Department of Epidemiology Tulane University School of Public Health and Tropical Medicine New Orleans LA.
Department of Medicine Tulane University School of Medicine New Orleans LA.
J Am Heart Assoc. 2020 Feb 4;9(3):e015118. doi: 10.1161/JAHA.119.015118. Epub 2020 Jan 29.
Background Diastolic dysfunction is one important causal factor for heart failure with preserved ejection fraction, yet the metabolic signature associated with this subclinical phenotype remains unknown. Methods and Results Ultra-high-performance liquid chromatography-tandem mass spectroscopy was used to conduct untargeted metabolomic analysis of fasting serum samples in 1050 white and black participants of the BHS (Bogalusa Heart Study). After quality control, 1202 metabolites were individually tested for association with 5 echocardiographic measures of left ventricular diastolic function using multivariable-adjusted linear regression. Measures of left ventricular diastolic function included the ratio of peak early filling velocity to peak late filling velocity, ratio of peak early filling velocity to mitral annular velocity, deceleration time, isovolumic relaxation time, and left atrial maximum volume index (LAVI). Analyses adjusted for multiple cardiovascular disease risk factors and used Bonferroni-corrected alpha thresholds. Eight metabolites robustly associated with left ventricular diastolic function in the overall population and demonstrated consistent associations in white and black study participants. N-formylmethionine (B=0.05; =1.50×10); 1-methylhistidine (B=0.05; =1.60×10); formiminoglutamate (B=0.07; =5.60×10); N2, N5-diacetylornithine (B=0.05; =1.30×10); N-trimethyl 5-aminovalerate (B=0.04; =5.10×10); 5-methylthioadenosine (B=0.04; =1.40×10); and methionine sulfoxide (B=0.04; =3.80×10) were significantly associated with the natural log of the ratio of peak early filling velocity to mitral annular velocity. Butyrylcarnitine (B=3.18; =2.10×10) was significantly associated with isovolumic relaxation time. Conclusions The current study identified novel findings of metabolite associations with left ventricular diastolic function, suggesting that the serum metabolome, and its underlying biological pathways, may be implicated in heart failure with preserved ejection fraction pathogenesis.
背景 舒张功能障碍是射血分数保留型心力衰竭的一个重要病因，但与这种亚临床表型相关的代谢特征尚不清楚。
方法和结果 使用超高效液相色谱-串联质谱法对 1050 名白人和黑人 BHS（博加卢萨心脏研究）参与者的空腹血清样本进行非靶向代谢组学分析。经过质量控制，使用多变量调整线性回归，对 1202 种代谢物分别与左心室舒张功能的 5 个超声心动图测量值进行关联分析。左心室舒张功能的测量值包括峰值早期充盈速度与峰值晚期充盈速度的比值、峰值早期充盈速度与二尖瓣环速度的比值、减速时间、等容舒张时间和左心房最大容积指数（LAVI）。分析调整了多种心血管疾病风险因素，并使用 Bonferroni 校正的 alpha 阈值。有 8 种代谢物与整体人群的左心室舒张功能显著相关，在白人和黑人研究参与者中均表现出一致的相关性。N-甲酰甲硫氨酸（B=0.05；=1.50×10）；1-甲基组氨酸（B=0.05；=1.60×10）；甲酰谷氨酸（B=0.07；=5.60×10）；N2、N5-二乙酰鸟氨酸（B=0.05；=1.30×10）；N-三甲基 5-氨基戊酸（B=0.04；=5.10×10）；5-甲基硫代腺苷（B=0.04；=1.40×10）；和甲硫氨酸亚砜（B=0.04；=3.80×10）与峰值早期充盈速度与二尖瓣环速度的自然对数呈显著相关。丁酰肉碱（B=3.18；=2.10×10）与等容舒张时间呈显著相关。
结论 本研究发现了代谢物与左心室舒张功能关联的新发现，提示血清代谢组及其潜在的生物学途径可能与射血分数保留型心力衰竭的发病机制有关。
