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Obesity-Related Genetic Determinants of Heart Failure Prognosis

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Abstract

Purpose

Recent advances in genomics offer a smart option for predicting future risk of disease and prognosis. The objective of this study was to examine the prognostic value in heart failure (HF) patients, of a series of single nucleotide polymorphisms (SNPs).

Methods

A selection of 192 SNPs found to be related with obesity, body mass index, circulating lipids or cardiovascular diseases were genotyped in 191 patients with HF. Anthropometrical and clinical variables were collected for each patient, and death and readmission by HF were registered as the primary endpoint.

Results

A total of 53 events were registered during a follow-up period of 438 (263–1077) days (median (IQR)). Eight SNPs strongly related to obesity and HF prognosis were selected as possible prognostic variables. From these, rs10189761 and rs737337 variants were independently associated with HF prognosis (HR 2.295 (1.287–4.089, 95% CI); p = 0.005), whereas rs10423928, rs1800437, rs737337 and rs9351814 were related with bad prognosis only in obese patients (HR 2.142 (1.438–3.192, 95% CI); p = 0.00018). Combined scores of the genomic variants were highly predictive of poor prognosis.

Conclusions

SNPs rs10189761 and rs737337 were identified, for the first time, as independent predictors of major clinical outcomes in patients with HF. The data suggests an additive predictive value of these SNPs for a HF prognosis. In particular for obese patients, SNPs rs10423928, rs1800437, rs737337 and rs9351814 were related with a bad prognosis. Combined scores weighting the risk of each genomic variant could effect interesting new tools to stratify the prognostic risk of HF patients.

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Funding

This study was funded by Instituto de Salud Carlos III, Spain, (ISCIII/PIE13/00024/Cofinanciado FEDER). The work of Beatriz Paradela-Dobarro was supported by ISCIII/FI11/00325. The genotyping service was carried out at CEGEN-PRB2-ISCIII, funded by grant PT13/0001, ISCIII-SGEFI/FEDER.

Author information

Author notes

  1. R. M. Agra, M. Gago-Dominguez, A. Carracedo and J. R. Gonzalez-Juanatey contributed equally to this work.

Authors and Affiliations

  1. Laboratorio no. 6. Edif. Consultas externas (planta -2), Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), Servicio de Cardiología y Unidad de Hemodinámica, Complexo Hospitalario Universitario de Santiago de Compostela (CHUS), SERGAS, Travesía da Choupana s/n, Santiago de Compostela, 15706, A Coruña, Spain

    R. M. Agra, B. Paradela-Dobarro, L. Alvarez, A. Fernandez-Trasancos, A. Varela-Roman, S. Eiras, E. Alvarez & J. R. Gonzalez-Juanatey

  2. CIBERCV, Madrid, Spain

    R. M. Agra, B. Paradela-Dobarro, L. Alvarez, A. Fernandez-Trasancos, A. Varela-Roman, S. Eiras, E. Alvarez & J. R. Gonzalez-Juanatey

  3. Fundación Pública Galega de Medicina Xenómica, SERGAS, Santiago de Compostela, Spain

    M. Gago-Dominguez & A. Carracedo

  4. Grupo de Medicina Xenómica, CeGen-PRB2, Instituto de Investigación Sanitaria de Santiago, Universidade de Santiago de Compostela, Santiago de Compostela, Spain

    M. Torres-Español

  5. Centro de Investigación en Medicina Molecular y Enfermedades Crónicas, CIMUS, Universidad de Santiago de Compostela, Santiago de Compostela, Spain

    M. Calaza

Authors
  1. R. M. Agra
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  2. M. Gago-Dominguez
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  3. B. Paradela-Dobarro
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  5. L. Alvarez
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  6. A. Fernandez-Trasancos
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  7. A. Varela-Roman
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  8. M. Calaza
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  9. S. Eiras
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  10. E. Alvarez
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  11. A. Carracedo
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  12. J. R. Gonzalez-Juanatey
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Corresponding author

Correspondence to E. Alvarez.

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The authors declare that they have no conflict of interest.

Ethical Approval

All procedures performed in this study involving human participants were in accordance with the ethical standards of the institutional and the Ethics Committee for Human Studies at Galicia (Spanish region) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Agra, R.M., Gago-Dominguez, M., Paradela-Dobarro, B. et al. Obesity-Related Genetic Determinants of Heart Failure Prognosis. Cardiovasc Drugs Ther 33, 415–424 (2019). https://doi.org/10.1007/s10557-019-06888-8

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