Relative contribution of cardiovascular risk factors and rheumatoid arthritis clinical manifestations to atherosclerosis

Abstract

Objective. To estimate the contribution of cardiovascular (CV) risk factors and rheumatoid arthritis (RA) disease manifestations to atherosclerosis in RA.Methods. We used high-resolution carotid ultrasound to measure the carotid intima-media thickness (IMT) and plaque in 631 RA patients. Using R 2 measures from multivariable models, we estimated the contribution of demographic characteristics (age, sex, and ethnic group), CV risk factors (diabetes mellitus, hypercholesterolemia, cigarette smoking, hypertension, and body mass index, and RA manifestations (joint tenderness, swelling, and deformity, nodules, erythrocyte sedimentation rate [ESR], C-reactive protein, rheumatoid factor, the HLA-DRB1 shared epitope, and cumulative glucocorticoid dose) to each of the outcomes. Estimates were obtained in the full sample, and within strata defined by age, sex, and ethnic group. We tested for interaction between CV risk factors and RA manifestations.Results. The contribution of demographic factors, CV risk factors, and RA manifestations to IMT and plaque R 2 varied depending on the patients' age stratum. Demographic features explained 11-16% of IMT variance, CV risk factors explained 4%-12%, and RA manifestations explained 1-6%. The greatest contribution of RA manifestations occurred in the youngest age group, while that of CV risk factors occurred in the older age groups. Results for carotid plaque were similar. There was a significant interaction between the number of CV risk factors present and the ESR, suggesting that the ESR's effect on IMT varied according to the number of CV risk factors.Conclusion. Both established CV risk factors and manifestations of RA inflammation contribute significantly to carotid atherosclerosis in RA, and may modify one another's effects. These findings may have implications regarding the prevention of atherosclerosis in RA.The mechanism underlying the high frequency of cardiovascular (CV) morbidity that occurs in rheumatoid arthritis (RA) is not completely understood (1-16). Earlier studies have indicated that the excess CV event rate in RA is not explained by an excess of established CV risk factors (17,18). Those studies did not address whether these risk factors operate similarly in RA as they do in the general population.Diabetes mellitus, hypercholesterolemia, hypertension, cigarette smoking, and obesity are powerful classifiers of CV risk (19). One or more established CV risk factors are present in at least 80% of people with symptomatic coronary artery disease in the general population (20). The prevalence is even higher, approaching 100%, among persons with fatal myocardial infarction (21).People with and those without RA have similar CV risk factor profiles (17,18,22). The resemblance suggests that established CV risk factors may play an important role in the CV morbidity that occurs in RA, as they do in the general population. In earlier studies that

Atherosclerosis in Rheumatoid Arthritis: What to Look for in Studies Using Carotid Ultrasound: Figure 1.

“…Also notable, the bulb IMT and plaque difference between RA and controls was present only among subjects under 65 years of age. These results are consistent with our finding that RA manifestations contributed more to carotid atherosclerosis in young RA patients 16 , and with Roman and colleagues' finding of a more pronounced difference between RA patients and controls among younger subjects 13 .…”

“…Thus, it cannot be concluded from them that CV risk factors are not associated with atherosclerosis in RA. In our study of 631 RA patients recruited consecutively, and without specifying CV risk factors as exclusion criteria, we reported that both CV risk factors and inflammation markers were significantly associated with carotid IMT and plaque 16 .…”

According to the Materials of the 2015/2016 New European League Against Rheumatism (Eular) Guidelines for Reducing Cardiovascular Risk in Patients With Inflammatory Arthritis: General Characterization and Discussion Problems

“…Сочетание РА-специфичных и традицион-ных кардиоваскулярных ФР ассоциируется с наличием атеросклероза в сонных артериях [83], а длительность и ак-тивность заболевания влияют на размер и нестабильность АТБ при РА [84,85].…”

Which Are the Determinants of Dyslipidemia in Rheumatoid Arthritis and Does Socioeconomic Status Matter in This Context?

“…However, dyslipidemia does participate in RA atherogenesis even when the disease is treated with DMARD 18,19 , and its determinants comprise more of the conventional dyslipidemia risk factors than of RA characteristics. The association of dyslipidemia risk factors with lipoproteins further differs markedly by socioeconomic status in RA.…”