Prevalence, Characteristics, and Prognostic Associations of Cachexia Diagnosed Using Asian Working Group for Cachexia 2023 Criteria in Older Adults With Heart Failure

Abstract

Background: Few studies have examined the characteristics of heart failure (HF) patients with cachexia using the Asian Working Group for Cachexia (AWGC) 2023 criteria. This study assessed the characteristics and clinical impact of cachexia in older adults with HF.

Methods and Results: Results of laboratory measurements, echocardiography, physical function, depression, nutritional status, and the prevalence of cachexia, frailty, and sarcopenia were assessed in older adults (≥65 years) with HF in a stable condition just before discharge. After discharge, all participants were prospectively followed for adverse clinical events. Patients were classified based on the presence or absence of cachexia, and their frailty, sarcopenia, and clinical outcomes were compared. The prevalence of cachexia diagnosed by AWGC 2023 and Evans criteria was 24.7% and 12.9%, respectively. Among HF patients with cachexia, 71.6% had frailty and 86.7% had sarcopenia. Patients with cachexia had significantly poorer physical function and nutrition than those without. Cox proportional hazards analysis identified cachexia as an independent predictor of all-cause and cardiovascular death.

Conclusions: Cachexia in older adults with HF is strongly associated with poor physical function, malnutrition, and adverse clinical outcomes. Early identification and management of cachexia may help improve the prognosis in this population.

Globally, the population is aging, leading to a rise in the number of patients with heart failure (HF).¹ In Japan, the number of older adults with newly diagnosed HF is expected to increase.^2,3 Older adults with HF often have reduced exercise tolerance and comorbidities such as cognitive impairment, depression,⁴ frailty,⁵ and sarcopenia.⁶ In addition, chronic inflammation and malnutrition in older adults may contribute to cachexia.^7,8

Cachexia is involuntary weight loss due to tissue loss caused by chronic disease.^9,10 Cachexia occurs with the progression of diseases such as cancer, chronic kidney disease, chronic obstructive pulmonary disease, and chronic HF. Cachexia associated with chronic HF is referred to as cardiac cachexia.¹¹ The prevalence of cardiac cachexia varies widely, but has been reported to range from 16% to 36%.^12–15 Because the presence of cachexia increases the risk of all-cause death and cardiovascular death,^12–14 the implementation of strategies to manage cachexia in older adults with HF is crucial.

The Evans criteria¹⁶ are commonly used to diagnose cachexia, particularly in cancer patients.¹⁷ Several studies have applied these criteria to Japanese HF patients,^13,14 diagnosing cachexia based on weight loss accompanied by muscle weakness, fatigue, anorexia, decreased lean body mass index, and abnormal biochemical markers. However, specific diagnostic criteria for Asian patients have not been established. To address this gap, the Asian Working Group for Cachexia (AWGC) 2023 proposed diagnostic criteria for cachexia in Asian populations.¹⁸ Since the introduction of the AWGC 2023 criteria, studies have reported their use in patients with cancer,^19–21 diabetes,²² hemodialysis,²³ and sarcopenic dysphagia.^24,25 A recent study in cardiovascular disease found that the prevalence of cachexia diagnosed using the AWGC 2023 criteria in older HF patients attending outpatient cardiac rehabilitation was 30% and that cachexia was associated with reduced exercise function.²⁶ In addition, cachexia, as assessed by AWGC 2023 criteria, was present in 74.1% of patients and was not associated with a worse prognosis within 2 years.²⁷ However, there are still few studies using the AWGC 2023 criteria to report on the prevalence or characteristics of cachexia in Japanese patients with chronic HF, and the association between cachexia and long-term prognosis remains unclear.

Therefore, the aims of the present study were to investigate the prevalence of cachexia in Japanese older adults with HF using the AWGC 2023 criteria, to assess the characteristics of patients with cachexia, and to explore the association between cachexia and prognosis.

Methods

Study Population

This study was conducted on participants admitted for worsening HF to the Cardiology Department of the National Center for Geriatrics and Gerontology (Obu, Aichi, Japan) between August 2016 and April 2024. All participants were at least 65 years old and underwent laboratory measurements, echocardiography, and physical function assessments, as well as completing the Geriatric Depression Scale-15 (GDS-15), and the Mini Nutritional Assessment Short-Form (MNA-SF). The prevalence of cachexia, frailty, and sarcopenia was also assessed in patients in a stable condition just before discharge. All participants were prospectively followed up for adverse clinical events after discharge.

The inclusion criteria for this study were symptomatic HF due to non-ischemic cardiomyopathy, tachycardia, bradycardia, valvular hypertension, or other causes in people aged 65 years or older. Non-ischemic cardiomyopathies were defined as ventricular myocardial abnormalities in the absence of coronary artery disease or valvular, pericardial, or congenital heart disease.²⁸ Tachycardia and bradycardia included atrial, supraventricular, and ventricular arrhythmias, as well as sick sinus syndrome and atrioventricular block in the absence of structural heart disease. Valvular heart disease was diagnosed based on hemodynamic or echocardiographic findings or a history of valvular or congenital cardiac surgery, according to the American College of Cardiology and American Heart Association guideline for the management of patients with valvular heart disease.²⁹ Hypertension was defined as systolic blood pressure ≥140 mmHg, diastolic blood pressure ≥90 mmHg, or a history of hypertension treatment. Worsening HF was defined as a clinical syndrome comprising symptoms and signs of structural and functional cardiac abnormalities, elevated natriuretic peptide levels, and objective evidence of pulmonary or systemic congestion.³⁰

The exclusion criteria included severe respiratory dysfunction (i.e., patients receiving long-term oxygen therapy due to respiratory disease), liver dysfunction (Child-Pugh Class C), renal dysfunction (glomerular filtration rate stage G5), and malignant tumors with a prognosis of less than 1 year.

The study protocol adhered to the Declaration of Helsinki, and written informed consent was obtained from each participant. The Ethics Review Board of the National Center for Geriatric and Gerontology approved the study (Approval no. 1272).

Clinical Characteristics

The background data of the participants included age, sex, body mass index (BMI), underlying diseases, HF phenotypes, HF stage, medication status, echocardiographic findings, left ventricular ejection fraction (LVEF), ratio of transmitral Doppler early filling velocity to tissue Doppler early diastolic mitral annular velocity, and blood tests, including plasma B-type natriuretic peptide (BNP), hemoglobin, albumin, C-reactive protein (CRP), and estimated glomerular filtration rate (eGFR).

Diagnosis of Cachexia, Frailty, and Sarcopenia

Cachexia The prevalence of cachexia was diagnosed using both the AWGC 2023 criteria (Supplementary File)¹⁸ and the Evans criteria.¹⁶ The AWGC 2023 criteria define cachexia based on the following: (1) the presence or absence of underlying diseases; (2) weight loss >2% over 3–6 months or low BMI (<21 kg/m²); and (3) 1 or more of the following: anorexia, decreased handgrip strength, or elevated CRP. In this study, the presence of cachexia was assessed based on the following criteria: (1) the presence of underlying disease; (2) decreased BMI; and (3) anorexia, decreased handgrip strength, or elevated CRP.

In this study, anorexia was defined as a positive response to the question, “Has food intake declined over the past 3 months due to loss of appetite, digestive problems, chewing or swallowing difficulties?” in the MNA-SF.³¹

Frailty The prevalence of frailty was evaluated using the Japanese version of the Cardiovascular Health Study (J-CHS) criteria.^32,33 The J-CHS criteria assess 5 components: weight loss, low physical activity, tiredness, muscle weakness, and slow gait speed. Frailty is defined as low scores on 3–5 components, whereas ‘prefrailty’ is defined as low scores on 1 or 2 components.

Sarcopenia The prevalence of sarcopenia was assessed according to the Asian Working Group for Sarcopenia (AWGS) 2019 criteria.³⁴ The AWGS 2019 criteria diagnose sarcopenia when there is a decrease in either or both physical function and muscle strength, alongside a decrease in skeletal muscle strength. In this study, physical function decline was determined using the Short Physical Performance Battery (SPPB), and skeletal muscle mass decline was measured using bioelectrical impedance analysis (InBody 770, Seoul, Korea).

Other Measurements

The SPPB, 10-m gait test (gait speed), handgrip strength, skeletal muscle mass index (SMI), Functional Independence Measure (FIM), GDS-15, and MNA-SF were measured at discharge.

Short Physical Performance Battery The SPPB was used to evaluate lower limb function.³⁵ The SPPB comprises 3 components: a balance test (closed leg, semitandem, and tandem standing), walking time, and the ability to stand from a seated position. The maximum score was 12 points, with higher scores indicating better physical function.

Ten-Meter Gait Test Participants were instructed to walk a distance of 16 m at a comfortable speed, twice.³⁶ The time taken to reach 10 m along the walkway was measured, and walking speed was calculated based on the measured time.

Handgrip Strength Grip strength was measured using a dynamometer (5030JI; JAMAR, Bolingbrook, IL, USA). Participants sat with their elbow joints flexed at 90° and performed the test, alternating between their right and left hands.³⁴ The maximum reading from the 2 trials using both hands was recorded in kilograms.¹⁴

Functional Independence Measure The FIM is used to measure activities of daily living (ADL), comprising motor (FIM-motor) and cognitive items.³⁷ In this study, we evaluated the FIM-motor. The FIM-motor consists of 13 items, and the degree of independence for each item was evaluated on a 7-point scale from total assistance to independence. FIM-motor scores ranged from 13 to 91, with higher scores indicating greater independence in ADL.

Geriatric Depression Scale-15 The GDS-15 is a 15-item indicator of depression, and its validity and reliability in Japan have been reported.³⁸ In this study, the maximum possible score on the GDS-15 was 15 points, with higher scores representing more severe depression.

Mini Nutritional Assessment Short-Form The MNA-SF is a nutrition screening tool specifically designed for older adults.³⁹ It consists of 6 items: change in food intake, change in weight, mobility, stress, psychiatric problems, and BMI. The total MNA-SF score was used to determine whether patients were undernourished, at risk of undernourishment, or in good nutritional condition.

Adverse Clinical Events

In this study, all-cause death was the primary endpoint, whereas a composite cardiovascular endpoint and cardiovascular death were secondary outcomes. Events were defined as follows: “all-cause death” refers to death from any cause; the composite cardiovascular endpoint included cardiovascular death and hospitalization for cardiovascular reasons; “cardiovascular death” encompassed sudden cardiac death, HF, and death due to other cardiovascular causes; and “cardiovascular hospitalization” included worsening HF, acute coronary syndrome, coronary revascularization hospitalization, and brain infarction.

Statistical Analysis

Normally distributed continuous variables are presented as the mean±SD, ordinal variables are presented as the median with interquartile range (IQR), and categorical variables are presented as percentages. Participants were divided into 2 groups based on the presence or absence of cachexia, and their background, alongside the coexistence rate of frailty and sarcopenia, were compared using unpaired t-tests, the Mann-Whitney U test, or the χ² test, as appropriate. Survival time analysis (Kaplan-Meier method) was used to examine the association of cachexia with all-cause death, the composite cardiovascular endpoint, and cardiovascular death. Event-free survival between the 2 groups was evaluated using log-rank tests. In Cox proportional hazards analysis, adverse clinical events were used as dependent variables. Age, sex, LVEF, E/e′, log-transformed BNP, hemoglobin, and eGFR, an established prognostic indicator for HF,¹ were used as explanatory variables.

Statistical analyses were performed using SPSS version 27 (SPSS Inc., Chicago, IL, USA), and statistical significance was set at P<0.05.

Results

Baseline Clinical Characteristics

Participants’ backgrounds and background comparisons for this study are presented in Table 1. There were 388 participants in this study, with a mean age of 82 years; 49.5% were male. The median BNP level was 108.0 pg/mL and the median LVEF was 60.0%.

Table 1.

Baseline Clinical Characteristics

	All participants (n=388)	Non-cachexia (n=292)	Cachexia (n=96)	P value
Age (years)	82±7	81±7	84±7	<0.001
Male sex	192 (49.5)	123 (42.1)	73 (76.0)	<0.001
BMI (kg/m2)	21.9±3.9	23.1±3.5	18.1±2.1	<0.001
HF phenotype
HFrEF and HFmrEF (LVEF <50%)	101 (26.0)	82 (28.1)	19 (19.8)	0.268
HFpEF (LVEF ≥50%)	287 (74.0)	210 (71.9)	77 (80.2)
Heart failure stage C/D
Stage C	320 (82.5)	245 (83.9)	85 (78.1)	0.147
Stage D	68 (17.5)	47 (16.1)	21 (21.9)
Underlying disease
Non-ischemic cardiomyopathy	46 (11.9)	31 (10.6)	15 (15.6)	0.001
Ischemic heart disease	76 (19.6)	65 (22.3)	11 (11.5)
Tachycardia-induced	95 (24.5)	80 (27.4)	15 (15.6)
Bradycardia	46 (11.9)	38 (13.0)	8 (8.3)
Valve	68 (17.5)	37 (12.7)	31 (32.3)
Hypertension	44 (11.3)	31 (10.6)	13 (13.5)
Other	13 (3.4)	10 (3.4)	3 (3.1)
Medication
Diuretic	220 (56.7)	162 (55.5)	58 (60.0)	0.408
Tolvaptan	78 (20.1)	54 (18.5)	24 (25.0)	0.171
ACEi/ARB/ARNI	173 (44.6)	134 (45.9)	39 (40.8)	0.767
β-blocker	184 (47.4)	143 (49.0)	41 (42.7)	0.270
Spironolactone	94 (24.2)	69 (23.6)	25 (26.0)	0.642
SGLT2 inhibitor	62 (16.0)	49 (16.8)	13 (13.5)	0.458
Laboratory data
BNP (pg/mL)	108.0 [42.0–223.3]	100.0 [35.0–222.3]	132.0 [66.3–224.0]	0.066
CRP (mg/dL)	0.4±0.6	0.3±0.5	0.6±0.9	<0.001
Hemoglobin (mg/dL)	12.2±1.8	12.4±1.9	11.9±1.5	0.039
Albumin (d/dL)	3.7±0.5	3.7±0.5	3.6±0.5	0.055
eGFR (mL/min/1.73 m2)	51.7±18.2	50.7±17.2	55.2±20.9	0.042
Echocardiography
LVEF (%)	60.0 [48.7–65.5]	60.8 [47.4–65.7]	60.4 [52.1–64.9]	0.767
E/e′	14.2 [11.3–18.4]	13.7 [11.2–17.7]	15.4 [11.0–20.0]	0.086
Other markers of physical/functional status
SPPB (points)	9 [7–12]	10 [7–12]	8 [5–11]	0.001
Gait speed (m/s)	0.9±0.3	0.9±0.3	0.7±0.3	0.043
Handgrip strength (kg)
Male	25.7±8.0	26.2±7.9	22.3±6.8	0.039
Female	15.1±5.4	16.6±5.5	12.6±4.0	<0.001
SMI (kg/m2)
Male	6.6±1.0	6.7±1.0	5.9±0.9	0.001
Female	5.3±1.0	5.7±0.8	4.5±0.7	<0.001
FIM-motor (points)	85 [73–90]	86 [75–91]	78 [66–86]	<0.001
GDS (points)	4 [2–7]	9 [2–7]	5 [2–8]	0.161
MNA-SF (points)	9 [7–11]	10 [9–11]	7 [5–8]	<0.001

Unless indicated otherwise, data are given as the mean±SD, median [interquartile range], or n (%). Groups were compared using unpaired t-tests, the Mann-Whitney U test, or the Chi-squared test, as appropriate. ACEi, angiotensin-converting enzyme inhibitor; ARB, angiotensin II receptor blocker; ARNI, angiotensin receptor-neprilysin inhibitor; BNP, B-type natriuretic peptide; CRP, C-reactive protein; E/e′, ratio of transmitral Doppler early filling velocity to tissue Doppler early diastolic mitral annular velocity; eGFR, estimated glomerular filtration rate; FIM-motor, Functional Independence Measure motor item; GDS, Geriatric Depression Scale; HFrEF, heart failure with reduced ejection fraction; HFmrEF, heart failure with mid-range ejection fraction; HFpEF, heart failure with preserved ejection fraction; LVEF, left ventricular ejection fraction; MNA-SF, Mini Nutritional Assessment Short-Form; SGLT2, sodium-glucose cotransporter 2; SMI, skeletal muscle mass index; SPPB, Short Physical Performance Battery.

When comparing participants’ backgrounds between the 2 groups, significant differences were observed in age, sex, BMI, underlying diseases, hemoglobin, and eGFR. In addition, the comparison of physical function and nutritional status showed that both were poorer in the cachexia than non-cachexia group, as evidenced by results for the SPPB (median 8 [IQR 5–11] vs. 10 [IQR 7–12] points, respectively; P=0.001), handgrip strength in both men (Male; 22.3±6.8 vs. 26.2±7.9 kg, respectively; P=0.039) and women (12.6±4.0 vs. 16.6±5.5 kg, respectively; P<0.001), SMI in men (5.9±0.9 vs. 6.7±1.0 kg/m², respectively; P=0.001) and women (4.5±0.7 vs. 5.7±0.8 kg/m², respectively; P<0.001), FIM-motor (78 [IQR 66–86] vs. 86 [IQR 75–91] points, respectively; P=0.001), and MNA-SF (7 [IQR 5–8] vs. 10 [IQR 9–11] points, respectively; P<0.001).

Prevalence of Cachexia, Frailty, and Sarcopenia

Figure 1 shows the prevalence of cachexia, frailty, and sarcopenia in all participants, as well as in the non-cachexia and cachexia groups. Among all participants the prevalence of cachexia, frailty, and sarcopenia was 24.7%, 53.3%, and 56.7%, respectively. Of the older adults with HF and cachexia, 71.6% had frailty and 86.7% had sarcopenia, both of which were significantly higher than in the non-cachexia group (P<0.001 for both). The prevalence of cachexia diagnosed by the Evans criteria was 12.9%.

Figure 1.

Prevalence of (A) cachexia, (B) frailty, and (C) sarcopenia. The prevalence of cachexia in older adults with heart failure was 24.7% (A). The prevalence of both frailty (B) and sarcopenia (C) was significantly higher in the cachexia than non-cachexia group.

Association of Cachexia With Clinical Adverse Events

The mean follow-up period after discharge in this study was 966 days. The incidence of clinical adverse events after discharge and the results of the Kaplan-Meier analysis are presented in Table 2 and Figure 2. Log-rank tests revealed significant differences in all-cause death (P=0.003; Figure 2A), cardiovascular death (P=0.003; Figure 2B), and the composite cardiovascular endpoint (P=0.022; Figure 2C) between the cachexia and non-cachexia groups.

Table 2.

Clinical Adverse Events

	All participants (n=388)	Non-cachexia (n=292)	Cachexia (n=96)	P value
All-cause death	87 (22.4)	58 (19.9)	29 (30.2)	0.035
Cardiovascular death	64 (16.5)	41 (14.0)	23 (24.0)	0.023
Composite cardiovascular endpoint	126 (32.5)	89 (30.5)	37 (38.5)	0.143

Unless indicated otherwise, data are given as n (%). Groups were compared using the Chi-squared test.

Figure 2.

Kaplan-Meier curves of adverse clinical events in the cachexia and non-cachexia groups: (A) all-cause death, (B) cardiovascular death, and (C) the composite cardiovascular endpoint. Log-rank tests revealed significant differences in all-cause and cardiovascular death between the cachexia and non-cachexia groups.

Table 3 presents results of the Cox proportional hazards analysis. Cachexia was significantly associated with all-cause death (hazard ratio [HR] 1.934; 95% confidence interval [CI] 1.058–3.543; P=0.032) and cardiovascular death (HR 2.761; 95% CI 1.334–5.716; P=0.006).

Table 3.

Cox Proportional Hazards Analysis of Factors Related to Adverse Clinical Events

	All-cause death			Cardiovascular death			Composite cardiovascular endpoint
	HR	95% CI	P value	HR	95% CI	P value	HR	95% CI	P value
Non-cachexia	Ref.			Ref.			Ref.
Cachexia	1.934	1.058–3.543	0.032	2.761	1.334–5.716	0.006	1.301	0.806–2.101	0.282
Age	1.055	1.015–1.096	0.006	1.071	1.023–1.121	0.003	1.046	1.016–1.078	0.003
Sex	0.590	0.340–1.024	0.061	0.432	0.214–0.870	0.019	0.910	0.599–1.382	0.658
LVEF	0.979	0.962–0.996	0.018	0.990	0.969–1.012	0.372	0.994	0.980–1.009	0.430
E/e′	0.995	0.959–1.031	0.771	1.007	0.966–1.050	0.742	0.851	0.974–1.032	0.851
Log[BNP]	1.002	1.001–1.003	0.001	1.002	1.001–1.003	0.001	1.002	1.001–1.003	<0.001
Hemoglobin	0.808	0.697–0.937	0.005	0.808	0.678–0.963	0.017	0.892	0.791–1.004	0.059
eGFR	0.992	0.977–1.007	0.279	0.984	0.967–1.002	0.084	0.987	0.976–0.999	0.036

CI, Confidence interval; HR, Hazard ratio; Log[BNP], log-transformed B-type natriuretic peptide. Other abbreviations as in Table 1.

Discussion

This study examined the prevalence of cachexia based on AWGC 2023 criteria, the characteristics of cachexia in older adults with HF, and the association of cachexia with prognosis. The main findings of the study are that: (1) the prevalence of cachexia diagnosed using the AWGC 2023 criteria in older adults with HF was 24.7%; (2) the AWGC 2023 criteria identified more patients with cachexia than did the Evans criteria; (3) physical function and nutritional status in older adults with HF were significantly poorer in those with than without cachexia; and (4) cachexia was significantly associated with all-cause death and cardiovascular death.

Prevalence of Cachexia, Frailty, and Sarcopenia

There have been several reports of cachexia in patients with HF.^{7–10,13–15} The prevalence of cachexia diagnosed using Evans criteria in older adults with HF aged ≥65 years in Japan has been reported to be approximately 33–36%.^13–15 The prevalence of cachexia diagnosed by AWGC 2023 criteria was previously reported to be 30% in the Japanese Sarcopenic Dysphagia Database (mean age 83.7 years).²⁶ However, in the present study, the prevalence of cachexia diagnosed by AWGC 2023 criteria in older adults with HF was 24.7%. The main reason for this difference may be patients’ comorbidities.

In addition, we found that 71.6% of older adults with HF and cachexia had frailty, and 86.7% had sarcopenia. Frailty and sarcopenia have been reported to worsen the prognosis of patients with HF.^40–42 Cachexia, frailty, and sarcopenia are interrelated syndromes with partial overlap, and each has been reported to be associated with a worse prognosis.^14,15 Diagnosing cachexia, frailty, and sarcopenia, whether they coexist independently or overlap, may be crucial.

Characteristics of Cachexia

Compared with the non-cachexia group, the cachexia group had poorer physical function, ADL, and nutritional status. Older adults with HF often have chronic inflammation and malnutrition, which leads to loss of skeletal muscle mass.^7,8 Our findings in the present study also suggest that cachexia in older adults with HF is associated with a high rate of overlapping frailty and sarcopenia, leading to poor physical function, ADL performance, and nutritional status.

In addition, the AWGC 2023 identifies mortality, quality of life, and functional status, including ADL, as important clinical outcomes in cachexia.¹⁸ It is evident that the coexistence of cachexia in older adults with HF results in poor prognosis, physical function, and ADL performance. A multidisciplinary approach that includes nutritional therapy, exercise therapy, psychotherapy, and pharmacotherapy is needed to combat cachexia, and the need for intervention studies is suggested.^18,43 Future studies verifying the effectiveness of cardiac rehabilitation and nutritional therapy for cachexia in older adults with HF are needed.

Association Between Cachexia and Prognosis

In the present study, cachexia diagnosed using the AWGC 2023 criteria was associated with all-cause and cardiovascular mortality, but not with a composite cardiovascular endpoint, in older adults with HF. In contrast, a previous study analyzing HF prognosis using the AWGC 2023 criteria found no association between cachexia and mortality events within 2 years.²⁷ This apparent discrepancy may be attributed to the longer follow-up period in our study. Furthermore, diuretic-induced weight loss (reflecting fluid loss from the interstitial compartment) may have contributed to these differing associations.

In addition, the prevalence of cachexia diagnosed by AWGC 2023 and Evans criteria differed between the present and previous studies.²⁷ Based on our clinical experience, there could be a significant bias in the intention-to-lose-weight assessment, as in patients undergoing intensive lifestyle intervention, and weight loss related to inflammation or cachexia may also occur. Patients diagnosed with cachexia in the present study were older, had a lower BMI, higher CRP levels, and a higher prevalence of HF with preserved ejection fraction (HFpEF) than in the previous study.²⁷ Because lower BMI and higher CRP levels are associated with increased mortality in HF patients,^44,45 the AWGC 2023 criteria used in the present study may have identified HF patients at higher risk of a poor prognosis. These findings suggest that the AWGC 2023 criteria may help predict the long-term prognosis of older adults with HF.

Clinical Implication

This study demonstrated that cachexia diagnosed using the AWGC 2023 criteria was associated with all-cause and cardiovascular death over a relatively long follow-up period. The AWGC 2023 criteria were designed to enable earlier diagnosis of cachexia.¹⁸ Indeed, compared with the Evans criteria, the AWGC 2023 criteria appear to detect cachexia at an earlier stage. In line with this concept, early diagnosis and intervention for cachexia in older adults with HF may help reduce long-term mortality.

Study Limitations

Certain limitations of the present study should be noted. First, this was a retrospective study in a single center with a relatively small sample size. Second, the prevalence of cachexia may have been underestimated because the diagnosis of cachexia was made retrospectively, and weight loss between 3 and 6 months was not assessed. Third, the reasons for body weight loss were not recorded and could not be classified as intentional or unintentional. Given the age and the prevalence of HFpEF in our population, we assume that most patients did not lose weight intentionally. In addition, treatment discontinuation may have contributed to the lack of effect in body weight observed after years of treatment. Weight loss should be included in the evaluation in future studies, and the prevalence of cachexia diagnosed using AWGC 2023 criteria should be investigated prospectively in multicenter studies.

Conclusions

We diagnosed cachexia using AWGC 2023 criteria in older adults with HF and investigated its prevalence, clinical characteristics, and association with clinical adverse events. Older adults with HF and cachexia have poor physical function, ADL, and nutritional status, and the cachexia associated with all-cause and cardiovascular death. The early identification and management of cachexia using AWGC 2023 criteria may help improve prognosis in this population.

Acknowledgments

The authors thank the staff members of the National Center for Geriatrics and Gerontology (Obu, Aichi, Japan), particularly Shunya Tanioku, Katsunori Hara, Koharu Oya, Junpei Sugioka, Shigeharu Tsuzuki, Moeka Isomura, and Hideki Yanagisawa (physical therapists), as well as Yoshiko Suzuki and Kaori Inaguma (research assistants).

Sources of Funding

This work was supported by the National Center for Geriatrics and Gerontology (Grant no. 22-9).

Disclosure

The authors have no conflicts of interest to declare.

Author Contributions

K.H., A.H., H.K., and H.A. contributed to study conception, design, and material preparation. K.H., A.H., I.U., T.Y., T.K., M.K., and A.S. collected the data. K.H. and K.K. performed data analysis. K.H. wrote the first draft of the manuscript. All authors read and approved the final version of the manuscript.

IRB Information

The study protocol complied with the Declaration of Helsinki, and written informed consent was obtained from each participant. The Ethics Review Board of the National Center for Geriatric and Gerontology approved this study (Approval no. 1272).

Data Availability

The deidentified participant data will not be shared.

Supplementary Files

Please find supplementary file(s);

https://doi.org/10.1253/circj.CJ-24-0805

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