Heart: first published as 10.1136/heartjnl-2019-315460 on 4 November 2019. Downloaded from http://heart.bmj.
com/ on November 14, 2019 at University of California San Francisco (UCSF).
►► Additional material is
published online only. To view,
please visit the journal online
(http://d​ x.​doi.o​ rg/​10.​1136/​
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For numbered affiliations see
end of article.
Correspondence to
Anne Vinggaard Christensen,
Centre for Cardiac, Vascular,
Pulmonary and Infectious
Diseases, Rigshospitalet,
Copenhagen University Hospital,
Copenhagen, Denmark;
a​ nne.​vinggaard.c​ hristensen@​
regionh.​dk
Received 27 May 2019
Revised 30 August 2019
Accepted 3 September 2019
© Author(s) (or their
employer(s)) 2019. No
commercial re-use. See rights
and permissions. Published
by BMJ.
To cite: Christensen AV,
Juel K, Ekholm O, et al.
Heart Epub ahead of
print: [please include Day
Month Year]. doi:10.1136/
heartjnl-2019-315460
Original research
Significantly increased risk of all-cause mortality
among cardiac patients feeling lonely
Anne Vinggaard Christensen,‍ ‍ 1 Knud Juel,2 Ola Ekholm,2 Lars Thrysøe,3
Charlotte Brun Thorup,4 Britt Borregaard,‍ ‍ 5 Rikke Elmose Mols,6
Trine Bernholdt Rasmussen,7 Selina Kikkenborg Berg‍ ‍ 1,2,8
ABSTRACT
Objective  To explore whether living alone and
loneliness 1) are associated with poor patient-reported
outcomes at hospital discharge and 2) predict cardiac
events and mortality 1 year after hospital discharge
in women and men with ischaemic heart disease,
arrhythmia, heart failure or heart valve disease.
Methods  A national cross-sectional survey including
patients with known cardiac disease at hospital
discharge combined with national register data at
baseline and 1-year follow-up. Loneliness was evaluated
using one self-reported question, and information on
cohabitation was available from national registers.
Patient-reported outcomes were Short Form-12, Hospital
Anxiety and Depression Scale and HeartQoL. Clinical
outcomes were 1-year cardiac events (myocardial
infarction, stroke, cardiac arrest, ventricular tachycardia/
fibrillation) and all-cause mortality from national
registers.
Results  A total of 13 443 patients (53%) with
ischaemic heart disease, arrhythmia, heart failure or
heart valve disease completed the survey. Of these, 70%
were male, and mean age was 66.1 among women and
64.9 among men. Across cardiac diagnoses, loneliness
was associated with significantly poorer patient-reported
outcomes in men and women. Loneliness predicted all-
cause mortality among women and men (HR 2.92 (95%
CI 1.55 to 5.49) and HR 2.14 (95% CI 1.43 to 3.22),
respectively). Living alone predicted cardiac events in
men only (HR 1.39 (95% CI 1.05 to 1.85)).
Conclusions  A strong association between loneliness
and poor patient-reported outcomes and 1-year mortality
was found in both men and women across cardiac
diagnoses. The results suggest that loneliness should be
a priority for public health initiatives, and should also be
included in clinical risk assessment in cardiac patients.
Introduction
Previous research has pointed to the importance of
social relationships to health as loneliness and lack
of social support is associated with an increased risk
of ischaemic morbidity and mortality.1 2 There are
numerous theoretical definitions of loneliness, but
most researchers within the field agree on three
elements: 1) loneliness is a result of perceived defi-
ciencies in a person’s social relationships, 2) it is a
subjective experience and is not the same as social
isolation and 3) it is unpleasant and distressing.3 A
systematic review concluded that poor social rela-
tionships were associated with a 29% increase in
Christensen AV, et al. Heart 2019;0:1–7. doi:10.1136/heartjnl-2019-315460
Cardiac risk factors and prevention
risk of coronary heart disease and a 32% increase in
the risk of stroke,1 and a recent study links loneli-
ness to an increased risk of incident cardiovascular
disease of 27%.4 Similarly, lack of social support
appears to play a role in the progression of cardio-
vascular disease.5 6 A meta-analysis found that
poor social support negatively affected cardiac and
all-cause mortality in prognostic studies (relative
risk (RR) range 1.59–1.71).5 Living alone is related
to loneliness, but living alone does not equal feeling
lonely. However, living alone has also been linked
to increased risk of mortality and cardiac events,
but evidence is not consistent.7 8 Recently, a study
showed that men living alone had a significantly
increased risk of both all-cause and cardiovascular
Protected by copyright.
mortality compared with men not living alone after
32 years of follow-up.9
The explanation for the link between loneli-
ness and health includes different pathways. One
pathway is behavioural as the existence of social
relationships has a direct health effect because
it promotes healthy behaviour such as exercise,
healthy eating, not smoking and greater adherence
to medical regimens.6 10 Feeling lonely on the other
hand impairs the capacity to self-regulate, mini-
mises the likelihood of performing physical activity
and is a risk factor for obesity and excessive alcohol
abuse.11 These differences become more evident
with age, as the effects of poor health behaviour
start to show.10
Other pathways are psychological and biolog-
ical. The existence of social relationships is benefi-
cial because it increases feelings of safety and trust
and ‘buffers’ the potentially harmful influences of
stress-induced cardiovascular reactivity.6 Further-
more, it is possible that social support helps reduce
the exposure to stressful events.6 The pathways may
impact each other and affect biological processes
with an impact on surrogate biological markers.10
Research on the health effects of loneliness and
living alone within cardiology has often focused on
ischaemic heart disease (IHD). Furthermore, studies
rarely include patient-reported outcomes (PROs),
which are important independent predictors of
health outcomes.12 Two previous studies including
patients with implantable cardioverter defibrillators
and congenital heart disease, respectively found
low perceived social support and chronic loneliness
to be associated with perceived health status and
depression symptoms.13 14 Therefore, the objectives
of this study were to explore:
  1

Cardiac risk factors and prevention
1. Whether living alone and loneliness are associated with poor
PROs at hospital discharge in women and men with IHD,
arrhythmia, heart failure, or heart valve disease.
2. Whether living alone and loneliness predict cardiac events
and mortality 1 year after hospital discharge in women and
men with IHD, arrhythmia, heart failure or heart valve
disease.
Methods
The methods are described in more detail in the prepublished
protocol.15 In the following, a brief overview of the DenHeart
study is presented.
Study design
The DenHeart study is a cross-sectional survey combined with
data from national registers at baseline and 1-year follow-up.
All patients hospitalised at a heart centre were invited to answer
a self-reported questionnaire at hospital discharge to evaluate
PROs across cardiac diagnostic groups. The present study
includes only patients with IHD, arrhythmia, heart failure and
heart valve disease.
Setting and participants
Over 1 year (15 April 2013 to 15 April 2014), all patients
discharged or transferred from the five Danish heart centres
were invited to participate in the study.
Eligibility criteria
All patients were consecutively included. Patients who were
under 18 years of age, who did not have a Danish civil registra-
tion number or who did not understand Danish were excluded
from the study. For ethical reasons, patients who were uncon-
scious at the time of transfer from a heart centre were also
excluded.
Recruitment
To avoid recall bias, patients were asked to complete and return
the questionnaire before they left the hospital or complete it
at home within 3 days of discharge and return it by mail in a
prepaid envelope.
Variables
Baseline
Survey data were combined with data from the following Danish
national registers at baseline: The Danish Civil Registration
System (gender, age, marital status),16 The Danish National
Patient Register (cardiac diagnosis at discharge, comorbidity)17
and Danish Education Registers (educational level).18
To combine patient-reported data with demographic and clin-
ical variables from the national registers, all responders were
matched to a hospital discharge in The Danish National Patient
Register.
Responders were divided into diagnostic groups based on
their primary ICD-10 action diagnosis obtained from The
Danish National Patient Register. Four diagnostic groups were
included in the analyses, and they were defined as follows: IHD:
I20-I25, T82.3D, Z95.1, Z95.5; arrhythmia: I44-I49, Z95.0,
R00.0, R00.1, R00.2, R00.8A, T75.0, T75.4, T82.1, T82.8;
heart failure: I11.0, I42.0-I43.8, I50, I51.7, R57.0 and heart
valve disease: I05.0-I06.0, I34.0-I37.2, I39.1, I39.2, I51.1A,
Z95.2-Z95.4.
Information on comorbidity was obtained from The Danish
National Patient Register and calculated 10 years back, not
2 Christensen AV, et al. Heart 2019;0:1–7. doi:10.1136/heartjnl-2019-315460
Heart: first published as 10.1136/heartjnl-2019-315460 on 4 November 2019. Downloaded from http://heart.bmj.com/ on November 14, 2019 at University of California San Francisco (UCSF).
including the index discharge. The Tu comorbidity index score
was calculated19 with information on primary and secondary
diagnoses for all patients. The following diseases were included:
congestive heart failure, cardiogenic shock, arrhythmia, pulmo-
nary oedema, malignancy, diabetes, cerebrovascular disease,
acute/chronic renal failure, chronic obstructive pulmonary
disease. A Tu comorbidity score of zero equals no comorbidities,
a score of one means one of the included comorbidities, etc. All
diagnoses were weighted equally.
Exposure
The objective information on cohabitation was obtained from
national registers. Living alone was defined as a man or woman
not in an identifiable cohabitation. Cohabitation was defined
by the following categories: married couple, other couple and
household consisting of several people from more than one
family (eg, nursing home or collective).
As a subjective measure of loneliness patients answered a
question about feeling lonely from the Danish National Health
Survey20:
“Does it ever happen that you are alone even though you
would prefer to be with other people?” Loneliness was defined
by the answers: “yes, often” and “yes, sometimes”. Other
possible responses were “yes, but rarely” and “no”.
Patient-reported outcomes
The following questionnaire instruments were included in the
Protected by copyright.
DenHeart questionnaire:
The Short Form-12 (SF-12), a brief measure of health-related
quality of life that generates both a physical component score
(PCS) and a mental component score (MCS). Higher scores indi-
cate a better health status.21 The Hospital Anxiety and Depres-
sion Scale (HADS), a 14-item questionnaire that assesses levels
of anxiety and depression symptoms in medically ill patients.
Scores of 8–10 suggest the presence of a mood disorder. Scores
≥11 indicate the probable presence of a mood disorder.22
HeartQoL, a disease-specific questionnaire that measures quality
of life in cardiac patients and produces a global score and two
subscales: a physical and an emotional scale ranging from 0 to 3
with higher scores indicating better quality of life status.23
Furthermore, patients answered questions about health
behaviour (current and previous smoking behaviour, alcohol
intake during a typical week and medicine compliance), height
and weight.
Prognostic outcomes
From The Danish Civil Registration System information on
all-cause mortality during the first year after the index admis-
sion was obtained. Information on cardiac events during the first
year was obtained from The Danish National Patient Register.
Cardiac events were defined as: myocardial infarction: I21;
stroke: I60-I64, I67; cardiac arrest: I46; ventricular tachycardia/
ventricular fibrillation: I49.
Study size
The study population consisted of all patients discharged from
the five heart centres during the project period. To avoid selec-
tion bias, all patients were included consecutively. Hospitalised
patients with lung disease and other non-cardiac diseases were
excluded. The analyses in this paper are based on 13 446 patients
with IHD (n=7169, 53%), arrhythmia (n=4316, 32%), heart
failure (n=987, 7%) and heart valve disease (n=974, 7%).

Figure 1  Flow chart.
Statistical methods
A total of 17 respondents were lost to follow-up in the registers
as they did not have an address in Denmark. These subjects were
excluded from the present analyses. Follow-up was continued
until the first cardiac event or until death, emigration or end of
follow-up.
Baseline differences in demographic, clinical and behavioural
variables were tested using χ2 tests. For continuous variables
t-tests were used.
To explore the association between loneliness and PROs,
linear regression models were used for continuous outcomes,
and logistic regression models were used for binary outcomes.
All analyses were adjusted for living alone (when loneliness is
the independent variable), loneliness (when living alone is the
independent variable), age, educational level, cardiac diagnosis,
comorbidity (Tu comorbidity index), body mass index, smoking
behaviour, alcohol intake and medicine compliance.
Multivariate Cox proportional hazards regression models,
with age as the time scale, were used to explore the predictive
value of loneliness at baseline, and cardiac events and all-cause
mortality after 1  year. Unadjusted and adjusted results are
presented. The proportional hazards assumption was checked
Christensen AV, et al. Heart 2019;0:1–7. doi:10.1136/heartjnl-2019-315460
Heart: first published as 10.1136/heartjnl-2019-315460 on 4 November 2019. Downloaded from http://heart.bmj.com/ on November 14, 2019 at University of California San Francisco (UCSF).
Cardiac risk factors and prevention
graphically using Kaplan-Meier curves and log-minus-log plots.
The resulting curves were found to be parallel, indicating that the
proportional hazards assumption was met. Results are presented
as hazard ratios (HRs) with 95% confidence intervals (CIs).
Differences between men and women and diagnostic groups
were tested by including interactions. Based on the results, anal-
yses were conducted for women and men separately. Further-
more, interactions between living alone and loneliness were
tested in all models.
All analyses were conducted using SAS V.9.4.
Patient and public involvement
In designing the study focus was on including PROs as an
important contribution to health assessment and further devel-
opment of care. Patients were involved in survey preparation.
The questionnaire was pretested for feasibility by 12 (10 males,
2 females) patients in the age range 52–81 years (mean 65.9)
from medical and surgical wards at three of the heart centres.
The questionnaire was adjusted accordingly.
Ethics
The study complies with the Declaration of Helsinki. DenHeart
is registered at ​ClinicalTrials.​gov (NCT01926145) and approved
by the institutional boards of the heart centres. Patients signed
informed consent.
Results
Inclusion of patients is presented in the flow chart (figure 1).
Protected by copyright.
A total of 13 446 (53%) patients were included in the analyses.
Demographic and clinical profile is presented in table 1 for
women and men stratified by loneliness. Significant baseline
differences were seen between those feeling lonely and those not
feeling lonely.
Loneliness and patient-reported outcomes
For both women and men living alone was associated with a
reduced risk of anxiety symptoms (odds ratio (OR)=0.71 (95%
CI 0.59 to 0.85) and OR 0.80 (95% CI 0.69 to 0.93)), respec-
tively (table 2). Women feeling lonely had a 6.15 (95% CI −7.20
to −5.09) point lower MCS score and a 1.81 (95% CI −2.71
to −0.83) point lower PCS score compared with women not
feeling lonely. Furthermore, women feeling lonely had approxi-
mately 2.7 times higher odds of reporting symptoms of anxiety
and depression and reported a significantly lower quality of
life score compared with women not feeling lonely. Likewise,
men feeling lonely reported significantly poorer MCS, PCS and
quality of life scores and had almost three times higher odds of
reporting symptoms of anxiety and depression compared with
men not feeling lonely (table 2). Mean values and proportions
for PROs and prognostic outcomes are presented in online
supplementary table 1.
No statistically significant interaction was found between
living alone and loneliness.
Loneliness and cardiac events and mortality
After adjustment for potential confounders, women feeling
lonely had an almost tripled risk of all-cause mortality compared
with women who did not feel lonely (HR=2.92 (95% CI 1.55
to 5.49)) (table 3).
After adjustment for potential confounders, men living alone
had an increased risk of cardiac events (HR 1.39 (95% CI 1.05
to 1.85)) and men feeling lonely had a doubled risk of all-cause
mortality (HR 2.14 (95% CI 1.43 to 3.22)) (table 3).
3
 Heart: first published as 10.1136/heartjnl-2019-315460 on 4 November 2019. Downloaded from http://heart.bmj.com/ on November 14, 2019 at University of California San Francisco (UCSF).
Cardiac risk factors and prevention

Table 1  Demographic and clinical profile at baseline for women and men stratified by loneliness
Women Men
Feeling lonely Not feeling lonely P value* Feeling lonely Not feeling lonely P value*
n, % 1264 (33) 2628 (67) 2139 (24) 6912 (76)
Age, mean (SD) 66.56 (14.44) 65.44 (12.90) 0.0141† 64.57 (12.64) 64.88 (11.23) >0.10†
Living alone (n, %) 784 (62) 763 (29) <0.0001 1000 (47) 946 (14) <0.0001
Marital status (n, %) <0.0001 <0.0001
 Married 423 (33) 1671 (63) 980 (45) 5404 (77)
 Divorced 262 (20) 363 (14) 667 (22) 667 (10)
 Widowed 460 (36) 421 (16) 357 (17) 349 (5)
 Unmarried 141 (11) 199 (8) 350 (16) 568 (8)
Educational level (n, %) <0.0001 <0.0001
 Basic school 583 (46) 964 (37) 749 (36) 1696 (25)
 Upper secondary or vocational school 450 (36) 978 (38) 907 (43) 3391 (50)
 Higher education 225 (18) 668 (26) 432 (21) 1763 (25)
Cardiac diagnosis (n, %) >0.10 >0.10
 Ischaemic heart disease 636 (50) 1265 (48) 1217 (56) 3850 (55)
 Arrhythmia 451 (35) 1010 (38) 625 (29) 2129 (31)
 Heart failure 81 (6) 180 (7) 187 (9) 519 (7)
 Heart valve disease 118 (9) 199 (8) 137 (6) 490 (7)
Comorbidity (n, %)
 Hypertension 536 (42) 913 (34) <0.0001 800 (37) 2283 (33) 0.0002
 Ventricular arrhythmia 51 (4) 85 (3) >0.10 123 (6) 352 (5) >0.10
 Ischaemic heart disease 540 (42) 972 (37) 0.0012 1088 (50) 3086 (44) <0.0001
 Myocardial infarction 210 (16) 323 (12) 0.0003 515 (24) 1423 (20) 0.0007

Protected by copyright.
 PCI 204 (16) 321 (12) 0.0011 487 (23) 1385 (20) 0.0072
 CABG 35 (3) 61 (2) >0.10 133 (6) 351 (5) 0.0423
 Diabetes 164 (13) 287 (11) 0.0731 262 (12) 561 (8) <0.0001
 Heart failure 47 (4) 59 (2) 0.0092 491 (23) 1241 (18) <0.0001
 Renal disease 212 (17) 336 (13) 0.0011 109 (5) 224 (3) <0.0001
 Chronic obstructive pulmonary disease 120 (9) 166 (6) 0.0005 198 (9) 377 (5) <0.0001
Tu comorbidity score (n, %) <0.0001† <0.0001†
 0 469 (37) 1084 (41) 832 (38) 2998 (43)
 1 486 (38) 992 (37) 689 (32) 2289 (33)
 2 208 (16) 408 (15) 639 (17) 1143 (16)
 ≥3 131 (10) 170 (6) 276 (13) 558 (8)
Life style factors (n, %)
 BMI≥25 673 (57) 1437 (57) >0.10 1455 (71) 4770 (71) >0.10
 BMI≥30 297 (25) 582 (23) >0.10 560 (28) 1642 (25) 0.0077
 Ever smoker 820 (65) 1541 (59) 0.0006 1588 (75) 4880 (71) 0.0007
 Alcohol intake above high-risk limit‡ 52 (5) 115 (5) >0.10 174 (9) 624 (10) >0.10
 Non-compliant§ 66 (6) 98 (4) 0.0588 146 (8) 296 (5) <0.0001
*χ2 tests.
†T-test.
‡The Danish National Board of Health defines the high-risk limit for alcohol consumption as a weekly intake of >21 standard drinks for men and >14 standard drinks for women.
§Patients were defined as non-compliant if they forgot to take their medication more than once a week (self-reported).
BMI, body mass index; CABG, coronary artery bypass graft;PCI, percutaneous coronary intervention.

No statistically significant interaction was found between and men. Among men only, living alone predicted increased risk
living alone and loneliness. of cardiac events.

Discussion Interpretation
The results of this study show that women and men who feel The present results show that loneliness is significantly associ-
lonely report significantly poorer mental and physical health, ated with PROs. This highlights the possible impairing effects
quality of life and are more likely to report anxiety and depres- on health associated with loneliness as experienced and reported
sion symptoms. In both women and men living alone was asso- by the patient. The findings of the predictive value of loneliness
ciated with reduced risk of anxiety symptoms. After adjustment on mortality in this study are in line with previous research in
for potential confounders loneliness was associated with a cardiovascular disease with loneliness significantly influencing
significantly increased risk of all-cause mortality among women the prognosis.1 2
4 Christensen AV, et al. Heart 2019;0:1–7. doi:10.1136/heartjnl-2019-315460
 Heart: first published as 10.1136/heartjnl-2019-315460 on 4 November 2019. Downloaded from http://heart.bmj.com/ on November 14, 2019 at University of California San Francisco (UCSF).
Cardiac risk factors and prevention

Table 2  Association between living alone, loneliness and patient-reported outcomes at hospital discharge
Mental component scale Physical component scale HADS-A ≥8 HADS-D ≥8 HeartQoL global
β (95% CI)‡ β (95% CI)‡ OR (95% CI)§ OR (95% CI)§ β (95% CI)‡
Women n=4078
 Living alone 1.33 (0.29 to 2.37) 0.04 (−0.93 to 1.01) 0.71 (0.59 to 0.85)** 0.82 (0.67 to 1.01) −0.004 (−0.06 to 0.02)
 Loneliness −6.15 (−7.20 to −5.09)** −1.81 (−2.79 to −0.83)** 2.78 (2.32 to 3.33)** 2.64 (2.16 to 3.23)** −0.27 (−0.33 to −0.21)**
Men n=9368
 Living alone −0.51 (−1.22 to 0.19) −0.36 (−1.05 to 0.33) 0.80 (0.69 to 0.93)* 0.93 (0.79 to 1.09) −0.02 (−0.06 to 0.03)
 Loneliness −5.54 (−6.31 to −4.96)** −1.87 (−2.54 to −1.21)** 3.02 (2.64 to 3.45)** 2.84 (2.45 to 3.30)** −0.28 (−0.32 to −0.23)**
*P<0.05.
**P<0.001.
‡Linear regression model adjusted for living alone (when loneliness is the independent variable), loneliness (when living alone is the independent variable), age, cardiac
diagnosis, educational level, comorbidity (Tu comorbidity index), BMI, smoking, alcohol intake and medicine compliance.
§Logistic regression model adjusted for living alone (when loneliness is the independent variable), loneliness (when living alone is the independent variable), age, cardiac
diagnosis, educational level, comorbidity (Tu comorbidity index), BMI, smoking, alcohol intake and medicine compliance.
BMI, body mass index; CI, confidence interval; HADS, Hospital Anxiety and Depression Scale; OR, odds ratio.

Looking at unadjusted estimates for cardiac events and
mortality there were significant risk differences between those
who felt lonely compared with those who did not, and those
who lived alone compared with those who lived with others,
both among men and women. After adjustment some significant
differences remain. Behavioural risk factors and comorbidity
therefore does not seem to explain the association between
loneliness and morbidity and mortality. This indicates that the
behavioural pathway cannot, in this study, fully explain the asso-
ciation. Conventional risk factors were found in another study
among younger patients.8 Yet another study does not find any
significant associations with risk of mortality or readmission.7
This is also evident in the finding that both men and women
living alone had a decreased risk of anxiety symptoms compared
with those living with someone. There can be both positive
and negative aspects of close relationships. Stressful social rela-
tions are associated with higher risk of incident IHD and can
increase mortality.26 Similarly, in an elderly population there is
greater risk of living with a sick spouse or partner which might
cause worry and anxiety. These are factors that patients living

to explain most of the risk of acute myocardial infarction and
stroke.2 Furthermore, a large cohort study found the excess
mortality among lonely people to be attributed to both unhealthy
lifestyle, and also socioeconomic conditions and lower mental
well-being.24
In the present study, the subjective measure of loneliness was a
much stronger predictor of both PROs and mortality compared
with the objective measure of living alone. Differing definitions
and measures of loneliness and cohabitation can make it diffi-
cult to compare results across studies directly.6 25 However, the
fact that the subjective feeling of loneliness is associated with
poor health outcomes is well established,10 while the findings
of health effects associated with living alone point in different
directions. Previous studies show an increased mortality risk
among patients living alone,9 but in one study this is only the case
Protected by copyright.
alone would not be facing to the same extent as those living
with someone and might help explain who they report a better
mental health.
Loneliness was a strong predictor of poor health outcomes
in both men and women but living alone was only a predictor
of cardiac events in men. Previous studies found that women
have larger networks than men and being separated, divorced or
single has a greater impact on men’s social networks compared
with women’s.27
Because of the design of this study it is not possible to make
conclusions about causal mechanisms. There is a possibility of
reverse causality, as it is unknown whether loneliness or disease
came first.28 Furthermore, the feeling of loneliness can change
within the first year after hospital discharge. However, the find-
ings are in line with previous research suggesting that loneliness

Table 3  Living alone and loneliness as a predictor of cardiac events and mortality after 1 year
Unadjusted results Adjusted results
Cardiac events‡ All-cause mortality Cardiac events‡ All-cause mortality
HR (95% CI)§ HR (95% CI)§ HR (95% CI)¶ HR (95% CI)¶
Women n=4078
 No. of events 160 121 160 121
 Living alone 1.52 (1.08 to 2.15)* 0.86 (0.51 to 1.43) 1.29 (0.85 to 1.97) 0.64 (0.33 to 1.24)
 Loneliness 1.38 (0.99 to 1.93) 1.90 (1.29 to 2.78)* 1.34 (0.78 to 2.06) 2.92 (1.55 to 5.49)**
Men n=9368
 No. of events 469 273 469 273
 Living alone 1.29 (1.04 to 1.60)* 1.83 (1.35 to 2.49)** 1.39 (1.05 to 1.85)* 1.20 (0.78 to 1.83)
 Loneliness 0.98 (0.79 to 1.23) 1.89 (1.46 to 2.44)** 0.84 (0.62 to 1.12) 2.14 (1.43 to 3.22)**
*P<0.05.
**P<0.001.
‡Cardiac events: myocardial infarction, stroke, ventricular tachycardia/ventricular fibrillation and cardiac arrest.
§Multivariate Cox proportional hazards regression model with age as the time scale.
¶Multivariate Cox proportional hazards regression model with age as the time scale adjusted for living alone (when loneliness is the independent variable), loneliness (when
living alone is the independent variable), cardiac diagnosis, educational level, comorbidity (Tu comorbidity index), BMI, smoking, alcohol intake and medicine compliance.
BMI, body mass index; CI, confidence interval; HR, hazard ratio.

Christensen AV, et al. Heart 2019;0:1–7. doi:10.1136/heartjnl-2019-315460 5


Cardiac risk factors and prevention
is associated with changes in cardiovascular, neuroendocrine and
immune function as well as unhealthy lifestyle choices which can
impact negative health outcomes.
Generalisability
This is a national Danish study and international differences may
exist in treatment as well as culture and social behaviour. The
response rate was 53%, which is not unexpected in a popula-
tion of severely ill patients. However, this may raise concerns
regarding representativeness. The proportion of patients in each
diagnostic group is comparable among responders and non-re-
sponders and they have similar sociodemographic and clinical
characteristics. However, a higher mortality rate was detected
among non-responders.29
Implications
There are indications that the burden of loneliness and social
isolation is growing.30 Furthermore, increasing evidence points
to their influence on poor health outcomes being equivalent to
the risk associated with severe obesity.11 30 Public health initia-
tives should therefore aim at reducing loneliness.
Strengths and limitations
This study includes a large sample of patients with IHD,
arrhythmia, heart failure and heart valve disease and found no
significant differences between diagnostic groups. This builds on
existing research primarily focused on IHD and indicates that the
association between loneliness and health outcomes may apply
to other diagnostic groups as well. We included both an objec-
tive measure (living alone) and a subjective measure (loneliness)
in the analyses. Furthermore, in addition to objective outcomes
such as mortality, we included PRO measures to further unfold
the effects of loneliness on health.
The presence of non-response bias is a possibility in survey-
based research. The response rate alone is often a poor indi-
cator of non-response bias. Survey estimates are only affected
if respondents and non-respondents differ on particular indi-
cators of interest. A larger proportion of patients were living
alone among non-responders. Furthermore, non-responders
seemed to be a little older, not married and have a lower educa-
tional level compared with responders (online supplementary
Key messages
What is already known on this subject?
►► Loneliness and poor social support have been linked to
both the development of ischaemic heart disease and
cardiovascular mortality.
►► Loneliness affects health outcomes through behavioural,
psychological and biological pathways.
What might this study add?
►► At hospital discharge, loneliness is associated with poor
patient-reported mental and physical health and is a strong
predictor of mortality after 1 year in both men and women
across cardiac diagnoses.
►► A subjective measure of loneliness is a stronger predictor of
poor outcomes than the objective measure of living alone.
How might this impact on clinical practice?
►► Loneliness should be included in clinical risk assessment of
cardiac patients.
6 Christensen AV, et al. Heart 2019;0:1–7. doi:10.1136/heartjnl-2019-315460
Heart: first published as 10.1136/heartjnl-2019-315460 on 4 November 2019. Downloaded from http://heart.bmj.com/ on November 14, 2019 at University of California San Francisco (UCSF).
table 2). Thus, we cannot rule out non-response bias in the
present survey. Self-reported outcomes are by nature subjec-
tive and therefore, sources of bias may exist. Recall bias is the
most serious problem in epidemiological surveys. Social desir-
ability bias can be an issue in self-reporting of lifestyle factors
or a sensitive subject such as loneliness. However, there is little
reason to suspect that such possible bias should differ systemat-
ically according to, for example, loneliness. Finally, we do not
have information about physical activity or clinical cardiac risk
factors such as serum cholesterol, blood pressure, life expectancy
or cardiac medication. If such variables can explain some of the
association between loneliness and health outcomes, we cannot
rule out that inclusion in the present analyses could have affected
the findings.
Author affiliations
1
Centre for Cardiac, Vascular, Pulmonary and Infectious Diseases, Rigshospitalet,
Copenhagen University Hospital, Copenhagen, Denmark
2
National Institute of Public Health, University of Southern Denmark, Copenhagen,
Denmark
3
4
Department of Cardiology, Odense University Hospital, Odense, Denmark
Department of Cardiology and Department of Cardiothoracic Surgery and Clinical
Nursing Research Unit, Aalborg University Hospital, Aalborg, Denmark
5
Cardiothoracic and Vascular Department, Odense University Hospital, Odense,
Denmark
6
Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark
7
Department of Cardiology, Herlev and Gentofte University Hospital, Hellerup,
Denmark
8
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University
of Copenhagen, Copenhagen, Denmark
Protected by copyright.
Acknowledgements  The authors would like to thank the patients who took the
time to participate in the survey, the 800 cardiac nurses involved in data collection
and the heart centres for prioritising this study in a busy clinic. The authors would
also like to thank the DenHeart research expert committee.
Contributors  SKB conceived the overall idea for the DenHeart study and all
authors designed the study. AVC performed the statistical analyses and wrote the
first draft of the manuscript. All revised the manuscript critically. All have given their
final approval of the version to be published.
Funding  This work was supported by Helsefonden; the Danish heart centres;
the Novo Nordisk Foundation, Familien Hede Nielsens Fond and The Danish Heart
Association.
Competing interests  None declared.
Patient consent for publication  Not required.
Ethics approval  According to Danish legislation, surveys should only be approved
by the Danish Data Protection Agency (2007-58-0015/30-0937). Use of register data
were permitted by The Danish National Board of Health.
Provenance and peer review  Not commissioned; externally peer reviewed.
Data availability statement  No data are available.
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