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Fatty liver may play role in CVD risk
ANAHEIM, Calif. — Fatty liver is associated with CVD risk, according to data presented during the American Heart Association Scientific Sessions.
The global prevalence of nonalcoholic fatty liver disease (NAFLD) is 25%, and 67% of patients with obesity have the disease.
“The epidemic of nonalcoholic fatty liver disease has swept across the globe, and this will have metabolic consequences on cardiovascular health,” Marja-Riitta Taskinen, MD, PhD, professor emeritus of internal medicine at University of Helsinki Central Hospital, said during the presentation.
Increased prevalence
In a study published in Hepatology in 2017, researchers found that the incidence of NAFLD has increased about fivefold and is parallel to increasing obesity rates, and it has increased sevenfold in younger adults. Patients with this disease have shorter life spans by about 4 years.
“This truly means that we are facing a big problem, and nonalcoholic fatty liver disease will have huge implications for health care being a real time bomb,” Taskinen said.
During the past few years, numerous studies have been published that showed the relationship between NAFLD and CVD. NAFLD is also a predictor of CV events and deaths and associated with increased subclinical CVD, excess prevalence of coronary plaques and coronary artery calcification, she said.
In a study published in Gut in 2017, patients with NAFLD had a higher coronary calcium score compared with those without the disease. Through this, NAFLD was associated with the progression of coronary atherosclerosis independent of established risk factors, according to the presentation.
“Nonalcoholic fatty liver disease is a new driving force for cardiovascular disease manifestations,” Taskinen said.
The “liver-heart axis” is associated with the risk for cardiac arrhythmias. Fatty livers have previously been linked to long QT syndrome, atrial fibrillation and ventricular arrhythmias.
“The exact biological mechanisms are not clear; however, it should be recognized that a biological proinflammatory and pro-oxidative mediators … may alter the electrophysiology and structural substrates in myocardium, and this makes it more vulnerable for cardiac arrhythmias,” Taskinen said.
In a study published in Circulation: Cardiovascular Imaging in 2015, researchers assessed fat depots with magnetic resonance spectroscopy and MRI in patients with obesity who did not have diabetes or CVD. Three different cardiac fat depots were measured: myocardial triglyceride content, epicardial fat and pericardial fat. These three depots increased with a growing amount of visceral adipose tissue and liver fat. Unadjusted and adjusted peak filling rate decreased with an increase of liver fat.
“We can say that fatty liver associates with a fatty heart,” Taskinen said.
Both a fatty heart and a fatty liver are associated with various cardiometabolic risk factors, including insulin resistance, endothelial dysfunction, proinflammatory cytokines, atherogenic dyslipidemia and unstable carotid plaque remodeling.
“The true challenge is to tease apart this complex interrelationship,” Taskinen said.
Liver fat produces various biomarkers and traditional risk factors, and this combination makes both the heart and liver vulnerable, according to the presentation. Fatty liver is also associated with lipotoxicity and cardiac steatosis, which is reflected in cardiac dysfunction.
Fat accumulations in the liver results from the imbalance between lipid input and output, which leads to hepatic steatosis and the overproduction of VLDL. This is reflected in the increase of plasma triglyceride levels.
The dysregulation of VLDL1-triglyceride metabolism in patients with obesity occurs through a synthesis pathway and a clearance pathway. In the synthesis pathway, the overproduction of VLDL1-triglyceride particles is related to fat mass and liver fat, which are independent predictors. In the clearance pathway, apolipoprotein C-III is a predictor of VLDL triglycerides and is inversely related to serum triglyceride levels, according to the presentation.
“The data altogether suggest that this impaired clearance of triglycerides is linked to the increased concentrations of ApoC-III, and that is, of course, an interesting issue,” Taskinen said.
Hypertriglyceridemia is caused by dual metabolic defects, increased secretion and impaired clearance of triglyceride lipoproteins.
Treatment to reduce risk
Fatty liver can be treated through diet, exercise and a less sedentary lifestyle. Currently, there are no approved drugs for the treatment of NAFLD.
“Lifestyle modification remains the critical tool in the battle against nonalcoholic fatty liver disease and CVD,” Taskinen said.
In a study currently under review, researchers gave an isocaloric carbohydrate-restricted diet for 14 days to 10 patients with NAFLD and obesity. This diet led to a slight weight reduction, decreased VLDL triglycerides and a rapid decrease in liver fat, which was seen already after 1 day on the diet. The gut microbiota and short-chain fatty acids were also affected by the isocaloric carbohydrate-restricted diet. Starch and sucrose metabolism decreased as folate biosynthesis increased throughout the study.
“We concluded that this short-term low carbohydrate diet promotes multiple metabolic benefits in obese subjects with fatty liver,” Taskinen said.
Even with this information, more needs to be researched regarding the link between fatty liver and CVD.
“This is the question that remains open: Can prevention and treatment of fatty liver also reduce CVD risk?” Taskinen said. – by Darlene Dobkowski
References:
Taskinen M. Ancel Keys Memorial Lecture: Lifestyle and Medical Therapy for CVD Prevention. Presented at: American Heart Association Scientific Sessions; Nov. 11-15, 2017; Anaheim, Calif.
Allen AM, et al. Hepatology. 2017;doi:10.1002/hep.29546.
Granér M, et al. Circ Cardiovasc Imaging. 2015;doi:10.1161/CIRCIMAGING.114.001979.
Sinn DH, et al. Gut. 2017;doi:10.1136/gutjnl-2016-311854.
Disclosure: Taskinen reports she received research grants, speaker fees, honoraria and consultant fees from Amgen and Novo Nordisk.