Increased Secondary/Primary Bile Acid Ratio in Chronic Heart Failure

• Published in: Journal of cardiac failure Vol. 23; no. 9; pp. 666 - 671
• Main Authors: Mayerhofer, Cristiane C.K., Ueland, Thor, Broch, Kaspar, Vincent, Royce P., Cross, Gemma F., Dahl, Christen P., Aukrust, Pål, Gullestad, Lars, Hov, Johannes R., Trøseid, Marius
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.09.2017; Elsevier
• Subjects: Adult; Aged; Bile Acids and Salts - blood; Bile acids profile; Biomarkers - blood; Chronic Disease; Chronic heart failure; Clinical medical disciplines: 750; clinical outcome; Cohort Studies; Cross-Sectional Studies; Gastrointestinal Microbiome - physiology; gut microbiota; Heart Failure - blood; Heart Failure - diagnostic imaging; Humans; Klinisk medisinske fag: 750; Medical disciplines: 700; Medisinske Fag: 700; Middle Aged; Prospective Studies; VDP; Chronic heart failure; Bile acids profile; clinical outcome; gut microbiota
• ISSN: 1071-9164; 1532-8414; 1532-8414
• DOI: 10.1016/j.cardfail.2017.06.007

•In this cross-sectional study, we found decreased serum levels of primary bile acids and increased levels of specific secondary bile acids, resulting in increased ratios of secondary to primary bile acids, in patients with chronic heart failure.•The ratio of secondary to primary bile acids was associated with reduced overall survival in univariate analysis, but not in multivariate analyses.•Although the production of secondary bile acids depends on the gut microbiota, several factors affecting the production, regulation, and elimination of bile acids could contribute to these findings.•Future studies should assess the potential role of bile acid composition in patients with heart failure and investigate whether manipulation of factors influencing bile acid metabolism, including the intestinal microbial community, could alter clinical outcome. Bile acids (BAs) are now recognized as signaling molecules and emerging evidence suggests that BAs affect cardiovascular function. The gut microbiota has recently been linked to the severity of heart failure (HF), and microbial metabolism has a major impact on BA homeostasis. We aimed to investigate the pattern of BAs, and particularly microbiota-transformed (secondary) BAs, in patients with chronic HF. This was a prospective, observational, single-center study including 142 patients with chronic HF and 20 age- and sex-matched healthy control subjects. We measured plasma levels of primary, secondary, and total BAs, and explored their associations with clinical characteristics and survival. Plasma levels of primary BAs were lower (P < .01) and the ratios of secondary to primary BAs higher (P < .001) in patients with HF compared with control subjects. Approximately 40% of patients in the upper tertile of the ratio of secondary to primary BAs died during 5.6 years of follow-up (unadjusted Cox regression: hazard ratio 1.93, 95% confidence interval 1.01–3.68, compared with the lower tertiles). However, this association was attenuated and no longer significant in multivariate analyses. Levels of primary BAs were reduced and specific secondary BAs increased in patients with chronic HF. This pattern was associated with reduced overall survival in univariate analysis, but not in multivariate analyses. Future studies should assess the regulation and potential role of BA metabolism in HF.