RA Autoantibodies Linked With Subclinical, Clinical Atherosclerosis

WASHINGTON – Rheumatoid arthritis–related autoantibodies are associated with subclinical and clinical atherosclerosis, according to findings from a prospective population-based study.

The results suggest that autoimmune factors play a role in the pathogenesis of atherosclerosis and cardiovascular disease (CVD) in rheumatoid arthritis (RA) patients, as well as in individuals without RA, Dr. Darcy S. Majka said at the annual meeting of the American College of Rheumatology.

Although the association between RA and CVD is well established, the exact mechanism is unknown.

"RA-related autoantibodies have been identified in individuals years before they develop RA, but most individuals with positive RA-related circulating autoantibodies do not develop clinical RA," said Dr. Majka of Northwestern University, Chicago.

In addition, preliminary data on stored serum samples from individuals without connective tissue disease demonstrated that circulating antiphospholipid antibodies measured in African Americans and whites were associated with subclinical atherosclerosis, she noted.

"This led us to develop the following conceptual model: We know that RA-related autoantibodies can produce inflammation and in some cases lead to possible progression to RA. In addition, the increased progression of subclinical atherosclerosis and cardiovascular events in RA is hypothesized to be mediated by the inflammation of clinically active RA. But we hypothesized that RA-related autoantibodies might be independently associated with subclinical atherosclerosis ... and this might potentially lead to progression to clinical cardiovascular events," she said, in describing the Multi-Ethnic Study of Atherosclerosis (MESA).

Indeed, in 6,557 middle-aged to elderly white, African American, Hispanic, and Chinese middle-aged to elderly adults who have been followed since 2000 as part of MESA, rheumatoid factor and anti-cyclic citrullinated peptide (anti-CCP-2) were associated with coronary artery calcium (CAC), a surrogate measure of subclinical atherosclerosis, in both white and African American women. The associations remained after investigators adjusted for traditional risk factors, including age, smoking status, blood pressure, body mass index, high-density lipoprotein cholesterol level, low-density lipoprotein cholesterol level, diabetes mellitus, aspirin use, and cholesterol and blood pressure medication use, she said.

A CAC level of at least 300 was present in 12.2% of participants at baseline, and after 7.1 years of follow-up, 3.0% experienced hard coronary heart disease (CHD) end points, including myocardial infarction, resuscitated cardiac arrest, and CHD death, and 4.8% experienced hard cardiovascular disease end points, including myocardial infarction, cardiac arrest, CHD death, stroke, and stroke death.

Rheumatoid factor (RF) IgM, RF IgA, and anti-CCP-2 were positive in 15.9%, 8.7%, and 2.0% of the MESA participants, respectively. In addition, 4.0% were positive for both RF IgM and RF IgA, and 20.6% were positive for one RF isotype.

The associations between baseline RF/anti-CCP and CAC were assessed and stratified based on race and sex, with adjustment for traditional cardiovascular risk factors.

Among the 1,323 white women in the study, those with RF IgA positivity, either RF IgM or RF IgA positivity, and/or anti-CCP-2 had an increased likelihood of having a CAC level greater than 300 (adjusted odds ratios of 2.3, 1.7, and 0.9 respectively, vs. a CAC of 0). Among 1,000 African American women in the study, those with RF IgA positivity or both RF IgM and RF IgA positivity had an increased likelihood of a CAC level between 100 and 300 (adjusted odds ratios, 2.2 and 2.7, respectively), and those with anti-CCP-2 had an increased likelihood of a CAC level greater than 300 (adjusted odds ratio, 4.0).

In addition, strong associations between RA-related autoantibodies and clinical cardiovascular disease events were seen in African American women in the study. For example, those with RF IgA positivity, either RF IgM or RF IgA positivity, or both RF isotypes were at increased risk of CHD hard end points (adjusted hazard ratios of 5, 2.5, and 4.5, respectively), Also, those with RF IgM positivity were at increased risk for CVD hard end points (adjusted hazard ratio, 2.1). Dr. Majka said.

No clear associations were seen between RA-related autoantibodies and CAC or CHD and CVD hard events in Hispanic and Chinese participants.

"RA-related autoantibodies appear to be independent risk factors for subclinical atherosclerosis and subsequent clinical CVD events," Dr. Majka concluded.

She reported having no relevant financial disclosures.

WASHINGTON – Rheumatoid arthritis–related autoantibodies are associated with subclinical and clinical atherosclerosis, according to findings from a prospective population-based study.

The results suggest that autoimmune factors play a role in the pathogenesis of atherosclerosis and cardiovascular disease (CVD) in rheumatoid arthritis (RA) patients, as well as in individuals without RA, Dr. Darcy S. Majka said at the annual meeting of the American College of Rheumatology.

Although the association between RA and CVD is well established, the exact mechanism is unknown.

"RA-related autoantibodies have been identified in individuals years before they develop RA, but most individuals with positive RA-related circulating autoantibodies do not develop clinical RA," said Dr. Majka of Northwestern University, Chicago.

In addition, preliminary data on stored serum samples from individuals without connective tissue disease demonstrated that circulating antiphospholipid antibodies measured in African Americans and whites were associated with subclinical atherosclerosis, she noted.

"This led us to develop the following conceptual model: We know that RA-related autoantibodies can produce inflammation and in some cases lead to possible progression to RA. In addition, the increased progression of subclinical atherosclerosis and cardiovascular events in RA is hypothesized to be mediated by the inflammation of clinically active RA. But we hypothesized that RA-related autoantibodies might be independently associated with subclinical atherosclerosis ... and this might potentially lead to progression to clinical cardiovascular events," she said, in describing the Multi-Ethnic Study of Atherosclerosis (MESA).

Indeed, in 6,557 middle-aged to elderly white, African American, Hispanic, and Chinese middle-aged to elderly adults who have been followed since 2000 as part of MESA, rheumatoid factor and anti-cyclic citrullinated peptide (anti-CCP-2) were associated with coronary artery calcium (CAC), a surrogate measure of subclinical atherosclerosis, in both white and African American women. The associations remained after investigators adjusted for traditional risk factors, including age, smoking status, blood pressure, body mass index, high-density lipoprotein cholesterol level, low-density lipoprotein cholesterol level, diabetes mellitus, aspirin use, and cholesterol and blood pressure medication use, she said.

A CAC level of at least 300 was present in 12.2% of participants at baseline, and after 7.1 years of follow-up, 3.0% experienced hard coronary heart disease (CHD) end points, including myocardial infarction, resuscitated cardiac arrest, and CHD death, and 4.8% experienced hard cardiovascular disease end points, including myocardial infarction, cardiac arrest, CHD death, stroke, and stroke death.

Rheumatoid factor (RF) IgM, RF IgA, and anti-CCP-2 were positive in 15.9%, 8.7%, and 2.0% of the MESA participants, respectively. In addition, 4.0% were positive for both RF IgM and RF IgA, and 20.6% were positive for one RF isotype.

The associations between baseline RF/anti-CCP and CAC were assessed and stratified based on race and sex, with adjustment for traditional cardiovascular risk factors.

Among the 1,323 white women in the study, those with RF IgA positivity, either RF IgM or RF IgA positivity, and/or anti-CCP-2 had an increased likelihood of having a CAC level greater than 300 (adjusted odds ratios of 2.3, 1.7, and 0.9 respectively, vs. a CAC of 0). Among 1,000 African American women in the study, those with RF IgA positivity or both RF IgM and RF IgA positivity had an increased likelihood of a CAC level between 100 and 300 (adjusted odds ratios, 2.2 and 2.7, respectively), and those with anti-CCP-2 had an increased likelihood of a CAC level greater than 300 (adjusted odds ratio, 4.0).

In addition, strong associations between RA-related autoantibodies and clinical cardiovascular disease events were seen in African American women in the study. For example, those with RF IgA positivity, either RF IgM or RF IgA positivity, or both RF isotypes were at increased risk of CHD hard end points (adjusted hazard ratios of 5, 2.5, and 4.5, respectively), Also, those with RF IgM positivity were at increased risk for CVD hard end points (adjusted hazard ratio, 2.1). Dr. Majka said.

No clear associations were seen between RA-related autoantibodies and CAC or CHD and CVD hard events in Hispanic and Chinese participants.

"RA-related autoantibodies appear to be independent risk factors for subclinical atherosclerosis and subsequent clinical CVD events," Dr. Majka concluded.

She reported having no relevant financial disclosures.

WASHINGTON – Rheumatoid arthritis–related autoantibodies are associated with subclinical and clinical atherosclerosis, according to findings from a prospective population-based study.

The results suggest that autoimmune factors play a role in the pathogenesis of atherosclerosis and cardiovascular disease (CVD) in rheumatoid arthritis (RA) patients, as well as in individuals without RA, Dr. Darcy S. Majka said at the annual meeting of the American College of Rheumatology.

Although the association between RA and CVD is well established, the exact mechanism is unknown.

"RA-related autoantibodies have been identified in individuals years before they develop RA, but most individuals with positive RA-related circulating autoantibodies do not develop clinical RA," said Dr. Majka of Northwestern University, Chicago.

In addition, preliminary data on stored serum samples from individuals without connective tissue disease demonstrated that circulating antiphospholipid antibodies measured in African Americans and whites were associated with subclinical atherosclerosis, she noted.

"This led us to develop the following conceptual model: We know that RA-related autoantibodies can produce inflammation and in some cases lead to possible progression to RA. In addition, the increased progression of subclinical atherosclerosis and cardiovascular events in RA is hypothesized to be mediated by the inflammation of clinically active RA. But we hypothesized that RA-related autoantibodies might be independently associated with subclinical atherosclerosis ... and this might potentially lead to progression to clinical cardiovascular events," she said, in describing the Multi-Ethnic Study of Atherosclerosis (MESA).

Indeed, in 6,557 middle-aged to elderly white, African American, Hispanic, and Chinese middle-aged to elderly adults who have been followed since 2000 as part of MESA, rheumatoid factor and anti-cyclic citrullinated peptide (anti-CCP-2) were associated with coronary artery calcium (CAC), a surrogate measure of subclinical atherosclerosis, in both white and African American women. The associations remained after investigators adjusted for traditional risk factors, including age, smoking status, blood pressure, body mass index, high-density lipoprotein cholesterol level, low-density lipoprotein cholesterol level, diabetes mellitus, aspirin use, and cholesterol and blood pressure medication use, she said.

A CAC level of at least 300 was present in 12.2% of participants at baseline, and after 7.1 years of follow-up, 3.0% experienced hard coronary heart disease (CHD) end points, including myocardial infarction, resuscitated cardiac arrest, and CHD death, and 4.8% experienced hard cardiovascular disease end points, including myocardial infarction, cardiac arrest, CHD death, stroke, and stroke death.

Rheumatoid factor (RF) IgM, RF IgA, and anti-CCP-2 were positive in 15.9%, 8.7%, and 2.0% of the MESA participants, respectively. In addition, 4.0% were positive for both RF IgM and RF IgA, and 20.6% were positive for one RF isotype.

The associations between baseline RF/anti-CCP and CAC were assessed and stratified based on race and sex, with adjustment for traditional cardiovascular risk factors.

Among the 1,323 white women in the study, those with RF IgA positivity, either RF IgM or RF IgA positivity, and/or anti-CCP-2 had an increased likelihood of having a CAC level greater than 300 (adjusted odds ratios of 2.3, 1.7, and 0.9 respectively, vs. a CAC of 0). Among 1,000 African American women in the study, those with RF IgA positivity or both RF IgM and RF IgA positivity had an increased likelihood of a CAC level between 100 and 300 (adjusted odds ratios, 2.2 and 2.7, respectively), and those with anti-CCP-2 had an increased likelihood of a CAC level greater than 300 (adjusted odds ratio, 4.0).

In addition, strong associations between RA-related autoantibodies and clinical cardiovascular disease events were seen in African American women in the study. For example, those with RF IgA positivity, either RF IgM or RF IgA positivity, or both RF isotypes were at increased risk of CHD hard end points (adjusted hazard ratios of 5, 2.5, and 4.5, respectively), Also, those with RF IgM positivity were at increased risk for CVD hard end points (adjusted hazard ratio, 2.1). Dr. Majka said.

No clear associations were seen between RA-related autoantibodies and CAC or CHD and CVD hard events in Hispanic and Chinese participants.

"RA-related autoantibodies appear to be independent risk factors for subclinical atherosclerosis and subsequent clinical CVD events," Dr. Majka concluded.

She reported having no relevant financial disclosures.