Metabolite signatures of heart failure, sleep apnoea, their interaction, and outcomes in the community

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.

Changes in human sweat metabolome conditioned by severity of obstructive sleep apnea and intermittent hypoxemia

“…Apnea was defined as a significant decrease (>90%) in oronasal flow for >10 s, and hypopnea as an evident decrease in airflow of >30%, but <90%, and associated with either oxygen desaturation ≥3% and/or arousal. Monitored respiratory variables were the AHI, defined as the sum of apnea and hypopnea events occurring per hour, minimum SpO 2 , ODI, described as the number of decreases in SpO 2 ≥3% per sleep hour, and finally, T90, which represents the hypoxemia severity (Dutta et al, 2021). PSGs were considered valid for diagnosis when >180 min sleep was recorded (Kapur et al, 2017).…”

“…/or arousal. Monitored respiratory variables were the AHI, defined as the sum of apnea and hypopnea events occurring per hour, minimum SpO 2 , ODI, described as the number of decreases in SpO 2 ≥3% per sleep hour, and finally, T90, which represents the hypoxemia severity(Dutta et al, 2021). PSGs were considered valid for diagnosis when >180 min sleep was recorded(Kapur et al, 2017).…”

Genomic, Proteomic, and Metabolic Comparisons of Small Animal Models of Heart Failure With Preserved Ejection Fraction: A Tale of Mice, Rats, and Cats

“…Analysis of metabolites from participants of the Framingham Heart Study and Women's Health Initiative revealed an association of HFpEF with sleep apnea because of the proteinogenic amino acid glycine and ribose, which can feed into the pentose phosphate pathway. 35 After multivariable adjustment for age, sex, and body mass index, 11 metabolites were associated with incident HFpEF. The top associated metabolite was ornithine, likely from perturbed arginine and NO metabolism.…”

Metabolomic Association and Risk Prediction With Heart Failure in Older Adults

“…Circulating metabolites from several pathways, that are amino acids, nucleotides, lipids, and acylcarnitines have been associated with HF risk among middle-aged populations. [3][4][5][6][7] Metabolic differences are observed in HF subtypes suggesting potential distinctions derived from underlying molecular pathways. Patients with HF with reduced ejection fraction (HFrEF) had higher levels of acylcarnitines than patients with HF with preserved ejection fraction (HFpEF), while patients with HFpEF had higher levels of metabolites reflecting inflammation or oxidative stress than patients with HFpEF.…”