Subclinical Atherosclerosis in Rheumatoid Arthritis and Systemic Lupus Erythematosus

https://doi.org/10.1016/j.amjmed.2008.06.010Get rights and content

Abstract

Rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) are associated with increased mortality, largely as a consequence of cardiovascular disease. Increased cardiovascular morbidity and mortality in patients with RA and SLE cannot be entirely explained by traditional risk factors, suggesting that the systemic inflammation that characterizes these diseases may accelerate atherosclerosis. We used carotid ultrasonography to investigate the prevalence and correlates to preclinical atherosclerosis in patients with RA and SLE. Because atherosclerosis is a systemic disease, assessment of carotid plaque by ultrasonography provides a robust, direct measure of systemic atherosclerosis. We observed a substantially increased prevalence of carotid plaque in RA and SLE patients compared with age- and sex-matched controls, which remained after adjustment for traditional risk factors. The presence of carotid atherosclerosis was associated with disease duration in both RA and SLE and damage in SLE. These data support the hypothesis that inflammation associated with RA and SLE contributes to accelerated atherosclerosis and argue that RA and SLE disease activity should be more aggressively managed.

Section snippets

Cardiovascular morbidity and mortality in the rheumatoid arthritis and systemic lupus erythematosus populations

Studies of populations and cohorts have clearly demonstrated that inflammatory diseases such as RA and SLE are associated with an increased mortality, largely as a consequence of cardiovascular disease. In a population-based cohort study of 606 rheumatoid factor–positive RA patients in Sweden between 1979 and 1994, the age-adjusted standardized mortality ratio for cardiovascular death was 50% higher in RA patients compared with age- and sex-matched controls.6 Similarly, data from the UK General

Carotid ultrasound studies to detect preclinical atherosclerosis in rheumatoid arthritis and systemic lupus erythematosus: Studies measuring intimal-medial thickness

Although it is apparent that RA and SLE may enhance the risk for cardiovascular disease, the prevalence of preclinical atherosclerosis in these patients compared with the general population has been unclear. An approach to assessing the presence and extent of preclinical atherosclerosis is carotid ultrasonography. Because atherosclerosis is a systemic disease, there is strong correlation between coronary atherosclerosis and that in the carotid arteries.24 In the general population, carotid

Accelerated preclinical atherosclerosis in rheumatoid arthritis and systemic lupus erythematosus: Increased presence of carotid plaque

Although carotid IMT strongly predicts cardiovascular events45, 46 and is correlated with the formation of plaque,47, 48, 49 the presence of carotid plaques (which can be measured in a reproducible, noninvasive manner by ultrasonography36, 50, 51, 52) is a more reliable predictor of cardiovascular events than IMT.33, 53, 54 Because of the conflicting data regarding assessment of premature preclinical atherosclerosis in RA and SLE, we chose a direct measure of atherosclerotic plaque rather than

Clinical implications

It is well established that patients with RA and SLE die prematurely relative to the general population and that cardiovascular disease is an important driver of the increased mortality in these populations. Moreover, the increase in cardiovascular events in patients with RA and SLE occurs even in the absence of traditional risk factors for CHD. The higher rates of cardiovascular death in patients with more severe disease, supported by the suggestion in some studies that elevated inflammatory

Author disclosures

The author who contributed to this article have disclosed the following industry relationships:

  • Jane E. Salmon, MD, serves as a consultant to Genentech, Roche, and Wyeth; and has received an investigator–initiated research grant from Genentech.

  • Mary J. Roman, MD, has no financial arrangement or affiliation with a corporate organization or a manufacturer of a product discussed in this article.

Acknowledgment

We thank Ali Hassan, PhD, for assistance in drafting the manuscript for this article.

References (56)

  • G. Belcaro et al.

    Carotid and femoral ultrasound morphology screening and cardiovascular events in low risk subjects: a 10-year follow-up study (the CAFES-CAVE study)

    Atherosclerosis

    (2001)
  • T. Pham et al.

    Cardiovascular risk and rheumatoid arthritis: clinical practice guidelines based on published evidence and expert opinion

    Joint Bone Spine

    (2006)
  • S.E. Gabriel et al.

    Survival in rheumatoid arthritis: a population-based analysis of trends over 40 years

    Arthritis Rheum

    (2003)
  • F. Wolfe et al.

    The mortality of rheumatoid arthritis

    Arthritis Rheum

    (1994)
  • S. Manzi et al.

    Age-specific incidence rates of myocardial infarction and angina in women with systemic lupus erythematosus: comparison with the Framingham Study

    Am J Epidemiol

    (1997)
  • L.T. Jacobsson et al.

    Rheumatoid arthritis and mortality: a longitudinal study in Pima Indians

    Arthritis Rheum

    (1993)
  • S. Wallberg-Jonsson et al.

    Cardiovascular morbidity and mortality in patients with seropositive rheumatoid arthritis in Northern Sweden

    J Rheumatol

    (1997)
  • C. Turesson et al.

    Cardiovascular risk factors, fitness and physical activity in rheumatic diseases

    Curr Opin Rheumatol

    (2007)
  • H. Maradit-Kremers et al.

    Cardiovascular death in rheumatoid arthritis: a population-based study

    Arthritis Rheum

    (2005)
  • P. Libby

    Inflammation in atherosclerosis

    Nature

    (2002)
  • D.J. Watson et al.

    All-cause mortality and vascular events among patients with rheumatoid arthritis, osteoarthritis, or no arthritis in the UK General Practice Research Database

    J Rheumatol

    (2003)
  • N.J. Goodson et al.

    Mortality in early inflammatory polyarthritis: cardiovascular mortality is increased in seropositive patients

    Arthritis Rheum

    (2002)
  • C.J. Edwards et al.

    Rheumatoid factor may be an Independent risk factor for ischaemic heart disease

    Heart

    (2007)
  • D.H. Solomon et al.

    Cardiovascular morbidity and mortality in women diagnosed with rheumatoid arthritis

    Circulation

    (2003)
  • I.D. del Rincón et al.

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

    Arthritis Rheum

    (2001)
  • M.M. Ward

    Premature morbidity from cardiovascular and cerebrovascular diseases in women with systemic lupus erythematosus

    Arthritis Rheum

    (1999)
  • J.M. Esdaile et al.

    Traditional Framingham risk factors fail to fully account for accelerated atherosclerosis in systemic lupus erythematosus

    Arthritis Rheum

    (2001)
  • C. Turesson et al.

    Severe extra-articular disease manifestations are associated with an increased risk of first ever cardiovascular events in patients with rheumatoid arthritis

    Ann Rheum Dis

    (2007)
  • Cited by (0)

    Statement of author disclosure: Please see the Author Disclosures section at the end of this article.

    View full text