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

BACKGROUND

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.

METHODS

We consecutively recruited eligible subjects with moderate-severe CAS ( = 60), aortic sclerosis (ASc) ( = 49) and age and gender-matched control subjects ( = 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.

RESULTS

Prevalence of traditional cardiovascular risk factors or co-morbidities did not differ among groups (all  > 0.05). CAS patients had higher plasma choline levels compared to both control ( < 0.001) and ASc ( = 0.006). Plasma betaine and TMAO levels were similar (both  > 0.05). Compared to the lowest quartile choline levels (<11.15 μM), patients with the highest quartile choline levels (≥14.98 μM) had higher aortic valvular ( < 0.001) and mitral annular ( = 0.013) calcification scores. Plasma choline levels were independently associated with aortic peak flow velocity (B ± SE:0.165 ± 0.060,  = 0.009). Choline levels were elevated in subjects who had aortic valves with denser lymphocyte infiltration ( < 0.001), neovascularization ( = 0.011), osseous metaplasia ( = 0.004), more severe tissue remodelling ( = 0.002) and calcification ( = 0.002).

CONCLUSION

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.