Elena Myasoedova

Is the incidence of rheumatoid arthritis rising?: Results from Olmsted County, Minnesota, 1955–2007

OBJECTIVE To examine trends in the incidence and prevalence of rheumatoid arthritis (RA) from 1995 to 2007. METHODS To augment our preexisting inception cohort of patients with RA (1955-1994), we assembled a population-based incidence cohort of individuals >or=18 years of age who first fulfilled the American College of Rheumatology 1987 criteria for the classification of RA between January 1, 1995 and December 31, 2007 and a cohort of patients with prevalent RA on January 1, 2005. Incidence and prevalence rates were estimated and were age-and sex-adjusted to the white population in the US in 2000. Trends in incidence rates were examined using Poisson regression methods. RESULTS The 1995-2007 incidence cohort comprised 466 patients (mean age 55.6 years), 69% of whom were female and 66% of whom were rheumatoid factor positive. The overall age- and sex-adjusted annual RA incidence was 40.9/100,000 population. The age-adjusted incidence in women was 53.1/100,000 population (versus 27.7/100,000 population in men). During the period of time from 1995 to 2007, the incidence of RA increased moderately in women (P = 0.02) but not in men (P = 0.74). The increase was similar among all age groups. The overall age- and sex-adjusted prevalence on January 1, 2005 was 0.72% (95% confidence interval [95% CI] 0.66, 0.77), which is an increase when compared with a prevalence of 0.62% (95% CI 0.55, 0.69) in 1995 (P < 0.001). Applying the prevalence on January 1, 2005 to the US population in 2005 showed that an estimated 1.5 million US adults were affected by RA. This is an increase from the previously reported 1.3 million adults with RA in the US. CONCLUSION The incidence of RA in women appears to have increased during the period of time from 1995 to 2007. The reasons for this recent increase are unknown, but environmental factors may play a role. A corresponding increase in the prevalence of RA was also observed.

Lipid paradox in rheumatoid arthritis: the impact of serum lipid measures and systemic inflammation on the risk of cardiovascular disease

Objective To examine the impact of systemic inflammation and serum lipids on cardiovascular disease (CVD) in rheumatoid arthritis (RA). Methods In a population-based RA incident cohort (1987 American College of Rheumatology criteria first met between 1988 and 2007), details were collected of serum lipid measures, erythrocyte sedimentation rates (ESRs), C-reactive protein (CRP) measures and cardiovascular events, including ischaemic heart disease and heart failure. Cox models were used to examine the association of lipids and inflammation with the risk of CVD and mortality, adjusting for age, sex and year of RA incidence. Results The study included 651 patients with RA (mean age 55.8 years, 69% female); 67% were rheumatoid factor positive. ESR was associated with the risk of CVD (HR=1.2 per 10 mm/h increase, 95% CI 1.1 to 1.3). Similar findings, although not statistically significant, were seen with CRP (p=0.07). A significant non-linear association for total cholesterol (TCh) with risk of CVD was found, with 3.3-fold increased risk for TCh <4 mmol/l (95% CI 1.5 to 7.2) and no increased risk of CVD for TCh ≥4 mmol/l (p=0.57). Low low-density lipoprotein cholesterol (LDL <2 mmol/l) was associated with marginally increased risk of CVD (p=0.10); there was no increased risk for LDL ≥2 mmol/l (p=0.76). Conclusion Inflammatory measures (particularly, ESR) are significantly associated with the risk of CVD in RA. Lipids may have paradoxical associations with the risk of CVD in RA, whereby lower TCh and LDL levels are associated with increased cardiovascular risk.

The lifetime risk of adult‐onset rheumatoid arthritis and other inflammatory autoimmune rheumatic diseases

OBJECTIVE Understanding of the personal risks for rheumatoid arthritis (RA) and other rheumatic diseases remains poor, despite advances in knowledge with regard to their pathogenesis, therapeutics, and clinical impact, in part because the personal lifetime risk of developing these diseases is unknown. This study was undertaken to estimate the lifetime risk of RA, as well as other inflammatory autoimmune rheumatic diseases, including systemic lupus erythematosus, psoriatic arthritis, polymyalgia rheumatica (PMR), giant cell arteritis, ankylosing spondylitis, and Sjögrens syndrome, and to provide an overall estimate of the risk of developing inflammatory autoimmune rheumatic disease over a lifetime. METHODS Using the incidence rates obtained from our population-based studies of rheumatic diseases among residents of Olmsted County, Minnesota, and mortality rates from life tables for the general population, we estimated the sex-specific lifetime risk of rheumatic disease. RESULTS The lifetime risk of RA developing in US adults was 3.6% for women and 1.7% for men, and the lifetime risk of rheumatoid factor-positive RA was 2.4% for women and 1.1% for men. The second most common inflammatory autoimmune rheumatic disease was PMR, with a lifetime risk of 2.4% for women and 1.7% for men. The overall lifetime risk of inflammatory autoimmune rheumatic disease was 8.4% for women and 5.1% for men. CONCLUSION One in 12 women and 1 in 20 men will develop an inflammatory autoimmune rheumatic disease during their lifetime. These results can serve as useful guides in counseling patients regarding their lifetime risk of these conditions and have important implications regarding disease awareness campaigns.

Total Cholesterol and LDL levels decrease before rheumatoid arthritis

Objectives To compare lipid profiles in patients with rheumatoid arthritis (RA) and in non-RA subjects during the 5 years before and 5 years after the RA incidence/index date. Methods Lipid measures were abstracted in a population-based incident cohort of patients with RA (1987 American College of Rheumatology criteria) first diagnosed between 1 January 1988 and 1 January 2008 and in non-RA subjects. Random-effects models adjusting for age, sex and calendar year were used to examine trends in lipid profiles, accounting for multiple measurements for each subject. Results The study population included a cohort of 577 patients with RA (a total of 3088 lipid measurements) and 540 non-RA subjects (a total of 3048 lipid measurements). There were significant decreases in total (TC) and low-density lipoprotein cholesterol (LDL) levels in the RA cohort during the 5 years before RA, compared with the non-RA cohort (p<0.001). Decreases of 0.58 mmol/l for TC and 0.61 mmol/l for LDL were noted in RA compared with decreases of 0.09 mmol/l for TC and 0.22 mmol/l for LDL in the non-RA cohort. Trends in other lipid measures (triglycerides (TGs) and high-density lipoprotein cholesterol (HDL)) were similar in RA and non-RA cohorts during the 5 years before and 5 years after the RA incidence/index date. During the 5 years before the RA incidence/index date, the proportion of patients with RA with elevated TC or LDL measures, but not with abnormal HDL and TG measures, significantly decreased compared with non-RA subjects. Lipid-lowering drugs (statins in particular) were less often prescribed to patients with RA than to non-RA subjects (34% vs 41%; p=0.02). Conclusion TC and LDL levels and the prevalence of abnormal TC or LDL measures decreased significantly during the 5 years before the RA incidence/index date in patients with RA as compared with the non-RA cohort. These trends in lipid profile in RA are unlikely to be solely due to lipid-lowering treatment.

Epidemiology of Rheumatoid Arthritis: Rheumatoid Arthritis and Mortality

Increased mortality in rheumatoid arthritis (RA) is widely recognized but not fully explained. Despite substantial improvements in management and growing knowledge of the determinants of increased mortality, evidence for reduction in mortality in RA has lagged behind. Indeed, most studies report no apparent reduction in mortality in RA. However, emerging evidence from some recent RA inception cohorts suggests no increased mortality, including cardiovascular mortality, but this awaits further confirmation. Although it is possible that recent advances in RA treatment may manifest in improvement of survival in the near future, other factors, including undertreated or unrecognized low-grade inflammation, comorbidities, and immunogenetic factors, may contribute to the excess mortality in RA and impede its improvement. In this review, we summarize the current knowledge of the rates and determinants of mortality in RA, identify and discuss potential explanations for excess mortality, and outline promising research avenues for targeting mortality in RA.

Increased prevalence of diastolic dysfunction in rheumatoid arthritis

Objective To compare the prevalence of left ventricular (LV) diastolic dysfunction in subjects with and without rheumatoid arthritis (RA), among those with no history of heart failure (HF), and to determine risk factors for diastolic dysfunction in RA. Methods A cross-sectional, community-based study comparing cohorts of adults with and without RA and without a history of HF was carried out. Standard two-dimensional/Doppler echocardiography was performed in all participants. Diastolic dysfunction was defined as impaired relaxation (with or without increased filling pressures) or advanced reduction in compliance or reversible or fixed restrictive filling. Results The study included 244 subjects with RA and 1448 non-RA subjects. Mean age was 60.5 years in the RA cohort (71% female) and 64.9 years (50% female) in the non-RA cohort. The vast majority (>98%) of both cohorts had preserved ejection fraction (EF≥50%). Diastolic dysfunction was more common in subjects with RA at 31% compared with 26% (age and sex adjusted) in non-RA subjects (OR=1.6; 95% CI 1.2 to 2.4). Patients with RA had significantly lower LV mass, higher pulmonary arterial pressure and higher left atrial volume index than non-RA subjects. RA duration and interleukin 6 (IL-6) level were independently associated with diastolic dysfunction in RA even after adjustment for cardiovascular risk factors. Conclusion Subjects with RA have a higher prevalence of diastolic dysfunction than those without RA. RA duration and IL-6 are independently associated with diastolic dysfunction, suggesting the impact of chronic autoimmune inflammation on myocardial function in RA. Clinical implications of these findings require further investigation.

The influence of rheumatoid arthritis disease characteristics on heart failure.

Objective. To examine the influence of rheumatoid arthritis (RA) characteristics and antirheumatic medications on the risk of heart failure (HF) in patients with RA. Methods. A population-based incidence cohort of RA patients aged ≥ 18 years (1987 American College of Rheumatology criteria first met between January 1, 1980, and January 1, 2008) with no history of HF was followed until onset of HF (defined by Framingham criteria), death, or January 1, 2008. We collected data on RA characteristics, antirheumatic medications, and cardiovascular (CV) risk factors. Cox models adjusting for age, sex, and calendar year were used to analyze the data. Results. The study included 795 RA patients [mean age 55.3 yrs, 69% women, 66% rheumatoid factor (RF)-positive]. During the mean followup of 9.7 years, 92 patients developed HF. The risk of HF was associated with RF positivity (HR 1.6, 95% CI 1.0, 2.5), erythrocyte sedimentation rate (ESR) at RA incidence (HR 1.6, 95% CI 1.2, 2.0), repeatedly high ESR (HR 2.1, 95% CI 1.2, 3.5), severe extraarticular manifestations (HR 3.1, 95% CI 1.9, 5.1), and corticosteroid use (HR 2.0, 95% CI 1.3, 3.2), adjusting for CV risk factors and coronary heart disease (CHD). Methotrexate users were half as likely to have HF as nonusers (HR 0.5, 95% CI 0.3, 0.9). Conclusion. Several RA characteristics and the use of corticosteroids were associated with HF, with adjustment for CV risk factors and CHD. Methotrexate use appeared to be protective against HF. These findings suggest an independent effect of RA on HF that may be further modified by antirheumatic treatment.

Increased Prevalence of Metabolic Syndrome Associated with Rheumatoid Arthritis in Patients without Clinical Cardiovascular Disease

Objective. To examine whether patients with rheumatoid arthritis (RA) with no overt cardiovascular disease (CVD) have a higher prevalence of metabolic syndrome (MetS) than subjects without RA or CVD. We also examined whether RA disease characteristics are associated with the presence of MetS in RA patients without CVD. Methods. Subjects from a population-based cohort of patients who fulfilled 1987 American College of Rheumatology criteria for RA between January 1, 1980, and December 31, 2007, were compared to non-RA subjects from the same population. All subjects with any history of CVD were excluded. Waist circumference, body mass index (BMI), and blood pressure were measured during the study visit. Data on CVD, lipids, and glucose measures were ascertained from medical records. MetS was defined using NCEP/ATP III criteria. Differences between the 2 cohorts were examined using logistic regression models adjusted for age and sex. Results. The study included 232 RA subjects without CVD and 1241 non-RA subjects without CVD. RA patients were significantly more likely to have increased waist circumference and elevated blood pressure than non-RA subjects, even though BMI was similar in both groups. Significantly more RA patients were classified as having MetS. In RA patients, MetS was associated with Health Assessment Questionnaire Disability Index, large-joint swelling, and uric acid levels, but not with C-reactive protein or RA therapies. Conclusion. Among subjects with no history of CVD, patients with RA are more likely to have MetS than non-RA subjects. MetS in patients with RA was associated with some measures of disease activity.

The role of rheumatoid arthritis (RA) flare and cumulative burden of RA severity in the risk of cardiovascular disease

Objective To examine the role of rheumatoid arthritis (RA) flare, remission and RA severity burden in cardiovascular disease (CVD). Methods In a population-based cohort of patients with RA without CVD (age ≥30 years; 1987 American College of Rheumatology criteria met in 1988–2007), we performed medical record review at each clinical visit to estimate flare/remission status. The previously validated RA medical Records-Based Index of Severity (RARBIS) and Claims-Based Index of RA Severity (CIRAS) were applied. Age- and sex-matched non-RA subjects without CVD comprised the comparison cohort. Cox models were used to assess the association of RA activity/severity with CVD, adjusting for age, sex, calendar year of RA, CVD risk factors and antirheumatic medications. Results Study included 525 patients with RA and 524 non-RA subjects. There was a significant increase in CVD risk in RA per time spent in each acute flare versus remission (HR 1.07 per 6-week flare, 95% CI 1.01 to 1.15). The CVD risk for patients with RA in remission was similar to the non-RA subjects (HR 0.90, 95% CI 0.51 to 1.59). Increased cumulative moving average of daily RARBIS (HR 1.16, 95% CI 1.03 to 1.30) and CIRAS (HR 1.38, 95% CI 1.12 to 1.70) was associated with CVD. CVD risk was higher in patients with RA who spent more time in medium (HR 1.08, 95% CI 0.98 to 1.20) and high CIRAS tertiles (HR 1.18, 95% CI 1.06 to 1.31) versus lower tertile. Conclusions Our findings show substantial detrimental role of exposure to RA flare and cumulative burden of RA disease severity in CVD risk in RA, suggesting important cardiovascular benefits associated with tight inflammation control and improved flare management in patients with RA.

Incidence and time trends of Herpes zoster in rheumatoid arthritis: a population-based cohort study

To determine the incidence, time trends, risk factors, and severity of herpes zoster in a population‐based cohort of patients with newly diagnosed rheumatoid arthritis (RA) compared to a group of individuals without RA from the same population.