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Keywords:

  • Rheumatoid arthritis;
  • Cardiovascular disease;
  • Cancer screening;
  • Epidemiology;
  • Health services research

Abstract

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. METHODS
  5. RESULTS
  6. DISCUSSION
  7. Acknowledgements
  8. REFERENCES

Objective

To compare frequencies of cancer screening and cardiovascular treatments aimed at reducing acute myocardial infarction in women with and without rheumatoid arthritis (RA).

Methods

Data from the prospective Nurses' Health Study were analyzed for the 491 women diagnosed with RA prior to 1998 and the 82,884 women without RA. Cardiovascular treatments included aspirin use, treatment with a cholesterol-lowering agent, cardiac catheterization, and coronary artery revascularization; cancer screening consisted of mammography and bimanual pelvic examinations. Adjustments were made for potential confounders using multivariate logistic regression.

Results

After adjusting for cardiovascular risk factors, use of nonsteroidal antiinflammatory drugs, and a history of gastric or duodenal ulcer, women with RA and no history of cardiac disease were 35% less likely to report taking aspirin regularly (odds ratio [OR] 0.65, 95% confidence interval [95% CI] 0.51–0.84). The use of cholesterol-lowering treatment, angiography, and revascularization was not statistically different in women with and without RA. After adjusting for cancer risk factors, there appeared to be an increased likelihood of mammography in women with RA compared with those without RA (OR 1.41, 95% CI 0.97–2.04), although this result was not statistically significant. Bimanual pelvic examination was reported with similar frequency between the 2 groups.

Conclusion

Other than aspirin use, care to prevent acute myocardial infarction and cancer screening practices were similar among women with RA compared with women without RA.


INTRODUCTION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. METHODS
  5. RESULTS
  6. DISCUSSION
  7. Acknowledgements
  8. REFERENCES

Individuals with rheumatoid arthritis (RA) experience a 5–10 year reduction in average life span for a variety of reasons, including an increased risk of cardiovascular disease and cancer (1–3). Many investigators have suggested that the underlying systemic inflammation associated with RA gives rise to endovascular inflammation and associated atherosclerosis (4). Similarly, the increased risk of cancer is thought due to both immune dysregulation and the use of immunosuppressive medications (5).

Although alterations in the immune system from RA and immunosuppressive medications may explain part of the increased risk of cancer and cardiovascular disease, alternatively, individuals with RA may have an increase in risk for nonrheumatic disease endpoints because they receive a different standard of care. In other words, if patients with RA received a different level of primary or secondary prevention for cancer and coronary artery disease, including decreased rates of screening or treatment, this may in part explain higher frequencies of certain cancers and cardiac endpoints.

Prior investigations support this hypothesis. Data from Redelmeier et al suggest that the presence of 1 chronic disease affects care for another, such that patients with shizophrenia were much less likely to receive treatment for arthritis (6). Similarly, MacLean and colleagues observed that women with RA in 1 large health maintenance organization (HMO) received cancer screening much less frequently than suggested by the US Preventive Services Task Force (7). Therefore, the rates of cancer and cardiovascular disease endpoints might be increased for patients with RA compared with persons without RA if they receive less screening or less preventive care. We hypothesized that cancer screening and care aimed at preventing acute myocardial infarctions would be less common in women with RA compared with those without RA.

METHODS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. METHODS
  5. RESULTS
  6. DISCUSSION
  7. Acknowledgements
  8. REFERENCES

Study population.

The Nurses' Health Study is a prospective cohort study comprised of 121,700 women who were between the ages of 30 and 55 years when they completed the baseline questionnaire in 1976. These women have been sent questionnaires every 2 years to update information concerning medical, lifestyle, and other health-related information (8). The biennially mailed questionnaires ask participants about recent illnesses, including RA, and other diagnoses; cardiovascular risk factors, including cigarette smoking, menopausal status, blood pressure, elevated cholesterol, and family history of myocardial infarction before age 60; specific screening measures for cancer, such as bimanual pelvic examination and mammography; personal and family history of specific cancers; and the use of a variety of medications, including nonsteroidal antiinflammatory drugs (NSAIDs) and oral glucocorticoids. No information is available on disease-modifying antirheumatic drug use. Women who reported RA and cancer (other than nonmelanoma skin cancer) at baseline were excluded. After exclusions, 83,375 women who answered the 1998 biennial questionnaire were eligible for these analyses. This study was approved by the Partners HealthCare System Institutional Review Board.

Assessment of rheumatoid arthritis.

Between 1978 and 1998, 12,691 women reported having RA on a biennial questionnaire. Attempts have been made to contact these participants to confirm their RA diagnosis, initially by completing a connective tissue disease screening questionnaire (9). In total, 8,173 women (64%) responded to the mailings, with 1,815 denying the diagnosis of RA, 603 denying permission to review medical records, and 47 responding that the onset of disease was prior to the start of followup in 1976. Of the remaining women, 2,454 had no symptoms suggestive of RA on the disease screening questionnaire and no additional followup was attempted. We requested medical records regarding 3,254 women and obtained sufficient information on 2,519. Two rheumatologists trained in chart abstraction independently reviewed the medical records using the 1987 American College of Rheumatology (formerly American Rheumatism Association) diagnostic criteria for RA (10). These criteria were assessed in a cumulative fashion examining all available medical records. Women with 4 of the 7 classification criteria were considered to have RA.

Data analysis.

The biennial questionnaire sent to the Nurses' Health Study participants in 1998 inquired about several different aspects of cancer screening and care to prevent acute myocardial infarctions. Relevant cardiovascular care included the regular use of aspirin, the use of cholesterol-lowering treatments, cardiac catheterization, and coronary artery revascularization. Persons were considered to be regular users of aspirin if they reported taking aspirin on 3 or more days of each week; dosage was not specified. Aspirin use was assessed in persons with and without evidence for cardiovascular disease, including any previous report of a myocardial infarction, cerebrovascular accident, angina, coronary artery bypass graft, or percutaneous transluminal coronary angioplasty. Cholesterol-lowering treatment was assessed in 2 groups of participants: persons reporting high cholesterol and all participants. Angina was assessed by asking patients if they had been diagnosed by a physician as having “angina pectoris” and whether it had been “confirmed by angiogram or stress test.” Only participants who ever reported angina were asked to report whether they had ever undergone coronary catheterization. Coronary artery revascularization was assessed in persons reporting a myocardial infarction or angina.

Cancer screening measures assessed on the 1998 questionnaire included mammography and bimanual pelvic examination. We examined these measures in all participants and then, in a subgroup analysis, excluded women who reported either a hysterectomy or having both ovaries removed.

The primary analyses examined the association between RA diagnosed before 1998 and, in separate models, cardiovascular care or cancer screening reported on the 1998 questionnaire. The age-adjusted models include only age and the diagnosis of RA as potential predictors. Multivariate logistic regression was used to control for age and other potential confounders. For the cardiovascular care analyses, the confounders included self-reported hypertension, diabetes, hypercholesterolemia, parental history of myocardial infarction before age 60, and cigarette smoking (current, past, or never). Report of NSAID use in 1998 and any history of gastric or duodenal ulcer was included as a covariate for the aspirin use analyses as well. For the cancer screening multivariate logistic regression, the potential confounders included age, hormone replacement therapy, parity, prior cancers (such as breast, ovarian, or uterine), and family history of breast, ovarian, or uterine cancer. We calculated the odds ratio (OR) and 95% confidence interval (95% CI). All analyses were conducted using SAS statistical software 6.12 (SAS, Cary, NC).

RESULTS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. METHODS
  5. RESULTS
  6. DISCUSSION
  7. Acknowledgements
  8. REFERENCES

We confirmed an incident diagnosis of RA in 527 women between 1978 and 1998. After exclusions, 491 cases were included in these analyses.

After adjusting for age, participants with RA and no known cardiovascular disease were almost half as likely to use aspirin regularly as non-RA controls (OR 0.52, 95% CI 0.41–0.66; Table 1). This result persisted after adjusting for cardiovascular risk factors, NSAID and oral glucocorticoid use, and a history of gastric or duodenal ulcer (OR 0.65, 95% CI 0.51–0.84). Stratified models based on NSAID use were examined and gave very similar results (data not shown). Women with RA were as likely to report use of a cholesterol-lowering treatment as women without RA, regardless of whether they reported hypercholesterolemia or not (Table 1). Among women reporting angina (n = 13 with RA and n = 2,732 without RA), cardiac catheterization was reported with similar frequency. Similarly, coronary artery revascularization occurred with similar frequency in women with RA and without RA (Table 1).

Table 1. The frequency of cardiovascular treatments aimed at reducing acute myocardial infarctions among participants of the Nurses' Health Study with and without rheumatoid arthritis*
Process of carePopulation assessedNPercentage treatedAge-adjusted OR (95% CI)Multivariate adjusted OR (95% CI)
RANon-RA
  • *

    RA = rheumatoid arthritis; OR = odds ratio; 95% CI = 95% confidence interval; CVD = cardiovascular disease, including cardiac and cerebrovascular disease; CAD = coronary artery disease.

Regular aspirin useHistory of CVD9,96143580.54 (0.33–0.88)0.71 (0.42–1.18)
Regular aspirin useNo history of CVD73,41420310.52 (0.41–0.66)0.65 (0.51–0.84)
Cholesterol-lowering treatmentElevated cholesterol29,22942401.06 (0.75–1.50)1.02 (0.72–1.46)
Cholesterol-lowering treatmentAll participants83,37514160.81 (0.62–1.04)0.82 (0.63–1.06)
Coronary catheterizationHistory of angina2,74531490.45 (0.14–1.47)0.34 (0.10–1.15)
Coronary revascularizationHistory of CAD8,39127251.10 (0.59–2.04)1.35 (0.71–2.58)

The use of cancer screening was not reduced for participants with RA compared with non-RA controls (Table 2). Women with and without RA reported bimanual pelvic examination at almost identical frequencies; these results were unchanged in the subgroup of women who had neither reported hysterectomy or bilateral oophorectomy. There was a suggestion that women with RA were more likely to receive a mammogram than non-RA controls (OR 1.41, 95% CI 0.97–2.04).

Table 2. The frequency of mammography and bimanual pelvic examination among participants of the Nurses' Health Study with and without rheumatoid arthritis*
Process of carePopulation assessedNPercentage screenedAge-adjusted OR (95% CI)Multivariate adjusted OR (95% CI)
RANon-RA
  • *

    RA = rheumatoid arthritis; OR = odds ratio; 95% CI = 95% confidence interval.

MammogramAll participants83,37594911.46 (1.01–2.10)1.41 (0.97–2.04)
Bimanual pelvic examinationAll participants83,37576780.96 (0.78–1.19)0.93 (0.75–1.15)
Bimanual pelvic examinationNo report of hysterectomy or bilateral oophorectomy49,81983831.07 (0.78–1.46)1.00 (0.72–1.40)

DISCUSSION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. METHODS
  5. RESULTS
  6. DISCUSSION
  7. Acknowledgements
  8. REFERENCES

We examined the use of cardiac treatments aimed at reducing acute myocardial infarctions and cancer screening for participants with RA compared with those without RA in the Nurses' Health Study. With respect to cardiovascular care, not surprisingly, aspirin use was significantly less common in women with RA without a history of cardiovascular disease compared with women without RA. Although the trend was in a similar direction, among the smaller group of women reporting a history of cardiovascular disease, this was not statistically significant. Other cardiovascular treatments studied were reported with similar frequency by women with and without RA. Mammography and bimanual pelvic examinations occurred with a frequency at least as high among women with RA compared with controls.

In light of data suggesting that acute myocardial infarctions occur at an increased rate in persons with RA compared with those without, the reduced aspirin use in this group needs to be examined (2, 11, 12). Recent pooled analyses suggest that aspirin in secondary prevention reduces acute myocardial infarction in the general population by ∼30% (13). These data have not been extended to people with RA, but there is little reason to doubt that this effect is generalizable. Several plausible explanations for the reduced aspirin use include a relative contraindication to aspirin use because of concomitant use of other medications for RA, patients' and doctors' reluctance to add another medicine to a complicated treatment regimen, and a general lack of attention to cardiovascular prevention. Although some data suggest that specific NSAIDs may be associated with a reduced risk of acute myocardial infarction, and persons with RA are more likely to be exposed to such agents, this potential cardioprotective effect appears related only to certain agents (14–16).

It is reassuring that women with RA appear to be receiving similar cancer screening compared with non-RA controls. Although a prior report suggested that women with RA in 1 large HMO did not receive cancer prevention services at recommended intervals (7), these investigators did not compare the frequency of services between persons with and without RA.

The major limitation of the data we present is that all participants in the Nurses' Health Study are health professionals, thus they may receive different levels of health services than the general population. However, we have no reason to believe that the comparisons between women with and without RA would not persist in other patient groups. It is interesting to note that mammography rate reported by women older than 50 years in the US Behavioral Risk Factor Surveillance System for 2000 was 76% compared with 91% among this study's participants (17). Another limit to these data is the small number of women with RA who also reported angina with subsequent coronary catheterization; thus, the confidence intervals around coronary catheterization are relatively wide. Finally, angina and coronary catheterization data are based on self report. Women may have mistakenly reported these conditions and introduced misclassification. However, in validation studies conducted on subgroups of this same population reporting hypertension, the diagnosis was confirmed in all women using the primary medical record as the gold standard (18). Although angina and coronary catheterization may not be as accurately self reported as hypertension, we do not have reason to believe that misclassification would have occurred differentially between women with and without RA.

Prior research has suggested that patients with 1 chronic illness, such as RA, may be less likely to receive medications for other conditions (6). The effect of chronic illnesses on the care of other conditions may depend on the specific health service, such that the use of routine screening (such as mammography) may be similar or increased for persons who have frequent contact with the health care system. In other words, persons with RA who are seen often by health care providers may undergo screening tests and physical examinations at rates comparable or higher than their counterparts without a chronic condition. In the case of cardiovascular treatment, such as adding an aspirin for acute myocardial infarction prevention, patients with chronic conditions (such as RA) and their doctors may be reluctant about introducing potential medication interactions or side effects. Future studies that assess the use of health services for comorbid conditions associated with RA, including cardiovascular disease and cancer, will help improve our understanding of the impact of RA on individuals with this chronic disease.

Acknowledgements

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. METHODS
  5. RESULTS
  6. DISCUSSION
  7. Acknowledgements
  8. REFERENCES

Jeffrey N. Katz provided helpful comments on an earlier version of this manuscript, and Elaine Coughlan provided excellent programming support for all aspects of this project.

REFERENCES

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. METHODS
  5. RESULTS
  6. DISCUSSION
  7. Acknowledgements
  8. REFERENCES