2025 Volume 32 Issue 4 Pages 502-512
Aims: Few studies have investigated the impact of sleep duration at night and daytime napping on mortality from aortic disease. In this study, we examined the associations of sleep duration at night with daytime napping and mortality from aortic disease.
Methods: We followed 67,269 participants (26,826 men and 40,443 women, aged 40–79 years) who were not night shift workers and had no history of stroke, heart disease, or cancer. The baseline survey was conducted in 1988–1990, and follow-up continued until the end of 2009. Sleep duration at night was classified into three categories: ≤ 6, 7, and ≥ 8 hours/day. We also asked the presence or absence of daytime napping. Hazard ratios (HRs) for mortality from aortic disease with 95% confidence intervals (CIs) were estimated using the Cox proportional hazards model.
Results: During an average 16.3-year follow-up period, we observed 87 deaths from aortic dissection and 82 from aortic aneurysms. There was no association between sleep duration at night and mortality from aortic disease, but daytime napping was associated with an increased risk of mortality from total aortic disease; the multivariable-adjusted HRs were 1.48 [95% CIs: 1.08–2.02]. Furthermore, the stratified analysis revealed a stronger association with medium sleep duration (7 hours at night) compared to the other shorter and longer sleep duration: the multivariable-adjusted HR for aortic disease, 2.02 [1.16–3.52].
Conclusion: Daytime napping but not sleep duration at night was associated with an increased risk of mortality from aortic disease.
Abbreviations: HRs, hazard ratios; CIs, confidence intervals; CVD, cardiovascular disease; The JACC study, The Japan Collaborative Cohort Study; BMI, body mass index; OSA, obstructive sleep apnea.
Aortic disease is a rare but life-threatening disease due to dissection or rupture of the aorta1). The worldwide mortality rate from aortic disease was 2.78 per 100,000 population2, 3), with the incidence of 5–10 per 100,000 person-years4, 5). A meta-analysis showed that the association between self-reported sleep duration and mortality from total cardiovascular disease (CVD), which included aortic disease, was a J-shaped relationship with the nadir of 7–8 hours of sleep6). Also, several cohort studies reported that daytime napping was associated with an elevated risk of total CVD mortality7-9). Sleep is a life activity consisting of sleep duration and daytime napping, which affects sympathetic nerve system and cardiovascular dynamics10, 11). However, the effect of sleep duration and daytime napping on mortality from aortic disease has been scarcely examined due to the lower incidence of aortic disease12). We, therefore, examined the associations of sleep duration at night and daytime napping with mortality from total aortic disease, aortic dissection and aortic aneurysm, in a large Japanese population-based cohort study.
The Japan Collaborative Cohort Study (JACC) for Evaluation of Cancer Risk, sponsored by the Japanese Ministry of Education, Science, Sports, and Culture, is a large population-based prospective cohort study performed in 45 regions out of 1718 municipalities of Japan. The JACC study has been described in detail previously13). Briefly, a total of 110,585 residents aged 40–79 years (46,395 men and 64,190 women) were enrolled in the JACC study from a baseline survey conducted between 1988 and 1990. In the baseline survey, participants completed self-administered questionnaires on their lifestyles and medical histories. In our study, 67,269 participants (26,826 men and 40,443 women) were used for the analysis after excluding the participants who were not asked (n=16,442) or did not answer (n=7209) questions about sleep duration and daytime napping; those who worked night and rotating shifts (n=15,731); and those who had a history of stroke, heart disease, or cancer (n=3,934). Individual informed consent was obtained from participants in 36 of the 45 regions, and group consent was obtained from regional leaders in the remaining nine regions. The study design was approved by the Medical Ethical Committees of Nagoya University (177), Hokkaido University (14-044), and Nippon Medical School (A-2021-069).
OutcomesThe dates of mortality and move-out were collected from the population register. The causes of death based on death certificates were coded according to the International Classification of Diseases-10th Revision: total aortic disease as I710–I719, aortic dissection (I710), and aortic aneurysm as I711–I719. Participants were followed up until the end of 2009 in 35 regions, 2008 in two regions, 2003 in four regions, and 1999 in four regions.
Main Exposures and Confounding FactorsSleep duration at night and daytime napping were obtained from baseline information collected using a self-administered questionnaire. Participants answered the question, “How many hours on average do you sleep on weekdays?”. Sleep duration at night was classified into three categories: ≤ 6, 7, and ≥ 8 hours/day. According to the method of Tamakoshi et al.14), fraction hours were rounded off (e.g., 7 hours represented responses from 6.5 to 7.4 hours). As for daytime napping, participants answered “yes” or “no” to the question “Do you take daytime napping?”. Potential confounding factors selected from the baseline information were age, sex, history of hypertension (yes, no), history of diabetes (yes, no), smoking habit (never, former, ≤ 9, 10–19, ≥ 20 cigarettes/day), drinking habit (never, former, ＜23, 23-46, 46-69, ≥ 69 g/day), body mass index (BMI; ＜18.5, 18.5–22.0, 22.0–25.0, ≥ 25.0 kg/m2), educational background, working status (regular employees, part-time or temporary employees, non-employee workers, homemakers, non-workers), walking time (never, ＜30, 30–60, ≥ 60 min/day), perceived mental stress (low, medium, high), depression (no symptoms, mild depression, moderate-to-severe depression).
As regards working status, participants who answered “others” to the question “Which of the following categories best describes your working status?” were categorized the same as those who answered “part-time or temporary employees.” Using the method of Tamakoshi et al.14), depressive symptoms were assessed using the following four questions:1) “Do you live your life with purpose?” 2) “Do you make decisions quickly?” 3) “Do you enjoy your life?” 4) “Do you think you are trusted by others?”. The number of “No” to the 4 questions was classified into 3 categories: 0 as “no symptoms,” 1 as “mild depression,” and 2 or more as “moderate-to-severe depression.”
Statistical AnalysisMean values (standard deviations) for age and number of participants (proportions) for the other selected risk factors were calculated according to sleep duration at night (≤ 6, 7, and ≥ 8 hours/day), daytime napping, and composite variables between the two. For the baseline characteristics, a generalized linear model was used to assess linear trend and difference between persons with categories of sleep duration at night. We also compare between persons with daily napping and without. The logit link and identity link were used for binary variables and continuous variables, respectively. Person-years were calculated from the date of the baseline survey to the end of the follow-up period, the date of move-out, the date of death from aortic disease, or the date of death from other causes. The sex- and age-adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) in both sex-combined analysis and the age-adjusted HRs with 95% CIs in the sex-specific analysis were respectively calculated by Cox proportional hazards models according to sleep duration of ≤ 6 and ≥ 8 hours as a reference to sleep duration of 7 hours, and daytime napping compared with no daytime napping. Multivariable-adjusted HRs with 95% CIs were estimated after adjusting for potential confounding factors, including age, sex, history of hypertension, history of diabetes, smoking and drinking habits, BMI, educational background, working status, walking time, perceived mental stress, and depression. Sleep duration at night and daytime napping were included and mutually adjusted. Missing values were used as a dummy variable for each confounding factor. We further examined the association between sleep duration at night and daytime napping and mortality from aortic disease using the Fine and Gray proportional subdistribution hazards model to account for the competing risk of pre-aortic disease mortality from stroke, coronary heart disease, or cancer.
In addition, we performed a stratified analysis of sleep duration at night to examine the combined effects of sleep duration at night and daytime napping. Multiplicative interactions between sexes for sleep duration and daytime napping and between sleep duration at night and daytime napping were tested using a cross-product term. Statistical significance was defined as a two-tailed p-value of ＜0.05. All statistical analyses were performed using SAS 9.4 (SAS Institute Inc., Cary, NC, USA).
During the average 16.3-year follow-up (1,093,425 person-years in total), we observed 87 deaths (36 men and 51 women) from aortic dissection and 82 deaths (54 men and 28 women) from aortic aneurysms. There were 4385 participants who were lost to follow-up or moved. Table 1 shows sex-specific baseline characteristics according to sleep duration at night. We observed associations of sleep duration in a dose-response manner with having daytime napping and higher mental stress in men and women, as well as overweight and current smokers in men. There were significant associations of being older, non-workers, and having a history of hypertension was also associated with sleep duration; whereas those did not show an obvious dose-response relationship but rather a J-shaped relationship. In addition, when compared to medium sleep duration of 7 hours, we found no associations between longer sleep duration (≥ 8 hours) and having moderate to severe depression, being current drinkers, and having a history of diabetes mellitus in men; and being underweight in women. As shown in Table 2, participants with daytime napping habits were more likely to be older and non-workers, to sleep longer at night, and to have moderate-to-severe depression and a history of hypertension and diabetes mellitus, whereas they were less likely to have high mental stress and high educational background. In addition, men with daytime napping habits were more likely to be underweight and have long walking times, whereas they were less likely to be current smokers and current drinkers. Women with daytime napping habits were more likely to be obese. Supplementary Table 1 shows the sex-specific baseline characteristics according to the composite variables of sleep duration at night and daytime napping. Moreover, Supplementary Table 2 shows sex-specific basic characteristics of participants who did not complete the questionnaire regarding to sleep duration at night and daytime napping.
| Sleep duration at night (hours/day) | ||||||||
|---|---|---|---|---|---|---|---|---|
| Men | Women | |||||||
|
≤ 6 hours (n=4156) |
7 hours (n=8984) |
≥ 8 hours (n=13 686) |
p-values |
≤ 6 hours (n=10 701) |
7 hours (n=15 590) |
≥ 8 hours (n=14 152) |
p-values | |
| Daytime napping, n (%) | 1206 (29.0) | 2615 (29.1) | 5295 (38.7)b | ＜0.001 | 2404 (22.5)b | 3792 (24.3) | 4917 (34.7)b | ＜0.001 |
| Age, yearsa | 57.3±10.2b | 55.1±9.7 | 58.4±10.2b | ＜0.001 | 56.3±10.2b | 55.3±9.5 | 60.1±10.0b | ＜0.001 |
| Body mass index, n (%) | ||||||||
| ＜18.5 kg/m2 | 233 (5.6)b | 382 (4.3) | 811 (5.9)b | 0.008 | 675 (6.3) | 907 (5.8) | 908 (6.4)b | 0.586 |
| 18.5-25.0 kg/m2 | 2953 (71.1)b | 6764 (75.3) | 10 134 (74.0)b | 0.015 | 7352 (68.7)b | 11 080 (71.1) | 9268 (65.5)b | ＜0.001 |
| ≥ 25.0 kg/m2 | 813 (19.6)b | 1551 (17.3) | 2143 (15.7)b | ＜0.001 | 2177 (20.3) | 3083 (19.8) | 3112 (22.0)b | ＜0.001 |
| Missing | 157 (3.8) | 287 (3.2) | 598 (4.4)b | 0.002 | 497 (4.6)b | 520 (3.3) | 864 (6.1)b | ＜0.001 |
| Current smokers, n (%) | 1943 (46.8)b | 4673 (52.0) | 7140 (52.2) | ＜0.001 | 517 (4.8)b | 611 (3.9) | 570 (4.0) | 0.004 |
| Current drinkers, n (%) | 2662 (64.1)b | 6031 (67.1) | 9073 (66.3) | 0.080 | 1703 (15.9)b | 2263 (14.5) | 1652 (11.7)b | ＜0.001 |
| Walking time ＞30min/day, n (%) | 2649 (63.7)b | 5956 (66.3) | 9175 (67.0) | ＜0.001 | 7307 (68.3)b | 10 832 (69.5) | 9508 (67.2)b | 0.030 |
| High mental stress, n (%) | 1111 (26.7)b | 1900 (21.1) | 2047 (15.0)b | ＜0.001 | 2426 (22.7)b | 2692 (17.3) | 1751 (12.4)b | ＜0.001 |
| Moderate to severe depression, n (%) | 254 (6.1)b | 390 (4.3) | 804 (5.9)b | 0.190 | 774 (7.2)b | 999 (6.4) | 1201 (8.5)b | ＜0.001 |
| Working status, n (%) | ||||||||
| Regular employees | 1641 (39.5)b | 3923 (43.7) | 4205 (31.1)b | ＜0.001 | 1788 (16.7) | 2723 (17.5) | 1281 (9.1)b | ＜0.001 |
| Non-workers | 833 (20.0)b | 1240 (13.8) | 2901 (21.2)b | ＜0.001 | 2069 (19.3)b | 2369 (15.2) | 4256 (30.1)b | ＜0.001 |
| Others | 1682 (40.5)b | 3821 (42.5) | 6535 (47.7)b | ＜0.001 | 6844 (64.0)b | 10 498 (67.3) | 8615 (60.9)b | ＜0.001 |
| High educational background, n (%) | 764 (18.4) | 1685 (18.8) | 1863 (13.6)b | ＜0.001 | 1120 (10.5) | 1543 (9.9) | 987 (7.0)b | ＜0.001 |
| History of hypertension, n (%) | 646 (15.5)b | 1201 (13.4) | 2245 (16.4)b | ＜0.001 | 1727 (16.1) | 2415 (15.5) | 2778 (19.6)b | ＜0.001 |
| History of diabetes mellitus, n (%) | 216 (5.2)b | 377 (4.2) | 633 (4.6) | 0.460 | 314 (2.9)b | 377 (2.4) | 494 (3.5)b | 0.003 |
a Average±standard deviation; b A statistically significant difference was observed compared with a sleep duration of 7 hours at night.
| Men | Women | |||||
|---|---|---|---|---|---|---|
|
No napping (n = 17 710) |
Napping (n = 9116) |
p-values |
No napping (n = 29 330) |
Napping (n = 11 113) |
p-values | |
| Sleep duration at night, n (%) | ||||||
| ≤ 6 hours | 2950 (16.7) | 1206 (13.2) | ＜0.001 | 8297 (28.3) | 2404 (21.6) | ＜0.001 |
| 7 hours | 6369 (36.0) | 2615 (28.7) | ＜0.001 | 11 798 (40.2) | 3792 (34.1) | ＜0.001 |
| ≥ 8 hours | 8391 (47.4) | 5295 (58.1) | ＜0.001 | 9235 (31.5) | 4917 (44.2) | ＜0.001 |
| Age, yearsa | 55.8±10.0 | 59.8±9.9 | ＜0.001 | 56.3±9.9 | 59.7±10.2 | ＜0.001 |
| Body mass index, n (%) | ||||||
| ＜18.5 kg/m2 | 898 (5.1) | 528 (5.8) | 0.013 | 1778 (6.1) | 712 (6.4) | 0.198 |
| 18.5-25.0 kg/m2 | 13 194 (74.5) | 6657 (73.0) | 0.009 | 20 492 (69.9) | 7208 (64.9) | ＜0.001 |
| ≥ 25.0 kg/m2 | 2991 (16.9) | 1516 (16.6) | 0.592 | 5822 (19.8) | 2550 (22.9) | ＜0.001 |
| Missing | 627 (3.5) | 415 (4.6) | ＜0.001 | 1238 (4.2) | 643 (5.8) | ＜0.001 |
| Current smokers, n (%) | 9407 (53.1) | 4349 (47.7) | ＜0.001 | 1236 (4.2) | 462 (4.2) | 0.799 |
| Current drinkers, n (%) | 11 812 (66.7) | 5954 (65.3) | 0.023 | 4088 (13.9) | 1530 (13.8) | 0.659 |
| Walking time ＞30min/day, n (%) | 11420 (64.5) | 6360 (69.8) | ＜0.001 | 20 019 (68.3) | 7628 (68.6) | 0.456 |
| High mental stress, n (%) | 3794 (21.4) | 1264 (13.9) | ＜0.001 | 5335 (18.2) | 1534 (13.8) | ＜0.001 |
| Moderate to severe depression, n (%) | 794 (4.5) | 654 (7.2) | ＜0.001 | 1893 (6.5) | 1081 (9.7) | ＜0.001 |
| Working status, n (%) | ||||||
| Regular employees | 7847 (44.3) | 1967 (21.6) | ＜0.001 | 5122 (17.5) | 670 (6.0) | ＜0.001 |
| Non-workers | 2705 (15.3) | 2269 (24.9) | ＜0.001 | 5555 (18.9) | 3139 (28.2) | ＜0.001 |
| Others | 7158 (40.4) | 4880 (53.5) | ＜0.001 | 18 653 (63.6) | 7304 (65.7) | ＜0.001 |
| High educational background, n (%) | 3113 (17.6) | 1199 (13.2) | ＜0.001 | 2779 (9.5) | 871 (7.8) | ＜0.001 |
| History of hypertension, n (%) | 2367 (13.4) | 1725 (18.9) | ＜0.001 | 4568 (15.6) | 2352 (21.2) | ＜0.001 |
| History of diabetes mellitus, n (%) | 735 (4.2) | 491 (5.4) | ＜0.001 | 718 (2.4) | 467 (4.2) | ＜0.001 |
a Average±standard deviation.
| Sleep duration at night (hours/day) | ||||||
|---|---|---|---|---|---|---|
| Men | ||||||
| ≤ 6 hours (n = 4156) | 7 hours (n = 8984) | ≥ 8 hours (n = 13 686) | ||||
|
No napping (n = 2950) |
Napping (n = 1206) |
No napping (n = 6369) |
Napping (n = 2615) |
No napping (n = 8391) |
Napping (n = 5295) |
|
| Age, yearsa | 56.3±10.2 b | 59.8±10.0 b | 54.1±9.6 | 57.6±9.7 b | 56.8±10.0 b | 60.9±9.9 b |
| Body mass index, n (%) | ||||||
| ＜18.5 kg/m2 | 159 (5.4) b | 74 (6.1) b | 271 (4.3) | 111 (4.2) | 468 (5.6) b | 343 (6.5) b |
| 18.5-25.0 kg/m2 | 2110 (71.5) b | 843 (69.9) b | 4792 (75.2) | 1972 (75.4) | 6292 (75.0) | 3842 (72.6) b |
| ≥ 25.0 kg/m2 | 571 (19.4) b | 242 (20.1) b | 1113 (17.5) | 438 (16.7) | 1307 (15.6) b | 836 (15.8) b |
| Missing | 110 (3.7) | 47 (3.9) | 193 (3.0) | 94 (3.6) | 324 (3.9) | 274 (5.2) b |
| Current smokers, n (%) | 1419 (48.1) b | 524 (43.4) b | 3404 (53.4) | 1269 (48.5) b | 4584 (54.6) | 2556 (48.3) b |
| Current drinkers, n (%) | 1908 (64.7) b | 754 (62.5) b | 4311 (67.7) | 1720 (65.8) b | 5593 (66.7) | 3480 (65.7) b |
| Walking time ＞30min/day, n (%) | 1847 (62.6) | 802 (66.5) | 4086 (64.2) | 1870 (71.5) b | 5487 (65.4) | 3688 (69.7) b |
| High mental stress, n (%) | 875 (29.7) b | 236 (19.6) b | 1510 (23.7) | 390 (14.9) b | 1409 (16.8) b | 638 (12.0) b |
| Moderate to severe depression, n (%) | 164 (5.6) b | 90 (7.5) b | 238 (3.7) | 152 (5.8) b | 392 (4.7) b | 412 (7.8) b |
| Working status, n (%) | ||||||
| Regular employees | 1349 (45.7) b | 292 (24.2) b | 3249 (51.0) | 674 (25.8) b | 3249 (38.7) b | 1001 (18.9) |
| Non-workers | 524 (17.8) b | 309 (25.6) b | 763 (12.0) | 477 (18.2) b | 1418 (16.9) b | 1483 (28.0) b |
| Others | 1077 (36.5) | 605 (50.2) b | 2357 (37.0) | 1464 (56.0) b | 3724 (44.4) b | 2811 (53.1) b |
| High educational background, n (%) | 588 (19.9) | 176 (14.6) b | 1305 (20.5) | 380 (14.5) b | 1220 (14.5) b | 643 (12.1) b |
| History of hypertension, n (%) | 417 (14.1) b | 229 (19.0) b | 765 (12.0) | 436 (16.7) b | 1185 (14.1) | 1060 (20.0) b |
| History of diabetes mellitus, n (%) | 130 (4.4) | 86 (7.1) b | 247 (3.9) | 130 (5.0) b | 358 (4.3) | 275 (5.2) b |
| Sleep duration at night (hours/day) | ||||||
|---|---|---|---|---|---|---|
| Women | ||||||
| ≤ 6 hours (n = 10 701) | 7 hours (n = 15 590) | ≥ 8 hours (n = 14 152) | ||||
|
No napping (n = 8297) |
Napping (n = 2404) |
No napping (n = 11 798) |
Napping (n = 3792) |
No napping (n = 9235) |
Napping (n = 4917) |
|
| Age, yearsa | 55.7±10.0 b | 58.3±10.4 b | 54.6±9.3 | 57.3±9.7 b | 59.0±9.9 b | 62.2±9.9 b |
| Body mass index, n (%) | ||||||
| ＜18.5 kg/m2 | 504 (6.1) | 171 (7.1) b | 684 (5.8) | 222 (5.9) | 590 (6.4) | 318 (6.5) |
| 18.5-25.0 kg/m2 | 5761 (69.4) b | 1591 (66.2) b | 8513 (72.2) | 2567 (67.7) b | 6218 (67.3) b | 3050 (62.0) b |
| ≥ 25.0 kg/m2 | 1656 (20.0) | 521 (21.7) b | 2227 (18.9) | 856 (22.6) b | 1939 (21.0) b | 1173 (23.9) b |
| Missing | 376 (4.5) b | 121 (5.0) b | 374 (3.2) | 146 (3.9) | 488 (5.3) b | 376 (7.6) b |
| Current smokers, n (%) | 390 (4.7) b | 127 (5.3) b | 473 (4.0) | 138 (3.6) | 373 (4.0) | 197 (4.0) |
| Current drinkers, n (%) | 1306 (15.7) b | 397 (16.5) b | 1706 (14.5) | 557 (14.7) | 1076 (11.7) b | 576 (11.7) b |
| Walking time ＞30min/day, n (%) | 5665 (68.3) | 1642 (68.3) | 8117 (68.8) | 2715 (71.6) b | 6237 (67.5) | 3271 (66.5) b |
| High mental stress, n (%) | 1994 (24.0) b | 432 (18.0) | 2151 (18.2) | 541 (14.3) b | 1190 (12.9) b | 561 (11.4) b |
| Moderate to severe depression, n (%) | 555 (6.7) b | 219 (9.1) b | 676 (5.7) | 323 (8.5) b | 662 (7.2) b | 539 (11.0) b |
| Working status, n (%) | ||||||
| Regular employees | 1589 (19.2) b | 199 (8.3) b | 2425 (20.6) | 298 (7.9) b | 1108 (12.0) b | 173 (3.5) b |
| Non-workers | 1522 (18.3) b | 547 (22.8) b | 1626 (13.8) | 743 (19.6) b | 2407 (26.1) b | 1849 (37.6) b |
| Others | 5186 (62.5) b | 1658 (69.0) b | 7747 (65.7) | 2751 (72.5) b | 5720 (61.9) b | 2895 (58.9) b |
| High educational background, n (%) | 895 (10.8) | 225 (9.4) | 1210 (10.3) | 333 (8.8) b | 674 (7.3) b | 313 (6.4) b |
| History of hypertension, n (%) | 1260 (15.2) | 467 (19.4) b | 1695 (14.4) | 720 (19.0) b | 1613 (17.5) b | 1165 (23.7) b |
| History of diabetes mellitus, n (%) | 212 (2.6) b | 102 (4.2) b | 243 (2.1) | 134 (3.5) b | 263 (2.8) b | 231 (4.7) b |
a Average±standard deviation; b A statistically significant difference was observed compared with a sleep duration of 7 hours at night with no napping.
| Men | Women | |||||
|---|---|---|---|---|---|---|
| Participants with lacked information of sleep and naps
(n=2302) |
Participants with information of sleep and naps
(n=26 826) |
p-values | Participants with lacked information of sleep and naps
(n=5780) |
Participants with information of sleep and naps
(n=40 443) |
p-values | |
| Age, yearsa | 62.0±9.6 | 57.1±10.1 | ＜0.001 | 60.7±9.6 | 57.2±10.1 | ＜0.001 |
| Body mass index, n (%) | ||||||
| ＜18.5 kg/m2 | 166 (7.2) | 1426 (5.3) | ＜0.001 | 356 (6.2) | 2490 (6.2) | 0.994 |
| 18.5-25.0 kg/m2 | 1581 (68.7) | 19851 (74.0) | ＜0.001 | 3589 (62.1) | 27700 (68.5) | ＜0.001 |
| ≥ 25.0 kg/m2 | 351 (15.2) | 4507 (16.8) | 0.055 | 1179 (20.4) | 8372 (20.7) | 0.595 |
| Missing | 204 (8.9) | 1042 (3.9) | ＜0.001 | 656 (11.3) | 1881 (4.7) | ＜0.001 |
| Current smokers, n (%) | 1069 (46.4) | 13756 (51.3) | ＜0.001 | 320 (5.5) | 1698 (4.2) | ＜0.001 |
| Current drinkers, n (%) | 928 (40.3) | 17 766 (66.2) | ＜0.001 | 379 (6.6) | 5618 (13.9) | ＜0.001 |
| Walking time ＞30min/day, n (%) | 956 (41.5) | 17780 (66.3) | ＜0.001 | 1982 (34.3) | 27 647 (68.4) | ＜0.001 |
| High mental stress, n (%) | 229 (9.9) | 6869 (17.0) | ＜0.001 | 466 (8.1) | 5058 (18.9) | ＜0.001 |
| Moderate to severe depression, n (%) | 96 (4.2) | 1448 (5.4) | 0.012 | 273 (4.7) | 2974 (7.4) | ＜0.001 |
| Working status, n (%) | ||||||
| Regular employees | 407 (17.7) | 9814 (36.6) | ＜0.001 | 266 (4.6) | 5792 (14.3) | ＜0.001 |
| Non-workers | 717 (31.1) | 12 038 (44.9) | ＜0.001 | 3378 (58.4) | 25 957 (64.2) | ＜0.001 |
| Others | 1178 (51.2) | 4974 (18.5) | ＜0.001 | 2136 (37.0) | 8694 (21.5) | ＜0.001 |
| High educational background, n (%) | 189 (8.2) | 4312 (16.1) | ＜0.001 | 201 (3.5) | 3650 (9.0) | ＜0.001 |
| History of hypertension, n (%) | 295 (12.8) | 4092 (15.3) | ＜0.001 | 663 (11.5) | 6920 (17.1) | ＜0.001 |
| History of diabetes mellitus, n (%) | 114 (5.0) | 1226 (4.6) | 0.401 | 160 (2.8) | 1185 (2.9) | 0.493 |
a Average±standard deviation.
No statistically significant association was observed between night sleep duration and the risk of mortality from total aortic disease, aortic dissection, or aortic aneurysm (Table 3). In all participants, the multivariable-adjusted HRs were 0.62 [95% CIs: 0.37–1.03] for ≤ 6 hours and 1.01 [0.72–1.43] for ≥ 8 hours as a reference to 7 hours; p for trend=0.084 for total aortic disease. In men, the multivariable-adjusted HRs were 0.80 [0.38–1.66] for ≤ 6 hours and 1.02 [0.63–1.64] for ≥ 8 hours; p for trend=0.553 for total aortic disease. In women, the multivariable-adjusted HRs were 0.51 [0.25–1.03] for ≤ 6 hours and 0.99 [0.60–1.63] for ≥ 8 hours; p for trend=0.086 for total aortic disease. No significant multiplicative interactions by sex were found between sleep duration at night and mortality from total aortic disease (p=0.703), aortic dissection (p=0.515), or aortic aneurysm (p=0.972).
| All participants | Sleep duration at night (hours/day) | |||
|---|---|---|---|---|
| ≤ 6 hours | 7 hours | ≥ 8 hours | p for trend | |
| Person-years | 239 335 | 411 907 | 443 200 | |
| Total aortic disease | 21 | 54 | 94 | |
| Sex- and age-adjusted HRs, (95% CIs) | 0.62 (0.37–1.03) | 1.00 | 1.08 (0.77–1.51) | 0.035 |
| Multivariable adjusted HRs, (95% CIs) | 0.62 (0.37–1.03) | 1.00 | 1.01 (0.72–1.43) | 0.084 |
| Aortic dissection | 12 | 25 | 50 | |
| Sex- and age-adjusted HRs, (95% CIs) | 0.76 (0.38–1.52) | 1.00 | 1.41 (0.86–2.29) | 0.038 |
| Multivariable adjusted HRs, (95% CIs) | 0.76 (0.38–1.52) | 1.00 | 1.26 (0.77–2.07) | 0.101 |
| Aortic aneurysm | 9 | 29 | 44 | |
| Sex- and age-adjusted HRs, (95% CIs) | 0.49 (0.23–1.04) | 1.00 | 0.83 (0.51–1.33) | 0.351 |
| Multivariable adjusted HRs, (95% CIs) | 0.51 (0.24–1.08) | 1.00 | 0.81 (0.50–1.32) | 0.435 |
| Men | ||||
| Person-years | 64 100 | 147 008 | 214 185 | |
| Total aortic disease | 10 | 26 | 54 | |
| Age-adjusted HRs, (95% CIs) | 0.75 (0.36–1.55) | 1.00 | 1.10 (0.69–1.77) | 0.269 |
| Multivariable adjusted HRs, (95% CIs) | 0.80 (0.38–1.66) | 1.00 | 1.02 (0.63–1.64) | 0.553 |
| Aortic dissection | 5 | 8 | 23 | |
| Age-adjusted HRs, (95% CIs) | 1.31 (0.43–4.02) | 1.00 | 1.69 (0.75–3.81) | 0.352 |
| Multivariable adjusted HRs, (95% CIs) | 1.51 (0.49–4.66) | 1.00 | 1.48 (0.65–3.35) | 0.721 |
| Aortic aneurysm | 5 | 18 | 31 | |
| Age-adjusted HRs, (95% CIs) | 0.51 (0.19–1.38) | 1.00 | 0.85 (0.48–1.53) | 0.500 |
| Multivariable adjusted HRs, (95% CIs) | 0.54 (0.20–1.47) | 1.00 | 0.84 (0.46–1.52) | 0.624 |
| Women | 1.00 | |||
| Person-years | 175 235 | 264 899 | 229 014 | |
| Total aortic disease | 11 | 28 | 40 | |
| Age-adjusted HRs, (95% CIs) | 0.53 (0.26–1.06) | 1.00 | 1.04 (0.64–1.71) | 0.065 |
| Multivariable adjusted HRs, (95% CIs) | 0.51 (0.25–1.03) | 1.00 | 0.99 (0.60–1.63) | 0.086 |
| Aortic dissection | 7 | 17 | 27 | |
| Age-adjusted HRs, (95% CIs) | 0.57 (0.24–1.37) | 1.00 | 1.24 (0.67–2.31) | 0.067 |
| Multivariable adjusted HRs, (95% CIs) | 0.55 (0.23–1.33) | 1.00 | 1.11 (0.59–2.08) | 0.123 |
| Aortic aneurysm | 4 | 11 | 13 | |
| Age-adjusted HRs, (95% CIs) | 0.46 (0.15–1.46) | 1.00 | 0.77 (0.34–1.74) | 0.528 |
| Multivariable adjusted HRs, (95% CIs) | 0.45 (0.14–1.44) | 1.00 | 0.82 (0.36–1.88) | 0.419 |
HRs, hazard ratios; 95% CIs, 95% confidence intervals; The number in parentheses indicates the number of deaths per 100,000 person-years; Multivariable-adjusted model included age, sex, daytime napping, body mass index, smoking habit, drinking habit, walking time, perceived mental stress, depression, working status, educational background, history of hypertension and history of diabetes mellitus.
Daytime napping was associated with a greater risk of mortality from total aortic disease and aortic dissection (Table 4). In all participants, the multivariable-adjusted HRs of daytime napping were 1.48 [1.08–2.02, p=0.015] for total aortic disease, 1.81 [1.17–2.81, p=0.008] for aortic dissection and 1.20 [0.76–1.88, p=0.434] for aortic aneurysm. Daytime napping is associated with a higher risk of mortality due to aortic dissection in women. The multivariable HRs of daytime napping were 1.51 [0.96–2.39, p=0.078] for total aortic disease, 1.93 [1.09–3.41, p=0.024] for aortic dissection, and 0.96 [0.43–2.13, p=0.914] for aortic aneurysm in women. A similar but nonsignificant association between daytime napping and mortality from aortic disease was observed in men. The multivariable-adjusted HRs of daytime napping were 1.45 [0.95–2.23, p=0.087] for total aortic disease, 1.61 [0.81–3.17, p=0.173] for aortic dissection, and 1.38 [0.79–2.40, p=0.253] for aortic aneurysm in men. Multiplicative interactions between daytime napping and sex were not found for total aortic disease (p=0.988), aortic dissection (p=0.737), or aortic aneurysm (p=0.506).
| All participants | Daytime napping | ||
|---|---|---|---|
| No napping | Napping | p-values | |
| Person-years | 776 693 | 317 748 | |
| Total aortic disease, n | 90 | 79 | |
| Sex- and age-adjusted HRs, (95% CIs) | 1.00 | 1.54 (1.14-2.10) | 0.006 |
| Multivariable adjusted HRs, (95% CIs) | 1.00 | 1.48 (1.08-2.02) | 0.015 |
| Aortic dissection, n | 44 | 44 | |
| Sex- and age-adjusted HRs, (95% CIs) | 1.00 | 1.90 (1.24-2.91) | 0.003 |
| Multivariable adjusted HRs, (95% CIs) | 1.00 | 1.81 (1.17-2.81) | 0.008 |
| Aortic aneurysm, n | 46 | 35 | |
| Sex- and age-adjusted HRs, (95% CIs) | 1.00 | 1.24 (0.80-1.93) | 0.343 |
| Multivariable adjusted HRs, (95% CIs) | 1.00 | 1.20 (0.76-1.88) | 0.434 |
| Men | |||
| Person-years | 286 734 | 179 190 | |
| Total aortic disease, n | 46 | 43 | |
| Age-adjusted HRs, (95% CIs) | 1.00 | 1.48 (0.97-2.25) | 0.067 |
| Multivariable adjusted HRs, (95% CIs) | 1.00 | 1.45 (0.95-2.23) | 0.087 |
| Aortic dissection, n | 18 | 18 | |
| Age-adjusted HRs, (95% CIs) | 1.00 | 1.72 (0.89-3.34) | 0.109 |
| Multivariable adjusted HRs, (95% CIs) | 1.00 | 1.61 (0.81-3.17) | 0.173 |
| Aortic aneurysm, n | 28 | 25 | |
| Age-adjusted HRs, (95% CIs) | 1.00 | 1.34 (0.78-2.30) | 0.288 |
| Multivariable adjusted HRs, (95% CIs) | 1.00 | 1.38 (0.79-2.40) | 0.253 |
| Women | |||
| Person-years | 489 959 | 138 559 | |
| Total aortic disease, n | 44 | 36 | |
| Age-adjusted HRs, (95% CIs) | 1.00 | 1.62 (1.03-2.54) | 0.035 |
| Multivariable adjusted HRs, (95% CIs) | 1.00 | 1.51 (0.96-2.39) | 0.078 |
| Aortic dissection, n | 26 | 26 | |
| Age-adjusted HRs, (95% CIs) | 1.00 | 2.04 (1.17-3.55) | 0.012 |
| Multivariable adjusted HRs, (95% CIs) | 1.00 | 1.93 (1.09-3.41) | 0.024 |
| Aortic aneurysm, n | 18 | 10 | |
| Age-adjusted HRs, (95% CIs) | 1.00 | 1.06 (0.49-2.31) | 0.889 |
| Multivariable adjusted HRs, (95% CIs) | 1.00 | 0.96 (0.43-2.13) | 0.914 |
HRs, hazard ratios; 95% CIs, 95% confidence intervals; The number in parentheses indicates the number of deaths per 100,000 person-years; Multivariable-adjusted model included age, sex, sleep duration at night, body mass index, smoking habit, drinking habit, walking time, perceived mental stress, depression, working status, educational background, history of hypertension and history of diabetes mellitus
Even after our analysis considered the competing risks of pre-aortic disease mortality from stroke, coronary heart disease, and cancer, daytime napping remained associated with mortality from total aortic disease and aortic dissection (Supplementary Table 3). The HRs of daytime napping were 1.45 [1.06–1.99, p=0.021] for total aortic disease and 1.78 [1.16–2.73, p=0.009] for aortic dissection. On the other hand, sleep duration at night was not significantly associated with mortality from total aortic disease. The HRs were 0.62 [0.37–1.03] for ≤ 6 hours and 1.00 [0.71–1.41] for ≥ 8 hours; p for trend=0.083 for total aortic disease.
| Multivariable adjusted HRs, (95% CIs) | |||||||
|---|---|---|---|---|---|---|---|
| Sleep duration at night (hours/day) | Daytime napping | ||||||
| ≤ 6 hours | 7 hours | ≥ 8 hours | p for trend | No napping | Napping | p-values | |
| All participants | |||||||
| Total aortic disease | 0.62 (0.37-1.03) | 1.00 | 1.00 (0.71-1.41) | 0.083 | 1.00 | 1.45 (1.06-1.99) | 0.021 |
| Aortic dissection | 0.76 (0.38-1.51) | 1.00 | 1.25 (0.76-2.04) | 0.112 | 1.00 | 1.78 (1.16-2.73) | 0.009 |
| Aortic aneurysm | 0.50 (0.24-1.08) | 1.00 | 0.81 (0.50-1.32) | 0.401 | 1.00 | 1.18 (0.74-1.87) | 0.491 |
| Men | |||||||
| Total aortic disease | 0.78 (0.37-1.65) | 1.00 | 1.01 (0.62-1.63) | 0.523 | 1.00 | 1.42 (0.92-2.18) | 0.116 |
| Aortic dissection | 1.46 (0.48-4.46) | 1.00 | 1.46 (0.64-3.34) | 0.722 | 1.00 | 1.58 (0.83-3.02) | 0.165 |
| Aortic aneurysm | 0.53 (0.19-1.46) | 1.00 | 0.83 (0.46-1.51) | 0.582 | 1.00 | 1.33 (0.75-2.37) | 0.323 |
| Women | |||||||
| Total aortic disease | 0.51 (0.25-1.02) | 1.00 | 0.97 (0.58-1.60) | 0.089 | 1.00 | 1.48 (0.93-2.34) | 0.097 |
| Aortic dissection | 0.55 (0.23-1.32) | 1.00 | 1.09 (0.59-2.00) | 0.122 | 1.00 | 1.88 (1.07-3.31) | 0.029 |
| Aortic aneurysm | 0.44 (0.13-1.45) | 1.00 | 0.80 (0.33-1.93) | 0.408 | 1.00 | 0.95 (0.42-2.16) | 0.911 |
HRs, hazard ratios; 95% CIs, 95% confidence intervals; The number in parentheses indicates the number of deaths per 100,000 person-years; Multivariable-adjusted model included age, sex, body mass index, smoking habit, drinking habit, walking time, perceived mental stress, depression, working status, educational background, history of hypertension, history of diabetes mellitus, and mutually adjusted for daytime napping and sleep duration at night.
In the stratified analysis of sleep duration at night, the multivariable-adjusted HRs of daytime napping were 1.14 [0.44–2.95, p=0.785] for ≤ 6 hours, 2.02 [1.16–3.52, p=0.013] for 7 hours and 1.33 [0.87–2.02, p=0.184] for ≥ 8 hours. We observed no multiplicative interaction between sleep durations at night and daytime napping in relation to total aortic disease (p for interaction =0.420).
In a large population-based prospective cohort study with an average follow-up of 16.3 years, daytime napping was associated with an increased risk of mortality from total aortic disease and aortic dissection, although sleep duration at night was not associated with the risk of mortality from aortic disease. The stronger association was observed among medium sleep duration of 7 hours. Our findings were not changed when we considered the competing risks of pre-aortic disease mortality, such as cancer, stroke, and coronary heart disease. This is the first prospective cohort study to examine the association between the sleep duration at night and daytime napping, and risk of aortic disease mortality.
As for sleep duration at night, few studies examined the association between sleep duration and mortality from aortic disease. On the other hand, many previous studies examined the association between sleep duration and risk of mortality from total CVD, stroke, and coronary heart disease. A meta-analysis conducted in 2018, consisting of 16 population-based cohort studies, showed a J-shaped relationship, with a nadir of 7–8 hours of sleep, between self-reported sleep duration and risk of total CVD mortality6). A similar J-shaped relationship was also observed for risk of stroke mortality6). However, the meta-analysis showed that self-reported sleep duration was not associated with risk of coronary heart disease mortality6).
As for daytime napping, the association between daytime napping and mortality from aortic disease has scarcely been examined. Only five previous cohort studies examined the association between daytime napping and risk of mortality from total CVD including aortic disease7-9, 15, 16). Also, few cohort studies examined the association between daytime napping and mortality from stroke and coronary heart disease7, 17). Our finding was consistent with the results of three population-based cohort studies, which showed the association between daytime napping and a higher risk of total CVD mortality7-9). Among the other two cohort studies15, 16), a prospective cohort study of 4869 colorectal cancer survivors in the United States showed no significant association between daytime napping and total CVD mortality (for napping ＜1 h, HR; 0.84, 95% CIs: 0.64–1.11; for napping ≥ 1 hour, HR: 1.78, 95% CIs: 0.91–1.78)15). Also, a British cohort study of 16,374 cancer patients aged 40–79 years showed that daytime napping was not significantly associated with risk of total CVD mortality (for napping ＜1 hour, HR: 1.00, 95% CIs: 0.81–1.22; for napping ≥ 1 hour, HR: 0.92, 95% CIs: 0.57–1.48)16). These inconsistent results may be influenced by the difference in the study population.
The causal mechanism underlying the association between daytime napping and an increased risk of mortality from aortic disease has not been discussed. A surge in blood pressure after daytime napping may increase risk of aortic disease. Heart rate and blood pressure decrease during daytime napping as during non-rapid eye movement sleep at night18). After daytime napping, the activation of the sympathetic nervous system causes a rapid increase in heart rate and blood pressure18). The sudden surge of blood pressure may increase shear stress and cause a tear of the aortic intima1, 18).
Obstructive sleep apnea (OSA) and physical comorbidities can confound the association between daytime napping and increased mortality from aortic disease. OSA is a primary sleep disorder characterized by episodic narrowing of the upper airway during sleep that can cause poor sleep quality and excessive daytime sleepiness. OSA is associated with an increased sympathetic nerve activity and large surges in blood pressure19, 20), which may lead to the development of aortic disease. However, a meta-analysis, consisting of 10 observational publications showed that OSA was associated with an increased diameter of the aorta but not the incidence of aortic disease21). Additionally, we adjusted for the history of hypertension and being overweight, which are comorbid with OSA19). Physical comorbidity could cause people to be less active and indulge in daytime napping, which may increase the risk of mortality from aortic disease and other diseases. In the basic characteristics of our study, participants with daytime napping habit tended to be older non-workers with longer sleep duration of ≥ 8 hours. However, our additional analysis, after excluding participants who died within the first 5 years of follow-up, remained the significant association between daytime napping and a higher mortality risk from aortic disease.
In the stratified analysis of sleep duration at night, daytime napping was associated with mortality from aortic disease among those with a medium sleep duration of 7 hours. Our finding was partly consistent with a global cohort study of 116,632 people (males: 41.8%). This study showed that daytime napping was significantly associated with an increased risk of the composite outcome of all-cause mortality and major cardiovascular events, among people with sleep duration of ＞6 hours, but not among those with ≤ 6 hours22). In our study, the reasons for the lack of significant associations between daytime napping and mortality from aortic disease among participants with shorter sleep durations of ≤ 6 hours and ≥ 8 hours at night were unclear. However, this can be explained by the mechanism that daytime napping may compensate for sleep loss among those with shorter sleep durations22). Also, daytime napping could be considered a fragmented part of a longer sleep duration, which could weaken the association of daytime napping with the risk of mortality from aortic disease among participants with a sleep duration of ≥ 8 hours at night. In the stratified analysis for each type of aortic diseases, a significant association between napping and mortality was found for aortic dissection, but not for aortic aneurysm. The possible reason for this may be the particularly small incidence of aortic aneurysms, but other possibilities are unknown due to the lack of previous literature.
The strength of the present study is that it is the first prospective cohort study to examine the association of sleep duration at night and daytime napping with risk of mortality from aortic disease. The JACC study, a long-term and large population-based prospective cohort study, enabled us to analyze the risk of mortality from aortic disease. However, this study has some limitations. First, information regarding sleep duration at night and daytime napping was obtained from self-administered questionnaires in the baseline survey. Most previous cohort studies used self-reported sleep duration and daytime napping in their analysis. Although the exact reasons for discrepancies between subjective and objective measures are not clear, it appears that self-reported sleep is only moderately correlated with objective measures of sleep, and multiple measures of sleep duration should be recommended for future studies23). Second, since sleep duration at night was measured at a single time point, it was not possible to account for changes in sleep duration over time. Third, we could not consider sleep quality factors such as insomnia, sleep disturbances, and napping time due to lack of the information. Fourth, we did not examine the effect of sleep duration at night of ≤ 5 hours and ≥ 9 hours because of the low proportion of participants and the few number of cases (number of case=4 and 3, respectively). The number of stratified analyses by sex and type of outcome was also insufficient. Future studies with a more sufficient sample size would be warranted to perform various stratified analyses to help understand the underlying mechanism.
Daytime napping was associated with an increased risk of mortality from aortic disease, especially among participants with medium sleep duration of 7 hours, whereas no significant association with sleep duration at night was observed in our study. Although the causal mechanisms remain unclear, fluctuations in blood pressure related to daytime napping may contribute to an increased risk of aortic disease. Future studies using a larger population-based study cohort are required to confirm the association between sleep duration at night and daytime napping and mortality from aortic disease.
The JACC Study has been supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT, Monbu Kagaku-sho), Tokyo [Grant numbers 61010076, 62010074, 63010074, 1010068, 2151065, 3151064, 4151063, 5151069, 6279102, 11181101, 17015022, 18014011, 20014026, 20390156, 26293138], JSPS KAKENHI Grant number JP16H06277, and Grants-in-Aid from the Ministry of Health, Labour and Welfare, Health and Labour Sciences Research Grants, Japan [H20–Junkankitou (Seishuu)–Ippan–013, H23-Junkankitou (Seishuu)-Ippan-005, H26-Junkankitou (Seisaku)-Ippan-001 and H29-Junkankitou (Seishuu)-Ippan-003] and JP20FA1002.
Nozomi Shimizu: Conceptualization, Methodology, Formal analysis, Writing – original draft, Writing - review & editing. Hiroshige Jinnouchi: Conceptualization, Methodology, Formal analysis, Writing – original draft, Writing - review & editing. Katsuhito Kato: Conceptualization, Methodology, Formal analysis, Writing – original draft, Writing - review & editing. Kazumasa Yamagishi: Methodology, Writing– review & editing. Tomomi Kihara: Methodology, Writing– review & editing. Midori Takada: Methodology, Writing - review & editing. Toshiaki Otsuka: Methodology, Writing - review & editing, Supervision. Tomoyuki Kawada: Methodology, Writing - review & editing, Supervision. Akiko Tamakoshi: Formal analysis, Investigation, Writing – review & editing, Supervision. Hiroyasu Iso: Conceptualization, Methodology, Formal analysis, Investigation, Writing – review & editing, Supervision.
The authors express their sincere appreciation to Dr. Kunio Aoki, Professor Emeritus, Nagoya University School of Medicine, former Chairman of the JACC Study Group, and Dr. Haruo Sugano, former Director of the Cancer Institute of the Japanese Foundation for Cancer Research, who greatly contributed to the initiation of the study. Members of the JACC Study and their affiliations have been presented previously13).
