Fatty liver is independently associated with sub-clinical heart failure in obese people, according to a new study. The findings add more support to the importance of dietary interventions in such patients, researchers said.
Non-alcoholic fatty liver disease (NAFLD), also known as hepatic steatosis, is the most common liver disease, with a prevalence of up to 30% in the general population and between 70% and 90% among persons who are obese or have type 2 diabetes. NAFLD is considered as a manifestation of the metabolic syndrome, a group of risk factors like high blood pressure, excess abdominal fat and unhealthy cholesterol levels that raise the risk of heart attacks, strokes and other health problems.
“One of the unique aspects of our study is that we took all of the individual components of the metabolic syndrome into account as possible confounders in this association, as the metabolic syndrome is associated with NAFLD and with cardiovascular disease,” said study lead author Dr Ralph L Widya, from the Leiden University Medical Centre in Leiden, the Netherlands.
For the study, Widya and colleagues used proton magnetic resonance spectroscopy to non-invasively measure hepatic triglyceride content, a measure of fat in the liver, and cardiac MRI to assess left ventricular diastolic function in 714 men and women aged 45 to 65 years. Of the 714 patients, 47% were categorised as overweight, and 13% were classified as obese.
The left ventricle is the heart’s main pumping chamber, and diastolic function refers to the phase of the heartbeat when the heart relaxes to fill with blood. Abnormalities of diastolic function, represented by inefficient filling of the heart, play a major role in exercise intolerance in patients presenting with heart failure.
Diastolic dysfunction has been clinically undervalued and is currently gaining major attention by cardiologists and general physicians, according to senior author Dr Hildo J Lamb, also from Leiden University Medical Centre.
Results indicated that an increase in hepatic triglyceride content was associated with a decrease in mean left ventricular diastolic function in the obese subgroup of the study population. The association between hepatic triglyceride content and left ventricular diastolic function existed independently of the metabolic syndrome, suggesting that fatty liver itself could, at least in obese people, pose a risk of heart dysfunction above and beyond known cardiovascular risk factors that are clustered within the metabolic syndrome.
“Our results may be of importance in cardiovascular risk stratification in obesity, because there is a large variation in the degree of hepatic steatosis in obesity,” Widya said. “Also, more emphasis should be put on dietary interventions to reduce or prevent hepatic steatosis.”
The reasons for the link between fatty liver and heart function are unknown, Widya said, but could be related to several factors, including the presence of infection-fighting white bloods cells called macrophages or increased expression in the liver of small proteins known as cytokines.
Future research is required to study the effect of NAFLD on cardiovascular events, according to Widya and Lamb, and further study is needed to investigate to what extent the association exists and differs among normal weight, overweight and obese persons.
To investigate the association between hepatic triglyceride content and left ventricular (LV) diastolic function while taking potential confounding factors into account, including the components of the metabolic syndrome.
Materials and Methods
The study was approved by the institutional review board, and all participants gave informed consent. In this cross-sectional analysis of baseline data from the Netherlands Epidemiology of Obesity study, a population-based, prospective cohort study, participants (45% men; mean age ± standard deviation, 55.3 years ± 6.2) underwent magnetic resonance (MR) spectroscopy and MR imaging to assess hepatic triglyceride content and LV diastolic heart function (ratio of peak filling rates of the early filling phase and atrial contraction [E/A ratio]). Multivariate linear regression analysis was performed while adjusting for confounding factors, and results were additionally stratified according to body mass index.
Adjustment for age, sex, heart rate, alcohol consumption, pack-years of smoking, all components of the metabolic syndrome, and visceral adiposity attenuated crude observed associations. A 10-fold increase in hepatic triglyceride content was associated with a change in mean E/A ratio of −0.004 (95% confidence interval [CI]: −0.134, 0.125) in the total study population, −0.194 (95% CI: −0.430, 0.042) in the normal-weight subgroup, 0.079 (95% CI: −0.090, 0.248) in the overweight subgroup, and −0.109 (95% CI: −0.186, −0.032) in the obese subgroup.
Fatty liver itself could, at least in obesity, pose a risk of myocardial dysfunction above and beyond known cardiovascular risk factors that are clustered within the metabolic syndrome. The association in the obese subgroup was small, and future studies with larger samples sizes are required to investigate to what extent the association exists and differs in normal-weight, overweight, and obese persons to unravel its clinical relevance.