Vitamin B-6 catabolism and long-term mortality risk in patients with coronary artery disease12

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ABSTRACT

Background:Low vitamin B-6 status has been related to increased risk of coronary artery disease (CAD), which is a condition that is associated with inflammation. The most common status marker, plasma pyridoxal 5′-phosphate (PLP), decreases during inflammation; therefore, causal relations are uncertain.

Objective:We evaluated the vitamin B-6 biomarkers PLP, pyridoxal, and pyridoxic acid (PA) and the pyridoxic acid:(pyridoxal + PLP) ratio (PAr), a proposed marker of vitamin B-6 catabolism during activated cellular immunity, as predictors of mortality.

Design:Associations with risks of long-term all-cause mortality and cardiovascular mortality were evaluated with the use of Cox regression in patients who were undergoing elective coronary angiography for suspected stable angina pectoris (SAP) (n= 4131) and an independent cohort of patients who were hospitalized for acute myocardial infarction (AMI) (n= 3665).

Results:Plasma PLP (AMI patients only) and PA predicted all-cause mortality in models that were adjusted for established risk predictors, but associations were attenuated or nonsignificant after additional adjustment for inflammatory markers. PAr was correlated with biomarkers of inflammation (Pearson’s r≥ 0.37) and predicted all-cause mortality and cardiovascular mortality after adjustment for established risk predictors. In SAP patients, PAr had greater predictive strength than did current smoking, diabetes, hypertension, apolipoproteins, or C-reactive protein. PAr provided multiadjusted HRs per SD of 1.45 (95% CI: 1.30, 1.63) and 1.31 (95% CI: 1.21, 1.41) in SAP and AMI patients, respectively. In both cohorts, PAr was a particularly strong predictor of all-cause mortality for patients with no previous CAD history (P-interaction ≤ 0.04).

Conclusion:PAr may capture unique aspects of inflammatory activation and thus provide new insights into disease mechanisms that may aid in identifying patients at increased risk of future fatal events.

Keywords:

biomarker
coronary artery disease
inflammation
mortality
vitamin B-6

ABBREVIATIONS

AMI
acute myocardial infarction
AOX1
aldehyde oxidase 1
apo A-I
apolipoprotein A-I
CAD
coronary artery disease
CRP
C-reactive protein
eGFR
estimated glomerular filtration rate
HPA
hypothalamic-pituitary-adrenal
KTR
kynurenine:tryptophan ratio
NORVIT
Norwegian Vitamin Trial
PA
pyridoxic acid
PAr
pyridoxic acid:(pyridoxal + pyridoxal 5′-phosphate) ratio
PLP
pyridoxal 5′-phosphate
SAP
stable angina pectoris
WECAC
Western Norway Coronary Angiography Cohort

Cited by (0)

1

Supported by The Western Norway Regional Health Authority (grant 911489), The Norwegian Cancer Society (grant 421798), and the Foundation to Promote Research into Functional Vitamin B12 Deficiency, Bergen Norway. The Norwegian Vitamin Trial and the Western Norway B-Vitamin Intervention Trial were supported by The Advanced Research Program and Research Council of Norway, the Norwegian Foundation for Health and Rehabilitation, the Norwegian Council on Cardiovascular Disease, the Norwegian Heart and Lung Patient Organization, the Norwegian Red Cross, the Northern Norway Regional Health Authority, the Western Norway Regional Health Authority, the Norwegian Ministry of Health and Care Services, the University of Tromsø, the University of Bergen, the Department of Heart Disease at Haukeland University Hospital, Foundation to Promote Research into Functional Vitamin B12 Deficiency, Bergen Norway, and Alpharma Inc., Copenhagen, Denmark. The posttrial follow-up was supported by the Norwegian Foundation for Health and Rehabilitation, the Department of Heart Disease at Haukeland University Hospital, the University of Tromsø, the University of Bergen, and the Foundation to Promote Research into Functional Vitamin B12 Deficiency, Bergen Norway.

2

Supplemental Tables 1and 2are available from the “Online Supporting Material” link in the online posting of the article and from the same link in the online table of contents at http://ajcn.nutrition.org.

Copyright © 2016 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.