Rheumatoid Arthritis: Maradit-Kremers H

Davis JM, Maradit-Kremers H, Gabriel SE. · No affiliation provided · J Rheumatol. · Pubmed #16206334 links to  free full text

This publication has no abstract.

Maradit-Kremers H, Crowson CS, Nicola PJ, Ballman KV, Roger VL, Jacobsen SJ, Gabriel SE. · Mayo Clinic, Rochester, Minnesota 55905, USA. · Arthritis Rheum. · Pubmed #15693010 links to  free full text

Abstract: OBJECTIVE: To examine the risk of clinical coronary heart disease (CHD) in patients with rheumatoid arthritis (RA) compared with age- and sex-matched non-RA subjects, and to determine whether RA is a risk factor for CHD after accounting for traditional CHD risk factors. METHODS: We assembled a population-based incidence cohort of 603 Rochester, Minnesota residents ages >or=18 years who first fulfilled the American College of Rheumatology (ACR) 1987 criteria for RA between January 1, 1955 and January 1, 1995, and 603 age- and sex-matched non-RA subjects. All subjects were followed up through their complete inpatient and outpatient medical records, beginning at age 18 years until death, migration, or January 1, 2001. Data were collected on CHD events and traditional CHD risk factors (diabetes mellitus, hypertension, dyslipidemia, body mass index, smoking) using established diagnostic criteria. CHD events included hospitalized myocardial infarction (MI), unrecognized MI, coronary revascularization procedures, angina pectoris, and sudden CHD deaths. Conditional logistic regression and Cox regression models were used to estimate the risk of CHD associated with RA, both prior to and following RA diagnosis, after adjusting for CHD risk factors. RESULTS: During the 2-year period immediately prior to fulfillment of the ACR criteria, RA patients were significantly more likely to have been hospitalized for acute MI (odds ratio [OR] 3.17, 95% confidence interval [95% CI] 1.16-8.68) or to have experienced unrecognized MIs (OR 5.86, 95% CI 1.29-26.64), and less likely to have a history of angina pectoris (OR 0.58, 95% CI 0.34-0.99) compared with non-RA subjects. After the RA incidence date, RA patients were twice as likely to experience unrecognized MIs (hazard ratio [HR] 2.13, 95% CI 1.13-4.03) and sudden deaths (HR 1.94, 95% CI 1.06-3.55) and less likely to undergo coronary artery bypass grafting (HR 0.36, 95% CI 0.16-0.80) compared with non-RA subjects. Adjustment for the CHD risk factors did not substantially change the risk estimates. CONCLUSION: Patients with RA have a significantly higher risk of CHD when compared with non-RA subjects. RA patients are less likely to report symptoms of angina and more likely to experience unrecognized MI and sudden cardiac death. The risk of CHD in RA patients precedes the ACR criteria-based diagnosis of RA, and the risk cannot be explained by an increased incidence of traditional CHD risk factors in RA patients.

Boers M, Dijkmans B, Gabriel S, Maradit-Kremers H, O'Dell J, Pincus T. · Department of Clinical Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, The Netherlands. · Arthritis Rheum. · Pubmed #15188348 links to  free full text

This publication has no abstract.

Icen M, Nicola PJ, Maradit-Kremers H, Crowson CS, Therneau TM, Matteson EL, Gabriel SE. · Department of Health Sciences Research, Mayo Foundation, 200 First St. SW, Rochester, MN 55905, USA. · J Rheumatol. · Pubmed #19004043 No free full text.

Abstract: OBJECTIVE: Features of systemic lupus erythematosus (SLE) are commonly observed in patients with rheumatoid arthritis (RA). However, their frequency and clinical significance are uncertain. We examined the frequency of SLE features in RA and their effect on overall mortality. METHODS: We assembled a population-based incidence cohort of subjects aged >or=18 years first diagnosed with RA [1987 American College of Rheumatology (ACR) criteria] between 1955 and 1995. Information regarding disease characteristics, therapy, comorbidities, and SLE features (1982 ACR criteria) were collected from the complete inpatient and outpatient medical records. Cox regression models were used to estimate the mortality risk associated with lupus features. RESULTS: The study population comprised 603 subjects with incident RA (mean age 58 yrs, 73% women) with a mean followup time of 15 years. By 25 years after RA incidence, >or=4 SLE features were observed in 15.5% of the subjects with RA. After adjustment for age and sex, occurrence of >or=4 SLE features was associated with increased overall mortality [hazard ratio (HR) 5.54, 95% confidence interval (CI) 3.59-8.53].With further adjustment for RA characteristics, therapy, and comorbidities, the association weakened but remained statistically significant (HR 2.56, 95% CI 1.60-4.08). After adjustment for age, sex, RA characteristics, therapy, and comorbidities, thrombocytopenia (2.0, 95% CI 1.2, 3.1) and proteinuria (1.8, 95% CI 1.3, 2.6) were significantly associated with mortality. CONCLUSION: SLE features were common in RA, given sufficient observation time. Subjects with RA who developed >or=4 SLE features had an increased risk of death. Proteinuria and thrombocytopenia were individually associated with an increased mortality risk.

Aubry MC, Maradit-Kremers H, Reinalda MS, Crowson CS, Edwards WD, Gabriel SE. · Divisions of Anatomic Pathology, Health Science Research, Biostatistics, and Rheumatology, Mayo Clinic, Rochester, Minnesota 55905, USA. · J Rheumatol. · Pubmed #17361987 No free full text.

Abstract: OBJECTIVE: Patients with rheumatoid arthritis (RA) are at increased risk for cardiovascular diseases (CVD). We compared the histologic features of coronary artery disease in patients with RA and non-RA controls. METHODS: Forty-one RA patients who died and underwent autopsy between 1985 and 2003 were matched to 82 non-RA controls of the same age and sex with similar history of CVD and autopsy date. Coronary arteries were submitted for histologic evaluation. The grade of stenosis was evaluated in each artery. The numbers of vulnerable plaques and acute coronary lesions were counted. The composition of a representative stable and vulnerable plaque from each vessel was evaluated. Chi-square tests were used to compare differences between groups. RESULTS: Patients and controls had similar age at death (mean 79 yrs) and 61% were female in both groups. Overall, there was no significant difference in grade of stenosis or number of acute coronary lesions. Among subjects with CVD, 54% of controls had grade 3-4 lesions in left main artery versus only 7% of patients (p = 0.023). Vulnerable plaques in left anterior descending (LAD) artery were significantly more common in patients than controls (p = 0.018). Inflammation was observed more frequently in patients, in both the media of left circumflex (p = 0.005) and adventitia of LAD artery (p = 0.024). Similar trends were seen for subjects with heart failure. CONCLUSION: There was less histologic evidence of atherosclerosis but greater evidence of inflammation and instability in RA patients compared to controls. These differences suggest that the mechanisms responsible for cardiovascular morbidity and mortality may be different in patients with RA.

Maradit-Kremers H, Nicola PJ, Crowson CS, Ballman KV, Jacobsen SJ, Roger VL, Gabriel SE. · Department of Health Sciences Research, Mayo Clinic, 200 1st St SW, Rochester, MN 55905, USA. · Ann Rheum Dis. · Pubmed #16818462 No free full text.

Abstract: BACKGROUND: Inflammatory markers are associated with heart failure. Patients with rheumatoid arthritis have twice the risk of heart failure compared with people without rheumatoid arthritis. OBJECTIVE: To assess whether heart failure in patients with rheumatoid arthritis is preceded by an inflammatory activation as shown by erythrocyte sedimentation rate (ESR), a systemic marker of inflammation. METHODS: A population-based inception cohort of 575 patients with rheumatoid arthritis, free of heart failure at their rheumatoid arthritis incidence date, was followed up longitudinally until death or 2001. During 15 years of follow-up, they had a median of 15 ESR tests, and 172 patients had new-onset heart failure (Framingham Heart Study criteria). The follow-up period, beginning with the rheumatoid arthritis incidence date and ending with date of the last follow-up, was divided into 6-month intervals. The proportions of patients with at least one ESR value >/=40 mm/h and with anaemia (haemoglobin <11 g/dl) within each 6-month interval were plotted against time from fulfilment of heart failure criteria. A binomial test was used to compare proportions. RESULTS: In patients with rheumatoid arthritis who developed heart failure, the proportion with ESR >/=40 mm/h was highest (23%) during the 6-month period immediately preceding the new-onset heart failure, as compared with the average ESR during the entire remaining follow-up period, both before and after heart failure (10.6%; p<0.01). The proportion of patients with anaemia peaked (54%) during the 6-month period after heart failure. CONCLUSIONS: Inflammatory stimuli may be involved in the initiation of heart failure among patients with rheumatoid arthritis.

Nicola PJ, Crowson CS, Maradit-Kremers H, Ballman KV, Roger VL, Jacobsen SJ, Gabriel SE. · Dept. of Health Sciences Research, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA. · Arthritis Rheum. · Pubmed #16385496 links to  free full text

Abstract: OBJECTIVE: Although mortality among patients with rheumatoid arthritis (RA) is higher than in the general population, the relative contribution of comorbid diseases to this mortality difference is not known. This study was undertaken to evaluate the contribution of congestive heart failure (CHF) and ischemic heart disease (IHD), including myocardial infarction, to the excess mortality in patients with RA, compared with that in individuals without RA. METHODS: We assembled a population-based inception cohort of individuals living in Rochester, Minnesota, in whom RA (defined according to the criteria of the American College of Rheumatology [formerly, the American Rheumatism Association]) first developed between 1955 and 1995, and an age- and sex-matched non-RA cohort. All subjects were followed up until either death, migration from the county, or until 2001. Detailed information from the complete medical records was collected. Statistical analyses included the person-years method, cumulative incidence, and Cox regression modeling. Attributable risk analysis techniques were used to estimate the number of RA deaths that would be prevented if the incidence of CHF was the same in patients with RA and non-RA subjects. RESULTS: The study population included 603 patients with RA and 603 subjects without RA. During followup, there was an excess of 123 deaths among patients with RA (345 RA deaths occurred, although only 222 such deaths were expected). The mortality rates among patients with RA and non-RA subjects were 39.0 and 29.2 per 1,000 person-years, respectively. There was a significantly higher cumulative incidence of CHF (but not IHD) in patients with RA compared with non-RA subjects (37.1% versus 27.7% at 30 years of followup, respectively; P < 0.001). The risk of death associated with either CHF or IHD was not significantly different between patients with RA and non-RA subjects. If the risk of developing CHF was the same in patients with RA and individuals without RA, the overall mortality rate difference between RA and non-RA hypothetically would be reduced from 9.8 to 8.0 excess deaths per 1,000 person-years; that is, 16 (13%) of the 123 excess deaths could be prevented. CONCLUSION: CHF, rather than IHD, appears to be an important contributor to the excess overall mortality among patients with RA. CHF contributes to this excess mortality primarily through the increased incidence of CHF in RA, rather than increased mortality associated with CHF in patients with RA compared with non-RA subjects. Eliminating the excess risk of CHF in patients with RA could significantly improve their survival.

Maradit-Kremers H, Nicola PJ, Crowson CS, O'Fallon WM, Gabriel SE. · Department of Health Sciences Research, Mayo Clinic, Rochester, MN 55905, USA. · J Rheumatol. · Pubmed #16358365 No free full text.

Abstract: OBJECTIVE: A major challenge in management of rheumatoid arthritis (RA) is prediction of longterm response to disease-modifying antirheumatic drug (DMARD) treatment. Our objective was to identify the predictors of DMARD discontinuation in an incidence cohort of patients with RA followed continuously from their incidence date. METHODS: Members of a population-based incidence cohort of Rochester, Minnesota, residents aged > or = 18 years diagnosed with RA (by 1987 American College of Rheumatology criteria) from January 1, 1955, to January 1, 1995, were followed longitudinally through their complete medical records until January 1, 2001. Detailed drug exposure data were collected on all DMARD and glucocorticoid regimens. Subjects were considered exposed to a DMARD if duration of use was > or = 30 days. Time to discontinuation of DMARD was estimated using survival analysis techniques. Andersen-Gill models with multiple events per patient were used to assess the influence of demographics, calendar time, comorbidities, disease characteristics [disease duration, rheumatoid factor (RF), erythrocyte sedimentation rate (ESR), joint counts, radiographic changes, nodules, RA complications], and therapy characteristics (DMARD use, singly or in combination, glucocorticoid use, first or subsequent regimen, effect of previous therapy) on time from DMARD initiation to discontinuation. RESULTS: The study population comprised 345 DMARD-treated patients (73% female) with mean age of 53.1 years and mean followup 15.4 years. Median time taking any DMARD was 16.0 months for the first, and 17.9 months for all regimens. Methotrexate (MTX) had the longest time to discontinuation, with a median of 30.3 months without folate, and 61.7 months with folate supplementation. Among the various disease characteristics examined, only higher ESR at DMARD initiation was significantly associated with a shorter time taking DMARD [hazard ratio (HR) 1.05 per 10 mm/h increase, 95% CI 1.02, 1.08]. In multivariable Andersen-Gill models considering all DMARD regimens, hydroxychloroquine use (HR 0.77, 95% CI 0.64, 0.92) and MTX use (HR with folate 0.39, 95% CI 0.30, 0.51; HR without folate 0.51, 95% CI 0.39, 0.67) were significantly associated with longer time to DMARD discontinuation, whereas prior MTX use (HR 1.96, 95% CI 1.57, 2.45) was associated with shorter time to DMARD discontinuation, after adjusting for age, sex, calendar year, Charlson comorbidity index, disease duration, and ESR at DMARD initiation. Disease duration was negatively associated with time to DMARD discontinuation; each 10 year increase in disease duration corresponded to a 14% decrease in the risk of discontinuation (HR 0.86, 95% CI 0.75, 0.98). CONCLUSION: Longer RA disease duration does not appear to increase the risk of DMARD discontinuation. However, high disease activity (as assessed by ESR) is associated with a higher likelihood of discontinuing DMARD. MTX failure may identify a subgroup of patients who are less likely to respond to other DMARD and therefore could be considered as candidates for biological therapies.

Maradit-Kremers H, Nicola PJ, Crowson CS, Ballman KV, Gabriel SE. · Mayo Clinic, Rochester, Minnesota 55905, USA. · Arthritis Rheum. · Pubmed #15751097 links to  free full text

Abstract: OBJECTIVE: To determine whether systemic inflammation confers any additional risk for cardiovascular death among patients with rheumatoid arthritis (RA), after adjusting for traditional cardiovascular risk factors and comorbidities. METHODS: Using the population-based data resources of the Rochester Epidemiology Project, we assembled an incidence cohort of all Rochester, Minnesota residents ages >or=18 years who first fulfilled the American College of Rheumatology 1987 criteria for RA between January 1, 1955 and January 1, 1995. All subjects were followed up longitudinally through their complete (inpatient, outpatient) medical records, beginning at age 18 years and continuing until death, migration, or January 1, 2001. Detailed information on the occurrence of various cardiovascular risk factors (personal history of coronary heart disease [CHD], congestive heart failure, smoking, hypertension, dyslipidemia, body mass index [BMI], diabetes mellitus, menopausal status) as well as indicators of systemic inflammation and RA disease severity (rheumatoid factor [RF] seropositivity, erythrocyte sedimentation rate [ESR], joint swelling, radiographic changes, RA nodules, RA complications, RA treatments, disease duration) and comorbidities were collected on all subjects. Causes of death were ascertained from death certificates and medical records. Cox regression models were used to estimate the independent predictors of cardiovascular death. RESULTS: This inception cohort comprised a total of 603 RA patients whose mean age was 58 years, of whom 73% were women. During a mean followup of 15 years, 354 patients died and cardiovascular disease was the primary cause of death in 176 patients. Personal history of CHD, smoking, hypertension, low BMI, and diabetes mellitus, as well as comorbidities, including peripheral vascular disease, cerebrovascular disease, chronic pulmonary disease, dementia, ulcers, malignancies, renal disease, liver disease, and history of alcoholism, were all significant risk factors for cardiovascular death (P < 0.01 for each). Multivariable Cox regression analyses, controlled for cardiovascular risk factors and comorbidities, revealed that the risk of cardiovascular death was significantly higher among RA patients with at least 3 ESR values of >or=60 mm/hour (hazard ratio [HR] 2.03, 95% confidence interval [95% CI] 1.45-2.83), RA vasculitis (HR 2.41, 95% CI 1.00-5.81), and RA lung disease (HR 2.32, 95% CI 1.11-4.84). CONCLUSION: These results indicate that markers of systemic inflammation confer a statistically significant additional risk for cardiovascular death among patients with RA, even after controlling for traditional cardiovascular risk factors and comorbidities.

Nicola PJ, Maradit-Kremers H, Roger VL, Jacobsen SJ, Crowson CS, Ballman KV, Gabriel SE. · Mayo Clinic, Rochester, Minnesota 55905, USA. · Arthritis Rheum. · Pubmed #15692992 links to  free full text

Abstract: OBJECTIVE: It is hypothesized that the systemic inflammation associated with rheumatoid arthritis (RA) promotes an increased risk of cardiovascular (CV) morbidity and mortality. We examined the risk and determinants of congestive heart failure (CHF) in patients with RA. METHODS: We assembled a population-based, retrospective incidence cohort from among all individuals living in Rochester, Minnesota, in whom RA (defined according to the American College of Rheumatology 1987 criteria) was first diagnosed between 1955 and 1995, and an age- and sex-matched non-RA cohort. After excluding patients in whom CHF occurred before the RA index date, all subjects were followed up until either death, incident CHF (defined according to the Framingham Heart Study criteria), migration from the county, or until January 1, 2001. Detailed information from the complete medical records (including all inpatient and outpatient care provided by all local providers) regarding RA, ischemic heart disease, and traditional CV risk factors was collected. Cox models were used to estimate the effect of RA on the development of CHF, adjusting for CV risk factors and/or ischemic heart disease. RESULTS: The study population included 575 patients with RA and 583 subjects without RA. The CHF incidence rates were 1.99 and 1.16 cases per 100 person-years in patients with RA and in non-RA subjects, respectively (rate ratio 1.7, 95% confidence interval [95% CI] 1.3-2.1). After 30 years of followup, the cumulative incidence of CHF was 34.0% in patients with RA and 25.2% in non-RA subjects (P< 0.001). RA conferred a significant excess risk of CHF (hazard ratio [HR] 1.87, 95% CI 1.47-2.39) after adjusting for demographics, ischemic heart disease, and CV risk factors. The risk was higher among patients with RA who were rheumatoid factor (RF) positive (HR 2.59, 95% CI 1.95-3.43) than among those who were RF negative (HR 1.28, 95% CI 0.93-1.78). CONCLUSION: Compared with persons without RA, patients with RA have twice the risk of developing CHF. This excess risk is not explained by traditional CV risk factors and/or clinical ischemic heart disease.

Aubry MC, Riehle DL, Edwards WD, Maradit-Kremers H, Roger VL, Sebo TJ, Gabriel SE. · Division of Anatomic Pathology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA. · Cardiovasc Pathol. · Pubmed #15210141 No free full text.

Abstract: OBJECTIVES: To describe the subtypes of lymphocytes in coronary arteries of two patients with rheumatoid arthritis (RA) and coronary artery disease (CAD). MATERIALS AND METHODS: The Mayo Clinic database was searched for patients with RA and CAD who underwent an autopsy in 2001. Medical records were reviewed, and coronary arteries were examined microscopically. The percentage of B- and T-lymphocytes was determined using histomorphometry on representative sections stained with CD20 and CD3 antibodies, respectively. RESULTS: Two men were diagnosed with RA at ages 52 and 70 years and died at ages 60 and 82 years. One sustained an acute myocardial infarction 2 years prior to the diagnosis of RA and had stable CAD until an arrhythmic death. The other developed congestive heart failure secondary to ischemic heart disease 5 years after RA was diagnosed. Both patients had severe three-vessel CAD with both stable fibrocalcific plaques and acute lesions. B- and T-lymphocytes were identified in the plaque and adventitia of all coronary arteries. The mean percentage of B-lymphocytes was 37% to 52% in the plaque and 78% to 85% in the adventitia, while that of T-lymphocytes was 38% to 51% and 28%, for plaque and adventitia, respectively. CONCLUSIONS: In typical CAD, lymphocytic infiltrates are almost exclusively T-cells. In contrast, the two patients with RA and CAD showed prominent infiltrates of B-lymphocytes within plaques and adventitia. Thus, the leukocytic response in atherosclerotic plaques may be altered in patients with autoimmune disorders. This warrants further study.