Prevalence of atrial fibrillation in a stroke case-control study

From the Division of Cardiovascular Diseases and Internal Medicine, Mayo Clinic, Rochester, Minnesota

Currently, approximately 2.3 million Americans have atrial fibrillation. By 2050, it is estimated that 5.6 million people in the United States will have the disorder, which has been labeled a growing epidemic.1,2 Atrial fibrillation is an independent predictor of mortality.3 It also causes significant morbidity, including stroke, and substantially increases health care costs.4 The Framingham study showed a significant increase in the prevalence of atrial fibrillation in men, but not in women, over the course of 22 years (1968—1989), even after adjusting for age and comorbid conditions.5 We conducted an analysis of the data collected over 30 years (1960–1989) in a longitudinal, population-based study of ischemic stroke in Rochester, Minnesota, to evaluate whether atrial fibrillation prevalence changed among patients with incident ischemic stroke and among age- and sex-matched control subjects.6

Patients and methods

Rochester, Minnesota, is comparatively isolated from other urban centers. Medical care is available from only a few health care providers, including the Mayo Clinic and its two affiliated hospitals, the Olmsted Medical Center and its affiliated hospital, and a small number of private practitioners. The Mayo Clinic, which has maintained a unified medical record with details of all inpatient and outpatient visits, laboratory reports, and patient-related correspondence, provides much of the health care in Rochester. A medical linkage system permits access to medical information on patients served by practices in the surrounding areas,7 and all patients in the community with a specific disease or diagnosis can be easily identified. A case-control study of the incidence of ischemic stroke in the Rochester area was performed, and the definitions of ischemic stroke and methods of selecting the control subjects have been previously reported.8,9 Based on this study, we evaluated the prevalence of a history of atrial fibrillation (referred to in this article as “prevalence of atrial fibrillation”) and specific comorbid conditions as of the date of stroke diagnosis for cases, and the reference date for control subjects. Atrial fibrillation was considered present only if it could be substantiated by an electrocardiogram. Definitions of comorbid conditions were applied over the entire period, as reported previously.8 Comorbid conditions were noted as present or absent, and the date of first mention was recorded, which permitted prevalence calculations for each of the three decades (1960—1969, 1970–1979, and 1980–

1989) to be performed.

In terms of statistical analyses, the effects of age, sex, and calendar time on the odds of a history of atrial fi-brillation and of each comorbid condition separately among case patients and control subjects were assessed using logistic regression models.10 Age, sex, and their associations were also examined. Calendar year, as both a continuous and a discrete (by decade) variable, was evaluated, adjusting for best-fit age and sex models. Associations of calendar year with age and sex were examined. Only significant associations with calendar year that affected the qualitative interpretation were reported.

The best logistic model was determined for each condition, and the proportions of case patients and control subjects with each condition (adjusted for the demographic variables in the model) were estimated by use of the logit function.10 To summarize the age-adjusted results, prevalence estimates obtained from the multivariate models are reported for age 75 years because this was the mean age for the cohort. For all model building, two-sided P values were used; a variable was considered significant only if P < .05.

Results

Effects of age, sex, and calendar time on prevalence of atrial fibrillation. The study population consisted of 3,742 residents of Rochester. The mean age was 75 ± 11 years (median age, 76 years; range, 45—105 years). Of 1,871 residents (838 men) with an ischemic stroke over the three decades, 327 (17%) had a history of atrial fibrillation before the date of stroke diagnosis. Among the 1,871 age- and sex-matched control subjects, 176 (9.4%) had a history of atrial fibrillation before the reference date. Table 1 shows the observed prevalence of atrial fibrillation among case patients and control subjects, stratified by age, sex, and calendar decade. A substantial increase in the prevalence of atrial fibrillation was shown with increasing age for stroke patients (odds ratio [OR] per 10 years of age, 1.81; 95% confidence interval [CI], 1.58–2.07; P < .001); however, there was no significant difference between the sexes. There was a significant “calendar-time effect” after adjustment for age and sex: the OR per 5 years was 1.13 (95% CI, 1.05–1.22; P = .001). This change in the prevalence of atrial fibrillation over calendar time did not vary according to sex or age (figure). In this multivariate model, the age-adjusted estimates of prevalence for the three decades (1960–1969, 1970-1979, and 1980–1989) were 11%, 13%, and 16% for men and 13%, 16%, and 20% for women, respectively. A substantial increase in the prevalence of atrial fibrillation with advancing age was shown for the control subjects (OR per 10 years, 2.22; 95% CI, 1.84–2.68), and male sex was associated with a greater likelihood of atrial fibrillation (OR, 1.50; 95% CI, 1.06–2.11). A significant calendar-time effect after adjustment for age and sex also existed: the OR per

5 years was 1.24 (95% CI, 1.12—1.37; P < .001). This change in the prevalence of atrial fibrillation over cal-endar time also did not vary according to sex or age (figure). In this multivariate model, the age-adjusted estimates of prevalence for the three decades were 5%, 8%, and 12% for men and 4%, 6%, and 8% for women, respectively.

The age-adjusted prevalence of atrial fibrillation increased significantly (P < .001) over the 30 years for the total sample of 3,742 individuals. The rates of increase were significant for both cases (P = .001) and control subjects (P < .001); however, they did not differ between the two groups

or between the two sexes within groups. The overall trends of prevalence of atrial fibrillation were based on age-adjusted prevalence values for the mean age of 75 years for cases and control subjects.

Time trends of comorbid conditions. Substantial increases in prevalent hypertension, coronary artery disease (CAD), and valvular heart disease were evident in both cases and controls from 1960 to 1989. Prevalent myocardial infarction (MI) increased significantly in cases and older controls; however, prevalent congestive heart failure (CHF), diabetes mellitus, and a history of cardiac surgery increased only in the cases (table 2).

Discussion

The prevalence rates of atrial fi-brillation for patients with incident stroke and in age- and sex- matched controls over the course of 30 years were assessed. Age was a strong risk factor for the development of atrial fibrillation, which was consistent with other studies.11-15 There was a doubling of the odds for atrial fibrillation for each decade of age (controls: OR, 2.22; 95% CI, 1.84—2.86; cases: OR, 1.81; 95% CI, 1.58–2.07). There was also a calendar-time effect on the prevalence of atrial fibrillation, independent of age. The age-adjusted prevalence of atrial fibrillation increased significantly (P < .001) over the 30-year period for the total sample of 3,742 residents (figure). The rates of increase were significant for both case patients and control subjects, but did not differ between the two groups. The rates of increase over time were significant for both men and women in the case and control groups, but they did not differ between the two sexes. Changes in the prevalence of comorbid conditions over time may be important factors in the development and continuation of this epidemic (table 2). The risk of atrial fibrillation development is a function not only of advancing age, but also of the total disease burden and the presence of selected comorbid conditions that are themselves risk factors for atrial fibril-lation among those who survive to older ages.

Conclusion

The prevalence of atrial fibrillation increased significantly in patients with ischemic stroke and in their age- and sex-matched controls over a 30-year period. The rates of increase were not significantly different between men and women.

An increase in the prevalence of specific comorbid conditions may have partly contributed to the observed trends in atrial fibrillation, but additional studies are needed to further our understanding of the mechanisms and control of this growing epidemic.