Cristiane C K Mayerhofer1, Thor Ueland2, Kaspar Broch3, Royce P Vincent4, Gemma F Cross4, Christen P Dahl5, Pål Aukrust6, Lars Gullestad7, Johannes R Hov8, Marius Trøseid9. 1. Department of Cardiology, Oslo University Hospital, Oslo, Norway; Research Institute of Internal Medicine, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway; K.G. Jebsen Inflammation Research Center, Institute of Clinical Medicine, University of Oslo, Oslo, Norway. 2. Research Institute of Internal Medicine, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway; K.G. Jebsen Thrombosis Research and Expertise Center, University of Tromsø, Tromsø, Norway. 3. Department of Cardiology, Oslo University Hospital, Oslo, Norway. 4. Department of Clinical Biochemistry (Viapath), King's College Hospital NHS Foundation Trust, London, UK. 5. Research Institute of Internal Medicine, Oslo University Hospital, Oslo, Norway. 6. Research Institute of Internal Medicine, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway; K.G. Jebsen Inflammation Research Center, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; K.G. Jebsen Thrombosis Research and Expertise Center, University of Tromsø, Tromsø, Norway; Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital, Oslo, Norway. 7. Department of Cardiology, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway. 8. Research Institute of Internal Medicine, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway; K.G. Jebsen Inflammation Research Center, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Norwegian PSC Research Center and Section of Gastroenterology, Department of Transplantation Medicine, Division of Surgery, Inflammation Medicine, and Transplantation, Oslo University Hospital, Oslo, Norway. 9. Research Institute of Internal Medicine, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway; K.G. Jebsen Inflammation Research Center, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital, Oslo, Norway. Electronic address: marius.troseid@medisin.uio.no.
Abstract
OBJECTIVE: 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. METHODS AND RESULTS: 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. CONCLUSIONS: 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.
OBJECTIVE: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. METHODS AND RESULTS: 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. CONCLUSIONS: 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.