Coronary artery disease in rheumatoid arthritis: Epidemiology, pathogenesis, and risk factors
- Katherine P Liao, MD, MPH
Katherine P Liao, MD, MPH
- Instructor in Medicine
- Harvard Medical School
The prevalence of atherosclerotic coronary artery disease (CAD) is increased in patients with chronic inflammatory diseases such as systemic lupus erythematosus or rheumatoid arthritis (RA).
The epidemiologic evidence, possible pathogenetic mechanisms, and clinical relevance of CAD in RA will be reviewed here. The impact of CAD on the management of RA; other cardiac manifestations of RA, including pericarditis, myocarditis, atrioventricular block, valvular regurgitation, embolic events, and rheumatoid nodules; and the general clinical manifestations of RA are presented separately. (See "Coronary artery disease in rheumatoid arthritis: Diagnostic and therapeutic implications" and "Overview of the systemic and nonarticular manifestations of rheumatoid arthritis", section on 'Cardiac disease' and "Rheumatoid nodules", section on 'Cardiac nodules' and "Clinical manifestations of rheumatoid arthritis".)
An increased risk of premature death is observed in patients with rheumatoid arthritis (RA). This is largely due to cardiovascular disease, particularly coronary artery disease (CAD). (See "Disease outcome and functional capacity in rheumatoid arthritis", section on 'Comorbidity and mortality'.)
The reported incidence and prevalence of CAD in patients with RA varies based upon the specific manifestations of the disease, the population evaluated, and/or the screening and diagnostic methods utilized [1-7]. A meta-analysis of 24 observational studies comprising 111,758 patients concluded that the risk of CAD mortality was 59 percent higher in patients with RA than in the general population . Risk may be increased once symptoms develop and before patients meet formal classification criteria for the diagnosis of RA [9-11].
Many of the underlying mechanisms of pathogenesis of atherosclerosis are shared in patients with and without rheumatoid arthritis (RA). Among the general population, it is increasingly clear that inflammation has a significant role in the development of coronary artery disease (CAD) and that the innate and adaptive immune systems play an important role in the initiation and progression of atherosclerosis.
- Turesson C, Jarenros A, Jacobsson L. Increased incidence of cardiovascular disease in patients with rheumatoid arthritis: results from a community based study. Ann Rheum Dis 2004; 63:952.
- del Rincón ID, Williams K, Stern MP, et al. High incidence of cardiovascular events in a rheumatoid arthritis cohort not explained by traditional cardiac risk factors. Arthritis Rheum 2001; 44:2737.
- Solomon DH, Karlson EW, Rimm EB, et al. Cardiovascular morbidity and mortality in women diagnosed with rheumatoid arthritis. Circulation 2003; 107:1303.
- Fischer LM, Schlienger RG, Matter C, et al. Effect of rheumatoid arthritis or systemic lupus erythematosus on the risk of first-time acute myocardial infarction. Am J Cardiol 2004; 93:198.
- Gonzalez-Juanatey C, Llorca J, Testa A, et al. Increased prevalence of severe subclinical atherosclerotic findings in long-term treated rheumatoid arthritis patients without clinically evident atherosclerotic disease. Medicine (Baltimore) 2003; 82:407.
- Solomon DH, Goodson NJ, Katz JN, et al. Patterns of cardiovascular risk in rheumatoid arthritis. Ann Rheum Dis 2006; 65:1608.
- Wolfe F, Michaud K. The risk of myocardial infarction and pharmacologic and nonpharmacologic myocardial infarction predictors in rheumatoid arthritis: a cohort and nested case-control analysis. Arthritis Rheum 2008; 58:2612.
- Aviña-Zubieta JA, Choi HK, Sadatsafavi M, et al. Risk of cardiovascular mortality in patients with rheumatoid arthritis: a meta-analysis of observational studies. Arthritis Rheum 2008; 59:1690.
- Maradit-Kremers H, Crowson CS, Nicola PJ, et al. Increased unrecognized coronary heart disease and sudden deaths in rheumatoid arthritis: a population-based cohort study. Arthritis Rheum 2005; 52:402.
- Kremers HM, Crowson CS, Therneau TM, et al. High ten-year risk of cardiovascular disease in newly diagnosed rheumatoid arthritis patients: a population-based cohort study. Arthritis Rheum 2008; 58:2268.
- Holmqvist ME, Wedrén S, Jacobsson LT, et al. No increased occurrence of ischemic heart disease prior to the onset of rheumatoid arthritis: results from two Swedish population-based rheumatoid arthritis cohorts. Arthritis Rheum 2009; 60:2861.
- Van Doornum S, McColl G, Wicks IP. Accelerated atherosclerosis: an extraarticular feature of rheumatoid arthritis? Arthritis Rheum 2002; 46:862.
- Wållberg-Jonsson S, Cvetkovic JT, Sundqvist KG, et al. Activation of the immune system and inflammatory activity in relation to markers of atherothrombotic disease and atherosclerosis in rheumatoid arthritis. J Rheumatol 2002; 29:875.
- Wållberg-Jonsson S, Cederfelt M, Rantapää Dahlqvist S. Hemostatic factors and cardiovascular disease in active rheumatoid arthritis: an 8 year followup study. J Rheumatol 2000; 27:71.
- Grisar J, Aletaha D, Steiner CW, et al. Depletion of endothelial progenitor cells in the peripheral blood of patients with rheumatoid arthritis. Circulation 2005; 111:204.
- Park YB, Choi HK, Kim MY, et al. Effects of antirheumatic therapy on serum lipid levels in patients with rheumatoid arthritis: a prospective study. Am J Med 2002; 113:188.
- Rho YH, Chung CP, Oeser A, et al. Inflammatory mediators and premature coronary atherosclerosis in rheumatoid arthritis. Arthritis Rheum 2009; 61:1580.
- Rho YH, Chung CP, Oeser A, et al. Interaction between oxidative stress and high-density lipoprotein cholesterol is associated with severity of coronary artery calcification in rheumatoid arthritis. Arthritis Care Res (Hoboken) 2010; 62:1473.
- Yiu KH, Wang S, Mok MY, et al. Role of circulating endothelial progenitor cells in patients with rheumatoid arthritis with coronary calcification. J Rheumatol 2010; 37:529.
- Wrigley BJ, Lip GY, Shantsila E. Coronary atherosclerosis in rheumatoid arthritis: could endothelial progenitor cells be the missing link? J Rheumatol 2010; 37:479.
- Mäki-Petäjä KM, Elkhawad M, Cheriyan J, et al. Anti-tumor necrosis factor-α therapy reduces aortic inflammation and stiffness in patients with rheumatoid arthritis. Circulation 2012; 126:2473.
- Niessner A, Sato K, Chaikof EL, et al. Pathogen-sensing plasmacytoid dendritic cells stimulate cytotoxic T-cell function in the atherosclerotic plaque through interferon-alpha. Circulation 2006; 114:2482.
- Liuzzo G, Goronzy JJ, Yang H, et al. Monoclonal T-cell proliferation and plaque instability in acute coronary syndromes. Circulation 2000; 101:2883.
- Dessein PH, Joffe BI. Insulin resistance and impaired beta cell function in rheumatoid arthritis. Arthritis Rheum 2006; 54:2765.
- Chung CP, Oeser A, Solus JF, et al. Inflammation-associated insulin resistance: differential effects in rheumatoid arthritis and systemic lupus erythematosus define potential mechanisms. Arthritis Rheum 2008; 58:2105.
- Chung CP, Oeser A, Solus JF, et al. Prevalence of the metabolic syndrome is increased in rheumatoid arthritis and is associated with coronary atherosclerosis. Atherosclerosis 2008; 196:756.
- Chung CP, Oeser A, Raggi P, et al. Increased coronary-artery atherosclerosis in rheumatoid arthritis: relationship to disease duration and cardiovascular risk factors. Arthritis Rheum 2005; 52:3045.
- Dixon WG, Watson KD, Lunt M, et al. Reduction in the incidence of myocardial infarction in patients with rheumatoid arthritis who respond to anti-tumor necrosis factor alpha therapy: results from the British Society for Rheumatology Biologics Register. Arthritis Rheum 2007; 56:2905.
- Aubry MC, Maradit-Kremers H, Reinalda MS, et al. Differences in atherosclerotic coronary heart disease between subjects with and without rheumatoid arthritis. J Rheumatol 2007; 34:937.
- Södergren A, Karp K, Boman K, et al. Atherosclerosis in early rheumatoid arthritis: very early endothelial activation and rapid progression of intima media thickness. Arthritis Res Ther 2010; 12:R158.
- Peters MJ, van Halm VP, Nurmohamed MT, et al. Relations between autoantibodies against oxidized low-density lipoprotein, inflammation, subclinical atherosclerosis, and cardiovascular disease in rheumatoid arthritis. J Rheumatol 2008; 35:1495.
- Solomon DH, Curhan GC, Rimm EB, et al. Cardiovascular risk factors in women with and without rheumatoid arthritis. Arthritis Rheum 2004; 50:3444.
- Boyer JF, Gourraud PA, Cantagrel A, et al. Traditional cardiovascular risk factors in rheumatoid arthritis: a meta-analysis. Joint Bone Spine 2011; 78:179.
- Chung CP, Oeser A, Avalos I, 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.
- Eurenius E, Stenström CH. Physical activity, physical fitness, and general health perception among individuals with rheumatoid arthritis. Arthritis Rheum 2005; 53:48.
- Roman MJ, Moeller E, Davis A, et al. Preclinical carotid atherosclerosis in patients with rheumatoid arthritis. Ann Intern Med 2006; 144:249.
- Del Rincón I, Williams K, Stern MP, et al. Association between carotid atherosclerosis and markers of inflammation in rheumatoid arthritis patients and healthy subjects. Arthritis Rheum 2003; 48:1833.
- Kao AH, Wasko MC, Krishnaswami S, et al. C-reactive protein and coronary artery calcium in asymptomatic women with systemic lupus erythematosus or rheumatoid arthritis. Am J Cardiol 2008; 102:755.
- Kao AH, Krishnaswami S, Cunningham A, et al. Subclinical coronary artery calcification and relationship to disease duration in women with rheumatoid arthritis. J Rheumatol 2008; 35:61.
- Davis JM 3rd, Maradit Kremers H, Crowson CS, et al. Glucocorticoids and cardiovascular events in rheumatoid arthritis: a population-based cohort study. Arthritis Rheum 2007; 56:820.
- McMahon M, Grossman J, FitzGerald J, et al. Proinflammatory high-density lipoprotein as a biomarker for atherosclerosis in patients with systemic lupus erythematosus and rheumatoid arthritis. Arthritis Rheum 2006; 54:2541.
- Charles-Schoeman C, Watanabe J, Lee YY, et al. Abnormal function of high-density lipoprotein is associated with poor disease control and an altered protein cargo in rheumatoid arthritis. Arthritis Rheum 2009; 60:2870.
- Charles-Schoeman C, Lee YY, Grijalva V, et al. Cholesterol efflux by high density lipoproteins is impaired in patients with active rheumatoid arthritis. Ann Rheum Dis 2012; 71:1157.