RA Disease Activity, Oxidized LDL, Anti-Oxidized LDL Antibodies and CVD Risk

In patients with RA, disease activity, erythrocyte sedimentation rate, disease duration, presence of anti-CCP antibodies, high oxLDL fraction and low level of anti-oxLDL antibodies may influence the risk for cardiovascular disease

Cardiovascular disease is largely responsible for the mortality gap that exists between those with rheumatoid arthritis (RA) and the general population. The risk for cardiovascular disease in those with RA is as high as for those with diabetes mellitus. Although the precise reasons for excess cardiovascular disease risk in RA are yet to be elucidated, persistent systemic inflammation, elevated serum levels of rheumatoid factor and antinuclear antibodies, and corticosteroid use have been proposed as possible precipitants.1 

A team of researchers from Wroclaw Medical University in Poland recently undertook a study to identify nonclassic risk factors that could account for the elevated cardiovascular disease risk in those with RA. The researchers, led by Dr Beata Nowak, evaluated cardiovascular disease risk in 37 persons with RA and 24 healthy controls using the European cardiovascular disease risk assessment model known as Systematic Coronary Risk Evaluation (SCORE) and by ultrasonographic measurement of carotid intima-media thickness.

 SCORE assessments were modified for patients in the RA group as per guidelines from the European League Against Rheumatism, which recommend that the derived cardiovascular risk estimate be increased by a factor of 1.5 if the person with RA meets 2 of the following 3 criteria: disease duration exceeding 10 years, rheumatoid factor or anti-cyclic citrullinated peptide (anti-CCP) positivity, and/or the presence of extra-articular manifestations.

A number of clinical characteristics were obtained and compared, including age, sex, medications, smoking status, diastolic and systolic blood pressure, anti-CCP and inflammatory markers, presence of hypertension or hyperlipidemia, lipid level, and levels of oxidized low-density lipoprotein (oxLDL) and anti-oxLDL antibodies. The authors found that the 10-year risk for fatal cardiovascular disease, as determined by SCORE, was significantly higher in the RA group. 

However, in contrast to results from previously published studies, the authors did not find any significant differences in intima-media thickness between those with RA and controls. However, they noted that this may have been caused by the higher-than-expected levels of LDL cholesterol in the control group. Patients with RA and anti-CCP antibodies demonstrated higher SCORE values and greater intima-media thickness, lending support to the thesis that anti-CCP positivity represents a nontraditional cardiovascular disease risk factor in RA. 

A correlation was also noted between higher SCORE values and disease activity, disease duration, and inflammation as indicated by erythrocyte sedimentation rate. Rheumatoid nodules were not associated with cardiovascular risk or intima-media thickness .

OxLDL levels are increased by the inflammatory processes in RA. The research team found a higher fraction of oxLDL in those with RA compared with controls, and in those with RA and carotid plaques compared with those with RA and no carotid plaques. 

They also found an inverse correlation between intima-media thickness and anti-oxLDL antibodies. “The negative correlation between the concentration of anti-oxLDL antibodies and intima-media thickness suggests that these antibodies may be protective and reduce the risk for cardiovascular disease,” the authors wrote.

Summary and Clinical Applicability

“The present study demonstrated that in [patients with] RA, disease activity, erythrocyte sedimentation rate, disease duration, presence of anti-CCP antibodies, high oxLDL fraction and low level of anti-oxLDL antibodies may influence the risk for cardiovascular disease,” concluded Dr Nowak and colleagues.

They noted that in the present study, the 10-year cardiovascular risk for those with RA in remission or with lower disease activity was significantly lower than for those with moderate to high disease activity.

“This supports the thesis that the best way to reduce cardiovascular disease occurrence in [those with] RA is RA treatment leading to disease control and remission,” they wrote.

Limitations and Disclosures

This study was financially supported by the Wroclaw Medical University grant for young researchers. The study authors disclosed no conflicts of interest. 

Read More: CVD Risk Mitigation in Rheumatic Disease


Nowak B, Madej M, Luczak A, Malecki R, Wiland P. Disease activity, oxidized-LDL fraction and anti-oxidized LDL antibodies influence cardiovascular risk in rheumatoid arthritis. Adv Clin Exp Med. 2016;25(1):43-50.