Serum trans fatty acids, asymmetric dimethylarginine and risk of acute myocardial infarction and mortality in patients with suspected coronary heart disease: a prospective cohort study.

Heidi Borgeraas,Per Magne Ueland,Rolf K Berge,Reinhard Seifert,Jens Kristoffer Hertel,Pavol Bohov,Ottar Nygård,Jøran Hjelmesæth

doi:10.1186/s12944-016-0204-9

Abstract

BackgroundTrans fatty acids (TFAs) have been found to impair flow mediated vasodilation and nitric oxide (NO) production. We sought to examine if serum TFA levels are associated with plasma levels of the NO inhibitor asymmetric dimethylarginine (ADMA) and if possible relationships between serum TFA and cardiovascular morbidity or mortality are mediated or modified by plasma ADMA levels.MethodsThe cohort included patients who underwent coronary angiography for suspected coronary heart disease in 2000–2001. Serum trans 16:1n7 and trans 18:1 isomers were determined by gas liquid chromatography and the summation of these two TFAs is reported as TFA (percentage by weight (wt%) or concentration). Associations between TFAs and ADMA were estimated by calculating the Spearman’s rank correlation coefficient (ρ), and risk associations with AMI, cardiovascular death and all-cause mortality across quartiles of TFAs (wt% or concentration) were explored by Cox modeling.ResultsA total of 1364 patients (75 % men) with median (25th,75th percentile) age 61 (54, 69) years, serum TFA 0.46 (0.36, 0.56) wt% and plasma ADMA 0.59 (0.50, 0.70) μmol/L were studied. Serum TFA levels (ρ = 0.21, p < 0.001), trans 16:1n7 (ρ = 0.22, p < 0.001) and trans 18:1 (ρ = 0.20, p < 0.001) levels were significantly correlated with plasma ADMA levels. During the median (25th,75th percentile) follow-up time of 5.8 (4.5, 6.4) years, 129 (9.5 %) patients experienced an AMI, 124 (9.1 %) died, whereof 66 (53 %) due to cardiovascular causes. After multivariate adjustments no significant associations between serum TFA levels (wt% or concentration) and incident AMI, CV death and all-cause mortality were observed. Similar results were obtained when repeating the analyses with trans 16:1n7 and trans 18:1 individually. Plasma ADMA levels did not significantly modify the associations between TFA levels and outcomes.ConclusionsSerum TFA levels were positively correlated with plasma ADMA levels. After multivariate adjustments, TFAs were not associated with incident AMI or mortality, and associations were not influenced by ADMA.Trial registrationClinicaltrials.gov Identifier: NCT00354081Electronic supplementary materialThe online version of this article (doi:10.1186/s12944-016-0204-9) contains supplementary material, which is available to authorized users.

Highlights

Trans fatty acids (TFAs) have been found to impair flow mediated vasodilation and nitric oxide (NO) production
asymmetric dimethylarginine (ADMA) is metabolized by the enzyme dimethylarginine dimethylamoniohydrolase (DDAH) [12, 13], which is a critical regulator of ADMA levels
TFAs are associated with higher levels of inflammatory markers, including TNF-α [18], which in turn may down-regulate DDAH activity [19]; TFAs may be a potential inhibitor of ADMA degradation, with a subsequent decrease of NO levels

Summary

Introduction

Trans fatty acids (TFAs) have been found to impair flow mediated vasodilation and nitric oxide (NO) production. Even beneficial cardiovascular (CV) effects of TFAs from dairy products and meat have been claimed, a high consumption of industrially produced TFAs have repeatedly been associated with an increased risk of CV disease [1, 2]. Asymmetric dimethylarginine (ADMA) is a potent inhibitor of NO synthesis, and numerous studies have linked increasing levels of ADMA with risk of CV disease [11]. TFAs are associated with higher levels of inflammatory markers, including TNF-α [18], which in turn may down-regulate DDAH activity [19]; TFAs may be a potential inhibitor of ADMA degradation, with a subsequent decrease of NO levels

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