European Heart Journal (2011) 32, 450–458 CLINICAL RESEARCH

doi:10.1093/eurheartj/ehq435 Heart failure/cardiomyopathy

Level of education and risk of heart failure: a

prospective cohort study with echocardiography
evaluation†
Stefan Christensen 1, Rasmus Mogelvang 2, Merete Heitmann 1, and Eva Prescott 1,3*

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1
Department of Cardiology, Bispebjerg University Hospital, Bispebjerg Bakke 23, DK-2400 Copenhagen, Denmark; 2Department of Medicine, Holbaek University Hospital,
Smedelundsgade 60, 4300 Holbaek, Denmark; and 3The Copenhagen City Heart Study, Bispebjerg University Hospital, Bispebjerg Bakke 23, DK-2400 Copenhagen, Denmark

Received 7 May 2010; revised 16 September 2010; accepted 13 October 2010; online publish-ahead-of-print 8 December 2010

Aims With increasing socioeconomic disparity in cardiovascular risk factors, there is a need to assess the role of socioe-
conomic factors in chronic heart failure (CHF) and to what extent this is caused by modifiable risk factors.
.....................................................................................................................................................................................
Methods In a prospective cohort of 18 616 men and women without known myocardial infarction or CHF examined in 1976–
and results 78, 1981–83, 1991 –94, and 2001–03 in the Copenhagen City Heart Study, we studied the effect of education on
CHF incidence. During a median follow-up of 21 years (range 0–31), 2190 participants were admitted to hospital
for CHF. Age-adjusted hazard ratio (HR) for intermediary (8– 10 years) and high level of education (.10 years)
with low (,8 years) as reference was 0.69 (0.62–0.78) and 0.52 (0.43– 0.63), respectively, with similar associations
in men and women. After adjusting for updated cardiovascular risk factors, corresponding HRs were 0.75 (0.67–0.85)
and 0.61 (0.50 –0.73). In a random subset of the population examined with echocardiography in 2001–03 (n ¼ 3589),
education was associated with left ventricular (LV) hypertrophy, LV dilatation, reduced LV ejection fraction, and
severe diastolic dysfunction (P for trend, all ,0.05), whereas no association was found for mild diastolic dysfunction
(P for trend, 0.61). With the exception of LV hypertrophy, significant associations persisted after adjustment for
potential mediating factors.
.....................................................................................................................................................................................
Conclusion In this cohort study, the level of education was associated with cardiac dysfunction and predicted future hospital
admission for CHF. Only a minor part of the excess risk was mediated through traditional cardiovascular risk
factors. Strategies to reduce this inequality should be strengthened.
-----------------------------------------------------------------------------------------------------------------------------------------------------------
Keywords Heart failure † Epidemiology † Morbidity † Echocardiography † Socioeconomic status

factors and whether this association is mediated by modifiable risk

Introduction
It is well accepted that socioeconomic deprivation is associated
with coronary heart disease (CHD) but much less is known of
the link with the development of chronic heart failure (CHF).
Although CHD and CHF share several risk factors, it has been esti-
mated that ,50% of CHF is caused by CHD.1 Despite improved
treatment, CHF remains a significant health problem with increas-
ing prevalence and associated high health costs.2 With growing dis-
parity in the distribution of cardiovascular risk factors such as
smoking, obesity, and physical inactivity, it is important to deter-
mine to which extent the risk of CHF is linked with socioeconomic
factors. In the few prospective studies that have addressed this
issue, methodology and results have differed and several have
included only men.3 – 7 Moreover, no study has taken changes in
risk factor distribution in recent decades into account.
The aim of the present study, the largest to our knowledge, is to
examine the longitudinal relationship between socioeconomic
factors and risk of hospital discharge with a diagnosis of CHF
and to determine whether any associations are mediated by poten-
tially modifiable risk factors, while adjusting for changes in these
risk factors during follow-up. In addition, since any analysis of hos-
pital admissions may exaggerate the effect of social deprivation

†
This is an observational study. Reporting follows the STROBE guidelines.
* Corresponding author. Tel: +45 4026 2134, Fax: +45 3531 3226, Email: epre0004@bbh.regionh.dk
Published on behalf of the European Society of Cardiology. All rights reserved. & The Author 2010. For permissions please email: journals.permissions@oup.com.
Level of education and risk of heart failure 451

because of a possible lower threshold for hospital admission in the
relatively deprived, association with early echocardiography signs
of heart failure is explored.
Methods
Study population
The data used in this study are from the Copenhagen City Heart Study
(CCHS), which is an ongoing population study in which a random
sample of the population living in a area of Copenhagen are invited
to participate at regular intervals. Details of the enrolment and exam-
ination have been described elsewhere.8 Briefly, the original sample
included in 1976 – 78 comprised 14 223 participants (response rate
74%). In 1981 – 83, 1991 – 94, and 2001 – 03, participants were
re-examined and new, primarily young subjects were invited in an
attempt to have a study population with representatives from all age
groups. A total of 18 974 subjects participated in one or more of
the examinations (see Figure 1 for flowchart). Participants reported
previous myocardial infarction (MI) at baseline. In addition, all subjects
with a hospital admission of MI or CHF according to the Danish
National Patient Register from this was established in 1977 until
study inclusion were excluded. A total of 358 subjects with previous
MI or CHF were thus excluded leaving 18 616 subjects eligible for ana-
lyses. The median duration of follow-up was 21 years (range 0 – 31).
Cardiovascular risk factors were assessed at each of the four examin-
ations using a self-administered questionnaire, a physical examination,

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Figure 1 Flow diagram of the study population. The entire study sample consisted of persons participating in at least one of the four exam-
inations (i.e. some persons participated in multiple examinations) in the Copenhagen City Heart Study who were free of previous MI or CHF at
their first examination in the study. The Echocardiography sub study consisted of randomly selected participants from the 4th examination. MI,
myocardial infarction; CHF, chronic heart failure.
452
and paraclinical tests. The Ethics Committee for the Copenhagen area
approved the study (KF 100.2039/91).
Socioeconomic variables
Two indicators of socioeconomic position were available: duration of
education (,8, 8 – 10, and .10 years, corresponding to lower primary
school, higher primary school, and secondary school, respectively) and
household income (categorized into three groups: low, medium, and
high). Household income does not accurately reflect the socioeco-
nomic position after retirement, whereas educational attainment is a
stable indicator of the socioeconomic position from relatively early
in the life course. Education was therefore used as the primary
exposure variable throughout.
Covariates
Potentially modifiable cardiovascular risk factors regarded as mediators
were measured as follows: smoking habits were categorized into never
smokers, ex-smokers, and current smokers of 1– 15, 15 – 24, and .24
cigarettes per day. Physical activity was measured as self-reported
leisure time activity in four categories: sedentary, moderate activity
2 – 4 h/week, moderate activity .4 h/week, and strenuous activity
.4 h/week. Heart rate, included as an indicator of physical fitness,
and systolic blood pressure were measured in a sitting position after
5 min rest. Treatment for hypertension was self-reported. Body mass
index (BMI) was calculated as weight (kg) divided by height squared
(m2). Alcohol consumption was categorized as abstainers, monthly,
weekly, and daily intake. Blood samples were drawn non-fasting and
analysed for lipids and glucose. Total cholesterol was available at all
examinations, whereas HDL-cholesterol was not available at the first
examination and LDL-cholesterol and triglycerides not available at
the second. Family history of CHD and diabetes were self-reported.
Echocardiography
In the 2001 – 03 survey, 6237 subjects were included (response rate
50%) and a random sample consisting of 3654 subjects (59%) under-
went an echocardiography. Proportion that underwent echocardiogra-
phy did not differ by educational attainment, age, gender, or any of the
baseline characteristics, thus minimizing the likelihood that any bias has
been introduced. Persons with atrial fibrillation, significant valvular ste-
nosis or regurgitation, or missing data on level of education (n ¼ 40)
were excluded as were participants with previous MI (n ¼ 25), result-
ing in the inclusion of echocardiography from 3589 study participants.
Three experienced echo technicians performed echocardiography.
Details of recording and analysing have been described elsewhere.9
Systolic dysfunction was defined as left ventricular ejection fraction
(LVEF) , 50%. Left ventricular mass index was calculated as the ana-
tomic mass10 divided by body surface area. Left ventricular hypertro-
phy was defined as LV mass index ≥104 g/m2 for women and
≥116 g/m2 for men.11 Left ventricular dilatation was considered
present if the diameter of the LV at end-diastole/height was
≥3.3 cm/m.12 Pulsed-wave Doppler at the apical position was used
to record mitral inflow between the tips of the mitral leaflets. Peak vel-
ocities of early (E) and atrial (A) diastolic filling and deceleration time
of the E-wave (DT) were measured and the E/A ratio was calculated.
Mild diastolic dysfunction was defined as E/A , 1 and DT . 240 ms.
Severe diastolic dysfunction was defined as DT , 140 ms and E/A,50
13
years .2.5, E/A50 – 70 years .2, or E/A.70 years .1.5. An abnormal
echocardiography examination identified subjects with LV hypertro-
phy, dilatation, ejection fraction ,50%, or mild or severe diastolic
dysfunction.
S. Christensen et al.
Endpoints
The primary endpoint of this study was first-ever hospital admission
with a diagnosis of CHF (ICD8 codes 425.99, 427.09– 11, 427.19,
and 428.99 until 1 January 1994 and ICD10 codes I11.0, I25.5, I42.0,
I42.6, I42.9, and I50.0 – 9 from 1994 onwards) from the Danish
National Patient Register. Follow-up was until first admission for
CHF, death, emigration or end of follow-up (9 July 2007), whichever
occurred first. Follow-up was more than 99.5% complete.
Analysis strategy
Main exposure variable was level of education. Age, gender, and family
history were considered confounders, whereas all other covariates
were considered mediating factors. Comparisons across groups were
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done with one-way analysis of variance (ANOVA), Pearson’s x 2, and
tests for trend by linear and logistic regression. A two-sided P-value
of 0.05 was considered significant. The contribution of education to
dichotomized echocardiography findings was analysed by multivariable
logistic regression.
Hospital admission data were first analysed by constructing cumulat-
ive survival curves for CHF according to exposure categories by the
Kaplan– Meier method. For multiple-adjusted survival analyses, we
used the Cox proportional hazard model with age (in days) as the
underlying time scale with delayed entry (thus ensuring optimal adjust-
ment for age) to examine the effects of education on the risk of CHF.
We further adjusted all analyses for changes in admission rates over
time by splitting observation time into 10-year periods beginning
from 1 January 1976 and adjusting for time period effect.
Analyses were performed by using updated information on edu-
cation and potential mediating factors whenever these were available
(time-dependent variables). As an example, a person could enter the
study in 1976 being a smoker. At re-examination in 1992, the
person had quit smoking. The person then died in 1997. This person
would contribute 16 years of time-at-risk as a smoker (1976 –92)
with no endpoint and then 5 years as an ex-smoker (1992– 97)
before being censored at death in 1997. All initial analyses were
gender-specific. Univariable Cox’s regression analyses, adjusted for
age as described, were used to evaluate potential mediators of the
association between education and outcome and were analysed as cat-
egorical or continuous variables as indicated. Evidence for non-linear
trends in increases in the risk of hospital admission was tested by com-
paring models of co-variables on a continuous scale with models of the
variable in quintiles or by adding the squared term. All variables listed
above were considered potential confounders or mediators and tested
in the multivariable model if they met the criteria of P , 0.15 in the
initial age-adjusted model. The effect of education and mediating vari-
ables was tested with respect to interaction with gender by a nested
log-likelihood test, comparing a model containing the variables as
single terms with a model also including the interaction terms.
The assumption of proportional hazards was tested formally by
Schoenfeld’s residuals. The assumption was violated with regard to
the effect of education in both men and women: during follow-up,
1089 women and 1101 men were admitted to hospital with a diagnosis
of CHF. In both genders, higher level of education was associated with
better survival free of CHF admission in the younger. However, as
illustrated by the Kaplan– Meier curve of survival free of hospital
admission for CHF (Figures 2 and 3), risk associated with education
could not be uniformly described for all age groups. Survival analyses
were therefore restricted to age below 80, i.e. all study participants
aged 79 or below at the time of their first study participation were
included in the analyses and contributed with time-at-risk until reach-
ing an endpoint, death, emigration, or age 80, whichever came first.
Level of education and risk of heart failure
Figure 2 Survival free of hospital admission for chronic heart
failure by level of education (men).
Figure 3 Survival free of hospital admission for chronic heart
failure by level of education (women).
With this restriction, model assumptions were not violated. One
hundred and thirty subjects were aged 80 or above at inclusion.
Censoring at age 80 reduced the number of participants from
18 616 to 18 486, person-years of follow-up from 375 609 to
349 492, and the number of hospital admissions from 2190 to 1473.
Data analyses were conducted using Stata version 10.0 (Stat Corp.,
College Station, TX, USA).
Results
Baseline characteristics
Of the 13 930 participants free of previous MI or CHF examined in
1976–78, information on level of education was available for
13 902. Table 1 shows the distribution of risk factors among
these 7611 women and 6291 men according to level of education.
As anticipated, both male and female participants with lowest level
of education were older and had significantly more adverse cardi-
ovascular risk profile. Similar associations were seen for risk factors
at the subsequent rounds of examination (results not shown).
453
Hospital admission for chronic heart
failure
Both educational attainment and household income predicted
admission for CHF with stronger associations seen for education
(Table 2). Risk for CHF in the group with highest education was
approximately half with similar associations in men and women. In
further analyses, men and women were pooled. The socioeconomic
gradient did not differ over time (test for interaction between
time period in four groups and level of education in three groups:
P ¼ 0.13). In a model including income and education, both were
significantly associated with risk of CHF: hazard ratio (HR) was
0.55 (0.46–0.68) and 0.81 (0.68–0.96) for high vs. low level of edu-
cation and income, respectively, after adjusting for age, gender, and
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time period. There was no statistical interaction, i.e. HR associated
with low income was similar in the three strata of education.
Table 3 gives HRs for hospital admission for CHF by educational
level with multivariable adjustments for cardiovascular risk factors
updated during follow-up. The modifiable risk factors systolic
blood pressure, treatment for hypertension, BMI, physical inactiv-
ity, and smoking were all associated with risk of developing CHF,
as were gender, diabetes, and family history whereas alcohol con-
sumption, heart rate and serum lipids (triglycerides, total-, HDL-,
and LDL-cholesterol) were not (results not shown). Association
between educational attainment and subsequent risk of developing
CHF was attenuated by adjustment but remained highly significant:
HR for high vs. low level of education was 0.52 (0.43–0.63)
before adjustment and 0.61 (0.50–0.73) after adjustment.
Repeated analyses including death from CHF in endpoints did
not alter results. To ensure that a socioeconomic gradient in
re-participation and thus in updating of risk factors did not bias
results, Cox’s regression analyses were repeated based only on
the 13 902 subjects examined in 1976– 78 without updating of
risk factors: results were similar (not shown).
To address the issue of possible interim coronary events during
follow-up, analyses were repeated after excluding 400 participants
with an MI after study inclusion but prior to admission for CHF.
Results were similar: age-, gender-, and time period-adjusted HRs
for medium and high level of education were 0.69 (0.60–0.78)
and 0.54 (0.44–0.67), respectively. Similarly, after excluding
further 1205 participants who suffered an MI at any time during
the follow-up results were also unaffected: corresponding HRs
were 0.69 (0.61–0.79) and 0.52 (0.42–0.64), respectively.
Echocardiography
Results of echocardiography by level of education in 3589 subjects
after excluding subjects with previous MI from the survey in 2001 –
03 are shown in Table 4. Overall, for each of the indices of cardiac
abnormalities defined, proportion increased with decreasing
educational attainment, resulting in one or more abnormalities
found in 27.7% of the lowest educated vs. 10.5% of the highest
(P , 0.001). However, there were also large age differences
between groups. In logistic regression adjusting for age and
gender, educational attainment remained associated with all indi-
cators of abnormal echocardiography with the exception of mild
diastolic dysfunction (Table 5). After further adjustment for poten-
tial confounders and mediators, associations were attenuated but
454 S. Christensen et al.

Table 1 Risk factor profile by level of education in 6291 men and 7611 women free of previous myocardial infarction or
chronic heart failure in the Copenhagen City Heart Study examined at baseline in 1976– 78.

Characteristic Level of education P-value (test for trend)

.............................................................................................
Low (<8 years) Medium (8–10 years) High (>10 years)
...............................................................................................................................................................................
Men n ¼ 2984 (47.4%) n ¼ 2233 (35.5%) n ¼ 1074 (17.1%)
Age (years) 55.1 (11.1) 51.3 (12.1) 47.7 (14.4) ,0.0001
Low income 885 (29.9%) 319 (14.5%) 145 (13.6%) ,0.0001
Systolic BP (mmHg) 141.0 (21.0) 140.3 (20.2) 137.8 (20.3) ,0.0001
Treated hypertension 157 (5.3%) 129 (5.8%) 48 (4.5%) 0.28
Diabetes 146 (5.2%) 78 (3.7%) 30 (2.9%) 0.002
BMI (kg/m2) 26.3 (3.9) 25.7 (3.6) 24.5 (3.2) ,0.0001

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Sedentary 722 (24.2%) 391 (17.5%) 150 (14.0%) ,0.0001
Current smoker 2169 (72.7%) 1562 (70.0%) 677 (63.0%) ,0.0001
Daily alcohol intake 1282 (43.2%) 889 (39.9%) 282 (26.3%) ,0.0001
Cholesterol (mmol/L) 6.00 (1.17) 5.97 (1.14) 5.73 (1.10) ,0.0001
Triglycerides (mmol/L) 2.16 (1.53) 2.10 (1.45) 1.79 (1.13) ,0.0001
Heart rate (b.p.m.) 77.3 (13.5) 77.8 (12.9) 79.2 (13.5) ,0.0001
Family history of MI 851 (32.3%) 657 (31.2%) 314 (30.0%) 0.36
CHF admission 532 (17.8%) 294 (13.2%) 136 (12.7%) ,0.0001
...............................................................................................................................................................................
Women n ¼ 3694 (48.5%) n ¼ 2945 (38.7%) n ¼ 972 (12.8%)
Age (years) 54.8 (10.3) 51.2 (11.6) 46.4 (13.8) ,0.0001
Low income 1523 (44.4%) 602 (21.4%) 206 (21.7%) ,0.0001
Systolic BP (mmHg) 137.2 (22.6) 133.9 (21.7) 128.3 (22.0) ,0.0001
Treated hypertension 307 (8.3%) 181 (6.2%) 47 (4.8%) ,0.0001
Diabetes 94 (2.7%) 40 (1.4%) 11 (1.1%) ,0.0001
BMI (kg/m2) 25.4 (4.8) 24.2 (4.0) 23.0 (3.5) ,0.0001
Sedentary 923 (25.0%) 450 (15.3%) 116 (12.0%) ,0.0001
Current smoker 2239 (60.6%) 1667 (56.6%) 504 (51.9%) ,0.0001
Daily alcohol intake 218 (5.9%) 170 (5.8%) 66 (6.8%) 0.49
Cholesterol (mmol/L) 6.41 (1.24) 6.21 (1.28) 5.84 (1.36) ,0.0001
Triglycerides (mmol/L) 1.59 (0.95) 1.43 (0.83) 1.29 (0.79) ,0.0001
Heart rate (b.p.m.) 77.3 (12.2) 77.9 (12.4) 78.1 (12.3) 0.02
Family history of MI 1271 (37.5%) 1067 (37.8%) 329 (34.6%) 0.17
CHF admission 559 (15.1%) 363 (12.3%) 60 (6.2%) ,0.0001

Values are number (%) or mean (SD) as indicated. P-value for linear trend for data on a continuous scale from linear regression and for categorical data from logistic regression.

remained statistically significant for LV dilatation, LVEF, severe dias-
tolic dysfunction, and any abnormality.
Discussion
The main finding of this study was the relationship between edu-
cational level and hospital admission for CHF with an almost 50%
lower risk with the highest level of education compared with the
lowest in both men and women. Participants with low level of edu-
cation in general had a poorer risk factor profile but this explained
only a minor part of the excess risk and a statistically significant
stepwise decrease in the risk of CHF with higher levels of education
persisted after multivariable adjustment. Correspondingly, in cross-
sectional data, early stages of cardiac dysfunction assessed by echo-
cardiography were associated with educational level.
We have identified four prospective studies of the effect of
socioeconomic factors on population risk of CHF, which all
report results similar to ours.5 – 7,14 In the NHANES, in which
13 000 subjects were studied in the period from 1971 to
1992, less than high school education conveyed a relative risk
(RR) of 1.22 (1.04–1.42) of hospital admission or death from
CHF after multivariable adjustment.5 In the Renfrew/Paisley
study, which followed 15 000 middle-aged individuals for 20
years after 1972– 76, the most deprived individuals had an RR of
CHF admission within 20 years of baseline screening of 1.39
(1.04–2.01) compared with the most affluent.7 Neither of these
studies found gender differences in this socioeconomic gradient.
In a Swedish study comprising 6999 middle-aged men followed
for 28 years, unadjusted RR comparing highest with lowest occu-
pational class was 1.92 (1.50– 2.45) and adjusted 1.72 (1.34–
2.20).14 Another Swedish study of 50-year-old men with adjust-
ment for interim MI found adjusted HR of 1.98 (1.07–3.68) for
lowest vs. highest education.6 Our results are consistent with
these other studies and further complement them by showing a
Level of education and risk of heart failure 455

Table 2 Hazard ratios for hospital admission for chronic heart failure by level of education and household income in
18 486 participants below age 80 and free of myocardial infarction and chronic heart failure at baseline in the Copenhagen
City Heart Study

Women (n 5 9994) Men (n 5 8492)

.................................................................. ..................................................................
a
No. of endpoints HR 95% CI No. of endpointsa HR 95% CI
...............................................................................................................................................................................
Education
,8 years 375 1 Ref. 479 1 Ref.
8 –10 years 215 0.72 0.61–0.85 253 0.67 0.58–0.78
.10 years 44 0.50 0.37–0.69 92 0.53 0.42–0.66
...............................................................................................................................................................................
Household income
Low 359 1 Ref. 325 1 Ref.

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Medium 202 0.72 0.65–0.92 349 0.75 0.64–0.88
High 62 0.67 0.51–0.89 148 0.66 0.54–0.81

Results from Cox’s regression analyses with adjustment for age and time period.
a
Number of endpoints does not add up to 1473 because of missing data on level of education or household income in some subjects.

Table 3 Level of education and risk of hospital admission for heart failure in 18 486 participants below age 80 and free of
myocardial infarction and chronic heart failure at baseline in the Copenhagen City Heart Study

No. of endpoints Adjusteda HR 95% CI Multivariable adjustedb HR 95% CI

...............................................................................................................................................................................
Education
,8 years 854 1 Ref. 1 Ref.
8 –10 years 468 0.69 0.62–0.78 0.75 0.67–0.85
.10 years 136 0.52 0.43–0.63 0.61 0.50–0.73

Results from Cox’s regression analysis with multivariable adjustment for CVD risk factors and changes in CVD risk factors during follow-up.
a
Adjusted for age, gender, and time period.
b
Adjusted for age, gender, time period, systolic blood pressure, medical treatment for hypertension, diabetes, BMI, smoking, physical inactivity, and interaction between smoking
and gender (P ¼ 0.001). Alcohol consumption, heart rate, and plasma lipids (triglycerides, total-, LDL-, and HDL-cholesterol) were not associated with CHF in the multivariable
adjusted model.

Table 4 Abnormal echocardiography findings according to level of education in 3589 study participants free of
myocardial infarction and chronic heart failure in the fourth examination in the Copenhagen City Heart Study

Level of education P-value

.......................................................................................................................
Low (<8 years, n 5 842) Medium (8– 10 years, n 5 1296) High (>10 years, n 5 1451)
...............................................................................................................................................................................
Age 69.6 (8.8) 62.5 (13.3) 47.3 (16.1) ,0.001
Echocardiography
LV hypertrophy 142 (16.9%) 151 (11.7%) 100 (6.9%) ,0.001
LV dilatation 81 (9.6%) 66 (5.1%) 43 (3.0%) ,0.001
LVEF , 50% 17 (2.0%) 12 (0.9%) 3 (0.2%) ,0.001
Mild diastolic dysfunction 60 (7.1%) 64 (4.9%) 33 (2.3%) ,0.001
Severe diastolic dysfunction 19 (2.3%) 11 (0.9%) 6 (0.4%) ,0.001
Abnormal echocardiography 233 (27.7%) 243 (18.8%) 153 (10.5%) ,0.001

Values are number (%) or mean (SD) as indicated. P-value from one-way ANOVA or x2. LV, left ventricular; EF, ejection fraction. Abnormal echocardiography defined as one or
more of the following: LV hypertrophy, LV dilatation, LVEF , 50%, and mild or severe diastolic dysfunction.

similar gradient in echocardiography indicators of cardiac dysfunc- associations seen for education after mutual adjustment. This may
tion. We found that educational attainment and income were inde- partly reflect imprecision in the two measures, particularly house-
pendently associated with heart failure development with strongest hold income as discussed above, but indicates that estimating risk
456 S. Christensen et al.

the present study. A large proportion of CHF is caused by CHD

Table 5 Association between level of education and and there is a well-known socioeconomic gradient in the risk of
abnormal echocardiography findings in 3589 CHD. Similar to previous studies,3 – 5,7,14 – 23 we found male sex,
participants free of myocardial infarction and chronic hypertension, diabetes, smoking, and obesity to be important
heart failure in the fourth examination in the risk factors for CHF, but adjustment for these risk factors did
Copenhagen City Heart Study not account for the excess risk. In an attempt to determine
Adjusteda Multivariable whether the socioeconomic gradient was partly caused by differ-
adjustedb ences in changes in cardiovascular risk factors during follow-up,
........................ ....................... we adjusted risk estimates for changes in these factors over the
HR 95% CI HR 95% CI
................................................................................ follow-up period. However, adjustment only attenuated HR from
LV hypertrophy 0.52 to 0.61 for the highest and from 0.69 to 0.75 for intermediary
,8 years 1 Ref. 1 Ref. educational attainment, indicating that only a minor part of the
8 –10 years 0.77 0.59–1.00 0.81 0.61–1.07 excess risk in the socially deprived was mediated by difference in

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.10 years 0.67 0.49–0.91 0.81 0.58–1.13 these cardiovascular risk factors. Other possible explanations
Test for trendc 0.01 0.19 include increased risk of developing disease through poorer pre-
................................................................................ ventive measures, lower medical compliance, and lower threshold
LV dilatation
for hospital admission. Previous studies have suggested that lower
,8 years 1 ref 1 Ref.
educational levels are related to limited access to higher-quality
8 –10 years 0.52 (0.37– 0.74) 0.62 0.43–0.90
healthcare and poor adherence to treatment of cardiovascular dis-
.10 years 0.34 (0.21– 0.53) 0.47 0.29–0.76
eases and CHF. Although the Danish national health system has
Test for trendc ,0.001 0.001
................................................................................ universal coverage and there are no private hospitals or clinics
LVEF , 50% that admit patients for treatment for heart failure, there are infor-
,8 years 1 Ref. 1 Ref. mal barriers and cost of medication that may contribute to inequity
8 –10 years 0.55 0.26–1.18 0.67 0.31–1.47 in disease management. Poorer treatment adherence and compli-
.10 years 0.20 0.05–0.75 0.26 0.07–0.96 ance in CHD including poorer treatment of acute coronary syn-
Test for trendc 0.009 0.04 drome, later presentation of MI, and less use of secondary
................................................................................
prevention treatment may cause more deprived patients to have
Mild diastolic dysfunction
higher risk of re-MI and subsequent development of CHF. Poor
,8 years 1 Ref. 1 Ref.
compliance may also lead to more frequent hospital admission
8 –10 years 0.93 0.64–1.36 0.96 0.66–1.40
due to poor disease control once CHF has developed. Other pos-
.10 years 0.89 0.56–1.42 0.89 0.56–1.42
sibilities include higher threshold for taking action on symptoms in
Test for trendc 0.61 0.63
................................................................................ the least educated group, leading to patients delay and worsening
Severe diastolic dysfunction of symptoms. Psychosocial factors that were not measured may
,8 years 1 Ref. 1 Ref. also play a role.
8 –10 years 0.47 0.22–1.00 0.44 0.20–0.94 Prevalence of both systolic and diastolic dysfunction in the present
.10 years 0.42 0.16–1.14 0.35 0.13–0.98 study was lower than reported in a previous study.24 This is likely to
Test for trendc 0.04 0.02 be caused both by differences in the underlying population, selection
................................................................................
Any abnormal echocardiography of study participants, age and gender distribution, and echocardio-
,8 years 1 Ref. 1 Ref. graphy evaluation methods employed. Conventional echocardiogra-
8 –10 years 0.73 0.58–0.92 0.79 0.62–1.01 phy, as employed in the present study, can be used to identify mild
.10 years 0.61 0.47–0.80 0.75 0.56–0.99 and severe diastolic dysfunction. Tissue Doppler imaging, as well as
Test for trendc ,0.001 0.04 pulmonal venous flow and Valsalva manoeuvre, can (sometimes)
be helpful in the identification of pseudo-normalization. Without
LV, left ventricular; EF, ejection fraction. Abnormal echocardiography defined as these measures, we were unable to differentiate between Grade 2
one or more of the following: LV hypertrophy, LV dilatation, LVEF , 50%, and mild (pseudo-normal) and normal diastolic function. However, we feel
or severe diastolic dysfunction.
a that it is unlikely that many of our participants were pseudo-
Adjusted for age and gender.
b
Adjusted for age, gender, systolic and diastolic blood pressure, medical treatment normalized without concomitant structural heart disease or
for hypertension, diabetes, BMI, smoking, alcohol consumption, plasma lipids decreased LVEF (abnormal echocardiography).
(triglycerides, total-, LDL-, and HDL-cholesterol), physical inactivity, and family
The number of subjects with abnormal echocardiography find-
history of MI.
c
Log-likelihood test for linear trend. ings was limited particularly in the group with high education.
Nevertheless, recordings show a socioeconomic gradient in all of
the markers of systolic and diastolic dysfunction with the exception
based on one socioeconomic measure may underestimate the true of mild diastolic dysfunction.
socioeconomic gradient. The results presented imply that the socioeconomic gradient in
There are several ways in which socioeconomic deprivation may CHF is not only present in advanced stages of disease as measured
contribute to excess CHF morbidity. Excess risk is clearly related by hospital admission or death but also present already at subclini-
to uneven distribution of cardiovascular risk factors as also seen in cal stages. Although it is has not been proven that systolic
Level of education and risk of heart failure
dysfunction leads to systolic heart failure and diastolic dysfunction
to heart failure with preserved ejection fraction (HFPEF), systolic
and diastolic dysfunction have been shown to be markers of
increased mortality in population-based studies.24,25 Thus, the
mechanisms responsible for the socioeconomic gradient should
probably not only be sought in threshold for hospital admission
or poor medicine compliance but also in the early development
of both systolic heart failure and HFPEF. We know of no previous
study examining socioeconomic gradient in early structural changes
of the heart in the general population and these findings add signifi-
cantly to our knowledge.
Strengths and limitations
The strengths of this study include the prospective design, large
number of outcomes, detailed registration of cardiovascular risk
factors, updating of risk factors, complete follow-up regarding
hospital admission, and the availability of echocardiographic
recordings in a subset. Limitations include that our case ascertain-
ment relied solely on hospital records and we did not identify
milder cases treated outside of hospital. The diagnosis of CHF
from our national hospital records have been shown to have low
sensitivity (29%) but high specificity (99%) when validated against
criteria based on symptoms, clinical signs, and echocardiography
evaluation.26 Thus, we probably underestimated the true incidence
of CHF but internal validity is high. Diagnostic inaccuracy may
have biased results if this is related to socioeconomic status but
we find this unlikely. Another limitation is the lack of information
on the type of CHF at admission (preserved vs. low ejection frac-
tion), or cause (valvular heart disease, hypertension, CHD, alco-
holic, metabolic, inflammatory) or other clinical data. In a recent
Swedish study, however, risk associated with occupational class
did not differ when distinguishing between CHF with or without
ischaemic origin.14 The socioeconomic gradient found in both
early abnormalities related to systolic and diastolic dysfunction
corroborates this.
In our study, neither education nor income predicted hospital
admission for CHF in the oldest subjects and these were excluded
from analyses. Another published study of risk factors for incident
CHF in 1749 subjects aged 65 or older (mean age 75) found no
association between education and CHF.3 This is likely to be
caused by selection mechanisms and competing mortality risks in
the very old.
Conclusion
In summary, we show that level of education is associated with
early systolic and diastolic dysfunction assessed by echocardiogra-
phy and is a strong predictor of future hospital admission for heart
failure. Only a minor part of the excess risk was mediated by differ-
ences in potentially modifiable cardiovascular risk factors. Further
studies are needed to explain the remaining excess just as strat-
egies to reduce this inequality should be strengthened.
Funding
This work was supported by unrestricted grants from The Danish
Heart Foundation (06-10-B381-A1313-22314F) and The Velux Foun-
dation. The authors are independent from funders.
457
Conflict of interest: none declared.
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doi:10.1093/eurheartj/ehq379
CARDIOVASCULAR FLASHLIGHT Online publish-ahead-of-print 7 October 2010
.............................................................................................................................................................................

Paradoxical pulmonary embolism

Downloaded from https://academic.oup.com/eurheartj/article/32/4/450/440414 by guest on 15 July 2021

Paola De Rango *, Valeria Silvestri , and Giacomo Isernia
Vascular and Endovascular Unit, University of Perugia, Hospital S. M. Misericordia, Piazza Mignini 1, 06134 Perugia, Italy
* Corresponding author. Tel: +39 075 5786436, Fax: +39 075 5786435, Email: pderango@unipg.it, plderango@gmail.com

A 79-year-old man presented

to the emergency department
with a 2-day history of pro-
gressive shortness of breath,
anuria, and abdominal pain.
Prior to admission, he had
experienced increasing
oedema, cyanosis, and bluish-
mottled lower extremities.
Laboratory data showed
impaired renal function (crea-
tinine 4.2 mg/mL) and 65%
arterial oxygen saturation in
ambient air. The patient
became markedly hypoten-
sive, hypoxaemic, and devel-
oped respiratory arrest
requiring intubation.
Immediate multidetector
row contrast-enhanced com-
puted tomography (CT)
evaluation revealed multiple
thrombi in the pulmonary
arteries, the largest occluding the superior left pulmonary artery (Panel A). An 8.0 cm abdominal aortic aneurysm (AAA), largely
thrombosed and ruptured in inferior vena cava (IVC), was also diagnosed: early and synchronous contrast enhancement of the
aorta and the IVC and a large (3 cm) aortocaval contrast passage just above the iliac bifurcation were visible (Panels B and C,
arrow shows fistula). An aortic aneurysm thrombus was the most likely source of paradoxical emboli through the aortocaval com-
munication (Panel D: pathophysiology).
The patient was immediately transferred to the operating room and underwent caval filter placement (OPTEASE, Cordis, Johnson &
Johnson, The Netherlands) and emergency repair of the ruptured aneurysm with an aortic bifurcated stent graft (Excluder, Gore, Flag-
staff, AZ, USA). Completion angiography showed successful exclusion of AAA, fistula coverage, and the presence of a small type II
endoleak.
The patient had a full and uneventful recovery and was discharged after 22 days with IVC filter in place. His oedema had resolved
and there was no evidence of congestive heart failure. He remained in good health during the next 6 months when follow-up CT
showed resolution of pulmonary thrombi, decreased AAA diameter (6.1 cm), and marked decrease in type II endoleak (Panel E:
black arrow, IVC filter; white arrow, stent graft).

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