Drugs Used in the Treatment of Rheumatoid Arthritis: Relationship between Current Use and Cardiovascular Risk Factors

Young Hee Rho, Annette Oeser, Cecilia P Chung, Ginger L Milne, C Michael Stein, Young Hee Rho, Annette Oeser, Cecilia P Chung, Ginger L Milne, C Michael Stein

Abstract

OBJECTIVES: Drugs used for the treatment of rheumatoid arthritis (RA) have the potential to affect cardiovascular risk factors. There is concern that corticosteroids, non-steroidal anti-inflammatory drugs (NSAIDs) and COX-2 inhibitors could affect cardiovascular risk adversely, while drugs such as the antimalarial, hydroxychloroquine, may have beneficial effects. However, there is limited information about cardiovascular risk factors in patients with RA receiving different drugs. METHODS: We measured cardiovascular risk factors including systolic and diastolic blood pressure, serum HDL and LDL cholesterol, glucose and homocysteine concentrations and urinary F(2)-isoprostane excretion in 169 patients with RA. Risk factors were compared according to current use of corticosteroids, methotrexate, antimalarials, NSAIDs, COX-2 inhibitors, leflunomide and TNF-alpha blockers. Comparisons were adjusted for age, sex, race, disease activity (DAS28 score), current hypertension, diabetes, smoking status and statin use. RESULTS: No cardiovascular risk factor differed significantly among current users and non-users of NSAIDs, COX-2 inhibitors, methotrexate and TNF-alpha blockers. Serum HDL cholesterol concentrations were significantly higher in patients currently receiving corticosteroids (42.2 +/- 10.5 vs. 50.2 +/- 15.3 mg/dL, adjusted P < 0.001). Diastolic blood pressure (75.9 +/- 11.2 vs. 72.0 +/- 9.1 mm Hg, adjusted P = 0.02), serum LDL cholesterol (115.6 +/- 34.7 vs. 103.7 +/- 27.8 mg/dL, adjusted P = 0.03) and triglyceride concentrations (157.7 +/- 202.6 vs. 105.5 +/- 50.5 mg/dL, adjusted P = 0.03) were significantly lower in patients taking antimalarial drugs. Plasma glucose was significantly lower in current lefunomide users (93.0 +/- 19.2 vs. 83.6 +/- 13.4 mg/dL, adjusted P = 0.006). CONCLUSIONS: In a cross-sectional setting drugs used to treat RA did not have major adverse effects on cardiovascular risk factors and use of antimalarials was associated with beneficial lipid profiles.

References

    1. Chung CP, Oeser A, Raggi P, Gebretsadik T, Shintani AK, Sokka T, et al. Increased coronary-artery atherosclerosis in rheumatoid arthritis: Relationship to disease duration and cardiovascular risk factors. Arthritis Rheum. 2005;52:3045–53.
    1. Pincus T, Callahan LF. Taking mortality in rheumatoid arthritis seriously—Predictive markers, socioeconomic status and comorbidity. J Rheumatol. 1986;13:841–5.
    1. Choi HK, Hernan MA, Seeger JD, Robins JM, Wolfe F. Methotrexate and mortality in patients with rheumatoid arthritis: A prospective study. Lancet. 2002;359:1173–7.
    1. Naranjo A, Sokka T, Descalzo MA, Calvo-Alen J, Horslev-Petersen K, Luukkainen RK, et al. Cardiovascular disease in patients with rheumatoid arthritis: Results from the QUEST-RA study. Arthritis Res Ther. 2008;10:R30.
    1. Bresalier RS, Sandler RS, Quan H, Bolognese JA, Oxenius B, Horgan K, et al. Cardiovascular events associated with rofecoxib in a colorectal adenoma chemoprevention trial. N Engl J Med. 2005;352:1092–102.
    1. Bertagnolli MM, Eagle CJ, Zauber AG, Redston M, Solomon SD, Kim K, et al. Celecoxib for the prevention of sporadic colorectal adenomas. N Engl J Med. 2006;355:873–84.
    1. Brooks PM. Non-steroidal anti-inflammatory drugs. In: Hochberg MC, Silman AJ, Smolen JS, Weinblatt ME, Weisman MH, editors. Rheumatology. 3rd edition. London: Elsevier; 2003. pp. 377–84.
    1. Buchman AL. Side effects of corticosteroid therapy. J Clin Gastroenterol. 2001;33:289–94.
    1. Petri M. Hydroxychloroquine use in the Baltimore lupus cohort: Effects on lipids, glucose and thrombosis. Lupus. 1996;5(suppl 1):S16–22.
    1. Chung CP, Oeser A, Avalos I, Gebretsadik T, Shintani A, Raggi P, et al. Utility of the Framingham risk score to predict the presence of coronary atherosclerosis in patients with rheumatoid arthritis. Arthritis Res Ther. 2006;8:R186.
    1. Chung CP, Oeser A, Solus JF, Gebretsadik T, Shintani A, Avalos I, et al. Inflammation-associated insulin resistance: Differential effects in rheumatoid arthritis and systemic lupus erythematosus define potential mechanisms. Arthritis Rheum. 2008;58:2105–12.
    1. Solus J, Chung CP, Oeser A, Avalos I, Gebretsadik T, Shintani A, et al. Amino-terminal fragment of the prohormone brain-type natriuretic peptide in rheumatoid arthritis. Arthritis Rheum. 2008;58:2662–9.
    1. Prevoo ML, van ‘t Hof MA, Kuper HH, van Leeuwen MA, van de Putte LB, van Riel PL. Modified disease activity scores that include twenty-eight-joint counts. Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheum. 1995;38:44–8.
    1. Montuschi P, Barnes P, Roberts LJ. Insights into oxidative stress: The isoprostanes. Curr Med Chem. 2007;14:703–17.
    1. Milne GL, Sanchez SC, Musiek ES, Morrow JD. Quantification of F2-isoprostanes as a biomarker of oxidative stress. Nat Protoc. 2007;2:221–6.
    1. Chung CP, Oeser A, Solus JF, Avalos I, Gebretsadik T, Shintani A, et al. Prevalence of the metabolic syndrome is increased in rheumatoid arthritis and is associated with coronary atherosclerosis. Atherosclerosis. 2007
    1. Sholter DE, Armstrong PW. Adverse effects of corticosteroids on the cardiovascular system. Can J Cardiol. 2000;16:505–11.
    1. Barter PJ, Caulfield M, Eriksson M, Grundy SM, Kastelein JJ, Komajda M, et al. Effects of torcetrapib in patients at high risk for coronary events. N Engl J Med. 2007;357:2109–22.
    1. Pearson H. When good cholesterol turns bad. Nature. 2006;444:794–5.
    1. Rho YH, Oeser A, Chung CP, Morrow JD, Stein CM. Drugs to treat systemic Lupus Erythematosus: Relationship between current use and cardiovascular risk factors. Arch Drug Inf. 2008;1:23–8.
    1. Desouza C, Keebler M, McNamara DB, Fonseca V. Drugs affecting homocysteine metabolism: Impact on cardiovascular risk. Drugs. 2002;62:605–16.
    1. Whittle SL, Hughes RA. Folate supplementation and methotrexate treatment in rheumatoid arthritis: A review. Rheumatology (Oxford) 2004;43:267–71.
    1. Petri M, Lakatta C, Magder L, Goldman D. Effect of prednisone and hydroxychloroquine on coronary artery disease risk factors in systemic lupus erythematosus: A longitudinal data analysis. Am J Med. 1994;96:254–9.
    1. Anigbogu CN, Adigun SA, Inyang I, Adegunloye BJ. Chloroquine reduces blood pressure and forearm vascular resistance and increases forearm blood flow in healthy young adults. Clin Physiol. 1993;13:209–16.
    1. Musabayane CT, Musvibe A, Wenyika J, Munjeri O, Osim EE. Chloroquine influences renal function in rural Zimbabweans with acute transient fever. Ren Fail. 1999;21:189–97.
    1. Rozman B, Praprotnik S, Logar D, Tomsic M, Hojnik M, Kos-Golja M, et al. Leflunomide and hypertension. Ann Rheum Dis. 2002;61:567–9.
    1. Coblyn JS, Shadick N, Helfgott S. Leflunomide-associated weight loss in rheumatoid arthritis. Arthritis Rheum. 2001;44:1048–51.
    1. Huvers FC, Popa C, Netea MG, van den Hoogen FH, Tack CJ. Improved insulin sensitivity by anti-TNFalpha antibody treatment in patients with rheumatic diseases. Ann Rheum Dis. 2007;66:558–9.
    1. Popa C, van den Hoogen FH, Radstake TR, Netea MG, Eijsbouts AE, den Heijer M, et al. Modulation of lipoprotein plasma concentrations during long-term anti-TNF therapy in patients with active rheumatoid arthritis. Ann Rheum Dis. 2007;66:1503–7.

Source: PubMed

3
Prenumerera