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JACC Heart Fail. 2017 Nov;5(11):823-832. doi: 10.1016/j.jchf.2017.07.009.

Targeted Metabolomic Profiling of Plasma and Survival in Heart Failure Patients.

Author information

1
Heart and Vascular Institute, Henry Ford Hospital, Detroit, Michigan; Center for Health Policy and Health Services Research, Henry Ford Hospital, Detroit, Michigan. Electronic address: dlanfea1@hfhs.org.
2
Heart and Vascular Institute, Henry Ford Hospital, Detroit, Michigan.
3
Department of Public Health Sciences, Henry Ford Hospital, Detroit, Michigan.
4
Sanford Burnham Prebys Medical Discovery Institute, Orlando, Florida.
5
Department of Cardiovascular Medicine, Cleveland Clinic Prevention Research Laboratory, Cleveland Clinic, Cleveland, Ohio.
6
Department of Cardiology, University of Amsterdam, Amsterdam, the Netherlands.
7
Center for Health Policy and Health Services Research, Henry Ford Hospital, Detroit, Michigan.

Abstract

OBJECTIVES:

This study sought to derive and validate plasma metabolite associations with survival in heart failure (HF) patients.

BACKGROUND:

Profiling of plasma metabolites to predict the course of HF appears promising, but validation and incremental value of these profiles are less established.

METHODS:

Patients (n = 1,032) who met Framingham HF criteria with a history of reduced ejection fraction were randomly divided into derivation and validation cohorts (n = 516 each). Amino acids, organic acids, and acylcarnitines were quantified using mass spectrometry in fasting plasma samples. We derived a prognostic metabolite profile (PMP) in the derivation cohort using Lasso-penalized Cox regression. Validity was assessed by 10-fold cross validation in the derivation cohort and by standard testing in the validation cohort. The PMP was analyzed as both a continuous variable (PMPscore) and dichotomized at the median (PMPcat), in univariate and multivariate models adjusted for clinical risk score and N-terminal pro-B-type natriuretic peptide.

RESULTS:

Overall, 48% of patients were African American, 35% were women, and the average age was 69 years. After a median follow-up of 34 months, there were 256 deaths (127 and 129 in derivation and validation cohorts, respectively). Optimized modeling defined the 13 metabolite PMPs, which was cross validated as both the PMPscore (hazard ratio [HR]: 3.27; p < 2 × 10-16) and PMPcat (HR: 3.04; p = 2.93 × 10-8). The validation cohort showed similar results (PMPscore HR: 3.9; p < 2 × 10-16 and PMPcat HR: 3.99; p = 3.47 × 10-9). In adjusted models, PMP remained associated with mortality in the cross-validated derivation cohort (PMPscore HR: 1.63; p = 0.0029; PMPcat HR: 1.47; p = 0.081) and the validation cohort (PMPscore HR: 1.54; p = 0.037; PMPcat HR: 1.69; p = 0.043).

CONCLUSIONS:

Plasma metabolite profiles varied across HF subgroups and were associated with survival incremental to conventional predictors. Additional investigation is warranted to define mechanisms and clinical applications.

KEYWORDS:

congestive heart failure; metabolomic profiling; prognosis; risk stratification

PMID:
29096792
PMCID:
PMC5679305
DOI:
10.1016/j.jchf.2017.07.009
[Indexed for MEDLINE]
Free PMC Article

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