The two articles needed for 4a and 4b

Copyright 2016 American Medical Association. All rights reserved.

Association Between Rotating Night Shift Work and Risk
of Coronary Heart Disease Among Women
Céline Vetter, PhD; Elizabeth E. Devore, ScD; Lani R. Wegrzyn, ScD; Jennifer Massa, ScD; Frank E. Speizer, MD;
Ichiro Kawachi, MD, ScD; Bernard Rosner, PhD; Meir J. Stampfer, MD, DrPH; Eva S. Schernhammer, MD, DrPH

IMPORTANCE Prospective studies linking shift work to coronary heart disease (CHD) have
been inconsistent and limited by short follow-up.

OBJECTIVE To determine whether rotating night shift work is associated with CHD risk.

DESIGN, SETTING, AND PARTICIPANTS Prospective cohort study of 189 158 initially healthy
women followed up over 24 years in the Nurses’ Health Studies (NHS [1988-2012]:
N = 73 623 and NHS2 [1989-2013]: N = 115 535).

EXPOSURES Lifetime history of rotating night shift work (�3 night shifts per month in
addition to day and evening shifts) at baseline (updated every 2 to 4 years in the NHS2).

MAIN OUTCOMES AND MEASURES Incident CHD; ie, nonfatal myocardial infarction, CHD
death, angiogram-confirmed angina pectoris, coronary artery bypass graft surgery, stents,
and angioplasty.

RESULTS During follow-up, 7303 incident CHD cases occurred in the NHS (mean age at
baseline, 54.5 years) and 3519 in the NHS2 (mean age, 34.8 years). In multivariable-adjusted
Cox proportional hazards models, increasing years of baseline rotating night shift work was
associated with significantly higher CHD risk in both cohorts. In the NHS, the association
between duration of shift work and CHD was stronger in the first half of follow-up than in the
second half (P=.02 for interaction), suggesting waning risk after cessation of shift work.
Longer time since quitting shift work was associated with decreased CHD risk among ever
shift workers in the NHS2 (P<.001 for trend). Baseline History of Rotating Night Shift Work P Value for TrendNone <5 y 5-9 y ≥10 y NHS cohort CHD incidence ratea 425.5 435.1 525.7 596.9 HR (95% CI)b 1 [Reference] 1.02 (0.97-1.08) 1.12 (1.02-1.22) 1.18 (1.10-1.26) <.001 First half of follow-up CHD incidence ratea 367.3 382.4 483.1 494.4 HR (95% CI)b 1 [Reference] 1.10 (1.01-1.21) 1.19 (1.03-1.39) 1.27 (1.13-1.42) <.001 Second half of follow-up CHD incidence ratea 436.6 424.8 520.7 556.2 HR (95% CI)b 1 [Reference] 0.98 (0.92-1.05) 1.08 (0.96-1.21) 1.13 (1.04-1.24) .004 NHS2 cohort CHD incidence ratea 122.6 130.6 151.6 178.0 HR (95% CI)b 1 [Reference] 1.05 (0.97-1.13) 1.12 (0.99-1.26) 1.15 (1.01-1.32) .01 a Age-adjusted rates per 100 000 person-years. b Multivariable-adjusted hazard ratio (HR). CONCLUSIONS AND RELEVANCE Among women who worked as registered nurses, longer duration of rotating night shift work was associated with a statistically significant but small absolute increase in CHD risk. Further research is needed to explore whether the association is related to specific work hours and individual characteristics. JAMA. 2016;315(16):1726-1734. doi:10.1001/jama.2016.4454 Author Video Interview and JAMA Report Video at jama.com Supplemental content at jama.com Author Affiliations: Author affiliations are listed at the end of this article. Corresponding Author: Céline Vetter, PhD, Channing Division of Network Medicine, 181 Longwood Ave, Boston, MA 02115 (celine.vetter @channing.harvard.edu). Research Original Investigation 1726 (Reprinted) jama.com Copyright 2016 American Medical Association. All rights reserved. Downloaded From: http://jama.jamanetwork.com/ by Suad Ghaddar on 04/30/2016 http://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2016.4454&utm_campaign=articlePDF%26utm_medium=articlePDFlink%26utm_source=articlePDF%26utm_content=jama.2016.4454 http://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2016.4454&utm_campaign=articlePDF%26utm_medium=articlePDFlink%26utm_source=articlePDF%26utm_content=jama.2016.4454 http://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2016.4454&utm_campaign=articlePDF%26utm_medium=articlePDFlink%26utm_source=articlePDF%26utm_content=jama.2016.4454 http://wwwjama.com/?utm_campaign=articlePDF%26utm_medium=articlePDFlink%26utm_source=articlePDF%26utm_content=jama.2016.4454 http://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2016.4454&utm_campaign=articlePDF%26utm_medium=articlePDFlink%26utm_source=articlePDF%26utm_content=jama.2016.4454 http://www.jama.com/?utm_campaign=articlePDF%26utm_medium=articlePDFlink%26utm_source=articlePDF%26utm_content=jama.2016.4454 mailto:[email protected] mailto:[email protected] http://www.jama.com/?utm_campaign=articlePDF%26utm_medium=articlePDFlink%26utm_source=articlePDF%26utm_content=jama.2016.4454 Copyright 2016 American Medical Association. All rights reserved. S ocietal and economic demands push toward an in-crease of employees’ 24-hour availability in health caresettings as well as in service and security industries. The resulting disruption of social and biological rhythms, occur- ring especially during shift work, has been hypothesized to in- crease chronic disease risk,1-5 and suggestive evidence sup- ports an association between shift work and coronary heart disease (CHD), metabolic disorders, and cancer.6 In 1995, Kawachi et al7 examined the association be- tween rotating night shift work and CHD in the Nurses’ Health Study (NHS) over 4 years of follow-up and reported a 51% sig- nificant increase in CHD risk (nonfatal myocardial infarction [MI] and CHD death) among women with more than 6 years of rotating night shift work after multivariable adjustment (incidence rate per 100 000 person-years, 156.1 compared with 75.4 among women who never worked night shifts). A recent systematic meta-analysis reported a 24% elevated CHD risk associated with most types of shift work but noted signifi- cant heterogeneity in exposure assessment and study de- signs across studies.8 The present study reassessed the asso- ciation of rotating night shift work and coronary health in the Nurses’ Health Studies (NHS and NHS2) with 24 years of follow-up and examined manifestations of CHD (angiogram- confirmed angina pectoris, coronary artery stents, angio- plasty, and coronary artery bypass graft [CABG] surgery), in addition to nonfatal MI and CHD death. Additionally, pos- sible differences in this association over time, including ef- fects of time since quitting shift work, were explored. The study also examined the excess risk of CHD associated with shift work among women without diabetes, hypertension, or hypercholesterolemia—potential comorbid mediators of CHD. Methods Study Population The NHS and NHS2 are ongoing, prospective cohort studies. The NHS began in 1976 when 121 701 female registered US nurses aged 30 to 55 years responded to a baseline questionnaire.9 The NHS2 started in 1989 and included 116 430 female registered US nurses aged 25 to 42 years. In both cohorts, biennial follow-up questionnaires have been mailed to update information on medical history, lifestyle factors, and newly diagnosed dis- eases. Follow-up rates were high in both cohorts, with approxi- mately 90% participation at each 2-year cycle. This study was reviewed and approved by the Brigham and Women’s Hos- pital Institutional Review Board; completion of the self- administered questionnaire was considered informed con- sent, so the requirement for oral or written consent was waived. Rotating Night Shift Work Assessment In the NHS, lifetime years of exposure to rotating night shift work (defined as ≥3 night shifts per month, in addition to day and evening shifts) was queried once, in 1988. In the NHS2, women indicated in 1989 how many years of rotating night shift work they had worked, with updates in 1991, 1993, 1997, 2001, 2005, and 2007; retrospective assessments for shift work in 1995, 1999, and 2003 were included on the 2001 and 2005 questionnaires, respectively. The analyses used baseline as- sessments of lifetime shift work history in each cohort (1988 for NHS and 1989 for NHS2), as well as cumulative shift work exposure through 2007 in the NHS2. In all analyses, night shift work information was carried forward for 1 questionnaire cycle in the case of missing data. Ascertainment of CHD On baseline and follow-up questionnaires, participants were asked to report physician-diagnosed CHD events. Those who reported nonfatal MI were asked for medical record access so that exposure-blinded physicians could confirm self-reported nonfatal MI. Nonfatal MI was confirmed using the World Health Organization criteria, which required diagnostic electrocardio- graphic findings or elevated enzyme levels in addition to typi- cal symptoms.10 Participant deaths were identified through the National Death Index, next of kin, or postal authorities, with pri- mary cause of death being determined by autopsy reports, hos- pital records, and death certificates. The primary outcome was incident CHD, including self-reported cases of CABG surgery, angina pectoris (confirmed by angiogram), angioplasty, and coronary artery stents, in addition to nonfatal MI and CHD death (including fatal MI), whichever came first. Secondary analyses were restricted to nonfatal MI and CHD death. Covariate Assessment In both cohorts, biennial questionnaires were used to collect information on medical history, anthropometric data, diet, and lifestyle. Most variables were updated biennially from base- line onward; physical activity and dietary data were obtained approximately every 4 years. Dietary habits were assessed using a semiquantitative, validated food frequency questionnaire11 calculating the Alternative Healthy Eating Index, which has pre- viously been found to be a reliable predictor of CHD in these cohorts.12 Parity was updated until 1996 and 2009 for the NHS and NHS2, respectively, and subsequently carried forward. Par- ticipants’ husbands’ educational attainment (a proxy for so- cioeconomic status assessed in 1992 in NHS and in 1999 in NHS2), family history of MI before age 60 years (1976 and 1984 in NHS and 1989, 1997, and 2001 in NHS2), and race (2004 in NHS and 1989 and 2005 in NHS2) were not updated through- out follow-up. Usual sleep duration assessed in 1986, 2000, and 2008 (NHS) and 2001 (NHS2), and social support (assessed by asking whether participants had a confidant) in 1992, 2000, 2004, and 2008 (NHS) and in 1993 (NHS2) were not regularly updated throughout follow-up. Statistical Analyses Age- and multivariable-adjusted Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals across rotating night shift work catego- ries (none, <5, 5-9, and ≥10 years). Women with no history of rotating night shift work comprised the reference category in all analyses. Calculations of P values for trend were based on the midpoint of rotating night shift work categories, with the highest category conservatively set to 10; the reported P value was based on the Wald test. The proportional hazards assump- tion was tested by including an interaction of shift work Rotating Night Shift Work and Risk of CHD Among Women Original Investigation Research jama.com (Reprinted) JAMA April 26, 2016 Volume 315, Number 16 1727 Copyright 2016 American Medical Association. All rights reserved. Downloaded From: http://jama.jamanetwork.com/ by Suad Ghaddar on 04/30/2016 http://www.jama.com/?utm_campaign=articlePDF%26utm_medium=articlePDFlink%26utm_source=articlePDF%26utm_content=jama.2016.4454 Copyright 2016 American Medical Association. All rights reserved. (ie, midpoint of categories) by time in all models, and its sig- nificance was evaluated using the Wald statistic. In sensitiv- ity analyses, the outcome was restricted to nonfatal MI and CHD death. Additional sensitivity analyses were restricted to par- ticipants with no baseline history of major comorbidities po- tentially mediating CHD (ie, diabetes, hypertension, and hy- percholesterolemia) and censored women who reported any of these conditions throughout follow-up. The following cardiovascular disease risk factors were in- cluded in multivariable-adjusted models: family history of MI before age 60 years, diet quality (Alternative Healthy Eating Index,12 without the alcohol and multivitamin components, in quintiles), physical activity (metabolic equivalent task–hours per week, in quintiles), body mass index (BMI, calculated as weight in kilograms divided by height in meters squared: <25, 25-29, 30-35, or >35), cumulative pack-years smoked (continuous), al-
cohol intake (none, 0.1-5, 5.1-10, 10.1-20, or >20 g/d), parity (nul-
liparous, 1, 2, or ≥3 children), menopausal status (premenopaus-
al or postmenopausal), hormone therapy (premenopausal, ever,
or never), race (white, black, or other), husband’s highest edu-
cational level (high school diploma or less, college degree, or
graduate school level or similar), multivitamin use (yes or no),
acetaminophen use (yes or no), nonsteroidal anti-inflammatory
drug use (yes or no), aspirin use (yes or no), hypertension (yes or
no), diabetes (yes or no), and hypercholesterolemia (yes or no).
In additional analyses, models were adjusted for sleep duration
(<6, 6-7, 8-9, or ≥10 hours per day) and social support (yes or no). Dummy variables were used to indicate missing covariate val- ues. For missing information on pack-years of smoking, the me- dian among smokers was imputed; in the case of missing BMI, information was carried forward once. On average, 9.5% of co- variate information was missing across 24 years of follow-up. In the NHS2, analyses also examined the association be- tween cumulative time since quitting rotating night shift work (never, current, <12, 12-24, or >24 years) and CHD risk. Time since
quitting rotating night shift work was estimated based on life-
time reports of exposure in 1989 and updated shift work infor-
mation throughout follow-up. If women reported rotating night
shifts at baseline only, time since quitting shift work was esti-
mated by subtracting 21 years (assumed age at starting shift
work) and the lower bound of the categorically reported dura-
tion of rotating night shift work from their age in 1989.

In additional secondary analyses, potential effect modi-
fication by BMI (<25, 25-30, or >30) was examined, adjusting
continuously for BMI within each stratum. To evaluate poten-
tial interactions, the log likelihood ratio test was used to com-
pare models with and without cross-product interaction terms;
corresponding P values were based on χ2 statistics.

The a priori hypothesis was that rotating night shift work in-
creased CHD risk, and all secondary analyses were preplanned.
Analyses were conducted with SAS software, version 9.4 (SAS
Institute Inc) with a 2-sided significance threshold of P < .05. Results A total of 103 525 NHS participants answered the 1988 ques- tionnaire. Of these, women with CHD, stroke, or cancer (n = 14 065) and those who did not answer the shift work question in 1988 (n = 15 837) were excluded, leaving 73 623 women for analysis. In the NHS2, 116 430 women answered the baseline questionnaire (1989), of whom 895 reported stroke or CHD prior to baseline, so that after the same exclu- sions, 115 535 women were left for analysis. For the NHS2 analysis with updated shift work information, women who did not answer shift work questions for 2 consecutive cycles (on average, 8.7% per cycle) were censored. Women were excluded from further follow-up after any self-reported stroke, incident CHD, or death. During 24 years of follow-up, a total of 10 822 incident CHD cases were observed (7303 in NHS and 3519 in the younger NHS2). Table 1 describes age and age-adjusted (within- cohort) characteristics of the study population across catego- ries of lifetime years of rotating night shift work at baseline. Compared with women in the NHS, women in the NHS2 were younger, more likely to be nulliparous, had slightly lower al- cohol consumption, reported fewer pack-years of smoking, had fewer comorbid conditions, and took fewer medications and multivitamin supplements. With increasing duration of rotat- ing night shift work, women were heavier in both cohorts. Also, in the NHS, a lower proportion of women had husbands with graduate-level education across increasing categories of shift work, while pack-years of smoking and self-reports of hyper- tension increased; in the NHS2, a greater proportion of nul- liparous women and acetaminophen users were observed with increasing duration of rotating night shift work. Compared with women without a history of rotating night shift work (incidence rates, 425.5 and 122.6 per 100 000 per- son-years in the NHS and NHS2, respectively), women who worked less than 5 years of shift work at baseline did not have a significantly increased CHD risk in age-adjusted analyses (Table 2 and Table 3), but there was a significant association between longer durations of shift work and CHD risk (in the NHS: incidence rate per 100 000 person-years for 5-9 years, 525.7; HR, 1.21 [95% CI, 1.11-1.33]; incidence rate for ≥10 years, 596.9; HR, 1.36 [95% CI, 1.27-1.46]; P<.001 for trend; in the NHS2: incidence rate for 5-9 years, 151.6; HR, 1.22 [95% CI, 1.08- 1.38]; incidence rate for ≥10 years, 178.0; HR, 1.34 [95% CI, 1.17- 1.53]; P<.001 for trend). Multivariable adjustment for known CHD risk factors attenuated these estimates, but the elevated risk observed for 5 years or more of shift work persisted in the NHS (multi- variable HR for 5-9 years, 1.12 [95% CI, 1.02-1.22]; multivari- able HR for ≥10 years, 1.18 [95% CI, 1.10-1.26]; P<.001 for trend), and for 10 years or more of shift work in the NHS2 (multivariable HR for 5-9 years, 1.12 [95% CI, 0.99-1.26]; mul- tivariable HR for ≥10 years, 1.15 [95% CI, 1.01-1.32]; P = .01 for trend). In the NHS, there was a significant interaction between rotating night shift work exposure and time ( by 2-year period, P<.001 for interaction) (Table 2), suggesting that CHD risk associated with shift work changes over time. During the first half of follow-up, higher effect estimates and signifi- cantly elevated risks also were observed with shorter dura- tions of shift work exposure (incidence rate per 100 000 person-years for <5 years, 382.4; multivariable HR, 1.10 [95% Research Original Investigation Rotating Night Shift Work and Risk of CHD Among Women 1728 JAMA April 26, 2016 Volume 315, Number 16 (Reprinted) jama.com Copyright 2016 American Medical Association. All rights reserved. Downloaded From: http://jama.jamanetwork.com/ by Suad Ghaddar on 04/30/2016 http://www.jama.com/?utm_campaign=articlePDF%26utm_medium=articlePDFlink%26utm_source=articlePDF%26utm_content=jama.2016.4454 Copyright 2016 American Medical Association. All rights reserved. CI, 1.01-1.21]; incidence rate for 5-9 years, 483.1; multivariable HR, 1.19 [95% CI, 1.03-1.39]; incidence rate for ≥10 years, 494.4; multivariable HR, 1.27 [95% CI, 1.13-1.42]; P < .001 for trend and P = .02 for interaction for first vs second half of follow-up). In the second half of follow-up, compared with women who never worked rotating night shifts (incidence Table 1. Age and Age-Adjusted Characteristics of Participating Women at Baseline by Rotating Night Shift Work Historya Characteristics Rotating Night Shift Work Exposure (≥3 Night Shifts Per Month) NHS (1988) NHS2 (1989) None (n=30 012) <5 y (n=30 122) 5-9 y (n=4955) ≥10 y (n=8534) None (n=43 657) <5 y (n=56 179) 5-9 y (n=9866) ≥10 y (n=5833) Age, mean (SD), y 54.0 (7.1) 54.3 (7.1) 54.9 (7.1) 56.2 (6.9) 34.8 (4.7) 34.5 (4.7) 35.1 (4.2) 37.1 (3.6) White race, No. (%) 29 390 (98) 29 424 (98) 4832 (98) 8250 (97) 42 075 (96) 53 501 (95) 9337 (95) 5479 (95) Parity, No. (%) Nulliparous 1434 (5) 1795 (6) 351 (7) 539 (6) 12 111 (28) 17 814 (31) 3440 (36) 1795 (37) 1 or 2 children 10 415 (34) 10 650 (35) 1761 (36) 2853 (35) 23 249 (53) 28 704 (51) 4889 (50) 2926 (48) ≥3 children 17 750 (60) 17 211 (57) 2743 (55) 4956 (57) 8290 (19) 9653 (18) 1536 (15) 1109 (16) Parental history of MI at age <60 y, No. (%) 4893 (16) 5081 (17) 879 (18) 1516 (18) 6105 (14) 8294 (15) 1670 (17) 1011 (16) Body mass index, mean (SD)b 25.2 (4.8) 25.4 (4.8) 26.0 (5.3) 26.6 (5.4) 23.9 (4.9) 24.0 (5.0) 24.8 (5.5) 25.1 (5.8) No. (%) <25 18 206 (61) 17 910 (59) 2683 (54) 4242 (50) 31 400 (72) 39 851 (71) 6365 (65) 3420 (62) 25-29.9 7926 (27) 8107 (27) 1455 (29) 2559 (30) 7693 (18) 10 300 (18) 2068 (21) 1330 (22) 30-34.9 2645 (9) 2877 (10) 545 (11) 1116 (13) 2837 (7) 3723 (7) 853 (9) 606 (9) ≥35 1235 (4) 1228 (4) 272 (6) 617 (7) 1727 (4) 2305 (4) 580 (6) 477 (7) Pack-years of smoking, median (IQR)c 18 (7-34) 18 (6-34) 20 (7-35) 24 (10-39) 10 (5-16) 9 (5-16) 10 (5-17) 11 (6-19) Husband holds graduate school degree, No. (%) 5841 (19) 6346 (21) 840 (17) 1028 (12) 9351 (21) 13 810 (25) 2079 (21) 1090 (18) Alcohol intake, median (IQR), g/dd 1.8 (0-7.6) 1.9 (0-8.3) 1.8 (0-7.3) 1.1 (0-6.2) 0.9 (0-3.1) 0.9 (0-3.7) 0.9 (0-3.6) 0.9 (0-2.9) Alternative Healthy Eating Index score (2010), mean (SD)e 45.7 (10.5) 46.0 (10.4) 46.0 (10.3) 45.3 (10.1) 43.6 (10.5) 44.3 (10.5) 44.2 (10.4) 44.1 (10.3) Physical activity, median (IQR), MET-hours/wkf 7.9 (2.9-20.2) 9.1 (3.4-20.9) 9.0 (3.4-21.5) 8.4 (3.2-21.5) 12.3 (4.7-27.4) 14.6 (5.5-31.6) 15.1 (5.8-33.3) 14.2 (5.2-32.1) Multivitamin use, No. (%) 18 518 (62) 19 011 (63) 3148 (64) 5325 (62) 23 704 (54) 30 053 (54) 5254 (53) 3242 (55) Aspirin use, No. (%) 18 482 (62) 19 105 (63) 3122 (63) 5374 (63) 4747 (11) 6119 (11) 1195 (12) 827 (13) NSAID use, No. (%) 9537 (31) 9680 (32) 1575 (32) 2728 (33) 7775 (18) 10 986 (20) 2206 (22) 1409 (22) Acetaminophen use, No. (%)g 11 110 (37) 11 315 (37) 1849 (38) 3204 (39) 9229 (21) 12 370 (22) 2292 (23) 1529 (26) Postmenopausal, No. (%) 20 735 (71) 21 254 (71) 3674 (72) 6866 (74) 965 (2) 1271 (2) 247 (2) 238 (3) Current hormone therapy, No. (%) 6833 (23) 7059 (24) 1122 (22) 1868 (21) 997 (2) 1263 (2) 246 (2) 236 (3) Self-reported hypertension, No. (%) 7464 (25) 7641 (26) 1448 (29) 2781 (30) 2270 (5) 2938 (5) 627 (6) 460 (7) Self-reported diabetes, No. (%) 1048 (4) 995 (3) 221 (4) 507 (6) 396 (1) 402 (1) 74 (1) 68 (1) Self-reported hypercholesterolemia, No. (%) 6683 (23) 6837 (23) 1171 (23) 2781 (24) 4493 (10) 5809 (10) 1100 (11) 722 (11) Usual sleep duration, No. (%), hh ≤6 6978 (23) 7506 (25) 1427 (29) 2901 (34) 8939 (20) 12 230 (22) 2542 (26) 1670 (28) 7 11 299 (38) 11 353 (38) 1770 (36) 2609 (31) 13 835 (32) 17 397 (31) 2779 (28) 1552 (26) 8-9 7661 (26) 7358 (24) 1044 (21) 1709 (19) 9593 (22) 11 178 (20) 1680 (17) 892 (16) ≥10 157 (1) 132 (0) 24 (0) 56 (1) 245 (1) 322 (1) 52 (1) 37 (1) Social support, No. (%)i 22 288 (94) 22 667 (94) 3617 (93) 6019 (94) 31 370 (94) 39 389 (95) 6822 (95) 3930 (94) Abbreviations: IQR, interquartile range; MET, metabolic equivalent task; MI, myocardial infarction; NHS, Nurses’ Health Study; NSAID, nonsteroidal anti-inflammatory drug. a Numbers that do not add up to 100% are attributable to missing data. b Calculated as weight in kilograms divided by height in meters squared. c Cumulative among smokers. d Assessed in 1986 for the NHS and in 1991 for the NHS2. e Assessed in 1986 for the NHS and in 1991 for the NHS2. Higher scores reflect a healthier diet.12 f Weekly energy expenditure in MET-hours from recreational and leisure time activities. g Assessed in 1990 for the NHS and in 1989 for the NHS2. h Assessed in 1986 for the NHS and in 2001 for the NHS2. i Assessed in 1992 for the NHS and in 1993 for the NHS2. Rotating Night Shift Work and Risk of CHD Among Women Original Investigation Research jama.com (Reprinted) JAMA April 26, 2016 Volume 315, Number 16 1729 Copyright 2016 American Medical Association. All rights reserved. Downloaded From: http://jama.jamanetwork.com/ by Suad Ghaddar on 04/30/2016 http://www.jama.com/?utm_campaign=articlePDF%26utm_medium=articlePDFlink%26utm_source=articlePDF%26utm_content=jama.2016.4454 Copyright 2016 American Medical Association. All rights reserved. rate per 100 000 person-years, 436.6), only those who worked 10 years or more of shift work had a significantly elevated CHD risk (incidence rate, 556.2; multivariable HR, 1.13 [95% CI, 1.04-1.24]; P = .004 for trend). The association between shift work and CHD risk was not significant in the last 4 years of follow-up (2008-2012; incidence rate for <5 years, 219.9; multivariable HR, 0.85 [95% CI, 0.70-1.03]; inci- dence rate for 5-9 years, 247.2; multivariable HR, 0.88 [95% CI, 0.62-1.26]; incidence rate for ≥10 years, 306.3; multivari- able HR, 1.04 [95% CI, 0.80-1.35]; P = .94 for trend) (eTable 1 in the Supplement). All categories of rotating night shift work showed a sig- nificantly elevated CHD risk when shift work history was cumulatively updated in the NHS2 (inc idence rate per 100 000 person-years for <5 years, 137.4; multivariable HR, 1.12 [95% CI, 1.01-1.24]; incidence rate for 5-9 years, 161.9; Table 2. Shift Work and Risk of Coronary Heart Disease in the NHSa Cohort Baseline History of Rotating Night Shift Workb P Value for Trendc P Value for Interaction, Shift Work × TimedNone <5 y 5-9 y ≥10 y Overall NHS, 1988 to 2012 Cases/person-years 2739/643 774 2857/644 857 568/103 574 1139/173 571 Incidence rate per 100 000 person-years (95% CI)e 425.5 (383.9-467.1) 435.1 (392.8-477.5) 525.7 (410.4-641.1) 596.9 (502.1-691.7) Age-adjusted model, HR (95% CI) 1 [Reference] 1.02 (0.96-1.07) 1.21 (1.11-1.33) 1.36 (1.27-1.46) <.001 Multivariable-adjusted model, HR (95% CI)f 1 [Reference] 1.02 (0.97-1.08) 1.12 (1.02-1.22) 1.18 (1.10-1.26) <.001 <.001 First vs second half of follow-up .02 June 1988 to May 2000 Cases/person-years 915/351 568 1021/352 490 213/57 612 455/97 899 Incidence rate per 100 000 person-years (95% CI)e 367.3 (302.4-432.3) 382.4 (316.8-448.1) 483.1 (306.6-659.7) 494.4 (370.1-618.8) Multivariable-adjusted model, HR (95% CI)f 1 [Reference] 1.10 (1.01-1.21) 1.19 (1.03-1.39) 1.27 (1.13-1.42) <.001 .03 June 2000 to May 2012 Cases/person-years 1824/305 036 1836/305 297 355/48 238 684/79 819 Incidence rate per 100 000 person-years (95% CI)e 436.6 (367.8-505.4) 424.8 (361.8-487.7) 520.7 (377.1-664.3) 556.2 (414.2-754.3) Multivariable-adjusted model, HR (95% CI)f 1 [Reference] 0.98 (0.92-1.05) 1.08 (0.96-1.21) 1.13 (1.04-1.24) .004 .08 Restricted to myocardial infarction and coronary heart disease death June 1988 to May 2000 Cases/person-years 443/353 659 491/354 846 117/58 026 226/99 022 Incidence rate per 100 000 person-years (95% CI)e 173.0 (128.3-217.8) 182.3 (137.2-227.4) 276.2 (142.6-409.9) 236.5 (151.8-321.3) Multivariable-adjusted model, HR (95% CI)f 1 [Reference] 1.12 (0.99-1.28) 1.35 (1.10-1.66) 1.29 (1.09-1.51) .001 .19 June 2000 to May 2012 Cases/person-years 444/316 989 428/318 083 65/50 714 176/84 689 Incidence rate per 100 000 person-years (95% CI)e 106.6 (73.1-140.0) 92.3 (69.1-115.5) 101.5 (36.4-166.5) 133.3 (76.4-190.1) Multivariable-adjusted model, HR (95% CI)f 1 [Reference] 0.95 (0.83-1.09) 0.77 (0.60-1.00) 1.09 (0.91-1.30) .84 .56 Abbreviations: HR, hazard ratio; NHS, Nurses’ Health Study. a A total of 7303 coronary heart disease cases (ie, nonfatal myocardial infarction, coronary heart disease–attributed death, angiogram-confirmed angina pectoris, angioplasty, coronary artery bypass graft surgery, and coronary artery stents) occurred during 24 years of follow-up in the NHS (N = 73 623). b Assessed in 1988. c Based on category midpoints, except for �10 years, for which the midpoint was set to 10 years. d Based on the interaction between shift work category midpoints (except for �10 years, for which the midpoint was set to 10 years) and time (in 2-year cycles). e Incidence rates and 95% CIs are adjusted to the age distribution of women who reported no history of rotating night shift work, separately for each cohort. f Multivariable-adjusted model included age, physical activity (metabolic equivalent task–hours per week, in quintiles), diet (Alternative Healthy Eating Index score,12 in quintiles), alcohol consumption (none, 0.1-5, 5.1-10, 10.1-20, or >20 g/d), pack-years of smoking (continuous), parental history
of myocardial infarction prior to age 60 years (yes or no), menopausal status
(premenopausal vs postmenopausal), parity (nulliparous, 1 child, 2 children,
or �3 children), hormone therapy (ever, never, or premenopausal),
multivitamin use (yes or no), acetaminophen use (yes or no), nonsteroidal
anti-inflammatory drug use (yes or no), aspirin use (yes or no), hypertension
(yes or no), hypercholesterolemia (yes or no), diabetes (yes or no),
body mass index (<25, 25-29.9, 30-34.9, or �35), race (white, black, or other), and husband’s highest educational level (up to high school diploma, college degree, or graduate school or similar). Research Original Investigation Rotating Night Shift Work and Risk of CHD Among Women 1730 JAMA April 26, 2016 Volume 315, Number 16 (Reprinted) jama.com Copyright 2016 American Medical Association. All rights reserved. Downloaded From: http://jama.jamanetwork.com/ by Suad Ghaddar on 04/30/2016 http://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2016.4454&utm_campaign=articlePDF%26utm_medium=articlePDFlink%26utm_source=articlePDF%26utm_content=jama.2016.4454 http://www.jama.com/?utm_campaign=articlePDF%26utm_medium=articlePDFlink%26utm_source=articlePDF%26utm_content=jama.2016.4454 Copyright 2016 American Medical Association. …