Metabolomic signatures of cardiac remodelling and heart failure risk in the community

Abstract

Aims Heart failure (HF) is associated with several metabolic changes, but it is unknown whether distinct components of the circulating metabolome may be related to cardiac structure and function, and with incident HF in the community. Methods and results We assayed 217 circulating metabolites in 2336 Framingham Study participants (mean age 55 ± 10 years, 53% women) without HF at baseline. We used linear and Cox regression to relate concentrations of metabolites to left ventricular (LV) diastolic dimension, LV wall thickness, LV ejection fraction, left atrial dimension, LV ventricular mass, and aortic root size cross-sectionally and to incident HF prospectively. Bonferroni-adjusted P-values <0.05 denoted statistical significance. Circulating concentrations of kynurenine [β = À0.12 cm per standard deviation (SD) increment in normalized residual of metabolite, P = 7.3 × 10 À8 ] and aminoadipate (À0.11 cm per SD increment, P = 2.61 × 10 À5) were associated with left ventricular diastolic dimension, phosphatidylcholine (carbon:double bound = 38:6) with left atrial dimension (0.10 cm per SD increment, P = 9.7 × 10 À6), and cholesterol ester (carbon:double bound = 20:5) with left atrial dimension (0.10 cm per SD increment, P = 1.4 × 10 À5) in multivariable-adjusted models. During an average follow-up of 15.8 (range 0.02-23.2) years, 113 participants (5%) were diagnosed with HF with reduced ejection fraction and 106 individuals (5%) with HF with preserved ejection fraction. In multivariable analyses, concentrations of phosphatidylcholine (hazard ratio 0.63, P = 1.3 × 10 À5) and ornithine (hazard ratio 1.44, P = 0.00014) were associated with HF with reduced ejection fraction. Conclusions Several metabolites, including the vasoactive metabolite kynurenine, were related to cardiac structure and function in our sample. Additional research is warranted to confirm our observations and investigate if these metabolites can risk stratify ambulatory individuals.

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

“…Glutamine was inversely associated with heart rate ( β = −13, P = 1 × 10 −4 ). As previously reported for prevalent association, 5 we also found asparagine to be associated with LV internal dimension.…”

“…We confirm several previous metabolite associations with cardiac remodelling parameters and heart failure. Increased α‐ketoglutarate correlated with increased LV wall thickness, while increased asparagine demonstrated an association with increased LV diastolic dimension 5,13 . Higher levels of ornithine, which has a role in the urea cycle, were associated with CHF 5 .…”

“…Metabolomics is emerging as a useful tool to uncover molecular signatures of heart failure and outcome 5 . Therefore, to help generate insight into the potential interaction of HFpEF and/or HFrEF with sleep apnoea, we explored the relationships between metabolites and cardiac structure, function, heart failure, and sleep apnoea indices in ~2000 individuals in the community.…”

Lipid Metabolite Biomarkers in Cardiovascular Disease: Discovery and Biomechanism Translation from Human Studies

“…Sample selection and storage specifications were not consistently reported across the studies. In some cases, samples were stored for 15 years or more prior to analysis [6,11,12,54] in which degradation of some metabolites is possible. We are not aware of any of the studies from our review that reported on the measurement of preanalytical quality markers or adjusted for sample preanalytical confounders.…”

Biomarkers in Heart Failure: Current and Future

“…В научной литературе появляется все больше работ, анализирующих ассоциацию метаболитов с параметрами ремоделирования миокарда и особенностями течения СН. Так, в ретроспективном исследовании данных метаболомного профиля 2 336 участников Фрамингемского исследования, период наблюдения за которыми составил в среднем 15,8 года, была продемонстрирована четкая связь трех метаболитов с параметрами ремоделирования ЛЖ: кинуренина, диацилглицерола и лейцина с конечным диастолическим размером ЛЖ [43]. В другом исследовании 74 пациентов с ишемической болезнью сердца обнаружена отрицательная корреляция уровня сфингозин-1-фосфата и сфингомиелина с величиной фракции выброса ЛЖ [44].…”