Journal of Psychosomatic Research 68 (2010) 139 – 147

Alexithymia, hypertension, and subclinical atherosclerosis in the

general population☆,☆☆
Hans Joergen Grabe a,⁎,1 , Christian Schwahn b,1 , Sven Barnow c , Carsten Spitzer d , Ulrich John e ,
Harald J. Freyberger a , Ulf Schminke f , Stephan Felix g , Henry Völzke b
a
Department of Psychiatry and Psychotherapy, University of Greifswald, Greifswald, Germany
b
Institute for Community Medicine, University of Greifswald, Greifswald, Germany
c
Department of Clinical Psychology, University of Heidelberg, Heidelberg, Germany
d
Department of Psychosomatic Medicine and Psychotherapy, University of Hamburg, Hamburg, Germany
e
Institute of Epidemiology and Social Medicine, University of Greifswald, Greifswald, Germany
f
Department of Neurology, University of Greifswald, Greifswald, Germany
g
Department of Internal Medicine B, University of Greifswald, Greifswald, Germany1
Received 10 March 2009; received in revised form 13 July 2009; accepted 21 July 2009

Abstract

Objectives: As a personality trait, alexithymia is assumed to
present a longstanding risk factor for emotional dysregulation
that also affects the autonomic nervous system. Therefore, we
hypothesize that alexithymia is associated with hypertension and
carotid atherosclerosis in the general population. Methods: A
total of 1168 subjects (age b65 years) from the Study of Health
in Pomerania (SHIP) were eligible for complete case analyses.
Alexithymia was assessed with the 20-item Toronto-Alexithy-
mia-Scale (TAS-20). An extensive interview and physical
examination were performed. Extracranial carotid arteries were
examined bilaterally with B-mode ultrasonography. Regression
models were adjusted for sociodemographic factors and classical
Keywords: Alexithymia; TAS-20; Hypertension; Carotid atherosclerosis; Study of health in pomerania; Type A personality; Type D personality
risk factors for cardiovascular diseases and mental distress.
Results: In the adjusted logistic regression models, alexithymia
was significantly associated with hypertension (OR=1.60; 95%
CI=1.14–2.25) and with atherosclerotic plaques (OR=1.70; 95%
CI=1.14–2.54). Hypertension changed the effect of alexithymia on
atherosclerosis only marginally (OR=1.76 to 1.70). Conclusion:
Alexithymia may represent a relevant and independent risk factor
for hypertension and carotid atherosclerosis at the population
level. None of the putative confounders mediated a relevant
proportion of the risk. Prospective studies are needed to confirm
this association.
© 2010 Elsevier Inc. All rights reserved.

Introduction

There is a longstanding public and scientific interest to the

☆
The work is part of the Community Medicine Research Net of the debate whether personality styles like type A and type D
University of Greifswald, Germany, which is funded by the Federal Ministry personality [1–3] increase the risk of cardiovascular diseases
of Education and Research (grant no. ZZ9603), the Ministry of Cultural
Affairs, as well as the Social Ministry of the Federal State of Mecklenburg-
(CVD). Different mechanisms for this putative association
West Pomerania. are conceivable: First, distinct personality patterns can be
☆☆
There are no conflicts of interest. See Appendix A for financial associated with behavioral risk factors for CVD like
support in the past 3 years. smoking, poor diet, and sedentary lifestyle. Second,
⁎ Corresponding author. Department of Psychiatry, HANSE-Klinikum
personality patterns and other psychosocial conditions may
Stralsund, University of Greifswald, Rostocker Chaussee 70, 18437
Stralsund, Germany. Tel.: +49 (0) 3831/45 2106; fax: +49 (0) 3831/45 2105.
directly alter the functional integrity of the autonomic
E-mail address: grabeh@uni-greifswald.de (H.J. Grabe). nervous and neuroendocrine system and thereby increase the
1
These authors contributed equally to the paper. risk of CVD [4–6]. Excessive activation of the sympathetic

0022-3999/09/$ – see front matter © 2010 Elsevier Inc. All rights reserved.
doi:10.1016/j.jpsychores.2009.07.015
140 H.J. Grabe et al. / Journal of Psychosomatic Research 68 (2010) 139–147
nervous system may cause endothelial dysfunction, hyper-
cortisolemia, adrenergic activation, a stimulated platelet
function, increased blood viscosity, coronary vasoconstric-
tion, and exaggerated responses of heart rate and blood
pressure (BP) to psychological stimuli [5,6]. A decreased
vagal function is associated with increased serum levels of
cortisol, fasting glucose, proinflammatory cytokines, and
acute-phase proteins [4,7].
Research investigating the alexithymia construct has
advanced rapidly over the past decade largely due to the
development of the self-report 20-item Toronto Alexithymia
Scale (TAS-20) [8,9], which provided investigators with a
reliable, valid, and common metric for measuring the construct
[10–12]. Subjects with alexithymia have difficulties in
identifying and expressing feelings, in distinguishing emo-
tions from bodily sensations, and have an externally orientated
style of thinking that lacks fantasies [13,14]. They are often
socially avoidant, cold, and less emotionally attached to others
[15]. Alexithymic personality traits are associated with deficits
in affect regulation, and, therefore, it is hypothesized that
alexithymia constitutes a longstanding risk factor for imbal-
ances in the autonomic nervous system and the neuroendo-
crine system. Most psychophysiological studies found an
elevated resting sympathetic tone in alexithymics or a greater
heart rate or BP reactivity to experimental stressors (see for
review Ref. [11]). In line with these results, alexithymia was
found to be significantly elevated in samples of newly
diagnosed yet untreated hypertensive men and women
[16,17]. Todarello et al. [18] found 55.3% of patients with
hypertension (n=114) to be alexithymic compared with 16.3%
of nonhypertensive controls (n=130).
Based on this line of evidence, our study is the first to
investigate the hypothesis that alexithymia is associated with
carotid atherosclerosis in the general population. We
expected that hypertension mediated some effects of
alexithymia on atherosclerosis. In the statistical models, we
adjusted for classical and behavioral risk factors for CVD as
well as for mental conditions like depression.
Materials and methods
General population sample
Data from the Study of Health in Pomerania (SHIP) were
used [19]. The target population comprised adult German
residents (20–79 years) in northeastern Germany living in
three cities and 29 communities with a total population of
212,157. A multistage sampling scheme was adopted from
the World Health Organization's MONICA Project, Ger-
many. From the total population, a sample of 7008 was
drawn from the residents' registration offices in 1996. The
net sample (after exclusion of migrated or deceased persons)
comprised 6267 eligible subjects, out of which 4310 persons
participated, corresponding to a baseline response proportion
of 68.8%. Follow-up examination was conducted 5 years
after baseline and comprised 3300 subjects. All participants
gave informed consent to the study and scientific use of the
data. The study conformed to the principles of the
Declaration of Helsinki as reflected by an a priori approval
of the Institutional Review Board of the University of
Greifswald. Alexithymia was assessed as part of an
associated tele-ECG project. All 3300 subjects were invited
to participate in this project. Mainly because of the complex
nature of this project (ECG recordings twice per day over a
1-month period at home), only 1889 participated in this
project. A total of 1572 TAS-20 (83.21%) questionnaires
were returned; 76 were excluded because of missing values.
Analytic sample
As in higher ages (≥ 65), the prevalence of atherosclerotic
plaques in the carotid arteries was N92%, only subjects up to
64 years were included into the analyses. In order to reduce
reverse causality (atherosclerosis leading to alexithymia),
subjects with a positive history of stroke and myocardial
infarction (MI) were excluded from the analyses. Due to
right hemispheric stroke, lesions, and dysfunctional coping
strategies after MI, levels of alexithymia may be elevated in
these patients [20,21]. The final analytic sample comprised
1178 subjects for the analyses of hypertension and 1168 for
atherosclerosis (Fig. 1).
Interview and examination
Sociodemographic factors, personal and family medical
history, medication, and traditional risk factors were
assessed by a computer-assisted face-to-face interview.
Having completed the interview, patients underwent a
routine medical examination including the measurement
of the systolic and diastolic BP as well as height and
weight to calculate the body mass index (BMI) (over-
weight=BMI ≥30).
After a 5-min resting period, systolic and diastolic BP was
measured three times on the right arm of seated subjects using
a digital BP monitor (HEM-705CP, Omron Corporation,
Tokyo, Japan) with each reading being followed by a further
resting period of 3 min. One of two differently sized cuffs
was applied according to the circumference of the partici-
pant's arm. The mean of the second and third measurement
was calculated and used for the present analyses. Hyperten-
sion was defined as a systolic BP of ≥140 mmHg, a diastolic
BP of ≥90 mmHg, or intake of antihypertensive medication.
Smoking was defined as current smoking (≥1 cigarette per
day), former smoking (former smoking of ≥1 cigarette per
day), and never smoking. Diabetes was considered to be
present if a self-reported physician diagnosis of diabetes was
given. Education was dichotomized into high school
graduation or not. Physical activity (weekly sportive activity
or exercise, e.g., walking, jogging, biking, swimming) was
assessed by interview in four categories: no physical activity
at all, less than 1 h/week, 1 to 2 h/week, and more than 2
 H.J. Grabe et al. / Journal of Psychosomatic Research 68 (2010) 139–147
Fig. 1. Description of the missing data and the generation of the final
analytic sample.
hours per week. The variable was categorized into less than 1
h/week (0) and N1 h/week (1).
Living in partnership was defined as living together in one
household (married or unmarried). All subjects were
informed to bring their packing containers from the
medication they had been taking during the last 7 days, as
well as their drug prescription sheets. Every compound was
recorded and categorized into the Anatomical Therapeutic
Chemical classification.
Nonfasting blood samples were taken and analyzed in a
central laboratory. Serum low-density lipoprotein (LDL)
cholesterol and high-density lipoprotein (HDL) cholesterol
(after precipitation) levels were measured photometrically
on a Hitachi 717 analyzer (Boehringer Mannheim,
Mannheim, Germany).
Assessment of alexithymia and mental distress
Alexithymia was assessed with the German version of the
widely used 20-item version of the Toronto Alexithymia
141
Scale (TAS-20) [8,9,22]. All items are rated on a five-point
scale (1=never applies; 5=applies always). The German
version of this self-report questionnaire has good psycho-
metric properties [internal consistency α=0.70; test–retest
reliability (r=0.71)] [22]. The three-factor structure has also
been confirmed in the German version: (1) difficulty
identifying feelings; (2) difficulty describing feelings; (3)
externally orientated thinking.
Mental distress during the last 12 months prior to the
examination was assessed during the face-to-face interview
by means of the Composite International Diagnostic
Screener [23]. The screening questions included the key
symptoms of mental disorders according to DSM-IV. The
screening questions for depressive disorders (“feelings of
sadness or depressed mood for a period of at least two
weeks” and “lack of interest, tiredness or loss of energy for a
period of at least two weeks”), for anxiety disorders (panic
attacks, generalized anxiety, agoraphobia, social phobia,
specific phobia), and for substance abuse (alcohol, medica-
tion, illegal drugs) were used. The variables for depression,
anxiety, and substance abuse were dichotomized (0=none,
1=at least one positive answer).
Ultrasound measurements
Certificated technicians examined the extracranial carotid
arteries bilaterally with B-mode ultrasonography using a 5-
MHz linear array transducer and a high-resolution instru-
ment (Diasonics VST Gateway, Santa Clara, CA, USA). The
far walls of the common carotid arteries, the internal carotid
arteries, as well as the carotid bifurcations on both sides were
evaluated online for the presence of atherosclerotic plaques.
Each vessel segment was visualized in multiple longitudinal
and transversal planes. Atherosclerotic plaques were defined
as a focal thickening of the vessel wall with protrusion into
the vessel lumen relative to adjacent segments or as a
localized roughness with increased echogenicity. All mea-
surements of intrareader, intrasonographer, interreader, and
intersonographer variations had Spearmen correlation coef-
ficients of N0.90.
Statistical analyses
Data on quantitative characteristics were expressed as
mean and standard error. Data on qualitative characteristics
were expressed as percent values. For continuous data,
comparisons between groups were done using the Mann–
Whitney U test, for nominal data with unadjusted logistic
regression analyses. Alexithymia (TAS-20) is psychometri-
cally a dimensional construct that follows a normal
distribution in the general population. The clinically used
cut-off score of N60 was not reasonable for the purpose of
our analyses in the general population because too few
subjects (2.5%) were classified as positive. Therefore, we
divided the study population into two groups using the
quintiles of the alexithymia score (≥49 for the top 20% of
142 H.J. Grabe et al. / Journal of Psychosomatic Research 68 (2010) 139–147
the participants aged 64 years or younger vs. b49). Logistic
regression analyses using hypertension or plaques as
dependent variables were performed, and the odds ratio
(OR) and its 95% confidence interval (CI) are presented. We
used the criterion of the change in the OR of interest in order
to estimate the effect of a confounder or, in case of
hypertension, to estimate the mediating effect on the relation
between alexithymia and atherosclerosis. A substantial
change was present if the inclusion in the model led to a
≥10% change in the OR of the TAS-20 score in relation to
hypertension and carotid atherosclerosis, respectively [24].
Analyses and diagnostics including plots for leverage,
residuals, and influence for checking model assumptions
were performed with Stata/SE software, version 10.0
(StataCorp LP, College Station, TX, USA). To present the
estimated prevalence across groups or predicted probabili-
ties, we used the procedure “prvalue” [25].
A two-tailed P value of b.05 was considered
statistically significant. P value functions were calculated
using Episheet [26].
Smoothed scatter plots were used to show the relation-
ships between the exposure and the two outcome variables in
more detail. The smoothing was generated with the STATA
command lowess. For the amount of smoothing, we chose a
bandwith of 0.8, meaning that 80% of the data are used in
smoothing each point. Logit specifies that the smoothed
curve be in terms of the log of the OR. Thus, a logit-
transformed value N0 means an OR N1.
Multiple imputations of missing data have been recom-
mended to reduce potential bias due to missing values in
complete case analysis [27]. We performed multiple
imputations for incomplete data containing both continuous
and categorical variables using S-PLUS 7.0 software
(Insightful Corporation, Seattle, WA, USA) and applying
methods established for the Cardiovascular Health Study
[27–29]. We chose gender, school education (three
categories), and smoking status (three categories) as
categorical variables of the saturated log-linear model; all
other variables were log transformed or dichotomized if they
were not normally distributed. The multivariable regression
model was designed by the 18 cells of the categorical
variables. For all analysis, we used a noninformative prior
[27–29] to generate 10 imputations.
Results
The descriptive characteristics of the analytic sample are
given in Table 1. In Table 2, the descriptive characteristics of
the analytic sample (complete case analysis) and the
excluded cases (due to missing data) are given (see Fig. 1).
Alexithymia (continuous and dichotomized scores) was
significantly associated with hypertension in the complete
case analyses (Table 3). None of the potential confounders
significantly interfered with this association and none
changed the OR of interest (TAS-20) ≥10%. However, in
imputation analyses for missing data, the association
between alexithymia and hypertension did not maintain
statistical significance.
Alexithymia (continuous and dichotomized scores) was
significantly associated with carotid atherosclerosis in the
complete case and in the combined imputation analyses
(Table 4). In the fully adjusted model, depression showed an
association with atherosclerosis (OR=1.51; 95% CI 0.95–
2.41; P=.08), whereas anxiety and addiction did not (PN.7).
Hypertension as potential mediator only slightly attenuated
the association between alexithymia and carotid atheroscle-
rosis (OR=1.76 to OR=1.70). Also, none of the other
potential confounders significantly interfered with the
association between TAS-20 and carotid atherosclerosis as
none of the confounders changed the OR of interest by
≥10%, based on the OR adjusted for age only. The
unadjusted OR of 1.5 (Table 4) corresponds to a difference
in prevalence of plaques between exposed (TAS-20 score
≥49) and unexposed subjects of about 10% [125/
238=52.5% (95% CI=46.2–58.9) among exposed vs. 401/
930=43.1% (95% CI=39.9–46.3) among unexposed sub-
jects] (Table 1 using row percentages instead of column
percentages as presented). As the OR is finally 1.7 (Table 4),
the corresponding adjusted difference in prevalence is over
10% [exposed: 52.1% (95% CI=43.0–61.2); unexposed:
39.0% (95% CI=34.4–43.6)].
With the exclusion of the dichotomous variable for
alexithymia (TAS score b49 or ≥49) from the fully adjusted
model, depression showed an association with plaques
(OR=1.58, 95% CI=0.99–2.51; P=.05), whereas the pres-
ence of anxiety had no effect (OR=1.01, 95% CI=0.54–1.70;
P=.95). With alexithymia entered into the model, the
association between depression and plaques became some-
what weaker (OR=1.51, 95% CI=0.95–2.41; P=.08).
In Fig. 2, the logit-transformed smoothing for the
relationships between alexithymia and the outcomes'
subclinical plaques or hypertension is shown. The differ-
ences in the two relationships suggest that the association
between alexithymia and subclinical plaques is not substan-
tially mediated by hypertension.
Discussion
Our results clearly demonstrated an association between
alexithymia, hypertension, and carotid atherosclerosis in the
general population. With regard to the definition of
hypertension, it is an inevitable problem that the prescription
and intake of antihypertensive medication, which is a
diagnostic criterion of our definition of hypertension, have
a clear behavioral dimension that is influenced by the
patient's health concerns, treatment-seeking behavior, and
adherence. These behavioral dimensions may be modified by
the degree of alexithymia traits [30]. Still, our results support
three previous reports on an association between alexithymia
and hypertension [16–18].
 H.J. Grabe et al. / Journal of Psychosomatic Research 68 (2010) 139–147 143

Table 1
Baseline characteristics of the analytic sample
Hypertension Plaques
No (n=675) Yes (n=503) No (n=642) Yes (n=526)
TAS-20 score, continuous 41.1±0.3 42.6±0.4 † 40.9±0.3 42.6±0.4 ‡
TAS-20 score ≥49 122 (18.1) 120 (23.9) ⁎ 113 (17.6) 125 (23.8) †
Age 42.7±0.4 51.0±0.4 ‡ 40.2±0.3 53.5±0.3 ‡
Gender (females) 417 (61.8) 247 (49.1) ‡ 371 (57.8) 286 (54.4)
School education
b10 years 85 (12.6) 142 (28.2) ‡ 55 (8.6) 171 (32.5) ‡
10 years (reference) 435 (64.4) 288 (57.3) 453 (70.6) 262 (49.8)
N10 years 155 (23.0) 73 (14.5) ⁎ 134 (20.9) 93 (17.7)
Marriage or cohabitation 571 (84.6) 435 (86.5) 538 (83.8) 460 (87.5)
Depression 131 (19.4) 86 (17.1) 110 (17.1) 105 (20.0)
Anxiety 138 (20.4) 109 (21.7) 131 (20.4) 114 (21.7)
Addiction 66 (9.8) 42 (8.3) 63 (9.8) 43 (8.2)
Physical activity 289 (42.8) 159 (31.6) ‡ 254 (39.6) 193 (36.7)
Overweight (BMI N30) 113 (16.7) 222 (44.1) ‡ 121 (18.8) 212 (40.3) ‡
Smoking status
Never smoker (reference) 274 (40.6) 224 (44.5) 275 (42.8) 221 (42.0)
Ex-smoker 164 (24.3) 159 (31.6) 164 (25.5) 157 (29.8)
Current smoker 237 (35.1) 120 (23.9) ‡ 203 (31.6) 148 (28.1)
Diabetes mellitus 14 (2.1) 58 (11.5) ‡ 16 (2.5) 56 (10.6) ‡
HbA1c 5.0±0.02 5.5±0.04 ‡
LDL Cholesterol 3.2±0.04 3.8±0.04 ‡
HDL Cholesterol 1.2±0.02 1.1±0.02 ‡
Hypertension (≥140/≥90 mmHg/medication) 179 (27.9) 320 (60.8) ‡
Values are shown as mean±S.E. or numbers (column percentages).
⁎ Pb.05.
†
Pb.01.
‡
Pb.001.

The diagnosis of subclinical carotid atherosclerotic
plaques is not confounded by such behavioral factors on
the probands' side and, therefore, may be considered as a
robust diagnostic end point. We aimed as much as possible to
reduce the effect of reverse causality by excluding subjects
with the prior diagnoses of MI and stroke as these conditions
may be associated with secondary alexithymic traits due to
primarily vascular events [20,21].
Moreover, the significant association between alexithy-
mia and carotid plaques was maintained through the
combined imputation analyses for missing data. It was
somewhat unexpected that the associations of alexithymia
with hypertension and atherosclerosis were virtually not
confounded by any of the introduced variables. Also,
depressive symptoms, anxiety, and substance abuse did not
interfere with the association between alexithymia, hyper-
tension, and atherosclerosis.
Although associated with alexithymia, hypertension did
not mediate the association between alexithymia and
atherosclerosis to a relevant degree. As illustrated in
Fig. 2, the risk for hypertension and atherosclerosis started
to increase at moderate TAS-20 scores. The differences in
the two curves also suggest that the association between
alexithymia and subclinical plaques is not substantially
mediated by hypertension. An almost linear association
between alexithymia and atherosclerosis emerged already at
low TAS-20 scores up to a TAS-20 score of 60.
An OR overestimates the relative risk, especially if the
prevalence of the disease is high as for hypertension and
plaques in the present study. Because of the high
prevalence, however, an OR N2 was not to be expected.
Unadjusted OR and fully adjusted OR correspond to a
difference in plaques between exposed and unexposed
subjects of about 10%. Such a difference in longitudinal
studies or clinical trials is usually considered to be a
relevant effect or a treatment success. Furthermore, for a
given case of plaque caused by alexithymia and other
conditions (e.g., smoking), alexithymia would be no less
important than any of the other conditions for that case. On
the population level, we would consider alexithymia to be a
relevant cause of plaque [31].
To our best knowledge, only one other study has
investigated alexithymia with regard to carotid atheroscle-
rosis [30]. Kauhanen et al. [30] demonstrated an associa-
tion between alexithymia and the prior diagnosis of
coronary heart disease (CHD) in a population-based
sample from Finland. In a subsample of patients with
CHD, alexithymia was not associated with a greater pre-
valence of ischemia on an exercise tolerance test and the
results of B-mode ultrasonography indicated that carotid
144 H.J. Grabe et al. / Journal of Psychosomatic Research 68 (2010) 139–147

Table 2
Variables for cases included (analytic sample) vs. excluded from complete case analyses
Excluded (n≤1103) Included (n=1168) P value
Age 48.0±0.3 46.2±0.3 b.001
Gender (females) 575 (52.1) 657 (56.3) .053
School education b.001
8 years 311 (28.3) 226 (19.3) b.001
10 years (reference) 598 (54.4) 715 (61.2)
12 years 190 (17.3) 227 (19.4) .995
Marriage or cohabitation 893 (81.3) 998 (85.4) .009
Depression 191 (17.4) 215 (18.4) .547
Anxiety 233 (21.2) 245 (21.0) .918
Addiction 85 (7.7) 106 (9.1) .258
Physical activity 371 (33.8) 447 (38.3) .026
Overweight 289 (26.3) 333 (28.5) .239
Smoking status .013
Never smoker (reference) 409 (37.2) 496 (42.5)
Ex-smoker 301 (27.4) 321 (27.5) .218
Current smoker 388 (35.3) 351 (30.1) .003
Diabetes mellitus 58 (5.4) 72 (6.2) .418
HbA1c 5.3±0.02 5.2±0.02 .030
LDL Cholesterol 3.6±0.03 3.5±0.03 .147
HDL Cholesterol 1.2±0.01 1.2±0.01 .100
Hypertension (≥140/≥90 mmHg/medication) 503 (45.7) 499 (42.7) .163
Plaques 578 (52.5) 526 (45.0) b.001
Alexithymia score, continuous 41.7±0.3
Imputation 1 42.5±0.3 .027
Imputation 2 43.0±0.3 b.001
Imputation 3 41.8±0.3 .722
Imputation 4 41.9±0.3 .516
Imputation 5 41.8±0.3 .500
Imputation 6 42.5±0.3 .027
Imputation 7 42.5±0.3 .015
Imputation 8 42.1±0.3 .257
Imputation 9 41.9±0.3 .422
Imputation 10 42.3±0.3 .035
Values are shown as mean±S.E. or numbers (column percentage).

atherosclerosis actually decreased as alexithymia scores
increased. Alexithymia was associated with higher perceived
exertion and with more self-reported symptoms during
the exercise tolerance test. However, these results were
limited to patients with CHD and suggest that alexi-
thymics, maybe because of a higher perceived symptom
load, were diagnosed earlier in the course of their CHD
than nonalexithymics.
In a systematic review on psychosocial risk factors on
stress and CHD, the National Heart Foundation of Australia

Table 3
Logistic regression analyses for hypertension using the continuous TAS-20 score and the dichotomized TAS-20 score with successive adjustment for
confounders
Complete case (n=1178) Combined imputation (n=2271)
Hypertension Continuous TAS-20 TAS ≥49 Continuous TAS-20 TAS ≥49
Unadjusted 1.019 (1.006–1.033) † 1.420 (1.069–1.886) ⁎ 1.015 (1.001–1.029) ⁎ 1.284 (0.986–1.671)
Successive adjustment for
Age 1.021 (1.006–1.036) † 1.509 (1.109–2.054) † 1.016 (1.001–1.031) ⁎ 1.331 (0.965–1.835)
Gender, school education, marriage or cohabitation 1.018 (1.002–1.033) ⁎ 1.442 (1.053–1.975) ⁎ 1.013 (0.998–1.028) 1.261 (0.919–1.729)
Depression, anxiety, addiction 1.019 (1.003–1.035) ⁎ 1.456 (1.051–2.017) ⁎ 1.013 (0.997–1.029) 1.248 (0.893–1.744)
Physical activity 1.018 (1.002–1.034) ⁎ 1.468 (1.059–2.034) ⁎ 1.012 (0.996–1.029) 1.251 (0.893–1.753)
Overweight, smoking status (three categories), 1.023 (1.006–1.040) † 1.604 (1.141–2.254) † 1.016 (0.999–1.034) 1.348 (0.937–1.939)
diabetes mellitus
Values are shown as OR (95% CI).
⁎ Pb.05.
†
Pb.01
 H.J. Grabe et al. / Journal of Psychosomatic Research 68 (2010) 139–147 145

Table 4
Logistic regression analyses for subclinical atherosclerosis using the continuous TAS-20 score and the dichotomized TAS-20 score with successive adjustment
for confounders
Complete case (n=1168) Combined imputation (n=2271)
Subclinical atherosclerosis Continuous TAS TAS ≥49 Continuous TAS TAS ≥49
‡ † †
Unadjusted 1.023 (1.010–1.037) 1.459 (1.097–1.942) 1.019 (1.006–1.032) 1.383 (1.108–1.727) †
Successive adjustment for
Age 1.035 (1.017–1.053) ‡ 1.891 (1.310–2.730) ‡ 1.027 (1.011–1.043) † 1.646 (1.207–2.246) †
Gender, school education, marriage, or cohabitation 1.031 (1.013–1.050) ‡ 1.852 (1.277–2.686) † 1.023 (1.007–1.039) † 1.568 (1.137–2.161) †
Depression, anxiety, addiction 1.029 (1.010–1.048) † 1.786 (1.216–2.624) † 1.021 (1.004–1.038) ⁎ 1.513 (1.082–2.117) ⁎
Physical activity 1.030 (1.011–1.049) † 1.780 (1.209–2.621) † 1.021 (1.004–1.039) ⁎ 1.513 (1.079–2.120) ⁎
Overweight, smoking status (three categories), 1.030 (1.011–1.049) † 1.791 (1.207–2.660) † 1.021 (1.003–1.039) ⁎ 1.506 (1.065–2.127) ⁎
diabetes mellitus
HbA1c, LDL cholesterol, HDL cholesterol 1.028 (1.009–1.048) † 1.762 (1.181–2.628) † 1.020 (1.002–1.037) ⁎ 1.481 (1.037–2.115) ⁎
Hypertension (≥140/≥90 mmHg/medication) 1.026 (1.007–1.046) † 1.700 (1.138–2.540) † 1.018 (1.001–1.036) ⁎ 1.443 (1.003–2.075) ⁎
Values are shown as OR (95% CI).
⁎ Pb.05.
†
Pb.01.
‡
Pb.001.

concluded that (i) there is strong and consistent evidence of
an independent causal association between depression,
social isolation, and lack of quality social support, and the
causes and prognosis of CHD; and (ii) there is no strong or
consistent evidence for a causal association between
chronic life events, work-related stressors (job control,
demands, and strain), type A behavior patterns, hostility,
anxiety disorders or panic disorders, and CHD [32]. In our
study, we can confirm the association between depression
and plaques and the lack of association between anxiety
and plaques. Although alexithymia and depression have
been related to each other [10,33], their associations with
plaques were largely independent from each other. As a
personality trait, alexithymia may act as a longstanding risk
factor. Moreover, it may be more directly associated with
pathophysiological processes than other psychosocial con-
structs (e.g., job strain).
Most likely, alexithymia is a consequence of psychosocial
factors as well as familial and genetic factors [34,35] that
influence early periods of affect differentiation [36]. The
results of the present study are in line with a model that links
alexithymia to emotional dysregulation and thereby to
Fig. 2. Logit-transformed smoothing for the association between alexithymia
and the outcomes' subclinical plaques or hypertension.
dysregulations of the autonomic nervous system. Excessive
activation of the sympathetic nervous system and a
decreased vagal function have been associated with various
cardiovascular risk factors [4–7]. This “dysregulation
hypothesis” is supported by the finding of a high correlation
(r=0.8) between alexithymia and the norepinephrine/cortisol
ratio in males [37].
Some limitations merit discussion: we did not perform
prospective analyses. Although we assume that alexithymia
represents a longstanding risk for autonomic dysregulations
that interfere with the integrity of the cardiovascular
system, our study cannot prove the causality of the
reported association. As alexithymia was assessed in an
associated subproject of SHIP, TAS-20 data were only
available in 45% of the 3300 subjects of the SHIP-1
cohort. However, state-of-the-art imputations justify gen-
eralizing the findings of a relevant association at
population level between alexithymia and atherosclerotic
plaques. In imputation analyses, the association between
alexithymia and hypertension did not maintain statistical
significance. Nevertheless, the P value functions for this
relationship (figure not shown) are compatible with the
presence of a small to moderate effect rather than with the
absence of an effect.
In future studies, the longitudinal effects of alexithymia
on the incidence of atherosclerosis and hypertension should
be evaluated. Furthermore, the association between the type
D personality construct (preferential experience of negative
emotions and social inhibition) which has been associated
with CHD and alexithymia should be clarified [3]. If the
association between alexithymia and atherosclerosis or CDH
is confirmed, intervention programs against alexithymia
could be developed especially for subjects at high risk for
CVD [38,39].
In all, we conclude that alexithymic personality traits are
likely to represent a long-term risk for CVD independently
from behavioral risk factors.
146 H.J. Grabe et al. / Journal of Psychosomatic Research 68 (2010) 139–147
Appendix A. External financial support in the past 3 years
Hans Joergen Grabe: German Research Foundation;
Federal Ministry of Education and Research Germany;
Salus-Institute for Trend Research and Therapy Evaluation
in Mental Health; speakers honoraria from Eli Lilly,
Novartis, Eisai, Wyeth, Boehringer Ingelheim, AstraZeneca,
and travel funds from Janssen-Cilag, AstraZeneca, and
Eli Lilly.
Christian Schwahn: None.
Sven Barnow: German Research Foundation, Federal
Ministry of Health.
Carsten Spitzer: Travel funds and speakers honoraria
from Janssen-Cilag; speakers honorarium from Boehringer
Ingelheim; research grant from Stiftung zur Aufarbeitung der
SED-Diktatur.
Ulrich John: Research funding: Association for the
Support of Rehabilitation Research, European Union;
Federal Ministry of Education and Research Germany;
German Research Foundation; German Cancer Society;
Social Ministry of the Federal State of Mecklenburg-West
Pomerania of Germany.
Harald J. Freyberger: German Research Foundation;
Social Ministry of the Federal State of Mecklenburg-West
Pomerania; Family Ministry of the Federal Republic of
Germany; Federal Ministry of Health; speakers honoraria
from AstraZeneca, Lilly, Novartis, and travel funds from
Janssen-Cilag.
Ulf Schminke: Speakers honoraria and travel funds from
the German Society of Neurology, Section on Neurological
Intensive Care Medicine; and from the Polish Stroke
Society; furthermore, speakers honoraria from GlaxoS-
mithKline and Boehringer Ingelheim.
Stephan Felix: Research grants from Deutsche For-
schungsgemeinschaft (DFG); Federal Ministry of Education
and Research (BMBF) Germany; ENDI Foundation; Krupp
von Bohlen und Halbach Foundation. Speakers honoraria
from AstraZeneca, Novartis, Biotronik, Medtronik, MSD,
Essex Pharma, BayerSchering.
Henry Völzke: Research grants by Sanofi-Aventis,
Biotronik, the Humboldt Foundation, the Federal Ministry
of Education and Research (Germany), and the German
Research Foundation.
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