PMCC PMCC

Search tips
Search criteria

Advanced
Results 1-25 (62)
 

Clipboard (0)
None

Select a Filter Below

Authors
more »
Year of Publication
Document Types
1.  Heart Disease and Rheumatoid Arthritis: Understanding the Risks 
Annals of the rheumatic diseases  2010;69(0 1):i61-i64.
Patients with rheumatoid arthritis (RA) are at increased risk of mortality compared with the general population. Evidence suggests that this increased mortality can largely be attributed to increased cardiovascular (CV) death. In a retrospective study of an inception cohort of RA patients in Rochester, MN, we investigated the contribution of traditional and RA-specific risk factors towards this increased risk of CV morbidity and mortality. Several traditional CV risk factors were found to behave differently in RA patients. In addition, their associations with CV disease are weaker in RA patients as increased inflammation associated with RA appears to also contribute substantially to the increased CV mortality. Furthermore, the impact of disease modifying anti-rheumatic drugs (DMARDs) and biologics on CV disease in RA patients is unclear. CV risk scores for the general population may underestimate risk for RA patients. Together with other studies that have demonstrated similar associations between RA and CV mortality, these data suggest that optimal control of CV risk factors is important, but not sufficient in RA patients. RA-specific CV risk prediction tools are needed, as well as clinical trials to assess the impact of therapies and tight control of inflammation in RA patients on CV outcomes and mortality.
doi:10.1136/ard.2009.119404
PMCID: PMC4308040  PMID: 19995747
2.  Large-Vessel Involvement in Giant Cell Arteritis: A Population-Based Cohort Study of the Incidence-Trends and Prognosis 
Annals of the rheumatic diseases  2012;72(12):1989-1994.
Objectives
To evaluate incidence trends and timing of large-vessel (LV) manifestations in patients with giant cell arteritis (GCA), and, to examine the influence of LV manifestations on survival.
Methods
A population-based incident cohort of patients diagnosed with GCA between 1950 and 2004 was used. LV involvement was defined as large artery stenosis or aortic aneurysm/dissection that developed in the 1 year prior to GCA diagnosis or any time thereafter. Patients were followed until death or December 31, 2009.
Results
The study included 204 patients, 80% women, mean age at diagnosis of GCA 76.0 years (± 8.2 years). Median length of follow-up was 8.8 years. The cumulative incidence of any LV manifestation at 10 years was 24.9% for patients diagnosed with GCA between 1980–2004 compared to 8.3% for patients diagnosed with GCA between 1950 and 1979. The incidence of any LV event was high within the first year of GCA diagnosis. The incidence of aortic aneurysm/dissection increased 5 years after GCA diagnosis.
Compared to the general population, survival was decreased in patients with an aortic aneurysm/dissection (p<0.001) but not in patients with large-artery stenosis (p=0.11). Patients with GCA and aortic manifestations had higher than expected number of deaths from cardiovascular and pulmonary causes compared to the general population. Among patients with GCA, aortic manifestations were associated with increased mortality (HR: 3.4; 95% CI: 2.2, 5.4).
Conclusions
Screening for aortic aneurysms should be considered in all patients with GCA with vigilance 5 years after incidence. Aortic aneurysm/dissection is associated with increased mortality in GCA.
doi:10.1136/annrheumdis-2012-202408
PMCID: PMC4112513  PMID: 23253927
Giant cell arteritis; aortic aneurysm; aortic dissection; large-artery stenosis; survival
3.  Rheumatoid Arthritis and Cardiovascular Disease 
American heart journal  2013;166(4):622-628.e1.
Background
Rheumatic disease and heart disease share common underpinnings involving inflammation. The high levels of inflammation that characterize rheumatic diseases provide a “natural experiment” to help elucidate the mechanisms by which inflammation accelerates heart disease. Rheumatoid arthritis (RA) is the most common of the rheumatic diseases and has the best studied relationships with heart disease.
Methods
Review of current literature on heart disease and rheumatoid arthritis
Results
Patients with RA have an increased risk of developing heart disease that is not fully explained by traditional cardiovascular risk factors. Therapies used to treat RA may also affect the development of heart disease; by suppressing inflammation, they may also reduce the risk of heart disease. However, their other effects, as in the case of steroids, may increase heart disease risk.
Conclusions
Investigations of the innate and adaptive immune responses occurring in RA may delineate novel mechanisms in the pathogenesis of heart disease, and help identify novel therapeutic targets for the prevention and treatment of heart disease.
doi:10.1016/j.ahj.2013.07.010
PMCID: PMC3890244  PMID: 24093840
4.  Are Young Women and Men with Rheumatoid Arthritis at Risk for Fragility Fractures? A Population-Based Study 
The Journal of rheumatology  2013;40(10):1669-1676.
Objective
Older women and men with rheumatoid arthritis (RA) are at increased risk for fractures, but limited information is available on fracture risk in younger individuals with RA, and whether such risk occurs early following disease onset or only when older. We determined the risk for fractures in both young and older women and men following RA diagnosis.
Methods
We studied a population-based inception cohort with RA from Olmsted County, Minnesota. We identified 822 women and 349 men diagnosed with RA between 1955 and 2007 (308 women and 110 men diagnosed before age 50) and an equal number of paired non-RA subjects, matched by sex and birth year. Incident fractures were collected through review of complete (inpatient and outpatient) medical records available through the linkage system of the Rochester Epidemiology Project.
Results
The hazard ratio (HR) [95% CI] for a non-pathologic fracture occurring from no more than moderate trauma was 1.63 [1.36–1.96] for women and 1.40 [1.02–1.93] for men with RA. Findings were consistent for women and men diagnosed with RA at age ≥ 50 years (HR: 1.43 [1.16–1.77] and 1.34 [0.92–1.94], respectively), or at age < 50 years (HR: 2.34 [1.61–3.42] and 1.74 [0.91–3.30], respectively). However, young women, but not young men, with RA were at increased fracture risk even before age 50 years (HR: 1.95 [1.08–3.51] and 0.82 [0.28–2.45], respectively).
Conclusion
Young men with RA are at increased risk for fractures only when older, whereas young women with RA have an elevated fracture risk even while still young.
doi:10.3899/jrheum.121493
PMCID: PMC3910326  PMID: 23950189
rheumatoid arthritis; bone fractures; osteoporosis; epidemiology
5.  The Impact of Statin Use on Lipid Levels in Statin-Naive Patients with Rheumatoid Arthritis (RA) vs. non-RA Subjects: Results from a Population-Based Study 
Arthritis care & research  2013;65(10):1592-1599.
Objectives
To examine lipid profiles among statin-naive patients with rheumatoid arthritis (RA) and those without RA before and after the initiation of statins.
Methods
Information regarding lipid measures and statin use was gathered in a population-based incident cohort of patients with RA (1987 ACR criteria first met between 1/1/1988 and 1/1/2008) and in a cohort of non-RA subjects from the same underlying population. Only patients with no prior history of statin use were included.
Results
The 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 (TC) and low-density lipoprotein cholesterol (LDL) were lower in RA vs non-RA cohort (p<0.001 and p=0.003, respectively). The absolute and percent change in LDL after at least 90 days of statin use tended to be smaller in RA vs non-RA cohort (p=0.03 and p=0.09). After at least 90 days of statin use patients with RA were less likely to achieve therapeutic goals for LDL than the non-RA subjects (p=0.046). Increased erythrocyte sedimentation rate (ESR) at baseline (OR 0.47; 95% CI 0.26, 0.85) was associated with lower likelihood of achieving therapeutic LDL goals.
Conclusion
Patients with RA had lower TC and LDL 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.
doi:10.1002/acr.22029
PMCID: PMC3788038  PMID: 23592565
rheumatoid arthritis; lipids; statins
6.  Accelerated Aging Influences Cardiovascular Disease Risk in Rheumatoid Arthritis 
Arthritis and rheumatism  2013;65(10):2562-2566.
OBJECTIVE
To determine whether the impact of aging on cardiovascular disease (CVD) risk in the general population (as estimated by the Framingham risk score [FRS]) differs in patients with rheumatoid arthritis (RA).
METHODS
A population-based inception cohort of Olmsted County, Minnesota residents aged ≥30 years who fulfilled 1987 ACR criteria for RA in 1988–2008 was assembled and followed until death, migration, or 7-1-2012. Data on CVD events were collected by medical record 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.
RESULTS
The study included 563 patients with RA without prior CVD (mean age: 55 years, 72% women; 69% seropositive [i.e., rheumatoid factor and/or anti-citrullinated protein antibody positive]). During a mean follow-up of 8.2 years, 98 patients developed CVD (74 seropositive and 24 seronegative), but 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 age effect 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).
CONCLUSION
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.
doi:10.1002/art.38071
PMCID: PMC3966134  PMID: 23818136
accelerated aging; rheumatoid arthritis; cardiovascular disease
7.  Hyperuricemia and Incident Cardiovascular Disease and Noncardiac Vascular Events in Patients with Rheumatoid Arthritis 
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.
doi:10.1155/2014/523897
PMCID: PMC4150464  PMID: 25197282
8.  Incidence and Mortality of Obstructive Lung Disease in Rheumatoid Arthritis: A Population-Based Study 
Arthritis care & research  2013;65(8):1243-1250.
OBJECTIVE
Pulmonary disease represents an important extra-articular manifestation of rheumatoid arthritis (RA). While the association of RA and interstitial lung disease is widely acknowledged, obstructive lung disease (OLD) in RA is less well understood. We therefore aimed to assess incidence, risk factors and mortality of OLD in patients with RA.
METHODS
We examined a population-based incident cohort of patients with RA and a comparison cohort of individuals without RA. OLD was defined using a strict composite criterion. Cox-proportional hazards models were used to compare OLD incidence between the RA and comparator cohort, to investigate risk factors and to explore the impact of OLD on patient survival.
RESULTS
594 patients with RA and 596 subjects without RA were followed for a mean of 16.3 and 19.4 years, respectively. The lifetime risk of developing OLD was 9.6% for RA patients and 6.2% for subjects without RA; hazard ratio (HR) 1.54 (95% CI 1.01 to 2.34). The risk of developing OLD was higher among male patients, current or former smokers and for individuals with more severe RA. Survival of RA patients diagnosed with OLD was worse compared to those without OLD (HR 2.09, 95% CI 1.47 to 2.97).
CONCLUSION
Patients with RA are at higher risk of developing OLD, which is significantly associated with premature mortality. Effective diagnostic and therapeutic strategies to detect and manage OLD in patients with RA may help to improve survivorship in these patients.
doi:10.1002/acr.21986
PMCID: PMC4017238  PMID: 23436637
obstructive lung disease; rheumatoid arthritis; incidence; risk factors; mortality
9.  Use of lipid lowering agents in rheumatoid arthritis: a population based cohort study 
The Journal of rheumatology  2013;40(7):1082-1088.
Objective
Rheumatoid arthritis (RA) is associated with an increased risk of cardiovascular disease and mortality. Lipid-lowering therapy is reportedly underused in patients with RA. However, longitudinal cohort studies comparing the use of lipid-lowering medications in patients with RA vs the general population are lacking.
Methods
Cardiovascular risk factors, lipid measures and use of lipid-lowering agents were assessed in a population-based inception cohort of patients with RA and a cohort of non-RA subjects followed from 1/1/1988 to 12/31/2008. The National Cholesterol Education Program (NCEP) adult treatment panel III (ATP III) guidelines were assessed at the time of each lipid measure throughout follow-up. Time from meeting guidelines to initiation of lipid-lowering agents was assessed using Kaplan-Meier methods.
Results
The study population included 412 RA and 438 non-RA patients with ≥1 lipid measure during follow-up and no prior use of lipid lowering agents. Rates of lipid testing were lower among patients with RA compared to non-RA subjects. Among patients who met NCEP ATP III criteria for lipid-lowering therapy (n=106 RA and n=120 non-RA), only 27% of RA and 26% of non-RA subjects initiated lipid-lowering agents within 2 years of meeting guidelines for initiation.
Conclusions
There was substantial undertreatment in both the RA and non-RA cohorts who met NCEP ATP III criteria for initiation of lipid-lowering agents. Patients with RA did not have as frequent lipid testing as individuals in the general population.
doi:10.3899/jrheum.121302
PMCID: PMC3891914  PMID: 23637326
rheumatoid arthritis; lipids; lipid lowering therapy
10.  Rheumatoid Arthritis is Associated with Left Ventricular Concentric Remodeling: Results of a Population-based Cross-sectional Study 
Arthritis and rheumatism  2013;65(7):1713-1718.
Objective
To study left ventricular (LV) geometry in patients with rheumatoid arthritis (RA) who have no heart failure (HF) versus subjects without either RA or HF, and to determine the impact of RA on LV remodeling.
Methods
A cross-sectional, community-based study was conducted among adult (≥50 years) RA patients and age- and sex-matched non-RA subjects without a history of HF. All participants underwent a standard 2D/Doppler echocardiography. LV geometry was classified into four categories based on relative wall thickness and sex-specific cut-offs for LV mass index: concentric remodeling, concentric hypertrophy, eccentric hypertrophy, or normal geometry.
Results
The study included 200 RA patients and 600 matched non-RA subjects (mean age 65; 74% female in both cohorts). RA patients were significantly more likely to have abnormal LV geometry than non-RA subjects (odds ratio [OR] 1.44; 95% confidence interval [CI] 1.03, 2.00), adjusting for cardiovascular risk factors and comorbidities. Among those with abnormal LV geometry, RA patients had significantly increased odds of concentric LV remodeling (OR 4.73; 95% CI 2.85, 7.83). In linear regression analyses, LV mass index appeared to be lower in RA patients currently using corticosteroids (Beta +/− standard error: −0.082 +/− 0.027; p=0.002), adjusting for cardiovascular risk factors and comorbidities.
Conclusion
RA was strongly associated with abnormal LV remodeling, particularly, with concentric LV remodeling, among patients without HF. This association was significant beyond adjustment for cardiovascular risk factors and comorbidities. RA disease related factors may promote changes in LV geometry. The biological mechanisms underlying LV remodeling warrant further investigation.
doi:10.1002/art.37949
PMCID: PMC3914147  PMID: 23553738
rheumatoid arthritis; left ventricular remodeling; risk factors
11.  Incidence and time trends of Herpes zoster in rheumatoid arthritis: a population-based cohort study 
Arthritis care & research  2013;65(6):854-861.
Objective
To determine the incidence, time trends, risk factors and severity of herpes zoster (HZ) in a population-based incidence cohort of patients with rheumatoid arthritis (RA) compared to a group of individuals without RA from the same population.
Methods
All residents of Olmsted County, MN who first fulfilled 1987 American College of Rheumatology criteria for RA between 1/1/1980 and 12/31/2007 and a cohort of similar residents without RA were assembled and followed by retrospective chart review until death, migration, or 12/31/2008.
Results
There was no difference in the presence of HZ prior to RA incidence/index date between the cohorts (p=0.85). During follow-up 84 patients with RA (rate: 12.1 per 1000 person-years) and 44 subjects without RA (rate: 5.4 per 1000 person-years) developed HZ. Patients with RA were more likely to develop HZ than those without RA (hazard ratio: 2.4; 95% confidence interval: 1.7, 3.5). Patients diagnosed with RA in 1995–2007 had a higher likelihood of developing HZ than those diagnosed in 1980–1994. Erosive disease, previous joint surgery, use of hydroxychloroquine and corticosteroids were significantly associated with the development of HZ in RA, while the use of methotrexate or biologic agents was not. Complications of HZ occurred at a similar rate in both cohorts.
Conclusion
The incidence of HZ is increased in RA and has risen in recent years. The increasing incidence of HZ in more recent years is also noted in the general population. RA disease severity is associated with development of HZ.
doi:10.1002/acr.21928
PMCID: PMC3674119  PMID: 23281295
rheumatoid arthritis; herpes zoster
12.  Incidence and Mortality of Interstitial Lung Disease in Rheumatoid Arthritis: A Population Based Study 
Arthritis and rheumatism  2010;62(6):1583-1591.
Objective
Interstitial lung disease (ILD) has been recognized as an important co-morbidity in rheumatoid arthritis (RA). We aimed to assess incidence, risk factors and mortality of RA associated ILD.
Methods
We examined a population-based incidence cohort of patients with RA and a matched cohort of individuals without RA. All subjects were followed longitudinally until death, migration or January 1, 2006. The lifetime risk of ILD was estimated and Cox models were used to compare the incidence of ILD between cohorts, to investigate possible risk factors and to explore the impact of ILD on patient survival.
Results
582 patients with RA and 603 subjects without RA were followed for a mean of 16.4 and 19.3 years, respectively. The lifetime risk of developing ILD was 7.7% for RA patients and 0.9% for subjects without RA. This difference translated into a hazard ratio of 8.96 (95% CI 4.02, 19.94). The risk of developing ILD was higher in patients with older age at RA onset, among male patients and for individuals with parameters that indicate more severe RA.
Survival of RA patients diagnosed with ILD was worse compared to RA patients without ILD (HR 2.86, 95% CI 1.98, 4.12). ILD contributed approximately 13% to the excess mortality of patients with RA patients when compared to the general population.
Conclusion
Our results emphasize the increased risk of ILD in patients with RA. The impact of ILD on patient survival provides evidence that development of better strategies for the treatment of ILD could significantly lower the excess mortality of individuals with RA.
doi:10.1002/art.27405
PMCID: PMC4028137  PMID: 20155830
Interstitial lung disease; rheumatoid arthritis; incidence; risk factors
13.  Lack of Association of High Body Mass Index with Risk for Developing Polymyalgia Rheumatica 
Background
High body mass index (BMI) may have modulatory effects on the immune system.
Objectives
To determine the association between BMI and PMR as well as the influence of BMI on glucocorticoid treatment duration and development of giant-cell arteritis (GCA) in patients with PMR.
Methods
The BMI of 364 patients with PMR from a population-based incidence cohort was compared to the BMI of non-PMR subjects from the same population. High and low BMI were defined as ≥ 25 kg/m2 and < 18.5 kg/m2, respectively. The association between BMI and case status was determined. The association between BMI and the duration of glucocorticoid therapy as well as the development of GCA after accounting for relevant variables was also examined.
Results
The mean BMI at index was similar in both groups (PMR: 26 ± 5.4 kg/m2; non-PMR: 25.9 ± 4.0 kg/m2). There was no association between BMI and the duration of glucocorticoid therapy. No significant association was found between BMI and the development of GCA in patients with PMR.
Conclusions
Patients with high BMI (≥ 25 kg/m2) are not more likely to develop PMR. BMI did not influence the duration of glucocorticoid therapy nor the occurrence of GCA in patients with PMR.
doi:10.1111/j.1756-185X.2010.01527.x
PMCID: PMC4012353  PMID: 20704602
Polymyalgia Rheumatica; Body mass index; Giant Cell Arteritis
14.  Long-Term Outcomes and Treatment After Myocardial Infarction in Patients with Rheumatoid Arthritis 
The Journal of rheumatology  2013;40(5):605-610.
Objective
To investigate the risk profiles, treatment utilization, and outcomes of myocardial infarction (MI) patients with rheumatoid arthritis (RA) and matched MI patients without RA.
Methods
We utilized a population-based cohort of Olmsted County, Minnesota, residents with MI from 1979–2009. Among these, we identified 77 patients who fulfilled the American College of Rheumatology (ACR) 1987 criteria for RA and 154 age, sex, and calendar year matched MI patients without RA. Data collection from medical records included RA and MI characteristics, antirheumatic and cardioprotective medications, and reperfusion therapy as well as outcomes (mortality, heart failure, and recurrent ischemia).
Results
The mean age at MI was 72.4 and 55% were female in both cohorts. Cardiovascular risk factor profiles, MI characteristics, and treatment with reperfusion therapy or cardioprotective medications were similar in MI patients with and without RA. However, patients with RA experienced poorer long-term outcomes compared to patients without RA (for mortality: hazard ratio [HR]: 1.47; 95% confidence interval [CI]: 1.04, 2.08, and for recurrent ischemia: HR: 1.51; 95% CI: 1.04, 2.18).
Conclusion
MI patients with RA receive similar treatment with reperfusion therapy and cardioprotective medications, and have similar short-term outcomes compared to patients without RA. However, patients with RA have poorer long-term outcomes. Thus, despite similar treatment, MI patients with RA have worse long-term outcomes than MI patients without RA.
doi:10.3899/jrheum.120941
PMCID: PMC3895921  PMID: 23418388
Rheumatoid arthritis; myocardial infarction
15.  Towards Improving Cardiovascular Risk Management in Patients with Rheumatoid Arthritis: the Need for Accurate Risk Assessment 
Annals of the rheumatic diseases  2011;70(5):719-721.
doi:10.1136/ard.2010.145482
PMCID: PMC3907170  PMID: 21345812
rheumatoid arthritis; cardiovascular disease
16.  Contribution of Obesity to the Rise in Incidence of Rheumatoid Arthritis 
Arthritis care & research  2013;65(1):71-77.
OBJECTIVE
To determine whether the “obesity epidemic” could explain the recent rise in the incidence of RA.
BACKGROUND
Obesity is an under-recognized risk factor for RA. In recent years both the prevalence of obesity and the incidence of RA have been rising.
METHODS
An inception cohort of Olmsted County, Minnesota residents who fulfilled 1987 American College of Rheumatology criteria for RA in 1980–2007 was compared to population-based controls (matched on age, sex and calendar year). Heights, weights and smoking status were collected from medical records. Obesity was defined as body mass index (BMI) ≥ 30 kg/m2. Conditional logistic regression was used to assess the influence of obesity on developing RA. Population attributable risk was used to estimate the incidence of RA in the absence of obesity.
RESULTS
The study included 813 patients with RA and 813 controls. Both groups had extensive medical history available prior to incidence/index date (mean 32.2 years), and approximately 30% of each group were obese at incidence/index date. The history of obesity was a significantly associated with developing RA (OR:1.24; 95 % CI: 1.01, 1.53 adjusted for smoking status). In 1985–2007 the incidence of RA rose by an increment of 9.2 per 100,000 among women. Obesity accounted for 4.8 per 100,000 (or 52%) of this increase.
CONCLUSION
Obesity is associated with a modest risk for developing RA. Given the rapidly increasing prevalence of obesity, this has had a significant impact on RA incidence and may account for much of the recent increase in incidence of RA.
doi:10.1002/acr.21660
PMCID: PMC3707391  PMID: 22514156
rheumatoid arthritis; obesity; incidence; population attributable risk; body mass index
17.  Immune response profiling in early rheumatoid arthritis: discovery of a novel interaction of treatment response with viral immunity 
Arthritis Research & Therapy  2013;15(6):R199.
Introduction
It remains challenging to predict the outcomes of therapy in patients with rheumatoid arthritis (RA). The objective of this study was to identify immune response signatures that correlate with clinical treatment outcomes in patients with RA.
Methods
A cohort of 71 consecutive patients with early RA starting treatment with disease-modifying antirheumatic drugs (DMARDs) was recruited. Disease activity at baseline and after 21 to 24 weeks of follow-up was measured using the Disease Activity Score in 28 joints (DAS28). Immune response profiling was performed by analyzing multi-cytokine production from peripheral blood cells following incubation with a panel of stimuli, including a mixture of human cytomegalovirus (CMV) and Epstein-Barr virus (EBV) lysates. Profiles identified via principal components analysis (PCA) for each stimulus were then correlated with the ΔDAS28 from baseline to follow-up. A clinically meaningful improvement in the DAS28 was defined as a decrease of ≥1.2.
Results
A profile of T-cell cytokines (IL-13, IL-4, IL-5, IL-2, IL-12, and IFN-γ) produced in response to CMV/EBV was found to correlate with the ΔDAS28 from baseline to follow-up. At baseline, a higher magnitude of the CMV/EBV immune response profile predicted inadequate DAS28 improvement (mean PCA-1 scores: 65.6 versus 50.2; P = 0.029). The baseline CMV/EBV response was particularly driven by IFN-γ (P = 0.039) and IL-4 (P = 0.027). Among patients who attained clinically meaningful DAS28 improvement, the CMV/EBV PCA-1 score increased from baseline to follow-up (mean +11.6, SD 25.5), whereas among patients who responded inadequately to DMARD therapy, the CMV/EBV PCA-1 score decreased (mean -12.8, SD 25.4; P = 0.002). Irrespective of the ΔDAS28, methotrexate use was associated with up-regulation of the CMV/EBV response. The CMV/EBV profile was associated with positive CMV IgG (P <0.001), but not EBV IgG (P = 0.32), suggesting this response was related to CMV exposure.
Conclusions
A profile of T-cell immunity associated with CMV exposure influences the clinical response to DMARD therapy in patients with early RA. Because CMV latency is associated with greater joint destruction, our findings suggest that changes in T-cell immunity mediated by viral persistence may affect treatment response and possibly long-term outcomes of RA.
doi:10.1186/ar4389
PMCID: PMC3978471  PMID: 24267267
18.  Usefulness of Risk Scores To Estimate the Risk of Cardiovascular Disease in Patients with Rheumatoid Arthritis 
The American Journal of Cardiology  2012;110(3):420-424.
Patients with rheumatoid arthritis (RA) suffer from an excess burden of cardiovascular disease (CVD). CV risk scores for the general population may not accurately predict CV risk for patients with RA. A population-based inception cohort of patients who fulfilled 1987 American College of Rheumatology criteria for RA in 1988–2007 was followed until death, migration, or 12/31/2008. CV risk factors and CVD (myocardial infarction, CV death, angina, stroke, intermittent claudication and heart failure) were ascertained by medical record review. The 10 year predicted CVD risk was calculated using the general Framingham and the Reynolds risk scores. Standardized incidence ratios were calculated to compare observed and predicted CVD risks. The study included 525 patients with RA aged ≥30 years without prior CVD. The mean follow-up was 8.4 years, during which 84 patients developed CVD. The observed CVD risk was 2-fold higher than the Framingham risk score predicted in women and 65% higher in men, and the Reynolds risk score revealed similar deficits. Patients aged ≥75 years had observed CVD risk >3 times the Framingham predicted risk. Patients with positive rheumatoid factor or persistently elevated erythrocyte sedimentation rate also experienced more CVD events than predicted. In conclusion, the Framingham and Reynolds risk scores substantially underestimated CVD risk in patients with RA of both sexes, especially in older ages and in patients with positive rheumatoid factor. These data underscore the need for more accurate tools to predict CVD risk in patients with RA.
doi:10.1016/j.amjcard.2012.03.044
PMCID: PMC3398213  PMID: 22521305
rheumatoid arthritis; cardiovascular disease; risk scores
19.  Hypothyroidism as a risk factor for development of cardiovascular disease in patients with rheumatoid arthritis 
The Journal of rheumatology  2012;39(5):954-958.
Background/Purpose
To determine the frequency of hypothyroidism in patients with rheumatoid arthritis (RA), and to elucidate the association of hypothyroidism and development of cardiovascular disease in these patients.
Method
A retrospective medical record review was performed using all incident cases of adult onset RA from a defined geographic population base that fulfilled criteria for RA in the years 1988–2007. Patients with and without thyroid disease were followed longitudinally for the development of cardiovascular disease (CVD).
Results
A cohort of 650 patients with RA and an age and sex matched comparison cohort of 650 patients without RA was assembled (both cohorts mean age 55.8; 69% female). There was no significant difference between cohorts in the presence of hypothyroid disease or subclinical hypothyroidism at time of RA diagnosis. No significant difference was found in the cumulative incidence of hypothyroid disease between the two cohorts. Hypothyroid disease was found to be significantly associated with CVD in patients with RA (hazard ratio 2; 95% confidence interval 1.1,3.6). This difference remained significant and unchanged after adjustment for traditional cardiovascular risk factors (HR: 2.0; 95% CI: 1.1, 3.6).
Conclusion
No significant difference was found in either incidence or prevalence of hypothyroidism between patients with or without RA. Hypothyroid disease was significantly associated with CVD in patients with RA, even after adjustment for other traditional cardiovascular risk factors.
doi:10.3899/jrheum.111076
PMCID: PMC3518421  PMID: 22337246
Rheumatoid arthritis; Hypothyroidism; Cardiovascular Disease
20.  Utilization of Orthopedic Surgery Among Patients with Rheumatoid Arthritis 1980–2007: A Population Based Study Focused on Rates of Surgery, Patient Gender and Mortality 
The Journal of rheumatology  2012;39(3):481-485.
Objective
To describe current trends in arthritis related joint surgery among a population based cohort of patients with rheumatoid arthritis (RA) and to examine the influence of joint surgery on mortality.
Methods
A retrospective medical record review was performed of all orthopedic surgeries following diagnosis in cases of adult onset RA in Olmsted County, Minnesota incident in 1980–2007. Surgeries included primary total joint arthroplasty, joint reconstructive procedures (JRP), soft tissue procedures (STP) and revision arthroplasty. Cumulative incidence (CI) of surgery was estimated using Kaplan-Meier methods. Time trends, sex differences and mortality were examined using Cox models with time-dependent covariates for surgery.
Results
A total of 189 of 813 patients underwent ≥1 surgical procedures involving joints during follow-up. The cumulative incidence of any joint surgery at 10 years after RA incidence for the 1980–1994 cohort was 27.3% compared to 19.5% for the 1995–2007 cohort (p=0.08). The greatest reduction was in STP, which decreased from 12.1% in 1980–1994 to 6.0% in 1995–2007 at 10 years after RA incidence (p=0.012). Obese patients, and women (cumulative incidence 26.6% at 10 years for women; 20.4% for men; p=0.049) had more surgery. JRP was significantly associated with mortality (hazard ratio [HR]: 2.6; 95 % CI 1.8, 3.9; p <0.001) compared to patients not requiring JRP.
Conclusion
The rates of joint surgery continue to decrease for patients more recently diagnosed with RA. JRP, is associated with increased mortality. These findings may reflect both improved treatments for RA as well as continued higher disease burden among some patients.
doi:10.3899/jrheum.111056
PMCID: PMC3634337  PMID: 22247350
21.  Asthma and Proinflammatory Conditions: A Population-Based Retrospective Matched Cohort Study 
Mayo Clinic Proceedings  2012;87(10):953-960.
Objective
To determine the association between asthma and proinflammatory conditions.
Participants and Methods
This population-based retrospective matched cohort study enrolled all asthmatic patients among Rochester, Minnesota, residents between January 1, 1964, and December 31, 1983. For each asthmatic patient, 2 age-and sex-matched nonasthmatic individuals were drawn from the same population. The asthmatic and nonasthmatic cohorts were followed forward in the Rochester Epidemiology Project diagnostic index for inflammatory bowel disease (IBD), rheumatoid arthritis (RA), diabetes mellitus (DM), and coronary heart disease (CHD) as outcome events. Data were fitted to Cox proportional hazards models.
Results
We identified 2392 asthmatic patients and 4784 nonasthmatic controls. Of the asthmatic patients, 1356 (57%) were male, and mean age at asthma onset was 15.1 years. Incidence rates of IBD, RA, DM, and CHD in nonasthmatic controls were 32.8, 175.9, 132.0, and 389.7 per 100,000 person-years, respectively; those for asthmatic patients were 41.4, 227.9, 282.6, and 563.7 per 100,000 person-years, respectively. Asthma was associated with increased risks of DM (hazard ratio, 2.11; 95% confidence interval, 1.43-3.13; P<.001) and CHD (hazard ratio, 1.47; 95% confidence interval, 1.05-2.06; P=.02) but not with increased risks of IBD or RA.
Conclusion
Although asthma is a helper T cell type 2–predominant condition, it may increase the risks of helper T cell type 1–polarized proinflammatory conditions, such as CHD and DM. Physicians who care for asthmatic patients need to address these unrecognized risks in asthmatic patients.
doi:10.1016/j.mayocp.2012.05.020
PMCID: PMC3538394  PMID: 22980164
CHD, coronary heart disease; CI, confidence interval; DM, diabetes mellitus; HR, hazard ratio; IBD, inflammatory bowel disease; ICD, International Classification of Diseases; RA, rheumatoid arthritis; REP, Rochester Epidemiology Project; TH, helper T cell
22.  Noncardiac vascular disease in Rheumatoid Arthritis: Increase in Venous Thromboembolic Events? 
Arthritis and rheumatism  2012;64(1):53-61.
Objective
To investigate the incidence of noncardiac vascular disease in a community-based incidence cohort of patients with rheumatoid arthritis (RA) and compare to that in the general population. To investigate trends in incidence of noncardiac vascular disease in patients with RA.
Methods
A population-based inception cohort of patients with RA in Olmsted County, Minnesota with incident RA between 1/1/1980 and 12/31/2007 and a cohort of non-RA subjects from the same population base was assembled and followed until 12/31/2008. Venous thromboembolic events (VTE), cerebrovascular events, and peripheral arterial events were ascertained by medical record review.
Results
The study population included 813 patients with RA (mean age [SD] 55.9 [15.7] years, 68% women), with average length of follow-up of 9.6 years [SD 6.9]. Compared to non-RA subjects of similar age and sex, patients diagnosed with RA between 1995 and 2007 had a higher incidence (%) of VTE compared to non-RA subjects (cumulative incidence [±SE] 6.7 ± 1.7 vs 2.8 ± 1.1, respectively; p=0.005), but similar rates of cerebrovascular and peripheral arterial events. Among patients with RA, the incidence of VTE, cerebrovascular events, and peripheral arterial events was similar in the 1995–2007 time period compared to the 1980–1994 time period.
Conclusion
The incidence of VTE appears to be increased in patients with RA compared to non-RA subjects. The incidence of cerebrovascular events and peripheral vascular disease events was similar in patients with RA compared to non-RA subjects. Among patients with RA, the incidence of noncardiac vascular disease has remained stable in recent decades.
doi:10.1002/art.33322
PMCID: PMC3474372  PMID: 21905005
23.  Cardiac and Thromboembolic Complications and Mortality in Patients Undergoing Total Hip and Total Knee Arthroplasty 
Annals of the Rheumatic Diseases  2011;70(12):2082-2088.
Objective
Study 90-day cardiac and thromboembolic complications and all-cause mortality following total hip or knee arthroplasty (THA/TKA).
Method
In a population-based cohort of all Olmsted County residents who underwent a THA or TKA between 1994 and 2008, we assessed 90-day occurrence and predictors of cardiac complications (myocardial infarction, cardiac arrhythmia or congestive heart failure), thromboembolic complications (deep venous thrombosis (DVT) or pulmonary embolism (PE)) and mortality.
Results
Among the Olmsted County THA and TKA cohorts, 90-day complication rates were as follows: cardiac, 15.8% and 6.9%; thromboembolic, 4.9% and 4.0%; and mortality, 0.7% and 0.4%, respectively. Unadjusted frequency of cardiac/thromboembolic events differed by history of prior respective event. In multivariable-adjusted logistic regression analyses, ASA class III–IV (OR, 6.1, 95% CI:1.6, 22.8) and higher Deyo-Charlson comorbidity score (OR, 1.2, 95% CI:1.0,1.4) were significantly associated with odds of 90-day cardiac event post-THA in patients with no known prior cardiac event. In those with known prior cardiac disease, ASA class III–IV (OR, 4.4, 95% CI:2.0, 9.9), male gender (OR, 0.5, 95% CI:0.3,0.9) and history of thromboembolic disease (OR, 3.2; 95% CI:1.4,7.0) were significantly associated with odds of cardiac complication 90-day post-THA. No significant predictors of thromboembolism were found in THA patients.
In TKA patients with no prior cardiac history, age >65 years (OR, 4.1, 95% CI:1.2, 14.0), and ASA class III–IV (OR, 2.8, 95% CI:1.1,6.8) and in TKA patients with known cardiac disease, ASA class III–IV (OR, 3.2, 95% CI:1.8,5.7) was significantly associated with odds of 90-day cardiac event. In TKA patients with no prior thromboembolic disease, male gender (OR, 0.5, 95% CI:0.2,0.9) and higher Charlson index (OR, 1.2, 95% CI:1.1,1.3) and in patients with known thromboembolic disease, higher Charlson index score (OR, 1.1, 95% CI:1.1,1.4) was associated with odds of 90-day thromboembolic event.
Conclusion
Older age, higher comorbidity, higher ASA class and prior history of cardiac/thromboembolic disease was associated with an increased risk of 90-day cardiac and thromboembolic complications.
doi:10.1136/ard.2010.148726
PMCID: PMC3315837  PMID: 22021865
Cardiac; Thromboembolic; Total Hip Arthroplasty; Total Knee Arthroplasty; Mortality
24.  Assessing Immune Function by Profiling Cytokine Release from Stimulated Blood Leukocytes and the Risk of Infection in Rheumatoid Arthritis 
Persons with rheumatoid arthritis (RA) suffer a high burden of infections, but currently no biomarkers are available to identify individuals at greatest risk. A prospective longitudinal study was therefore conducted to determine the association between the responsiveness of ex vivo cytokine production and 6-month risk of infections. Infections were identified by billing codes and validated by medical record review. At baseline, the release of 17 cytokines by peripheral blood mononuclear cells in response to stimulation, or media alone, was measured using multiplexed cytokine analysis. Production of IL-2, IL-8, IL-10, IL-17, TNF-α, IFN-γ, and GM-CSF, induced by various conditions, was significantly associated with the occurrence of infections. A multivariable prediction model based on these data provided new information on the risk of infection beyond standard assessments of disease activity, severity, and treatment. Future studies could utilize this information to devise new biomarkers for the prediction of infection in patients with RA.
doi:10.1016/j.clim.2011.05.008
PMCID: PMC3183136  PMID: 21703930
Immune signature; immune response; peripheral blood mononuclear cells
25.  The Impact of Rheumatoid Arthritis Disease Characteristics on Heart Failure 
The Journal of Rheumatology  2011;38(8):1601-1606.
Objective
To examine the impact of rheumatoid arthritis (RA) characteristics and antirheumatic medications on the risk of heart failure (HF) in RA.
Methods
A population-based incidence cohort of RA patients aged ≥18 (1987 ACR criteria first met between 1/1/1980 and 1/1/2008) without a history of HF was followed until HF onset (defined by Framingham criteria), death, or 1/1/2008. 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 years, 69% females, 66% rheumatoid factor [RF] positive). During the mean follow-up 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 extra-articular 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 non-users (HR 0.5, 95%CI 0.3, 0.9).
Conclusion
Several RA characteristics and the use of corticosteroids were associated with HF adjusting for CV risk factors and CHD. Methotrexate use appeared to be protective against HF. These findings suggest an independent impact of RA on HF which may be further modified by antirheumatic treatment.
doi:10.3899/jrheum.100979
PMCID: PMC3337549  PMID: 21572155
rheumatoid arthritis; heart failure; determinants

Results 1-25 (62)