein I, antiprothrombin antibodies and lupus anticoagulant in patients with systemic lupus erythematosus with a history of thrombosis. J Rheumatol. 1997, 24: 1710-1715. PubMed
Pengo V, Tripodi A, Reber G, Rand JH, Ortel TL, Galli M, De Groot PG: Update of the guidelines for lupus anticoagulant detection. Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibody of the Scientific and Standarisation Committee of the International Society on Thrombosis and Haemostasis. J Thromb Haemost. 2009, 7: 1737-1740. 10.1111/j.1538-7836.2009.03555.x. CrossRefPubMed
Miyakis S, Lockshin MD, Atsumi T, Branch DW, Brey RL, Cervera R, Derksen RH, De Groot PG, Koike T, Meroni PL, Reber G, Shoenfeld Y, Tincani A, Vlachoyiannopoulos PG, Krilis SA: International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Heamost. 2006, 4: 295-306. 10.1111/j.1538-7836.2006.01753.x. CrossRef
Permarheum SLEDAI Calculator. [ http://www.permarheum.org/SLEDAI.html]
Lin CC, Ding HJ, Chen YW, Wang JJ, Ho ST, Kao A: Usefulness of technetium-99 m sestamibi myocardial perfusion SPECT in detection of cardiovascular involvement in patients with systemic lupus erythematosus or systemic sclerosis. Int J Cardiol. 2003, 92: 157-161. 10.1016/S0167-5273(03)00106-2. CrossRefPubMed
Vanzetto G, Ormezzano O, Fagret D, Comet M, Denis B, Machecourt J: Long term additive prognostic value of thalium-201 myocardial perfusion imaging over clinical and exercise stress test in low to intermediate risk patients: study in 1137 patients with 6-year follow-up. Circulation. 1999, 100: 1521-1527. CrossRefPubMed
Hachamovitch R, Berman DS, Shaw LJ, Kiat H, Cohen I, Cabico JA, Friedman J, Diamond GA: Incremental prognostic value of myocardial perfusion single photon emission computed tomography for the prediction of cardiac death: differential stratification for risk of cardiac death and myocardial infarction. Circulation. 1998, 97: 535-543. CrossRefPubMed
Kao AH, Wasko MCM, Krishnaswami S, Wagner J, Edmundowicz D, Shaw P, Cunningham AL, Danchenko N, Sutton-Tyrrell K, Tracy RP, Kuller LH, Manzi S: C-reactive protein and coronary artery calcium in asymptomatic women with systemic lupus erythematosus or rheumatoid arthritis. Am J Cardiol. 2008, 102: 755-760. 10.1016/j.amjcard.2008.04.059. PubMedCentralCrossRefPubMed
Uebleis C, Becker A, Griesshammer I, Cumming P, Becker C, Schmidt M, Barterstein P, Hacker M: Stable coronary artery disease: prognostic value of myocardial perfusion SPECT in relation to coronary calcium scoring - long-term follow-up. Radiology. 2009, 252: 682-690. 10.1148/radiol.2531082137. CrossRefPubMed
Srivastana M, Rencic A, Diglio G, Santana H, Bonitz P, Watson R, Ha E, Anhalt GJ, Provost TT, Nousari CH: Drug-induced, Ro/SSA-positive cutaneous lupus erythematosus. Arch Dermatol. 2003, 139: 45-49. 10.1001/archderm.139.1.45.
Long BR, Leya F: The role of antiphospholipid syndrome in cardiovascular disease. Hematol Oncol Clin N Am. 2008, 22: 79-94. 10.1016/j.hoc.2007.10.002. CrossRef
- Influence of atorvastatin on coronary calcifications and myocardial perfusion defects in systemic lupus erythematosus patients: a prospective, randomized, double-masked, placebo-controlled study
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