Matteson, Eric L.

ObjectiveTo determine trends in the incidence and clinical presentation of ankylosing spondylitis (AS), the incidence of cardiovascular disease (CVD), and cardiovascular (CV) risk factors among patients with AS and compare the observed incidence of CVD with that predicted by the Framingham Risk Score (FRS).MethodsA population‐based inception cohort of residents of Olmsted County, Minnesota age ≥18 years who fulfilled Modified New York Criteria for AS in 1980–2009 was assembled. Clinical features at presentation were recorded. Age‐ and sex‐adjusted incidence rates and survival were estimated. Incident CVD and CV risk factors were identified. The 10‐year CVD risk was calculated using the FRS. Standardized incidence ratios (ratios of observed CVD in AS to that predicted by the FRS) were calculated.ResultsEighty‐six patients were diagnosed with AS over the study period with an age‐ and sex‐adjusted incidence of 3.1 per 100,000 (95% confidence interval [95% CI] 2.5–3.8). The mean age at diagnosis was 35 years (range 19–69 years). Inflammatory back pain, seen in 90% of patients, was the most common presenting manifestation. The 10‐year mean ± SD cumulative incidence of CVD was 15.8% ± 6.1%, three times higher than the predicted events based on the FRS (standardized incidence ratio 3.01, 95% CI 1.35–6.69; P = 0.007). Overall survival was similar to the general population.ConclusionAS occurs in approximately 3 persons per 100,000 per year. Clinical features, extraarticular manifestations, and interval from symptom onset to diagnosis have remained constant in this population over the study period. The CVD risk in these patients is higher than expected and underestimated by the FRS.

Objective Epidemiologic studies comparing the incidence and prevalence of systemic lupus erythematosus (SLE) and isolated cutaneous lupus erythematosus (CLE) are few. Olmsted County, Minnesota provides a unique setting for such a study owing to resources of the Rochester Epidemiology Project. We sought to describe and compare the incidence and prevalence of SLE and CLE from 1993–2005. Methods SLE cases were identified from review of medical records and fulfilled the 1982 American College of Rheumatology classification criteria. CLE cases included patients with classic discoid lupus erythematosus, subacute CLE, lupus panniculitis, and bullous lupus erythematosus. Age‐ and sex‐adjusted incidence and prevalence were standardized to the 2000 US white population. Results The age‐ and sex‐adjusted incidence of SLE (2.9 per 100,000; 95% confidence interval [95% CI] 2.0–3.7) was similar to that of CLE (4.2 per 100,000; 95% CI 3.1–5.2, P = 0.10). However, the incidence of CLE was 3 times higher than SLE in men (2.4 versus 0.8 per 100,000; P = 0.009). The age‐ and sex‐adjusted prevalence of CLE on January 1, 2006 was higher than that of SLE (70.4 versus 30.5 per 100,000; P < 0.001). The prevalences of CLE and SLE in women were similar, but the prevalence of CLE was higher in men than in women (56.9 versus 1.6 per 100,000; P < 0.001). The incidence of CLE rose steadily with age and peaked at 60–69 years. Conclusion The incidences of CLE and SLE are similar, but CLE is more common than SLE in men and in older adults. These findings may reflect differences in genetic or environmental etiology of CLE.

Objective. To evaluate whether hyperuricemia is a risk factor for cardiovascular disease (CVD) in patients with rheumatoid arthritis (RA).Methods. A population-based inception cohort of patients diagnosed between 1980 and 2007 with adult-onset RA was assembled. A comparison cohort of age- and sex-matched subjects without RA (non-RA) was also assembled. All clinically obtained uric acid values were collected. CVD and noncardiac vascular events were recorded for each patient. Cox proportional hazards models were used to assess the impact of hyperuricemia on development of CVD, mortality, and noncardiac vascular disease.Results. In patients without RA, hyperuricemia was associated with heart failure (HR: 1.95; 95% CI: 1.13–3.39) and CVD (HR: 1.59; 95% CI: 0.99–2.55). In patients with RA, hyperuricemia was not significantly associated with CVD but was significantly associated with peripheral arterial events (HR: 2.52; 95% CI: 1.17–5.42). Hyperuricemia appeared to be more strongly associated with mortality among RA patients (HR: 1.96; 95% CI: 1.45–2.65) than among the non-RA subjects (HR: 1.57; 95% CI: 1.09–2.24).Conclusion. In patients with RA, hyperuricemia was a significant predictor of peripheral arterial events and mortality but not of CVD.

Objective To assess the occurrence of acute coronary syndrome (ACS) in patients with giant cell arteritis (GCA) compared to subjects without GCA. Methods We retrospectively reviewed a population‐based incidence cohort of Olmsted County, Minnesota residents with GCA diagnosed in 1950–2009. We compared this cohort with a cohort of patients without GCA of similar age, sex, and calendar year from the same population. Results The study included 245 patients with GCA and 245 non‐GCA subjects. The mean ± SD Framingham cardiovascular risk score was 30% ± 19% in GCA patients and 34% ± 23% in non‐GCA subjects ( P = 0.096) at the incidence/index date. Diabetes mellitus was significantly less common in GCA patients than non‐GCA subjects at the index date. The mean high‐density lipoprotein was higher and triglycerides were lower, with fewer patients taking lipid‐lowering medications in the GCA cohort compared to the non‐GCA cohort at the index date. During followup, no difference between the 2 cohorts was noted in the overall rate of ACS events (hazard ratio 0.74, 95% confidence interval 0.44–1.26). Overall thrombosis in myocardial infarction scores were similar in both cohorts. Revascularization procedures were done less frequently in GCA than in non‐GCA subjects (19% versus 50%; P = 0.015). Post‐ACS hospital length of stays and complications were similar in both cohorts. Conclusion Multiple cardiovascular risk factors are less atherogenic at incidence of GCA. There is no overall increased risk of ACS in patients with GCA.

ObjectiveTo examine trends in glucocorticoid (GC) use and dosing among patients diagnosed with rheumatoid arthritis (RA) over time.MethodsA population‐based inception cohort of RA patients diagnosed during 1980–2007 was followed longitudinally through their medical records until death, migration, or December 31, 2008. GC start and stop dates were collected, along with doses in prednisone equivalents.ResultsThe study population comprised 349 patients (68% women) diagnosed in 1980–1994 and 464 (69% women) diagnosed in 1995–2007, with a median followup of 15.3 and 5.7 years, respectively. A higher proportion of patients started GCs in their first year of disease in 1995–2007 (68% versus 36%; P < 0.001), but the starting dose (mean 8.7 versus 10.3 mg; P = 0.08) and cumulative dose in the first year of use (mean 1.8g [mean daily dose 4.9 mg] versus 2.1 gm [mean daily dose 5.8 mg]; P = 0.48) were not different. A higher proportion also discontinued GCs in their first year of disease in the 1995–2007 cohort (P < 0.001). These differences in GC initiation and discontinuation persisted throughout followup. Prevalence of GC use was higher in the 1995–2007 cohort for the first 3 years of disease.ConclusionMore patients are starting GCs early in their disease course now compared to previously, which is consistent with established treatment guidelines. A higher proportion are also discontinuing GCs, but the proportion of patients taking GCs at any given point of disease during the first 4 years is higher now than previously. Despite early addition of a disease‐modifying antirheumatic drug, some patients may not be able to discontinue GCs over the long term.

Objective A very few studies describe the epidemiology of primary Sjögren's syndrome (pSS). The reported frequency of pulmonary involvement in pSS varies widely depending on the detection method employed, and consists mainly of various forms of airways disease. We aimed to evaluate the incidence and mortality of pSS and of lung disease in pSS, focusing on interstitial lung disease (ILD). Methods A population-based incidence cohort of patients diagnosed with pSS in 1976–2005 was assembled. Diagnosis was based on the 2002 American-European Consensus Group criteria for pSS. Cumulative incidence adjusted for the competing risk of death was estimated. A Cox model with a time-dependent covariate was used to determine the incidence and the standardised mortality HR of pSS. Results 85 patients with pSS were identified (mean age 59.9 years; 91% women). The annual incidence of pSS was 4.2, 95% CI (3.3 to 5.1)/100 000 population and it increased with higher age at pSS diagnosis (18–44 years: 2.1/100 000 vs ≥75 years: 12.3/100 000). Standardised mortality ratio in pSS compared with the general population was 0.92, 95% CI (0.57 to 1.41). A total of 105 patients with pSS and ILD were identified (mean age 58.1 years; 91% women). Among patients with pSS without prior ILD, the cumulative incidence of ILD in patients with pSS was 10% (±3%) at 1 year after diagnosis of pSS and increased to 20% (±4%) by 5 years after pSS. The development of lung disease in pSS was associated with poor survival (HR 2.16; 95% CI 0.99 to 4.74). Conclusions pSS incidence seems to be almost the same as was reported in a previous study conducted among Olmsted County Minnesota population. Survival among patients with pSS and general population does not differ substantially. However, patients with pSS who have ILD likely have increased premature mortality.

ObjectiveTo determine whether the impact of aging on cardiovascular disease (CVD) risk in patients with rheumatoid arthritis (RA) differs from that in the general population (as estimated by the Framingham Risk Score [FRS]).MethodsA population‐based inception cohort of Olmsted County, Minnesota residents ages ≥30 years who fulfilled the American College of Rheumatology 1987 criteria for RA in 1988–2008 was assembled and followed up until death, migration, or July 1, 2012. Data on CVD events were collected by medical records review. The 10‐year FRS for CVD was calculated. Cox models adjusted for FRS were used to examine the influence of age on CVD risk.ResultsThe study included 563 patients with RA without prior CVD (mean age 55 years, 72% women, and 69% seropositive [i.e., rheumatoid factor and/or anti–citrullinated protein antibody positive]). During a mean followup of 8.2 years, 98 patients developed CVD (74 seropositive and 24 seronegative), but the FRS predicted only 59.7 events (35.4 seropositive and 24.3 seronegative). The gap between observed and predicted CVD risk increased exponentially across age, and the effect of age on CVD risk in seropositive RA was nearly double its effect in the general population, with additional log(age) coefficients of 2.91 for women (P = 0.002) and 2.06 for men (P = 0.027).ConclusionOur findings indicate that age exerts an exponentially increasing effect on CVD risk in seropositive RA, but no increased effect among seronegative patients. The causes of accelerated aging in patients with seropositive RA deserve further investigation.

Abstract Altered B cell function is important in the pathogenesis of rheumatoid arthritis (RA). In this report, we show that patients with active RA have an increased frequency of CD32B low/neg cells in the CD27+IgD− memory B cell subset and that these changes are associated with phenotypic and functional B cell activation. Studies using PBMCs from healthy donors revealed that downregulation of CD32B on B cells is mediated by CD40–CD40L interactions and is potentiated by IL-4 and inhibited by both IL-10 and IL-21. These findings appear physiologically relevant because CD4 T cell expression of CD40L correlated with the frequency of CD32B low/neg cells in the CD27+IgD− memory B subset in patients with RA. Our data support a model in which high levels of CD40L, present on circulating T cells in patients with RA, causes B cell activation and CD32B downregulation, resulting in secondary protection of memory B cells from CD32B-mediated cell death.

ObjectiveTo examine lipid profiles among statin‐naive patients with rheumatoid arthritis (RA) and those without RA before and after the initiation of statins.MethodsInformation regarding lipid measures and statin use was gathered in a population‐based incident cohort of patients with RA (1987 American College of Rheumatology criteria first met between January 1, 1988 and January 1, 2008) and in a cohort of non‐RA subjects from the same underlying population. Only patients with no prior history of statin use were included.ResultsThe study included 161 patients with RA (mean age 56.3 years, 57% female) and 221 non‐RA subjects (mean age 56.0 years, 66% female). Prior to the start of statins, the levels of total cholesterol and low‐density lipoprotein (LDL) cholesterol were lower in the RA versus the non‐RA cohort (P < 0.001 and P = 0.003, respectively). The absolute and percentage change in LDL cholesterol after at least 90 days of statin use tended to be smaller in the RA versus the non‐RA cohort (P = 0.03 and P = 0.09, respectively). After at least 90 days of statin use, patients with RA were less likely to achieve therapeutic goals for LDL cholesterol than the non‐RA subjects (P = 0.046). Increased erythrocyte sedimentation rate (ESR) at baseline (odds ratio 0.47, 95% confidence interval 0.26–0.85) was associated with lower likelihood of achieving therapeutic LDL goals.ConclusionPatients with RA had lower total cholesterol and LDL cholesterol levels before statin initiation and lower likelihood of achieving therapeutic LDL goals following statin use than the non‐RA subjects. Some RA disease characteristics, in particular ESR at baseline, may have an adverse impact on achieving therapeutic LDL goals.