New findings suggest that NAFLD may be an independent risk factor for CVD

Non-alcoholic fatty liver (NAFLD) is the most common chronic liver disorder increasing morbidity and mortality worldwide with cardiovascular disease (CVD) being the main cause of death.1 Recent findings from a meta-analysis of observational studies demonstrated an increased cardiovascular risk with NAFLD, especially with advanced fibrosis.2 Therefore, with several studies highlighting this association, it may be important to consider cardiovascular screening in NAFLD patients in addition to the management of liver disease due to its potential in decreasing the disease burden.3

Non-alcoholic fatty liver (NAFLD) is the most common chronic liver disorder affecting around 25% of the adult population globally and leading to liver-related morbidity and mortality.1 It is also a common cause of end-stage liver disease, primary liver cancer, and liver transplantation, increasing the health economic burden substantially and leading to death.1

NAFLD, occurring in association with metabolic risk factors such as obesity and type 2 diabetes mellitus, is characterized by a broad range of clinicopathologic findings that include steatosis with or without mild inflammation (NAFL) and the necroinflammatory subtype with hepatocellular injury (NASH).1 Determining the degree of liver fibrosis is necessary due to its correlation with disease severity, liver-related complications, and poor prognosis.1 Cardiovascular disease (CVD), particularly coronary heart disease, is a predominant cause of death in NAFLD patients, accounting for 40% of total death.3 Although the underlying mechanism of this association is not fully understood, NAFLD progression may accelerate atherogenesis.3


A Korean cohort study examined the association of hepatic steatosis with or without fibrosis and progression of carotid atherosclerosis in patients with type 2 diabetes, who underwent repeated carotid artery ultrasonography.4 Of the 1,120 patients included, 56.8% had hepatic steatosis at baseline, and after 6-8 years, 38.5% showed atherosclerotic progression.4 The presence of hepatic steatosis with fibrosis, but not hepatic steatosis alone, significantly increased the risk of carotid plaque progression among all metabolic subgroups irrespective of age, body mass index, presence of metabolic syndrome, or insulin sensitivity.4


Since multiple studies showed conflicting evidence, a meta-analysis was conducted to examine the association between NAFLD and the risk of CVD events.5 A total of 16 observational prospective and retrospective studies of 34,043 patients with 36.3% having NAFDL and 2,600 CVD outcomes during 6.9 years were included.5 Results showed that NAFLD was associated with an increased risk of fatal and non-fatal CVD events, but further studies were needed.5

As a result, a similar recent meta-analysis of observational studies published in the Lancet Gastroenterology and Hepatology was performed to quantify the magnitude of the association between NAFLD and risk of CVD events defined as CVD death, non-fatal CVD events, or both.2 This study included 36 longitudinal studies on 5,802,226 patients with a mean age of 53 years and identified 99,668 cases of fatal and non-fatal CVD events during a follow-up period of 6.5 years.2 A moderate increase in the risk of CVD events was observed (HR=1.45; 95% CI: 1.31-1.61) with a substantial increase seen in severe NFLD, especially fibrosis (HR=2.50; 95% CI: 1.68-3.72).2 The results observed were consistent in the sensitivity analysis and independent of age, sex, adiposity measures, diabetes, and other common cardiometabolic risk factors.2

Hence, clinicians should not only focus on liver disease but also suspect CVD and consider risk modifications in NAFLD patients including CVD risk estimation, healthy active lifestyle, smoking cessation, blood pressure management, diabetes optimization, and lipid-lowering therapy.3

Dr. Cynthia Kos, a cardiologist and heart failure specialist at Deborah Heart and Lung Center in New Jersey, mentioned that “studies such as this have the potential to garner interest from the cardiologists, especially if the evidence suggests that a novel CV risk factor is emerging.”

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