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J Am Heart Assoc. 2013 Dec 5;2(6):e000542. doi: 10.1161/JAHA.113.000542.

A plasma long-chain acylcarnitine predicts cardiovascular mortality in incident dialysis patients.

Author information

1
Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA.

Abstract

BACKGROUND:

The marked excess in cardiovascular mortality that results from uremia remains poorly understood.

METHODS AND RESULTS:

In 2 independent, nested case-control studies, we applied liquid chromatography-mass spectrometry-based metabolite profiling to plasma obtained from participants of a large cohort of incident hemodialysis patients. First, 100 individuals who died of a cardiovascular cause within 1 year of initiating hemodialysis (cases) were randomly selected along with 100 individuals who survived for at least 1 year (controls), matched for age, sex, and race. Four highly intercorrelated long-chain acylcarnitines achieved the significance threshold adjusted for multiple testing (P<0.0003). Oleoylcarnitine, the long-chain acylcarnitine with the strongest association with cardiovascular mortality in unadjusted analysis, remained associated with 1-year cardiovascular death after multivariable adjustment (odds ratio per SD 2.3 [95% confidence interval, 1.4 to 3.8]; P=0.001). The association between oleoylcarnitine and 1-year cardiovascular death was then replicated in an independent sample (n=300, odds ratio per SD 1.4 [95% confidence interval, 1.1 to 1.9]; P=0.008). Addition of oleoylcarnitine to clinical variables improved cardiovascular risk prediction using net reclassification (NRI, 0.38 [95% confidence interval, 0.20 to 0.56]; P<0.0001). In physiologic profiling studies, we demonstrate that the fold change in plasma acylcarnitine levels from the aorta to renal vein and from pre- to posthemodialysis samples exclude renal or dialytic clearance of long-chain acylcarnitines as confounders in our analysis.

CONCLUSIONS:

Our data highlight clinically meaningful alterations in acylcarnitine homeostasis at the time of dialysis initiation, which may represent an early marker, effector, or both of uremic cardiovascular risk.

KEYWORDS:

cardiovascular disease; dialysis; metabolism; mortality; risk factors

PMID:
24308938
PMCID:
PMC3886735
DOI:
10.1161/JAHA.113.000542
[Indexed for MEDLINE]
Free PMC Article
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