Cardiovascular
Lipid Profiles in Patients with Rheumatoid Arthritis: Mechanisms and the Impact of Treatment

https://doi.org/10.1016/j.semarthrit.2008.01.015Get rights and content

Objective

To describe the impact of rheumatoid arthritis (RA), and its treatment, on lipoprotein levels with potential implications for atherosclerosis.

Methods

A PubMed literature search was undertaken for studies published between 1990 and May 2007, using the search terms “rheumatoid arthritis” AND “lipid” OR “lipoprotein,” and including all relevant drug treatment terms for glucocorticoids, disease-modifying antirheumatic drugs, and biologics.

Results

Patients with RA face an increased risk of developing premature cardiovascular disease and limited ability to modify risk factors, eg, through exercise. RA is associated with an abnormal lipoprotein pattern, principally low levels of high density lipoprotein (HDL) cholesterol. Most treatments for RA tend to improve the atherogenic index (total/HDL cholesterol ratio), with more evidence for biologics in this regard. The improvement in the lipoprotein profile in RA appears to be associated with suppression of inflammation.

Conclusions

Lipid levels should be monitored and managed in patients with RA to minimize the long-term risk of cardiovascular disease. More research is needed to quantify the relationship between systemic inflammation and lipoprotein levels and to determine the impact of specific lipoprotein particles, eg, small dense low-density lipoprotein and subfractions of HDL on long-term risk. Control of inflammation may have an effect on modifying cardiovascular risk.

Section snippets

Methods

A PubMed literature search was undertaken for studies published between 1990 and May 2007, using the search terms “rheumatoid arthritis” AND “lipid” OR “lipoprotein” OR “cholesterol,” and including all relevant drug treatment terms for glucocorticoids, disease-modifying antirheumatic drugs, and biologics. Preference was given to clinical studies (including randomized clinical studies), meta-analyses, and guidelines. Review articles focused on lipid abnormalities in RA were evaluated and the

Risk Factors for Coronary Heart Disease

Cardiovascular risk factors may be classified as modifiable (lipid levels, blood pressure, smoking, obesity, sedentary lifestyle) or nonmodifiable (age, gender, family history). The effects of these factors on risk are additive, and therefore, the National Cholesterol Education Program Adult Treatment Panel III guidelines for modifying lipid levels grade the intensity of treatment to the number of risk factors (13). National Cholesterol Education Program Adult Treatment Panel III guidelines

Discussion

Clearly, more research is needed to elucidate fully the relationship between inflammation and atherosclerosis in RA, and the nature of the effect of RA on lipoprotein profiles. For example, it is now understood that the structure and function of lipoproteins differ, even within the subclasses of LDL and HDL, and that density and size of lipoprotein particles change their cellular effect. Small, dense LDL particles are more atherogenic than large ones (53, 66), whereas small, dense HDL particles

Acknowledgments

Catherine Colebourn contributed to the writing and editing of this article. Financial support for the development of this manuscript was provided by Hoffmann-La Roche Inc., Nutley, NJ.

References (68)

  • D.W. McCarey et al.

    Trial of Atorvastatin in Rheumatoid Arthritis (TARA): double-blind, randomised placebo-controlled trial

    Lancet

    (2004)
  • K.M. Maki-Petaja et al.

    Ezetimibe and simvastatin reduce inflammation, disease activity, and aortic stiffness and improve endothelial function in rheumatoid arthritis

    J Am Coll Cardiol

    (2007)
  • L. Klareskog et al.

    Statins in rheumatoid arthritis—two birds with one stone?

    Lancet

    (2004)
  • A.C. Li et al.

    The macrophage foam cell as a target for therapeutic intervention

    Nat Med

    (2002)
  • P. Libby et al.

    Inflammation and atherosclerosis

    Circulation

    (2002)
  • T.A. Pearson et al.

    Markers of inflammation and cardiovascular disease: application to clinical and public health practice: a statement for healthcare professionals from the Centers for Disease Control and Prevention and the American Heart Association

    Circulation

    (2003)
  • D.H. Solomon et al.

    Patterns of cardiovascular risk in rheumatoid arthritis

    Ann Rheum Dis

    (2006)
  • C. Turesson et al.

    Increased incidence of cardiovascular disease in patients with rheumatoid arthritis: results from a community based study

    Ann Rheum Dis

    (2004)
  • N. Goodson et al.

    Cardiovascular admissions and mortality in an inception cohort of patients with rheumatoid arthritis with onset in the 1980s and 1990s

    Ann Rheum Dis

    (2005)
  • K.J. Warrington et al.

    Rheumatoid arthritis is an independent risk factor for multi-vessel coronary artery disease: a case control study

    Arthritis Res Ther

    (2005)
  • H. Maradit-Kremers et al.

    Cardiovascular death in rheumatoid arthritis: a population-based study

    Arthritis Rheum

    (2005)
  • I. del Rincon et al.

    Association between carotid atherosclerosis and markers of inflammation in rheumatoid arthritis patients and healthy subjects

    Arthritis Rheum

    (2003)
  • N. Sattar et al.

    Explaining how “high-grade” systemic inflammation accelerates vascular risk in rheumatoid arthritis

    Circulation

    (2003)
  • NCEP. Third report of the National Cholesterol Education Program (NCEP) expert panel on: Detection, evaluation, and...
  • S.M. Grundy et al.

    Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines

    Circulation

    (2004)
  • S.A. Karvounaris et al.

    Metabolic syndrome is common among middle-to-older aged Mediterranean patients with rheumatoid arthritis and correlates with disease activity: a retrospective, cross-sectional, controlled, study

    Ann Rheum Dis

    (2007)
  • P.H. Dessein et al.

    Subclinical hypothyroidism is associated with insulin resistance in rheumatoid arthritis

    Thyroid

    (2004)
  • P.H. Dessein et al.

    Metabolic syndrome and subclinical atherosclerosis in rheumatoid arthritis

    J Rheumatol

    (2006)
  • P.H. Dessein et al.

    Insulin resistance and impaired beta cell function in rheumatoid arthritis

    Arthritis Rheum

    (2006)
  • E.T.H. Yeh

    CRP as a mediator of disease

    Circulation

    (2004)
  • M.J. Kaplan

    Cardiovascular disease in rheumatoid arthritis

    Curr Opin Rheumatol

    (2006)
  • P. Emery et al.

    Evidence-based review of biologic markers as indicators of disease progression and remission in rheumatoid arthritis

    Rheumatol Int

    (2007)
  • P. Dessein et al.

    Biomarkers of endothelial dysfunction, cardiovascular risk factors and atherosclerosis in rheumatoid arthritis

    Arthritis Res Ther

    (2005)
  • B. Seriolo et al.

    Effects of anti-TNF-a treatment on lipid profile in patients with active rheumatoid arthritis

    Ann NY Acad Sci

    (2006)
  • Cited by (134)

    • Autoimmune heart disease

      2022, Translational Autoimmunity: Autoimmune Diseases in Different Organs
    • Statins and autoimmunity: State-of-the-art

      2020, Pharmacology and Therapeutics
    View all citing articles on Scopus
    View full text