ISSN ONLINE: 2558-815X
ISSN PRINT: 1584-9244
ISSN-L: 1584-9244

The risk of cardiovascular disease and use of statins in adults with nonalcoholic fatty liver disease


Nonalcoholic fatty liver disease (NAFLD) is a major cause of chronic liver disease on a global scale. It encompasses a range of conditions, beginning with hepatic steatosis and progressing to nonalcoholic steatohepatitis (NASH) and liver cirrhosis(1). The incidence of NAFLD has experienced a substantial rise throughout the years, currently affecting around 32% of adults worldwide(2). This epidemiological phenomenon exhibits a direct correlation with the worldwide epidemics of obesity and diabetes, which are significant risk factors for cardiovascular diseases(1). According to a recent meta-analysis of 116 research papers, the prevalence of NAFLD among overweight or obese adults is 50.7%(3).
The proposal to rename NAFLD as metabolic-associated fatty liver disease (MAFLD) underscores the significance of metabolic abnormalities in these patients(4). The prevalence of dyslipidemia is significant in patients with NAFLD, which is characterized by elevated triglycerides and low-density lipoprotein cholesterol (LDL-c) levels, together with decreased high-density lipoprotein cholesterol (HDL-c) levels(4). An example is the retrospective study of Yoneda et al., which found that patients with NAFLD had a significantly higher incidence of dyslipidemia than those without this hepatic disorder (63.6% versus 20.2%)(5). Furthermore, atherogenic dyslipidemia has been identified as a significant risk factor for cardiovascular diseases, which are the leading cause of mortality in individuals with NAFLD(4). Recent studies have shown an obvious relationship between the accumulation of fats in the liver tissue and the development of atherosclerotic plaques in the coronary arteries. This association is particularly strong with non-calcified plaques(5). Additionally, there is a link between steatosis, liver fibrosis, and cardiac diastolic dysfunction(5). Patients with NAFLD can experience a substantial improvement in their prognosis through the appropriate management of dyslipidemia.
Despite concerns regarding the potential for liver damage in individuals with NAFLD who are undergoing statin treatment, studies have shown that statins have a favorable safety profile, even in patients with moderately high liver enzyme levels and dyslipidemia(4). Furthermore, a recent study has shown that statins may have a beneficial impact on inflammation and liver fibrosis related to NAFLD. This effect is attributed to the wide-ranging properties of statins(4). Studies conducted on animal models have revealed that statins not only lower serum cholesterol levels but also reduce the levels of pro-inflammatory cytokines such as tumor necrosis factor alpha (TNF-alpha), transforming growth factor beta 1 (TGF-1β), IL-1β, and IL-6(4). Additional important regulators that demonstrate anti-inflammatory and antifibrotic properties in individuals with NAFLD have been identified as small guanine triphosphate binding proteins (GTPases), paraoxonase 1, and proliferator-activated receptor α(4). Also, there is evidence indicating that statin therapy can effectively decrease serum aminotransferases levels in patients with NASH(4). Therefore, statin therapy in patients with chronic liver disease can decelerate the advancement of fibrosis. In patients with liver cirrhosis, it may decrease the risk of liver disease decompensation and mortality(6).
Despite the beneficial effects of statins in patients with NAFLD, which have been demonstrated in multiple studies, these drugs have been underutilized(6). A recent study by Yeoh et al. examined the association between the use of statins and the risk of atherosclerotic cardiovascular disease (ASCVD) in patients with NAFLD(6). These authors concluded that more than 46% of patients with NAFLD have a medium or high risk of ASCVD at 10 years(6). However, the use of statins among these patients was only 48.3%(6). Furthermore, the multivariate analysis revealed that older patients had a higher incidence of statin use compared to younger patients. Additionally, patients with diabetes or hypertension were found to have a greater likelihood of using statins compared to people without these illnesses(6). Another noteworthy finding was that patients who possessed health insurance utilized statins with a higher frequency than those who did not have health insurance(6). Therefore, it is suggested that the financial constraints faced by patients may account for the limited use of statins. These findings are alarming, given the high risk of cardiovascular diseases among patients with NAFLD and dyslipidemia.

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Camelia C. DIACONU


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Diaconu CC. The risk of cardiovascular disease and use of statins in adults with nonalcoholic fatty liver disease. Arch Balk Med Union. 2023;58(4):307-309.