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Metabolomics may clarify their interaction and relationships to outcome.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>We assayed 372 circulating metabolites and lipids in 1919 and 1524 participants of the Framingham Heart Study (FHS) (mean age 54 \u00b1 10 years, 53% women) and Women's Health Initiative (WHI) (mean age 67 \u00b1 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% (\u03b2 = 2.3 min, P = 2.3 \u00d7 10\u22125). 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].<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ehf2.13631","type":"journal-article","created":{"date-parts":[[2021,10,21]],"date-time":"2021-10-21T01:12:49Z","timestamp":1634778769000},"page":"5392-5402","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Metabolite Signatures of Heart Failure, Sleep Apnoea, their Interaction, and Outcomes in the Community"],"prefix":"10.1093","volume":"8","author":[{"given":"Shashwati","family":"Dutta","sequence":"first","affiliation":[{"name":"Heart Research Institute, Charles Perkins Centre, The University of Sydney , Camperdown, Sydney, NSW, 2006 ,","place":["Australia"]},{"name":"School of Mathematics and Statistics, The University of Sydney , Camperdown, Sydney, NSW ,","place":["Australia"]},{"name":"Precision Cardiovascular Laboratory, The University of Sydney , Camperdown, Sydney, NSW 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