Prevalence, Predictors and Prognosis of Patients With Heart Failure Requiring Nursing Care

– Report From the CHART-2 Study –

Abstract

Background: Although the need for nursing care (NC) in heart failure (HF) patients is recognized, detailed information on the current status in Japan is lacking.

Methods and Results: In the CHART-2 Study, we obtained information on daily life, physical ability, nutrition and mental status for 4,174 patients (mean age, 67.1±10.8 years; 73.3% male) out of 10,219 patients. We examined the prevalence, baseline characteristics and clinical outcomes of stage B and C/D HF patients requiring NC. The prevalence of HF requiring NC was significantly higher in stage C/D (38.6%) than in stage B (30.4%; P<0.001). Among the reasons for requiring NC, physical dysfunction was most prevalent in both stage B (20.6%) and C/D (29.0%). Compared with the non-NC group, the NC group was characterized by higher age, higher prevalence of female gender and cerebrovascular disease, and increased plasma brain natriuretic peptide regardless of HF stage. During a median follow-up of 12.7 months after the survey, the NC group had a significantly higher mortality compared with the non-NC group (9.6% vs. 3.6%, P<0.001). On multivariate logistic analysis depressive mental status (hazard ratio [HR], 3.61; P<0.001) and dementia (HR, 2.70; P<0.001) were significantly associated with NC need.

Conclusions: In HF patients, NC need is considerably high and is associated with increased mortality regardless of HF stage in Japan.

There are approximately 23 million patients with heart failure (HF) worldwide, and 2 million patients with HF are newly diagnosed every year.¹ Furthermore, given that the speed at which society is aging has been increasing since the 1970 s in the developed countries, especially in Japan, it is expected that the number of HF patients will be increasing much faster.^2,3 In Japan, the number of HF patients in stage B (without prior history of HF but at high risk for HF development) and stage C/D (with overt HF) has been rapidly increasing due to westernization of dietary pattern, reduced physical ability, increased prevalence of obesity, diabetes and hypertension, and rapid society aging.^4,5

Although the management of stage B and C/D HF has improved over the past decades, many patients with stage B and C/D HF are currently aging with progressive cardiac dysfunction and increased comorbidities, likely resulting in greater disability and need for nursing care (NC).⁶ Gure et al reported that HF patients had a significantly greater burden of illness due to geriatric conditions, functional limitations, in-home caregiving needs, and nursing home admission.⁷ Furthermore, HF patients who needed NC were characterized by urinary incontinence, injury by fall, and dementia.⁷ Thus, it is important to develop medical and social systems that can help stage B and C/D HF patients stay healthier. Detailed information on the prevalence, baseline characteristics and clinical outcomes of HF patients requiring NC in Japan, however, is lacking. Thus, the aim of the present study was to address these important issues in HF patients registered in our HF registry, the Chronic Heart Failure Analysis and Registry in the Tohoku District Study-2 (CHART-2; NCT00418041, n=10,219).^5,8–10

Methods

Subjects and Inclusion Criteria

Details of the design, purpose and basic characteristics of the CHART-2 Study have been described previously.^5,8–10 Briefly, eligible patients were aged ≥20 years with significant coronary artery disease or in stage B, C or D defined by the American College of Cardiology/American Heart Association guidelines for the diagnosis and management of HF in adults.¹¹ Patients were classified as having HF by experienced cardiologists using the criteria of the Framingham Heart Study.¹² The present study was approved by the local ethics committee in each participating hospital. Eligible patients were consecutively recruited after written informed consent was obtained. The CHART-2 Study was started in October 2006 and the entry period was successfully closed in March 2010 with 10,219 patients registered from the 24 participating hospitals.⁵ All data and events will be surveyed at least once a year until March 2018.⁵

We conducted a questionnaire survey, regarding daily life, physical ability, nutritional status, and mental status for the patients in the CHART-2 study in August 2011. The questionnaire consisted of 25 questions (Table 1). Questions (Q) 1–5 and 16–20 were related to daily life, Q6–10 physical ability, Q11–Q15 to nutrition and oral condition, and Q21–Q25 to mental status. These questions were based on the questionnaire of NC prevention published by the Japanese Ministry of Health, Labour and Welfare (JMHLW).¹³ In Q1–8, 16, 20, if applicable, patients answered ‘No’. In Q9–11, 13–15, 17, 18 and Q20–25, if applicable, patients answered ‘Yes’. Need for NC, according to the JMHLW definition, was defined as follows: (1) ≥10 questions from Q1 to Q20; and (2) physical dysfunction (≥3 questions in the physical ability section; Q6–10); and (3) poor nutrition (both Q11 and body mass index [BMI] <18.5); or (4) poor oral condition (≥2 questions in the oral condition section; Q13–15).¹³ According to the questionnaire results, the patients were divided into 2 groups as follows: those who needed NC (NC group) and those who did not (non-NC group). Furthermore, we considered the patients for whom at least 1 question was applicable among Q18–20 as high risk for dementia, and those for whom at least 2 questions were applicable among Q21–25 as high risk for depression according to the JMHLW definition.¹³

Table 1. NC Questionnaire

Daily life-1

Q1 Do you usually travel by bus or train by yourself?

Q2 Do you go out and buy daily necessities by yourself?

Q3 Do you manage your own deposits and savings at the bank?

Q4 Do you often go out to visit your friends?

Q5 Do you consult with your family or friends about their problems?

Physical ability

Q6 Are you able to go upstairs without holding rail or wall?

Q7 Are you able to stand up from the chair without any aids?

Q8 Are you able to keep walking for approximately 15 min?

Q9 Have you fallen during the past year?

Q10 Do you worry about falling down?

Nutrition and oral condition

Q11 Have you lost more than 2–3 kg in the past 6 months?

Q12 Please fill out: your height (　　　cm) and your weight (　　　kg)

Q13 Compared with 6 months ago, do you have difficulty in eating hard food?

Q14 Do you choke when you drink tea or soup?

Q15 Do you often feel your mouth dry?

Daily life-2

Q16 Do you go out more than once in a week?

Q17 Compared with last year, do you go out less often?

Q18 Do people around you say you repeat same thing and have become forgetful?

Q19 Do you make phone calls by yourself?

Q20 Do you find yourself not knowing today’s date?

Mental status

Q21 I don’t feel any fulfillment in my life during the last 2 week.

Q22 I cannot enjoy things I used to enjoy during the last 2 weeks.

Q23 During the last 2 weeks, I am not willing to do what I could do easily before.

Q24 During the last 2 weeks, I do not feel I am useful to anyone.

Q25 During the last 2 weeks, I feel I am exhausted without any reason.

NC, nursing care.

Figure 1 shows the study flow. Among 10,219 patients registered in the CHART-2 study, we sent the questionnaire to 8,846 patients who were alive in August 2011. At the end of 2011, we received a reply from 5,818 patients (65.8%). Among the 5,818 patients, we finally included the 4,174 patients who were eligible for the follow-up survey by the end of May 2013.

Figure 1.

Study flow diagram.

Follow-up Survey and Study Outcome

We conducted the follow-up survey for survival from January to May in 2013, and the median follow-up period was 12.7 months after the questionnaire. The outcome of this study was a composite of all-cause death, admission for HF, acute myocardial infarction (AMI) and stroke.

Statistical Analysis

Statistical analysis was done for both non-HF (stage B) and HF (stage C/D) patients. Comparison of data between 2 groups was done using chi-squared test and Student’s t-test. Continuous data are described as mean±SD. Kaplan-Meier curves were plotted to evaluate the association between NC and composite outcome. We also constructed the following 3 Cox proportional hazard regression models: (1) unadjusted; (2) adjusted for age and sex; and (3) fully adjusted including medical treatment. In model (3) we included the following covariates that can potentially influence outcome: age, sex, New York Heart Association class, history of malignant tumor, BMI, systolic blood pressure, heart rate, serum sodium, serum albumin, estimated glomerular filtration rate (eGFR), blood urea nitrogen (BUN), comorbidities (anemia defined as hemoglobin <12 g/dl in women and <13 g/dl in men, diabetes mellitus, hyperuricemia, atrial fibrillation and cerebrovascular disease), left ventricular ejection fraction (LVEF), ischemic etiology of HF, and treatment (β-blocker, renin-angiotensin system inhibitors and aldosterone antagonists). We also performed subgroup analyses based on age (<median age or ≥median age), sex, cause of HF (ischemic HF vs. non-ischemic HF) and history of cerebrovascular disease. Finally, we also constructed a logistic regression model to elucidate the predictors for NC need. We included several covariates, including age, sex, HF stage, history of malignant tumor, BMI, systolic blood pressure, heart rate, eGFR, serum albumin, comorbidities (anemia, diabetes mellitus, hyperuricemia, atrial fibrillation, and cerebrovascular disease), LVEF, ischemic etiology, and risk of dementia and that of depression.

Statistical analysis was done using SPSS Statistics 19.0 (SPSS, Chicago, IL, USA) and statistical significance was defined as 2-sided P<0.05.

Results

Prevalence of NC and Baseline Patient Characteristics

Mean age was 67.1±10.9 years and male patients accounted for 73.3% of the subjects. Female patients were older than male patients (68.3±11.5 vs. 66.6±10.6 years, P<0.001). Coronary artery disease was noted in 56.5% and mean LVEF in 62.0±13.6%. The prevalence of cerebrovascular disease was 14.7%. The prevalence of NC was significantly higher in stage C/D (38.6%) than in stage B (30.4%; P<0.001; Table 2; Figure 2B).

Table 2. Baseline Subject Characteristics

	All patients (n=4,174)	Stage B (n=2,380)		P-value	Stage C/D (n=1,794)		P-value
		NC (n=723)	Non-NC (n=1,657)		NC (n=692)	Non-NC (n=1,102)
Age (years)	67.1±10.9	71.3 ±10.2	65.4±10.6	<0.001	70.8±9.7	64.4±10.9	<0.001
Male	73.3	62.1	78.6	<0.001	63.0	79.1	<0.001
History of admission for HF	23.1	0.0	0.0	–	58.5	50.7	0.001
Comorbidity
Hypertension	73.4	76.8	73.5	0.09	72.4	71.7	0.74
Diabetes	22.1	24.1	19.3	0.009	25.1	23.1	0.33
Hyperuricemia	32.9	24.6	28.2	0.07	40.6	40.6	0.99
AF	22.4	16.8	16.3	0.94	33.8	28.0	0.02
Coronary artery disease	56.5	60.3	61.8	0.49	48.0	51.3	0.17
Cerebrovascular disease	14.7	19.6	11.5	<0.001	20.7	12.5	<0.001
Clinical status
NYHA class 3 and 4	2.8	0.1	0.3	<0.001	11.1	3.4	<0.001
BMI (kg/m2)	24.2±3.4	24.0±3.4	24.4±3.2	0.008	23.7±3.8	24.2±3.4	0.003
SBP (mmHg)	128±18	130±18	129±17	0.86	126±19	126±17	0.91
DBP (mmHg)	74±11	74±11	75±11	<0.001	71±12	74±11	<0.001
Heart rate (beats/min)	70±13	70±12	69±13	0.16	72±15	71±14	0.12
Measurement
LVEF (%)	62.0±13.6	66.1±11.0	65.6±11.2	0.34	57.0±15.0	57.2±14.9	0.85
Hemoglobin (g/dl)	13.7±1.8	13.3±1.6	13.9±1.6	<0.001	13.0±1.8	13.8±2.1	<0.001
BUN (mg/dl)	17.1±6.6	16.9±6.2	15.9±5.1	<0.001	19.8±8.9	17.3±6.4	<0.001
GFR (ml·min–1·1.73 m–2)	66.3±21.6	65.6±21.1	69.1±17.4	<0.001	59.9±19.9	66.5±27.1	0.001
Serum sodium (mEq/L)	141±2.5	141±2.5	141±2.2	0.23	141±2.6	141±2.6	0.86
Serum potassium (mEq/L)	4.3±0.4	4.4±0.4	4.3±0.4	0.20	4.1±0.4	4.4±0.4	0.31
BNP (pg/ml)	56†	55†	36†	<0.001	108†	72†	<0.001
Medications
RAS inhibitor	63.0	54.1	57.2	0.16	69.7	73.2	0.10
β-blocker	42.5	34.0	34.8	0.73	52.5	53.6	0.63
Calcium channel blocker	46.6	53.8	51.2	0.25	42.5	37.4	0.03
Diuretics	29.7	19.8	11.8	<0.001	58.4	44.9	<0.001
Aldosterone inhibitor	12.2	6.5	3.2	<0.001	26.7	20.2	0.001
Statin	44.8	47.9	42.9	0.02	39.5	44.8	0.03
Digitalis	14.2	8.4	7.9	0.66	23.3	21.9	0.49

Data given as mean±SD, % or ^†median.

AF, atrial fibrillation; BNP, brain natriuretic peptide; BUN, blood urea nitrogen; DBP, diastolic blood presure; GFR, glomerular filtration rate; HF, heart failure; LVEF, left ventricular ejection fraction; NYHA, New York Heart Association; RAS, renin-angiotensin system; SBP, systolic blood pressure. Other abbreviation as in Table 1.

Figure 2.

(A) Questionnaire results: stage B vs. stage C/D. Q1–8, 16, 20 are answered ‘No’. Q9–11, 13–15, 17, 18, 20–25 are answered ‘Yes’. (B) Prevalence of and reasons for nursing care (NC) need in stage B vs. stage C/D. Q11, Q12: ‘Yes’ and body mass index <18.5, respectively. ^*P<0.05.

More than 30% of the patients in stage C/D did not go out by themselves using bus or train (Q1), did not visit their friend’s house (Q4), could not go upstairs without holding onto the railing (Q6), and had serious concerns and/or fears for falling (Q10; Figure 2A). Furthermore, approximately one-quarter of the patients in both stage B and C/D had an experience of falling (Q9).

Among the reasons for requiring NC, physical dysfunction (Q6–10) was the most prevalent in both stage B and C/D (Figure 2B). Female patients had a higher prevalence of impaired physical activity (female 38.3% vs. male 19.1%, P<0.001), and impaired oral condition (female 20.6% vs. male 15.9%, P<0.001). The baseline characteristics of the NC patients are listed in Table 2. In both stage B and C/D, the patients who needed NC were characterized by older age, higher prevalence of female gender and history of cerebrovascular disease, lower BMI and hemoglobin, and higher BUN and B-type natriuretic peptide. In both stage B and C/D, the patients who needed NC were more frequently treated with diuretics.

Impact of NC on Composite Outcome

During the median follow-up period of 12.7 months after the questionnaire, the composite outcome occurred in 234 patients (5.6%). In stage B patients, 90 composite outcomes occurred, including all-cause death in 38 (42.2%), AMI in 7 (7.8%), admission for HF in 25 (27.8%), and stroke in 20 (22.2%). In stage C/D patients, 144 composite outcomes occurred, including all-cause death in 68 (47.2%), AMI in 5 (3.4%), admission for HF in 55 (38.2%), and stroke in 17 (11.8%).

Kaplan-Meier curves showed that the NC group had significantly higher occurrence of the composite outcome in both stage B and C/D (Figure 3). Table 3 lists the results of multivariate Cox proportional hazard regression analysis for composite outcome. In the unadjusted model (1), as compared with the non-NC group (reference), the NC group had more than 2-fold increase in risk for composite outcome in both stage B and C/D (all P<0.001). In model (2), as compared with the non-NC group, the hazard ratios (HR) and 95% confidence interval (95% CI) for the composite outcome of the NC group in stage B and C/D was 1.73 (1.11–2.6) and 2.59 (1.82–3.69), respectively. Importantly, the significance of HR for the composite outcome of the NC group in stage B and C/D remained robust even after the adjustment in model (3).

Figure 3.

Kaplan-Meier curves for composite outcome in (A) stage B and (B) stage C/D. NC, nursing care.

Table 3. Risk of Need for NC

HR categories	Stage B		Stage C/D
	Non-NC group (reference)	NC group	Non-NC group (reference)	NC group
n	1,656	722	1,102	692
(1) Unadjusted
HR	1.00	2.17	1.00	3.00
95% CI		1.44–3.28		2.13–4.21
P-value		<0.001		<0.001
(2) Adjusted for age and sex
HR	1.00	1.73	1.00	2.59
95% CI		1.11–2.69		1.82–3.69
P-value		0.015		<0.001
(3) Fully adjusted
HR	1.00	1.62	1.00	2.31
95% CI		1.01–2.59		1.57–3.39
P-value		0.045		<0.001

Model (3) was adjusted for age, sex, NYHA class, SBP, heart rate, diabetes mellitus, hyperulicemia, BMI, anemia, estimated GFR, BUN, serum sodium, ischemic etiology, AF, LVEF, history of cerebrovascular disease and medication (RAS inhibitor, β-blocker, and aldosterone blocker).

CI, confidence interval; HR, hazard ratio. Other abbreviations as in Tables 1,2.

Figure 4 shows subgroup analyses for composite outcome. In the stage B patients, there were no interactions between age, sex, etiology of the HF or history of cerebrovascular disease. In contrast, there was an interaction between age and etiology of HF in stage C/D patients. Older patients and those with ischemic heart disease had higher HR for composite endpoints.

Figure 4.

Subgroup analysis for the patients in stage B and in stage C/D.

Predictors for NC Need

Figure 5 shows the predictors for NC need. According to the analysis, older age, female gender, diabetes mellitus, cerebrovascular disease and stage C/D were significantly associated with NC need. Particularly, HR for NC need for depression and dementia were 3.61 (95% CI: 3.06–4.25, P<0.001) and 2.70 (95% CI: 2.30–3.16, P<0.001), respectively.

Figure 5.

Predictors of nursing care (NC) need. BMI, body mass index; eGFR, estimated glomerular filtration rate; HR, heart rate; LVEF, left ventricular ejection fraction; SBP, systolic blood pressure.

Discussion

The novel findings of the present study are that (1) >30% of HF patients needed NC regardless of HF stage; (2) NC patients had worse prognosis compared with non-NC patients regardless of HF stage; and (3) the predictors of NC need included older age, female gender, greater severity of HF status, history of cerebrovascular disease, diabetes, depression and dementia. To the best of our knowledge, this is the first study to describe the prevalence, baseline characteristics and clinical outcome of HF patients requiring NC in Japan. Indeed, the present study underlines the importance of NC in the management of HF.

Prevalence and Clinical Characteristics of Non-HF Patients Needing NC

In the present study, we found that >30% of HF patients needed NC. Furthermore, the patients in stage C/D had higher prevalence of NC need compared with the stage B patients. Gure et al reported that HF patients were more likely to have impaired activity of daily living (ADL) or instrumental activities of daily living (IADL) compared with those without HF.⁷ Their ADL and IADL instruments were almost identical to the questionnaire on daily life and physical ability used in the present study. Furthermore, the present questionnaire covered a broad spectrum of daily life, not only physical activity but also nutrition, oral condition and depression. Thus, the present results may reflect the real situation of NC need in HF patients more comprehensively than the previous reports.

NC need was mostly likely due to physical dysfunction in both stage B and C/D patients. The questionnaire on physical ability found that >40% of the stage C/D patients were unable to go upstairs without holding onto the railing. Furthermore, >20% of the patients in both stage B and C/D experienced falling down, and >30% had serious concerns and/or fears about falling. This suggests the presence of serious physical dysfunction in HF patients in the present study. Given that it has been reported that higher physical activity is associated with better prognosis¹⁴ and that exercise training is associated with improved physical function, a heightened sense of quality of life (QOL) may be important to improve ADL and prognosis, regarding ventilatory parameters, muscle function, endothelial function and neurohumoral factors and cardiac rehabilitation.^15,16 Furthermore, neurological rehabilitation in addition to cardiac rehabilitation may be beneficial in HF patients with a history of cerebrovascular disease.

In the present study, poor nutritional status was one of the reasons for NC need. We previously reported that poor nutritional status was associated with increased incidence of death in stage B patients.⁷ The present results also indicate that poor nutritional status may influence the prognosis of stage C/D patients. In addition, oral condition was one of the reasons for requiring NC, possibly in association with poor nutritional status. Taken together, these results underlie the importance of dietary life in the management of HF patients.

Prognosis of Patients Who Need NC

In the present study, the patients who needed NC had worse prognosis regardless of severity of HF. It was reported that nurse educator-delivered teaching session at the time of hospital discharge resulted in improved clinical outcome, increased self-care measure adherence, and reduced cost of care in hospitalized patients with systolic HF.¹⁷ Furthermore, home-based intervention that consisted of a single home visit by a nurse and a pharmacist was associated with reduced frequency of unplanned readmission and mortality in HF patients,¹⁸ and nurse-led follow-up in HF clinic improved survival and self-care behavior in HF patients.¹⁹ Thus, education and implementation of home-based intervention for self-care in HF patients who need NC may be important to improve prognosis.

Predictors of NC Need in HF Patients

In the present study, predictors of NC need in HF patients included older age, female gender, diabetes, anemia, cerebrovascular disease, severe HF status, depression and dementia. Several studies reported that female patients with HF had a better prognosis and longer survival after diagnosis compared with male patients.^20,21 We also reported that female chronic HF patients had better survival than male patients after adjustment for baseline differences.⁸ The crude mortality rate, however, was similar between female and male patients.⁸ The clinical manifestations of HF appeared to be more severe in women compared with men,⁸ which may be associated with NC need. In the present study, we found that female patients were older than male patients. Older patients may have exercise intolerance as a strong determinant of decreased QOL, an independent negative predictor of survival and thus a key therapeutic target.²² Furthermore, older HF patients tend to have more comorbidities than young HF patients.²³ Indeed, in the present study, female patients had higher prevalence of impaired physical activity and impaired oral condition. Thus, older patients and/or female patients may have physical disability or comorbidities that lead to NC need.

In the present study, several comorbidities (diabetes, anemia and cerebrovascular disease) were associated with NC need in HF patients. Diabetes and anemia were risk factors for the cardiovascular events causing severe HF status.²³ Furthermore, patients with cerebrovascular disease usually have neurological dysfunction associated with physical dysfunction. Thus, secondary prevention for these lifestyle diseases is important for avoiding NC need in HF patients.

In the present study, depression and dementia were also important predictors of NC need in HF patients. Kato et al reported that depressive symptoms were strongly associated with impaired QOL, independently of disease severity.²² Furthermore, Hjelm et al reported that HF patients had a significantly higher prevalence of dementia compared with those without HF.²⁴ Considering that patients with dementia usually have a high prevalence of depressive symptoms²⁵ and that physical ability intervention was effective for both depression and dementia,²⁶ cardiac rehabilitation may be useful for patients with depression and/or dementia to prevent NC need.

Study Limitations

Several limitations should be mentioned for the present study. First, we used the JMHLW questionnaire, the relevance of which has been reported for the Japanese population,²⁷ but although the questionnaire covers a broad range of QOL, the present results should be extrapolated with caution to other cohorts or populations. Second, the follow-up period was relatively short. Although we obtained several positive findings that should be useful for daily practice, further study with a longer follow-up period is needed to examine the influencing factors on NC need and the prognostic impact on HF patients. Third, the collection rate of the questionnaire was 65.8% (5,818/8,846 patients). Furthermore, in the present study, we were unable to follow up 28.2% of the patients after the questionnaire. In addition, the patients included in the present study were characterized by younger age and relatively mild status compared with the patients excluded (Table S1). Thus, caution is needed when interpreting the present results in this regard.

Conclusions

One-third of the present HF patients required NC associated with increased mortality, indicating that NC for HF patients is an emerging issue in the health-care system and that earlier intervention is needed to improve QOL and mortality.

Acknowledgments

We thank all members of the Tohoku Heart Failure Society and staff of the Department of Evidence-based Cardiovascular Medicine for their kind contributions (Supplementary File 1). This study was supported by Grants-in-Aid from a Research Grant from the Ministry of Health, Labour, and Welfare (H.S. and N.S.), and a Research Grant from the Ministry of Education, Culture, Sports, Science, and Technology (N.S.), Japan.

Disclosures

Conflict of Interest: The Department of Evidence-based Cardiovascular Medicine, Tohoku University Graduate School of Medicine, is supported in part by unrestricted research grants from Daiichi Sankyo (Tokyo, Japan), Bayer Yakuhin (Osaka, Japan), Kyowa Hakko Kirin (Tokyo, Japan), Kowa Pharmaceutical (Tokyo, Japan), Novartis Pharma (Tokyo, Japan), Dainippon Sumitomo Pharma (Osaka, Japan), and Nippon Boehringer Ingelheim (Tokyo, Japan). H.S. has received lecture fees from Bayer Yakuhin (Osaka, Japan), Daiichi Sankyo (Tokyo, Japan) and Novartis Pharma (Tokyo, Japan).

Supplementary Files

Supplementary File 1

Table S1. Baseline subject characteristics vs. study exclusion

Organization of the CHART-2 Study

Please find supplementary file(s);

http://dx.doi.org/10.1253/circj.CJ-14-0387

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