Heart failure represents one of the most significant global health challenges, affecting millions worldwide and requiring subsequent hospitalization for many patients due to complications. For older adults in particular, heart failure rarely exists in isolation, often appearing alongside other chronic conditions that may compound its effects.
Because of this, the relationship between cardiovascular disease, kidney dysfunction, and metabolic disorders (such as diabetes) has gained increased attention in recent years. However, most clinical research on this topic has focused primarily on younger populations and excluded adults over 75—despite this demographic representing the majority of real-world heart failure patients. Thus, our understanding of how the overlap of multiple chronic conditions impacts outcomes in older populations with heart failure remains underexplored.
Against this backdrop, a research team led by Assistant Professor Taisuke Nakade from the Juntendo University Graduate School of Medicine, Japan, examined the association between overlapping cardiovascular, kidney, and metabolic conditions on physical function and prognosis in older heart failure patients. Their paper, published in the European Journal of Preventive Cardiology on May 6, 2025, examines these relationships in one of the largest studies specifically targeting heart failure patients aged 65 and older exclusively. The study was co-authored by Yuya Matsue, Nobuyuki Kagiyama, and Tohru Minamino, also from the Juntendo University Graduate School of Medicine.
The researchers analyzed data from 1,113 patients with an average age of 80 years who had been hospitalized for heart failure. The team categorized patients based on whether they had none, one, or multiple overlapping conditions among three key areas: atherosclerotic cardiovascular disease, chronic kidney disease, and type 2 diabetes, which were collectively referred to as cardiovascular-kidney-metabolic (CKM) conditions. While the main outcome was all-cause mortality or rehospitalization due to heart failure, the researchers also assessed physical function through various standardized tests, including walking speed, the ability to rise from a chair, and six-minute walk distance.
The results revealed that nearly half (49.5%) of the patients had two or three overlapping CKM conditions, while only 17.3% had none. Patients with multiple conditions performed significantly worse on physical function tests compared to those with fewer conditions, even after accounting for age, sex, and heart failure severity. Moreover, these patients faced a substantially higher risk of death or rehospitalization within two years following discharge.
To validate their findings, the team conducted an external validation using a separate cohort of 558 patients, which confirmed the results of the main study. This dual-cohort approach strengthens the reliability of the conclusions and their applicability to broader populations of older heart failure patients.
“ The implications of our study are twofold. For society, the findings support early identification of vulnerable individuals, enabling timely intervention and reducing the burden of rehospitalization and long-term care ,” notes Dr. Nakade. “ Meanwhile, for the healthcare industry, this research provides a cost-effective and accessible method for risk stratification without requiring advanced diagnostics, which is particularly valuable in settings with limited resources .”
To clarify this last point, incorporating CKM overlap assessment into clinical practice requires no specialized equipment or complex procedures. It is a simple evaluation that provides valuable insight into which patients may benefit most from closer monitoring and targeted interventions, such as exercise programs or nutritional support. “ By proposing a clinically feasible way to assess risk in older adults, this study contributes to improving patient outcomes, optimizing resource allocation, and promoting more sustainable healthcare systems ,” concludes Dr. Nakade.
Hopefully, as populations continue to age worldwide, researchers will bridge more existing gaps between clinical trials and real-world patient demographics, leading to better healthcare services for vulnerable individuals.
Reference
Authors
Taisuke Nakade 1 , Yuya Matsue 1 , Yoshiaki Ikeda 1 , Daichi Maeda 1,2 , Nobuyuki Kagiyama 1,3 , Yudai Fujimoto 1 , Hanako Inoue 1 , Tsutomu Sunayama 1 , Taishi Dotare 1 , Kentaro Jujo 4 , Kazuya Saito 5 , Kentaro Kamiya 6 , Hiroshi Saito 7 , Yuki Ogasahara 8 , Emi Maekawa 9 , Masaaki Konishi 10 , Takeshi Kitai 11 , Kentaro Iwata 12 , Hiroshi Wada 13 , Takatoshi Kasai 1,14 , Hirofumi Nagamatsu 15 , Misako Toki 16 , Kenji Yoshioka 17 , Shin-ichi Momomura 18 , and Tohru Minamino 1,19
Title of original paper
Association of Cardiovascular-Kidney-Metabolic Overlap with Physical Function and Prognosis in Older Patients with Heart Failure: A Post-Hoc Analysis of the FRAGILE-HF and SONIC-HF
Journal
European Journal of Preventive Cardiology
DOI
Affiliations
1 Department of Cardiovascular Biology and Medicine, Juntendo University Graduate School of Medicine
2 Department of Cardiology, Hirakata City Hospital
3 Department of Cardiology, The Sakakibara Heart Institute of Okayama
4 Department of Cardiology, Nishiarai Heart Centre Hospital
5 Department of Rehabilitation, The Sakakibara Heart Institute of Okayama
6 Department of Rehabilitation, School of Allied Health Sciences, Kitasato University
7 Department of Rehabilitation, Kameda Medical Centre
8 Department of Nursing, The Sakakibara Heart Institute of Okayama
9 Department of Cardiovascular Medicine, Kitasato University School of Medicine
10 Division of Cardiology, Yokohama City University Medical Centre
11 Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Centre
12 Department of Rehabilitation, Kobe City Medical Centre General Hospital
13 Department of Cardiovascular Medicine, Saitama Medical Centre, Jichi Medical University
14 Cardiovascular Respiratory Sleep Medicine, Juntendo University Graduate School of Medicine
15 Department of Cardiology, Tokai University School of Medicine
16 Department of Clinical Laboratory, The Sakakibara Heart Institute of Okayama
17 Department of Cardiology, Kameda Medical Centre
18 Saitama Citizens Medical Centre
19 Japan Agency for Medical Research and Development-Core Research for Evolutionary Medical Science and Technology (AMED-CREST)
About Assistant Professor Taisuke Nakade from Juntendo University Graduate School of Medicine
Taisuke Nakade is a Doctor of Medicine and Assistant Professor in the Department of Cardiovascular Biology and Medicine at the Juntendo University Graduate School of Medicine, Japan. His research encompasses a wide range of topics in cardiology, including heart failure and exercise-based cardiac rehabilitation, and he has published over 15 articles in this field. He is also a member of prestigious societies, such as the European Society of Cardiology (ESC) and the Heart Failure Association (HFA) of the ESC.
Observational study
People
6-May-2025
Disclosures: Nobuyuki Kagiyama is affiliated with a department funded by Paramount Bed Co., Ltd., based on collaborative research agreements and received honoraria from Novartis Japan, Otsuka Pharmaceutical Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., Eli Lilly Japan, AstraZeneca, AMI Inc., and EchoNous. K.K. Kentaro Kamiya received funding outside the submitted work from Eiken Chemical Co., Ltd. and SoftBank Corporation, Ltd. Takatoshi Kasai is affiliated with a department sponsored by Philips, ResMed, and Fukuda Denshi. Yuya Matsue received honoraria from Otsuka Pharmaceutical Co., Novartis Pharma K.K., Bayer Inc., and AstraZeneca, and a collaborative research grant from Pfizer Japan Inc., Otsuka Pharmaceutical Co., EN Otsuka Pharmaceutical Co., Ltd., and Nippon Boehringer Ingelheim Co., Ltd.