Associations of the serum metabolite profile with a healthy Nordic diet and risk of coronary artery disease

Abstract

Background & aim: A healthy Nordic diet (HND) rich in wholegrain cereals, berries, vegetables, and fish, has been associated with a lower risk of cardiovascular disease, but the molecular links remain unclear. Here, we present the application of nontargeted metabolic profiling based on liquid chromatography with tandem mass spectrometry (LC-MS/MS) to identify metabolites that would potentially reflect the adherence to HND and their relationship with the risk of coronary artery disease (CAD).

Methods: From a Finnish population-based prospective cohort (Kuopio Ischaemic Heart Disease Risk Factor Study; KIHD), we collected 364 baseline serum samples in 4 groups: 1) 94 participants with high adherence to HND who developed CAD during the follow-up of 20.4 ± 7.6 years (cases), 2) 88 participants with high adherence who did not develop CAD during follow-up (controls), 3) 93 CAD cases with low adherence, and 4) 89 controls with low adherence.

Results: Indolepropionic acid, proline betaine, vitamin E derivatives, and medium-chain acylcarnitines were associated with adherence to HND after adjustments for age, waist-to-hip ratio (WHR), physical activity, and total cholesterol. These metabolites also correlated negatively with blood lipid profiles, BMI, insulin, inflammation marker high-sensitivity C reactive protein (hsCRP), smoking, and alcohol consumption, as well as positively with physical activity. Predictors of CAD risk included several lipid molecules, which also indicated lower adherence to HND. But, only the associations with the plasmalogens PC(O-16:0/18:2) and PC(O-16:1/18:2) remained significant after adjusting for age, smoking, systolic blood pressure, LDL cholesterol, and WHR. These plasmalogens did not correlate with any investigated risk factors of CAD at baseline, which may highlight their potential as novel predictors of CAD risk. Interestingly, the metabolic profile predicting CAD risk differed based on the adherence to HND. Also, HND adherence was more distinct within CAD cases than controls, which may emphasize the interaction between HND adherence and CAD risk.

Conclusions: The association between higher adherence to HND and a lower risk of CAD likely involves a complex interaction of various endogenous, plant-, and microbial-derived metabolites.

Keywords: Coronary artery disease; Healthy Nordic diet; LC-MS; Metabolic phenotype; Metabolomics; Serum.