Metabolomic Profiles and Heart Failure Risk in Black Adults: Insights From the Jackson Heart Study

Circ Heart Fail. 2021 Jan;14(1):e007275. doi: 10.1161/CIRCHEARTFAILURE.120.007275. Epub 2021 Jan 19.


Background: Heart failure (HF) is a heterogeneous disease characterized by significant metabolic disturbances; however, the breadth of metabolic dysfunction before the onset of overt disease is not well understood. The purpose of this study was to determine the association of circulating metabolites with incident HF to uncover novel metabolic pathways to disease.

Methods: We performed targeted plasma metabolomic profiling in a deeply phenotyped group of Black adults from the JHS (Jackson Heart Study; n=2199). We related metabolites associated with incident HF to established etiological mechanisms, including increased left ventricular mass index and incident coronary heart disease. Furthermore, we evaluated differential associations of metabolites with HF with preserved ejection fraction versus HF with reduced ejection fraction.

Results: Metabolites associated with incident HF included products of posttranscriptional modifications of RNA, as well as polyamine and nitric oxide metabolism. A subset of metabolite-HF associations was independent of well-established HF pathways such as increased left ventricular mass index and incident coronary heart disease and included homoarginine (per 1 SD increase in metabolite level, hazard ratio, 0.77; P=1.2×10-3), diacetylspermine (hazard ratio, 1.34; P=3.4×10-3), and uridine (hazard ratio, 0.79; P, 3×10-4). Furthermore, metabolites involved in pyrimidine metabolism (orotic acid) and collagen turnover (N-methylproline) among others were part of a distinct metabolic signature that differentiated individuals with HF with preserved ejection fraction versus HF with reduced ejection fraction.

Conclusions: The integration of clinical phenotyping with plasma metabolomic profiling uncovered novel metabolic processes in nontraditional disease pathways underlying the heterogeneity of HF development in Black adults.

Keywords: heart diseases; heart failure; medicine; metabolomics; plasma.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • African Americans*
  • Aged
  • Case-Control Studies
  • Collagen / metabolism
  • Coronary Disease / epidemiology
  • Coronary Disease / metabolism*
  • Effect Modifier, Epidemiologic
  • European Continental Ancestry Group
  • Female
  • Heart Disease Risk Factors
  • Heart Failure / epidemiology
  • Heart Failure / metabolism*
  • Heart Failure / physiopathology
  • Homoarginine / metabolism
  • Humans
  • Hypertrophy, Left Ventricular / epidemiology
  • Hypertrophy, Left Ventricular / metabolism*
  • Incidence
  • Longitudinal Studies
  • Male
  • Metabolomics*
  • Middle Aged
  • Nitric Oxide / metabolism
  • Orotic Acid / metabolism
  • Polyamines / metabolism
  • Proline / analogs & derivatives
  • Proline / metabolism
  • Proportional Hazards Models
  • Pyrimidines / metabolism
  • RNA Processing, Post-Transcriptional
  • Risk
  • Spermine / analogs & derivatives
  • Spermine / metabolism
  • Stroke Volume / physiology
  • Uridine / metabolism


  • N-methylproline
  • Polyamines
  • Pyrimidines
  • Homoarginine
  • Spermine
  • Nitric Oxide
  • Orotic Acid
  • N',N''-diacetylspermine
  • Collagen
  • Proline
  • Uridine