Associations between life’s essential 8 and non-alcoholic fatty liver disease among US adults

Non-alcoholic fatty liver disease (NAFLD) refers to a broad range of clinical and pathological findings which is characterized by excess fat accumulation in hepatocytes in the absence of excessive alcohol consumption or other competing causes for hepatic steatosis [1, 2]. It has become one of the most prevalent chronic liver diseases and affects 25% general population worldwide [3, 4]. NAFLD is recognized as the liver component of a collection of conditions that are associated with systematic metabolic dysfunction, including abdominal obesity, hypertension, atherogenic dyslipidemia, and insulin resistance, which are also well-established risk factors of cardiovascular disease (CVD) [5–7]. Increasing evidence indicates the presence of NAFLD is associated with an increased prevalence and incidence of CVD.

In 2010, the American Heart Association (AHA) proposed Life’s Simple 7 (LS7) as a measurement of cardiovascular health (CVH) to further improve the general population health [8]. Extensive subsequent evidence has proved the ideal CVH defined by LS7 was associated with greater CVD-free survival and total longevity and higher quality of life [9–12]. However, limitations of the original LS7 CVH score were also identified. Accordingly, the AHA recently updated the assessment tool for quantification of CVH namely “Life’s Essential 8” (LE8) [9]. LE8 is a more sensitive scoring system to inter-individual differences and highlights social determinants of health and psychological health for maintaining or improving CVH [13].

Given the close associations between NAFLD and the established CVD risk factors, promoting CVH may be an appropriate prevention and management strategy for reducing the burden of NAFLD. To date, several studies have indicated that optimal LS7 level was associated with decreased risk of incidents of NAFLD [14–17], while no study has investigated the association between the novel CVH construct and NAFLD. In this study, using the lasted available National Health and Nutrition Examination Surveys (NHANES) data, we aim to assess the association of LE8 and NAFLD in a nationally representative population of US adults.

In this nationally representative cross-sectional study, we found inverse dose–response associations between the LE8 score and its health behavior and health factors subscales with NAFLD in US adults. Subgroup analysis indicated that the negative association between LE8 score and NAFLD was stronger among younger, Asian, and high-income participants. The associations remained significant after excluding participants with CVD history.

To our knowledge, several studies have assessed the association between LS7 and NAFLD. A U.S.-based multiethnic cohort revealed that a more favorable LS7 level was associated with a lower prevalence of NAFLD [14]. In a Korean cohort, higher LS7 scores were associated with a decreased risk of incident NAFLD as well as the regression of existing NAFLD among younger adults [17]. In a cross-sectional study from Northern China, the prevalence rates of NAFLD were inversely associated with LS7 summary score quartiles [25]. Our finding is consistent with the current knowledge that NAFLD is inversely associated with CVH levels. However, as the predecessor of LE8, LS7 features definitions may not be able to reflect the full scope of health behaviors and practices in the current situation. In addition, research has revealed limitations in how the metrics are quantified [9]. The CHV definitions of LS7 were categorized into ideal, intermediate, and poor CVH for each component. This definition is less sensitive to interindividual differences and is unable to be used to assess dose–response effects.

The present study added notable evidence of the relationship between CVH and NAFLD by using LE8 as the definition of CVH. We found that the ORs in the association of health factors score with NAFLD decreased sharply in the lower range of the value. The benefits plateaued and then persisted unchanged across the higher values. While the trend was reversed in the association between health behavior score and NAFLD. ORs remain unchanged in the lower range of health behaviors score value and decrease quickly in the higher range. The saturation effect was observed in the association of health factors with NALFD while not in health behavior which indicates a more rigorous standard of health behavior might be preferable. In addition, the association between LE8 score and NAFLD was found to be stronger among younger, Asian, and higher education and income participants. These findings reveal that LE8 enhanced methods for quantification of CVH to increase the sensitivity of scoring to inter-individual differences in both individuals and populations. In addition, these results also highlight the disparity in the potential beneficial value of CHV components and population-level approaches should be implemented to promote CVH.

Although the mechanism between LE8 and NAFLD remains unclear, studies have demonstrated that NAFLD is significantly associated with metabolic syndrome and healthy lifestyles which are intrinsic health factors and health behaviors metrics of LE8 [26–30]. Obesity, a well-established risk factor of cardiovascular disease, is correlated with the expansion of adipose tissue, which leads to dysfunction and death of adipocytes. In the setting of adipose dysfunction, macrophages infiltrate into the adipose tissue and induce inflammation that promotes insulin resistance [2]. In the context of insulin resistance, inappropriate lipolysis and the compromised fat-storing ability of adipose tissue result in the release of free fatty acids into the circulation, which then becomes available for uptake by the liver and overwhelms its metabolic capacity [1, 2]. Both adipose tissue dysfunction and hepatic de-novo lipogenesis were considered as major NAFLD-inducing factors. Inflammation also plays an important role both in CVD and NAFLD. It was reported that Bisphenol A, an endocrine disruptor, could increase the relative risk of both CVD and NAFLD by inducing pro-inflammatory activities and overproduction of interleukin 1β (IL-1β) and IL-6 [31]. Systematic inflammation and circulating cyto- and chemokines including C-reactive protein, IL-6, IL1β, and TNFα fuel CVD through endothelial dysfunction, altered vascular tone, enhanced plaque formation, and coagulation [32]. Increased circulating inflammation markers are also associated with NAFLD. Blood levels of IL-6 were increased in accordance with the histological severity of non-alcoholic steatohepatitis. It is therefore not surprising a composite score of all the LE8 metrics is associated with NAFLD.

Several potential pharmacologic therapies for NAFLD have been studied. Vincenzo et.al found that Empagliflozin, a sodium-glucose cotransporter 2 inhibitor, reduced hepatic and cardiac inflammation in doxorubicin-treated mice which could be effective to reduce the presence and progression of both NAFLD and cardiovascular diseases [33]. However, most evidence remains experimental and there is no licensed drug for NAFLD until now. Therefore, the lifestyle modification approach remains the foundation of NAFLD management [34–37]. However, most previous studies have focused on individual factors in relation to NAFLD and all-around lifestyle recommendations for NAFLD patients are lacking. LE8 is a comprehensive and easily applicable assessment tool in clinical settings to promote adherence to healthy behaviors and ideal health factors. Our study extends the range of health outcomes associated with a beneficial role of ideal CVH metrics in NAFLD in addition to CVD and indicates that adherence to ideal CVH metrics may be an appropriate prevention and management strategy for reducing the burden of NAFLD as well as other chronic diseases including CVD.

The main strength of this study is the use of a large nationally representative sample of US adults which allows the findings to be generalized to a broader population. In addition, we addressed the dose–response relationship between CVH and NAFLD and identified the minimal threshold for the beneficial association. Several potential limitations should also be considered. Firstly, health behavior metrics assessments were based on self-report questionnaires which are subject to measurement errors. Secondly, we used the VTCE result as the diagnosis standard of hepatic steatosis. However, for its well-known limitations, it is neither practical nor feasible to perform liver biopsies on a vast population. Considering VTCE is a sensitive measurement of liver fat [38], it could be regarded as a satisfactory assessment tool in a large population-based epidemiologic study setting. Finally, although we controlled for several potential confounders, the nature of the cross-sectional study design precludes us from concluding causality and temporality between CVH and NAFLD risk.

In this nationally representative sample of US adults, higher LE8 and its subscales scores were independently associated with the lower presence of NAFLD in non-linear fashions. Furthermore, the strength of the association between LE8 score and NAFLD differed within the study population. Our study results indicate a potential beneficial role of LE8 as a feasible and effective approach for promoting hepatic health. Further research on the longitudinal and causality association of LE8 and NAFLD risk is needed.