Background:
The heart has close interactions with other organs’ functions and concomitant systemic factors such as oxidative stress, nitric oxide (NO), inflammation, and nutrition in systolic heart failure (HF). Recently, plasma amino acid (AA) profiling as systemic metabolic indicator has attracted considerable attention in predicting the future risk of human cardiometabolic diseases, but it has been scarcely studied in HF.
Methods:
Thirty-eight stable but symptomatic patients with left ventricular ejection fraction (LVEF) <45% and 33 asymptomatic individuals with normal brain natriuretic peptide (BNP) value were registered as the HF and control groups, respectively. We analyzed fasting plasma concentrations of 41 AAs using high-performance liquid chromatography, serum NO metabolite concentration, hydroperoxide and high-sensitivity C-reactive protein measurements, echocardiography, and flow-mediated dilatation. Univariate and stepwise multivariate analyses including potential confounders were subsequently performed in the HF group.
Results:
(1) In the HF group, 17 AAs and two ratios significantly changed compared with those in the control group. (2) Univariate and multivariate analyses revealed that Fischer ratio and five specific AAs, ie, monoethanolamine, methionine, tyrosine, 1-methylhistidine, and histidine have significant correlation with BNP value, LVEF, LV end-diastolic volume index, inferior vena cava diameter, mitral E/e’, and BNP value, respectively (p<0.05). (3) Unexpectedly, further exploratory factor analysis categorized these AAs into hepatic-related (monoethanolamine, tyrosine, and Fischer ratio) and skeletal muscle-related (histidine, methionine, and 1-methylhistidine) factors. (4) Some categorized AAs showed unique correlations with concomitant systemic factors: monoethanolamine, tyrosine, and Fischer ratio with serum NO concentration (p<0.05); histidine with serum albumin (p = 0.0001); and 1-methylhistidine with flow-mediated dilatation (p<0.05).
Conclusions:
Plasma AA profiling identified correlations of specific AAs with cardiac function and concomitant systemic factors and highlighted the cardio-hepatic-skeletal muscle axis in patients with systolic HF.
Plasma Amino Acid Profiling Identifies Specific Amino Acid Associations with Cardiovascular Function in Patients with Systolic Heart Failure
