Heart Failure in Patients with Sarcopenia: Systematic Review and Meta-Analysis

Article information

Ann Geriatr Med Res. 2025;29(3):295-304

Publication date (electronic) : 2025 April 10

doi : https://doi.org/10.4235/agmr.24.0186

Pedro Ivo Carmo Campos^,1,2, Juliano Bergamaschine Mata Diz², Amanda Aparecida Oliveira Leopoldino¹, Marcus Vinicius Bolivar Malachias¹

¹Faculty of Medical Sciences, Fundação Educacional Lucas Machado (FELUMA), Belo Horizonte, Minas Gerais, Brazil

²Faculty of Medicine of Barbacena, Barbacena, Minas Gerais, Brazil

Corresponding Author: Pedro Ivo Carmo Campos, MD Faculty of Medical Sciences, Lucas Machado Educational Foundation, Belo Horizonte, Minas Gerais 30130-110, Brazil E-mail: pivocampos@gmail.com

Received 2024 December 9; Revised 2025 March 2; Accepted 2025 March 31.

Abstract

INTRODUCTION

Heart failure (HF) is one of the most common chronic diseases in the world, with global prevalence between 1% and 3% in individuals under 60.1,2) When it comes to individuals over 60 years old, this percentage rises to 11.8%.1) The latest prevalence projections indicate an increase up to 34% in the next decades.2) HF presents a mortality rate of 50% within 1 year after hospitalization and a 65% risk of readmission.1,3)

Prior to the 2020s, the characterization of HF was considered ambiguous and unstandardized. In 2021, international scientific societies came to a consensus. They established a universal definition of HF as “a clinical syndrome with signs and/or symptoms caused by a structural and/or functional cardiac abnormality, supported by at least one of the following: elevated natriuretic peptide levels and/or objective evidence of pulmonary or systemic congestion.”4)

The functional capacity to perform daily tasks is closely related to cardiovascular health. Once this function is compromised, symptoms such as dyspnea and/or exercise intolerance appear, directly impacting the patient’s quality of life.5) However, an exercise tolerance decrease can also be related to muscle strength loss, a consequence of the natural aging process, requiring a distinction between these conditions.6)

Sarcopenia is the process of muscle loss that affects strength, mass, and quality. It is considered severe in cases of low physical performance.7) Its prevalence varies according to the diagnostic criteria, requiring physical tests to verify muscle strength and mass loss. The gold standard methods for that are computed tomography (CT) or magnetic resonance imaging (MRI). More affordable acceptable techniques are dual-energy X-ray absorptiometry (DEXA) or bioelectrical impedance analysis (BIA).7)

There are several common factors in sarcopenia and HF natural history: the lack of physical activity increases the adrenergic tone, which leads to a phenomenon described as perpetuating HF factor; the rise of insulin resistance; atherosclerosis; inflammaging; hyperactivity of the renin-angiotensin-aldosterone system; mitochondrial dysfunction increasing reactive oxygen species; and endothelial dysfunction. These changes also promote cardiac remodeling, and leading to sarcopenia.8-10)

Sarcopenia’s prevalence in patients with HF has been estimated to be close to 34%, varying from 10% to 69%.11,12) These high rates indicate the importance of evaluating this condition as one of the causes of functional deterioration in these patients. The prevalence of HF in patients diagnosed with sarcopenia, as well as the main phenotypes and prognosis of this disease association, remains unknown.13)

In this context, this study presents a systematic review and a meta-analysis of the HF prevalence among individuals with sarcopenia by analyzing the prevalence related to left ventricular ejection fraction (LVEF), and assessing the death risk from this disease association. By doing this, it was possible to understand the impact of this comorbidity association.

MATERIALS AND METHODS

The protocol for this review was registered with PROSPERO (CRD42024531109). The methods followed the recommendations of the Joanna Briggs Institute (JBI)14) and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guideline.15)

Study Selection

Two independent reviewers (P.I.C.C. and J.B.M.D.) conducted a rigorous evaluation of titles and abstracts using the Rayyan tool,16) followed by pertinent data extraction based on a predefined form in a digital spreadsheet. Discrepancies were resolved by a third independent reviewer (A.A.O.L.). Relevant data extracted included the year of study publication, country, total population, and available data such as age, sex, diagnostic criteria used for sarcopenia and HF, and the prevalence of HF among individuals with sarcopenia. Subgroups of individuals according to outpatient or inpatient settings, available outcomes such as the hazard ratio of death, echocardiographic data, and prevalence according to LVEF were also identified.

Abstracts without complete articles, studies that did not provide population data for prevalence calculation, and those that did not clearly define the diagnoses of HF and sarcopenia or used generic terminology were excluded. Additionally, studies with a sample size smaller than 45 individuals were also excluded after sample calculation applying the Daniel & Cross formula,17) considering the general prevalence of 3% for HF.18) The systematic review flowchart was constructed according to PRISMA recommendations (Fig. 1).

Fig. 1.

The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) flow diagram of studies through the review (n=16).

RESULTS

The systematic review identified 7,080 potential titles, from which 206 full-text articles were read, incorporating 16 studies in the review.23-38) The systematic review’s evidence was described according to the selection criteria and outcomes (Table 1). As demonstrated, the primary studies included patients of both sexes, totaling 20,724 individuals with sarcopenia, of whom 92.86% were outpatients, with an estimated mean age of 62.88±11.53 years. It was possible to assess the sex difference among 9,603 individuals from 10 of the 16 primary studies, based on the available data. There is a low risk of methodological quality bias in the studies, with a Cohen's Kappa coefficient higher than 0.70 among the reviewers (Supplementary Table S3).39)

Table 1.

Characteristics of the articles included in review (16 studies)

The meta-analysis outcomes are described as follows. A prevalence of 32.84% (95% CI, 0.06–0.64; p<0.001, I²=100%) of HF was observed in patients with sarcopenia (Figs. 2, 3). There was a high risk of publication bias, as indicated by funnel plot (Supplementary Fig. S1). It was impossible to perform a sensitivity analysis of inpatients due to a single study identification, with a prevalence of 88.8% (95% CI, 0.85–0.92; p<0.05) for HF diagnosis.23) The sensitivity analysis (Fig. 2) for the prevalence of HF in outpatients with sarcopenia led to a 32.06% (95% CI, 0.06–0.61; p<0.001, I²=100%).

Fig. 2.

Central figure of the systematic review with meta-analysis: heart failure in patients with sarcopenia.

Fig. 3.

Sensitive analysis of seven studies that described the prevalence of heart failure in patients with sarcopenia. (A) Meta-analysis of prevalence of heart failure in patients with sarcopenia. (B) Sensitive analysis of prevalence of heart failure in outpatients with sarcopenia.

Subgroup analysis using random-effects model was conducted (Supplementary Fig. S2) for sarcopenia diagnostic criteria and found 76% prevalence of HF (95% CI, 0.40–1.00; p<0.001, I²=99%) in patients from Asia using the Asian Working Group on Sarcopenia criteria, 15% (95% CI, 0.02–0.34; p<0.001, I²=91%) using the European Working Group on Sarcopenia, and 38% (95% CI, 0.30–0.48; p<0.001, I²=99%) using BIA. Analysis for study design demonstrated 34% prevalence in retrospective cohort studies (95% CI, 0.29–0.39; p=0.77, I²=0%), 15% for case-control (95% CI, 0.02–0.34; p=0.02, I²=91%), and 37% for prospective studies (95% CI, 0.14–0.64; p<0.001, I²=99%). The outpatient subgroup had 30% (95% CI, 0.16–0.46; p<0.001, I²=100%). Finally, the prevalence in China was 45% (95% CI, 0.12–0.80; p<0.001, I²=99%) and in South Korea 29% (95% CI, 0.08–0.54; p<0.001, I²=99%).

The meta-analysis of the prevalence of each HF phenotype according to LVEF in individuals with sarcopenia resulted in 96.00% of prevalence for HFpEF (95% CI, 0.00–1.00; p<0.001, I²=99%), 0.5% for HFmrEF (95% CI, 0.00–0.17; p<0.001, I²=99%), and 2.00% for HFrEF (95% CI, 0.00–0.51; p<0.001, I²=99%) (Figs. 2, 4). The studies by Ko et al.24) and Zhang et al.30) were removed from the sensitivity analysis as they consisted entirely of patients with HFpEF and accounted for more than half of the population for this outcome, being considered outliers. After the sensitivity analysis the prevalence was estimated by 29.1% for HFpEF (95% CI, 0.14– 0.45; p<0.001, I²=99%), 10.3% for HFmrEF (95% CI, 0.00–0.29; p<0.001, I²=99%) and 45.9% for HFrEF (95% CI, 0.34–0.58; p<0.001, I²=90.69%) (Figs. 2, 4). Lastly, the meta-analysis of the hazard ratio of all-cause mortality in the association of sarcopenia and heart failure was 2.36 (95% CI, 1.86–3.01; p=0.99, I²=0%) (Figs. 2, 5).

Fig. 4.

Meta-analysis of the four studies that described the hazard ratio of death from all-cause in patients with sarcopenia and heart failure: (A) heart failure with preserved ejection fraction (HFpEF) prevalence, (B) heart failure with mildly reduced ejection fraction (HFmrEF) prevalence, (C) heart failure with reduced ejection fraction (HFrEF) prevalence, (D) sensitivity analysis of HFpEF prevalence, (E) sensitivity analysis of HFmrEF prevalence, (F) sensitivity analysis of HFrEF prevalence.

Fig. 5.

Meta-analysis of the four studies that described the hazard ratio of death from all-cause in patients with sarcopenia and heart failure.

DISCUSSION

This study demonstrates a prevalence of 32.84% of HF in patients with sarcopenia. This prevalence is more than 10 times the global prevalence of HF, which is 3%, and nearly three times the global population over 60, which is 11.8%.1,40) The GLISTEN study has already reported higher prevalences of HF in populations with sarcopenia and its increase with left ventricular mass.41) Sensitivity analysis showed a 32.06% prevalence of HF in outpatients with sarcopenia. In community settings, isolated HF can reach from 1.4% to 16.1%.42) Only one study allowed the evaluation of the prevalence of HF among inpatients with sarcopenia, which was 88.8% in this review. Other studies have reported a prevalence rating from 0.1% to 24.8%43,44) demonstrating Bian et al.23) influence as an outlier.

In this analysis, the average age of patients was 62.9 years; however, this value may be underestimated due to the unavailability of data from two primary studies, despite attempts to contact the authors. Two studies in this review included samples of individuals under 60 years old.25,26) It is important to note that primary sarcopenia is related to aging and can begin at 40 years old, with its prevalence in individuals under 60 years old still being poorly understood.45,46) It was impossible to estimate different types of sarcopenia in this sample, although, among non-elderly adults, a higher prevalence of secondary sarcopenia would be expected.

The universal classification of HF employs LVEF threshold for classification of HF as follows: reduced ejection fraction (HFrEF) if LVEF <40%; mildly reduced ejection fraction (HFmrEF) when LVEF is between 41%–49%; improved ejection fraction (HFimpEF) when a baseline LVEF <40% shows an increase of >10% with a subsequent measurement of LVEF >40%; and preserved ejection fraction (HFpEF) with LVEF >50%.4)

After conducting the sensitivity analyses, it was observed that among outpatients with sarcopenia associated with HF, the prevalences were 29.1% for HFpEF, 10.3% for HFmrEF, and 45.9% for HFrEF without the description of HFimpEF. One nationwide study found prevalences of 38% for HFpEF, 4% for HFmrEF, 49% for HFrEF, and 9% for HFimpEF, among the entire population with HF.47) A meta-analysis that evaluated patients with HF and sarcopenia found a 28% prevalence for HFrEF and 18% for HFpEF.48) As expected, the review found a higher prevalence of HFrEF in patients with sarcopenia, consistent with global reports from general patients.49)

The hazard ratio of all-cause mortality in the association of sarcopenia and HF was estimated at 2.36 (Figs. 2, 5). A cohort identified the all-cause mortality hazard ratio to be 2.150) in patients with HF compared to the general population. Another evidence revealed that HF alone has a mortality hazard ratio of 2.2,4) with an increase of 1.7351) for every 10-year increase over the age of 60 and 1.14 increase51) for every 5% reduction in LVEF below 45%. Previous reviews showed a mortality hazard ratio of 2.2852) in patients with sarcopenia in intensive care and 1.9952) in inpatients. Another recent meta-analysis estimated the hazard ratio of death in individuals with sarcopenia overlapping with HF to be 2.06.48) We speculate that the association of sarcopenia and HF increases the hazard ratio of death from all causes, regardless of LVEF and the outpatient, inpatient, or even intensive care setting.

Subgroup analysis showed a higher prevalence of HF using adapted criteria for sarcopenia based on population characteristics, which can be attributed to an underdiagnosis of HF in patients with sarcopenia, considering that most of the population was from an Asian background. The correct criteria enable an adequate diagnosis and provide an accurate perspective of epidemiological data.45) Retrospective cohort studies have shown a prevalence of 34%, corroborating the meta-analysis prevalence with low heterogeneity. Other subgroup analyses persist with high heterogeneity or do not reflect any clinical relevance beyond the characteristics of the primary studies.53)

This study has some limitations. There is high heterogeneity in the outcomes, even using IVhet, which does not reduce the external validity, considering that prevalence studies can reflect population heterogeneity.54,55) Regardless of the heterogeneity of this analysis, composed exclusively of observational studies, and the high risk of publication bias, there was a low risk of methodological quality bias, as estimated by the JBI tool.19) It was not possible to estimate the sex-related prevalences of HF and its LVEF phenotypes due to the absence of available data.

The prevalence of HF in patients with sarcopenia remained uncertain until the present study. Considering the importance of identifying sarcopenia as a primary disease and not merely as a comorbidity, we demonstrated a high prevalence of HF among patients with sarcopenia, and this association presents a greater death risk than these conditions individually. It is possible that other conditions, such as aging-related inflammation (inflammaging), pro-inflammatory factors leading to worsening oxidative stress, and progressive physical effort restriction, among others, may predispose to HF as an underlying condition to sarcopenia, which by itself justifies the present study.10)

Our findings highlight a significant reality, demonstrating that one-third of outpatients with sarcopenia presents HF, and HFrEF is the most prevalent phenotype. Therefore, this study underscores the need for a more thorough investigation of patients with reduced exercise capacity or oligosymptomatic conditions, aiming to identify both sarcopenia and HF, with special attention to the possibility of HFpEF as another subdiagnosed condition. It’s essential to consider that these conditions are typically underdiagnosed and undertreated, and their association results in a higher risk of death.

Numerous factors are inherent to the natural history of sarcopenia and HF. The limitation in physical exertion leads to the hyperactivation of muscle ergoreceptors, increasing adrenergic tone, causing a phenomenon described as perpetuating HF, and downregulating genes related to glucose and lipid metabolism. This contributes to insulin resistance and atherosclerosis, exacerbates inflammaging, a process associated with aging characterized by elevated levels of pro-inflammatory plasmatic substances. These lead to progressive immune dysregulation, hyperactivity of the renin-angiotensin-aldosterone system, mitochondrial dysfunction with increased reactive oxygen species, and endothelial dysfunction. All those changes promote cardiac remodeling, marked by cardiomyocyte atrophy with compensatory hypertrophy of the remaining cells, resulting in sarcopenia.8-10)

Not all patients with HF got dyspnea from pulmonary congestion and elevated cardiac filling pressures or fatigue caused by low muscle perfusion. Sarcopenia itself appears to reduce exercise intolerance. Studies in patients with both conditions have shown improvements in exercise tolerance with physical training, independent of improvement in cardiac diastolic dysfunction, which lead to the hypotheses of “peripheral” mechanisms that mediate effort intolerance.56)

In conclusion, the prevalence of HF in adults with sarcopenia was estimated at 32%, which is more than 10 times higher than the global population. Among patients with sarcopenia and associated HF, prevalences were 45.9% for HFrEF, 29.1% for HFpEF, and 10.3% for HFmrEF. The diagnosis of HF in patients with sarcopenia presents an all-cause death hazard ratio of 2.36, higher than the mortality rates of these individual conditions. These findings underscore the need for higher-quality primary studies to evaluate further association and impact of HF among individuals with sarcopenia. Healthcare professionals should be vigilant in identifying sarcopenia and the potential association with HF, especially HFpEF, in patients with reduced exercise capacity and oligosymptomatic conditions. These conditions are usually underdiagnosed and related to a worse prognosis.

SUPPLEMENTARY MATERIALS

Article information Continued