Association of dietary and gut microbiota-related metabolites with calcific aortic stenosis

Histopathological changes in calcific aortic stenosis (CAS) resemble changes in coronary atherosclerosis. Concerning recent evidence on dietary and gut microbiota-related metabolites representing players in atherosclerosis, we aimed to investigate the link between dietary and gut microbiota-derived metabolites and CAS. We consecutively recruited eligible subjects with moderate-severe CAS (<i>n</i> = 60), aortic sclerosis (ASc) (<i>n</i> = 49) and age and gender-matched control subjects (<i>n</i> = 48) in May 2016-December 2016. Plasma dietary and gut microbiota-related metabolite levels, namely choline, betaine, and trimethylamine N-oxide (TMAO), were measured using ultra-performance liquid chromatography-tandem mass spectroscopy method. Histopathological examinations were performed in patients that underwent aortic valve surgery. Prevalence of traditional cardiovascular risk factors or co-morbidities did not differ among groups (all <i>p</i> &gt; 0.05). CAS patients had higher plasma choline levels compared to both control (<i>p</i> p = 0.006). Plasma betaine and TMAO levels were similar (both <i>p</i> &gt; 0.05). Compared to the lowest quartile choline levels (&lt;11.15 μM), patients with the highest quartile choline levels (≥14.98 μM) had higher aortic valvular (<i>p</i> p = 0.013) calcification scores. Plasma choline levels were independently associated with aortic peak flow velocity (B ± SE:0.165 ± 0.060, <i>p</i> = 0.009). Choline levels were elevated in subjects who had aortic valves with denser lymphocyte infiltration (<i>p</i> p = 0.011), osseous metaplasia (<i>p</i> = 0.004), more severe tissue remodelling (<i>p</i> = 0.002) and calcification (<i>p</i> = 0.002). We found a significant association between choline levels and CAS presence and severity depicted on imaging modalities and histopathological examinations. Our study may open new horizons for prevention of CAS.