Rheumatoid Arthritis - Clinical & Epidemiology
- Abstract 278: Systemic Inflammation and Cardiovascular Risk Factors Predict Rapid Progression of Atherosclerosis in Rheumatoid Arthritis
- Abstract 1188: Smoking Cessation and Improvement in RA Disease Activity
- Abstract 1203: Rheumatoid Arthritis-Related Antibody Positivity is Associated with Serum Cytokine Elevations in RA-Free First-Degree Relatives of RA Probands
- Abstract 1935: Circulating 25-OH Vitamin D Concentrations in African Americans with Recent-Onset Rheumatoid Arthritis
- Abstract 1937: Periodontal Symptoms are Independently Associated with Rheumatoid Arthritis Disease Activity
- Abstract 1938: Rheumatoid Arthritis is Associated with a Higher Prevalence of Carotid Plaque in the Internal, but not Common, Carotid Artery
Abstract 278: Systemic Inflammation and Cardiovascular Risk Factors Predict Rapid Progression of Atherosclerosis in Rheumatoid Arthritis
Authors:
Del Rincon, Polak, O’Leary, Escalante; San Antonio, Texas, USA
Background:
Several cross-sectional investigations have demonstrated an increase in carotid and coronary atherosclerosis in RA patients. In these, systemic inflammation has not been strongly associated in a consistent way, possibly due to their cross-sectional designs. Del Rincon reported the results of a study investigating progression of carotid atherosclerosis in RA.
Methods:
RA patients underwent high resolution ultrasound scanning of the common carotid arteries at baseline and at follow-up an average of 2.8 years later (range 1 to 4.3 years). Sociodemographic, cardiovascular, and RA disease and treatment characteristics were explored as predictors of progression of common carotid intima-media thickness (IMT). Rapid progression was defined as those in the 75th percentile for change in IMT.
Results:
A total of 487 subjects had baseline and follow-up carotid scans, representing 86% of the originally enrolled cohort. Common carotid IMT increased a mean of 0.050 ± 0.055 mm over follow-up, a statistically significant increase (p<0.001). Those with rapid progression had an increase in IMT of 0.119 ± 0.062 mm. The number of traditional cardiovascular risk factors was associated with rapid progression, with the odds of rapid progression increasing 27% for every cardiovascular risk factor (OR 1.27 (95% CI 1.01 – 1.61)). The odds of rapid progression also increased 12% for every 10mm/hr increase in ESR (OR 1.12 (95%CI 1.02 – 1.23)), independent of CV risk factors, sociodemographics, time between scans, baseline IMT, and RA disease and treatment characteristics.
Conclusions:
Both cardiovascular risk factors and interval systemic inflammation contribute to progression of common carotid atherosclerosis in RA patients.
Editorial Comment:
To date, this is the largest longitudinal study of carotid atherosclerosis in RA patients and demonstrates convincingly that those RA patients with higher interval systemic inflammation are at greater risk for progressive atherosclerosis than patients with lower levels of inflammation. However, traditional risk factors appeared to play as large, if not a larger, role than inflammation; emphasizing that control of both inflammatory and traditional risk factors are likely required in order to impact cardiovascular morbidity in RA patients.
Abstract 1188: Smoking Cessation and Improvement in RA Disease Activity
Authors:
Fisher, El-Taha, Kremer, Peng, Greenberg; New York, United States
Background:
Cigarette smoking, particularly in the context of anti-CCP antibodies and the HLA-DRB1 “shared epitope”, is a potent risk factor for the development of RA. However, the impact of smoking on disease progression and severity is less studied. Fisher and colleagues investigated the association of smoking cessation on RA disease related parameters.
Methods:
The CORRONA registry was used to identify RA patients who reported current smoking at enrollment and subsequently reported smoking cessation with at least three study visits (at least two consecutive in which smoking was not reported). Changes in RA disease related parameters with smoking cessation were explored.
Results:
Among the 16,251 RA patients enrolled in CORRONA, 2,328 (14%) were current smokers at enrollment. Of these, 1,673 had 3 or more study visits, 318 of whom stopped smoking. Mean age, disease duration, and gender and race distributions were similar between those who stopped and those who continued smoking. The use of biologic DMARDs was significantly higher among those who continued (41% vs. 34%) and follow-up time was longer among those who stopped smoking (3.8 vs. 2.8 years). Baseline Clinical Disease Activity Index (CDAI) scores were higher in those who continued to smoke vs. those who stopped (18.9 vs. 17.6; p<0.05). CDAI scores at the last follow-up visit were also higher for those who continued to smoke vs. those who stopped. After adjusting for factors significantly associated with follow-up CDAI score (baseline CDAI, prednisone use, and duration of follow-up), the adjusted log CDAI score was -0.14 units lower in the group that stopped smoking compared to the group that continued (p=0.067). The proportion of patients in remission at follow-up was higher for those who stopped smoking vs. those who continued (18.6% vs. 12.3%; p<0.05). After adjusting for baseline biologic DMARD use, the odds of remission was 49% higher in those that stopped smoking vs. those who continued (OR 1.49 (95% CI 1.05 – 2.0; p = 0.025)).
Conclusions:
Smoking cessation was associated with a reduction in RA disease activity and an increase in RA remission rates.
Editorial Comment:
This is the first investigation of its kind to propose that smoking cessation may result in improvements in disease outcomes. The mechanism of improvement could relate to decreases in systemic inflammation and/or immune activation cause by smoking. However, there may be other mechanisms underlying the association. For one, people who stop smoking may engage in other healthy lifestyle activities that may be associated with more favorable self-report of disease status measures (like tender joint counts, global health assessment, or HAQ).
Abstract 1203: Rheumatoid Arthritis-Related Antibody Positivity is Associated with Serum Cytokine Elevations in RA-Free First-Degree Relatives of RA Probands
Authors:
Deane, Robinson, Majka, Parrish, BenBarak, Weisman, O’Dell, Gregersen, Buckner, Norris, Holers; Colorado, United States
Background:
Because RA-associated immune responses may be detected in RA patients many years before the development of symptoms, studying the earliest stages of disease initiation and propagation are challenging. One solution is to study family members of affected individuals with evidence of early RA specific immune responses. Deane and colleagues reported one such investigation exploring antibody responses in disease-free relatives of individuals with RA.
Methods:
Clinical and serologic examination was performed on RA-free first degree relatives of RA patients. The associations of autoantibody status, in particular a “high-risk” profile defined as anti-CCP antibody positivity or two or more rheumatoid factor (RF) isotypes, with the levels of systemic inflammatory cytokines were explored.
Results:
A total of 582 first degree relatives underwent clinical examinations. Of these, none met classification criteria for RA. A single RF isotype was observed in 55 first-degree relatives (9.5%) while the “high risk” antibody profile was observed in 27 (4.6%). Antibody positive first degree relatives had significantly higher levels of GM-CSF, IL-1α and IL-1β compared to antibody negative first degree relatives.
Conclusions:
Disease free first-degree relatives of RA patients with serologic evidence of RA-associated autoimmunity have evidence of elevated systemic inflammation.
Editorial Comment:
These are interesting findings that help to define the immunologic processes occurring during the early initiating and propagating phases of RA. Longer term follow-up is needed to determine whether the relatives with the “high risk” profile eventually develop RA or other autoimmune disorders. For those that do not, comparing the immunologic differences between those with progression and those without may help determine the key factors involved in the transition from asymptomatic serologic findings to symptomatic disease.
Abstract 1935: Circulating 25-OH Vitamin D Concentrations in African Americans with Recent-Onset Rheumatoid Arthritis
Authors:
Mikuls, Yu, Craig, Moreland, Bridges; Omaha, Nebraska, United States
Background:
Vitamin D plays an important role in calcium homeostasis and maintenance of bone. It is also implicated in immune function, including autoimmunity. Low vitamin D intake has been implicated as a risk factor for the development of inflammatory arthritis in Caucasians. African Americans often have lower vitamin D levels than Caucasians; however, no investigations have explored whether vitamin D is a risk factor for RA or RA severity in this population.
Methods:
Subjects enrolled in the CLEAR registry of African Americans with recent onset RA were studied. The associations of low baseline 25-OH vitamin D (defined as below 37.5 nmol/ml) with RA characteristics at baseline and after 36 months of follow-up were explored.
Results:
Among the 266 enrolled subjects, 132 (50%) were classified as vitamin D deficient. Vitamin D deficiency was associated with enrollment in winter months, alcohol consumption, and inversely associated with reported supplementation with vitamin D. The use of supplemental vitamin D was reported in 15% of subjects; however, 11% of subjects with vitamin D deficiency reported using vitamin D supplements.
At baseline, mean DAS28 was 3.9, mean swollen and tender joint counts were 5 and 8, respectively, and the mean HAQ was 1.6. Vitamin D deficiency was associated with higher levels of pain at enrollment; however, differences were reduced after adjusting for age, gender, and season of enrollment. Vitamin D deficiency was not associated, either positively or negatively, with baseline or follow-up DAS28, joint counts, HAQ, erosions, CRP, or the presence of rheumatoid nodules.
Conclusions:
Although very common in African American RA patients, vitamin D deficiency was not associated with RA activity or severity characteristics.
Editorial Comment:
There has been increasing interest in the last few years in the role of vitamin D as a mediator of health and disease. The immunomodulating effects of vitamin D are well documented, making it a potential candidate for intervention in immune mediated disease. However, the magnitude of vitamin D deficiency in initiating or driving RA inflammation and symptoms remains to be thoroughly investigated. It is somewhat unclear whether the lack of association in this study is more related to biology or methodology, as patients were dichotomized on a somewhat arbitrary level of vitamin D deficiency. In addition, the effect of supplementation of vitamin D to robust levels on disease parameters has not been evaluated.
Abstract 1937: Periodontal Symptoms are Independently Associated with Rheumatoid Arthritis Disease Activity
Authors:
Bingham III, Bartlett, Hildebrant, Jones, Moni, Towns, Bathon, Giles; Baltimore, Maryland, United States
Background:
Both RA and periodontal disease are driven by similar inflammatory mechanisms, suggesting interaction between the two disease processes. Despite this, little is known about the possible impact of periodontal disease in driving RA disease activity and severity. Bingham and colleagues presented results of a study exploring the associations of self-reported periodontal symptoms with RA disease characteristics.
Methods:
Patients enrolled in a cohort study of subclinical cardiovascular disease in RA were queried regarding self-reported oral health and oral dryness, including current periodontal symptoms and past periodontal treatment. The associations of periodontal symptoms with RA disease activity and severity measures were modeled.
Results:
Among the 183 patients studied, most (60%) were female with an average age of 60 years. The median RA duration was 10 years. Approximately 70% were seropositive for RF or anti-CCP antibodies. The median DAS28 score was 3.12 and the median HAQ score was 0.75. Almost 12% of patients were current smokers. A majority of patients (79%) reported at least one periodontal symptom, including receding gums (37%), bleeding gums with brushing (67%), bleeding gums without brushing (9%), and swollen gums (19%). Oral dryness was reported in 36% of patients.
In univariate analyses, patients who reported both gum bleeding and swelling had significantly higher DAS28, HAQ, and physician global assessment of disease scores, and were more likely to have rheumatoid nodules on exam. After adjusting for age, gender, race, aspirin use, smoking, alcohol intake, education, treatment, and oral hygiene habits, higher DAS28 scores and rheumatoid nodules remained significantly associated with periodontal symptoms. Within groups stratified by periodontal symptoms, patients who reported oral dryness had significantly higher DAS28 scores.
In a sub-study validating self-report against full mouth exams (n=26), the odds of having exam verified periodontal disease was 2.6 times higher in those reporting symptoms, resulting in a specificity of 0.75; sensitivity of 0.40, and positive predictive value of 0.60.
Conclusions:
Self-reported oral and periodontal symptoms were highly associated with disease activity in RA patients, independent of important sociodemographic and disease related confounders and oral hygiene habits.
Editorial Comment:
This study, originating from our center, is one of the first to identify a strong link between periodontal disease and disease activity in RA. Whether periodontal disease contributes to RA disease activity or whether RA disease activity drives periodontal disease cannot be addressed within the context of this cross-sectional design. Longitudinal evaluation will help to determine whether RA therapies improve periodontal disease, independent of the possible confounding effects of improvement in physical function; however, whether effective treatment for periodontal disease may result in improvements in RA is another intriguing possibility. If proven, periodontal treatment may represent a non-pharmacologic adjunctive therapy for RA.
Abstract 1938: Rheumatoid Arthritis is Associated with a Higher Prevalence of Carotid Plaque in the Internal, but not Common, Carotid Artery
Authors:
Kobayashi, Giles, Polak, Blumenthal, Szklo, Petri, Gelber, Post, Bathon; Baltimore, Maryland, United States
Background:
Whether RA patients have more carotid atherosclerosis compared to non-RA controls has not been consistently demonstrated in the literature. One explanation is that most studies have studied only the common carotid artery; however, studies in non-RA populations have determined that internal carotid atherosclerosis may be more highly associated with inflammation than the common carotid and that internal carotid artery atherosclerosis may be more highly associated with cardiovascular outcomes, such as stroke and myocardial infarction. Kobayashi and colleagues reported the results of an ultrasonographic study of the common and internal carotid arteries in RA patients without known cardiovascular disease.
Methods
Men and women 45 – 84 years of age enrolled in a cohort study of subclinical cardiovascular disease in RA underwent high-resolution B-mode ultrasonography of both common and internal carotid arteries. Intima-media thickness (IMT) was measured for the common and internal carotid arteries and the presence of plaque in the internal carotid was assessed and compared between RA patients and a group of non-RA patients frequency matched to the RA group based on age, gender, and race. The association of RA characterisitics with carotid IMT and plaque was also explored.
Results
A total of 195 RA patients were compared to 198 demographically matched non-RA controls. Most (60%) of patients were female with an average age of 60 years. Traditional cardiovascular risk factors were balanced between the two groups; however, CRP and IL-6 levels were significantly higher in RA patients.
The mean internal carotid IMT was higher in RA patients vs. controls (1.16 vs. 1.02 mm; p<0.001) after adjusting for demographics and cardiovascular risk factors, a difference that was larger in men than women. In contrast, mean common carotid IMT did not differ between RA and control subjects in either crude or adjusted analyses. The prevalence of internal carotid plaque was higher in RA patients (22%) compared to control patients (12%), yielding an adjusted odds ratio of 2.3 for plaque in RA (p=0.011). The largest relative difference in plaque between RA patients and controls was observed in the youngest age group studied (45-54 years), in which the adjusted odds of plaque was 10 times higher in the RA patients compared to controls (OR 10.02; p=0.035).
The associations of traditional cardiovascular risk factors with common and internal carotid IMT and plaque were similar in both the RA and control groups, with the exception of IL-6, which was highly associated with internal carotid IMT and plaque in control patients but showed no association in RA patients.
The only RA characteristic significantly associated with an increased risk of plaque was the HLA-DRB1 shared epitope, in which patients with one or more copies had an almost 3 times greater odds of plaque compared to those with no shared epitope alleles (OR 2.8 (95% CI 1.07-7.33)) in adjusted models.
Conclusions
RA patients demonstrated greater IMT and plaque in the internal carotid, but not common carotid, than controls. This may explain discrepant findings in previously published studies of carotid ultrasound in RA.
Editorial Comment
This study, originating from our center, raises the possibility of site-specific atherosclerotic risk in RA patients. Prior findings from the Framingham study demonstrating that internal carotid atherosclerosis may be more highly associated with elevated inflammatory markers could explain why RA patients would be more prone to atherosclerosis at this site. However, there was no detected association of current IL-6 or CRP levels with internal carotid IMT or plaque in RA patients in this study. This may indicate a true lack of association or, more likely, may reflect instability in current IL-6 levels in these patients with, in general, long-standing disease. Longitudinal investigation with follow-up ultrasound assessments will help to determine the impact of intercurrent inflammation on carotid atherosclerosis progression.
