Metabolomic Profiles and Heart Failure Risk in Black Adults: Insights From the Jackson Heart Study.
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.
['Tahir|Usman A|UA|', 'Katz|Daniel H|DH|', 'Zhao|Tianyi|T|', 'Ngo|Debby|D|', 'Cruz|Daniel E|DE|', 'Robbins|Jeremy M|JM|', 'Chen|Zsu-Zsu|ZZ|', 'Peterson|Bennet|B|', 'Benson|Mark D|MD|', 'Shi|Xu|X|', 'Dailey|Lucas|L|', 'Andersson|Charlotte|C|', 'Vasan|Ramachandran S|RS|', 'Gao|Yan|Y|', 'Shen|Changyu|C|', 'Correa|Adolfo|A|', 'Hall|Michael E|ME|', 'Wang|Thomas J|TJ|', 'Clish|Clary B|CB|', 'Wilson|James G|JG|', 'Gerszten|Robert E|RE|']
D000328:Adult D001741:African Americans D000368:Aged D016022:Case-Control Studies D003094:Collagen D003327:Coronary Disease D015987:Effect Modifier, Epidemiologic D005260:Female D000082742:Heart Disease Risk Factors D006333:Heart Failure D006709:Homoarginine D006801:Humans D017379:Hypertrophy, Left Ventricular D015994:Incidence D008137:Longitudinal Studies D008297:Male D055432:Metabolomics D008875:Middle Aged D009569:Nitric Oxide D009963:Orotic Acid D011073:Polyamines D011392:Proline D016016:Proportional Hazards Models D011743:Pyrimidines D012323:RNA Processing, Post-Transcriptional D012306:Risk D013096:Spermine D013318:Stroke Volume D014529:Uridine D044465:Whites
metabolomics heart failure plasma heart diseases medicine