Novel Findings From a Metabolomics Study of Left Ventricular Diastolic Function: The Bogalusa Heart Study

Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease

Jovia L. Nierenberg¹  Shengxu Li²  Mengyao Shi³  Marie Krousel‐Wood³  Changwei Li³  Jiang He³  Lydia A. Bazzano³  Alexander C. Razavi³  Camilo Fernandez³  Jason Kinchen³  Xuenan Mi⁴  Tanika N. Kelly⁵  Seamus P. Whelton⁶ 

[1] Clinics of Minnesota Minneapolis MN;;Children's Minnesota Research Institute Children's Hospitals &Department of Epidemiology Tulane University School of Public Health and Tropical Medicine New Orleans LA;Department of Epidemiology and Biostatistics University of Georgia College of Public Health Athens GA;Metabolon, Inc. Durham NC;The Ciccarone Center for the Prevention of Heart Disease Johns Hopkins University School of Medicine Baltimore MD;

关键词: biomarker;    diastolic function;    epidemiology;    heart failure;    metabolomics;   

DOI  :  10.1161/JAHA.119.015118

来源: DOAJ

【 摘 要 】

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; P=1.50×10−7); 1‐methylhistidine (B=0.05; P=1.60×10−7); formiminoglutamate (B=0.07; P=5.60×10−7); N2, N5‐diacetylornithine (B=0.05; P=1.30×10−7); N‐trimethyl 5‐aminovalerate (B=0.04; P=5.10×10−6); 5‐methylthioadenosine (B=0.04; P=1.40×10−5); and methionine sulfoxide (B=0.04; P=3.80×10−6) were significantly associated with the natural log of the ratio of peak early filling velocity to mitral annular velocity. Butyrylcarnitine (B=3.18; P=2.10×10−6) 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.

【 授权许可】

Unknown