Dear Editor,
We read with great interest the article of Petri et al [1] addressing the important issue of the effects of statins on vascular disease of patients with systemic lupus erythematosus (SLE). This randomized clinical trial showed no benefit of atorvastatin in the progression of subclinical atherosclerosis in 200 patients with SLE, most of them with normal lipid levels. This result is of high clinical relevance, however, some questions regarding the homogeneity of both treatment arms may limit its
interpretation.
There were no differences between both groups in the frequency of hypertension and diabetes mellitus, the proportion of men, the age at recruitment or the baseline lipid levels. However, there is no mention to smoking. Moreover, treatments received by the patients up to recruitment or during the study period are not reported.
Chronic treatment with glucocorticoids may increase the risk of developing atherosclerosis. In the general population, doses above 7.5 mg/day of prednisone used during 1 to 5 years increased the risk of cardiovascular
disease [2]. In 539 patients with SLE from the Hopkins Lupus Cohort [3], cardiovascular damage was associated with prednisone therapy, either the cumulative dose (coronary artery disease) or the use of doses over 60 mg/day (stroke). On the other hand, the antiinflammatory effects of prednisone may have beneficial effects on the progression of atherosclerotic plaques [4].
Antimalarials may have a beneficial effect on the lipid profile of patients with rheumatoid arthritis and SLE, especially those treated with steroids [5-10]. In a previous study by Petri et al [6] studying 264 SLE
patients of the Baltimore Lupus Cohort, HCQ was associated with lower serum cholesterol levels in the longitudinal regression analysis. The authors calculated that HCQ was able to "balance" the adverse effect of 10mg of prednisone on cholesterol levels. Roman et al found a significant
negative association between the use of HCQ and the presence of carotid plaques in 197 SLE patients [4]. Although data on this issue are conflicting, a beneficial affect of antimalarial therapy on the development and progression of atherosclerosis cannot be excluded [11].
Thus, to fully understand the clinical applicability of the results of this study [1], patients included in both therapeutic arms should prove homogeneous in terms of the proportion of those smoking and receiving treatment with prednisone and hydroxychloroquine.
References
1. Petri MA, Kiani AN, Post W, et al. Lupus
Atherosclerosis Prevention Study (LAPS). Ann Rheum Dis 2010 Dec 21:[Epub ahead of print].
2. Wei L, MacDonald TM, Walker BR. Taking glucocorticoids by prescription is associated with subsequent cardiovascular disease. Ann Intern Med 2004;141(10):764-770.
3. Zonana-Nacach A, Barr SG, Magder LS, et al. Damage in systemic lupus erythematosus and its association with corticosteroids. Arthritis Rheum 2000;43(8):1801-1808.
4. Roman MJ, Shanker BA, Davis A, et al. Prevalence and correlates of accelerated atherosclerosis in systemic lupus erythematosus. N Engl J Med 2003;349(25):2399-2406.
5. Rahman P, Gladman DD, Urowitz MB, et al. The
cholesterol lowering effect of antimalarial drugs is enhanced in patients with lupus taking corticosteroid drugs. J Rheumatol 1999;26(2):325-330.
6. Petri M, Lakatta C, Magder L, et al. Effect of prednisone and hydroxychloroquine on coronary artery disease risk factors in systemic lupus erythematosus: a longitudinal data analysis. Am J Med 1994;96(3):254-259.
7. Hodis HN, Quismorio FP, Jr., Wickham E, et al. The lipid, lipoprotein, and apolipoprotein effects of hydroxychloroquine in patients with systemic lupus erythematosus. J Rheumatol 1993;20(4):661-665.
8. Wallace DJ, Metzger AL, Stecher VJ, et al.
Cholesterol-lowering effect of hydroxychloroquine in patients with rheumatic disease: reversal of deleterious effects of steroids on lipids. Am J Med 1990;89(3):322-326.
9. Munro R, Morrison E, McDonald AG,et al. Effect of disease modifying agents on the lipid profiles of patients with rheumatoid arthritis. Ann Rheum Dis 1997;56(6):374-377.
10. Costedoat-Chalumeau N, Leroux G, Piette J-C, et al. Antimalarials and systemic lupus erythematosus. In: Lahita RG, Tsokos G, Buyon JP, Koike T. Systemic lupus erythematosus. Elsevier. 5th Edition 2010;1061-81.
11. Ruiz-Irastorza G, Ramos-Casals M, Brito-Zeron P, et al. Clinical efficacy and side effects of antimalarials in systemic lupus erythematosus: a systematic review. Ann Rheum Dis 2010;69(1):20-28.
Dear Editor,
We read with great interest the article of Petri et al [1] addressing the important issue of the effects of statins on vascular disease of patients with systemic lupus erythematosus (SLE). This randomized clinical trial showed no benefit of atorvastatin in the progression of subclinical atherosclerosis in 200 patients with SLE, most of them with normal lipid levels. This result is of high clinical relevance, however, some questions regarding the homogeneity of both treatment arms may limit its interpretation.
There were no differences between both groups in the frequency of hypertension and diabetes mellitus, the proportion of men, the age at recruitment or the baseline lipid levels. However, there is no mention to smoking. Moreover, treatments received by the patients up to recruitment or during the study period are not reported. Chronic treatment with glucocorticoids may increase the risk of developing atherosclerosis. In the general population, doses above 7.5 mg/day of prednisone used during 1 to 5 years increased the risk of cardiovascular disease [2]. In 539 patients with SLE from the Hopkins Lupus Cohort [3], cardiovascular damage was associated with prednisone therapy, either the cumulative dose (coronary artery disease) or the use of doses over 60 mg/day (stroke). On the other hand, the antiinflammatory effects of prednisone may have beneficial effects on the progression of atherosclerotic plaques [4].
Antimalarials may have a beneficial effect on the lipid profile of patients with rheumatoid arthritis and SLE, especially those treated with steroids [5-10]. In a previous study by Petri et al [6] studying 264 SLE patients of the Baltimore Lupus Cohort, HCQ was associated with lower serum cholesterol levels in the longitudinal regression analysis. The authors calculated that HCQ was able to "balance" the adverse effect of 10mg of prednisone on cholesterol levels. Roman et al found a significant negative association between the use of HCQ and the presence of carotid plaques in 197 SLE patients [4]. Although data on this issue are conflicting, a beneficial affect of antimalarial therapy on the development and progression of atherosclerosis cannot be excluded [11].
Thus, to fully understand the clinical applicability of the results of this study [1], patients included in both therapeutic arms should prove homogeneous in terms of the proportion of those smoking and receiving treatment with prednisone and hydroxychloroquine.
References
1. Petri MA, Kiani AN, Post W, et al. Lupus Atherosclerosis Prevention Study (LAPS). Ann Rheum Dis 2010 Dec 21:[Epub ahead of print].
2. Wei L, MacDonald TM, Walker BR. Taking glucocorticoids by prescription is associated with subsequent cardiovascular disease. Ann Intern Med 2004;141(10):764-770.
3. Zonana-Nacach A, Barr SG, Magder LS, et al. Damage in systemic lupus erythematosus and its association with corticosteroids. Arthritis Rheum 2000;43(8):1801-1808.
4. Roman MJ, Shanker BA, Davis A, et al. Prevalence and correlates of accelerated atherosclerosis in systemic lupus erythematosus. N Engl J Med 2003;349(25):2399-2406.
5. Rahman P, Gladman DD, Urowitz MB, et al. The cholesterol lowering effect of antimalarial drugs is enhanced in patients with lupus taking corticosteroid drugs. J Rheumatol 1999;26(2):325-330.
6. Petri M, Lakatta C, Magder L, et al. Effect of prednisone and hydroxychloroquine on coronary artery disease risk factors in systemic lupus erythematosus: a longitudinal data analysis. Am J Med 1994;96(3):254-259.
7. Hodis HN, Quismorio FP, Jr., Wickham E, et al. The lipid, lipoprotein, and apolipoprotein effects of hydroxychloroquine in patients with systemic lupus erythematosus. J Rheumatol 1993;20(4):661-665.
8. Wallace DJ, Metzger AL, Stecher VJ, et al. Cholesterol-lowering effect of hydroxychloroquine in patients with rheumatic disease: reversal of deleterious effects of steroids on lipids. Am J Med 1990;89(3):322-326.
9. Munro R, Morrison E, McDonald AG,et al. Effect of disease modifying agents on the lipid profiles of patients with rheumatoid arthritis. Ann Rheum Dis 1997;56(6):374-377.
10. Costedoat-Chalumeau N, Leroux G, Piette J-C, et al. Antimalarials and systemic lupus erythematosus. In: Lahita RG, Tsokos G, Buyon JP, Koike T. Systemic lupus erythematosus. Elsevier. 5th Edition 2010;1061-81.
11. Ruiz-Irastorza G, Ramos-Casals M, Brito-Zeron P, et al. Clinical efficacy and side effects of antimalarials in systemic lupus erythematosus: a systematic review. Ann Rheum Dis 2010;69(1):20-28.