CE: Swati; JH-D-19-00293; Total nos of Pages: 8;
JH-D-19-00293
Original Article
Blood pressure dipping and sleep quality in the
Wisconsin Sleep Cohort
Beini Lyu, Erika W. Hagen, Laurel A. Ravelo, and Paul E. Peppard
Aims: Nondipping blood pressure (BP) is associated with
higher risk for hypertension and advanced target organ
damage. Insomnia is the most common sleep complaint in
the general population. We sought to investigate the
association between sleep quality and insomnia and BP
nondipping cross-sectionally and longitudinally in a large,
community-based sample.
Methods: A subset of the Wisconsin Sleep Cohort
(n ¼ 502 for cross-sectional analysis and n ¼ 260 for
longitudinal analysis) were enrolled in the analysis.
Polysomnography measures were used to evaluate sleep
quality. Insomnia symptoms were obtained by
questionnaire. BP was measured by 24-h ambulatory BP
monitoring. Logistic regression models estimated cross-
sectional associations of sleep quality and insomnia with
BP nondipping. Poisson regression models estimated
longitudinal associations between sleep quality and
incident nondipping over a mean 7.4 years of follow-up.
Systolic and diastolic nondipping were examined
separately.
Results: In cross-sectional analyses, difficulty falling asleep,
longer waking after sleep onset, shorter and longer total
sleep time, lower sleep efficiency and lower rapid eye
movement stage sleep were associated with higher risk of
SBP and DBP nondipping. In longitudinal analyses, the
adjusted relative risks (95% confidence interval) of incident
systolic nondipping were 2.1 (1.3–3.5) for 1-h longer
waking after sleep onset, 2.1 (1.1–5.1) for 7–8 h total
sleep time, and 3.7 (1.3–10.7) for at least 8-h total
sleep time (compared with total sleep time 6–7 h), and
1.9 (1.1–3.4) for sleep efficiency less than 0.8,
respectively.
Conclusion: Clinical features of insomnia and poor sleep
quality are associated with nondipping BP. Our findings
suggested nondipping might be one possible mechanism
by which poor sleep quality was associated with worse
cardiovascular outcomes.
Keywords: blood pressure nondipping, hypertension,
insomnia, sleep quality, Wisconsin sleep cohort
Abbreviations: ABPM, ambulatory blood pressure
monitoring; AHI, apnea–hypopnea index; PSG,
polysomnography; REM, rapid eye movement; WASO,
waking after sleep onset
Journal of Hypertension
Copyright © 2019 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
INTRODUCTION
S
ystemic blood pressure (BP) varies with different
physiologic states and is typically 10–20% lower
during sleep compared with wake [1]. However,
some individuals do not experience this BP reduction
(BP ‘dipping’) during sleep. A nocturnal BP that decreases
less than 10% is defined as ‘nondipping’. Nondipping BP is
associated with higher risk for hypertension in a normo-
tensive population, and advanced target organ damage
and poor cardiovascular prognosis among hypertensive
patients [2–6].
Sleep has a ‘toning-down’ effect on a number of physio-
logic parameters, including the aforementioned effect of
sleep on BP [7]. There is some evidence that both day-to-
night and nighttime regulation of BP are associated with
autonomic changes occurring during the wake-sleep cycle,
suggesting that BP should be particularly sensitive to dis-
turbances occurring during sleep, especially in the pres-
ence of hyperactivation of the sympathetic nervous system,
such as that which may occur in people with insomnia [8].
Insomnia is the most common sleep complaint in the
general population, with prevalence estimates ranging from
5 to 50% [9]. Insomnia refers to the subjective experience of
insufficient restorative sleep due to difficulty falling asleep,
difficulty maintaining sleep or early awakening [10]. There
is emerging epidemiological evidence linking insomnia to
higher cardiovascular morbidity and mortality [11–13]. In
addition to subjective sleep complaints, objective measure-
ments by polysomnography (PSG) have been used to assess
sleep quality [14]. Studies have shown that PSG markers,
including decreased sleep duration, poorer sleep continu-
ity, total sleep time and longer sleep latency can be impor-
tant for a variety of clinical outcomes [15,16].
There are only a few small cross-sectional studies [17–
20], and no longitudinal studies that have assessed associ-
ations of insomnia and sleep quality with night-time BP
Journal of Hypertension 2019, 37:000–000
Department of Population Health Sciences, University of Wisconsin School of Medi-
cine and Public Health, Madison, Wisconsin, USA
Correspondence to Paul E. Peppard, PhD, Department of Population Health Sciences,
University of Wisconsin School of Medicine and Public Health, WARF Building, #611,
610 Walnut St., Madison, WI 53726, USA. Tel: +1 608 262 2680; e-mail: ppep-
pard@wisc.edu
Received 24 March 2019 Revised 30 August 2019 Accepted 21 September 2019
J Hypertens 37:000–000 Copyright ß 2019 Wolters Kluwer Health, Inc. All rights
reserved.
DOI:10.1097/HJH.0000000000002283
www.jhypertension.com 1
CE: Swati; JH-D-19-00293; Total nos of Pages: 8;
JH-D-19-00293
Lyu et al.
nondipping, which, as a precursor to cardiovascular disease
[2,4,21], could be one mechanism linking insomnia and
sleep quality with cardiovascular morbidity and mortality.
In the current study, we investigate whether self-reported
insomnia symptoms and objective measures of sleep qual-
ity: first, are cross-sectionally associated with BP nondip-
ping; and second, predict incident BP nondipping at an
average 7.4 years (range: 3–15 years) follow-up in the
Wisconsin Sleep Cohort study, an ongoing investigation
of the natural history, causes and consequences of common
sleep disorders in a community-based sample of adults.
MATERIALS AND METHODS
Participants and data collection
Briefly, study participants composed a probability sample
of employees of four Wisconsin state agencies, aged 30–60
years at the time of recruitment. Participants were invited to
undergo overnight studies at baseline and follow-up at
approximate 4-year intervals. All study volunteers provided
signed informed consent prior to participating in study
protocols. The informed consent documents and study
protocols for the ongoing Wisconsin Sleep Cohort Study,
described in detail previously [22], were reviewed for
compliance with the principles outlined in the Declaration
of Helsinki and were approved by the University of Wis-
consin-Madison Health Science Institutional Review Board.
Of 1533 baseline cohort participants, 502 met the inclu-
sion criteria for the cross-sectional analysis: first, having an
overnight PSG study; and second, having ambulatory BP
monitoring (ABPM) data collected within less than 5
months of PSG (mean ¼ 3.7 months) (Supplemental Fig.
1A, http://links.lww.com/HJH/B158). Self-reported insom-
nia symptoms were assessed during the overnight PSG
study visit. Participants taking antihypertensive medications
were excluded; thus, the final cohort for the cross-sectional
analysis included 399 participants.
Study participants with two or more ABPM studies were
included in the longitudinal analyses. Among 702 participants
with baseline ABPM studies, 368 men and women completed
two or more 24-h ABPM follow-up studies at follow-up
intervals ranging from 3 to 15 years (Supplemental Fig. 1B,
http://links.lww.com/HJH/B158). Reasons for lack of follow-
up data included: not all baseline ABPM participants were
invited for follow-up studies; refusal (mostly due to inconve-
nience); laboratory scheduling difficulties; and insufficient
wear-time (e.g., a lack of sleeping ABPM observations). For
analysis of incident nondipping BP, we excluded participants
who were nondipping at their baseline ABPM studies
(assessed separately for SBP and DBP analyses). We also
excluded participants who were on antihypertensive medi-
cations at baseline. The remaining sample consisted of 260
participants to follow for development of SBP nondipping
and 281 to follow for development of DBP nondipping.
Sleep studies were conducted at the University of Wis-
consin-Madison Clinical Research Unit, in a sleep-labora-
tory suite with home-like bedrooms.
Subjective sleep quality
Subjective sleep quality was assessed with responses to
questions about insomnia symptoms and sleep satisfaction.
2 www.jhypertension.com
Copyright © 2019 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
The health questionnaire and mailed surveys included four
items on insomnia: difficulty in getting to sleep (referred to
as difficulty in falling asleep or initiating sleep), waking up
repeatedly during the night (repeated nocturnal awaken-
ings), waking up too early in the morning and being unable
to get back to sleep (awakening too early), and waking up
during the night and having a hard time getting back to
sleep (difficulty getting back asleep). Response categories
were never or rarely (once per month), sometimes (two to
four times per month), often (five to 15 times per month),
and almost always (16–30 times per month). Individual
symptom severity was defined with a dichotomous vari-
able: often/almost always (5 times per month) vs. some-
times/less (<5 times per month). General insomnia (0, 1)
was defined as having any of the insomnia symptoms at a
frequency of ‘often or almost always’. Surveys also included
questions about how often sleep was satisfactory (most of
the time, some of the time, not usually or never), and the
frequency of naps.
For the longitudinal analyses, we used two consecutive
surveys to define insomnia. Participants were excluded
from the longitudinal analyses of subjective sleep problems
if they did not complete two or more surveys or if the self-
report of insomnia or sleep complaints were not consistent
on these surveys (n ¼ 79 excluded from the SBP cohort and
n ¼ 87 excluded from the DBP cohort).
Polysomnographically assessed markers
Objective data on sleep latency, waking after sleep onset
(WASO), sleep efficiency and total sleep time were
obtained during the overnight protocol by means of full
18-channel PSG (Grass Heritage PSG Digital Sleep System;
Grass Technologies, Warwick, Rhode Island, USA). Sleep
stage for each 30-s epoch was scored according to conven-
tional criteria [23]. ‘Sleep latency’ was defined as the amount
of time (minutes) from ‘lights off’ to the first of three
consecutive epochs of stage 1 sleep or the first epoch of
any other stage of sleep; ‘waking after sleep onset’ as the
amount of time (minutes) spent awake after first sleep
onset; ‘total sleep time’ as the total amount of time spent
sleeping (minutes); and ‘sleep efficiency’ (%) as the pro-
portion of total sleep time out of total duration of time in
bed from ‘lights out.’ Total sleep time was analyzed as a
continuous variable, as well as a categorical variable with
less than 6, 6–7 (reference), 7–8 and more than 8 h of sleep.
24-H ambulatory blood pressure monitoring
The baseline 24-h ABPM was performed within 4 months
(range: 0.03–5 months) following the overnight sleep
study, with the Accutracker II (Suntech Medical Instru-
ments/Eutectics Electronics, Raleigh, North Carolina,
USA). Details of the study protocol and ABPM quality data
have been previously published [24]. Briefly, ABPM read-
ings were obtained at random intervals averaging every 15–
20 min during wakefulness and every 30 min during sleep.
Individual wake and sleep mean BPs were computed by
averaging ABPM measurements during sleep and wake
defined by participants’ recorded sleep and wake times.
The time participants reported falling asleep and waking
were used to establish the ABPM sleep period. SBP
Volume 37  Number 1  Month 2019
CE: Swati; JH-D-19-00293; Total nos of Pages: 8;
JH-D-19-00293
nondipping was defined as having a ratio of mean systolic
sleep BP to mean systolic wake BP ratio more than 0.9. DBP
nondipping was defined analogously.
For longitudinal analyses, incidence of BP nondipping
status was prospectively examined among 260 participants
for SBP and 281 participants for DBP over the entire follow-
up time period. An outcome variable was created to repre-
sent the change in dipping status: no development of
nondipping over the entire follow-up or incident nondip-
ping (development of nondipping during any subsequent
follow-up visit). Those individuals who fluctuated between
dipping, nondipping, and dipping again were excluded
(n ¼ 11 for SBP and n ¼ 8 for DBP). The mean follow-up
period was 7.4 years. A variable for the length of time of
participants’ follow-up intervals was used in all analyses to
account for individual differences.
Other data collection
BMI was calculated from measured body weight and height
(kg/m2). Participants completed a questionnaire on the
night of the sleep study regarding the following covariates:
current smoking, alcohol consumption (number of alco-
holic drinks per week), caffeine consumption (number of
caffeinated drinks per week), self-reported hours of exer-
cise, and reported usual sleep duration on weekdays and
weekends. Habitual sleep time in hours was calculated as
the weighted average of weekday and weekend sleep time
[i.e. (5  weekday þ 2  weekend)/7]. Alcohol and caffeine
consumption were categorized into 0, 1–2 and more than
two drinks/day. Self-reported physician-diagnosed chronic
illness (coronary heart disease, hypertension and diabetes)
and medications, including sedatives and antihyperten-
sives, were obtained. On the same evening as the overnight
studies, participants completed the Zung Self-Rating
Depression Scale [25] and provided information on regu-
larly taken medications for depression. As previously
reported [16], we used a ‘modified’ Zung scale that excluded
two items (‘I have trouble sleeping through the night’ and ‘I
get tired for no reason’) which may indicate insomnia and
result in a built-in association between insomnia and
depression.
Sleep-disordered breathing status was assessed by PSG
and summarized as the apnea–hypopnea index (AHI).
Using conventional cut points [23], the AHI was categorized
as less than five events/h (little or no sleep-disordered
breathing), five to less than 15 events/h (mild) or at least
15 events/h (moderate or worse). Individuals who used
continuous positive airway pressure therapy on the over-
night PSG were categorized with the moderate or worse
sleep-disordered breathing group. Counts of sleep leg
movements per hour of sleep were recorded. In 2014, a
question about times of nocturia was added to the sleep
questionnaire and nocturia frequency (1 vs. >1 times per
night) was collected. On average, nocturia measurement
was collected 10 years after BP measurement.
Data analysis
All analyses were performed with SAS software, release 9.4
(SAS Institute Inc., Cary, North Carolina, USA). Between-
group comparisons were performed by two sample t test or
by Wilcoxon signed rank tests (for non-normally distributed
Journal of Hypertension
Copyright © 2019 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Blood pressure dipping and sleep quality
variables). Assessment of normality was performed using
the Shapiro–Wilk test. In cross-sectional analyses, linear
regression was performed to estimate the association
between these markers and the sleep/awake BP ratio, for
systolic and diastolic separately; logistic regression was
performed to estimate the association between sleep qual-
ity markers and BP nondipping. Multivariable models also
included the following covariates: age; sex; BMI; current
smoking; alcohol and caffeine consumption; chronic ill-
nesses, including coronary heart disease, hypertension,
diabetes, depression; nap (1 time vs. >1 times per
day); self-reported hours of weekly physical exercise; sleep
apnea; use of sedative medications; leg movements; and the
interval between the ABPM data collection and the over-
night study visit, when the sleep data were collected.
For longitudinal analyses, Poisson regression models
were performed to estimate the associations between sleep
quality and incident nondipping over a mean (SD) 7.4 (3.1)
years follow-up, for systolic nondipping and diastolic non-
dipping separately. In addition to baseline insomnia
markers, the models included the following covariates:
age, sex, BMI at baseline, BMI at follow-up, current smok-
ing, alcohol and caffeine consumption, hypertension based
on data from baseline visit, duration of follow-up, AHI, nap,
physical exercise, use of sedative medications, leg move-
ments and whether or not an individual was on antihyper-
tensive medication at any time during the follow-up period.
RESULTS
Characteristics of participants
Demographic and clinical characteristics of the study par-
ticipants are shown in Table 1. In the cross-sectional study,
21% of participants were defined as having nondipping
SBP, and 38% defined as having insomnia symptoms.
Participants with insomnia symptoms were on average
older, had a higher prevalence of depression, and were
more likely to be female, compared with participants with-
out insomnia. No significant differences were noted
between participants with insomnia and those without with
respect to BMI, smoking, alcohol and coffee consumption,
self-reported physician-diagnosed chronic illness or AHI.
Participants with insomnia also had higher SBP and DBP
sleep/awake ratios, a higher sleeping heart rate, and were
more likely to have nondipping DBP.
Participants with insomnia symptoms had shorter self-
reported sleep duration and less satisfaction with their usual
sleep than participants who did not report insomnia symp-
toms (Table 2). Repeated nocturnal awakening was the
most frequently reported insomnia symptom. Participants
with insomnia symptoms had shorter PSG-measured sleep
duration, slightly greater WASO and significantly less sleep
efficiency. No significant differences were noted in different
percent of time in sleep stages between participants with
and without insomnia.
Cross-sectional associations of sleep
characteristics and blood pressure nondipping
The unadjusted and adjusted odds ratios (ORs) for sleep
characteristics and SBP and DBP nondipping are shown in
Table 3. Difficulty falling asleep was associated with both
www.jhypertension.com 3
CE: Swati; JH-D-19-00293; Total nos of Pages: 8;
JH-D-19-00293

Lyu et al.

TABLE 1. Study sample demographic and characteristics stratified by insomnia (n ¼ 399)

Total No insomnia Insomnia
N (%) 399 247 (61.9) 152 (38.1)
Sex, female, N (%) 167 (41.9) 94 (38.1) 73 (48.0)
Age (years) 51.7  8.3 51.1  8.0 52.8  8.6
BMI (kg/m2) 30.2  6.3 30.4  6.4 29.8  6.2
Sedative medication, N (%) 13 (3.3) 7 (2.8) 6 (4.0)
Current smoker, N (%) 71 (17.8) 42 (17.0) 29 (19.2)
Alcohol, >2 drinks/week, N (%) 162 (40.7) 100 (40.5) 62 (41.1)
Caffeine, >2 drinks/week, N (%) 212 (53.3) 130 (52.6) 82 (54.3)
Hypertension, N (%) 32 (8.0) 20 (8.1) 12 (7.9)
Diabetes, N (%) 15 (3.8) 10 (4.1) 5 (3.3)
Coronary heart disease, N (%) 11 (2.8) 4 (1.6) 7 (4.6)
Depression, N (%) 87 (22.5) 42 (17.6) 45 (30.4)
Sleep SBP (mmHg) 108.0  12.4 107.5  11.5 108.7  13.7
Sleep DBP (mmHg) 62.3  7.8 61.9  7.4 63.0  8.3
Awake SBP (mmHg) 126.7  12.2 127.2  11.6 126.0  13.1
Awake DBP (mmHg) 76.9  7.5 77.0  7.1 76.7  8.1
Ratio of SBP sleep/awake 0.85  0.06 0.85  0.06 0.86  0.06
Ratio of DBP sleep/awake 0.81  0.07 0.80  0.07 0.82  0.08
SBP nondipper, N (%) 82 (20.6) 46 (18.6) 36 (23.7)
DBP nondipper, N (%) 46 (11.5) 20 (8.1) 26 (17.1)
Sleeping heart rate (bpm) 65.3  9.1 64.7  9.3 66.3  8.6
Waking heart rate (bpm) 76.8  9.7 76.8  9.5 76.8  10.2
AHI < 5 174 (43.6) 112 (45.3) 62 (40.8)
5  AHI < 15 132 (33.1) 81 (32.8) 51 (33.5)
AHI  15 93 (23.3) 54 (21.9) 39 (25.7)

Continuous variables were presented as mean  SD. AHI, apnea–hypopnea index.


P < 0.05 for comparison between not insomnia and insomnia groups.

P < 0.01 for comparison between not insomnia and insomnia groups.

SBP nondipping after adjusting for possible cofounders
[OR ¼ 2.6, 95% confidence interval (CI), 1.2–5.5] and
DBP nondipping (OR ¼ 4.5, 95% CI, 1.9–10.8). Insomnia
was associated with DBP nondipping (OR ¼ 2.4, 95% CI,
1.2–4.7) but not significantly with SBP nondipping.
PSG-measured wake after sleep onset, sleep efficiency
and % time in rapid eye movement (REM) sleep all were
associated with SBP and DBP nondipping in unadjusted
models. After full adjustment, the association of WASO and
sleep efficiency and SBP nondipping remained [OR (95%
CI) ¼ 1.6 (1.1, 2.3) and 0.7 (0.5, 0.9) for WASO and sleep
efficiency, respectively]. In addition, the fully adjusted
associations of WASO and % time in REM sleep and DBP
nondipping were not attenuated [OR (95% CI) ¼ 1.6 (0.98,
2.5) and 0.4 (0.2, 0.8), respectively]. Compared with par-
ticipants with total sleep time of 6–7 h, those sleeping less
than 6 h per night had an adjusted OR for SBP nondipping
of 2.0 (95% CI, 1.1–3.9), and those sleeping 7–8 h had an
adjusted OR of 0.3 (95% CI, 0.1–0.9).
SBP and DBP nondipping were not significantly associ-
ated with difficulty getting back to sleep, early morning
awakening, repeated nocturnal awakening, sleep latency

TABLE 2. Study sample sleep characteristics stratified by insomnia (n ¼ 399)

Total No insomnia Insomnia
N (%) 399 247 (61.9) 152 (38.1)
Habitual sleep time (h) 7.1  0.9 7.2  0.8 6.9  0.9
Most of time satisfied with sleep, N (%) 269 (67.4) 203 (82.2) 66 (43.4)
Difficulty getting back to sleep, N (%) 53 (13.3) 0 53 (34.9)
Difficulty falling sleep, N (%) 46 (11.5) 0 46 (30.3)
Early morning awakenings, N (%) 59 (14.8) 0 59 (38.8)
Repeated nocturnal awakenings, N (%) 111 (27.8) 0 111 (73.0)
Nap >1 time per day 239 (59.9) 141 (57.1) 98 (64.5)
PSG assessed markers of insomnia
Sleep latency (h) 0.2  0.2 0.2  0.2 0.2  0.2
WASO (h) 1.0  0.7 1.0  0.7 1.0  0.6
Total sleep time (h) 6.5  1.0 6.6  1.0 6.3  0.9
Sleep efficiency (%) 83.9  9.6 84.6  9.8 82.8  9.0
% of stage REM sleep 18.1  6.1 18.2  5.8 17.8  6.5
% of stage 1 sleep 9.9  6.3 9.9  6.1 10.0  6.7
% of stage 2 sleep 64.2  9.0 64.0  8.41 64.6  9.9
% of stage 3/4 sleep 7.7  7.2 7.9  7.1 7.5  7.3

Continuous variables were presented as mean  SD. PSG, polysomnography, REM, rapid eye movement; WASO, waking after sleep onset.

P < 0.05 for comparison between not-insomnia and insomnia groups.

P < 0.01 for comparison between not-insomnia and insomnia groups.

4 www.jhypertension.com Volume 37  Number 1  Month 2019

Copyright © 2019 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
CE: Swati; JH-D-19-00293; Total nos of Pages: 8;
JH-D-19-00293

Blood pressure dipping and sleep quality

TABLE 3. Cross-sectional associations between SBP and DBP nondipping and sleep characteristics
Systolic nondipping Diastolic nondipping
OR (95% CI) OR (95% CI)
Unadjusted Adjusted Unadjusted Adjusted
Self-report symptoms
Difficulty getting back to sleep 1.3 (0.7, 2.6) 1.5 (0.7, 3.0) 2.0 (0.9, 4.4) 1.9 (0.8, 4.4)
Difficulty falling sleep 2.3 (1.2, 4.5) 2.6 (1.2, 5.5) 3.8 (1.8, 7.9) 4.5 (1.9, 10.8)
Early morning awakenings 1.0 (0.5, 2.0) 1.0 (0.5, 2.4) 1.1 (0.4, 2.5) 1.2 (0.5, 3.0)
Repeated nocturnal awakenings 1.1 (0.6, 1.9) 1.1 (0.6, 2.0) 1.6 (0.9, 3.1) 1.8 (0.9, 3.7)
Insomnia (no. of symptoms)
0 Ref Ref Ref Ref
1 1.1 (0.6, 2.1) 1.3 (0.6, 2.6) 1.7 (0.8, 3.8) 1.7 (0.7, 4.2)
2 2.5 (1.1, 5.4) 2.9 (1.2, 6.8) 4.8 (2.0, 11.4) 5.6 (2.1, 15.3)
3 0.9 (0.3, 2.8) 0.9 (0.3, 3.2) 0.5 (0.1, 3.9) 0.5 (0.06, 4.2)
4 1.5 (0.4, 5.6) 1.7 (0.4, 6.9) 3.7 (0.9, 14.6) 5.5 (1.2, 25.5)
Habitual sleep time (h) 1.0 (0.95, 1.12) 0.8 (0.6, 1.1) 0.9 (0.7, 1.4) 0.9 (0.6, 1.3)
PSG assessed markers
Sleep latency (h) 2.6 (0.9, 7.8) 2.5 (0.7, 8.7) 1.3 (0.3, 5.8) 1.4 (0.3, 7.0)
WASO (h) 1.5 (1.1, 2.1) 1.6 (1.1, 2.3) 1.5 (1.02, 2.3) 1.6 (0.98, 2.5)
Total sleep time
TST < 6 h 1.9 (1.6, 3.4) 2.0 (1.1, 3.9) 1.3 (0.7, 2.6) 1.3 (0.6, 2.7)
6 h  TST < 7 h 1.0 (Ref) 1.0 (Ref) 1.0 (Ref) 1.0 (Ref)
7 h TST < 8 h 0.4 (0.2, 0.9) 0.3 (0.1, 0.9) 0.4 (0.2, 1.2) 0.3 (0.1, 1.01)
TST  8 h 1.6 (0.6, 4.0) 1.7 (0.6, 4.6) 0.3 (0.054, 2.1) 0.2 (0.03, 2.1)
Sleep efficiency, per 10% increment 0.7 (0.5, 0.9) 0.7 (0.5, 0.9) 0.7 (0.6, 0.9) 0.7 (0.5, 1.0)
% of REM sleep, per 10% increment 0.6 (0.4, 0.9) 0.7 (0.4, 1.0) 0.5 (0.3, 0.8) 0.4 (0.2, 0.8)

Analysis adjusted for age, sex, BMI, smoke, caffeine and alcohol consumption, diabetes, coronary heart disease, hypertension, depression, use of sedative medication, nap frequency,
self-reported hours of weekly physical exercise, AHI, leg movements, and time between ABPM and insomnia survey. AHI, apnea–hypopnea index; CI, confidence interval; OR, odds ratio;
REM, rapid eye movement; TST: total sleep time WASO, waking after sleep onset.

P < 0.05.

P < 0.01.

and other sleep stages. When further adjusting for nocturia,
most of the associations remained similar (data not shown).
However, difficulty falling asleep was more strongly asso-
ciated with both SBP nondipping (OR ¼ 3.6, 95% CI, 1.6–
8.3) and DBP nondipping (OR 5.7, 95% CI, 2.2–14.7) with
adjustment for nocturia.
Longitudinal association of sleep quality and
blood pressure nondipping
Those with longitudinal 24-h ABPM data (2 data points)
had a higher average BMI and higher prevalence of SBP and
DBP nondipping than the total sample with ABPM (1 data
point) (Supplemental Table 1, http://links.lww.com/HJH/
B158). No significant differences in baseline characteristics
were found between systolic cohort participants included
in the subjective insomnia analysis and those excluded
(Supplemental Table 2, http://links.lww.com/HJH/B158).
Participants excluded from the subjective insomnia analy-
ses (due to missing insomnia data) in the diastolic cohort
were less likely to have ever used antihypertensive medi-
cation than those who remained in the analyses. (Supple-
mental Table 3, http://links.lww.com/HJH/B158.)
The mean (range) follow-up period was 7.4 (3–15)
years, during which 49 (20%) developed systolic nondip-
ping and 36 (13%) developed diastolic nondipping. Gen-
eral insomnia (having any of the four symptoms) and the
specific symptom of difficulty falling asleep at baseline
were both associated with higher risk (though nonsignifi-
cant) of incident SBP and DBP nondipping (Tables 4 and 5).
No significant associations were found between other sleep
complaints and BP nondipping (data not shown). Longer
duration of WASO was associated with greater incident SBP
nondipping risk (OR ¼ 2.1, 95% CI, 1.3–3.5). Adjusted SBP
nondipping risk was two to three-fold higher for partic-
ipants with total sleep time more than 8 h vs. those with total
sleep time 6–7 h. Higher risk of SBP nondipping was
observed for lower sleep efficiency (<0.8) in adjusted
analyses (OR ¼ 1.9, 95% CI, 1.1–3.4). The associations
remained similar after adjusting for nocturia. There were
no significant associations between sleep quality markers
and DBP nondipping in adjusted analyses.
Sleep blood pressure to wake blood pressure
ratio
In addition to testing the dichotomous dipping outcomes,
we also evaluated the associations of sleep quality markers
and the BP sleep/wake ratios as continuous variables
(Supplemental Table 4, http://links.lww.com/HJH/B158).
The results of these analyses were consistent with the
results of the main analyses of SBP and DBP nondipping.
DISCUSSION
In this population-based study, we documented significant
cross-sectional associations of subjective and objective
sleep quality markers with BP nondipping. In cross-sec-
tional analyses, the blunted BP fall occurred in association
with the symptom of difficulty falling asleep, longer dura-
tion of WASO and shorter total sleep time. Lower sleep
efficiency was associated with risk of SBP nondipping while
lower %REM sleep was associated with DBP nondipping. In
longitudinal analyses, longer WASO, longer total sleep time
and lower sleep efficiency were associated with higher risk

Journal of Hypertension www.jhypertension.com 5

Copyright © 2019 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
CE: Swati; JH-D-19-00293; Total nos of Pages: 8;
JH-D-19-00293

Lyu et al.

TABLE 4. Relative risk of SBP nondipping at 7.4-year follow-up according to sleep quality
RR (95% CI)
Characteristics Total sample, n Incident nondipping, n (%) Unadjusted Adjusted
Insomnia
Yes 55 14 (25.5) 1.5 (0.8, 3.1) 1.4 (0.5, 3.0)
No 115 19 (16.5) 1.0 (Ref) 1.0 (Ref)
Missing 79
Difficulty falling asleep
Often/Almost always 15 4 (26.7) 1.4 (0.5, 4.1) 1.3 (0.4, 3.9)
Sometimes/Less 184 26 (18.5) 1.0 (Ref) 1.0 (Ref)
Missing 50
Sleep latency (h) 249 49 (19.7) 1.1 (0.4, 3.7) 1.1 (0.3, 3.5)
WASO (per hour) 249 48 (19.7) 1.7 (1.1, 2.6) 2.1 (1.3, 3.5)
Total sleep time
TST < 6 h 85 18 (21.2) 1.9 (0.9, 4.0) 1.8 (0.9, 4.1)
6 h  TST < 7 h 96 11 (11.5) 1.0 (Ref) 1.0 (Ref)
7 h  TST < 8 h 53 14 (26.4) 2.3 (1.0, 5.1) 2.1 (1.1, 5.1)
TST  8 h 15 6 (40.0) 3.5 (1.3, 9.4) 3.7 (1.3, 10.7)
Sleep efficiency
Sleep efficiency 0.8 191 32 (16.8) 1.0 (Ref) 1.0 (Ref)
Sleep efficiency <0.8 58 17 (29.3) 1.8 (1.0, 3.3) 1.9 (1.1, 3.4)

Analysis adjusted for baseline age, sex, BMI at baseline and follow-up, current smoking, hypertension, alcohol consumption from the baseline visit; duration of follow-up; self-reported
hours of weekly physical exercise, use of sedative medication, and whether or not an individual was on antihypertensive medication at any time during the follow-up time period, nap
frequency, leg movements, and AHI. AHI, apnea–hypopnea index; CI, confidence interval; RR, relative risk; TST, total sleep time; WASO, waking after sleep onset.

P < 0.05.

P ¼ 0.05.

of incident SBP nondipping. These findings suggest that
sleep quality – measured both subjectively and objectively
– may have a role in the development of BP nondipping.
Our results are consistent with other published cross-
sectional studies. Loredo et al. [26] observed that nocturnal
BP nondipping correlated with polysomnographic indices
of poor sleep, including less stage 4 sleep and longer
duration of WASO. Hypertensive nondippers also had less
stage 4 sleep and higher microarousal rates [27]. Yilmaz
et al. [17] found that in younger hypertensive participants,
sleep quality, sleep efficiency and sleep disturbance scores
measured by the Pittsburgh Sleep Quality Index were
significantly higher in nondippers. Blunted SBP dipping
also has been observed in normotensive participants with
chronic insomnia, and is associated with higher activity in
electroencephalography b frequency [18]. Matthews et al.
[19] found that greater sleep/awake ratios of BP were
associated with more fragmented sleep, more light sleep
and less REM sleep. Another study found that poor sleep
quality, stressful status and higher activation of the

TABLE 5. Relative risk of DBP nondipping at 7.4-year follow-up according to sleep quality
RR (95% CI)
Characteristics Total sample, n Incident nondipping, n (%) Unadjusted Adjusted
Insomnia
Yes 62 11 (17.7) 1.5 (0.7, 3.2) 1.3 (0.5, 3.2)
No 124 15 (12.1) 1.0 (Ref) 1.0 (Ref)
Missing 87
Difficulty falling asleep
Often/almost always 18 4 (22.2) 1.9 (0.7, 5.5) 1.6 (0.5, 5.4)
Sometimes/less 198 23 (11.6) 1.0 (Ref) 1.0 (Ref)
Missing 57
Sleep latency (h) 273 36 (13.2) 0.5 (0.05, 3.7) 0.5 (0.05, 4.0)
WASO (per hour) 273 36 (13.2) 0.9 (0.5, 1.7) 1.00 (0.5, 2.2)
Total sleep time
TST < 6 h 91 9 (9.9) 0.7 (0.3, 1.7) 0.8 (0.3, 1.9)
6 h  TST < 7 h 104 14 (13.5) 1.0 (Ref) 1.0 (Ref)
7 h  TST < 8 h 62 8 (12.9) 1.0 (0.4, 2.3) 1.0 (0.4, 2.4)
TST  8 h 16 5 (31.3) 2.3 (0.8, 6.4) 2.1 (0.7, 6.7)
Sleep efficiency
Sleep efficiency 0.8 213 28 (13.2) 1.0 (Ref) 1.0 (Ref)
Sleep efficiency <0.8 60 8 (13.3) 1.0 (0.5, 2.3) 1.2 (0.5, 2.8)

Analysis adjusted for baseline age, sex, BMI at baseline and follow-up, current smoking, hypertension, alcohol consumption from the baseline visit; duration of follow-up; self-reported
hours of weekly physical exercise, use of sedative medication, and whether or not an individual was on antihypertensive medication at any time during the follow-up time period, nap
frequency, leg movements, and AHI. AHI, apnea–hypopnea index; CI, confidence interval; RR, relative risk; TST, total sleep time; WASO, waking after sleep onset.

6 www.jhypertension.com Volume 37  Number 1  Month 2019

Copyright © 2019 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
CE: Swati; JH-D-19-00293; Total nos of Pages: 8;
JH-D-19-00293
sympathetic nervous system were predictors of nondipping
hypertension [20].
We also found that, compared with sleep time that was
between 6 and 7 h, shorter and longer sleep time both were
associated with higher risk of SBP nondipping in cross-
sectional and longitudinal analyses. Studies have shown
that short and long self-reported sleep durations (compared
with 6–8 h) are associated with an increased risk of cardio-
vascular events and all-cause mortality [28,29]. Our study
and the results from these other published studies are
consistent with a U-shaped association of sleep duration
with SBP nondipping and mortality, with worse outcomes
at both ends of the distribution.
Our findings, as well as prior findings, of an association
between sleep quality and nocturnal nondipping are
important because of demonstrated associations between
nondipping and advanced target organ damage and poor
cardiovascular prognosis [4,5,21]. Studies have underscored
a significant association between symptoms of insomnia
and long-term cardiovascular mortality, independent of
identified risk factors [12,30]. Difficulty falling asleep was
found to predict cardiovascular mortality in a middle-aged
population [30,31]. These data suggest that, as with other
cardiovascular risk factors, poor sleep quality may exert
negative effects on the cardiovascular system over a long
time before onset of overt disease.
Our data suggest that nondipping may be one of several
possible mechanisms by which such outcomes may be
initiated or exacerbated among people with poor sleep
quality. Studies have shown that individuals with chronic
insomnia suffer from increased arousal and sympathetic
activation, implying that they could be at increased risk for
development of coronary artery disease [13,32]. The activity
of the hypothalamic–pituitary–adrenal axis and the
sympathetic nervous system have been found to relate
positively to the degree of objectively assessed sleep dis-
turbance [33]. It is possible the presence of higher nocturnal
BP and lack of dipping could induce a persistently
higher cardiovascular burden, and lead to cardiovascular
damage and increase long-term cardiovascular risk. Exam-
ining dipping patterns has been suggested as part of hyper-
tension treatment guidelines [34]. Evidence suggests that
chronotherapy to reverse a nondipping pattern back to a
dipping pattern is feasible and useful [35,36]. An alternative
(though not mutually exclusive) interpretation of our find-
ings is that BP nondipping and insomnia may be parallel
epiphenomena of an underlying derangement of auto-
nomic nervous system function (in which case, e.g., treat-
ment of insomnia or sleep disturbance may not affect
nondipping status if the underlying cause of both remains
unaltered).
Our study has several strengths. First, to our knowledge,
this study is the first to investigate the longitudinal associa-
tion between sleep quality and BP nondipping, with sleep
quality measured before the emergence of nondipping
status. This strengthens the evidence that sleep quality
might play a causal role in the development of systolic
nondipping. Second, our study was performed in a com-
munity-based cohort, enabling us to measure the associa-
tion of sleep quality and nondipping in a nonclinical
population. Third, our data were based on ABPM using
Journal of Hypertension
Copyright © 2019 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Blood pressure dipping and sleep quality
actual sleep time and wake time recorded by participants
and not arbitrary preset times. This allowed for better
accuracy in defining sleep and wake BP. Lastly, we were
able to control for confounding effects of many potentially
important covariates, such as sleep-disordered breathing,
hypertension, smoking, alcohol consumption, physical
activity, BMI and change in BMI over time.
Our study has limitations. One important limitation is the
small sample size in our longitudinal analysis. Only 49
participants developed SBP nondipping. Larger study sam-
ples yielding greater numbers of incident nondipping
events are warranted for confirmation of our findings.
Second, we did not follow-up all participants who had a
baseline 24-h BP study. Our analysis of the population
characteristics in the total eligible follow-up sample vs.
the actual follow-up sample showed a higher BMI and
higher percentage of SBP and DBP nondipping in the total
sample. However, we adjusted for baseline and follow-up
BMI, and all the baseline nondippers were excluded for the
longitudinal analysis. It is possible that the difference
reflects better health among those who underwent multiple
follow-up ABPM assessments and may have led to fewer
cases of nondipping. Third, our objective measures of sleep
quality are based on a single night of PSG. If participants
with nondipping BP, compared with participants with
dipping BP, had more trouble sleeping in the laboratory,
their sleep quality could be relatively underestimated.
However, participants were asked to compare their sleep
during the PSG night with their usual night’s sleep (much
worse, worse, about the same, better, much better), and we
found no difference by BP dipping status. Fourth, despite
adjusting for many variables, there may have been other
potential cofounding factors associated with both sleep
quality and nondipping that were not accounted (or fully
accounted) for, such as nocturia and periodic limb move-
ments. Participants with nocturia had a lesser drop in BP
during sleep compared with those without nocturia [37,38],
and generally have lower sleep quality [39]. Though asso-
ciations between sleep quality and nondipping remained
similar after we further adjusted for nocturia, we might not
be able to fully account for the confounding given the time
gap between BP and nocturia assessments.
Our findings of the longitudinal association of sleep
quality with nocturnal SBP nondipping may have clinical
and public health relevance, since insomnia, poor sleep
quality and hypertension are prevalent in the general
population [10,40]. Our findings are consistent with a
potential cause–effect relationship between poor sleep
quality and SBP nondipping; SBP nondipping may be
one mechanism by which sleep quality is associated with
poor cardiovascular outcomes; and sleep quality may be
relevant for both quality of life and cardiovascular health.
ACKNOWLEDGEMENTS
We thank the staff and participants of the Wisconsin Sleep
Cohort for their important contributions and Drs K. Mae Hla
and Terry Young for oversight of the ABPM data collection.
The current work was supported by the National Heart,
Lung, and Blood Institute (R01HL62252), National Institute
on Aging (1R01AG036838) and the National Center for
www.jhypertension.com 7
CE: Swati; JH-D-19-00293; Total nos of Pages: 8;
JH-D-19-00293
Lyu et al.
Research Resources (1UL1RR025011) at the US National
Institutes of Health.
Conflicts of interest
The article has not been published and is not being con-
sidered for publication elsewhere, in whole or in part, in
any language. There are no relevant conflicts of interest on
the part of any study authors. There are no relevant finan-
cial, personal or professional relationships with other peo-
ple or organizations to disclose.
REFERENCES
1. Parati G, Ochoa JE, Lombardi C, Bilo G. Assessment and management
of blood-pressure variability. Nat Rev Cardiol 2013; 10:143.
2. Fagard RH, Celis H, Thijs L, Staessen JA, Clement DL, De Buyzere ML,
et al. Daytime and nighttime blood pressure as predictors of death and
cause-specific cardiovascular events in hypertension. Hypertension
2008; 51:55–61.
3. Boggia J, Li Y, Thijs L, Hansen TW, Kikuya M, Björklund-Bodegård K,
et al. Prognostic accuracy of day versus night ambulatory blood
pressure: a cohort study. Lancet 2007; 370:1219–1229.
4. Routledge FS, McFetridge-Durdle JA, Dean C. Night-time blood pres-
sure patterns and target organ damage: a review. Can J Cardiol 2007;
23:132–138.
5. Udani S, Lazich I, Bakris GL. Epidemiology of hypertensive kidney
disease. Nat Rev Nephrol 2011; 7:11.
6. Ohkubo T, Hozawa A, Yamaguchi J, Kikuya M, Ohmori K, Michimata
M, et al. Prognostic significance of the nocturnal decline in blood
pressure in individuals with and without high 24-h blood pressure: the
Ohasama study. J Hypertens 2002; 20:2183–2189.
7. Tobaldini E, Costantino G, Solbiati M, Cogliati C, Kara T, Nobili L, et al.
Sleep, sleep deprivation, autonomic nervous system and cardiovascu-
lar diseases. Neurosci Biobehav Rev 2017; 74:321–329.
8. Thomas SJ, Calhoun D. Sleep, insomnia, and hypertension: current
findings and future directions. J Am Soc Hypertens 2017; 11:122–129.
9. Morin CM, Benca R. Chronic insomnia. Lancet 2012; 379:1129–1141.
10. Ohayon MM. Epidemiology of insomnia: what we know and what we
still need to learn. Sleep Med Rev 2002; 6:97–111.
11. Chien KL, Chen PC, Hsu HC, Su TC, Sung FC, Chen MF, et al. Habitual
sleep duration and insomnia and the risk of cardiovascular events and
all-cause death: report from a community-based cohort. Sleep 2010;
33:177.
12. Sofi F, Cesari F, Casini A, Macchi C, Abbate R, Gensini GF. Insomnia
and risk of cardiovascular disease: a meta-analysis. Eur J Prev Cardiol
2014; 21:57–64.
13. Javaheri S, Redline S. Insomnia and risk of cardiovascular disease. Chest
2017; 152:435–444.
14. Young T, Rabago D, Zgierska A, Austin D, Laurel F. Objective and
subjective sleep quality in premenopausal, perimenopausal, and post-
menopausal women in the Wisconsin Sleep Cohort Study. Sleep 2003;
26:667–672.
15. Terzano MG, Parrino L, Spaggiari MC, Palomba V, Rossi M, Smerieri A.
CAP variables and arousals as sleep electroencephalogram markers for
primary insomnia. Clin Neurophysiol 2003; 114:1715–1723.
16. Szklo-Coxe M, Young T, Peppard PE, Finn LA, Benca RM. Prospective
associations of insomnia markers and symptoms with depression. Am J
Epidemiol 2010; 171:709–720.
17. Yilmaz MB, Yalta K, Turgut OO, Yilmaz A, Yucel O, Bektasoglu G, et al.
Sleep quality among relatively younger patients with initial diagnosis of
hypertension: dippers versus non-dippers. Blood Press 2007; 16:101–
105.
18. Lanfranchi PA, Pennestri MH, Fradette L, Dumont M, Morin CM,
Montplaisir J. Nighttime blood pressure in normotensive subjects with
chronic insomnia: implications for cardiovascular risk. Sleep 2009;
32:760–766.
8 www.jhypertension.com
Copyright © 2019 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
19. Matthews KA, Kamarck TW, M HH, Strollo PJ, Owens JF, Buysse DJ,
et al. Blood pressure dipping and sleep disturbance in African-
American and Caucasian men and women. Am J Hypertens 2008;
21:826–831.
20. Huang Y, Mai W, Hu Y, Wu Y, Song Y, Qiu R, et al. Poor sleep quality,
stress status, and sympathetic nervous system activation in nondipping
hypertension. Blood Press Monit 2011; 16:117–123.
21. Staessen JA, Thijs L, Fagard R, O’brien ET, Clement D, de Leeuw PW,
et al. Predicting cardiovascular risk using conventional vs ambulatory
blood pressure in older patients with systolic hypertension. JAMA 1999;
282:539–546.
22. Young T, Palta M, Dempsey J, Skatrud J, Weber S, Badr S. The
occurrence of sleep-disordered breathing among middle-aged adults.
N Engl J Med 1993; 328:1230–1235.
23. Rechtschaffen A, Kales A. (eds) A Manual of Standardized
Terminology, Techniques and Scoring System for Sleep Stages of
Human Subjects. Washington, DC: Government Printing Office;
1968. NIH publication 204.
24. Hla KM, Young TB, Bidwell T, Palta M, Skatrud JB, Dempsey J. Sleep
apnea and hypertension: a population-based study. Ann Intern Med
1994; 120:382–388.
25. Zung WW. A self-rating depression scale. Arch Gen Psychiatry 1965;
12:63–70.
26. Loredo JS, Nelesen R, Ancoli-Israel S, Dimsdale JE. Sleep quality and
blood pressure dipping in normal adults. Sleep 2004; 27:1097–1103.
27. Routledge F, McFetridge-Durdle J. Nondipping blood pressure patterns
among individuals with essential hypertension: a review of the liter-
ature. Eur J Cardiovasc Nurs 2007; 6:9–26.
28. Cappuccio FP, Cooper D, D’elia L, Strazzullo P, Miller MA. Sleep
duration predicts cardiovascular outcomes: a systematic review and
meta-analysis of prospective studies. Eur Heart J 2011; 32:1484–1492.
29. Sabanayagam C, Shankar A. Sleep duration and cardiovascular disease:
results from the National Health Interview Survey. Sleep 2010; 33:1037–
1042.
30. Mallon L, Broman JE, Hetta J. Sleep complaints predict coronary artery
disease mortality in males: a 12-year follow-up study of a middle-aged
Swedish population. J Intern Med 2002; 251:207–216.
31. Grandner MA, Jackson NJ, Pak VM, Gehrman PR. Sleep disturbance is
associated with cardiovascular and metabolic disorders. J Sleep Res
2012; 21:427–433.
32. Li Y, Vgontzas AN, Fernandez-Mendoza J, Bixler EO, Sun Y, Zhou J,
et al. Insomnia with physiological hyperarousal is associated with
hypertension. Hypertension 2015; 65:644–650.
33. Vgontzas AN, Bixler EO, Lin HM, Prolo P, Mastorakos G, Vela-Bueno A,
et al. Chronic insomnia is associated with nyctohemeral activation of
the hypothalamic–pituitary–adrenal axis: clinical implications. J Clin
Endocrinol Metab 2001; 86:3787–3794.
34. Nerenberg KA, Zarnke KB, Leung AA, Dasgupta K, Butalia S, McBrien
K, et al. Hypertension Canada’s 2018 guidelines for diagnosis, risk
assessment, prevention, and treatment of hypertension in adults and
children. Can J Cardiol 2018; 34:506–525.
35. Sleight P, Yusuf S, Pogue J, Tsuyuki R, Diaz R, Probstfield J, et al. Blood-
pressure reduction and cardiovascular risk in HOPE study. Lancet 2001;
358:2130–2131.
36. Svensson P, de Faire U, Sleight P, Yusuf S, O?stergren J. Comparative
effects of ramipril on ambulatory and office blood pressures: a HOPE
substudy. Hypertension 2001; 38:e28–e32.
37. Agarwal R, Light RP, Bills JE, Hummel LA. Nocturia, nocturnal activity,
and nondipping. Hypertension 2009; 54:646–651.
38. Matsumoto T, Tabara Y, Murase K, Setoh K, Kawaguchi T, Nagashima
S, et al. Nocturia and increase in nocturnal blood pressure: the
Nagahama study. J Hypertens 2018; 36:2185–2192.
39. Zeitzer JM, Bliwise DL, Hernandez B, Friedman L, Yesavage JA.
Nocturia compounds nocturnal wakefulness in older individuals with
insomnia. J Clin Sleep Med 2013; 9:259–262.
40. Ayas NT, White DP, Manson JE, Stampfer MJ, Speizer FE, Malhotra A,
et al. A prospective study of sleep duration and coronary heart disease
in women. Arch Intern Med 2003; 163:205–209.
Volume 37  Number 1  Month 2019