Metabolomics of aortic valve stenosis: Are aortic valve stenosis and sclerosis different diseases?

Abstract

Background and aims: Calcific aortic valve disease (CAVD) shares the same risk factors as atherosclerotic vascular diseases (ASVD). However, in contrast to ASVD, treating the risk factors has not been shown to be effective in preventing CAVD and its progression to aortic stenosis (AS). Thus, the ultimate pathophysiology of CAVD remains unknown. This study aimed to evaluate metabolic signatures associated with CAVD.

Methods: We carried out metabolomic analyses on a total of 255 subjects: 82 patients with AS, 72 patients with aortic valve sclerosis (ASc) and 101 healthy controls. Blood lipoproteins and metabolites, including lipids, amino acids, and inflammatory markers, were measured using nuclear magnetic resonance (NMR) metabolomics.

Results: There were no significant differences in total cholesterol, HDL cholesterol, LDL cholesterol, or triglycerides. However, levels of small HDL particles were significantly lower in the AS group compared to the ASc and control groups, whereas no differences were found between the ASc and control groups. In addition, the levels of albumin and several amino acids were lower in the AS group when compared to the ASc group. These results suggest that patients with AS and ASc have different metabolic profiles.

Conclusions: Our study is the first to show that the levels of small HDL rather than plasma HDL concentration are significantly lower in AS patients. This suggests that small HDL may be one missing link in the pathophysiologic process between dyslipidemia and CAVD and generate innovative approaches for preventing CAVD. The results also prompt the question whether AS and ASc are distinct diseases.

Keywords: Aortic valve sclerosis; Aortic valve stenosis; Calcific aortic valve disease; Cardiovascular diseases; High density lipoprotein; Metabolomics.