“A Fatty Liver May Result in a Broken Heart,” According to New Research

Strict monitoring of cardiovascular disease recommended when managing nonalcoholic fatty liver disease, reports the Journal of Hepatology

Amsterdam, April 26, 2016

Cardiovascular disease (CVD) is primarily the cause of death of patients with nonalcoholic fatty liver disease (NAFLD). The extent to which NAFLD itself, rather than associated conditions such as diabetes, obesity, or atherogenic dyslipidemia, is responsible for increased cardiovascular death has been a matter of debate. In a new study, investigators from the Pitié-Salpêtrière Hospital, Pierre and Marie Curie University conclude that NAFLD is an independent risk factor for atherosclerosis and therefore CVD. Their findings, published in the Journal of Hepatology, recommend strict monitoring of cardiovascular health and metabolic complications in patients with NAFLD.

NAFLD is an increasingly common condition in patients with obesity, type 2 diabetes, atherogenic dyslipidemia and arterial hypertension. “Evidence indicates that the fatty and inflamed liver expresses several pro-inflammatory and procoagulant factors, as well as genes involved in accelerated atherogenesis,” explained lead investigator Raluca Pais, MD, PhD, of the Pierre and Marie Curie University, INSERM, and the CDR Saint Antoine, Institute of Cardiometabolism and Nutrition (ICAN), Paris, France. “This raises the possibility that the link between NAFLD and cardiovascular mortality might not simply be mediated by shared, underlying, common risk factors, but rather that NAFLD independently contributes to increasing this risk,” added senior author Professor Vlad Ratziu, MD, PhD.

Investigators undertook a large retrospective study of close to 6,000 patients referred to the Primary Cardiovascular Prevention Center at Pitié-Salpêtrière Hospital, Paris between 1995 and 2012 to assess whether NAFLD is incidental to or is the cause of atherosclerosis of the carotid arteries, the major blood vessels in the neck that supply blood to the brain, neck, and face.

All patients were examined using carotid ultrasound with measurement of carotid intima-media thickness and carotid plaques. Using the Fatty Liver Index (FLI) a well-validated biomarker panel, researchers observed that steatosis (fatty liver) is associated with carotid intima-media thickness (C-IMT), a pre-atherosclerotic lesion that predicts cardiovascular events. C-IMT increased proportionally with FLI, and this association was independent of traditional cardiometabolic risk factors.

Steatosis predicted C-IMT better than diabetes or dyslipidemia, after adjustment for metabolic syndrome and cardiovascular risk factors, in 5,671 patients. Long-term follow-up in 1,872 patients after eight years added a further critical piece of information by confirming that patients with fatty liver were more likely to develop carotid plaque over time. Steatosis occurred in 12% and carotid plaques in 23% of these patients. C-IMT increased in patients with steatosis, but did not change in those who stayed free of steatosis. Steatosis at baseline predicted the occurrence of carotid plaques independent of age, sex, type-2 diabetes, tobacco use, and other cardiovascular risk factors.

The team concluded that in patients with metabolic syndrome at risk for cardiovascular events, NAFLD contributes to early atherosclerosis and its progression, independent of traditional cardiovascular risk factors.

“Regardless of the mechanisms involved, the clinical implications are of critical importance since patients at cardiovascular risk presenting with one or more metabolic syndrome characteristics are at even greater risk if they have steatosis,” noted Dr. Pais. “We also found that patients with steatosis, but not overweight, not type 2 diabetic, or without arterial hypertension are at higher risk of developing these complications than individuals without steatosis. This indicates that NAFLD is a precursor of metabolic syndrome. It follows that the diagnosis of steatosis is extremely important and therefore a thorough cardiovascular and metabolic work-up and strict monitoring of CVD or metabolic complications are needed in the clinical management of NAFLD.”

“Taken as a whole, the bulk of evidence suggests NAFLD increases cardiovascular risk, although this relationship may be modified by other factors. The clinical implications of this paradigm may alter the decision to institute primary prevention strategies with anti-platelet, lipid lowering or anti-hypertensive drugs. A further intriguing thought is whether fatty liver can be a therapeutic target for cardiovascular risk reduction,” commented noted experts Leon Adams, PhD, of the University of Western Australia, and Quentin M. Anstee, PhD, of Newcastle University, UK, in an accompanying editorial.

“Clinicians should be aware of the increased cardiovascular risk in patients with NAFLD and consequently screen for conventional cardiovascular risk factors and use accepted risk calculators to make decisions regarding preventative pharmacotherapy, including statins,” emphasized Dr. Adams and Dr. Anstee.

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Notes for editors
“Fatty liver is an independent predictor of early carotid atherosclerosis,” by Raluca Pais, Philippe Giral, Jean-Francois Khan, David Rosenbaum, Chantal Housset, Thierry Poynard, and Vlad Ratziu, for the LIDO Study Group. (doi: 10.1016/j.jhep.2016.02.023).

“Editorial: A fatty liver leads to a broken heart?” by Leon Adams, MBBS PhD and Quentin M. Anstee, BSc, MB BS, PhD, MRCP (doi: 10.1016/j.jhep.2016.03.012).

Published online in the Journal of Hepatology in advance of Volume 65, Issue 1 (July 2016) by Elsevier.

Full text of these articles is available to credentialed journalists upon request; contact Sybrand Boer Iwema at +31 204 85 2 781 or hmsmedia@elsevier.com. Journalists wishing to interview the study authors should contact Vlad Ratziu at + 33 637 356 000, vlad.ratziu@upmc.fr or vratziu@teaser.fr. To reach Dr. Anstee for comment please contact Helen Rae at +44 1912087374 or Helen.Rae@newcastle.ac.uk. For questions concerning the Journal of Hepatology, contact Editor-in-Chief Rajiv Jalan at hmsmedia@elsevier.com.

About the Journal of Hepatology
The Journal of Hepatology is the official journal of the European Association for the Study of the Liver (EASL). It publishes original papers, reviews, case reports and letters to the Editor concerned with clinical and basic research in the field of hepatology. The journal, with an Impact Factor of 11.336, is the top ranking journal in Hepatology according to the 2014 Journal Citation Reports® published by Thomson Reuters, 2015.

About EASL
In the forty plus years since EASL was founded, it has grown from a small organization that played host to 70 participants at its first meeting, to becoming the leading liver association in Europe. EASL attracts the foremost hepatology experts as members and has an impressive track record in promoting research in liver disease, supporting wider education and promoting changes in European liver policy.

About Elsevier
Elsevier is a world-leading provider of information solutions that enhance the performance of science, health, and technology professionals, empowering them to make better decisions, deliver better care, and sometimes make groundbreaking discoveries that advance the boundaries of knowledge and human progress. Elsevier provides web-based, digital solutions — among them ScienceDirect, Scopus, Research Intelligence and ClinicalKey— and publishes over 2,500 journals, including The Lancet and Cell, and more than 35,000 book titles, including a number of iconic reference works. Elsevier is part of RELX Group, a world-leading provider of information and analytics for professional and business customers across industries. www.elsevier.com

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