Cachectic Biomarkers As Confounders Behind the Obesity Paradox in Patients with Acute Decompensated Heart Failure

Overview

Journal Int J Obes (Lond)

Date 2025 Jan 25

PMID 39863776

Authors

Yusuke Miura

Satoshi Higuchi

Takashi Kohno

Yasuyuki Shiraishi

Mitsunobu Kitamura

Yuji Nagatomo

Yumiko Kawakubo Ichihara

Atsushi Mizuno

Shintaro Nakano

Kyoko Soejima

Ayumi Goda

Shun Kohsaka

Tsutomu Yoshikawa

Affiliations

Soon will be listed here.

Abstract

Background: Obesity is a risk factor for heart failure (HF) development but is associated with a lower incidence of mortality in HF patients. This obesity paradox may be confounded by unrecognized comorbidities, including cachexia.

Methods: A retrospective assessment was conducted using data from a prospectively recruiting multicenter registry, which included consecutive acute heart failure patients. A low, normal, and high body mass index (BMI) was defined as <20 kg/m, 20-25 kg/m, and ≥25 kg/m, respectively. Cachexia was defined as a combination of BMI < 20 kg/m and any biochemical abnormalities including albumin, hemoglobin, or C-reactive protein. Patients with either of the three biochemical abnormalities were categorized as those with cachectic biomarkers. Two-year all-cause, cardiac, and noncardiac mortality were evaluated.

Results: This study evaluated 3314 patients (mean BMI, 22 ± 4 kg/m [low BMI with cachexia, 828 (25%); low BMI without cachexia, 273 (8%); normal BMI, 1584 (48%); high BMI, 629 (19%)]). Overall, an increase of 1 point in BMI was associated with a decreased incidence of all-cause mortality (adjusted hazard ratio [HR], 0.92; 95% confidence interval [CI], 0.90-0.94; p < 0.001). Regardless of the mode of death, the low BMI with cachexia indicated the worst prognosis, while the low BMI without cachexia showed a similar prognosis to the normal BMI. Cachectic biomarkers, which were observed more frequently in the low BMI, predicted a higher incidence of 2-year all-cause mortality across the BMI categories (adjusted HR for the low BMI, 1.90; 95% CI, 1.30-2.77; p = 0.001; adjusted HR for the normal BMI, 1.94; 95% CI, 1.34-2.79; p < 0.001; adjusted HR for the high BMI, 3.60; 95% CI, 1.61-8.08; p = 0.002).

Conclusions: BMI could be only a surrogate marker. The cachectic biomarkers may reflect the underlying conditions and contribute to elucidating the obesity paradox.

References

Savarese G, Lund L . Global Public Health Burden of Heart Failure. Card Fail Rev. 2017; 3(1):7-11. PMC: 5494150. DOI: 10.15420/cfr.2016:25:2. View

Kenchaiah S, Evans J, Levy D, Wilson P, Benjamin E, Larson M . Obesity and the risk of heart failure. N Engl J Med. 2002; 347(5):305-13. DOI: 10.1056/NEJMoa020245. View

Horwich T, Fonarow G, Hamilton M, Maclellan W, Woo M, TILLISCH J . The relationship between obesity and mortality in patients with heart failure. J Am Coll Cardiol. 2001; 38(3):789-95. DOI: 10.1016/s0735-1097(01)01448-6. View

Shah R, Gayat E, Januzzi Jr J, Sato N, Cohen-Solal A, DiSomma S . Body mass index and mortality in acutely decompensated heart failure across the world: a global obesity paradox. J Am Coll Cardiol. 2013; 63(8):778-85. DOI: 10.1016/j.jacc.2013.09.072. View

Horwich T, Fonarow G, Clark A . Obesity and the Obesity Paradox in Heart Failure. Prog Cardiovasc Dis. 2018; 61(2):151-156. DOI: 10.1016/j.pcad.2018.05.005. View

Seko Y, Kato T, Morimoto T, Yaku H, Inuzuka Y, Tamaki Y . Association between body mass index and prognosis of patients hospitalized with heart failure. Sci Rep. 2020; 10(1):16663. PMC: 7542148. DOI: 10.1038/s41598-020-73640-w. View

Jones N, Ordonez-Mena J, Roalfe A, Taylor K, Goyder C, Hobbs F . Body mass index and survival in people with heart failure. Heart. 2023; 109(20):1542-1549. PMC: 10579501. DOI: 10.1136/heartjnl-2023-322459. View

Ruan G, Deng L, Xie H, Shi J, Liu X, Zheng X . Systemic inflammation and insulin resistance-related indicator predicts poor outcome in patients with cancer cachexia. Cancer Metab. 2024; 12(1):3. PMC: 10809764. DOI: 10.1186/s40170-024-00332-8. View

Chailleux E, Laaban J, Veale D . Prognostic value of nutritional depletion in patients with COPD treated by long-term oxygen therapy: data from the ANTADIR observatory. Chest. 2003; 123(5):1460-6. DOI: 10.1378/chest.123.5.1460. View

10.

Alahmad M, Acharya P, Gibson C, Wiley M, Hockstad E, Gupta K . Cachexia Is Associated With Adverse Outcomes in Patients Admitted With Heart Failure. Am J Cardiol. 2022; 186:30-35. DOI: 10.1016/j.amjcard.2022.10.017. View

11.

Evans W, Morley J, Argiles J, Bales C, Baracos V, Guttridge D . Cachexia: a new definition. Clin Nutr. 2008; 27(6):793-9. DOI: 10.1016/j.clnu.2008.06.013. View

12.

Franssen C, Chen S, Hamdani N, Paulus W . From comorbidities to heart failure with preserved ejection fraction: a story of oxidative stress. Heart. 2015; 102(4):320-30. DOI: 10.1136/heartjnl-2015-307787. View

13.

Shiraishi Y, Kohsaka S, Abe T, Mizuno A, Goda A, Izumi Y . Validation of the Get With The Guideline-Heart Failure risk score in Japanese patients and the potential improvement of its discrimination ability by the inclusion of B-type natriuretic peptide level. Am Heart J. 2015; 171(1):33-9. DOI: 10.1016/j.ahj.2015.10.008. View

14.

Ho K, Anderson K, Kannel W, Grossman W, Levy D . Survival after the onset of congestive heart failure in Framingham Heart Study subjects. Circulation. 1993; 88(1):107-15. DOI: 10.1161/01.cir.88.1.107. View

15.

Ota T, Takamura T, Hirai N, Kobayashi K . Preobesity in World Health Organization classification involves the metabolic syndrome in Japanese. Diabetes Care. 2002; 25(7):1252-3. DOI: 10.2337/diacare.25.7.1252. View

16.

Hickson M . Malnutrition and ageing. Postgrad Med J. 2006; 82(963):2-8. PMC: 2563720. DOI: 10.1136/pgmj.2005.037564. View

17.

Higuchi S, Kohno T, Kohsaka S, Shiraishi Y, Takei M, Goda A . Different Impact of Beta-Blockers on Long-Term Mortality in Heart Failure Patients with and without Chronic Obstructive Pulmonary Disease. J Clin Med. 2021; 10(19). PMC: 8509631. DOI: 10.3390/jcm10194378. View

18.

Sato Y, Yoshihisa A, Kimishima Y, Yokokawa T, Abe S, Shimizu T . Prognostic factors in heart failure patients with cardiac cachexia. J Geriatr Cardiol. 2020; 17(1):26-34. PMC: 7008099. DOI: 10.11909/j.issn.1671-5411.2020.01.008. View

19.

Kanda Y . Investigation of the freely available easy-to-use software 'EZR' for medical statistics. Bone Marrow Transplant. 2012; 48(3):452-8. PMC: 3590441. DOI: 10.1038/bmt.2012.244. View

20.

Higuchi S, Matsumoto H, Masaki R, Hirano T, Fuse S, Tanisawa H . Potential confounders of the obesity paradox in older patients following transcatheter aortic valve replacement. Eur Geriatr Med. 2023; 15(1):179-187. DOI: 10.1007/s41999-023-00855-1. View