title: Homocysteine predicts increased NT-pro-BNP through impaired fatty acid oxidation.
abstract: BACKGROUND
  The deficiency in methyl donors, folate and vitamin B12, increases homocysteine and produces myocardium hypertrophy with impaired mitochondrial fatty acid oxidation and increased BNP, through hypomethylation of peroxisome-proliferator-activated-receptor gamma co-activator-1α, in rat. This may help to understand better the elusive link previously reported between hyperhomocysteinemia and BNP, in human. We investigated therefore the influence of methyl donors on heart mitochondrial fatty acid oxidation and brain natriuretic peptide, in two contrasted populations.
  
  
  METHODS
  Biomarkers of heart disease, of one carbon metabolism and of mitochondrial fatty acid oxidation were assessed in 1020 subjects, including patients undergoing coronarography and ambulatory elderly subjects from OASI cohort.
  
  
  RESULTS
  Folate deficit was more frequent in the coronarography population than in the elderly ambulatory volunteers and produced a higher concentration of homocysteine (19.3 ± 6.8 vs. 15.3 ± 5.6, P<0.001). Subjects with homocysteine in the upper quartile (≥ 18 μmol/L) had higher concentrations of NT-pro-BNP (or BNP in ambulatory subjects) and of short chain-, medium chain-, and long chain-acylcarnitines, compared to those in the lower quartile (≤ 12 μmol/L), in both populations (P<0.001). Homocysteine and NT-pro-BNP were positively correlated with short chain-, medium chain-, long chain-acylcarnitines and with acylcarnitine ratios indicative of decreased mitochondrial acyldehydrogenase activities (P<0.001). In multivariate analysis, homocysteine and long chain acylcarnitines were two interacting determinants of NT-pro-BNP, in addition to left ventricular ejection fraction, body mass index, creatinine and folate.
  
  
  CONCLUSIONS
  This study showed that homocysteine predicts increased NT-pro-BNP (or BNP) through a link with impaired mitochondrial fatty oxidation, in two contrasted populations.
authors.affiliation: INSERM U954, Medical Faculty and CHU of Nancy, University Henri Poincaré, Nancy, France. rm.rodriguez@chu-nancy.fr
authors.forename: R M
authors.initials: RM
authors.lastname: Guéant Rodriguez
authors.forename: R
authors.initials: R
authors.lastname: Spada
authors.forename: S
authors.initials: S
authors.lastname: Pooya
authors.forename: E
authors.initials: E
authors.lastname: Jeannesson
authors.forename: M A
authors.initials: MA
authors.lastname: Moreno Garcia
authors.forename: G
authors.initials: G
authors.lastname: Anello
authors.forename: P
authors.initials: P
authors.lastname: Bosco
authors.forename: M
authors.initials: M
authors.lastname: Elia
authors.forename: A
authors.initials: A
authors.lastname: Romano
authors.forename: J M
authors.initials: JM
authors.lastname: Alberto
authors.forename: Y
authors.initials: Y
authors.lastname: Juillière
authors.forename: J L
authors.initials: JL
authors.lastname: Guéant
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D005227:Fatty Acids / Q000037:antagonists & inhibitors / Q000097:blood*; D005260:Female; D006331:Heart Diseases / Q000097:blood / Q000175:diagnosis*; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008929:Mitochondria, Heart / Q000378:metabolism; D020097:Natriuretic Peptide, Brain / Q000096:biosynthesis* / Q000097:blood*; D010084:Oxidation-Reduction; D010446:Peptide Fragments / Q000096:biosynthesis* / Q000097:blood*; D011237:Predictive Value of Tests; D011795:Surveys and Questionnaires
chemical_list: D015415:Biomarkers; D005227:Fatty Acids; D010446:Peptide Fragments; C109794:pro-brain natriuretic peptide (1-76); D006710:Homocysteine; D020097:Natriuretic Peptide, Brain