Miscellaneous
Cardiovascular Outcomes in Male Veterans With Rheumatoid Arthritis

https://doi.org/10.1016/j.amjcard.2007.11.076Get rights and content

In men with rheumatoid arthritis (RA), the confounding effect of adverse cardiovascular risk profile on the independent association of RA disease activity score (DAS) and major adverse cardiovascular events (MACEs) continues to be debated. The aim was to analyze the association of RA DAS with MACEs in a prospective cohort of men with RA enrolled in the VARA Registry at the Dallas site from January 2003 to October 2006. All subjects met American College of Rheumatology criteria for RA. All events were obtained by reviewing patient clinical data. DAS was categorized as low, 0 to 3.2; moderate, 3.2 to 5.09; and high, ≥5.1. Of 282 men (mean age 66 ± 11.1 years), 231 had valid DASs (150, low; 60, moderate; and 21, high DAS) and were followed up for 4.4 ± 2 years. Ninety-two subjects (32.6%; 95% confidence interval 27 to 38) experienced an MACE, a composite end point of death (9 patients; 10%), acute coronary syndrome (38 patients; 42%), coronary revascularization (47 patients; 49%), new-onset heart failure (37 patients; 40%), and stroke (15 patients; 16%). DAS was a significant predictor of MACEs (hazard ratio 1.31, 95% confidence interval 1.1 to 1.6, p = 0.01) independent of traditional risk factors. Compared with patients with low or moderate DASs, patients with high DASs had a lower mean event-free period (35 and 30 vs 19 years, respectively; p = 0.03). In conclusion, in a population of male US veterans aged >50 years, (1) patients with RA were at high risk of MACEs, and (2) RA DAS was a significant predictor of MACEs independent of traditional cardiovascular risk factors.

Section snippets

Methods

VARA is a multicenter prospective registry of patients with RA treated at Veterans Affairs medical centers. The present study included only patients from the Dallas Veterans Affairs Medical Center aged ≥50 years at the time of enrollment. All patients met American College of Rheumatology diagnostic criteria for RA.17 In addition to serving as a biologic repository for both serum and deoxyribonucleic acid, VARA included baseline and longitudinal clinical data collected and recorded during the

Results

Men comprised >90% of the sample (282 of 312 patients). Therefore, our analyses focused on only men with RA enrolled in the VARA Registry. Mean age was 65.2 ± 11.2 years and most were Caucasian (79%). Baseline characteristics are listed in Table 1.

During a mean follow-up of 4.4 ± 2 years, 92 of 282 study subjects (32.6%; 95% confidence interval [CI] 27 to 38) experienced an MACE. Of 92 patients, 38 (42%) had an acute coronary syndrome requiring hospitalization, 37 experienced new-onset

Discussion

Our study shows for the first time that (1) men >50 years of age with RA were at high risk of MACEs, and (2) RA disease activity was a significant predictor of MACEs independent of traditional CV risk factors in a male population of US veterans.

The annual MACE rate in our study was high at ∼8%, nearly double the rate of the general US population (6), and agreed with similar observations made in many earlier studies. A similar >2-fold higher risk of myocardial infarction was reported in women

References (31)

  • G.S. Alarcon

    Predictive factors in rheumatoid arthritis

    Am J Med

    (1997)
  • G.S. Bhatia et al.

    Left ventricular systolic dysfunction in rheumatoid disease: an unrecognized burden?

    J Am Coll Cardiol

    (2006)
  • H.K. Choi et al.

    Methotrexate and mortality in patients with rheumatoid arthritis: a prospective study

    Lancet

    (2002)
  • R.C. Lawrence et al.

    Estimates of the prevalence of arthritis and selected musculoskeletal disorders in the United States

    Arthritis Rheum

    (1998)
  • S. Van Doornum et al.

    Accelerated atherosclerosis: an extraarticular feature of rheumatoid arthritis?

    Arthritis Rheum

    (2002)
  • F. McLaughlin et al.

    Tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta down-regulate intercellular adhesion molecule (ICAM)-2 expression on the endothelium

    Cell Adhes Commun

    (1998)
  • C. Mitaka et al.

    Effects of TNF-alpha on hemodynamic changes and circulating endothelium-derived vasoactive factors in dogs

    Am J Physiol

    (1994)
  • I.D. del Rincon et al.

    High incidence of cardiovascular events in a rheumatoid arthritis cohort not explained by traditional cardiac risk factors

    Arthritis Rheum

    (2001)
  • D.H. Solomon et al.

    Cardiovascular morbidity and mortality in women diagnosed with rheumatoid arthritis

    Circulation

    (2003)
  • E. Lindquist et al.

    Mortality in rheumatoid arthritis patients with disease onset in the 1980s

    Ann Rheum Dis

    (1999)
  • E.J. Kroot et al.

    No increased mortality in patients with rheumatoid arthritis: up to 10 years of follow up from disease onset

    Ann Rheum Dis

    (2000)
  • R. Peltomaa et al.

    Mortality in patients with rheumatoid arthritis treated actively from the time of diagnosis

    Ann Rheum Dis

    (2002)
  • E. Krishnan et al.

    Declines in mortality from acute myocardial infarction in successive incidence and birth cohorts of patients with rheumatoid arthritis

    Circulation

    (2004)
  • H. Maradit-Kremers et al.

    Increased unrecognized coronary heart disease and sudden deaths in rheumatoid arthritis: a population-based cohort study

    Arthritis Rheum

    (2005)
  • A.G. Kvalvik et al.

    Mortality in a cohort of Norwegian patients with rheumatoid arthritis followed from 1977 to 1992

    Scand J Rheumatol

    (2000)
  • Cited by (27)

    • Cardiovascular disease in inflammatory rheumatic diseases

      2016, Best Practice and Research: Clinical Rheumatology
      Citation Excerpt :

      High CRP levels conferred risk of CVD even in RA patients in whom the disease was clinically quiescent. A baseline disease activity score 28 of ≥5.1, which indicates high disease activity, was shown to be a predictor of CV events in RA [84]. As discussed before, CRP levels were found to correlate with thicker cIMT in a study involving 47 patients with RA without traditional CVRFs at the time of the carotid US assessment [31], and in another study, the annual mean CRP level was associated with the risk of CV events and CV mortality in long-standing RA patients [85].

    • Cardiovascular Risk in Inflammatory Rheumatic Disease

      2016, Kelley and Firestein's Textbook of Rheumatology: Volumes 1-2, Tenth Edition
    • Cardiovascular Risk in Rheumatic Disease

      2012, Kelley's Textbook of Rheumatology: Volume 1-2, Ninth Edition
    • Rheumatoid arthritis

      2010, Best Practice and Research: Clinical Rheumatology
      Citation Excerpt :

      Therefore, conclusions from co-morbidity studies should be judged cautiously. In the vast majority of studies, patients with RA show a higher risk of major adverse CV events than controls, and RA activity appears as a predictor of major adverse CV events independent of traditional CV risk factors [31–33]. Patients with very early disease, or even pre-RA, may also be at risk [34,35].

    • Cardiovascular complications of rheumatoid arthritis: Assessment, prevention, and treatment

      2010, Rheumatic Disease Clinics of North America
      Citation Excerpt :

      CV events occur approximately a decade earlier in RA than in controls21 and patients with RA are twice as likely to suffer a myocardial infarction6,8,16 with the increased relative risk for CV events being concentrated in younger patients with RA and individuals without known prior CV events.22 However, in a population of male United States' veterans older than 50 years, RA has also been associated with a higher risk for major adverse CV events, particularly in patients with increased disease activity independent of traditional risk factors.23 Patients with prolonged arthritis have more atherosclerosis than patients of the same age with more recent disease onset, suggesting that atherogenesis accelerates after the onset of RA.24,25

    View all citing articles on Scopus
    View full text