Abstract
Background
Microflora-dependent trimethylamine-N-oxide (TMAO) formation, which results from intake
of choline and L-carnitine-rich food, shows promise as a predictor of cardiovascular
disease (CVD) risk, but these associations have not been examined in ethnically diverse
populations. In a multiethnic population-based study of adults in Canada, we assessed
the stability of TMAO and L-carnitine in stored serum samples and their association
with intimal medial thickness, prevalent risk factors, and clinical events.
Methods
In a randomly sampled cross-sectional study of 1286 Canadians, fasting serum samples
were collected and stored. In 292 consecutive individuals (99 CVD cases and 193 unmatched
control subjects), L-carnitine and TMAO concentrations were assessed using validated
analytical approaches.
Results
The mean (± SD) TMAO level was 1.998 ± 3.13 μM and L-carnitine was 42.29 ± 11.35 μM.
The relative levels of the samples did not appreciably change after 3 freeze-thaw
cycles (coefficient of variation, 5.6% and 4.7%, respectively). No significant association
between L-carnitine levels and prevalent CVD was found, with adjustment for covariates
(odds ratio, 1.57; 95% confidence interval, 0.58-4.26; P trend = 0.65), for highest vs lowest quintile group. TMAO levels showed a significant,
graded association with prevalent CVD (odds ratio, 3.17; 95% confidence interval,
1.05-9.51; P trend = 0.02). After further adjustment for diabetes status, meat, fish, and cholesterol
intake, the association remained significant. No significant association between carotid
intimal medial thickness and L-carnitine (P = 0.64) or TMAO (P = 0.18) was found.
Conclusions
Serum TMAO and L-carnitine analysis on stored samples is reliable. Our findings support
an association between TMAO with prevalent CVD in a multiethnic population. This finding
requires replication in larger studies in which dietary intake and stored serum samples
exist.
Résumé
Introduction
La formation d’oxyde de triméthylamine (OTMA) dépendant de la microflore, qui résulte
d’un apport d’aliments riches en choline et L-carnitine, semble prometteur pour la
prédiction du risque de maladies cardiovasculaires (MCV), mais ces associations n'ont
pas été examinées dans des populations ayant des origines ethniques diverses. Dans
une étude basée sur une population multiethnique d’adultes au Canada, nous avons évalué
la stabilité de l’OTMA et la L-carnitine dans des échantillons sériques stockés et
leur association avec l’épaisseur de l'intima-média, les facteurs de risque les plus
courants et les événements cliniques.
Méthodes
Dans une étude transversale avec un échantillonnage aléatoire de 1 286 Canadiens,
des échantillons de sérum à jeun ont été collectés et stockés. Pour 292 individus
consécutifs (99 cas de MCV et 193 sujets témoins non appariés), les concentrations
de L-carnitine et d’OTMA ont été évaluées selon des approches analytiques validées.
Résultats
Le niveau moyen (± DS) d’OTMA était de 1,998 ± 3,13 uM et de L-carnitine était de
42,29 ± 11,35 uM. Les niveaux relatifs des échantillons n'ont pas changé de façon
appréciable après trois cycles de congélation-décongélation (coefficient de variation,
5,6 % et 4,7 %, respectivement). Aucune association significative entre les niveaux
de L-carnitine et la prévalence des MCV n’a été trouvé, avec un ajustement des covariables
(ratio d'incidence approché, 1,57; intervalle de confiance à 95 %, 0,58 à 4,26; tendance
du P = 0,65), pour le quintile le plus haut vs le plus bas. Les niveaux d’OTMA ont montré
une association significative et graduée avec la prévalence de MCV (ratio d'incidence
approché, 3,17; intervalle de confiance à 95 %, 1,05 à 9,51; tendance du P = 0,02). Après un ajustement supplémentaire pour le statut du diabète, de l’apport
en viande, en poisson et en cholestérol, l'association est restée significative. Aucune
association significative n’a été trouvée entre l’épaisseur de l’intima-média et la
L-carnitine (P = 0,64) ou l’OTMA (P = 0,18) .
Conclusions
L’analyse du sérum de l’OTMA et de la L-carnitine sur des échantillons stockés est
fiable. Nos résultats confirment une association entre l'OTMA et la prévalence de
MCV dans une population multiethnique. Ce constat nécessite d’être répliqué dans des
études plus vastes intégrant l’apport alimentaire et des échantillons stockés de sérum.
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Article info
Publication history
Published online: June 24, 2015
Accepted:
June 17,
2015
Received:
April 23,
2015
Footnotes
See page 1193 for disclosure information.
Identification
Copyright
© 2015 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.
