Open AccessNeopterin as an Effect Modifier of the Cardiovascular Risk Predicted by Total Homocysteine: A Prospective 2‐Cohort Study
Author(s) -
Bjørnestad Espen Ø.,
Borsholm Robert A.,
Svingen Gard F. T.,
Pedersen Eva R.,
Seifert Reinhard,
Midttun Øivind,
Ueland Per M.,
Tell Grethe S.,
Bønaa Kaare H.,
Nygård Ottar
Publication year - 2017
Publication title -
journal of the american heart association
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.494
H-Index - 85
ISSN - 2047-9980
DOI - 10.1161/jaha.117.006500
Subject(s) - medicine , neopterin , homocysteine , prospective cohort study , cohort , cohort study
Background Plasma total homocysteine ( tH cy) is related to plasma neopterin, an indicator of interferon‐γ‐mediated immune activation, and both biomarkers positively predict cardiovascular risk. We examined whether the association between tH cy and subsequent risk of acute myocardial infarction ( AMI ) was modified by systemic concentrations of neopterin and C‐reactive protein among patients with coronary heart disease. Methods and Results By Cox modeling, we explored the association between tH cy and risk of AMI in 4164 patients with suspected stable angina pectoris. Subgroup analyses were performed according to median levels of neopterin and C‐reactive protein. A replication study was performed among 3749 patients with AMI at baseline. Median follow‐up was 7.3 and 8.3 years among patients with stable angina pectoris and AMI , respectively. tH cy and neopterin correlated in both cohorts ( r s =0.34 and r s =0.30 among stable angina pectoris and AMI patients, respectively, both P <0.001). tH cy predicted AMI in both cohorts, independent of B‐vitamin treatment. However, significant risk associations were confined to patients with plasma neopterin above the median (hazard ratios [95% confidence interval] per 1‐ SD increment of log‐transformed tH cy 1.38 [1.26–1.50] and 1.18 [1.10–1.26] among stable angina pectoris and AMI patients, respectively) ( P int <0.005 in both cohorts). Further, adding information on the interaction between tH cy and neopterin improved model discrimination and reclassification. tH cy and C‐reactive protein were weakly related, and no effect modification was found by C‐reactive protein. Conclusions Among patients with coronary heart disease, tH cy predicted risk of AMI only in subjects with concomitantly elevated plasma neopterin. Our results motivate further research on the relationship between homocysteine metabolism, cellular immune activation, and atherothrombosis.