Although sleep quality and duration have been related to cardiovascular end points, little is known about the association between sleep duration and incident atrial fibrillation (AF). Hence, we prospectively examined the association between sleep duration and incident AF in a cohort of 18,755 United States male physicians. Self-reported sleep duration was ascertained during a 2002 annual follow-up questionnaire. Incident AF was ascertained through annual follow-up questionnaires. Cox regression analysis was used to estimate the relative risks of AF. The average age at baseline was 67.7 ± 8.6 years. During a mean follow-up of 6.9 ± 2.1 years, 1,468 cases of AF occurred. Using 7 hours of sleep as the reference group, the multivariate adjusted hazard ratio for AF was 1.06 (95% confidence interval 0.92 to 1.22), 1.0 (reference), and 1.13 (95% confidence interval 1.00 to 1.27) from the lowest to greatest category of sleep duration (p for trend = 0.26), respectively. In a secondary analysis, no evidence was seen of effect modification by adiposity (p for interaction = 0.69); however, prevalent sleep apnea modified the relation of sleep duration with AF (p for interaction = 0.01). From the greatest to the lowest category of sleep duration, the multivariate-adjusted hazard ratio for AF was 2.26 (95% confidence interval 1.26 to 4.05), 1.0 (reference), and 1.34 (95% confidence interval 0.73 to 2.46) for those with prevalent sleep apnea and 1.01 (95% confidence interval 0.87 to 1.16), 1.0 (reference), and 1.12 (95% confidence interval 0.99 to 1.27) for those without sleep apnea, respectively. Our data showed a modestly elevated risk of AF with long sleep duration among United States male physicians. Furthermore, a shorter sleep duration was associated with a greater risk of AF in those with prevalent sleep apnea.
Atrial fibrillation (AF) is a highly prevalent cardiac arrhythmia in clinical practice, affecting >2 million people in the United States (US) and >4 million people across the European Union. Because the prevalence of AF increases with advancing age, it has been anticipated that the burden of AF will gradually increase with the aging US population. Data from previous studies have demonstrated beneficial effects of light-to-moderate physical activity on AF risk, positive associations with obesity, inflammation, sleep apnea, heavy alcohol consumption, hypertension (HTN), type 2 diabetes (T2D), and dyslipidemia. Recent data have suggested that too little sleep or too much sleep can each be associated with adverse health outcomes, including obesity, inflammation, HTN, T2D, dyslipdemia, cardiovascular disease, and total mortality. However, the association between sleep duration and incident AF has not been investigated in a prospective cohort study. Therefore, the present study sought to prospectively assess the association of sleep duration with incident AF among US male physicians. Because adiposity and sleep apnea can have a negative effect on sleep quality, we also examined whether sleep apnea modified the sleep duration–AF association.
Methods
The Physicians’ Health Study (PHS) I is a completed, randomized, double-blind, placebo-controlled trial, designed to study the effects of low-dose aspirin and β-carotene on cardiovascular disease and cancer among US male physicians. In 1997, PHS II trial enrolled 7,641 physicians from PHS I and 7,000 new physicians to study the effects of vitamins on cardiovascular disease and cancer. A detailed description of PHS I and II has been published. Self-reported sleep duration was ascertained during the 2002 annual follow-up questionnaire. Of the total 29,067 PHS subjects, we excluded those who had died before the sleep duration assessment (n = 381), those with missing data on sleep duration (n = 7,621), and those with prevalent AF (n = 2,310). Thus, a final sample of 18,755 participants was used for the present analyses. Each participant gave written informed consent, and the institutional review board at Brigham and Women’s Hospital approved the study protocol.
For self-reported sleep duration, participants were asked, “On average, how many total hours of sleep do you get in typical 24-hour period?” The possible responses were “<5 hours,” “6 hours,” “7 hours,” “8 hours,” “9 hours,” “10 hours,” and “≥11 hours.”
Incident AF was ascertained through annual follow-up questionnaires. In the PHS, self-reported AF was previously validated in a random sample of 400 PHS participants using a more detailed questionnaire on the diagnosis of AF and the review of medical records by cardiologists.
Data on the demographics, anthropometrics, exercise frequency, smoking, and alcohol consumption, and a history of HTN, T2D, dyslipidemia, coronary heart disease, congestive heart failure, sleep apnea, and snoring were obtained at baseline. Age and body mass index were used as continuous variables. Race was dichotomized as white and nonwhite. Exercise was classified as rarely/never, 1 to 3 times/mo, 1 to 4 times/wk, and 5 to 7 times/wk. Smoking was classified as never, past, and current smokers. For alcohol consumption, the subjects were asked the following question: “How often do you usually consume alcoholic beverages?” Possible responses were rarely/never, 1 to 3 times/mo, 1 time/wk, 2 to 4 times/wk, 5 to 6 times/wk, daily, and ≥2 times/day. These responses were interpreted as the number of alcoholic drinks consumed during the specified period. For the present analyses, alcohol consumption was classified as 0 to 4, 5 to 7, and >7 drinks/wk. HTN was defined as a self-reported diagnosis of HTN, blood pressure >140/90 mm Hg, or the use of antihypertensive drugs. A diagnosis of coronary heart disease (angina, myocardial infarction, and coronary artery bypass grafting) was validated by the PHS End Point Committee. Congestive heart failure and T2D diagnoses were also self-reported and validated by detailed review of the medical records in a subsample. The diagnoses of sleep apnea (yes vs no) and snoring (rarely/never, few/occasionally, mostly/always, and unknown/missing) were based on self-report.
We classified each subject into 1 of the following categories of average sleep duration: ≤6, 7, and ≥8 hours. We computed the person-time of follow-up from the time when the sleep duration was assessed until the first occurrence of AF, death, or the date of the last available follow-up examination. The baseline demographic variables were recorded and compared across the categories of sleep duration.
We used Cox proportional hazard models to compute multivariate adjusted hazard ratios with the corresponding 95% confidence intervals using participants reporting 7 hours of sleep duration as the reference group. Potential confounding was assessed for the established risk factors of AF. First, we adjusted for age and race in model 1. Second, we also controlled for body mass index, exercise frequency, alcohol consumption, smoking status, sleep apnea, and snoring in model 2. Finally, in model 3, we adjusted for the factors included in model 2 and for potential mediators such as a history of HTN, T2D, dyslipidemia, coronary heart disease, and congestive heart failure.
In the secondary analyses, we evaluated whether statistically significant interactions were present between sleep duration and body mass index or sleep apnea using a product term of both variables in a hierarchical model. Assumptions for the proportional hazard models were tested (by including the main effects and product terms of sleep duration and logarithmic-transformed time factor) and were met (p >0.05 for all). All analyses were conducted using SAS, version 9.2 (SAS Institute, Cary, North Carolina). The significance level was set at 0.05.
Results
The baseline characteristics according to sleep duration are listed in Table 1 . The mean age of the study participants at baseline was 67.7 ± 8.6 years. A long (≥8 hours) sleep duration was associated with a lower prevalence of never smokers and a greater prevalence of >7 times/wk alcohol consumption, HTN, T2D, dyslipidemia, and coronary heart disease.
| Variable | Average Sleep Duration (h) | ||
|---|---|---|---|
| ≤6.0 (n = 4,835) | 7.0 (n = 7,773) | ≥8.0 (n = 6,147) | |
| Age (yrs) | 65 ± 8 | 67 ± 8 | 71 ± 9 |
| White race | 4,135 (86%) | 7,087 (92%) | 5,714 (93%) |
| Body mass index (kg/m 2 ) | 26 ± 4 | 26 ± 4 | 26 ± 4 |
| Exercise frequency | |||
| Rarely/never | 1,691 (36%) | 2,474 (32%) | 2,264 (37%) |
| 1–3/month | 172 (4%) | 227 (3%) | 134 (2%) |
| 1–4/week | 2,055 (43%) | 3,646 (47%) | 2,571 (42%) |
| 5–7/week | 846 (18%) | 1,351 (18%) | 1,138 (19%) |
| Smoker | |||
| Never | 2,819 (58%) | 4,539 (59%) | 3,205 (52%) |
| Past | 1,879 (39%) | 3,034 (39%) | 2,717 (44%) |
| Current | 130 (3%) | 184 (2%) | 216 (4%) |
| Alcohol consumption (drinks/week) | |||
| 0–4 | 3,092 (64%) | 4,470 (58%) | 3,230 (53%) |
| 5–7 | 1,029 (21%) | 1,933 (25%) | 1,444 (24%) |
| >7 | 689 (14%) | 1,333 (17%) | 1,451 (24%) |
| History of snoring | |||
| Rarely/never | 881 (18%) | 1,481 (19%) | 1,239 (20%) |
| Few/occasionally | 1,831 (38%) | 3,169 (41%) | 2,437 (40%) |
| Mostly/always | 1,734 (36%) | 2,500 (32%) | 1,921 (31%) |
| Unknown/missing | 389 (8%) | 623 (8%) | 550 (9%) |
| Sleep apnea | 227 (5%) | 270 (3%) | 267 (4%) |
| Hypertension (by history) | 2,328 (48%) | 3,760 (48%) | 3,599 (59%) |
| Diabetes mellitus | 367 (8%) | 551 (7%) | 615 (10%) |
| Dyslipidemia (by history) | 2,429 (50%) | 3,869 (50%) | 3,220 (52%) |
| Previous coronary heart disease | 564 (12%) | 939 (12%) | 945 (15%) |
| Previous congestive heart failure | 42 (1%) | 90 (1%) | 135 (2%) |
A comparison of the baseline characteristics between subjects with missing data on sleep duration (after excluding those who died before the assessment of baseline information and those with prevalent AF) and those with complete data on sleep duration is provided in Table 2 . Overall, the participants with missing data on sleep duration were older, had a greater prevalence of sleep apnea, current smokers, and sedentary lifestyle, and had a lower prevalence of HTN, dyslipidemia, and congestive heart failure compared to those with complete data on sleep duration.
| Variable | Missing Data | p Value | |
|---|---|---|---|
| Yes (n = 6,873) | No (n = 18,755) | ||
| Age (y) | 70 ± 9.2 | 68 ± 8.6 | <0.0001 |
| White race | 4,458 (90%) | 16,936 (91%) | 0.345 |
| Body mass index (kg/m 2 ) | 25 ± 4.1 | 26 ± 3.7 | <0.0001 |
| Exercise frequency | <0.0001 | ||
| Rarely/never | 1,810 (45%) | 6,429 (35%) | |
| 1–3/mo | 284 (7.1%) | 533 (2.9%) | |
| 1–4/wk | 1,238 (31%) | 8,272 (45%) | |
| 5–7/wk | 663 (17%) | 3,335 (18%) | |
| Smoker | <0.0001 | ||
| Never | 1,918 (46%) | 10,563 (56%) | |
| Past | 2,028 (49%) | 7,630 (41%) | |
| Current | 205 (4.9%) | 530 (2.8%) | |
| Alcohol consumption (drinks/wk) | <0.006 | ||
| 0–4 | 2,398 (61%) | 10,792 (58%) | |
| 5–7 | 877 (22%) | 4,406 (24%) | |
| >7 | 684 (17%) | 3,473 (19%) | |
| History of snoring | <0.0001 | ||
| Rarely/never | 127 (1.9%) | 6,155 (33%) | |
| Few/occasionally | 151 (2.2%) | 7,437 (40%) | |
| Mostly/always | 72 (1.1%) | 3,601 (19%) | |
| Unknown/missing | 6,523 (95%) | 1,562 (8.3%) | |
| Sleep apnea | 70 (5.4%) | 764 (4.1%) | 0.018 |
| Hypertension (by history) | 2,644 (38%) | 9,687 (52%) | <0.0001 |
| Diabetes mellitus | 552 (8.0%) | 1,533 (8.2%) | 0.712 |
| Dyslipidemia (by history) | 1,881 (27%) | 9,518 (51%) | <0.0001 |
| Previous coronary heart disease | 926 (13%) | 2,448 (13%) | 0.378 |
| Previous congestive heart failure | 46 (0.7%) | 267 (1.4%) | <0.0001 |
During a mean follow-up of 6.9 ± 2.1 years, 1,468 cases of AF occurred. The crude incidence rate of AF was 9.6, 9.9, and 14.9 cases/1,000 person-years for those reporting an average sleep duration of ≤6, 7, and ≥8 hours, respectively ( Table 3 ). Using 7 hours of sleep as the reference group, the multivariate adjusted hazard ratios for AF were 1.06 (95% confidence interval 0.92 to 1.22), 1.0 (reference), and 1.13 (95% confidence interval 1.00 to 1.27) from the lowest to the highest category of sleep duration (p for trend = 0.26; Table 3 ).
| Sleep Duration (h) | Cases (n)/Person-yrs | Crude Incidence Rate (1,000 Person-yrs) | Unadjusted HR (95% CI) | Adjusted HR (95% CI) | ||
|---|---|---|---|---|---|---|
| Model 1 | Model 2 | Model 3 | ||||
| ≤6.0 | 325/33,794 | 9.6 | 0.97 (0.85–1.12) | 1.08 (0.94–1.24) | 1.06 (0.92–1.22) | 1.06 (0.92–1.22) |
| 7.0 | 540/54,651 | 9.9 | 1.0 | 1.0 | 1.0 | 1.0 |
| ≥8.0 | 603/40,370 | 14.9 | 1.51 (1.35–1.70) | 1.16 (1.03–1.31) | 1.14 (1.01–1.28) | 1.13 (1.00–1.27) |
| p Value (linear trend) | <0.0001 | 0.15 | 0.19 | 0.26 | ||
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