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 ≥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.

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.

Objective: Overall mortality rates in the general US population have declined substantially over the last 4–5 decades, but it is unclear whether patients with rheumatoid arthritis (RA) have experienced the same improvements in survival. The purpose of this study was to determine the mortality trends among RA patients compared with those in the general population.Methods: A population‐based incidence cohort of RA patients was assembled, comprising all residents of Rochester, Minnesota ages ≥18 years in whom RA was first diagnosed (according to the American College of Rheumatology [formerly, the American Rheumatism Association] 1987 criteria) between 1955 and 1995 and all residents of Olmsted County, Minnesota in whom RA was first diagnosed between 1995 and 2000. The patients were followed up longitudinally through their complete (inpatient and outpatient) medical records until death or January 1, 2007. Expected mortality was estimated from the National Center for Health Statistics life tables on the white population in Minnesota, using person‐year methods. Poisson regression was used to model the observed mortality rates, adjusting for age, sex, and disease duration.Results: A cohort of 822 RA patients (72% women, mean age at RA incidence 58 years) was followed up for a median of 11.7 years, during which 445 of the RA patients died. Between 1965 and 2005, the mortality rates across the calendar years for female and male RA patients were relatively constant at 2.4 and 2.5 per 100 person‐years, respectively. In contrast, the expected mortality rate in the Minnesota white population decreased substantially over the same time period in both sexes. Mortality in the female general population declined from 1.0 per 100 person‐years in 1965 to 0.2 per 100 person‐years in 2000. Mortality in the male general population decreased from 1.2 per 100 person‐years in 1965 to 0.3 per 100 person‐years in 2000. Therefore, the difference between the observed and expected mortality rates increased in more recent years, resulting in a widening of the mortality gap.Conclusion: Our findings show that RA patients have not experienced improvements in survival over the past 4 decades, despite dramatic improvements in the overall rates of mortality in the general US population. Further research into the causes of the widening gap in mortality between RA patients and the general population, and the influence of current therapeutic strategies on mortality, is needed in order to develop strategies to reduce the excess mortality observed in RA patients.

Objective: To determine the relationship between glucocorticoid exposure and cardiovascular (CV) events in patients with rheumatoid arthritis (RA).Methods: A total of 603 adult residents of Rochester, Minnesota with incident RA between 1955 and 1995 were followed up through their medical records for a median of 13 years (total of 9,066 person‐years). Glucocorticoid exposure was defined 3 ways: tertiles of cumulative exposure; recent use (≤3 months) versus past use (>3 months); and average daily dosage (≤7.5 mg/day or >7.5 mg/day). CV events, including myocardial infarction, heart failure, and death from CV causes, were defined according to validated criteria. Cox regression models were adjusted for demographic features, CV risk factors, and RA characteristics.Results: Rheumatoid factor (RF)–negative patients with exposure to glucocorticoids were not at increased risk of CV events, irrespective of the glucocorticoid dosage or timing of use, as compared with the reference group of RF‐negative patients who had never been exposed to glucocorticoids. In contrast, RF‐positive patients were at increased risk of CV events, particularly with higher cumulative exposure, higher average daily dosage, and recent use of glucocorticoids. RF‐positive patients with high cumulative exposure to glucocorticoids had a 3‐fold increased risk of CV events (hazard ratio 3.06 [95% confidence interval 1.81–5.18]), whereas RF‐negative patients with high cumulative exposure were not at increased risk (hazard ratio 0.85 [95% confidence interval 0.39–1.87]).Conclusion: RF‐positive but not RF‐negative patients were at increased risk of CV events following exposure to glucocorticoids. These findings suggest that glucocorticoids interact with RF status to modulate the occurrence of CV events in patients with RA. The mechanisms underlying this interaction are unknown and should be the subject of further research.

Objective: Various etiologic mechanisms have been implicated in the observed increase in cardiovascular mortality in rheumatoid arthritis (RA). Body mass index (BMI) is associated with cardiovascular mortality in the general population. This study compared the effect of BMI on cardiovascular mortality in a population‐based cohort of subjects with RA with that in a cohort of individuals without RA from the same population.Methods: The RA cohort comprised all members of an incidence cohort of Rochester, Minnesota residents ages ≥18 years who were first diagnosed with RA (by the American College of Rheumatology 1987 criteria) from 1955 through 1994. An age‐ and sex‐matched comparison cohort of subjects without RA was assembled. Both cohorts 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, and the details of weight and height changes during this period were recorded. High BMI was defined as a BMI >30 kg/m² and low BMI as <20 kg/m². Cox regression models were used to estimate the effect of BMI on cardiovascular mortality after accounting for traditional cardiac risk factors and malignancies.Results: RA subjects with low BMI at incidence had a significantly higher risk of cardiovascular death (hazard ratio [HR] 3.34, 95% confidence interval [95% CI] 2.23–4.99) compared with non‐RA subjects with normal BMI, after adjusting for age, sex, personal cardiac history, smoking status, and presence of diabetes, hypertension, and malignancies. RA subjects with normal BMI at incidence who experienced low BMI during followup also had a higher risk of cardiovascular death (HR 2.09, 95% CI 1.50–2.92) when compared with non‐RA subjects who maintained normal BMI throughout followup.Conclusion: Among patients with RA, low BMI is associated with a significantly increased risk of cardiovascular death.