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Increased comorbidities in heart failure patients ≥ 85 years but declined from > 90 years: Data from the Swedish Heart Failure Registry
International Journal of Cardiology 167 (2013) 2747–2752
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Increased comorbidities in heart failure patients ≥85 years but declined from >90 years: Data from the Swedish Heart Failure Registry Alexandra Holmström a, Runa Sigurjonsdottir a, Magnus Edner b, Åsa Jonsson c, Ulf Dahlström d, Michael LX Fu a,⁎ a
Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska University Hospital, University of Gothenburg, Gothenburg, Sweden Karolinska Institutet, Department of Medicine, Karolinska University Hospital Solna, Stockholm, Sweden Department of Cardiology, Ryhov County Hospital, Jönköping, Sweden d Department of Cardiology, Linköping University Hospital, Linköping, Sweden b c
a r t i c l e
i n f o
Article history: Received 5 April 2012 Received in revised form 4 June 2012 Accepted 24 June 2012 Available online 16 July 2012 Keywords: Heart failure Registry Epidemiology Elderly Comorbidity
a b s t r a c t Objectives: Epidemiological studies of elderly heart failure (HF) patients (≥85 years) are limited with inconsistent findings. Our objective is to confirm and extend epidemiological study in elderly (≥ 85 years) patients using the Swedish Heart Failure Registry database. Methods: This retrospective study included 8,347 HF patients aged ≤ 65 years and 15,889 HF patients aged ≥ 85 years. Elderly population was further divided into two subgroups: 11,412 patients were 85–90 years and 4,477 patients were > 90 years. Results: The ≥ 85 year group was characterized by more women, higher systolic blood pressure (SBP), lower body-mass index (BMI), more than twice as many HF with normal left ventricular ejection fraction (HFNEF), higher incidence of cardiovascular and non-cardiovascular comorbidities and less use of proven therapeutics compared with the ≤65 year group. Compared with the 85–90 year subgroup, the >90 year subgroup had a decline in cardiovascular and non-cardiovascular comorbidities except renal insufficiency and anaemia which continued to increase with ageing (p b 0.01). Tendency was the same regardless of gender but slightly different between systolic HF (SHF) and HFNEF. In the group with HFNEF, there were more women, higher SBP, lower N-terminal pro-B-type natriuretic peptide levels, less ischaemic heart disease, more hypertension and left bundle branch block regardless of age. Atrial fibrillation was more frequent in patients with HFNEF than with SHF in the elderly group (p b 0.01). Patients with HFNEF in the > 90 year subgroup had increasing incidence of ischaemic heart disease compared to 85–90 year group (p b 0.01). Conclusions: HF patients ≥85 years had increased cardiovascular and non-cardiovascular comorbidities but with a decline from > 90 years. Crown Copyright © 2012 Published by Elsevier Ireland Ltd. All rights reserved.
1. Introduction Heart failure (HF) is still one of the leading causes of death, and it increases with age in line with comorbidity and mortality [1–12]. Previous landmark randomized clinical trials have mostly been conducted in younger systolic HF (SHF) patients with an average age of b63 years and a left ventricular ejection fraction (LVEF) of b 40%. Available HF studies on the so-called “elderly” have generally focused on a population aged around 65–75 years, and patients ≥85 years are rarely Abbreviations: ACEi, ACE inhibitors; BNP, B-type natriuretic peptide; BB, Beta blockers; eGFR, Estimated glomerular filtration rate; HF, Heart failure; HFNEF, Heart failure with normal left ventricular ejection fraction; LVEF, Left ventricular ejection fraction; NT-proBNP, N-terminal pro B-type natriuretic peptide; S-HFR, Swedish National Heart Failure Registry; SHF, Systolic heart failure. ⁎ Corresponding author at: Section of Cardiology, Department of Medicine, Östra Hospital Sahlgrenska University Hospital, University of Gothenburg, SE 413 45 Gothenburg, Sweden. E-mail address: [email protected] (M.LX Fu).
studied [1–12,19]. As a consequence, HF in patients aged ≥85 years remains poorly understood. Findings from the few studies that have been performed in this age group have not been consistent, particularly with regard to both cardiovascular and non-cardiovascular comorbidities [6,8,9,13–18]. For instance, the incidence of hypertension has been reported to be both lower [14,17,18] and higher [6,7,15] and the incidence of ischaemic heart disease has been shown to be similar [17], higher [15] and lower in elderly patients [14,18]. These differences may be due to small sample sizes in previous studies, a limitation because of the highly heterogeneous nature of the elderly HF patient population. Moreover, HF with normal left ventricular ejection fraction (HFNEF) was reported to be more frequent in the elderly. Differences in comorbidity between SHF and HFNEF in those ≥85 years remain largely unknown. The need for in-depth characterization and understanding of HF in elderly populations is important, particularly for those aged ≥85 years, because the number of people with HF in this age group is increasing rapidly as the aged population increases worldwide. In addition, because
0167-5273/$ – see front matter. Crown Copyright © 2012 Published by Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijcard.2012.06.095
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advanced medical technology allows us to offer a wider range of therapies, further information to help us make the correct choice becomes more important. The internet-based Swedish Heart Failure Registry commenced in 2003 [20]. It is an important source of information about the epidemiology and characteristics of HF in elderly patients. In the present study, our main objective is not only to confirm previous epidemiological finding in the ≥ 85 year group but also to extend the study by dividing this group further into two subgroups: 85–90 year and > 90 year, and moreover making comparisons between SHF and HFNEF in this elderly population. 2. Methods 2.1. Swedish Heart Failure Registry The Swedish Heart Failure Registry has been described previously in the introduction [20]. This internet-based registry was created in 2003 and allows participating units to register their HF patients online after diagnosis by a clinician (www.rikssvikt.se). During an initiation visit, staff receive training from a registry coordinator on how to register patients and how to use the registry. More than 70 variables, including demographics, concomitant diseases, diagnostic procedures, hemodynamics, laboratory data, and medication, are recorded at discharge from hospital (within 1 month) or after visits to outpatient clinics. Sixty of these variables in the registry are obligatory and the other 10 are optional. The registry recommends that patients be re-registered after each hospitalization due to HF. All patients are informed that their hospital or primary care centre is participating in the registry and patients who do not wish to participate are assured that all registered data related to them will be deleted. Patients are consecutively entered. The registry and analysis of the database were approved by the regional ethical review board. 2.2. Subgroups and definitions The ≥85 year group was further subdivided into two groups: 85–90 year and >90 year. Additionally a younger population (≤65 years) was included for comparison. Patients aged 66–84 years were not included in this study because of two reasons: 1) to not include the transient age group to show the greatest contrast as possible between the much younger and much elderly and 2) to make the focus of current study on the ≥85 year group. HF was diagnosed individually by physicians from participating registration sites where the current guidelines for the diagnosis and treatment of acute and chronic HF is strongly recommended [21,22]. Cut-off for LVEF is defined as b50% in SHF, and ≥50% for HFNEF. Tachycardia is defined as heart rate >100 beats/min, whereas bradycardia is b60 beats/min. In the registry, the estimated glomerular filtration rate (eGFR) was calculated using the Cockroft–Gaults formula. 2.3. Statistics The results are presented as percentage and mean±standard deviation (SD), or as median and interquartile range (IQR) when values were not distributed normally. In the case of continuous variables, statistical analysis was performed using Student's unpaired t-test or the Mann–Whitney U-test for abnormally distributed variables. For discrete variables, the chi-square test was used. The PASW Statistics 18 (USA) statistical package was used for all the data analyses. pb 0.05 was regarded as statistically significant.
3. Results Up until 31 December 2009, 8,348 younger (≤65 years) and 15,889 elderly (≥85 years) HF patients were registered. In the ≥85 year HF patient group, 11,412 patients were 85–90 years and 4,477 were >90 years. Patients aged 66–84 years were not included in this study. Natriuretic peptide testing was performed in 2,938 patients (35%) in the ≤65 year group, 2,890 (25%) in the 85–90 year group and 723 (16%) in the >90 year group. Among comorbidity, only 5% of the data set was completely filled for both depression and malignancy. The majority of HF patients had been registered by hospital clinicians. Only 2.1% of the ≤65 year group, 4.5% of the 85–90 year group, and 1.2% of the >90 year group were registered by primary care clinicians.
≥85 year group was characterized by more women, lower BMI, higher systolic blood pressure (SBP), lower diastolic blood pressure (DBP), more left bundle brunch block (LBBB), more than twice as many patients with HFNEF, more cardiovascular comorbidities (ischaemic heart disease, hypertension and atrial fibrillation), more non-cardiovascular comorbidities (anaemia, pulmonary disease, stroke and renal insufficiency) except diabetes which decreased with ageing (pb 0.01 for each of these variables). Compared to the 85–90 year group, the >90 year group had a decline in cardiovascular and non-cardiovascular comorbidities except renal insufficiency and anaemia which continued to increase with ageing (Table 1). As shown in Table 1, moderate renal insufficiency in terms of GFR b60 mL/min kept increasing from 10.9% in patients ≤65 years to 89.8% in patients 85–90 years and continued increasing to 97.2% in patients >90 years. An even more dramatic increase was observed in severe renal insufficiency in terms of GFR b30 mL/min from 1.8% in patients ≤65 years to 28.0% in patients 85–90 years and continued increasing to 53.1% in those >90 years. Likewise, the incidence of anaemia increased from 22.4% in patients ≤65 years to 44.3% in patients 85–90 years and furthermore to 47.2% in those >90 years. HFNEF occurred more than twice as often in the 85–90 and >90 year groups compared with the ≤65 year group. The incidences of HFNEF were different depending on how they were calculated. In cases where the sample size was only the number of those with available echocardiography, HFNEF was present in 27.3% and 33.0% of the patients in the 85–90 and >90 year subgroups, respectively, compared with 12.3% in the ≤65 year group. However, in cases where the sample size was the total number of patients including those without available echocardiography, HFNEF was present in 22.2% and 20.4% of the patients in the 85–90 and >90 year subgroups, respectively. Moreover, both B-type natriuretic peptide (BNP) and N-terminal pro B-type natriuretic peptide (NT-pro BNP) levels were twice as high for the 85–90 and >90 year subgroups compared to the ≤65 year group (Fig. 1). 3.2. SHF and HFNEF profile differences among the age groups As shown in Table 2, the SHF and HFNEF patient profiles varied not only between the ≤65 and ≥85 year groups, but also between the 85–90 and >90 year subgroups. In general, patients with HFNEF were more likely to be women and had higher SBP, narrower QRS width, lower P-creatinine (Cr) levels, lower NT-proBNP levels (Fig. 1), less ischaemic heart disease and more hypertension compared with those with SHF (p b 0.01 for each of these variables). However, there were several differences between SHF and HFNEF. In the ≥85 year group, HFNEF patients had significantly higher frequency of atrial fibrillation compared to those with SHF; this was not the case for HFNEF patients in the ≤65 year group (Fig. 2). In the ≥90 year group, ischaemic heart diseases continued to increase in HFNEF but decreased in SHF. However, diabetes incidence and BMI decreased with age regardless of SHF or HFNEF. 3.3. Hemodynamic disorders As compared to the ≤65 year group, the incidences of tachycardia did not increase until >90 years. By contrast the incidence of bradycardia decreased from ≥85 years and continued decreasing despite >90 years. Similarly, the incidence of hypertension with SBP >140 mm Hg was higher and hypotension was lower in the 85–90 and >90 year subgroups compared to the ≤65 year group (data not shown). 3.4. Distinct treatment profiles among the different age groups
3.1. Differences in demographic and clinical characteristics among the age groups As shown in Table 1, both the 85–90 year group and the >90 year group had characteristics that differed from those of the younger population ≤65 years. In general, compared with the ≤65 year group, the
At the time of discharge from hospital, prescriptions of beta receptor blockers (BB), ACE inhibitors (ACEi), angiotensin receptor blockers (ARB) and aldosterone antagonists were less common whereas diuretics were more common for ≥85 year patients than for ≤65 year group. Even less BB, ACEi, ARB and aldosterone antagonists were
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Table 1 Demographic and clinical characteristics in older and younger HF patients in the total study population. Variables Patient characteristics
Clinical examinations
Laboratory examinations
Cardiovascular comorbidity
Non-cardiovascular comorbidity
Treatment
N Age (mean ± SD) Male (%) BMI (mean ± SD) SBP (mm Hg) (mean ± SD) DBP (mm Hg) (mean ± SD) Heart rate (beats/min) (mean ± SD) ECGa sinus rhythm (%) Atrial fibrillation (%) LBBB (%) QRS (ms) (mean ± SD) PM rhythm (%)b LVEFc ≥50 (%)d LVEF 40–49 (%) LVEF 30–39 (%) LVEF b30 (%) LVEF unknowne Hb (g/L) (mean ± SD) BNP (ng/L) (median (IQR)) NT-proBNP (ng/L) (median (IQR)) P-creatinine (μmol/L) (mean ± SD) eGFR (mL/min)f (mean ± SD) Ischaemic heart diseases (%) Hypertension (%) Atrial fibrillation (%)g Diabetes mellitus (%) Pulmonary diseases (%) Stroke (%) eGFR b60 (mL/min)f (%) eGFR b30 (mL/min)f (%) Anaemia (%)j ACE inhibitors (ACEi) (%) Beta blockers (BB) (%) Angiotensin receptor blockers (%) Aldosterone antagonists (%) ACEi + BB (%) RAAS blockade (%) Diuretics (%)
≤65 years
85–90 years
>90 years
8,348 56 ± 8 76.4 28.7 ± 6.3 122 ± 21 75 ± 13 74 ± 15 70.2 22.7 13.8 109.3 ± 26.9 7.0 11.8 17.5 25.4 40.8 4.5 138.7 ± 17.2 254 (91–727)
11,412 87 ± 2⁎⁎ 53.3⁎⁎
616 (247–1420)⁎⁎
4,477 94 ± 3##,¶¶ 41.1##, ¶¶ 23.2 ± 4.1##,¶¶ 130 ± 23##,¶¶ 71 ± 13 77 ± 17##,¶¶ 40.5## 48.8##,¶ 14.0¶¶ 110.9 ± 29.2##,¶¶ 10.7## 20.4##,¶ 14.3##,¶¶ 15.3##,¶¶ 12.0##,¶¶ 38.0##,¶¶ 124.7 ± 15.8##,¶ 863 (340–1643)##
1440 (520–3655)
3990 (1846–9000)⁎⁎
5493 (2375–11,899)##,¶¶
97.0 ± 56.5 102.6 ± 49.8 34.8 37.7 29.7 24.4 13.3 7.9 10.9 1.8 22.4 74.4 91.4 23.5 36.1 68.9 92.3 69.9
125.5 ± 64.1⁎⁎ 39.9 ± 16.6⁎⁎ 56.1⁎⁎ 49.5⁎⁎ 57.3⁎⁎ 20.0⁎⁎ 19.1⁎⁎ 15.7⁎⁎ 89.8⁎⁎ 28.0⁎⁎ 44.3⁎⁎ 56.3⁎⁎ 80.3⁎⁎
128.0 ± 15.9##,¶ 30.9 ± 13.5##,¶¶ 53.5##,¶¶ 45.6##,¶¶ 56.1##,¶ 14.6##,¶¶ 15.5##,¶¶ 11.3##,¶¶ 97.2##,¶¶ 53.1##,¶¶ 47.2##,¶¶ 43.5##,¶¶ 70.0##,¶¶ 11.0##,¶¶ 26.7##,¶ 32.0##,¶¶ 53.2##,¶¶ 91.1##,¶¶
25.1 ± 4.5⁎⁎ 129 ± 22⁎⁎ 71 ± 12⁎⁎ 75 ± 16 41.5⁎⁎ 47.2⁎⁎ 16.2⁎⁎
112.6 ± 30.3⁎⁎ 11.3⁎⁎ 22.2⁎⁎ 17.6 21.4⁎⁎ 19.9⁎⁎ 18.9⁎⁎ 127.0 ± 16.3⁎⁎
19.3 28.8⁎⁎ 46.0⁎⁎ 73.1⁎⁎ 89.1⁎⁎
a
According to ECG recording at the time of registration. Pacemaker rhythm. c Left ventricular ejection fraction. d % was calculated on the basis of total sample size including those with unknown LVEF. e % of unknown echocardiography examinations based on total number of registered patients. f Cockroft–Gaults formula. g Atrial fibrillation in medical history recordings. j Anaemia according to WHO b130 g/L (male) and b120 g/L (female). ⁎ p b 0.05 between ≤65 and 85–90 years groups. ⁎⁎ p b 0.01 between ≤65 and 85–90 years groups. # p b 0.05 between ≤65 and >90 years groups. ## p b 0.01 between ≤65 and >90 years groups. ¶ p b 0.05 between 85–90 and >90 years groups. ¶¶ pb 0.01 between 85–90 and >90 years groups. b
prescribed and even more diuretics were prescribed in the >90 year group compared with the 85–90 year group (Table 1). A similar pattern of pharmacological treatment was found not only in SHF but also in HFNEF except that in HFNEF prescription of aldosterone antagonist continued increasing despite higher age (Table 2). 4. Discussion
Fig. 1. Comparison of the median NT-proBNP (ng/L) levels between SHF and HFNEF patients. ⁎⁎pb 0.01 between SHF and HFNEF patients in the same age group.
Our study demonstrated an increase in most of the cardiovascular and non-cardiovascular comorbidities in the 85–90 year group compared with the ≤65 year group but with a decline in the > 90 year group of the Swedish patients with HF. To date, most studies of HF have been conducted on populations with an average age of around 65–75 years, or on sample populations selected for interventional clinical trials. HF patients ≥85 years have rarely been studied. This is a huge group that is estimated to constitute
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Table 2 SHF and HFNEF profiles in elderly vs. “younger HF patients with available echocardiography. ≤65 years
Variables
HFNEF Patient characteristics
N Age Male (%) BMI SBP (mm Hg) DBP (mm Hg) Heart rate Atrial fibrillationa LBBB (%) QRS (ms) Hb (g/L) BNP (ng/L) [median (IQR)]
981 57 ± 8 63.4 30.1 ± 7.6 Clinical examinations 128 ± 22 76 ± 13 72 ± 15 21.3 5.9 98.1 ± 18.1 Laboratory examinations 139.0 ± 20.0 161 (37–371) NT-proBNP (ng/L) [median 723 (IQR)] (212–1746) P-Cr (μmol/L) 94.5 ± 54.9 b eGFR (mL/min) 102.3 ± 50.4 Cardiovascular comorbidity Ischaemic heart disease 24.8 (%) Hypertension 48.8 Atrial fibrillationc 31.1 Noncardiovascular Diabetes mellitus 26.4 comorbidity (%) Pulmonary diseases 15.1 Stroke 8.0 Anaemiad 24.9 b eGFR b60 (mL/min) 8.7 b eGFR b30 (mL/min) 1.3 e Treatment (%) ACEi 60.4 BBf 81.6 ARBg 26.3 Aldosterone antagonists 27.0 Diuretics 64.8
85–90 years
>90 years
SHF
HFNEF
SHF
HFNEF
SHF
6,989 56 ± 8 78.4## 28.5 ± 6.0## 120 ± 21## 75 ± 13 74 ± 15# 22.5 18.4## 111.0 ± 27.6## 139 ± 16.9 260 (92–747)# 1628 (587–3964)## 97.2 ± 55.7## 103.8 ± 45.9 36.3## 35.9## 29.2 23.9## 13.1# 7.9 22.2## 11.2# 1.9 78.3## 93.4## 23.1 38.2## 70.2##
2,528 87 ± 2⁎⁎ 39.3⁎⁎ 25.9 ± 4.9⁎⁎ 133 ± 23⁎⁎ 72 ± 13⁎⁎ 75 ± 16⁎⁎ 58.5⁎⁎ 11.8⁎⁎
6,726 87 ± 2⁎⁎,## 61.3⁎⁎,## 24.8 ± 4.3⁎⁎,## 126 ± 22⁎⁎,## 71 ± 12⁎⁎,## 74 ± 15⁎⁎ 51.0⁎⁎,## 26.6⁎⁎,## 118.0 ± 30.0⁎⁎,## 128.1 ± 16.4⁎⁎,##
914 94 ± 3¶¶ 28.6¶¶ 23.4 ± 4.2¶¶ 132 ± 24¶¶ 71 ± 13¶¶ 77 ± 16¶¶ 58.2¶¶ 11.0¶¶ 104.2 ± 31.3¶¶ 123.9 ± 16.0¶¶ 578 (306–1625) 4512 (1902–10,374)¶¶ 120.2 ± 54.4¶¶ 31.3 ± 12.6¶¶ 47.6¶¶ 51.5¶¶ 59.7¶¶ 15.7¶¶ 15.4¶¶ 11.1 46.8 97.0¶¶ 52.2¶¶ 39.4¶¶ 71.1¶¶ 11.2¶¶ 31.7 92.2¶¶
1,859 93 ± 2¶¶,## 52.0¶¶,## 23.4 ± 3.7¶¶ 127 ± 22## 70 ± 12# 75 ± 15¶¶ 51.9## 24.7## 117.5 ± 29.6¶¶,## 125.4 ± 15.6¶¶,# 1110 (575–1960)¶ 7341 (34,555–15,579)¶¶,## 136.3 ± 69.0¶¶,## 30.4 ± 12.8¶¶ 62.2¶¶,## 42.2¶¶,## 54.7¶¶,## 15.2¶¶ 16.3 14.3 48.0¶¶ 97.8¶¶ 53.9¶¶ 51.7¶¶,## 77.4¶¶,## 12.5¶¶ 27.4¶¶,# 91.6¶
102.7 ± 25.8⁎⁎ 125.1 ± 15.6⁎⁎ 382 (183–1147)⁎⁎ 2794 (1367–6035)⁎⁎ 119.0 ± 60.3⁎⁎ 40.1 ± 16.9⁎⁎ 43.9⁎⁎ 55.9⁎⁎ 63.7⁎⁎ 18.8⁎⁎ 23.2⁎⁎ 13.6 46.1⁎⁎ 88.9⁎⁎ 26.0⁎⁎ 50.3⁎⁎ 77.3⁎⁎ 19.2⁎⁎ 28.6 90.5⁎⁎
733 (335–1619)⁎⁎,## 4900 (2258–10,900)⁎⁎,## 128.2 ± 62.0⁎⁎,## 39.6 ± 16.3⁎⁎,## 63.5⁎⁎,## 46.7⁎⁎,## 55.2⁎⁎,## 20.8⁎⁎,# 17.5⁎⁎,## 12.5 44.1⁎⁎ 90.5⁎⁎,# 28.8⁎⁎,## 61.2⁎⁎,## 84.3⁎⁎,## 19.9⁎⁎ 30.8⁎⁎,# 89.7⁎⁎
a
Atrial fibrillation on ECG at the time of registration. Cockroft–Gaults formula. c Atrial fibrillation in medical history. d Anaemia according to WHO b130 g/L (male) and b120 g/L (female). e ACE inhibitors (ACEi). f Beta receptor blockers (BB). g Angiotensin receptor blockers (ARB). ⁎ p b 0.05 between ≤65 and 85–90 year groups in the same HF category. ⁎⁎ p b 0.01 between ≤65 and 85–90 year groups in the same HF category. # p b 0.05 between HFNEF and SHF in the same age group. ## p b 0.01 between HFNEF and SHF in the same age group. ¶ p b 0.05 between 85–90 and >90 year groups in the same HF category. ¶¶ p b 0.01 between 85–90 and >90 year groups in the same HF category. b
one-fourth of the HF population aged >65 years [9]. Although there have been some studies of this elderly population, the sample sizes are usually quite small. One of these studies is the EuroHeart Failure
Fig. 2. Comparison between younger and older HF patients in terms of frequency of atrial fibrillation (%). ⁎⁎pb 0.01 between ≤65 years and 85–90 years or >90 years. ##pb 0.01 between 85–90 years and >90 years.
Survey II (EHFSII) [6], in which 3,577 patients were included. However, only 741 participants were ≥80 years. Another was the Italian Survey on Acute Heart Failure in which 2,807 patients were included and only 28% of enrolees were 84± 4 years [7]. Recently, Mogensen et al. reported an elderly HF cohort in which 825 patients ≥85 years were included [18]. Therefore, the strength of the present study is its large sample size of HF patients ≥85 years (n= 15,889) which is almost 20 times larger than in previous studies. Because of the large sample size of our study, we were able to confirm and extend previously observed clinical differences between elderly and younger patients [5–12]. Both the 85–90 and >90 year subgroups had characteristics that not only distinguished them from the ≤65 year group but also were heterogeneous between the 85–90 and >90 year subgroups. In general, the 85–90 year group had more than twice as many patients with HFNEF, more cardiovascular diseases and moreover more associated non-cardiovascular comorbidities. Comorbidities did not increase parallel with age. In fact, compared with the 85–90 year group, the >90 year group had a decline in most comorbidities, regardless of whether they were cardiovascular or non-cardiovascular. However, there were several exceptions, in those aged ≥85 years, diabetes decreased rather than increased with age. This was in line with the data from previous reports [6,14,15,17,18] in which the frequency of
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diabetes was shown to be lower in elderly patients. One possible explanation is that HF with a comorbidity such as diabetes is associated with higher mortality, which decreases the likelihood of survival until the age of 85 years and beyond. Another explanation is that diabetes is under-diagnosed in elderly adults with HF. By contrast, renal insufficiency and anaemia continued to increase with age although many other comorbidities started to decline in the >90 year group. For instance, patients ≥85 years had almost 9-fold increased incidence of moderate renal insufficiency and at least 15-fold increased incidence of severe renal insufficiency, as compared with those ≤65 years. Among those ≥85 years, patients in the >90 year group had almost twice as much severe renal dysfunction as those in the 85–90 year group. Likewise, incidence of anaemia has almost doubled from patients ≤65 years to those ≥85 years. Since previous findings regarding age-related comorbidity have not been consistent [6,8,9,13–18] due to either limited sample size or different databases, therefore our results bring clarification to this field. In our study, echocardiography was done in 81% and 62% of the 85–90 and >90 years HF patients respectively. These rates of echocardiography were similar to those seen in EHFSII [6]. Nevertheless, echocardiography has remained a less-common diagnostic option in >90 year patients. In line with previous results, HFNEF was more frequently seen in the ≥85 year population. In EHFSII [6], LVEF >45% was present in 39% of patients >80 years, whereas in our study, LVEF ≥50% was present in 22.2% and 20.4% of the patients in the 85–90 and >90 year subgroups, respectively, based on total sample size including those with unknown LVEF, but in 27.3% and 33.0% of the patients in the 85–90 and >90 year subgroups respectively, based on the sample size with available echocardiography. Our results differed from EHFSII because the cut off values of LVEF were set differently for HFNEF (LVEF ≥50% in our study compared to ≥45% in EHFSII), which made comparisons difficult. Measurement of natriuretic peptides is often necessary to confirm HFNEF diagnosis together with echocardiography. In our study, natriuretic peptide testing was performed in 35%, 25% and 16% of patients in the ≤65, 85–90 and >90 year groups respectively. This might make HFNEF diagnosis in the elderly somewhat uncertain. The statistical strength in each of the age categories was sufficient for the natriuretic peptide testing. HFNEF occurred more than twice as often in the 85–90 and >90 year groups compared with the ≤65 year group regardless of whether natriuretic peptide testing was applied. Moreover, similar demographic and clinical variable patterns were found in the younger and elderly HF populations regardless of natriuretic peptide testing. This may be due to the fact that the majority of HF patients in registry were registered while they were under the care of hospital clinicians. It is interesting to note that both BNP and NT-proBNP levels were twice as high in the 85–90 and >90 year groups compared with the ≤65 year group. When NT-pro BNP levels were compared between HFNEF and SHF patients, NT-proBNP levels in patients with HFNEF were much lower than those in SHF patients within the same age category. In line with an earlier report [6], and in our report compared with SHF patients, patients with HFNEF were more likely to be women and had higher SBP, narrower QRS width, lower NT-proBNP levels, less ischaemic heart disease and more hypertension. In ≥ 85 year HFNEF patients, the frequency of occurrence of atrial fibrillation was as high as 64%, compared with 55% in patients with SHF. Moreover, atrial fibrillation increased in prevalence with increased age and was a major contributor to morbidity in this population due to associated strokes, HF and quality-of-life impairment. In our study, at the time of discharge from hospital, medications such as BB, ACEi, ARB, aldosterone antagonists were less commonly prescribed for ≥85 year patients than for to ≤65 year patients. Even fewer prescriptions of the above medications were observed in >90 years compared with 85–90 years. Nevertheless, both subgroups of elderly HF patients had significantly more prescriptions for BB compared with the patients in EHFSII [6]. Conversely, elderly HF patients
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had significantly fewer prescriptions for aldosterone antagonists compared with the patients in EHFSII [6]. The difference in treatment modalities between younger and older HF patients might be due to the lack of documented efficacy, concern for safety, comorbidity and polypharmacy in elderly patients. 4.1. Limitations The present study was limited by the low number of patients who were registered by primary care clinicians. Moreover, not all hospitals and outpatient clinics in Sweden have registered their patients in the registry. Some variables are underreported. For example, only 5% of the data set was completely filled for both depression and malignancy. This might be explained by the fact that some variables such as malignancy and depression were first introduced in registry in February 2010 and it then took time to implement the change. In addition, diagnosis was reported individually by physicians from participating registration sites. With the consideration that natriuretic peptide testing was not widely used, a diagnosis of HF in the absence of natriuretic peptide testing and/or echocardiography is questionable in particular in the oldest population where comorbidity (e.g. pulmonary disease) is easily wrongly diagnosed as HF because of similar symptoms. 5. Conclusions Our study of a large population from a Swedish Heart Failure Register database demonstrated that HF patients ≥85 years had increased cardiovascular and non-cardiovascular comorbidities but that these comorbidities declined in the >90 year group. Acknowledgements This study was supported by the Swedish Heart-Lung Foundation. The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology. References [1] Fu M. Heart failure therapy in the elderly: where are we? What are we doing? Int J Cardiol 2008;125:147–8. [2] Jensen J, Ma LP, Bjurman C, Hammarsten O, Fu ML. Prognostic values of NT-proBNP/BNP ratio in comparison with NT-proBNP or BNP alone in elderly patients with chronic heart failure in a 2-year follow up. Int J Cardiol 2012;155: 1–53. [3] Jensen J, Ma LP, Fu ML, Svaninger D, Lundberg PA, Hammarsten O. Inflammation increases NT-proBNP and the NT-proBNP/BNP ratio. Clin Res Cardiol 2010;99: 445–52. [4] Jensen J, Hedin L, Widell C, Agnhom P, Andersson B, Fu M. Characteristics of heart failure in the elderly—a hospital cohort registry-based study. Int J Cardiol 2008;125:191–6. [5] Komajda M, Follath F, Swedberg K, et al. The EuroHeart Failure Survey programme — a survey on the quality of care among patients with heart failure in Europe. Part 2: treatment. Eur Heart J 2003;24:464–74. [6] Komajda M, Hanon O, Hochadel M, et al. Contemporary management of octogenarians hospitalized for heart failure in Europe: Euro Heart Failure Survey II. Eur Heart J 2009;30:478–86. [7] Miani D, Fresco C, Lucci D, et al. Clinical characteristics, management, and prognosis of octogenarians with acute heart failure admitted to cardiology wards: results from the Italian Survey on Acute Heart Failure. Am Heart J 2009;158:126–32. [8] Mahjoub H, Rusinaru D, Soulière V, Durier C, Peltier M, Tribouilloy C. Long-term survival in patients older than 80 years hospitalised for heart failure. A 5-year prospective study. Eur J Heart Fail 2008;10:78–84. [9] Havranek EP, Masoudi FA, Westfall KA, Wolfe P, Ordin DL, Krumholz HM. Spectrum of heart failure in older patients: results from the National Heart Failure project. Am Heart J 2002;143:412–7. [10] Pulignano G, Del Sindaco D, Tavazzi L, et al. Clinical features and outcomes of elderly outpatients with heart failure followed up in hospital cardiology units: data from a large nationwide cardiology database (IN-CHF Registry). Am Heart J 2002;143:45–55. [11] Manzano L, Babalis D, Roughton M, et al. Predictors of clinical outcomes in elderly patients with heart failure. Eur J Heart Fail 2011;13:528–36. [12] Alehagen U, Dahlström U, Lindahl TL. Cystatin C and NT-proBNP, a powerful combination of biomarkers for predicting cardiovascular mortality in elderly patients
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A. Holmström et al. / International Journal of Cardiology 167 (2013) 2747–2752 with heart failure: results from a 10-year study in primary care. Eur J Heart Fail 2009;11:354–60. Gambassi G, Forman DE, Lapane KL, et al. Management of heart failure among very old persons living in long-term care: has the voice of trials spread? The SAGE study group. Am Heart J 2000;139:85–93. Komajda M, Hanon O, Hochadel M, et al. Management of octogenarians hospitalized for heart failure in Euro Heart Failure Survey I. Eur Heart J 2007;28: 1310–8. Miani D, Fresco C, Lucci D, et al. Clinical characteristics, management, and prognosis of octogenarians with acute heart failure admitted to cardiology wards: results from the Italian Survey on Acute Heart Failure. Am Heart J 2009;158:126–32. Rich MW, McSherry F, Williford WO, Yusuf S. Effect of age on mortality, hospitalizations and response to digoxin in patients with heart failure: the DIG study. J Am Coll Cardiol 2001;38:806–13. Martin-Pfitzenmeyer I, Gauthier S, Bailly M, et al. Prognostic factors in stage D heart failure in the very elderly. Gerontology Gerontology 2009;55:719–26.
[18] Mogensen UM, Ersbøll M, Andersen M, et al. Clinical characteristics and major comorbidities in heart failure patients more than 85 years of age compared with younger age groups. Eur J Heart Fail 2011;13:1216–23. [19] Fu M. Beta-blocker therapy in heart failure in the elderly. Int J Cardiol 2008;125: 149–53. [20] Jonsson A, Edner M, Alehagen U, Dahlström U. Heart failure registry: a valuable tool for improving the management of patients with heart failure. Eur J Heart Fail 2010;12:25–31. [21] Dickstein K, Cohen-Solal A, Filippatos G, et al. ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2008. Eur Heart J 2008;29: 2388–442. [22] Paulus WJ, Tschöpe C, Sanderson JE, et al. How to diagnose diastolic heart failure: a consensus statement on the diagnosis of heart failure with normal left ventricular ejection fraction by the Heart Failure and Echocardiography Associations of the European Society of Cardiology. Eur Heart J 2007;28:2539–50.
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Increased comorbidities in heart failure patients ≥85 years but declined from >90 years: Data from the Swedish Heart Failure Registry Alexandra Holmström a, Runa Sigurjonsdottir a, Magnus Edner b, Åsa Jonsson c, Ulf Dahlström d, Michael LX Fu a,⁎ a
Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska University Hospital, University of Gothenburg, Gothenburg, Sweden Karolinska Institutet, Department of Medicine, Karolinska University Hospital Solna, Stockholm, Sweden Department of Cardiology, Ryhov County Hospital, Jönköping, Sweden d Department of Cardiology, Linköping University Hospital, Linköping, Sweden b c
a r t i c l e
i n f o
Article history: Received 5 April 2012 Received in revised form 4 June 2012 Accepted 24 June 2012 Available online 16 July 2012 Keywords: Heart failure Registry Epidemiology Elderly Comorbidity
a b s t r a c t Objectives: Epidemiological studies of elderly heart failure (HF) patients (≥85 years) are limited with inconsistent findings. Our objective is to confirm and extend epidemiological study in elderly (≥ 85 years) patients using the Swedish Heart Failure Registry database. Methods: This retrospective study included 8,347 HF patients aged ≤ 65 years and 15,889 HF patients aged ≥ 85 years. Elderly population was further divided into two subgroups: 11,412 patients were 85–90 years and 4,477 patients were > 90 years. Results: The ≥ 85 year group was characterized by more women, higher systolic blood pressure (SBP), lower body-mass index (BMI), more than twice as many HF with normal left ventricular ejection fraction (HFNEF), higher incidence of cardiovascular and non-cardiovascular comorbidities and less use of proven therapeutics compared with the ≤65 year group. Compared with the 85–90 year subgroup, the >90 year subgroup had a decline in cardiovascular and non-cardiovascular comorbidities except renal insufficiency and anaemia which continued to increase with ageing (p b 0.01). Tendency was the same regardless of gender but slightly different between systolic HF (SHF) and HFNEF. In the group with HFNEF, there were more women, higher SBP, lower N-terminal pro-B-type natriuretic peptide levels, less ischaemic heart disease, more hypertension and left bundle branch block regardless of age. Atrial fibrillation was more frequent in patients with HFNEF than with SHF in the elderly group (p b 0.01). Patients with HFNEF in the > 90 year subgroup had increasing incidence of ischaemic heart disease compared to 85–90 year group (p b 0.01). Conclusions: HF patients ≥85 years had increased cardiovascular and non-cardiovascular comorbidities but with a decline from > 90 years. Crown Copyright © 2012 Published by Elsevier Ireland Ltd. All rights reserved.
1. Introduction Heart failure (HF) is still one of the leading causes of death, and it increases with age in line with comorbidity and mortality [1–12]. Previous landmark randomized clinical trials have mostly been conducted in younger systolic HF (SHF) patients with an average age of b63 years and a left ventricular ejection fraction (LVEF) of b 40%. Available HF studies on the so-called “elderly” have generally focused on a population aged around 65–75 years, and patients ≥85 years are rarely Abbreviations: ACEi, ACE inhibitors; BNP, B-type natriuretic peptide; BB, Beta blockers; eGFR, Estimated glomerular filtration rate; HF, Heart failure; HFNEF, Heart failure with normal left ventricular ejection fraction; LVEF, Left ventricular ejection fraction; NT-proBNP, N-terminal pro B-type natriuretic peptide; S-HFR, Swedish National Heart Failure Registry; SHF, Systolic heart failure. ⁎ Corresponding author at: Section of Cardiology, Department of Medicine, Östra Hospital Sahlgrenska University Hospital, University of Gothenburg, SE 413 45 Gothenburg, Sweden. E-mail address: [email protected] (M.LX Fu).
studied [1–12,19]. As a consequence, HF in patients aged ≥85 years remains poorly understood. Findings from the few studies that have been performed in this age group have not been consistent, particularly with regard to both cardiovascular and non-cardiovascular comorbidities [6,8,9,13–18]. For instance, the incidence of hypertension has been reported to be both lower [14,17,18] and higher [6,7,15] and the incidence of ischaemic heart disease has been shown to be similar [17], higher [15] and lower in elderly patients [14,18]. These differences may be due to small sample sizes in previous studies, a limitation because of the highly heterogeneous nature of the elderly HF patient population. Moreover, HF with normal left ventricular ejection fraction (HFNEF) was reported to be more frequent in the elderly. Differences in comorbidity between SHF and HFNEF in those ≥85 years remain largely unknown. The need for in-depth characterization and understanding of HF in elderly populations is important, particularly for those aged ≥85 years, because the number of people with HF in this age group is increasing rapidly as the aged population increases worldwide. In addition, because
0167-5273/$ – see front matter. Crown Copyright © 2012 Published by Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijcard.2012.06.095
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advanced medical technology allows us to offer a wider range of therapies, further information to help us make the correct choice becomes more important. The internet-based Swedish Heart Failure Registry commenced in 2003 [20]. It is an important source of information about the epidemiology and characteristics of HF in elderly patients. In the present study, our main objective is not only to confirm previous epidemiological finding in the ≥ 85 year group but also to extend the study by dividing this group further into two subgroups: 85–90 year and > 90 year, and moreover making comparisons between SHF and HFNEF in this elderly population. 2. Methods 2.1. Swedish Heart Failure Registry The Swedish Heart Failure Registry has been described previously in the introduction [20]. This internet-based registry was created in 2003 and allows participating units to register their HF patients online after diagnosis by a clinician (www.rikssvikt.se). During an initiation visit, staff receive training from a registry coordinator on how to register patients and how to use the registry. More than 70 variables, including demographics, concomitant diseases, diagnostic procedures, hemodynamics, laboratory data, and medication, are recorded at discharge from hospital (within 1 month) or after visits to outpatient clinics. Sixty of these variables in the registry are obligatory and the other 10 are optional. The registry recommends that patients be re-registered after each hospitalization due to HF. All patients are informed that their hospital or primary care centre is participating in the registry and patients who do not wish to participate are assured that all registered data related to them will be deleted. Patients are consecutively entered. The registry and analysis of the database were approved by the regional ethical review board. 2.2. Subgroups and definitions The ≥85 year group was further subdivided into two groups: 85–90 year and >90 year. Additionally a younger population (≤65 years) was included for comparison. Patients aged 66–84 years were not included in this study because of two reasons: 1) to not include the transient age group to show the greatest contrast as possible between the much younger and much elderly and 2) to make the focus of current study on the ≥85 year group. HF was diagnosed individually by physicians from participating registration sites where the current guidelines for the diagnosis and treatment of acute and chronic HF is strongly recommended [21,22]. Cut-off for LVEF is defined as b50% in SHF, and ≥50% for HFNEF. Tachycardia is defined as heart rate >100 beats/min, whereas bradycardia is b60 beats/min. In the registry, the estimated glomerular filtration rate (eGFR) was calculated using the Cockroft–Gaults formula. 2.3. Statistics The results are presented as percentage and mean±standard deviation (SD), or as median and interquartile range (IQR) when values were not distributed normally. In the case of continuous variables, statistical analysis was performed using Student's unpaired t-test or the Mann–Whitney U-test for abnormally distributed variables. For discrete variables, the chi-square test was used. The PASW Statistics 18 (USA) statistical package was used for all the data analyses. pb 0.05 was regarded as statistically significant.
3. Results Up until 31 December 2009, 8,348 younger (≤65 years) and 15,889 elderly (≥85 years) HF patients were registered. In the ≥85 year HF patient group, 11,412 patients were 85–90 years and 4,477 were >90 years. Patients aged 66–84 years were not included in this study. Natriuretic peptide testing was performed in 2,938 patients (35%) in the ≤65 year group, 2,890 (25%) in the 85–90 year group and 723 (16%) in the >90 year group. Among comorbidity, only 5% of the data set was completely filled for both depression and malignancy. The majority of HF patients had been registered by hospital clinicians. Only 2.1% of the ≤65 year group, 4.5% of the 85–90 year group, and 1.2% of the >90 year group were registered by primary care clinicians.
≥85 year group was characterized by more women, lower BMI, higher systolic blood pressure (SBP), lower diastolic blood pressure (DBP), more left bundle brunch block (LBBB), more than twice as many patients with HFNEF, more cardiovascular comorbidities (ischaemic heart disease, hypertension and atrial fibrillation), more non-cardiovascular comorbidities (anaemia, pulmonary disease, stroke and renal insufficiency) except diabetes which decreased with ageing (pb 0.01 for each of these variables). Compared to the 85–90 year group, the >90 year group had a decline in cardiovascular and non-cardiovascular comorbidities except renal insufficiency and anaemia which continued to increase with ageing (Table 1). As shown in Table 1, moderate renal insufficiency in terms of GFR b60 mL/min kept increasing from 10.9% in patients ≤65 years to 89.8% in patients 85–90 years and continued increasing to 97.2% in patients >90 years. An even more dramatic increase was observed in severe renal insufficiency in terms of GFR b30 mL/min from 1.8% in patients ≤65 years to 28.0% in patients 85–90 years and continued increasing to 53.1% in those >90 years. Likewise, the incidence of anaemia increased from 22.4% in patients ≤65 years to 44.3% in patients 85–90 years and furthermore to 47.2% in those >90 years. HFNEF occurred more than twice as often in the 85–90 and >90 year groups compared with the ≤65 year group. The incidences of HFNEF were different depending on how they were calculated. In cases where the sample size was only the number of those with available echocardiography, HFNEF was present in 27.3% and 33.0% of the patients in the 85–90 and >90 year subgroups, respectively, compared with 12.3% in the ≤65 year group. However, in cases where the sample size was the total number of patients including those without available echocardiography, HFNEF was present in 22.2% and 20.4% of the patients in the 85–90 and >90 year subgroups, respectively. Moreover, both B-type natriuretic peptide (BNP) and N-terminal pro B-type natriuretic peptide (NT-pro BNP) levels were twice as high for the 85–90 and >90 year subgroups compared to the ≤65 year group (Fig. 1). 3.2. SHF and HFNEF profile differences among the age groups As shown in Table 2, the SHF and HFNEF patient profiles varied not only between the ≤65 and ≥85 year groups, but also between the 85–90 and >90 year subgroups. In general, patients with HFNEF were more likely to be women and had higher SBP, narrower QRS width, lower P-creatinine (Cr) levels, lower NT-proBNP levels (Fig. 1), less ischaemic heart disease and more hypertension compared with those with SHF (p b 0.01 for each of these variables). However, there were several differences between SHF and HFNEF. In the ≥85 year group, HFNEF patients had significantly higher frequency of atrial fibrillation compared to those with SHF; this was not the case for HFNEF patients in the ≤65 year group (Fig. 2). In the ≥90 year group, ischaemic heart diseases continued to increase in HFNEF but decreased in SHF. However, diabetes incidence and BMI decreased with age regardless of SHF or HFNEF. 3.3. Hemodynamic disorders As compared to the ≤65 year group, the incidences of tachycardia did not increase until >90 years. By contrast the incidence of bradycardia decreased from ≥85 years and continued decreasing despite >90 years. Similarly, the incidence of hypertension with SBP >140 mm Hg was higher and hypotension was lower in the 85–90 and >90 year subgroups compared to the ≤65 year group (data not shown). 3.4. Distinct treatment profiles among the different age groups
3.1. Differences in demographic and clinical characteristics among the age groups As shown in Table 1, both the 85–90 year group and the >90 year group had characteristics that differed from those of the younger population ≤65 years. In general, compared with the ≤65 year group, the
At the time of discharge from hospital, prescriptions of beta receptor blockers (BB), ACE inhibitors (ACEi), angiotensin receptor blockers (ARB) and aldosterone antagonists were less common whereas diuretics were more common for ≥85 year patients than for ≤65 year group. Even less BB, ACEi, ARB and aldosterone antagonists were
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Table 1 Demographic and clinical characteristics in older and younger HF patients in the total study population. Variables Patient characteristics
Clinical examinations
Laboratory examinations
Cardiovascular comorbidity
Non-cardiovascular comorbidity
Treatment
N Age (mean ± SD) Male (%) BMI (mean ± SD) SBP (mm Hg) (mean ± SD) DBP (mm Hg) (mean ± SD) Heart rate (beats/min) (mean ± SD) ECGa sinus rhythm (%) Atrial fibrillation (%) LBBB (%) QRS (ms) (mean ± SD) PM rhythm (%)b LVEFc ≥50 (%)d LVEF 40–49 (%) LVEF 30–39 (%) LVEF b30 (%) LVEF unknowne Hb (g/L) (mean ± SD) BNP (ng/L) (median (IQR)) NT-proBNP (ng/L) (median (IQR)) P-creatinine (μmol/L) (mean ± SD) eGFR (mL/min)f (mean ± SD) Ischaemic heart diseases (%) Hypertension (%) Atrial fibrillation (%)g Diabetes mellitus (%) Pulmonary diseases (%) Stroke (%) eGFR b60 (mL/min)f (%) eGFR b30 (mL/min)f (%) Anaemia (%)j ACE inhibitors (ACEi) (%) Beta blockers (BB) (%) Angiotensin receptor blockers (%) Aldosterone antagonists (%) ACEi + BB (%) RAAS blockade (%) Diuretics (%)
≤65 years
85–90 years
>90 years
8,348 56 ± 8 76.4 28.7 ± 6.3 122 ± 21 75 ± 13 74 ± 15 70.2 22.7 13.8 109.3 ± 26.9 7.0 11.8 17.5 25.4 40.8 4.5 138.7 ± 17.2 254 (91–727)
11,412 87 ± 2⁎⁎ 53.3⁎⁎
616 (247–1420)⁎⁎
4,477 94 ± 3##,¶¶ 41.1##, ¶¶ 23.2 ± 4.1##,¶¶ 130 ± 23##,¶¶ 71 ± 13 77 ± 17##,¶¶ 40.5## 48.8##,¶ 14.0¶¶ 110.9 ± 29.2##,¶¶ 10.7## 20.4##,¶ 14.3##,¶¶ 15.3##,¶¶ 12.0##,¶¶ 38.0##,¶¶ 124.7 ± 15.8##,¶ 863 (340–1643)##
1440 (520–3655)
3990 (1846–9000)⁎⁎
5493 (2375–11,899)##,¶¶
97.0 ± 56.5 102.6 ± 49.8 34.8 37.7 29.7 24.4 13.3 7.9 10.9 1.8 22.4 74.4 91.4 23.5 36.1 68.9 92.3 69.9
125.5 ± 64.1⁎⁎ 39.9 ± 16.6⁎⁎ 56.1⁎⁎ 49.5⁎⁎ 57.3⁎⁎ 20.0⁎⁎ 19.1⁎⁎ 15.7⁎⁎ 89.8⁎⁎ 28.0⁎⁎ 44.3⁎⁎ 56.3⁎⁎ 80.3⁎⁎
128.0 ± 15.9##,¶ 30.9 ± 13.5##,¶¶ 53.5##,¶¶ 45.6##,¶¶ 56.1##,¶ 14.6##,¶¶ 15.5##,¶¶ 11.3##,¶¶ 97.2##,¶¶ 53.1##,¶¶ 47.2##,¶¶ 43.5##,¶¶ 70.0##,¶¶ 11.0##,¶¶ 26.7##,¶ 32.0##,¶¶ 53.2##,¶¶ 91.1##,¶¶
25.1 ± 4.5⁎⁎ 129 ± 22⁎⁎ 71 ± 12⁎⁎ 75 ± 16 41.5⁎⁎ 47.2⁎⁎ 16.2⁎⁎
112.6 ± 30.3⁎⁎ 11.3⁎⁎ 22.2⁎⁎ 17.6 21.4⁎⁎ 19.9⁎⁎ 18.9⁎⁎ 127.0 ± 16.3⁎⁎
19.3 28.8⁎⁎ 46.0⁎⁎ 73.1⁎⁎ 89.1⁎⁎
a
According to ECG recording at the time of registration. Pacemaker rhythm. c Left ventricular ejection fraction. d % was calculated on the basis of total sample size including those with unknown LVEF. e % of unknown echocardiography examinations based on total number of registered patients. f Cockroft–Gaults formula. g Atrial fibrillation in medical history recordings. j Anaemia according to WHO b130 g/L (male) and b120 g/L (female). ⁎ p b 0.05 between ≤65 and 85–90 years groups. ⁎⁎ p b 0.01 between ≤65 and 85–90 years groups. # p b 0.05 between ≤65 and >90 years groups. ## p b 0.01 between ≤65 and >90 years groups. ¶ p b 0.05 between 85–90 and >90 years groups. ¶¶ pb 0.01 between 85–90 and >90 years groups. b
prescribed and even more diuretics were prescribed in the >90 year group compared with the 85–90 year group (Table 1). A similar pattern of pharmacological treatment was found not only in SHF but also in HFNEF except that in HFNEF prescription of aldosterone antagonist continued increasing despite higher age (Table 2). 4. Discussion
Fig. 1. Comparison of the median NT-proBNP (ng/L) levels between SHF and HFNEF patients. ⁎⁎pb 0.01 between SHF and HFNEF patients in the same age group.
Our study demonstrated an increase in most of the cardiovascular and non-cardiovascular comorbidities in the 85–90 year group compared with the ≤65 year group but with a decline in the > 90 year group of the Swedish patients with HF. To date, most studies of HF have been conducted on populations with an average age of around 65–75 years, or on sample populations selected for interventional clinical trials. HF patients ≥85 years have rarely been studied. This is a huge group that is estimated to constitute
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Table 2 SHF and HFNEF profiles in elderly vs. “younger HF patients with available echocardiography. ≤65 years
Variables
HFNEF Patient characteristics
N Age Male (%) BMI SBP (mm Hg) DBP (mm Hg) Heart rate Atrial fibrillationa LBBB (%) QRS (ms) Hb (g/L) BNP (ng/L) [median (IQR)]
981 57 ± 8 63.4 30.1 ± 7.6 Clinical examinations 128 ± 22 76 ± 13 72 ± 15 21.3 5.9 98.1 ± 18.1 Laboratory examinations 139.0 ± 20.0 161 (37–371) NT-proBNP (ng/L) [median 723 (IQR)] (212–1746) P-Cr (μmol/L) 94.5 ± 54.9 b eGFR (mL/min) 102.3 ± 50.4 Cardiovascular comorbidity Ischaemic heart disease 24.8 (%) Hypertension 48.8 Atrial fibrillationc 31.1 Noncardiovascular Diabetes mellitus 26.4 comorbidity (%) Pulmonary diseases 15.1 Stroke 8.0 Anaemiad 24.9 b eGFR b60 (mL/min) 8.7 b eGFR b30 (mL/min) 1.3 e Treatment (%) ACEi 60.4 BBf 81.6 ARBg 26.3 Aldosterone antagonists 27.0 Diuretics 64.8
85–90 years
>90 years
SHF
HFNEF
SHF
HFNEF
SHF
6,989 56 ± 8 78.4## 28.5 ± 6.0## 120 ± 21## 75 ± 13 74 ± 15# 22.5 18.4## 111.0 ± 27.6## 139 ± 16.9 260 (92–747)# 1628 (587–3964)## 97.2 ± 55.7## 103.8 ± 45.9 36.3## 35.9## 29.2 23.9## 13.1# 7.9 22.2## 11.2# 1.9 78.3## 93.4## 23.1 38.2## 70.2##
2,528 87 ± 2⁎⁎ 39.3⁎⁎ 25.9 ± 4.9⁎⁎ 133 ± 23⁎⁎ 72 ± 13⁎⁎ 75 ± 16⁎⁎ 58.5⁎⁎ 11.8⁎⁎
6,726 87 ± 2⁎⁎,## 61.3⁎⁎,## 24.8 ± 4.3⁎⁎,## 126 ± 22⁎⁎,## 71 ± 12⁎⁎,## 74 ± 15⁎⁎ 51.0⁎⁎,## 26.6⁎⁎,## 118.0 ± 30.0⁎⁎,## 128.1 ± 16.4⁎⁎,##
914 94 ± 3¶¶ 28.6¶¶ 23.4 ± 4.2¶¶ 132 ± 24¶¶ 71 ± 13¶¶ 77 ± 16¶¶ 58.2¶¶ 11.0¶¶ 104.2 ± 31.3¶¶ 123.9 ± 16.0¶¶ 578 (306–1625) 4512 (1902–10,374)¶¶ 120.2 ± 54.4¶¶ 31.3 ± 12.6¶¶ 47.6¶¶ 51.5¶¶ 59.7¶¶ 15.7¶¶ 15.4¶¶ 11.1 46.8 97.0¶¶ 52.2¶¶ 39.4¶¶ 71.1¶¶ 11.2¶¶ 31.7 92.2¶¶
1,859 93 ± 2¶¶,## 52.0¶¶,## 23.4 ± 3.7¶¶ 127 ± 22## 70 ± 12# 75 ± 15¶¶ 51.9## 24.7## 117.5 ± 29.6¶¶,## 125.4 ± 15.6¶¶,# 1110 (575–1960)¶ 7341 (34,555–15,579)¶¶,## 136.3 ± 69.0¶¶,## 30.4 ± 12.8¶¶ 62.2¶¶,## 42.2¶¶,## 54.7¶¶,## 15.2¶¶ 16.3 14.3 48.0¶¶ 97.8¶¶ 53.9¶¶ 51.7¶¶,## 77.4¶¶,## 12.5¶¶ 27.4¶¶,# 91.6¶
102.7 ± 25.8⁎⁎ 125.1 ± 15.6⁎⁎ 382 (183–1147)⁎⁎ 2794 (1367–6035)⁎⁎ 119.0 ± 60.3⁎⁎ 40.1 ± 16.9⁎⁎ 43.9⁎⁎ 55.9⁎⁎ 63.7⁎⁎ 18.8⁎⁎ 23.2⁎⁎ 13.6 46.1⁎⁎ 88.9⁎⁎ 26.0⁎⁎ 50.3⁎⁎ 77.3⁎⁎ 19.2⁎⁎ 28.6 90.5⁎⁎
733 (335–1619)⁎⁎,## 4900 (2258–10,900)⁎⁎,## 128.2 ± 62.0⁎⁎,## 39.6 ± 16.3⁎⁎,## 63.5⁎⁎,## 46.7⁎⁎,## 55.2⁎⁎,## 20.8⁎⁎,# 17.5⁎⁎,## 12.5 44.1⁎⁎ 90.5⁎⁎,# 28.8⁎⁎,## 61.2⁎⁎,## 84.3⁎⁎,## 19.9⁎⁎ 30.8⁎⁎,# 89.7⁎⁎
a
Atrial fibrillation on ECG at the time of registration. Cockroft–Gaults formula. c Atrial fibrillation in medical history. d Anaemia according to WHO b130 g/L (male) and b120 g/L (female). e ACE inhibitors (ACEi). f Beta receptor blockers (BB). g Angiotensin receptor blockers (ARB). ⁎ p b 0.05 between ≤65 and 85–90 year groups in the same HF category. ⁎⁎ p b 0.01 between ≤65 and 85–90 year groups in the same HF category. # p b 0.05 between HFNEF and SHF in the same age group. ## p b 0.01 between HFNEF and SHF in the same age group. ¶ p b 0.05 between 85–90 and >90 year groups in the same HF category. ¶¶ p b 0.01 between 85–90 and >90 year groups in the same HF category. b
one-fourth of the HF population aged >65 years [9]. Although there have been some studies of this elderly population, the sample sizes are usually quite small. One of these studies is the EuroHeart Failure
Fig. 2. Comparison between younger and older HF patients in terms of frequency of atrial fibrillation (%). ⁎⁎pb 0.01 between ≤65 years and 85–90 years or >90 years. ##pb 0.01 between 85–90 years and >90 years.
Survey II (EHFSII) [6], in which 3,577 patients were included. However, only 741 participants were ≥80 years. Another was the Italian Survey on Acute Heart Failure in which 2,807 patients were included and only 28% of enrolees were 84± 4 years [7]. Recently, Mogensen et al. reported an elderly HF cohort in which 825 patients ≥85 years were included [18]. Therefore, the strength of the present study is its large sample size of HF patients ≥85 years (n= 15,889) which is almost 20 times larger than in previous studies. Because of the large sample size of our study, we were able to confirm and extend previously observed clinical differences between elderly and younger patients [5–12]. Both the 85–90 and >90 year subgroups had characteristics that not only distinguished them from the ≤65 year group but also were heterogeneous between the 85–90 and >90 year subgroups. In general, the 85–90 year group had more than twice as many patients with HFNEF, more cardiovascular diseases and moreover more associated non-cardiovascular comorbidities. Comorbidities did not increase parallel with age. In fact, compared with the 85–90 year group, the >90 year group had a decline in most comorbidities, regardless of whether they were cardiovascular or non-cardiovascular. However, there were several exceptions, in those aged ≥85 years, diabetes decreased rather than increased with age. This was in line with the data from previous reports [6,14,15,17,18] in which the frequency of
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diabetes was shown to be lower in elderly patients. One possible explanation is that HF with a comorbidity such as diabetes is associated with higher mortality, which decreases the likelihood of survival until the age of 85 years and beyond. Another explanation is that diabetes is under-diagnosed in elderly adults with HF. By contrast, renal insufficiency and anaemia continued to increase with age although many other comorbidities started to decline in the >90 year group. For instance, patients ≥85 years had almost 9-fold increased incidence of moderate renal insufficiency and at least 15-fold increased incidence of severe renal insufficiency, as compared with those ≤65 years. Among those ≥85 years, patients in the >90 year group had almost twice as much severe renal dysfunction as those in the 85–90 year group. Likewise, incidence of anaemia has almost doubled from patients ≤65 years to those ≥85 years. Since previous findings regarding age-related comorbidity have not been consistent [6,8,9,13–18] due to either limited sample size or different databases, therefore our results bring clarification to this field. In our study, echocardiography was done in 81% and 62% of the 85–90 and >90 years HF patients respectively. These rates of echocardiography were similar to those seen in EHFSII [6]. Nevertheless, echocardiography has remained a less-common diagnostic option in >90 year patients. In line with previous results, HFNEF was more frequently seen in the ≥85 year population. In EHFSII [6], LVEF >45% was present in 39% of patients >80 years, whereas in our study, LVEF ≥50% was present in 22.2% and 20.4% of the patients in the 85–90 and >90 year subgroups, respectively, based on total sample size including those with unknown LVEF, but in 27.3% and 33.0% of the patients in the 85–90 and >90 year subgroups respectively, based on the sample size with available echocardiography. Our results differed from EHFSII because the cut off values of LVEF were set differently for HFNEF (LVEF ≥50% in our study compared to ≥45% in EHFSII), which made comparisons difficult. Measurement of natriuretic peptides is often necessary to confirm HFNEF diagnosis together with echocardiography. In our study, natriuretic peptide testing was performed in 35%, 25% and 16% of patients in the ≤65, 85–90 and >90 year groups respectively. This might make HFNEF diagnosis in the elderly somewhat uncertain. The statistical strength in each of the age categories was sufficient for the natriuretic peptide testing. HFNEF occurred more than twice as often in the 85–90 and >90 year groups compared with the ≤65 year group regardless of whether natriuretic peptide testing was applied. Moreover, similar demographic and clinical variable patterns were found in the younger and elderly HF populations regardless of natriuretic peptide testing. This may be due to the fact that the majority of HF patients in registry were registered while they were under the care of hospital clinicians. It is interesting to note that both BNP and NT-proBNP levels were twice as high in the 85–90 and >90 year groups compared with the ≤65 year group. When NT-pro BNP levels were compared between HFNEF and SHF patients, NT-proBNP levels in patients with HFNEF were much lower than those in SHF patients within the same age category. In line with an earlier report [6], and in our report compared with SHF patients, patients with HFNEF were more likely to be women and had higher SBP, narrower QRS width, lower NT-proBNP levels, less ischaemic heart disease and more hypertension. In ≥ 85 year HFNEF patients, the frequency of occurrence of atrial fibrillation was as high as 64%, compared with 55% in patients with SHF. Moreover, atrial fibrillation increased in prevalence with increased age and was a major contributor to morbidity in this population due to associated strokes, HF and quality-of-life impairment. In our study, at the time of discharge from hospital, medications such as BB, ACEi, ARB, aldosterone antagonists were less commonly prescribed for ≥85 year patients than for to ≤65 year patients. Even fewer prescriptions of the above medications were observed in >90 years compared with 85–90 years. Nevertheless, both subgroups of elderly HF patients had significantly more prescriptions for BB compared with the patients in EHFSII [6]. Conversely, elderly HF patients
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had significantly fewer prescriptions for aldosterone antagonists compared with the patients in EHFSII [6]. The difference in treatment modalities between younger and older HF patients might be due to the lack of documented efficacy, concern for safety, comorbidity and polypharmacy in elderly patients. 4.1. Limitations The present study was limited by the low number of patients who were registered by primary care clinicians. Moreover, not all hospitals and outpatient clinics in Sweden have registered their patients in the registry. Some variables are underreported. For example, only 5% of the data set was completely filled for both depression and malignancy. This might be explained by the fact that some variables such as malignancy and depression were first introduced in registry in February 2010 and it then took time to implement the change. In addition, diagnosis was reported individually by physicians from participating registration sites. With the consideration that natriuretic peptide testing was not widely used, a diagnosis of HF in the absence of natriuretic peptide testing and/or echocardiography is questionable in particular in the oldest population where comorbidity (e.g. pulmonary disease) is easily wrongly diagnosed as HF because of similar symptoms. 5. Conclusions Our study of a large population from a Swedish Heart Failure Register database demonstrated that HF patients ≥85 years had increased cardiovascular and non-cardiovascular comorbidities but that these comorbidities declined in the >90 year group. Acknowledgements This study was supported by the Swedish Heart-Lung Foundation. The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology. References [1] Fu M. Heart failure therapy in the elderly: where are we? What are we doing? Int J Cardiol 2008;125:147–8. [2] Jensen J, Ma LP, Bjurman C, Hammarsten O, Fu ML. Prognostic values of NT-proBNP/BNP ratio in comparison with NT-proBNP or BNP alone in elderly patients with chronic heart failure in a 2-year follow up. Int J Cardiol 2012;155: 1–53. [3] Jensen J, Ma LP, Fu ML, Svaninger D, Lundberg PA, Hammarsten O. Inflammation increases NT-proBNP and the NT-proBNP/BNP ratio. Clin Res Cardiol 2010;99: 445–52. [4] Jensen J, Hedin L, Widell C, Agnhom P, Andersson B, Fu M. Characteristics of heart failure in the elderly—a hospital cohort registry-based study. Int J Cardiol 2008;125:191–6. [5] Komajda M, Follath F, Swedberg K, et al. The EuroHeart Failure Survey programme — a survey on the quality of care among patients with heart failure in Europe. Part 2: treatment. Eur Heart J 2003;24:464–74. [6] Komajda M, Hanon O, Hochadel M, et al. Contemporary management of octogenarians hospitalized for heart failure in Europe: Euro Heart Failure Survey II. Eur Heart J 2009;30:478–86. [7] Miani D, Fresco C, Lucci D, et al. Clinical characteristics, management, and prognosis of octogenarians with acute heart failure admitted to cardiology wards: results from the Italian Survey on Acute Heart Failure. Am Heart J 2009;158:126–32. [8] Mahjoub H, Rusinaru D, Soulière V, Durier C, Peltier M, Tribouilloy C. Long-term survival in patients older than 80 years hospitalised for heart failure. A 5-year prospective study. Eur J Heart Fail 2008;10:78–84. [9] Havranek EP, Masoudi FA, Westfall KA, Wolfe P, Ordin DL, Krumholz HM. Spectrum of heart failure in older patients: results from the National Heart Failure project. Am Heart J 2002;143:412–7. [10] Pulignano G, Del Sindaco D, Tavazzi L, et al. Clinical features and outcomes of elderly outpatients with heart failure followed up in hospital cardiology units: data from a large nationwide cardiology database (IN-CHF Registry). Am Heart J 2002;143:45–55. [11] Manzano L, Babalis D, Roughton M, et al. Predictors of clinical outcomes in elderly patients with heart failure. Eur J Heart Fail 2011;13:528–36. [12] Alehagen U, Dahlström U, Lindahl TL. Cystatin C and NT-proBNP, a powerful combination of biomarkers for predicting cardiovascular mortality in elderly patients
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[18] Mogensen UM, Ersbøll M, Andersen M, et al. Clinical characteristics and major comorbidities in heart failure patients more than 85 years of age compared with younger age groups. Eur J Heart Fail 2011;13:1216–23. [19] Fu M. Beta-blocker therapy in heart failure in the elderly. Int J Cardiol 2008;125: 149–53. [20] Jonsson A, Edner M, Alehagen U, Dahlström U. Heart failure registry: a valuable tool for improving the management of patients with heart failure. Eur J Heart Fail 2010;12:25–31. [21] Dickstein K, Cohen-Solal A, Filippatos G, et al. ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2008. Eur Heart J 2008;29: 2388–442. [22] Paulus WJ, Tschöpe C, Sanderson JE, et al. How to diagnose diastolic heart failure: a consensus statement on the diagnosis of heart failure with normal left ventricular ejection fraction by the Heart Failure and Echocardiography Associations of the European Society of Cardiology. Eur Heart J 2007;28:2539–50.