SAN FRANCISCO – The atypical presentation of cardiovascular disease in patients with rheumatoid arthritis often masks its presence until the patient dies suddenly, according to Dr. Vibeke Strand.
The mortality in patients with RA is twice that of the normal population, with the average life span being reduced by 15-18 years in RA, which is comparable to the early mortality seen in patients with diabetes. Cardiovascular disease (CVD) explains almost all of the excess mortality seen in patients with RA, said Dr. Strand of the division of immunology and rheumatology at Stanford (Calif.) University.
CVD risk factors are atypical in RA patients. They are less likely to be obese or to have hypertension, hyperlipidemia, or diabetes (J. Rheumatol. 2011;38:29-35). Heart failure is more common in the RA population, especially in rheumatoid factor (RF)-positive patients. However despite their heart failure, their ejection fraction often remains normal.
Patients’ body mass index tends to be low, suggesting that their heart failure may result from reduced myocardial mass rather than from hypertrophy. Those with a BMI less than 20 kg/m2 have a significantly decreased survival, she said at the Perspectives in Rheumatic Diseases 2011 meeting.
Because their CVD presentation is atypical, RA patients tend to get recognized later in the course of their heart disease and to be treated less aggressively. RA patients are less likely than those without the disease to undergo revascularization or receive cardiovascular medications after an MI.
Until recently, rheumatologists have been unable to lessen early mortality among RA patients. However, data from a study of 3,862 RA patients diagnosed with RA either before 1970, between 1970 and 1980, or after 1990 showed a drop in excess mortality among the 1,240 patients diagnosed after 1995. The researchers attributed the prolonged survival to the use of methotrexate (Lancet 2002;359:1173-7; Circulation 2004;110:1774-9).
With the advent of the biologics era, particularly the widespread use of tumor necrosis factor (TNF) inhibitors, rheumatologists have been wondering whether the anti-inflammatory properties of these agents would lower CVD mortality among RA patients.
Data presented at the 2005 Congress of the European League Against Rheumatism (EULAR) (abstract OP0095) showed that use of TNF inhibitors lowers the hazard ratio of all-cause mortality to 0.72 among RA patients. These findings were based on 63,811 patient-years of follow-up of 19,580 RA patients, among whom there were 1,129 deaths. Use of methotrexate was associated with an HR of 0.82. Prednisone increased the risk to an HR of 1.60, which is consistent with the well-documented risk of CVD associated with the use of even small doses of this agent, he said at the meeting, which was sponsored in part by the Skin Disease Education Foundation (SDEF).
Standard risk scores such as the Framingham score underestimate the risk for heart disease in an RA population. The underestimation is clear in the results of a study that compared mortality risk as calculated by the Framingham score with actual events in 341 women with RA aged 30-74 years and 150 men with RA aged 30-74 years. According to the Framingham score, the 10-year CVD risk for the women was 4.6%. In fact, it was 11.1%. For the men, the Framingham risk was 12%. The actual cardiovascular risk was 25.8% (Arthritis Rheum. 2009;60:S264).
The excess CVD risk persists even after traditional risk factors seen in normal populations are controlled for. The biggest remaining risk is the burden of inflammation. There are increased levels of TNF-alpha and interleukin-6 in the serum, myocardium, and synovitis of RA, according to Dr. Strand.
Recommendations on limiting the increased risk for CVD issued by EULAR (Ann. Rheum. Dis. 2010;69:325-31) suggest modifying the risk score by multiplying it by 1.5 when the patient has two of the three following signs of severe disease: RA duration of more than 10 years; rheumatoid factor and anti-CCP antibody positivity; and/or extra-articular disease manifestations.
The following steps should be taken in such patients:
• Monitor total cholesterol/high-density lipoprotein levels.
• Manage appropriate treatment with statins, angiotensin-converting enzyme inhibitors, or angiotensin II receptor blockers.
• Prescribe steroids at the lowest possible dose, if at all.
• Urge caution regarding the use of nonsteroidal anti-inflammatory drugs and COX-2 inhibitors.
• Urge patients to stop smoking.
Dr. Strand disclosed that she has financial relationships with many companies that make treatments for RA.
SDEF and this news organization are owned by Elsevier.