Does rheumatoid arthritis equal diabetes mellitus as an independent risk factor for cardiovascular disease? A prospective study.

OBJECTIVE Rheumatoid arthritis (RA) is associated with an increased risk of cardiovascular disease (CVD), but longitudinal observations are limited and the precise magnitude is unknown. We prospectively assessed the incidence of CVD in patients with RA compared with patients with type 2 diabetes mellitus (DM) and the general population. METHODS The 3-year incidence rate of CVD was determined in a prospective cohort (the Cardiovascular Research and Rheumatoid Arthritis Study) of 353 outpatients with RA, and was compared with that in 1,852 population-based cohort study participants (155 had type 2 DM). We investigated fatal and nonfatal CVD (according to International Classification of Diseases, Ninth Revision criteria) and used Cox proportional hazards models to assess the incidence of CVD in RA, type 2 DM, and the general population. RESULTS The 3-year incidence of CVD was 9.0% in patients with RA and 4.3% in the general population, corresponding with an incidence rate of 3.30 per 100 patient-years (95% confidence interval [95% CI] 2.08-4.25) and 1.51 per 100 person-years (95% CI 1.18-1.84), respectively. Compared with the general population, the age- and sex-adjusted hazard ratio (HR) for RA was 1.94 (95% CI 1.24-3.05, P = 0.004). Neither exclusion of patients with prior CVD at baseline nor adjustment for cardiovascular risk factors significantly influenced this. Compared with the nondiabetic population, nondiabetic patients with RA and those with type 2 DM had comparable HRs, 2.16 (95% CI 1.28-3.63, P = 0.004) and 2.04 (95% CI 1.12-3.67, P = 0.019), respectively. CONCLUSION The risk of CVD in RA was significantly elevated compared with the general population, and comparable with the magnitude of risk in type 2 DM.

[1]  B. Cronstein,et al.  Atheroprotective effects of methotrexate on reverse cholesterol transport proteins and foam cell transformation in human THP-1 monocyte/macrophages. , 2008, Arthritis and rheumatism.

[2]  B. Dijkmans,et al.  Rheumatoid arthritis versus diabetes as a risk factor for cardiovascular disease: a cross-sectional study, the CARRÉ Investigation , 2008, Annals of the rheumatic diseases.

[3]  Y. Shoenfeld,et al.  Tobacco smoking and autoimmune rheumatic diseases , 2007, Nature Clinical Practice Rheumatology.

[4]  T. Therneau,et al.  The widening mortality gap between rheumatoid arthritis patients and the general population. , 2007, Arthritis and rheumatism.

[5]  E. Pérez-Pampín,et al.  All-cause and cause-specific mortality in rheumatoid arthritis are not greater than expected when treated with tumour necrosis factor antagonists , 2007, Annals of the rheumatic diseases.

[6]  B. Dijkmans,et al.  Disease-modifying antirheumatic drugs are associated with a reduced risk for cardiovascular disease in patients with rheumatoid arthritis: a case control study , 2006, Arthritis research & therapy.

[7]  Yasmin,et al.  Rheumatoid Arthritis Is Associated With Increased Aortic Pulse-Wave Velocity, Which Is Reduced by Anti–Tumor Necrosis Factor-&agr; Therapy , 2006, Circulation.

[8]  A. Silman,et al.  Baseline levels of C-reactive protein and prediction of death from cardiovascular disease in patients with inflammatory polyarthritis: a ten-year followup study of a primary care-based inception cohort. , 2005, Arthritis and rheumatism.

[9]  M. González-Gay,et al.  High-grade C-reactive protein elevation correlates with accelerated atherogenesis in patients with rheumatoid arthritis. , 2005, The Journal of rheumatology.

[10]  C. Turesson,et al.  Treatment with tumor necrosis factor blockers is associated with a lower incidence of first cardiovascular events in patients with rheumatoid arthritis. , 2005, The Journal of rheumatology.

[11]  J. Schwartz,et al.  Arterial Stiffness in Chronic Inflammatory Diseases , 2005, Hypertension.

[12]  B. Joffe,et al.  Traditional and nontraditional cardiovascular risk factors are associated with atherosclerosis in rheumatoid arthritis. , 2005, The Journal of rheumatology.

[13]  S. Gabriel,et al.  Cardiovascular death in rheumatoid arthritis: a population-based study. , 2005, Arthritis and rheumatism.

[14]  S. Gabriel,et al.  Increased unrecognized coronary heart disease and sudden deaths in rheumatoid arthritis: a population-based cohort study. , 2005, Arthritis and rheumatism.

[15]  C. Cooper,et al.  Use of oral glucocorticoids and risk of cardiovascular and cerebrovascular disease in a population based case–control study , 2004, Heart.

[16]  C. Turesson,et al.  Increased incidence of cardiovascular disease in patients with rheumatoid arthritis: results from a community based study , 2004, Annals of the rheumatic diseases.

[17]  B. Dijkmans,et al.  Specific autoantibodies precede the symptoms of rheumatoid arthritis: a study of serial measurements in blood donors. , 2004, Arthritis and rheumatism.

[18]  M. Bots,et al.  [Trends in cardiovascular morbidity and mortality in the Netherlands, 1980-2000]. , 2004, Nederlands tijdschrift voor geneeskunde.

[19]  L. Bouter,et al.  Cardiovascular events in type 2 diabetes: comparison with nondiabetic individuals without and with prior cardiovascular disease. 10-year follow-up of the Hoorn Study. , 2003, European heart journal.

[20]  D. O'leary,et al.  Association between carotid atherosclerosis and markers of inflammation in rheumatoid arthritis patients and healthy subjects. , 2003, Arthritis and rheumatism.

[21]  H. Tunstall-Pedoe,et al.  Estimation of ten-year risk of fatal cardiovascular disease in Europe: the SCORE project. , 2003, European heart journal.

[22]  J. Cockcroft,et al.  Arterial stiffness and central blood pressure, as determined by pulse wave analysis, in rheumatoid arthritis , 2003, Annals of the rheumatic diseases.

[23]  J. Manson,et al.  Cardiovascular Morbidity and Mortality in Women Diagnosed With Rheumatoid Arthritis , 2003, Circulation.

[24]  J. Robins,et al.  Methotrexate and mortality in patients with rheumatoid arthritis: a prospective study , 2002, The Lancet.

[25]  G. McColl,et al.  Accelerated atherosclerosis: an extraarticular feature of rheumatoid arthritis? , 2002, Arthritis and rheumatism.

[26]  G L Freeman,et al.  High incidence of cardiovascular events in a rheumatoid arthritis cohort not explained by traditional cardiac risk factors. , 2001, Arthritis and rheumatism.

[27]  S. Houterman,et al.  Trends in total and high density lipoprotein cholesterol and their determinants in The Netherlands between 1993 and 1997. , 2001, International journal of epidemiology.

[28]  A. T. N. Group,et al.  Risk factors for cardiovascular mortality and morbidity: The WHO multinational study of vascular disease in diabetes. , 2001, Diabetologia.

[29]  S. Rantapää-Dahlqvist,et al.  Extent of inflammation predicts cardiovascular disease and overall mortality in seropositive rheumatoid arthritis. A retrospective cohort study from disease onset. , 1999, The Journal of rheumatology.

[30]  D. Levy,et al.  Prediction of coronary heart disease using risk factor categories. , 1998, Circulation.

[31]  C. Helmick,et al.  Estimates of the prevalence of arthritis and selected musculoskeletal disorders in the United States. , 1998, Arthritis and rheumatism.

[32]  S. R. Dahlqvist,et al.  Cardiovascular morbidity and mortality in patients with seropositive rheumatoid arthritis in Northern Sweden. , 1997, The Journal of rheumatology.

[33]  H. Valkenburg,et al.  Prevalence and Determinants of Glucose Intolerance in a Dutch Caucasian Population: The Hoorn Study , 1995, Diabetes Care.

[34]  F. Wolfe,et al.  The mortality of rheumatoid arthritis. , 1994, Arthritis and rheumatism.

[35]  F. Arnett Revised criteria for the classification of rheumatoid arthritis. , 1990, Orthopedic nursing.

[36]  W. Kannel,et al.  Cardiac failure and sudden death in the Framingham Study. , 1988, American heart journal.

[37]  M. Liang,et al.  The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. , 1988, Arthritis and rheumatism.

[38]  S. Gabriel,et al.  Survival in rheumatoid arthritis: a population-based analysis of trends over 40 years. , 2003, Arthritis and rheumatism.

[39]  M. Prevoo,et al.  Modified disease activity scores that include twenty-eight-joint counts. Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. , 1995, Arthritis and rheumatism.

[40]  H. Holman,et al.  Measurement of patient outcome in arthritis. , 1980, Arthritis and rheumatism.