γ-Butyrobetaine, L-carnitine and acylcarnitines and their association with incident atrial fibrillation among men and women with suspected chronic coronary syndrome

Carnitine-metabolites play a key role in cell energy metabolism and have been implicated in the pathogenesis of atrial fibrillation (AF). However, any associations between L-carnitine and the precursor γ-butyrobetaine (γBB) with new-onset AF are not established. We therefore examined the relationship between serum γBB, L-carnitine and selected acylcarnitines with incident AF.

We studied 3815 patients who underwent coronary angiography due to suspected chronic coronary syndrome and followed up for incident CVD events, including new-onset AF. Risk associations between the biomarkers and incident AF were explored by logistic regression for the total population and stratified according to sex. The majority (71.6%) of the patients were men, the median age was 61 years. Over a median follow-up of 7.3 years, 412 (10.8%) were reported with new-onset AF. In a multivariate model higher serum γBB, L-carnitine and palmitoylcarnitine [OR per 1SD (95% CI): 1.15 (1.01–1.31), P = 0.04; 1.14 (1.01–1.27), P = 0.03 and 1.15 (1.03–1.28), P = 0.01] were associated with increased risk of incident AF. These associations were particularly stronger among women (P for interaction < 0.04, all).

In this large cohort of patients with suspected chronic coronary syndrome elevated circulating levels of γBB, L-carnitine and palmitoylcarnitine were associated with increased risk of incident AF, with stronger associations among women. Our results motivate further studies examining the relationship between carnitine metabolites and cardiac arrhythmias and highlight the need for sex specific analyses.