Young patients with heart failure: clinical
characteristics and outcomes. Data from the
Swedish Heart Failure, National Patient,
Population and Cause of Death Registers
Carmen Basic
1*
, Annika Rosengren
1, Urban Alehagen
2, Ulf Dahlström
3,
Magnus Edner
4, Michael Fu
1, Masuma Novak
5, Tatiana Zverkova Sandström
1,
and Maria Schaufelberger
11Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden;2Division of Cardiovascular Medicine, Department of Medical and Health Sciences, Linköping University, Linköping, Sweden;3Department of Cardiology and Department of Medial and Health Sciences, Linköping University, Linköping, Sweden;4Division of Family Medicine, NVS, Karolinska Institutet, Stockholm, Sweden; and5Institute of Health and Care Science, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
Received 7 April 2020; revised 17 June 2020; accepted 26 June 2020 ; online publish-ahead-of-print 3 August 2020
Aims The prevalence and hospitalizations of patients with heart failure (HF) aged<55 years have increased in Sweden
during the last decades. We aimed to compare characteristics of younger and older patients with HF, and examine
survival in patients<55 years compared with matched controls.
... Methods
and results
All patients≥18 years in the Swedish Heart Failure Register from 2003 to 2014 were included. Data were merged
with National Patient and Cause of Death Registers. Among 60 962 patients, 3752 (6.2%) were<55 years, and were
compared with 7425 controls from the Population Register. Compared with patients≥55 years, patients <55 years
more frequently had registered diagnoses of obesity, dilated cardiomyopathy, congenital heart disease, and an ejection
fraction<40% (9.8% vs. 4.7%, 27.2% vs. 5.5%, 3.7% vs. 0.8%, 67.9% vs. 45.1%, respectively; all P < 0.001). One-year
all-cause mortality was 21.2%, 4.2%, and 0.3% in patients ≥55 years, patients <55 years, and controls <55 years,
respectively (all P< 0.001). Patients <55 years had a five times higher mortality risk compared with controls [hazard
ratio (HR) 5.48, 95% confidence interval (CI) 4.45–6.74]; the highest HR was in patients 18–34 years (HR 38.3, 95%
CI 8.70–169; both P< 0.001). At the age of 20, the estimated life-years lost was up to 36 years for 50% of patients,
with declining estimates with increasing age.
... Conclusion Patients with HF<55 years had different comorbidities than patients ≥55 years. The highest mortality risk relative
to that of controls was among the youngest patients.
...
Keywords Heart failure • Young adults • Comorbidity • Mortality
Introduction
The incidence of heart failure (HF) increases exponentially with age
and thus the majority of patients with HF are older.1In recent years,
an increase in hospitalization and prevalence of HF in younger
*Corresponding author. Department of Medicine, Sahlgrenska University Hospital/Östra, S-416 85 Göteborg, Sweden. Tel: +46 31 3434000, Fax: +46 31 258933, Email: carmen.basic@gu.se
...
people has been documented in Sweden and Denmark in contrast
to an overall decrease in older patients.1–3
Patients with HF are well characterized, but data mainly originate
from older patients.4 Subgroup analyses from the Candesartan in
Heart Failure Assessment of Reduction in Mortality and Morbidity
© 2020 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and
(CHARM) study5 and the Meta-analysis Global Group in Chronic
Heart Failure (MAGGIC) meta-analysis6described young patients
with HF, but both studies contained selected patient populations to some extent. Accordingly, there are few data on characteristics and survival in unselected young patients with HF.
In the last three decades, treatment of HF has markedly improved. This is especially the case in patients with a reduced ejection fraction (EF), which include the majority of young patients
with HF.4 However, recent population-based data from Canada
show persistently high mortality rates in young adults (<44 years), with 1-year mortality of 12% and 5-year mortality of 28% of
these patients.7 To the best of our knowledge, no studies have
compared mortality in young patients with HF and the general population.
Linkage of national Swedish registers offers the potential of obtaining detailed data on characteristics and outcomes in large populations of patients with HF. It also enables comparison of sur-vival of these patients with that of individuals without HF, matched for age, sex, and region. In the present study we aimed to: (i) pro-vide a comprehensive and detailed description of young patients <55 years with HF, who were identified from the Swedish Heart Failure Register (SwedeHF), and compare them with older patients who form the majority in SwedeHF; and (ii) compare survival in
patients<55 years with that of population-based controls matched
for age, sex, and county and estimate life-years lost for patients <55 years.
Methods
Study population and procedures
All patients≥18 years registered in SwedeHF from 2003 to 2014 were included with baseline represented by the first date of registration. The patients were divided into patients <55 years and ≥55 years. Patients with HF<55 years were subdivided into the following three age categories: 18–34, 35–44, and 45–54 years. For each patient with HF<55 years, we identified two control individuals who were matched for age at the time of diagnosis, sex, and county, from the Population Register held by Statistics Sweden.8
SwedeHF, a nationwide quality register for patients with HF, was introduced in 2003.9 The single inclusion criterion for the study was
physician-diagnosed HF with detailed information available at http:// www.ucr.uu.se/rikssvikt. Individual patient’s consent was not required, but patients were informed that they had a right to opt out.
All discharge diagnoses are recorded in the National Patient Register (NPR), with nationwide coverage from 1987. Information on comor-bidities for patients and controls was obtained from the NPR. The International Classification of Disease (ICD) 9 codes were used to identify principal and contributory diagnoses in the NPR from 1987 to 1996, and ICD-10 codes were used from 1997 (online supplemen-tary Table S1). Comorbidities at baseline were defined as present at the date of inclusion for HF in the NPR.
Outcomes
Date and underlying cause of death was provided from the Swedish Cause of Death Register,10using the diagnostic code for the underlying
and first contributory cause of death, with the latest update in ...
...
...
December 2015. The diagnosis in the principal position had the highest hierarchical order when defining the underlying cause of death. Death due to cardiovascular causes was defined using the ICD-10 code I00-I99 and codes for congenital heart disease (Q20–Q28, Q87, Q89). Mortality rates and survival were analysed from the inclusion date in the SwedeHF, with a corresponding date set for controls.
This study was approved by the Ethics Committee of the University of Gothenburg in Sweden and Confidentiality Clearance at Statistics Sweden. The study conforms to the principles defined in the Declara-tion of Helsinki.
Statistical analysis
Comparisons between categorical variables were made using the Pear-son chi-square test and the Student’s t-test was used for continuous variables. Logistic regression with adjustment for sex was performed to investigate the effect of age on the prevalence of different comorbidi-ties. Variables from the SwedeHF that had more than 30% of missing values were excluded from all analyses.
Cox regression was used to study the association between age at inclusion due to HF and the risk of outcomes compared with matched controls. In patients, we estimated the excess risk of all-cause mor-tality using Cox regression similar to the model by Rawshani et al.,11
under the observation period of 1 January 2003 to 31 December 2015 starting at the inclusion in SwedeHF until death or end of follow-up, whichever occurred first. Registration in the NPR with a diagnosis of HF was followed by a registration in the SwedeHF within 1 month in approximately 60%, with another 17% of patients reg-istered within 6 months. Controls were individuals without a prior diagnosis of HF, consequently duration of HF was zero. Univariate and multivariable analyses were performed. Adjustments for age, sex, duration of HF prior to inclusion, ischaemic heart disease (IHD), dia-betes mellitus, dilated cardiomyopathy (DCM), hypertrophic cardiomy-opathy/hypertrophic obstructive cardiomyopathy (HCM/HOCM), and cancer were performed in multivariable analysis. Survival analyses were performed in the whole cohort in patients≥55 years, patients <55 years, and controls, and presented with Kaplan–Meier curves. Conditional survival for patients<55 years was presented as median, and estimated every fifth year at 20, 25, 30, 35, 40 and 45 years of age. Life expectancy tables from Statistics Sweden,12 were used as
reference to the conditional life expectancy for controls calculated from 2003 to 2014 at the age 20, 25, 30, 35, 40 and 45 years and are available at the following website: https://www.lifetable.de/cgi-bin/ index.php. Life-years lost were calculated as the difference between conditional life expectancy and conditional survival for patients with HF. All P-values are two-sided, and P< 0.05 was considered sta-tistically significant. All statistical analyses were performed using SPSS, Windows version 18.0 (SPSS Inc., Chicago, IL, USA), SAS 9.3, and R 3.5.3.
Results
Patient characteristics
From SwedeHF, we identified 60 962 patients among which 3752
(6.2%) were<55 years. For the latter group, we identified 7425
matched controls. Mean (standard deviation) age in patients<55
was 46 (7.6) years and 74.1% were men (Table 1), while patients ≥55 years were, on average, 77.2 (9.6) years, with 59.5% men.
Table 1 Characteristics of patients with heart failure<55 years, ≥55 years and matched controls Controls <55 years (n= 7425) Patients <55 years (n= 3752) Patients ≥55 years (n= 57 210) P-value patients <55 vs. ≥55 years P-value patients <55 years vs. controls . . . .
Age, years, mean (SD) 45.9 (7.6) 46 (7.6) 77.2 (9.6) <0.0001 NS
Men 5608 (74.1) 2781 (74.1) 34 050 (59.5) <0.0001 <0.0001
Co-morbidities, diagnoses according to the NPR
Obesity 104 (1.4) 367 (9.8) 2706 (4.7) <0.0001 <0.0001
Ischaemic heart disease 101 (1.4) 972 (25.9) 31 982 (55.9) <0.0001 <0.0001
Atrial fibrillation 54 (0.7) 933 (24.9) 31 364 (54.8) <0.0001 <0.0001 Hypertension 265 (3.6) 1186 (31.6) 33 197 (58) <0.0001 <0.0001 Diabetes mellitus 173 (2.3) 627 (16.7) 14 975 (25.6) <0.0001 <0.0001 Valvular disease 22 (0.3) 467 (12.4) 11 556 (20.2) <0.0001 <0.0001 Dilated cardiomyopathy 0 1020 (27.2) 3165 (5.5) <0.0001 <0.0001 Hypertrophic cardiomyopathya 0 75 (2.0) 532 (0.9) <0.0001 <0.0001 Myocarditis 6 (0.1) 78 (2.1) 257 (0.4) <0.0001 <0.0001
Congenital heart disease 27 (0.4) 140 (3.7) 456 (0.8) <0.0001 <0.0001
Kidney disease 30 (0.4) 183 (4.9) 7023 (11.5) <0.0001 <0.0001
Depression 307 (4.1) 332 (8.8) 33 203 (5.6) <0.0001 <0.0001
Cancer 228 (3.1) 320 (8.5) 14 175 (24.8) <0.0001 <0.0001
Patient characteristics according to SwedeHF
Missing values
Smokers 7205 (11.8) <0.0001
Former and current 1588 (42.3) 20 597 (36.0)
High alcohol intake 7569 (12.4) 492 (13.1) 2222 (3.9) <0.0001
NYHA class 128 (0.2) <0.0001 I 605 (16.1) 3901 (16.8) II 1505 (40.1) 17 267 (30.2) III 770 (20.5) 14 305 (25.0) IV 67 (1.8) 1916 (3.3) EF 154 (0.3) <0.0001 ≥50% 357 (9.5) 11 246 (19.7) 40–49% 625 (16.7) 10 289 (18) <40% 2549 (67.9) 25 788 (45.1) Hb<130 g/L 359 (0.6) 907 (24.1) 26 906 (47) <0.0001 Creatinine≥130 μmol/L 203 (0.3) 239 (6.4) 12 919 (22.6) <0.0001 Medical treatment ACEI/ARB 118 (0.2) 3471 (92.5) 45 026 (78.7) <0.0001 Beta-blockers 132 (0.2) 3370 (89.8) 47 542 (83.1) <0.0001 MRA 137 (0.2) 1232 (32.8) 16 065 (28.1) <0.0001 Diuretics 124 (0.2) 2236 (59.6) 46 246 (80.8) <0.0001 Digitalis 130 (0.2) 476 (12.7) 9424 (16.5) <0.0001 Oral anticoagulants 136 (0.2) 1220 (32.5) 21 864 (38.2) <0.0001 Device therapy 581 (1.0) <0.0001 Pacemaker 96 (2.6) 5289 (9.2) CRT and/or ICD 234 (6.2) 1979 (3.5)
Values are expressed as n (%) unless otherwise stated.
ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; CRT, cardiac resynchronization therapy; EF, ejection fraction; Hb, haemoglobin; ICD, implantable cardioverter-defibrillator; MRA, mineralocorticoid receptor antagonist; NPR, National Patient Register; NYHA, New York Heart Association; SD, standard deviation; SwedeHF, Swedish Heart Failure Register.
aIncluding patients with hypertrophic obstructive cardiomyopathy.
(27.2% vs. 5.5% P< 0.001), with the highest prevalence among
patients 18–34 years (33.7%; online supplementary Table S2). Addi-tionally, obesity, congenital heart disease, and myocarditis were
more prevalent in patients <55 years than in those ≥55 years
(P< 0.001). Patients ≥55 years had higher rates of IHD, atrial ...
fibrillation and hypertension than those <55 years (P < 0.001)
(Table 1).
Approximately 80% of patients<55 years and 13.5% of controls
had at least one comorbidity at baseline (online supplemen-tary Figure S1). Age-specific rates of comorbidities are shown
p < 0.0001 0.0 0.2 0.4 0.6 0.8 1.0 0 2 4 6 8 10 12 Time in years Sur viv al probability 7415 6707 5281 3779 2410 1313 661 3747 3249 2484 1728 1058 554 272 56953 44466 32179 21797 14088 8760 5497 3 Patients = 55 Patients < 55 Controls < 55 0 2 4 6 8 10 12 Time in years Number at risk Patients vs. controls p < 0.0001 0.5 0.6 0.7 0.8 0.9 1.0 0 2 4 6 8 10 12 Time in years Sur viv al probability 350 285 195 134 72 16 5 697 614 432 309 175 42 12 826 711 511 334 157 47 8 1645 1487 1122 770 379 129 24 2576 2083 1516 976 480 159 27 5083 4425 3365 2267 1182 423 78 Controls 45−54 Patients 45−54 Controls 35−44 Patients 35−44 Controls 18−34 Patients 18−34 0 2 4 6 8 10 12 Time in years Number at risk
Patients vs. controls <55 years
Figure 1 Age-specific survival curves for cases and controls for the entire observation period.
in online supplementary Table S2. DCM was present in about one third of patients aged 18–34 and 35–44 years, but only in
5.5% and 6.9% in those aged 45–54 and≥55 years. Myocarditis
and congenital heart disease was present in 6.9% and 11.1% among patients 18–34, but was very rare in patients 45 and over. The rates of DCM, congenital heart disease and myocardi-tis were highest in the youngest group, with an odds ratio 8 to 16 times higher in this group compared with in the older
ones (online supplementary Table S3). Patients <55 years were
more likely to have an EF <40% (67.9%) compared with those
≥55 years (45.1%, P < 0.001). Poor functional class (New York Heart Association classes III–IV) was present in 25.8% among the youngest patients, in 22.0% and 21.9% in those aged 35–54, and
in 28.1% among patients aged ≥55 years (online supplementary
Table S2). Patients <55 years were significantly more frequently treated with guideline-recommended therapy compared with
those≥55 years.
Outcome
The total follow-up time was 12 years. Among patients<55 years,
survival did not vary greatly by age, with median survival rates of 4.53, 5.13, and 5.10 years for patients 18–34, 35–44, and 45–54 years, respectively. Age-specific survival curves for cases and controls for the entire observation period are shown in Figure 1. Total all-cause mortality rates were markedly higher in patients <55 years than in matched controls (16.1% vs. 2.1%, P < 0.001) (Table 2), with 1-year and 2-year all-cause mortality rates much higher than in controls (4.2% vs. 0.3% and 7.4% vs. 0.7%,
respec-tively; both P< 0.001). All-cause mortality per 1000 person-years
(95% confidence interval) in patients was highest in those ...
44–54 years [34.2 (31.2–37.6) vs. 4.84 (4.10–5.71) in matched
controls]. Compared to matched controls, patients<55 years had
higher all-cause mortality [hazard ratio (HR) 5.48 (4.45–6.74)] after adjustment for age, sex, duration of HF, IHD, diabetes mellitus, DCM, HCM/HOCM, and cancer. The highest HR was in patients 18–34 years [38.3 (8.70–169)], declining with increasing age (Table 2). Readmission rate for HF within 1 and 2 years was
signif-icantly lower in patients<55 years than in those ≥55 years (online
supplementary Table S2).
Next, we investigated the effect of comorbidities on mortality
in patients <55 years by their age. Patients with at least one
comorbidity had HR 1.80 (1.12–2.91) and 2.12 (1.65–2.73) for 1-year all-cause and total mortality, respectively, compared to patients without comorbidities (online supplementary Table S4). After adjustment for age, sex and other comorbidities (online supplementary Table S5), the presence of cancer at baseline was associated with a three times higher mortality risk compared with patients without cancer. The integrated time-dependent area under the curve for this model was 0.82 (online supplementary Figure S2).
Finally, we estimated conditional survival of patients expressed as a median. At age 20, 25, 30, 35, 50, and 45, a patient with HF lost estimated 36, 29.6, 25.6, 23.1, 20.1, and 18.6 life-years compared with the estimated life expectancy of the general population in Sweden (Figure 2). The majority of the patients were included in SwedeHF at the time of diagnosis, but some were diagnosed with HF prior to inclusion in SwedeHF, mostly within 6 months (not shown). Thus, the inclusion time was reasonably close to the time of diagnosis for HF. Patients <55 years died mostly from cardiovascular death, followed by cancer (Figure 3).
Table 2 Mortality in patients with heart failure<55 years and matched controls from the general population from 2003 to 2014
All-cause mortality All-cause mortality per
1000 person-years (95% CI)
HR (95% CI)a
. . . . . . . .
Years Case, n (%) Control,
n (%)
P-value Case Control P-value Case
. . . . 18–34 48 (13.7) 2 (0.3) <0.0001 27.2 (20.5–36.1) 0.52 (0.13–2.06) <0.0001 38.3 (8.70–169) 35–44 106 (12.8) 18 (1.1) <0.0001 24.3 (20.1–29.4) 1.89 (1.19–3.00) <0.0001 7.58 (4.23–13.6) 45–54 450 (17.5) 139 (2.7) <0.0001 34.2 (31.2–37.6) 4.84 (4.10–5.71) <0.0001 4.61 (3.67–5.80) Total 604 (16.1) 159 (2.1) <0.0001 26.1 (24.1–28.2) 3.21 (2.75–3.75) <0.0001 5.48 (4.45–6.74) Values are expressed as n (%) unless otherwise stated.
CI, confidence interval; HR, hazard ratio.
aFor all-cause mortality; adjusted for age, sex, duration of heart failure, ischaemic heart disease, diabetes, dilated cardiomyopathy, hypertrophic cardiomyopathy/hypertrophic obstructive cardiomyopathy, congenital heart disease and/or valve disease and cancer.
Figure 2 Conditional survival of heart failure patients compared with the estimated life expectancy of the general population in Sweden.
Discussion
In this register-based cohort study, we compared patients with HF <55 years with those ≥55 years and matched controls <55 years from the general population. Comorbidities were distributed as expected between age categories. The mortality rate was lower in
patients<55 than in those ≥55, but when compared with controls,
patients<55 had a five times higher mortality risk. Mortality risk
relative to controls and life-years lost were highest in the youngest patients and both of these variables decreased with increasing age. Cardiomyopathy, congenital heart disease and myocarditis had the highest prevalence among patients 18–34 years. DCM was one
of the most common comorbidities in patients<55 years (27.2%).
The CHARM study5 and the MAGGIC meta-analysis6 reported
a higher occurrence of DCM in patients <50 years compared
with our study (50% and 48.5%, respectively), probably partly explained by selected patient populations in CHARM and the ...
MAGGIC meta-analysis, the latter comprised a mix of registries and randomized clinical trials, also including CHARM. SwedeHF has approximately 50% coverage, potentially representing less
selected populations of patients with HF.9 The prevalence of
cardiomyopathy from this study is comparable to that in a study
by Barasa et al.2 based on the NPR. Most patients with HCM
do not develop overt HF,13,14 which explains the few cases of
HCM in our study. Current survival of patients with congenital
heart disease into adulthood is 75% to 85%.15,16 They are prone
to developing ventricular dysfunction,17,18thereby present in our
cohort. Obesity is associated with an increased risk for early
HF,19 and causality between obesity and HF has been shown.20
Obesity was significantly more common in patients <55 years,
which is similar to the findings in CHARM5 and a study by
Christiansen et al.3Hypertension, IHD and atrial fibrillation were
present in all age groups, rising with increasing age, as previously
Figure 3 Causes of death in patients<55 years.
Consistent with previous reports,5,6 patients <55 years were
more likely to have a severely reduced EF and were more
fre-quently on guideline-recommended treatment4 compared with
those ≥55 years. Patients ≥55 years more frequently had a
pre-served EF and thereby lacked indication for this treatment.4
Notably, patients 18–34 years more frequently had preserved and
mid-range EF than the remaining patients<55 years, thereby lacked
indication for guideline-recommended treatment.
Patients in our study had lower 1-year all-cause mortality
com-pared with those from Alberta, Canada7(4.2% vs. 11.5%). Patients
<55 years from Alberta had higher prevalence of diabetes melli-tus (28.5% and 38.3% in incident and prevalent cases, respectively) compared with that in our study (16.7%). In our study, patients with HF and concomitant diabetes had a higher risk of mortality. There-fore, the different prevalence of diabetes between studies might have contributed to a difference in mortality rates.
The prevalence of comorbidities differed in different age cate-gories in our cohort, and also affected survival. The total burden
of comorbidities was high among patients<55 years, approximately
two thirds had four coexisting conditions (online supplementary Figure S1). Compared to patients without comorbidities presence of at least one comorbidity was associated with almost doubled rel-ative mortality risk within 1 year and during the whole study. After
adjustment, in patients<55 years, the presence of cancer increased
the mortality risk up to three times and up to 12.3% of patients had cancer as the underlying cause of death. A probable explana-tion for these results may lie in the nature of cancer itself, but also aggressive treatment modalities that are used may contribute to
deterioration of heart function and adverse events.22Additionally,
the presence of diabetes was associated with an increased risk of
mortality. Rawshani et al.11recently showed that being diagnosed
with diabetes mellitus type 1 early in life resulted in a high risk of developing cardiovascular disorders, including HF. However, only
16.7% of patients<55 years had diabetes mellitus in our cohort.
Presence of congenital heart disease at baseline was associated with a 45% increase in mortality, a finding consistent with previous
studies.23,24 ...
...
...
This study suggests the importance of age when HF is diagnosed, especially if diagnosed early in life. To the best of our knowledge, this issue has not been addressed in previous studies. When adjusted for duration of HF and comorbidities, patients with HF<55 years had a five times higher HR for all-cause mortality compared with controls. Most of the young patients died between 45 and 54 years. However, the highest relative risk of mortality was in patients 18–34 years, who had a 38 times higher risk than the controls. This risk decreased with increasing age categories.
The most common cause of death in patients <55 years was
cardiovascular death. Estimation of life-years lost showed that half of the patients at the age of 20 may lose more than 40% of the expected length of life. Similar to risk of mortality, years lost decreased with increasing age. This finding demonstrates the impact of being diagnosed with HF at a young age, as patients might lose almost half of their life expectancy compared to their age-matched counterparts.
Strengths and limitations
This study has some strengths but also some limitations. One strength is that SwedeHF has a nationwide distribution, includ-ing a large number of patients from inpatient and outpatient settings, reflecting everyday clinical practice. However, participa-tion in SwedeHF is not mandatory. Therefore, selecparticipa-tion bias is still a potential limitation of this study. Notwithstanding this, the prevalence of cardiomyopathy is similar to that found in previ-ous studies from the NPR, which has almost complete coverage
(>99% of all discharges).25 This suggests that the patient
popu-lation that is included in SwedeHF is comparable to all hospi-talized patients with HF in Sweden, also presenting a strength. Furthermore, validation of the HF diagnosis in the NPR of patients who were treated in internal medicine wards was 86%
and in cardiology wards 91%.26 SwedeHF, as in other large-scale
registries,25 contains variables with missing values, which is one
limitation. Details on how this was handled are described in the Methods section.
Evaluation of specific forms of cardiomyopathy, such as idio-pathic DCM, could not be performed. It would add value to this study but, according to the latest definition of cardiomy-opathies, presence of comorbidities does not preclude a diagnosis
of cardiomyopathy.27A recently published study from our group
showed a high validity of diagnoses of cardiomyopathy in western
Sweden.28
Young patients in this study had many heterogenic co-existing
conditions. A total of 604 (16.1%) patients<55 years died during
the follow-up. Analysis of the effect of baseline comorbidities on mortality, especially cancer, including many different forms, should thus be interpreted with caution. Only few patients were diagnosed with HF more than 1 year before inclusion in SwedeHF, therefore we believe that they could not have affected survival analysis. As the vast majority of the patients were included in SwedeHF at the time of diagnosis for HF or within a 6-month period, the survival after inclusion in the register correlates well with the survival after the time of diagnosis for HF.
Conclusion
Heart failure among young patients is uncommon. Young patients with HF more frequently had cardiomyopathy, congenital heart disease and myocarditis than did older patients. Young patients had a higher occurrence of all comorbidities compared with controls and they were associated with a worse prognosis, especially cancer. After cardiovascular death, cancer was the second most common cause of death in young patients. Being diagnosed with HF before the age of 35 involved the highest relative risk of mortality. The estimated life-years lost were highest among the youngest patients, with an estimated loss of life-years if diagnosed at age 20 of 36 years.
Supplementary Information
Additional supporting information may be found online in the Supporting Information section at the end of the article.
Table S1. International Classification of Disease (ICD) 9 and ICD-10 codes used to identify comorbidities in the National Patient Register.
Table S2. Characteristics of patients with heart failure in the Swedish National Heart Failure Register in different age groups, and controls, matched for age, sex, and county.
Table S3. Impact of age on prevalence of comorbidities in patients diagnosed with heart failure by age category in the Swedish Heart Failure and National Patient Registers.
Table S4. The effect of the number of coexisting conditions on
mortality in patients with heart failure <55 years and matched
controls.
Table S5. Effect of baseline comorbidities on all-cause mortality
per age category in patients with heart failure<55 years. Data from
the Swedish Heart Failure, National Patient, Cause of Death and Population Registers.
Figure S1. Total burden of comorbidities per age category in
patients with heart failure<55 years.
Figure S2. Time-dependent area under the curve for the mul-tivariate model adjusted for age, sex, duration of heart failure, ischaemic heart disease, diabetes, dilated cardiomyopathy, hyper-trophic cardiomyopathy/hyperhyper-trophic obstructive cardiomyopathy, congenital heart disease and/or valve disease and cancer.
Acknowledgements
We thank Georg Lappas, and Araz Rawshani for their contri-bution to statistical analyses. We thank Ellen Knapp, PhD, from Edanz Group (www.edanzediting.com/ac) for editing a draft of this manuscript.
Funding
This work was supported by the Swedish Research Council (2013-5187 SIMSAM); the Swedish state under the agree-ment concerning research and education of doctors (grant numbers:ALFGBG-433211, ALFGBG-725081, ALFGBG-717211); The Swedish Heart and Lung Foundation (grant numbers: 2013-0307 and 2018-0419 and 2015-0438); Västra Götaland ...
...
...
Region; and The Gothenburg Society of Medicine (grant number:GLS-328971 to the first author); The Swedish Coun-cil for Health, Working Life and Welfare (FORTE) [2013-0325]; Cardiology Research Foundation at the Medical Clinic at Sahlgren-ska University Hospital / Östra. The SwedeHF is funded by the Swedish National Board of Health and Welfare, the Swedish Association of Local Authorities and Regions, and the Swedish Society of Cardiology and Cardiology Research Foundation. Conflict of interest: none declared.
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