Daytime baroreflex sensitivity in patients with primary insomnia

1 23

Clinical Research inCardiology ISSN 1861-0684Volume 100Number 4 Clin Res Cardiol (2011)100:351-358DOI 10.1007/s00392-010-0253-4

Daytime baroreflex sensitivity in patientswith primary insomnia

1 23

Your article is protected by copyright and

all rights are held exclusively by Springer-

Verlag. This e-offprint is for personal use only

and shall not be self-archived in electronic

repositories. If you wish to self-archive your

work, please use the accepted author’s

version for posting to your own website or

your institution’s repository. You may further

deposit the accepted author’s version on a

funder’s repository at a funder’s request,

provided it is not made publicly available until

12 months after publication.

ORIGINAL PAPER

Daytime baroreflex sensitivity in patients with primary insomnia

Jan Giso Peter • Martin Glos • Alexander Blau •

Thomas Penzel • Gert Baumann • Ingo Fietze

Received: 20 April 2010 / Accepted: 3 November 2010 / Published online: 24 November 2010

� Springer-Verlag 2010

Abstract Insomnia has been linked to cardiovascular

disease and among these especially hypertension and

changes in autonomic function. One marker for cardio-

vascular risk is baroreflex sensitivity (BRS). We investi-

gate daytime BRS in patients with primary insomnia in

order to assess cardiovascular risk. Twenty-one patients

(18 females/3 males) with primary insomnia according to

DSM-IV were recruited. Careful investigations excluded

confounding sleep disorders such as sleep-disordered

breathing and periodic limb movements. An age-matched

control group with 21 healthy subjects (18 females/3

males) underwent the same investigations. To assess BRS,

an experimental protocol with paced breathing during

daytime was performed. ECG and continuous non-invasive

blood pressure were recorded to obtain spontaneous BRS

by calculating the a index (BRS-a) and also by transfer

function analysis (TF-BRS). There were no differences at

daytime between insomnia patients and controls neither in

BRS-a (8.1 ms/mmHg, range 5.8–14.7 vs. 9.6 ms/mmHg,

range 6.9–15.8) nor in TF-BRS (5.8 ms/mmHg, range

2.4–16.8 vs. 5.4 ms/mmHg, range 2.3–11.4). Also there

were no differences in absolute, low or high frequency

bands of heart rate or blood pressure variability between

the two groups. We could show that primary insomnia may

be not associated with daytime parameters of autonomic

imbalance (e.g., baroreflex sensitivity) which are known as

non-classical risk markers of cardiovascular disease.

Keywords Insomnia � Primary insomnia � Baroreflex

sensitivity � Baroreceptor � Heart rate variability

Introduction

Insomnia has been associated to altered autonomous

function in experimental studies and to increased cardio-

vascular risk in epidemiologic studies. A previous study in

patients with psychophysiological insomnia found an

impaired heart rate variability during sleep [1]. A higher

24-h-metabolic rate and a reduced decline in glucose

metabolism in wake promoting brain areas during sleep

were demonstrated in patients with psychophysiological

and primary insomnia [2, 3]. These findings paved the

concept for assuming a state of hyperarousal in patients

with insomnia based on altered psychological and physio-

logical functioning [4].

A meta-analysis on ten epidemiological studies inves-

tigating the relation between insomnia and coronary heart

disease revealed that a subjective insomnia complaint is

related to an increased cardiac risk [5]. A recent study by

Vgontzas et al. showed a significant association between

insomnia with short sleep duration and hypertension [6].

The Sleep Heart Health Study revealed a link between

habitual short sleep duration and hypertension as a major

cardiovascular risk factor in this cross-sectional observa-

tional study. However, the presence or absence of insomnia

complaints was not relevant for the magnitude of the

association between habitual short sleep and hypertension

[7]. In a study assessing the Atherosclerosis Risk in

Communities (ARICs) insomnia complaints, defined as

J. G. Peter � M. Glos (&) � A. Blau � T. Penzel � I. Fietze

Sleep Medicine Center, CCM-CC13, Charite

Universitatsmedizin Berlin, Chariteplatz 1, 10117 Berlin,

Germany

e-mail: [email protected]

G. Baumann

Clinic of Cardiology and Angiology, CCM-CC13, Charite

Universitatsmedizin Berlin, Berlin, Germany

123

Clin Res Cardiol (2011) 100:351–358

DOI 10.1007/s00392-010-0253-4

Author's personal copy

waking up repeatedly and morning sleepiness, were asso-

ciated with a slightly increased risk in cardiovascular dis-

eases after 6 years [8] however sleep apnea was not

excluded in this study. Furthermore the authors stated that

there is a dependency of the CV risk on the insomnia

definition.

Finally, many studies provide evidence that insomnia is

linked to an increase in cardiovascular risk especially to

arterial hypertension. What actually causes hypertension

still needs further investigations. The hyperarousal state

based on altered sympathicovagal balance seems to be

one important mechanism. One possible consequence in

this context could be a reduced baroreceptor sensitivity

which is recognized as a marker of cardiovascular risk

and which has not been investigated until now in chronic

insomniacs.

The baroreflex regulates blood pressure quickly to

maintain stability. Baroreflex sensitivity (BRS) has a

recognized prognostic value for long-term cardiac mor-

tality after myocardial infarction [9] and long-term out-

come after acute ischemic stroke [10]. It yields additional

information compared to heart rate variability data alone

[9]. A reduced BRS is associated with a variety of con-

ditions with increased cardiovascular risk such as diabetes

[11], temporal lobe epilepsy [12], depression [13],

hypertension [14] and obstructive sleep apnea [15–17]. A

reduced BRS persists during daytime when autonomic

control of cardiovascular function during sleep is dis-

turbed [17, 18].

BRS could be assessed by either provocation of the

carotid baroreceptors with vasoactive drugs (phenyleph-

rine), mechanical stimulation (neck chamber technique,

head-up–tilt test) or by evaluating the spontaneous BRS.

The latter which observes spontaneous fluctuations of the

systolic blood pressure and corresponding RR-interval

changes has the advantage to determine BRS in a ‘‘natural’’

environment and therefore this does not influence subjects.

This seems important especially when investigating

patients with primary insomnia. Spectral estimates of the

spontaneous baroreflex gain are strongly correlated to

phenylephrine test [19, 20]. Among them the a index

(BRS-a) [21] and the transfer function (TF-BRS) approach

[22, 23] seem to achieve reliable BRS estimates [24]. The

BRS-a was used in a wide range of patient populations to

describe cardiovascular risk and the TF-BRS has demon-

strated to detect pathological cases where highly depressed

BRS is present. [25]. Based on the hypothesis that the

autonomous cardiovascular regulation is disturbed in

patients with chronic primary insomnia due to a state of

hyperarousability the aim of the present study is to inves-

tigate one established cardiovascular risk marker under

well-controlled conditions which is spontaneous BRS

during daytime.

Materials and methods

Study protocol

Consecutive patients with complaints of insomnia in the

outpatient department of the Center of Interdisciplinary

Sleep Medicine were asked to participate in this study. A

recording of non-invasive continuous blood pressure and

ECG as well as breathing frequency was performed under

standardized conditions during daytime. Data were ana-

lyzed for BRS. Patients were matched for age with control

subjects with healthy sleep from an earlier subject registry.

The study protocol was approved by the Charite ethics

committee.

Patients

Thirty-three patients were recruited and gave informed

consent. Subject history, blood pressure, body weight, size

and BMI were assessed. Physical examination and an ECG

recording followed. Blood analysis included fasting glu-

cose, blood counts, hemoglobin, creatinine, thyroid hor-

mone function and liver enzymes. A test for cocaine,

amphetamines, benzodiazepines, cannabinoids and alcohol

was performed.

Subjects had to present a low subjective sleep quality

assessed by the Pittsburgh Sleep Quality Index (PSQI [5)

and a complaint of insomnia following DSM-IV criteria

[26] for primary insomnia. These criteria include a chronic

difficulty in initiating or maintaining sleep causing signif-

icant distress or impairment in social, occupational, or

other functions not being due to an organic, medical or

mental disorder.

Exclusion criteria were secondary insomnia; alcohol

intake of more than 30 g/day on a regular basis; chronic

disease conditions such as hypertension, diabetes mellitus,

chronic pain syndromes, uncontrolled thyroid, renal, liver,

pulmonary and other medical disorders as well as acute

disease conditions that could affect sleep behaviour or alter

autonomic functions; any psychopharmacological medica-

tion or other medication with central nervous effects that

could affect sleep such as beta blockers within the last

4 weeks; alcohol or drug abuse; smoking; irregular blood

test results; restless legs complaints, and a lifetime history

of shift work.

Sleep-related breathing disorders (apnea hypopnea

index C5/h) were excluded by portable monitoring using a

six-channel recording system (Embletta� PDS, Embla

Systems, Broomfield, CO, USA) recording airflow and

snoring derived from nasal pressure signal, thoracic and

abdominal efforts, oxygen saturation, leg movements

and body position. A periodic limb movement disorder

(periodic limb movement index C5/h) was excluded too.

352 Clin Res Cardiol (2011) 100:351–358

123


The Mini-International Neuropsychiatric Interview

(M.I.N.I.) was conducted to assess mental disorders [27].

The Pittsburgh Sleep Quality Index (PSQI) [28], Beck

Depression Inventory (BDI) [29], and Epworth Sleepiness

Scale (ESS) [30] were assessed in the patient group in

order to characterize sleep quality and insomnia

complaints.

From our 33 patients, 12 patients were excluded due to

having ectopic beats during daytime ECG (3), positive

benzodiazepine urine test (3), suspected affective disorder

(2), ectopic beats during 12-channel ECG (1), elevated

liver enzymes (1), suspected anxiety disorder (1), not

showing up for the actual testing (1), not completing the

daytime testing (1). Four patients took medication as fol-

lows: hormone replacement therapy (1), oral contraception

(1), iodide for prevention of goiter (1) in regularly evalu-

ated euthyroid functional status, thyroxine for long-term

therapy of hypothyroid condition and a proton pump

inhibitor if needed for gastroesophageal reflux disease (1).

There was no temporal relation between these conditions or

medication use and insomnia complaints. Seventeen

patients did not take any medication on a regular basis.

There was no temporal relation between past medical

conditions or past medication use and insomnia complaints.

The reported duration of insomnia complaints ranged from

8 to 240 months. Median duration was 80 months. 50% of

patients reported durations between 54 and 120 months.

Regarding cardiovascular risk factors, insomnia patients

were excluded if they had a history of smoking, diabetes,

hypertension, other cardiovascular disease, pulmonary,

renal, uncontrolled thyroid or any kind of systemic disease

with possible cardiac affection. Blood pressure had to be

normal on two different occasions according to WHO

definitions. Lipids and uric acid were not investigated but

blood tests revealed normal fasting glucose levels, creati-

nine and thyroid functional status. All patients were lean.

These criteria were also applied for the control group.

Control group

In a previous study, a group of 47 healthy sleepers

(27 males/20 females) had been carefully selected out of

225 volunteers aged between 18 and 75 years in order to

compare autonomic activity especially BRS during day-

time [31, 32]. Sleep disorders and other medical disorders

were excluded by careful investigation, including history

taking, structured subjective sleep and general health data

and objective data derived from ECG, lung function test,

urine drug screening, blood tests, and two nights of atten-

ded cardiorespiratory polysomnography. None of the sub-

jects had a short sleep duration or a complaint of initiating

or maintaining sleep or early awakening at morning. None

of the subjects was under chronic medication.

Baroreflex sensitivity testing

The test was conducted between 9 and 11 a.m. during

wakefulness in a quiet examination room. Patients were

studied in a 45� head-up position and were trained in

metronomically controlled breathing for 5–10 min. Non-

invasive blood pressure was recorded with the Portapres�

system (Finapres Medical Systems, Amsterdam, The

Netherlands) [33, 34]. This method correlates well with

intra-arterial blood pressure values [35] and proved to be

valid for time- and frequency-domain analysis of blood

pressure variability and BRS [36]. In parallel, ECG (lead

II), respiration with a thoracic effort belt and nasal air-

flow were recorded using a polysomnography recorder

(SOMNOScreenTM

, SOMNOmedics GmbH, Randersacker,

Germany). Subjects were breathing at a fixed rate of 12

breaths/min. The digital sampling rate was set to 200 Hz

for the ECG and blood pressure signals and to 50 Hz for

the respiration signal. The recording time for each test was

5–7 min duration.

Signal analysis

The ECG and the blood pressure signal were analyzed

using the MATLAB software (The Math-Works Inc.,

Natick, MA, USA) with previously described algorithms

[32, 37]. RR-intervals and systolic blood pressure were

calculated. Artifacts were removed and episodes with 180

consecutive heart beats were selected. The time series were

interpolated using cubic splines, and were re-sampled at

4 Hz. Fast Fourier transform was applied to calculate

power spectra. To reduce spectral leakage, a sliding win-

dow (Hanning model, 256 points) with overlapping sec-

tions based on Welch’s method [38] was used. With this we

calculated heart rate variability (HRV) and systolic blood

pressure variability (SBPV) power spectra. From the two

spectra, the low frequency (LF 0.04–0.15 Hz) and high

frequency (HF 0.15–0.4 Hz) spectral bands were

calculated.

In HRV, vagal activity is the main contributor to the HF

component for subjects in supine position under controlled

respiration without pharmacological or physical interven-

tions whilst the LF component reflects both sympathetic

and vagal autonomic activity [39]. The LF/HF-HRV ratio

was calculated as a surrogate for sympathovagal balance.

An increase in the LF/HF-HRV ratio indicates a shift

towards a sympathetic predominance in which higher

sympathetic activity is causative as long as the HF com-

ponent is unchanged. SBPV components in the LF range

are related to sympathetic activity although not being

specific. HF-SBPV components’ modulations are due to

mechanical effects of respiration. The spontaneous baro-

receptor sensitivity is based on the permanent activity of

Clin Res Cardiol (2011) 100:351–358 353

123


the baroreflex feedback loop and uses spontaneous fluctu-

ations in the baroreflex feedback loop. The spontaneous

BRS was calculated in two ways (BRS-a, TF-BRS) using

spectral analysis.

The BRS-a was calculated using the squared root of the

ratio of RR-interval and SBP power spectra. This was

performed separately for the LF (0.04–0.15 Hz) and HF

(0.15–0.4 Hz) bands resulting in a-LF and a-HF [21]. The

squared coherence function (k2) was used to evaluate the

statistical reliability of the a-LF and a-HF. Data were

further utilized if k2 exceeded 0.56 [40, 41]. Finally, the

a-tot was calculated as the mean of a-LF and a-HF [42].

The a-LF displays the gain of the arterial pressure

RR-interval relationship in the spectral region not linked to

the breathing frequency whilst the a-HF component mirrors

the gain in the spectral region of the breathing frequency

[21]. The a-tot provides an evaluation of the overall

baroreceptor gain [43].

Since the use of the coherence criterion could in some

cases preclude the measurement of depressed baroreceptor

sensitivity in pathological subjects we also computed the

TF-BRS.

The TF-BRS was calculated by evaluating the transfer

function between time series of systolic blood pressure

and RR-Interval. For each frequency, the gain of the

transfer function describes the amount of transformation

of sinusoidal systolic blood pressure waves into corre-

sponding RR-Interval waves. The TF-BRS was given

by averaging the gain function in the LF band

(0.04–0.15 Hz) regardless of a given coherence between

systolic blood pressure and RR-Interval time series. As

for the BRS-a TF-BRS values are expressed in ms/mmHg

[22, 23].

Statistics

First, a sample size estimation was performed based on a

previous study comparing BRS in snorers and healthy

subjects [44]. We took the BRS as the primary endpoint

and planed for 6 ms/mmHg difference for the a-tot with

a standard deviation of 6.7 ms/mmHg. A two-tailed

statistical significance level was taken for p \ 0.05.

Power was set at 80% and this yielded a sample size of

21 subjects.

For statistical analyses of the results, the software

package SPSS for Windows (version 12.0, SPSS, Chicago,

IL) was used. Age and body mass index (BMI) values are

given as means with standard deviation. The other

parameters were presented with median, lower and upper

quartile in order to be free of distribution assumptions. For

testing, the non-parametric Mann–Whitney U test was

applied. Differences were considered significant at a two-

tailed p \ 0.05.

Results

Subject characteristics

Twenty-one patients (18 females, 3 males) were taken for

subsequent analysis. Mean age was 48.2 years (SD ±

10.4 years) and mean BMI was 23.7 kg/m2 (SD 3.0 kg/m2).

Subjects were matched for age to 21 controls (18 females, 3

males). Their mean age was 48.5 years (SD ± 11.1 years)

and their mean BMI was 23.8 kg/m2 (SD ± 2.1 kg/m2).

More characteristics are described in the ‘‘Materials and

methods’’ section.

Questionnaires

The results of the questionnaires for PSQI, BDI, and ESS

are presented in Table 1. ESS scores were higher in the

insomnia group (p = 0.025). The number of patients

according to BDI categories of depressive symptoms is

given in Table 2. PSQI and BDI data were not assessed in

the control group.

Time and frequency domain parameters

Time domain parameters for HRV, diastolic and systolic

blood pressure showed no significant difference between the

patient group and the control subjects as demonstrated in

Table 3. Frequency domain parameters calculated by spec-

tral analysis for HRV and SBPV showed no significant dif-

ferences (see Table 4). Our main parameter, BRS presented

as the a-LF, the a-HF, the a-tot, and the TF-BRS showed no

significant differences between both groups. Summarizing

values are given in Table 4 and the values are depicted in

Fig. 1 as statistical box plots for better presentation.

Table 1 Questionnaire results

Questionnaire Patients score:

range

Patients score: median

(lower quartile, upper quartile)

PSQI 10–17 13 (12, 14)

BDI 1–26 11 (8, 14)

ESS 0–16 8 (4, 10)

PSQI Pittsburgh Sleep Quality Index, BDI Beck Depression Inven-

tory, ESS Epworth Sleepiness Scale

Table 2 Beck Depression Inventory (BDI) categories

BDI score Level of depressive symptoms Number of patients

0–13 Minimal 14

14–19 Mild 4

20–28 Moderate 3

29–63 Severe 0

354 Clin Res Cardiol (2011) 100:351–358

123


Discussion

In our patients with primary insomnia and definitely no

other sleep disorders or other disorders which could

influence sleep or the autonomic system we could not find a

blunted baroreceptor sensitivity at daytime. Therefore, we

cannot confirm the hypothesis that insomnia is associated

to blunted daytime parameters of autonomic function, e.g.,

HRV, SBPV and BRS.

A possible factor limiting our findings may be the

selection of the patient group. Since the diagnostic

assessment of insomnia was based on the clinical interview

(DSM-IV), subjective complaints, and questionnaires

results it is not always possible to distinguish between

primary, paradoxical and psychophysiological insomnia.

Secondary causes for insomnia such as pain, other disor-

ders, and external factors are easier to assess. Subjective

sleep quality represents mainly the amount of wakefulness

[45] and reported sleep duration is influenced by possible

sleep-misperception. The importance of sleep duration

assessed by sleep EEG on cardiovascular risk had been

assessed by Vgontzas et al. [6] recently. In their popula-

tion-based study, patients with insomnia and a short sleep

duration developed hypertension. Whether this holds true

for self reported short sleep duration remains to be

answered since other studies investigating the relation

between insomnia and hypertension revealed deviating

results [46].

Table 3 Time domain

parameters

RR RR-interval, STD-RRstandard deviation of RR-

intervals, RMSSD-RR root mean

square of successive differences

of RR-intervals, SBP systolic

blood pressure, DBP diastolic

blood pressure

Parameter Patients: median (lower quartile,

upper quartile)

Control subjects: median, (lower

quartile, upper quartile)

p

RR (ms) 918.4 (866.5, 959.5) 871.5 (800.3, 947.7) 0.204

SDNN (ms) 36.7 (27.0, 49.7) 34.2 (27.8, 43.1) 0.505

RMSSD (ms) 29.8 (23.7, 40.1) 29.1 (18.6, 38.5) 0.505

DBP (mmHg) 72.6 (58.1, 78.0) 62.8 (53.8, 70.7) 0.148

SBP (mmHg) 124.8 (113.6, 139.7) 121.6 (115.4, 145.8) 0.870

Table 4 Frequency domain

parameters

HRV heart rate variability,

HRV-TOT total heart rate

variability, LF low frequency in

the LF domain, HF high

frequency in the HF domain,

LF/HF-HRV ratio of low

frequency and high frequency

heart rate variability, SBPVsystolic blood pressure

variability, SBPV-TOT total

systolic blood pressure, BRSbaroreceptor sensitivity, a-tota-tot of BRS

Parameter Patients: median

(lower quartile,

upper quartile)

Control subjects:

median (lower quartile,

upper quartile)

p

HRV

LF ? HF (ms2) 35.8 (22.4, 72.6) 33.1 (24.6, 70.0) 0.940

LF (ms2) 13.4 (9.8, 19.8) 15.1 (7.3, 20.8) 0.606

HF (ms2) 23.4 (9.6, 44.2) 22.7 (12.0, 48.8) 0.678

LF/HF 0.72 (0.43, 1.01) 0.45 (0.30, 0.70) 0.081

SBPV

LF ? HF (mmHg2) 0.48 (0.38, 0.82) 0.43 (0.27, 0.81) 0.589

LF (mmHg2) 0.32 (0.19, 0.47) 0.32 (0.14, 0.45) 0.930

HF (mmHg2) 0.17 (0.13, 0.26) 0.10 (0.06, 0.17) 0.263

BRS

a-LF (ms/mmHg) 6.5 (4.3, 11.3) 6.0 (5.1, 9.4) 0.772

a-HF (ms/mmHg) 10.8 (6.0, 17.3) 10.9 (8.9, 24.3) 0.473

a-tot (ms/mmHg) 8.1 (5.8, 14.7) 9.6 (6.9, 15.8) 0.554

TF-BRS (ms/mmHg) 5.8 (2.4, 16.8) 5.4 (2.3, 11.4) 0.745

Fig. 1 Baroreflex sensitivity value a. LF low frequency in the LF

domain, HF high frequency in the HF domain, a-tot overall a-tot in

the low and high frequency domain, patients n = 21, controls n = 21.

Group differences were non-significant

Clin Res Cardiol (2011) 100:351–358 355

123


An overnight polysomnography quantifies sleep dura-

tion which is important for exclusion of sleep state mis-

perception and is required for exclusion of sleep-related

movement disorders or other sleep disorders. Portable

monitoring of sleep with a reduced number of channels

provides limited reliability on these issues.

Additional factors influencing the cardiovascular risk in

patients with chronic insomnia are sleep duration, devel-

opment of insomnia over time, the patient age at the

beginning of insomnia and the severity of insomnia com-

plaints. In our patient group, the number of subjects was

too low to distinguish these factors systematically.

Our study confirms previous contradictory results

regarding the cardiovascular risk in insomnia patients and

underlines the need for a uniform selection of patients and

randomizing them in terms of sleep duration, co-morbidity,

co-morbidity medication, subjective complaints, duration

of insomnia complaints, age of insomnia onset, or type of

insomnia. Still it may be possible that with very short sleep

duration, a long persistence of insomnia, an early onset of

insomnia or a high susceptibility to hyperarousal, there

may be changes in BRS during daytime. In a discussion on

hyperarousal Bonnet and Varkevisser also underlined the

importance of well defined inclusion and exclusion criteria

for studies on insomnia patients [47, 48]. In contrast to this,

if the insomnia patients are extremely carefully selected

then this may lead to mere theoretical conclusion which is

not applicable to real patient settings [49].

A limiting factor our findings may be the selected

sample size and method. Twenty-one patients with

insomnia and 21 healthy controls matched to age and

gender were included in the study. Since it is difficult to

find healthy sleepers in the middle-aged population [31],

the number of subjects limits the statistical strength of our

study. Another limitation is the fact that nocturnal assess-

ment of HRV, SBPV, and BRS in which changes in the

autonomic tone are eventually more pronounced could not

be performed. In future studies it might be reasonable to

asses additional risk markers in parallel like NT-pro BNT

[50] which has not been investigated in insomniacs until

now. The application of a Holter ECG for identification of

premature ventricular beats and for assessment of 24-h

HRV might be used for the identification of patients with

primary insomnia [51].

But finally the spontaneous baroreflex measurements

with the chosen two different spectral approaches have

been successfully applied already to a variety of patient

populations and they are able to demonstrate true barore-

ceptor sensitivity behavior with a high reliability [24] and

are accepted as being equivalent to invasive techniques.

Due to this high correlation with drug induced and other

spontaneous forms of cardiac baroreflex measurement

[21, 52, 53] the BRS-a [25, 54] and the TF-BRS [50, 55] of

baroreceptor sensitivity were recommended for comparison

of group differences. Additional frequency domain

parameters for HRV have been used as measures of auto-

nomic balance and severity of sleep disorders or other

neurological disorders before [56, 57].

We found no differences between controls and

insomnia patients in the time domain and the frequency

domain parameters for HRV and SBPV. Different BRS

measures do not show significant differences between

groups.

In order to further describe the relevance of our findings

age-related reference values or pathologic threshold values

of BRS are needed. Different approaches in handling the

different response times of the sympathetic and parasym-

pathetic nervous system between methods create different

absolute values of baroreceptor sensitivity limiting com-

parability between methods in terms of absolute values.

Reference values are not available. We assume that we had

a very reliable control group because the subjects complied

with the restrictive inclusion and exclusion criteria. To

finally include 46 healthy subjects we had to investigate

225 persons [31].

Concerning the matching between control and patients

groups it has to be stated that gender differences account

for only approximately 1% of variance of baroreceptor

sensitivity [58] so that this does not influence our results.

Age has a high impact on baroreceptor sensitivity [58] and

this we considered in our study by matching for age.

Similar to age, BMI accounts for variances in BRS. BMI

was also the same in both groups with a low standard

deviation.

The questionnaires’ data demonstrate that our patient

group is comparable to groups in other studies on chronic

insomnia patients. PSQI scores show high values indicating

a very low subjective sleep quality. BDI scores in our

patient group show minimal to mild depression, as has been

shown previously to predominate in patients with primary

insomnia [59]. Although BDI scores in our study are used

unmodified in contrast to the study of Moul et al.—and thus

tended to result in higher scores as they included sleep-

related items—the BDI scores still mostly range from the

minimal to the mild depressive symptoms categories. ESS

scores have been shown to be in the high normal range in

patients with primary insomnia mostly without reaching

the clearly pathologic threshold values [30, 59]. These

characteristics are confirmed for our patient group. Taken

together the results of the standardized M.I.N.I and eval-

uation on history taking the questionnaires underline the

validity of the primary insomnia diagnosis in contrast to

depression-related insomnia and show a strong severity of

insomnia symptoms.

In conclusion, our study revealed no change in the

analyzed indirect cardiovascular risk parameters like HRV,

356 Clin Res Cardiol (2011) 100:351–358

123


BPV and baroreceptor sensitivity at daytime which can be

interpreted as a good message for all primary chronic

insomnia patients. Nevertheless due to methodological

limitations, an elevated CV risk at daytime cannot be

excluded in general and should be investigated in further

extended studies implementing different methods for

objectifying the CV risk.

Acknowledgments This study has been funded by Charite univer-

sity resources.

Conflict of interest None.

References

1. Bonnet MH, Arand DL (1998) Heart rate variability in insom-

niacs and matched normal sleepers. Psychosom Med

60:610–615

2. Bonnet MH, Arand DL (1995) 24-Hour metabolic rate in

insomniacs and matched normal sleepers. Sleep 18:581–588

3. Nofzinger EA, Buysse DJ, Germain A, Price JC, Miewald JM,

Kupfer DJ (2004) Functional neuroimaging evidence for hyper-

arousal in insomnia. Am J Psychiatry 161:2126–2128

4. Bonnet MH, Arand DL (1997) Hyperarousal and insomnia. Sleep

Med Rev 1:97–108

5. Schwartz S, McDowell AW, Cole SR, Cornoni-Huntley J, Hays

JC, Blazer D (1999) Insomnia and heart disease: a review of

epidemiologic studies. J Psychosom Res 47:313–333

6. Vgontzas AN, Liao D, Bixler EO, Chrousos GP, Vela-Bueno A

(2009) Insomnia with objective short sleep duration is associated

with a high risk for hypertension. Sleep 32:491–497

7. Gottlieb DJ, Redline S, Nieto FJ et al (2006) Association of usual

sleep duration with hypertension: the Sleep Heart Health Study.

Sleep 29:1009–1014

8. Phillips B, Mannino DM (2007) Do insomnia complaints cause

hypertension or cardiovascular disease? J Clin Sleep Med

3:489–494

9. La Rovere MT, Bigger JT Jr, Marcus FI, Mortara A, Schwartz PJ

(1998) Baroreflex sensitivity and heart-rate variability in pre-

diction of total cardiac mortality after myocardial infarction.

ATRAMI (autonomic tone and reflexes after myocardial infarc-

tion) investigators. Lancet 351:478–484

10. Robinson TG, Dawson SL, Eames PJ, Panerai RB, Potter JF

(2003) Cardiac baroreceptor sensitivity predicts long-term out-

come after acute ischemic stroke. Stroke 34:705–712

11. Frattola A, Parati G, Gamba P et al (1997) Time and frequency

domain estimates of spontaneous baroreflex sensitivity provide

early detection of autonomic dysfunction in diabetes mellitus.

Diabetologia 40:1470–1475

12. Dutsch M, Hilz MJ, Devinsky O (2006) Impaired baroreflex

function in temporal lobe epilepsy. J Neurol 253:1300–1308

13. Broadley AJ, Frenneaux MP, Moskvina V, Jones CJ, Korszun A

(2005) Baroreflex sensitivity is reduced in depression. Psychosom

Med 67:648–651

14. Harrington F, Murray A, Ford GA (2000) Relationship of baro-

reflex sensitivity and blood pressure in an older population.

J Hypertens 18:1629–1633

15. Cortelli P, Parchi P, Contin M et al (1991) Cardiovascular dys-

autonomia in fatal familial insomnia. Clin Auton Res 1:15–21

16. Fietze I, Glos M (2003) Baroreceptor sensitivity, sleep and

OSAS. Somnologie 7:140–146

17. Parati G, Di RM, Bonsignore MR et al (1997) Autonomic cardiac

regulation in obstructive sleep apnea syndrome: evidence from

spontaneous baroreflex analysis during sleep. J Hypertens

15:1621–1626

18. Cortelli P, Parchi P, Sforza E et al (1994) Cardiovascular auto-

nomic dysfunction in normotensive awake subjects with

obstructive sleep apnoea syndrome. Clin Auton Res 4:57–62

19. Parati G, Di RM, Mancia G (2000) How to measure baroreflex

sensitivity: from the cardiovascular laboratory to daily life.


20. Pitzalis MV, Mastropasqua F, Passantino A et al (1998) Com-

parison between non-invasive indices of baroreceptor sensitivity

and the phenylephrine method in post-myocardial infarction

patients. Circulation 97:1362–1367

21. Pagani M, Somers V, Furlan R et al (1988) Changes in autonomic

regulation induced by physical training in mild hypertension.

Hypertension 12:600–610

22. Pinna GD, Maestri R (2002) New criteria for estimating barore-

flex sensitivity using the transfer function method. Med Biol Eng

Comput 40:79–84

23. Pinna GD, Maestri R, Raczak G, La Rovere MT (2002) Mea-

suring baroreflex sensitivity from the gain function between

arterial pressure and heart period. Clin Sci (Lond) 103:81–88

24. Laude D, Elghozi JL, Girard A et al (2004) Comparison of var-

ious techniques used to estimate spontaneous baroreflex sensi-

tivity (the EuroBaVar study). Am J Physiol Regul Integr Comp

Physiol 286:R226–R231

25. La Rovere MT, Pinna GD, Raczak G (2008) Baroreflex sensi-

tivity: measurement and clinical implications. Ann Noninvasive

Electrocardiol 13:191–207

26. American Psychiatric Association (APA). Diagnostic and Sta-

tistical Manual of Mental Disorders, 4th Edition (DSM-IV).

Washington DC: APA, 1994

27. Sheehan DV, Lecrubier Y, Sheehan KH et al (1998) The Mini-

International Neuropsychiatric Interview (M.I.N.I.): the devel-

opment and validation of a structured diagnostic psychiatric

interview for DSM-IV and ICD-10. J Clin Psychiatry 59(Suppl

20):22–33

28. Buysse DJ, Reynolds CF III, Monk TH, Berman SR, Kupfer DJ

(1989) The Pittsburgh Sleep Quality Index: a new instrument for

psychiatric practice and research. Psychiatry Res 28:193–213

29. Backhaus J, Junghanns K, Broocks A, Riemann D, Hohagen F

(2002) Test-retest reliability and validity of the Pittsburgh Sleep

Quality Index in primary insomnia. J Psychosom Res 53:737–740

30. Johns MW (1991) A new method for measuring daytime sleep-

iness: the Epworth sleepiness scale. Sleep 14:540–545

31. Fietze I, Diefenbach K (2003) Healthy sleepers are rare: problems

and success rates in establishing a control group for sleep studies.

Neuropsychopharmacology 28:558–561

32. Fietze I, Romberg D, Glos M et al (2004) Effects of positive-

pressure ventilation on the spontaneous baroreflex in healthy

subjects. J Appl Physiol 96:1155–1160

33. Penaz J (1973) Photoelectric measurement of blood pressure,

volume and flow in the finger. Dresden, p 104

34. Wesseling KH, De Wit B, van der Hoeven GM, van Goudoever J,

Settels JJ (1995) Physiocal, calibrating finger vascular physiology

for FINAPRES. Homeostasis 36:67–82

35. Parati G, Casadei R, Groppelli A, Di RM, Mancia G (1989)

Comparison of finger and intra-arterial blood pressure monitoring

at rest and during laboratory testing. Hypertension 13:647–655

36. Gizdulich P, Imholz BP, van den Meiracker AH, Parati G,

Wesseling KH (1996) Finapres tracking of systolic pressure and

baroreflex sensitivity improved by waveform filtering. J Hyper-

tens 14:243–250

37. Glos M, Romberg D, Endres S, Fietze I (2007) Estimation of

spontaneous baroreflex sensitivity using transfer function

Clin Res Cardiol (2011) 100:351–358 357

123


analysis: effects of positive pressure ventilation. Biomed Tech

(Berl) 52:66–72

38. Welch PD (1967) The use of fast fourier transform for the esti-

mation of power spectra: a method based on time averaging over

short, modified periodograms. IEEE Trans Audio Electroacoust

AU- 15:70–73

39. Task Force NASPE of the ESC (1996) Heart rate variability.

Standards of measurement, physiological interpretation, and

clinical use. Task Force of the European Society of Cardiology

and the North American Society of Pacing and Electrophysiol-

ogy. Eur Heart J 17:354–381

40. de Boer RW, Karemaker JM, Strackee J (1987) Hemodynamic

fluctuations and baroreflex sensitivity in humans: a beat-to-beat

model. Am J Physiol 253:H680–H689

41. Pitzalis MV, Mastropasqua F, Massari F et al (1998) Effect of

respiratory rate on the relationships between RR-interval and

systolic blood pressure fluctuations: a frequency-dependent phe-

nomenon. Cardiovasc Res 38:332–339

42. Lucini D, Porta A, Milani O, Baselli G, Pagani M (2000)

Assessment of arterial and cardiopulmonary baroreflex gains

from simultaneous recordings of spontaneous cardiovascular and

respiratory variability. J Hypertens 18:281–286

43. Lucini D, Guzzetti S, Casiraghi S, Pagani M (2002) Correlation

between baroreflex gain and 24-h indices of heart rate variability.


44. Schary I, Glos M, Blau A, Fietze I (2005) Barorezeptorsensitivitat

bei Patienten mit primarem Schnarchen. Pneumologie 59[S1]

45. Akerstedt T, Kecklund G, Axelsson J (2008) Subjective and

objective quality of sleep. Somnologie 12:104–109

46. Suka M, Yoshida K, Sugimori H (2003) Persistent insomnia is a

predictor of hypertension in Japanese male workers. J Occup

Health 45:344–350

47. Bonnet MH (2005) Hyperarousal as the basis for insomnia: effect

size and significance. Sleep 28:1500–1501

48. Varkevisser M, Van Dongen HP, Kerkhof GA (2005) Physiologic

indexes in chronic insomnia during a constant routine: evidence

for general hyperarousal? Sleep 28:1588–1596

49. Varkevisser M, Van Dongen HP, Kerkhof GA (2006) Hyper-

arousal as a basis for chronic insomnia: statistical misconceptions

and individual differences. Sleep 29:719

50. Simon T, Becker R, Voss F et al (2008) Elevated B-type natri-

uretic peptide levels in patients with nonischemic cardiomyopa-

thy predict occurrence of arrhythmic events. Clin Res Cardiol

97:306–309

51. Smilde TD, van Veldhuisen DJ, van den Berg MP (2009) Prog-

nostic value of heart rate variability and ventricular arrhythmias

during 13-year follow-up in patients with mild to moderate heart

failure. Clin Res Cardiol 98:233–239

52. Robbe HW, Mulder LJ, Ruddel H, Langewitz WA, Veldman JB,

Mulder G (1987) Assessment of baroreceptor reflex sensitivity by

means of spectral analysis. Hypertension 10:538–543

53. Watkins LL, Grossman P, Sherwood A (1996) Non-invasive

assessment of baroreflex control in borderline hypertension. Com-

parison with the phenylephrine method. Hypertension 28:238–243

54. Persson PB, DiRienzo M, Castiglioni P et al (2001) Time versus

frequency domain techniques for assessing baroreflex sensitivity.


55. Pinna GD, Maestri R, Capomolla S et al (2005) Applicability and

clinical relevance of the transfer function method in the assess-

ment of baroreflex sensitivity in heart failure patients. J Am Coll

Cardiol 46:1314–1321

56. Wang W, Tretriluxana S, Redline S, Surovec S, Gottlieb DJ,

Khoo MC (2008) Association of cardiac autonomic function

measures with severity of sleep-disordered breathing in a com-

munity-based sample. J Sleep Res 17:251–262

57. Buob A, Winter H, Kindermann M et al (2010) Parasympathetic

but not sympathetic cardiac dysfunction at early stages of Par-

kinson’s disease. Clin Res Cardiol 99:701–706

58. Kardos A, Watterich G, de MR, Csanady M, Casadei B, Rudas L

(2001) Determinants of spontaneous baroreflex sensitivity in a

healthy working population. Hypertension 37:911–916

59. Moul DE, Nofzinger EA, Pilkonis PA, Houck PR, Miewald JM,

Buysse DJ (2002) Symptom reports in severe chronic insomnia.

Sleep 25:553–563

358 Clin Res Cardiol (2011) 100:351–358

123


Daytime baroreflex sensitivity in patients with primary insomnia

Documents

Transcript of Daytime baroreflex sensitivity in patients with primary insomnia