Prognostic impact of malnutrition assessed using geriatric nutritional risk index in patients aged ⩾80 years with heart failure

Abstract

Aims:

Malnutrition in elderly patients is one of the important issues in an aging society. We aimed to investigate the prevalence and prognostic impact of malnutrition assessed using the geriatric nutritional risk index in very elderly patients hospitalized owing to heart failure.

Methods:

We enrolled 213 consecutive patients aged ⩾80 years who were hospitalized with heart failure. The mean age was 87.2 ± 4.9 years, and 43.7% of them were male. The nutritional status on admission was evaluated using the geriatric nutritional risk index, which was calculated as follows: 14.89 × serum albumin (g/dL) + 41.7 × body mass index/22. The patients were divided into two groups, a low geriatric nutritional risk index group (<92) with malnutrition risk and a high geriatric nutritional risk index group (⩾92) without malnutrition risk.

Results:

The mean geriatric nutritional risk index of all patients was 90.7 ± 10.6, and 108 patients (50.7%) had low geriatric nutritional risk index. During the 540-day follow-up, the all-cause mortality was significantly higher in the low geriatric nutritional risk index group than in the high geriatric nutritional risk index group (35.7% vs. 12.9%, p < 0.001). The Cox proportional-hazards regression analysis revealed that low geriatric nutritional risk index was an independent predictor of mortality (hazard ratio, 2.28; 95% confidence interval, 1.15–4.49; p = 0.02).

Conclusions:

Low geriatric nutritional risk index on admission was common and was associated with poor prognosis in patients aged ⩾80 years who were hospitalized owing to heart failure.

Keywords

Heart failure malnutrition prognosis

Introduction

The prevalence and mortality of heart failure have increased in the aging society – the so-called “HF pandemic.”¹ The prevalence of heart failure has increased to ⩾10% among people aged ⩾80 years, and the prognosis is poor.^2,3 According to the Annual Health, Labor, and Welfare 2017 report, the mean life expectancy is 80.98 years old for Japanese men and 87.14 years old for Japanese women. Therefore, the management for very elderly patients with heart failure has become an important issue in aging societies. Most elderly patients have problems, including presence of comorbidities, frailty, cognitive dysfunction, and social background; therefore, comprehensive assessment and management have been emphasized.^4,5 Malnutrition, which is also an issue for elderly patients with heart failure, is associated with worse prognosis because it could lead to disease progression due to loss of skeletal mass, the vicious cycle associated with cytokine activation, and cachexia.^6–8 Some clinical studies have reported that malnutrition is a strong independent predictor of mortality in patients with heart failure.^9–11 However, the prevalence of malnutrition and its impact on the prognosis of very elderly patients with heart failure are still unclear, since the previous studies enrolled patients aged >65 years.

Several methods can be used for nutritional assessment, and the geriatric nutritional risk index (GNRI) is a simple and established tool for elderly populations.^12,13 To evaluate the clinical significance of malnutrition on prognosis, we investigated the GNRI and prognosis in patients aged ⩾80 years hospitalized with heart failure.

Methods

Subjects and data collection

This study is an observational and retrospective study. From January 2015 to December 2016, we enrolled consecutive 214 subjects aged ⩾80 years who were admitted to Saitama Citizens Medical Center because of worsening heart failure, which was diagnosed by at least two experienced cardiologists on the basis of the Framingham criteria.¹⁴ In the present study, 213 subjects were included (mean age ± SD, 87.2 ± 4.9 years; range, 80–104 years), of whom 93 were male and 120 were female. We enrolled all consecutive patients aged ⩾80 years who were hospitalized owing to heart failure because the exclusion criteria were not defined.

We retrospectively reviewed each subject’s medical chart to obtain information regarding clinical variables, medical history, comorbidities, medication, and clinical course. Baseline characteristics were obtained from the data on admission. We determined the left ventricular ejection fraction (LVEF) by using echocardiography performed within 1 week of admission. We also collected information on the medications prescribed on discharge. Heart failure was classified according to LVEF as follows: heart failure with preserved EF (HFpEF; LVEF, ⩾50%), heart failure with mid-range EF (HFmrEF; LVEF, 40–49%), and heart failure with reduced EF (HFrEF; LVEF, <40%). Body mass index (BMI: kg/m²) on admission was calculated as the weight in kilograms divided by the square of the height in meters. Creatinine clearance was calculated using the Cockcroft–Gault equation.¹⁵

The study was approved by the Institutional Review Board for Human Investigation of Saitama Citizens Medical Center (IRB No. 2018-7). The investigation conforms with the principles outlined in the Declaration of Helsinki.¹⁶ Written informed consent for using clinical data was obtained from all patients on admission.

Geriatric nutritional risk index

The original GNRI reported by Bouillanne et al. is calculated by ideal body weight, which is calculated by knee height and age, and the subject’s body weight.¹² In the present study, we calculated GNRI on admission by using the following formula, using the height and body weight of patients, which was reported by Yamada et al.:¹⁷

\begin{array}{l} G N R I = 14.89 \times s e r u m a l b u m i n (g / d L) \\ + 41.7 \times B M I / 22 k g / m^{2} \end{array}

We defined two grades of nutritional risk as follows: a low-GNRI group (GNRI < 92) with a malnutrition risk and a high-GNRI group (GNRI ⩾ 92) with low or no risk based on a definition described in a previous report.¹²

Outcomes

We investigated the clinical outcomes during the 540-day follow-up period by conducting a medical chart review or telephone interviews. The clinical outcome was defined as all-cause death.

Statistical analyses

All values are expressed as mean ± SD, median, and interquartile range when non-normally distributed, or percentage. Continuous variables were analyzed using a t-test for normally distributed variables, and the Mann–Whitney U-test for non-normally distributed variables. Categorical data were analyzed using the chi-square test. Cumulative event-free rates during follow-up were estimated using the Kaplan–Meier method and compared using the log-rank test. The Cox proportional-hazards regression analysis aimed to assess independent predictors of all-cause mortality. This analysis was performed with age, sex, and other factors that could influence the subjects’ prognosis; BMI used in the calculation of GNRI was excluded. For all the analyses, a two-tailed p value of <0.05 was considered statistically significant. All statistical analyses were performed using EZR (Jichi Medical University Saitama Medical Center, Saitama, Japan), which is a graphical user interface for R (The R Foundation for Statistical Computing, Vienna, Austria).¹⁸

Results

The distribution of GNRI in all the subjects of the present study is shown in Figure 1. The mean GNRI score was 90.7 ± 10.6, and 108 patients (50.7%) had a low GNRI (GNRI < 92). The clinical baseline characteristics of the low- and high-GNRI groups are shown in Table 1. The low-GNRI group consisted of patients with the following characteristics: older age; lower incidences of diabetes mellitus, dyslipidemia, and coronary artery disease; impaired renal function; higher B-type natriuretic peptide (BNP) level; and less β-blocker use.

Table 1.

Patient characteristics.

	Low GNRI	High GNRI	p value
	(n = 112)	(n = 101)	p value
Age, years	88 ± 5.2	86 ± 4.2	<0.01
Male, n (%)	50 (44.6)	43 (42.6)	0.78
BMI, kg/m²	18.2 ± 2.3	23.0 ± 3.0	<0.01
Smoking, n (%)	26 (23.2)	32 (31.7)	0.17
Comorbidities, n (%)
Diabetes mellitus	18 (16.1)	34 (33.7)	<0.01
Hypertension	90 (80.4)	88 (87.1)	0.20
Dyslipidemia	21 (18.8)	37 (36.6)	<0.01
Atrial fibrillation	63 (56.3)	60 (59.4)	0.68
Coronary artery disease	25 (22.3)	44 (43.6)	<0.01
COPD	41 (36.6)	24 (23.8)	0.05
Stroke	29 (25.9)	26 (25.7)	1.0
Heart rate, beats per min	93 ±26	88 ± 30	0.21
Systolic BP, mmHg	138 ± 31	143 ± 29	0.20
Diastolic BP, mmHg	80 ± 23	80 ± 19	0.81
LVEF, %	50.3 ±18	53.8 ± 17	0.15
LVEF classification, n (%)			0.21
HFrEF	34 (30.4)	25 (24.8)
HFmrEF	11 (9.8)	18 (17.8)
HFpEF	67 (59.8)	58 (57.4)
Serum sodium, mmol/L	139 ± 6.1	140 ±4.3	0.15
Creatinine clearance, mL/min	30.7 ± 15	38.1 ± 18	<0.01
Serum albumin, g/dL	3.2 ± 0.4	3.7 ± 0.3	<0.01
Hemoglobin, g/dL	11.1 ± 2.0	11.5 ±2.0	0.18
BNP, pg/mL	876 [400, 1668]	574 [259, 1077]	0.04
Medication at discharge, n (%)
Beta blocker	35 (31.3)	55 (54.5)	<0.01
ACE-I or ARB	53 (47.3)	57 (56.4)	0.22
Loop diuretics	100 (89.3)	94 (93.1)	0.47
Spironolactone	49 (43.8)	44 (43.6)	1.0
Statin	25 (22.3)	31 (30.7)	0.21
DOAC	27 (24.1)	31 (30.7)	0.29
Warfarin	12 (10.7)	19 (18.8)	0.12

Values are expressed as mean ± SD, or median [first quartile, third quartile].

BMI, body mass index; COPD, chronic obstructive pulmonary disease; BP, blood pressure; LVEF, left ventricular ejection fraction; HFrEF, heart failure with reduced ejection fraction; HFmrEF, heart failure with mid-range ejection fraction; HFpEF, heart failure with preserved ejection fraction; BNP, brain natriuretic peptide; ACE-I, angiotensin converting enzyme inhibitor; ARB, angiotensin II receptor blocker; DOAC, direct oral anticoagulant.

The Kaplan–Meier curve during the 540-day follow-up showed that all-cause mortality was significantly higher in the low-GNRI group than in the high-GNRI group (35.7% vs. 12.9%, p < 0.001; Figure 2). The Cox proportional-hazards regression analysis indicated that low GNRI was an independent predictor of death (hazard ratio, 2.28; 95% confidence interval, 1.15–4.49; p = 0.02; Table 2).

Table 2.

Cox proportional-hazards regression predictors for the endpoint of total death.

	Univariate analysis			Multivariate analysis
	Hazard ratio	95% CI	p value	Hazard ratio	95% CI	p value
Age, years	1.10	1.05–1.16	0.0001	1.06	1.00–1.11	0.04
Male	0.68	0.38–1.18	0.17	0.86	0.45–1.64	0.64
Diabetes mellitus	0.84	0.44–1.61	0.67
Hypertension	1.00	0.96–1.05	0.88
Dyslipidemia	0.36	0.16–0.79	0.01	0.55	0.24–1.24	0.15
Atrial fibrillation	1.00	0.58–1.73	1.00
Coronary artery disease	0.71	0.39–1.31	0.28
COPD	1.81	1.05–3.13	0.03	1.46	0.82–2.60	0.20
Heart rate, beats per min	1.01	1.00–1.02	0.11
Systolic blood pressure, mmHg	0.99	0.98–1.00	0.007	0.99	0.98–1.00	0.01
Serum sodium, mmol/L	0.96	0.92–1.01	0.10
Hemoglobin, g/dL	0.98	0.89–1.07	0.61
Log BNP, pg/mL	3.19	1.62–6.30	0.001	1.98	0.93–4.20	0.08
LVEF, %	0.99	0.98–1.00	0.07
Creatinine clearance, mL/min	0.96	0.94–0.98	0.0002	0.98	0.96–1.00	0.08
Low GNRI	4.10	2.15–7.80	<0.0001	2.28	1.15–4.49	0.02

CI, confidence interval; COPD, chronic obstructive pulmonary disease; BNP, brain natriuretic peptide; LVEF, left ventricular ejection fraction; GNRI, geriatric nutritional risk index.

Discussion

The present study on very elderly patients with heart failure demonstrates that malnutrition assessed on the basis of GNRI was recognized in more than half of patients and was associated with worse prognosis. Low GNRI was an independent predictor of all-cause death, while BNP level and LVEF did not predict prognosis.

Elderly patients with heart failure have several comorbidities, including various diseases such as infection, anemia, stroke, renal dysfunction, chronic respiratory disease, and malignancy, and each disease can influence prognosis. Moreover, social problems about care and nursing will be highlighted because of dementia, psychiatric disorder, bone fracture, and decreased physical activities due to frailty. In elderly heart failure patients with multiple problems, a multidisciplinary intervention is important for treatment and care.^4,5,19 Malnutrition, which is also an issue in elderly populations, could cause loss of skeletal mass, decreased immune system function, impaired respiratory function, fluid retention, and cachexia. As a result, malnutrition is associated with decreased physical activity and worsening prognosis.^6–8,20,21

Several screening tools for malnutrition are available. Among these screening tools, the Prognostic Nutritional Index (PNI), Controlling Nutritional Status (CONUT) score, and GNRI have been studied in patients with heart failure. PNI is calculated from the serum albumin level and total lymphocyte counts.²² Cheng et al. reported that PNI is an independent prognostic factor for long-term survival in patients hospitalized for acute heart failure.²³ The CONUT score is an index calculated from serum albumin level, total lymphocyte counts, and total cholesterol level,²⁴ and was reported to be an independent determinant of long-term death in acute heart failure.²⁵ However, because of its dependence on the total cholesterol level, the CONUT score may not be suitable for evaluating patients who receive statin therapy to prevent cardiovascular complications. Although assessments of PNI, CONUT, and GNRI are reported to be useful prognostic factors,²⁶ Sze et al. suggested that among PNI, CONUT, and GNRI as screening tools, GNRI had the greatest incremental value in predicting risk.²⁷ Moreover, they stated that these simple malnutrition scores are more closely related to outcome than BMI, and that BMI should not be used as a surrogate of nutritional status in patients with heart failure. GNRI is an index for hospitalized elderly patients that was first reported by Bouillanne et al.¹² The original GNRI was calculated from the serum albumin level, body weight, and ideal body weight by using the following equation: Original GNRI = 14.89 × serum albumin (g/dL) + 41.7 × actual body weight/ideal body weight. The ideal body weight in the original GNRI was calculated with the Lorentz formula. In the present study, we calculated GNRI using the following formula with the ideal BMI of 22 kg/m²: GNRI = 14.89 × serum albumin (g/dL) + 41.7 × BMI/22 kg/m². Yamada et al. reported little difference between the two formulas.¹⁷ As GNRI is based on serum albumin level and BMI, Bouillanne et al. have stated that GNRI is a “nutrition-related risk index,” and not just a malnutritional index.¹² They also have concluded that GNRI is a more reliable prognostic indicator of morbidity and mortality in hospitalized elderly patients than indexes that use albumin or BMI alone.

Some reports indicated that GNRI is associated with duration of hospital stay, congestion, cardiovascular events, and long-term prognosis in patients with heart failure.^9,10,26–30 These studies enrolled patients aged >65 years; therefore, the present study, which investigated the prevalence of malnutrition and its impact on the prognosis of patients aged ⩾80 years with heart failure, is significant. In our study, similar to that observed in previous studies, low GNRI, but not BNP level and LVEF, was an independent predictor of mortality in very elderly patients with heart failure. Although whether nutritional intervention could improve the clinical outcome in patients with heart failure is still unclear, we speculate that multidisciplinary care management, including nutritional assessment, is important in the care of patients with heart failure in the aging society.

This study had several limitations. First, this was a single-center, retrospective, small-sample study with a short follow-up duration. Second, we failed to clarify the prognostic impact of heart failure, malnutrition and malnutrition-related complications, as it was difficult to identify the cause of death. Although the relationship between New York Heart Association (NYHA) functional class and prognosis has already been established, it is often difficult to assess NYHA functional class in elderly heart failure patients with frailty and impaired physical activity, and we could not investigate NYHA functional class at discharge in this study. Third, we did not investigate food intake, physical activities, quantity of muscle and serum inflammatory markers such as C-reactive protein, tumor necrosis factor-α, and interleukin-6. Fourth, we applied a cut-off value of 92 in the present study; however, whether it should adjust according to race or age is unclear. Further studies are warranted to validate the clinical application of GNRI in the management of heart failure.

In conclusion, malnutrition assessed using GNRI was common in patients aged ⩾80 years hospitalized owing to heart failure, and was an independent factor for predicting their poor prognosis.

Footnotes

Acknowledgements

We thank Dr Yusuke Ugata, Jichi Medical University Saitama Medical Center, for his helpful advice about the statistical analysis.

Implications for Practice

Malnutrition, assessed using geriatric nutritional risk index, is common in patients aged ⩾80 years hospitalized owing to heart failure.

Low geriatric nutritional risk index on admission is an independent predictor of all-cause mortality, while B-type natriuretic peptide and left ventricular ejection fraction do not predict prognosis.

Recognition of the high prevalence and poor prognosis of malnutrition could facilitate the importance of comprehensive care in patients with heart failure.

Declaration of Conflicting Interests

The authors declare that there are no conflict of interest.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

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