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Sex differences in Cardiorenal Syndrome: Insights from CARDIOREN Registry

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Abstract

Purpose of the Work

Although sex-specific differences in heart failure (HF) or kidney disease (KD) have been analyzed separately, the predominant cardiorenal phenotype by sex has not been described. This study aims to explore the sex-related differences in cardiorenal syndrome (CRS) in a contemporary cohort of outpatients with HF.

Findings

An analysis of the Cardiorenal Spanish registry (CARDIOREN) was performed. CARDIOREN Registry is a prospective multicenter observational registry including 1107 chronic ambulatory HF patients (37% females) from 13 Spanish HF clinics. Estimated Glomerular Filtration Rate (eGFR) < 60 ml/min/1.73 m2 was present in 59.1% of the overall HF population, being this prevalence higher in the female population (63.2% vs. 56.6%, p = 0.032, median age: 81 years old, IQR:74–86). Among those with kidney dysfunction, women displayed higher odds of showing HF with preserved ejection fraction (HFpEF) (odds ratio [OR] = 4.07; confidence interval [CI] 95%: 2.65–6.25, p < 0.001), prior valvular heart disease (OR = 1.76; CI 95%:1.13–2.75, p = 0.014), anemia (OR: 2.02; CI 95%:1.30–3.14, p = 0.002), more advanced kidney disease (OR for CKD stage 3: 1.81; CI 95%:1.04–3.13, p = 0.034; OR for CKD stage 4: 2.49, CI 95%:1.31–4.70, p = 0.004) and clinical features of congestion (OR:1.51; CI 95%: 1.02–2.25, p = 0.039). On the contrary, males with cardiorenal disease showed higher odds of presenting HF with reduced ejection fraction (HFrEF) (OR:3.13; CI 95%: 1.90–5.16, p < 0.005), ischemic cardiomyopathy (OR:2.17; CI 95%: 1.31–3.61, p = 0.003), hypertension (OR = 2.11; CI 95%:1.18–3.78, p = 0.009), atrial fibrillation (OR:1.71; CI 95%: 1.06–2.75, p = 0.025), and hyperkalemia (OR:2.43, CI 95%: 1.31–4.50, p = 0.005).

Summary

In this contemporary registry of chronic ambulatory HF patients, we observed sex-related differences in patients with combined heart and kidney disease. The emerging cardiorenal phenotype characterized by advanced CKD, congestion, and HFpEF was predominantly observed in women, whereas HFrEF, ischemic etiology, hypertension, hyperkalemia, and atrial fibrillation were more frequently observed in men.

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Data Availability

The raw data supporting the conclusion of this article will be made available by the authors, under request.

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Acknowledgements

The editors would like to thank Dr. Eduardo Zatarain for taking the time to handle the review of this manuscript.

Funding

Supported by AstraZeneca Farmacéutica Spain, S.A.

Author information

Author notes

  1. Marta Cobo Marcos, Rafael de la Espriella equally first authors.

Authors and Affiliations

  1. Department of Cardiology, Hospital Universitario Puerta de Hierro Majadahonda (IDIPHISA), Madrid, Spain

    Marta Cobo Marcos & Ramón Garrido González

  2. Centro de Investigación Biomédica en Red en Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain

    Marta Cobo Marcos & Julio Núñez

  3. Department of Cardiology, Hospital Clínico Universitario de Valencia (INCLIVA), Valencia, Spain

    Rafael de la Espriella & Julio Núñez

  4. Department of Cardiology, Hospital Universitario Arnau de Vilanova, Institut de Recerca Biomèdica de Lleida (IRBLleida), Lleida, Spain

    Jara Gayán Ordás

  5. Department of Cardiology, Hospital de La Santa Creu I Sant Pau, Barcelona, Spain

    Isabel Zegrí & Antonia Pomares

  6. Internal Medicine Department, Hospital Universitario Ramón Y Cajal, IRYCIS, Madrid, Spain. Department of Medicine and Medical Specialties, Facultad de Medicina y Ciencias de la Salud, Universidad de Alcalá, Madrid, Spain

    Pau Llácer

  7. Department of Cardiology, Hospital Universitari Dr. Josep Trueta., Girona, Spain

    Aleix Fort

  8. Department of Cardiology, Hospital Universitario La Paz, Madrid, Spain

    Adriana Rodríguez Chavarri & Almudena Castro

  9. Department of Cardiology, Hospital Universitario Vall d´Hebron, Barcelona, Spain

    Ana Méndez

  10. Department of Cardiology, Hospital Universtiario Gregorio Marañón, Madrid, Spain

    Zorba Blázquez

  11. Department of Cardiology, Hospital Universitario Doce de Octubre, Madrid, Spain

    Pedro Caravaca Pérez

  12. Department of Internal Medicine, Hospital Universitario Lozano Blesa, University of Zaragoza, Saragossa, Spain

    Jorge Rubio Gracia

  13. Department of Cardiology, Hospital Universitario Virgen Macarena, Seville, Spain

    Alejandro Recio-Mayoral

  14. Department of Cardiology, Hospital Universitario Virgen de La Victoria, Málaga, Spain

    Jose Manuel García Pinilla

  15. Department of Nephrology, Hospital Universitario Vall d´Hebron, Barcelona, Spain

    Maria Jose Soler

  16. Department of Nephrology, Hospital Clínico Universitario Valencia (INCLIVA), University of Valencia, Valencia, Spain

    Jose Luis Górriz & Miguel González Rico

Authors
  1. Marta Cobo Marcos
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  2. Rafael de la Espriella
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  3. Jara Gayán Ordás
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Corresponding author

Correspondence to Julio Núñez.

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Conflict of Interest

All the authors report grants from Astra Zeneca during the conduct of the study. Dr. Cobo Marcos reports personal fees from ASTRA ZENECA, VIFOR PHARMA, NOVARTIS, ROVI, BOEHRINGHER INGELHEIM, NOVONORDISK, ESTEVE and BAYER; Dr Pomares reports personal fees from PFIZER, and support for attending meetings from NOVARTIS AND BAYER, Dr Méndez reports personal fees from ASTRA ZENECA, support for attending meetings from NOVARTIS, and participation on a Data Safety Monitoring Board or Advisory Board from BAYER; Dr Rubio reports personal fees from ASTRA ZENECA, NOVARTIS, BOEHRINGHER INGELHEIM, ESTEVE, and BAYER; Dr Recio reports personal fees from ASTRA ZENECA, NOVARTIS, BOEHRINGHER INGELHEIM, JANSSEN, BAYER, MSD and support for attending meetings from BAYER, MSD and NOVARTIS;. Dr Garía Pinilla reports personal fees from ASTRA ZENECA, VIFOR PHARMA, NOVARTIS, BOEHRINGHER INGELHEIM, PFIZER and BAYER, Dr Soler Romeo reports personal fees from NovoNordisk, Jansen, Boehringer, Mundipharma, Esteve, Fresenius, Ingelheim Lilly, Vifor, ICU Medical, Travere Therapeutics, GE Healthcare, grants and personal fees from AstraZeneca, Editor in Chief of CKJ; In addition, Dr. Soler Romeo has a patent 202131356 issued; Dr Núñez reports, grants from VIFOR PHARMA, personal fees from NOVARTIS, ROVI, BOEHRINGHER INGELHEIM, NOVONORDISK and BAYER. All other authors declare no competing interests.

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11897_2023_598_MOESM1_ESM.docx

Supplementary file 1 Sex stratified basal characteristics across kidney disease categories. eGFR: estimated glomerular filtration rate; COPD, chronic obstructive pulmonary disease; HF: heart failure; BMI: body mass index; NYHA, New York Heart Association; SBP: systolic blood pressure; DBP: diastolic blood pressure; LVEF: left ventricular ejection fraction; LVH: left ventricular hypertrophy; TAPSE: tricuspid annular plane systolic excursion; sPAP: systolic pulmonary artery pressure; NTproBNP: N-terminal pro-brain natriuretic peptide; CA125: cancer antigen 125; ACEi, angiotensin-converting enzyme inhibitors; ARB, angiotensin II receptor blockers; MRA: mineralocorticoids receptor antagonists; SLGT2i: Sodium-glucose cotransporter inhibitors; IV: intravenous; ESA: erythropoiesis-stimulating agent; VKa: Vitamin K antagonists; DOACs: Direct oral anticoagulants. * Values expressed as median (interquartile range). Ç Defined as serum ferritin <100 ng/mL or, serum ferritin 100-299 ng/mL + transferrin saturation <20%. Data available in 1020 patients. † Last 3 months (DOCX 41 KB)

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Cobo Marcos, M., de la Espriella, R., Gayán Ordás, J. et al. Sex differences in Cardiorenal Syndrome: Insights from CARDIOREN Registry. Curr Heart Fail Rep 20, 157–167 (2023). https://doi.org/10.1007/s11897-023-00598-x

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