Abstract

Aims

Sleep apnoea and congestive heart failure (CHF) commonly co‐exist, but their interaction is unclear. Metabolomics may clarify their interaction and relationships to outcome.

Methods and results

We assayed 372 circulating metabolites and lipids in 1919 and 1524 participants of the Framingham Heart Study (FHS) (mean age 54 ± 10 years, 53% women) and Women's Health Initiative (WHI) (mean age 67 ± 7 years), respectively. We used linear and Cox regression to relate plasma concentrations of metabolites and lipids to echocardiographic parameters; CHF and its subtypes heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF); and sleep indices. Adenine dinucleotide phosphate (ADP) associated with left ventricular (LV) fractional shortening; phosphocreatine with LV wall thickness; lysosomal storage molecule sphingomyelin 18:2 with LV mass; and nicotine metabolite cotinine with time spent with an oxygen saturation less than 90% (β = 2.3 min, P = 2.3 × 10−5). Pro‐hypertrophic metabolite hydroxyglutarate partly mediated the association between LV wall thickness and HFpEF. Central sleep apnoea was significantly associated with HFpEF (P = 0.03) but not HFrEF (P = 0.5). There were three significant metabolite canonical variates, one of which conferred protection from cardiovascular death [hazard ratio = 0.3 (0.11, 0.81), P = 0.02].

Conclusions

Energetic metabolites were associated with cardiac function; energy‐ and lipid‐storage metabolites with LV wall thickness and mass; plasma levels of nicotine metabolite cotinine were associated with increased time spent with a sleep oxygen saturation less than 90%, a clinically significant marker of outcome, indicating a significant hazard for smokers who have sleep apnoea.

Details

Title
Metabolite signatures of heart failure, sleep apnoea, their interaction, and outcomes in the community
Author
Dutta, Shashwati 1 ; Li, Desmond 2 ; Wang, Andy 3 ; Ishak, Mark 4 ; Cook, Kristina 5 ; Farnham, Melissa 4 ; Dissanayake, Hasthi 5 ; Cistulli, Peter 5 ; Hunyor, Imre 6 ; Liu, Renping 7 ; Wilcox, Ian 6 ; Koay, Yen Chin 7 ; Yang, Jean 8 ; Lal, Sean 9 ; O'Sullivan, John F. 10   VIAFID ORCID Logo 

1  Heart Research Institute, Charles Perkins Centre, The University of Sydney, Camperdown, Sydney, NSW, Australia, School of Mathematics and Statistics, The University of Sydney, Camperdown, Sydney, NSW, Australia, Precision Cardiovascular Laboratory, The University of Sydney, Camperdown, Sydney, NSW, Australia 
2  Heart Research Institute, Charles Perkins Centre, The University of Sydney, Camperdown, Sydney, NSW, Australia, Precision Cardiovascular Laboratory, The University of Sydney, Camperdown, Sydney, NSW, Australia 
3  Northern Clinical School, Sydney Medical School, The University of Sydney, Camperdown, Sydney, NSW, Australia 
4  Heart Research Institute, Charles Perkins Centre, The University of Sydney, Camperdown, Sydney, NSW, Australia 
5  Northern Clinical School, Sydney Medical School, The University of Sydney, Camperdown, Sydney, NSW, Australia, Charles Perkins Centre, The University of Sydney, Camperdown, Sydney, NSW, Australia 
6  Department of Cardiology, Royal Prince Alfred Hospital, Camperdown, Sydney, NSW, Australia, Central Clinical School, Sydney Medical School, The University of Sydney, Camperdown, Sydney, NSW, Australia 
7  Heart Research Institute, Charles Perkins Centre, The University of Sydney, Camperdown, Sydney, NSW, Australia, Precision Cardiovascular Laboratory, The University of Sydney, Camperdown, Sydney, NSW, Australia, Central Clinical School, Sydney Medical School, The University of Sydney, Camperdown, Sydney, NSW, Australia 
8  School of Mathematics and Statistics, The University of Sydney, Camperdown, Sydney, NSW, Australia, Charles Perkins Centre, The University of Sydney, Camperdown, Sydney, NSW, Australia 
9  Precision Cardiovascular Laboratory, The University of Sydney, Camperdown, Sydney, NSW, Australia, Charles Perkins Centre, The University of Sydney, Camperdown, Sydney, NSW, Australia, Department of Cardiology, Royal Prince Alfred Hospital, Camperdown, Sydney, NSW, Australia, Central Clinical School, Sydney Medical School, The University of Sydney, Camperdown, Sydney, NSW, Australia 
10  Heart Research Institute, Charles Perkins Centre, The University of Sydney, Camperdown, Sydney, NSW, Australia, Precision Cardiovascular Laboratory, The University of Sydney, Camperdown, Sydney, NSW, Australia, Charles Perkins Centre, The University of Sydney, Camperdown, Sydney, NSW, Australia, Department of Cardiology, Royal Prince Alfred Hospital, Camperdown, Sydney, NSW, Australia, Central Clinical School, Sydney Medical School, The University of Sydney, Camperdown, Sydney, NSW, Australia, Faculty of Medicine, TU Dresden, Dresden, Germany 
Pages
5392-5402
Section
Original Articles
Publication year
2021
Publication date
Dec 1, 2021
Publisher
Oxford University Press
e-ISSN
20555822
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1002/ehf2.13631
ProQuest document ID
2614533046
Copyright
© 2021. This work is published under http://creativecommons.org/licenses/by-nc-nd/4.0/ (the "License"). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.