Gender-Specific Associations of Short Sleep Duration With Prevalent and Incident Hypertension
Gender-Specific Associations of Short Sleep Duration With Prevalent and Incident Hypertension
Gender-Specific Associations of Short Sleep Duration With Prevalent and Incident Hypertension
AbstractSleep deprivation (5 hour per night) was associated with a higher risk of hypertension in middle-aged
American adults but not among older individuals. However, the outcome was based on self-reported diagnosis of
incident hypertension, and no gender-specific analyses were included. We examined cross-sectional and prospective
associations of sleep duration with prevalent and incident hypertension in a cohort of 10 308 British civil servants aged
35 to 55 years at baseline (phase 1: 19851988). Data were gathered from phase 5 (19971999) and phase 7
(20032004). Sleep duration and other covariates were assessed at phase 5. At both examinations, hypertension was
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defined as blood pressure 140/90 mm Hg or regular use of antihypertensive medications. In cross-sectional analyses
at phase 5 (n5766), short duration of sleep (5 hour per night) was associated with higher risk of hypertension
compared with the group sleeping 7 hours, among women (odds ratio: 2.01; 95% CI: 1.13 to 3.58), independent of
confounders, with an inverse linear trend across decreasing hours of sleep (P0.003). No association was detected in
men. In prospective analyses (mean follow-up: 5 years), the cumulative incidence of hypertension was 20.0% (n740)
among 3691 normotensive individuals at phase 5. In women, short duration of sleep was associated with a higher risk
of hypertension in a reduced model (age and employment) (6 hours per night: odds ratio: 1.56 [95% CI: 1.07 to 2.27];
5 hour per night: odds ratio: 1.94 [95% CI: 1.08 to 3.50] versus 7 hours). The associations were attenuated after
accounting for cardiovascular risk factors and psychiatric comorbidities (odds ratio: 1.42 [95% CI: 0.94 to 2.16]; odds
ratio: 1.31 [95% CI: 0.65 to 2.63], respectively). Sleep deprivation may produce detrimental cardiovascular effects
among women. (Hypertension. 2007;50:693-700.)
Key Words: sleep duration blood pressure hypertension gender differences confounders comorbidities
Received May 30, 2007; first decision June 24, 2007; revision accepted August 3, 2007.
From the Clinical Sciences Research Institute (F.P.C., S.S., N-B.K., M.A.M., F.M.T.), Warwick Medical School, Coventry, United Kingdom; and the
International Centre for Health and Society (M.K., J.E.F., M.J.S., E.J.B., M.G.M.), University College London Medical School, London, United Kingdom.
Correspondence to Francesco P. Cappuccio, Clinical Sciences Research Institute, Warwick Medical School, UHCW Campus, Clifford Bridge Rd,
Coventry CV2 2DX, United Kingdom. E-mail [email protected]
2007 American Heart Association, Inc.
Hypertension is available at http://hyper.ahajournals.org DOI: 10.1161/HYPERTENSIONAHA.107.095471
693
694 Hypertension October 2007
proinflammatory responses, endothelial dysfunction, and re- medication. At both phase 5 and 7 screening examinations, anthro-
nal impairment.18,19 On the other hand, intervention studies to pometric measures were recorded, including height, weight, and
waist circumference; body mass index (BMI) was calculated as
improve duration and quality of sleep have been effective in
weight in kilograms divided by height in meters squared. Blood
reducing both daytime and nighttime blood pressures.19,20 pressure was measured 3 times using a standard mercury manometer
However, there is concern that sleep habits may represent a by trained and certified technicians in both examinations. The onsets
marker of health status and quality of life rather than a casual of the first-phase (systolic) and fifth-phase (diastolic) Korotkoff
factor for hypertension and other health outcomes.21 sounds were recorded. The mean of the second and third measures
were used in the analyses. At both examinations, hypertension was
In the present analysis, we sought to examine both the
defined as blood pressure 140/90 mm Hg or regular use of
cross-sectional and prospective associations of sleep duration antihypertensive medications.
with prevalent and incident hypertension in the Whitehall II
Study, a prospective cohort of 10 308 white-collar British Ethical Approval
civil servants aged 35 to 55 at baseline (phase 1: 19851988). Ethical approval for the Whitehall II Study was obtained from the
Because reduced durations of sleep might be associated with University College London Medical School committee on the ethics
of human research.
more detrimental effects on cardiovascular outcomes among
women,6 9 unlike previous investigations, we conducted Statistical Analysis
gender-specific analyses with the inclusion of a number of For continuous and categorical variables, respectively, Kruskal
potential confounding variables. Wallis and 2 tests were used to determine the statistical significance
of any difference in the distribution of baseline variables at phase 5
Methods across categories of sleep duration. The statistical significance of the
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Table 1. Baseline Characteristics (Phase 5: 19971999) Across Categories of Sleep Duration: The
Whitehall II Study (n5766)
Sleep Duration
Characteristics 5 h 6h 7h 8h 9 h P*
Men (n4199)
No. of subjects 265 1383 1886 620 45
Age, y 54.6 (5.6) 54.6 (5.7) 55.5 (6.1) 57.5 (6.1) 57.7 (5.4) 0.001
DBP, mm Hg 79.2 (10.9) 78.2 (10.4) 78.6 (10.5) 79.0 (10.9) 78.1 (10.6) 0.57
SBP, mm Hg 124.0 (16.7) 122.3 (15.4) 123.9 (15.8) 125.1 (17.3) 122.5 (16.6) 0.009
Pulse pressure, mm Hg 44.7 (11.5) 44.1 (10.7) 45.3 (11.0) 46.1 (12.4) 44.4 (11.1) 0.003
Lowest employment, n (%) 26 (9.8) 66 (4.8) 62 (3.3) 18 (2.9) 3 (6.7) 0.001
BMI, kg/m2 27.0 (4.1) 26.4 (3.5) 25.9 (3.4) 25.4 (3.3) 25.7 (3.3) 0.001
Waist, cm 94.9 (11.6) 92.8 (10.2) 91.6 (9.7) 90.2 (9.9) 91.5 (8.5) 0.001
Weekly alcohol, units 18.0 (21.2) 16.9 (15.9) 16.5 (15.9) 16.3 (17.1) 17.7 (20) 0.58
CVD drugs, n (%) 49 (18.6) 185 (13.4) 259 (13.8) 111 (18.0) 9 (20.0) 0.013
Physical activity, n (%) 108 (40.8) 687 (49.7) 930 (49.3) 320 (51.6) 17 (37.8) 0.022
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SF-36 mental (score) 47.1 (12.2) 50.5 (9.2) 52.5 (8.2) 53.7 (7.5) 52.0 (9.9) 0.001
SF-36 physical (score) 50.2 (8.8) 52.1 (7.1) 52.4 (6.4) 51.9 (6.8) 50.9 (8.5) 0.019
Use of hypnotics, n (%) 7 (2.7) 8 (0.6) 4 (0.2) 2 (0.3) 0 (0.0) 0.001
Depression cases, n (%) 62 (23.8) 178 (13.1) 173 (9.3) 55 (9.0) 4 (8.9) 0.001
Current smoking, n (%) 30 (11.5) 123 (8.9) 154 (8.2) 49 (7.9) 4 (8.9) 0.45
Hypertensive, n (%) 84 (31.7) 358 (25.9) 533 (28.3) 205 (33.1) 14 (31.1) 0.014
No medication 45 (17.0) 218 (15.8) 323 (17.1) 115 (18.6) 9 (20.0)
Medication 38 (14.3) 140 (10.1) 208 (11.0) 90 (14.5) 5 (11.1)
Women (n1567)
No. of subjects 157 511 597 272 30
Age, y 56.4 (5.9) 56.1 (6.1) 55.7 (6.1) 56.8 (6.1) 54.7 (5.7) 0.07
DBP, mm Hg 75.7 (10.4) 74.9 (10.1) 74.4 (9.8) 74.2 (10.0) 74.0 (10.0) 0.50
SBP, mm Hg 124.2 (18.3) 121.2 (16.8) 120.3 (17.1) 121.4 (16.8) 118 (17.2) 0.07
Pulse pressure, mm Hg 48.5 (13.8) 46.3 (12.3) 45.9 (12.3) 47.2 (11.6) 44.0 (10.9) 0.07
Lowest employment, n (%) 52 (33.1) 143 (28.1) 162 (27.2) 67 (25.0) 11 (36.7) 0.003
BMI, kg/m2 27.1 (5.8) 26.2 (5.1) 25.9 (4.4) 26.3 (5.0) 25.8 (4.6) 0.31
Waist, cm 82.5 (14.3) 80.2 (11.8) 80.1 (11.2) 80.4 (11.9) 81.5 (12.0) 0.66
Weekly alcohol, units 7.3 (10.8) 8.0 (8.5) 8.2 (9.5) 8.4 (10.0) 9.8 (9.4) 0.10
CVD drugs, n (%) 36 (23.1) 58 (11.4) 94 (15.8) 46 (16.9) 4 (13.3) 0.007
Physical activity, n (%) 38 (24.2) 169 (33.1) 215 (36) 108 (39.7) 6 (20.0) 0.006
SF-36 mental (score) 42.9 (13.1) 49.0 (10.3) 50.8 (9.2) 52.6 (8.8) 46.9 (15.0) 0.001
SF-36 physical (score) 46.0 (12.5) 50.2 (8.4) 49.8 (9.0) 49.9 (8.8) 45.2 (10.1) 0.001
Use of hypnotics, n (%) 2 (1.3) 5 (1.0) 4 (0.7) 2 (0.7) 1 (3.3) 0.60
Depression cases, n (%) 50 (32.5) 72 (14.4) 66 (11.2) 20 (7.4) 5 (16.7) 0.001
Current smoking, n (%) 20 (12.9) 79 (15.5) 76 (12.8) 31 (11.4) 1 (3.3) 0.22
Hypertensive, n (%) 58 (36.9) 124 (24.3) 152 (25.5) 66 (24.3) 7 (23.3) 0.024
No medication 27 (17.2) 72 (14.1) 69 (11.6) 29 (10.7) 5 (16.7)
Medication 31 (19.7) 52 (10.2) 83 (13.9) 37 (13.6) 2 (6.7)
Data are expressed as the mean (SD) or as n (%). DBP indicates diastolic blood pressure; SBP, systolic blood pressure.
*P value for comparison across sleep duration groups using the 2 analysis for categorical variables and Kruskal-Wallis test for
continuous variables.
One value is missing.
Two values are missing.
for CVD drugs or hypnotics, more likely to be depressed, and duration. For blood pressures, there was a consistent pattern
reported lower scores for mental and physical health than of association among female participants sleeping 5 hours,
other categories. No significant differences in drinking and who reported higher mean levels of systolic blood pressure
smoking habits were reported across categories of sleep (and pulse pressure), as well as a significantly higher preva-
696 Hypertension October 2007
Table 2. OR (95% CI) of Prevalent Hypertension Across Categories of Sleep Duration at Phase 5 (19971999): The Whitehall II Study
(n5766)
Sleep Duration P*
lence of hypertension than other participants (in both treated higher risk of hypertension compared with the group sleeping
and untreated individuals). 7 hours (OR: 2.01; 95% CI: 1.13 to 3.58), independent of
several potential confounders, with a significant inverse
Cross-Sectional Analysis linear trend across decreasing hours of sleep (P0.003).
Table 2 displays the odds ratios (ORs) and 95% CIs of
prevalent hypertension across categories of sleep duration at Prospective Analysis
phase 5, using 7 hours of sleep as the reference category. Table 3 displays the ORs (and 95% CIs) of incident hyper-
Among men, no consistent pattern of association was noted. tension at phase 7 among participants who were normoten-
Among women, in fully adjusted analyses, short duration of sive at phase 5. During a mean follow-up of 5 years, the
sleep (5 hours per night) was associated with a significantly cumulative incidence of hypertension was 20.0% (740 of
Table 3. OR (95% CI) of Incident Hypertension at Phase 7 (20022003) Across Categories of Sleep Duration at Phase 5 (19971999):
The Whitehall II Study (n3691)
Sleep Duration P*
3691 total: 539 of 2686 in men and 201 of 1005 in women). Other Analyses
Among men, no consistent pattern of association was seen We also carried out linear regression analyses to test the
across categories of sleep duration. Among women, short association between sleep duration and blood pressures (sys-
duration of sleep was associated with significantly higher tolic, diastolic, and pulse pressures) at phase 5 (cross-
risks of hypertension compared with the group sleeping 7 sectional analyses), as well as the association between sleep
hours in unadjusted analyses, as well as in a reduced model duration at phase 5 and changes in blood pressures between
(age and employment; 6 hours per night: OR: 1.56 [95% CI: the 2 phases (prospective analyses), among participants not
1.07 to 2.27], 5 hours per night: OR: 1.94 [95% CI: 1.08 to taking antihypertensive medications. In cross-sectional anal-
3.50]). However, these associations were attenuated after yses, there were consistent, significant inverse associations
(P0.05) between duration of sleep and either systolic blood
accounting for cardiovascular risk factors and psychiatric
pressure (1.24 mm Hg per hour of sleep; 95% CI:
comorbidities (OR: 1.42 [95% CI: 0.94 to 2.16]; OR: 1.30
2.23 to 0.24 mm Hg per hour of sleep) or pulse pressure
[95% CI: 0.65 to 2.62], respectively). The proportion of the
(0.91 mm Hg per hour of sleep; 95% CI: 1.63 to
variance of the risk of developing hypertension explained by
0.20 mm Hg per hour of sleep), only among women, in
the age- and employment-adjusted model was 2.95%. In the fully adjusted models. In prospective analyses, no significant
fully adjusted model it was 6.14%. The major contributor in associations were found for any of the blood pressure
the full multivariate model was body mass index (explaining measures among either male or female participants (data not
2.23% of the added variance), whereas the remaining covari- shown).
ates all accounted for 1% of the remaining difference.
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emphasizing the critical role of sympathetic overactivity in larly vulnerable times for women, because they are associated
the etiology of SDB-related hypertension,24,25 although other with major hormonal turmoil and psychosocial stresses that
mechanisms are likely to be involved.19 More recently, sleep may, in turn, lead to adverse health outcomes.27 For example,
deprivation has been indicated as a risk factor for several in our sample of female participants, the prevalence of
chronic health outcomes in individuals without overt sleep depression cases was higher among women reporting short
disorders.6 12 However, we are aware of only 2 population- duration of sleep (5 hours per night) than in other sub-
based studies so far, both coming from the United States, that groups. In addition, as shown in our descriptive analyses, the
have attempted to examine the association between self- distribution of correlates of short sleep duration that have the
reported durations of sleep and risk of hypertension.13,14 potential to affect hypertension risk was different between
Specifically, in a longitudinal analysis of the NHANES-I genders and may have partially contributed to the observed
(n4810), short sleep duration (5 hours per night) was associations. Finally, we cannot rule out the possibility of
associated with a 60% higher risk of incident hypertension, in differential self-reporting of sleep habits between men and
fully adjusted models, among middle-aged (32 to 59 years) women, as suggested in a previous analysis from the Sleep
American adults without apparent sleep disorders.13 No Heart Health Study examining the relationship of gender to
association was found in individuals 60 years of age. subjective measures of sleepiness.28
However, in this study, the diagnosis of incident hypertension Second, although findings from cross-sectional analyses
was based on self-report with a potential of misclassification consistently showed a strong, significant association between
(underdiagnosis), as suggested by a lower cumulative inci- short sleep duration and risk of hypertension among women,
dence (647 of 4810 [13.5%]) as compared with that in prospective analyses, the risk estimates were attenuated
observed in our study (740 of 3691 [20.0%]), despite com- after accounting for cardiovascular risk factors, measures of
parable age ranges between the 2 studies and a longer general health, and psychiatric comorbidities. Thus, these
follow-up period in the NHANES-I (8 to 10 years versus 5 findings emphasize the importance of a comprehensive ex-
years, respectively). In addition, no gender-specific analyses amination of correlates that are likely to confound or may be
were included in the NHANES-I. Moreover, in a cross- on the causal pathway between sleep deprivation and adverse
sectional analysis of the large sample of the Sleep Heart health outcomes. Nevertheless, recent prospective analyses
Health Study (6000 US adults), a significantly higher from the Monitoring Trends Determinants in Cardiovascular
prevalence of hypertension was reported among either short Disease Augsburg survey indicate a modest but significant
(6 hours per night) or long sleepers (9 hours per night) as association between short sleep duration and incident myo-
compared with the median duration of sleep of 7 to 8 hours cardial infarction in middle-aged women, but not men, from
per night.14 However, the association was stronger among the general population.29
short sleepers than in long sleepers (ie, 66% versus 30% Third, our descriptive analyses clearly demonstrate that
higher risk of hypertension, respectively). Although this both short and long duration of sleep may indeed identify
study accounted for a number of potential covariates, includ- population subgroups with a distinct cluster of sociodemo-
ing psychiatric and cardiovascular comorbidities, the cross- graphic characteristics, lifestyle behaviors, and disease con-
sectional design does not allow us to exclude the possibility ditions that are likely to be affected by the cultural setting in
of residual confounding by unknown variables, as well as to which the research is being conducted.30 33 In this regard, the
exclude the potential of reverse causality. In addition, the study of health consequences related to curtailments of sleep
Sleep Heart Health Study sample cohort was, on average, seems to be epidemiologically relevant in the general popu-
older than those in both NHANES-I and Whitehall II, thus lation, given the downward trends in the average duration of
with a higher likelihood of geriatric comorbidities potentially sleep and the increasingly higher prevalence of short sleep-
affecting sleep patterns.26 ers in many Western countries.34,35 Conversely, it may be
Cappuccio et al Short Sleep Duration and Hypertension 699
16. Lusardi P, Mugellini A, Preti P, Zoppi A, Derosa G, Fogari R. Effects of daytime somnolence in the Sleep Heart Health Study. Sleep. 2004;27:
a restricted sleep regimen on ambulatory blood pressure monitoring in 305311.
normotensive subjects. Am J Hypertens. 1996;9:503505. 29. Meisinger C, Heier M, Lowel H, Schneider A, Doring A. Sleep duration
17. Lusardi P, Zoppi A, Preti P, Pesce RM, Piazza E, Fogari R. Effects of and sleep complaints and risk of myocardial infarction in middle-aged
insufficient sleep on blood pressure in hypertensive patients: a 24-h study. men and women from the general population. The MONICA/KORA
Am J Hypertens. 1999;12:63 68. Augsburg Cohort Study. Sleep. In press.
18. Miller MA, Cappuccio FP. Inflammation, sleep, obesity and cardiovas- 30. Moore P, Adler N, Williams D, Jackson J. Socioeconomic status and
cular disease. Curr Vasc Pharmacol. 2007;5:95102. health: the role of sleep. Psychosom Med. 2002;64:337344.
19. Wolk R, Somers VK. Sleep and the metabolic syndrome. Exp Physiol. 31. Groeger JA, Zijlstra FR, Dijk DJ. Sleep quantity, sleep difficulties and
2007;92:6778. their perceived consequences in a representative sample of some 2000
20. Scheer FA, Van Montgrans GA, van Someren EJ, Mairuhu G, Buijs RM. British adults. J Sleep Res. 2004;13:359 371.
Daily night-time melatonin reduces blood pressure in male patients with 32. Adams J. Socioeconomic position and sleep quantity in UK adults.
essential hypertension. Hypertension. 2004;43:192197. J Epidemiol Community Health. 2006;60:267269.
21. Zee PC, Turek FW. Sleep and health: everywhere and in both directions.
33. Patel SR, Malhotra A, Gottlieb DJ, White DP, Hu FB. Correlates of long
Arch Intern Med. 2006;166:1686 1688.
sleep duration. Sleep. 2006;29:881 889.
22. Marmot MG, Davey Smith G, Stansfeld S, Patel C, North F, Head J,
34. National Sleep Foundation. Sleep in America Poll 2005: Summary of
White I, Brunner E, Feeney A. Health inequalities among British civil
Findings. Washington, DC: National Sleep Foundation; 2005.
servants: the Whitehall II study. Lancet. 1991;337:13871393.
35. Egan BM. Sleep and hypertension: burning the candle at both ends really
23. Brazier JE, Harper R, Jones NM, OCathain A, Thomas KJ, Usherwood
T, Westlake L. Validating the SF-36 health survey questionnaire: new is hazardous to your health. Hypertension. 2006;47:816 817.
outcome measure for primary care. BMJ. 1992;305:160 164. 36. Knutson KL, Turek FW. The U-shaped association between sleep and
24. Narkiewicz K, Somers VK. The sympathetic nervous system and health: the 2 peaks do not mean the same thing. Sleep. 2006;29:878 879.
obstructive sleep apnea: implications for hypertension. J Hypertens. 37. Hauri PJ, Wisbey J. Wrist actigraphy in insomnia. Sleep. 1992;15:
1997;15:16131616. 293301.
Downloaded from http://hyper.ahajournals.org/ by guest on April 15, 2017
25. Fletcher EC. Sympathetic overactivity in the etiology of hypertension of 38. Lockley SW, Skene DJ, Arendt J. Comparison between subjective and
obstructive sleep apnea. Sleep. 2003;26:1519. actigraphic measurement of sleep and sleep rhythms. J Sleep Res. 1999;
26. Quan SF, Zee P. Evaluating the effects of medical disorders on sleep in 8:175178.
the older patient. Geriatrics. 2004;59:37 42. 39. Knutson KL, Spiegel K, Penev P, Van Cauter E. The metabolic conse-
27. Parry BL, Newton RP. Chronobiological basis of female-specific mood quences of sleep deprivation. Sleep Medicine Rev. 2007;11:163178.
disorders. Neuropsychopharmacology. 2001;25:S102S108. 40. Currie A, Cappuccio FP. Sleep in children and adolescents: a worrying
28. Baldwin CM, Kapur VK, Holberg CJ, Rosen C, Nieto FJ. Sleep Heart scenario. Can we understand the sleep deprivation obesity epidemic?
Health Study Group. Associations between gender and measures of Nutr Metab Cardiovasc Dis. 2007;17:230 232.
Gender-Specific Associations of Short Sleep Duration With Prevalent and Incident
Hypertension: The Whitehall II Study
Francesco P. Cappuccio, Saverio Stranges, Ngianga-Bakwin Kandala, Michelle A. Miller,
Frances M. Taggart, Meena Kumari, Jane E. Ferrie, Martin J. Shipley, Eric J. Brunner and
Michael G. Marmot
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In the Hypertension article by Cappuccio et al (Cappuccio FP, Stranges S, Kandala N-B, Miller
MA, Taggart FM, Kumari M, Ferrie JE, Shipley MJ, Brunner EJ, Marmot MG. Gender-specific
associations of short sleep duration with prevalent and incident hypertension. The Whitehall II
study. Hypertension. 2007;50:693700), the OR, 95% CI, and P values reported in the Abstract
and Results as OR: 2.01; 95% CI: 1.13 to 3.58; P 0.003 should be OR: 1.72; 95% CI: 1.07 to
2.75; P 0.037. These values are listed correctly in Table 2. The authors regret the error.
(Hypertension. 2007;50:e170.)
2007 American Heart Association, Inc.
Hypertension is available at http://hyper.ahajournals.org DOI: 10.1161/HYPERTENSIONAHA.107.009592
e170