Further insight into the association of Life’s Essential 8 and MAFLD

Life’s Essential 8 and MAFLD in the United StatesJournal of HepatologyVol. 78Issue 2PreviewThe American Heart Association (AHA) recently proposed Life’s Essential 8 (LE8) as an update of Life’s Simple 7 (LS7) to quantify cardiovascular health (CVH), which included five health behaviors (nicotine exposure, physical activity, diet, body mass index, and sleep health) and three health factors (blood lipids, blood pressure, and blood glucose).1 By adding a new sleep metric and being redefined on a more continuous scale, LE8 better reflects recent clinical guidelines, interindividual difference and intraindividual change than LS7. Full-Text PDF I read with great interest the recent study by Xinyu Wang et al. published in the Journal of Hepatology,[1]Wang X. Wang A. Zhang R. Cheng S. Pang Y. Life’s essential 8 and MAFLD in the United States.J Hepatol. 2023; 78: e61-e63https://doi.org/10.1016/j.jhep.2022.10.014Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar which cross-sectionally investigated the association between Life’s Essential 8 (LE8) and metabolic dysfunction-associated fatty liver disease (MAFLD) in a representative sample of the US population. The main finding of this article was that after adjusting for age, sex, ethnicity, marital status, and education, individuals with high cardiovascular health (CVH) had a lower risk of MAFLD compared to those with low CVH (odds ratio 0.04, 95% CI 0.01-0.15). Meanwhile, I have some further thoughts and considerations about this article. First, the presence of potential confounding factors. The results of this article were adjusted for demographic variables only, and potential confounding factors still need to be considered (e.g., poverty index, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyltransferase, hepatitis B/C virus infection, or co-morbidity status). Second, considerations for special populations. Pregnant participants and participants under 20 years old were excluded from this study, but participants with cardiovascular disease (CVD) were not excluded or adjusted for as a covariate, which may be an important consideration given the effect of CVD on CVH. Additionally, the presence of sarcopenia is now considered an important indicator of non-alcoholic fatty liver disease (NAFLD) severity and prognosis in previous studies and can be extrapolated to MAFLD due to its substantial overlap with NAFLD.[2]Chun H.S. Kim M.N. Lee J.S. Lee H.W. Kim B.K. Park J.Y. et al.Risk stratification using sarcopenia status among subjects with metabolic dysfunction-associated fatty liver disease.J Cachexia Sarcopenia Muscle. 2021; 12: 1168-1178https://doi.org/10.1002/jcsm.12754Crossref PubMed Scopus (16) Google Scholar Ho Soo Chun et al. analyzed data from the Korea National Health and Nutrition Examination Survey and found that among individuals with MAFLD, those with sarcopenia were at higher risk for atherosclerotic CVD and significant liver fibrosis.[2]Chun H.S. Kim M.N. Lee J.S. Lee H.W. Kim B.K. Park J.Y. et al.Risk stratification using sarcopenia status among subjects with metabolic dysfunction-associated fatty liver disease.J Cachexia Sarcopenia Muscle. 2021; 12: 1168-1178https://doi.org/10.1002/jcsm.12754Crossref PubMed Scopus (16) Google Scholar Moreover, recent studies have demonstrated that obstructive sleep apnea (OSA) is associated with the development and evolution of NAFLD.[3]Mesarwi O.A. Loomba R. Malhotra A. Obstructive sleep apnea, hypoxia, and nonalcoholic fatty liver disease.Am J Respir Crit Care Med. 2019; 199: 830-841https://doi.org/10.1164/rccm.201806-1109TRCrossref PubMed Scopus (107) Google Scholar Considering the high prevalence of OSA in patients with CVD and the important role of sleep health in the assessment of CVH, OSA may also be another important subgroup to study.[4]Yeghiazarians Y. Jneid H. Tietjens J.R. Redline S. Brown D.L. El-Sherif N. et al.Obstructive sleep apnea and cardiovascular disease: a scientific statement from the American heart association.Circulation. 2021; 144: e56-e67https://doi.org/10.1161/CIR.0000000000000988Crossref PubMed Scopus (242) Google Scholar,[5]Lloyd-Jones D.M. Allen N.B. Anderson C.A.M. Black T. Brewer L.C. Foraker R.E. et al.Life’s essential 8: updating and enhancing the American heart association’s construct of cardiovascular health: a presidential advisory from the American heart association.Circulation. 2022; 146: e18-e43https://doi.org/10.1161/CIR.0000000000001078Crossref PubMed Scopus (219) Google Scholar Furthermore, in the study by Lili Wang et al. on LE8 and NAFLD, there were significant interactions between LE8 score and age, race, education level, and poverty rate.[6]Wang L. Yi J. Guo X. Ren X. Associations between life’s essential 8 and non-alcoholic fatty liver disease among US adults.J Transl Med. 2022; 20: 616https://doi.org/10.1186/s12967-022-03839-0Crossref PubMed Scopus (3) Google Scholar Therefore, further research on the application of LE8 in different special populations, age groups, races and social backgrounds will be of great importance. Third, only participants with complete CVH metrics were included in this study, which may have caused selection bias. LE8 is more complex to assess compared to LS7; it was not possible to calculate a complete score for each LE8 component for most participants in NHANES. My further analysis of the study by Xinyu Wang et al. found that those excluded from the study had poorer CVH, were older, and had a lower level of education (data not shown). In addition, Fanny Petermann-Rocha et al. considered that the mean LE8 score assumes equal weighting for each health metric which is counter-intuitive given that different risk factors have differential weightings for different outcomes.[7]Petermann-Rocha F. Deo S. Celis-Morales C. Ho F.K. Bahuguna P. McAllister D. et al.An opportunity for prevention: associations between the life’s essential 8 score and cardiovascular incidence using prospective data from UK biobank.Curr Probl Cardiol. 2022; 48101540https://doi.org/10.1016/j.cpcardiol.2022.101540Crossref PubMed Scopus (7) Google Scholar In conclusion, allowing a certain degree of missing data for LE8 components or setting a weight for each LE8 component may be a viable alternative. Considering the prevalence of MAFLD, it is necessary to further investigate how to apply, promote and enhance LE8 in the real world to better evaluate the relationship between CVH and MAFLD. Fourth, MAFLD is known to be heterogeneous and can be divided into different subtypes, including the overweight/obesity subtype, lean metabolic disorder subtype, and diabetes subtype.[8]Eslam M. Newsome P.N. Sarin S.K. Anstee Q.M. Targher G. Romero-Gomez M. et al.A new definition for metabolic dysfunction-associated fatty liver disease: an international expert consensus statement.J Hepatol. 2020; 73: 202-209https://doi.org/10.1016/j.jhep.2020.03.039Abstract Full Text Full Text PDF PubMed Scopus (1735) Google Scholar A study by Xu Chen et al. found that MAFLD was not associated with all-cause mortality, but individuals with lean or diabetic MAFLD may be at a higher risk of all-cause mortality than those with overweight/obese MAFLD.[9]Chen X. Chen S. Pang J. Tang Y. Ling W. Are the different MAFLD subtypes based on the inclusion criteria correlated with all-cause mortality?.J Hepatol. 2021; 75: 987-989https://doi.org/10.1016/j.jhep.2021.06.013Abstract Full Text Full Text PDF PubMed Scopus (30) Google Scholar Further consideration of MAFLD subtypes in the assessment of the relationship between LE8 and MAFLD may be important for precise therapeutic interventions. In conclusion, the relationship between LE8 and MAFLD needs to be further investigated in the context of precision medicine and primary prevention. The author received no financial support to produce this manuscript. The author declares no conflicts of interest that pertain to this work. Please refer to the accompanying ICMJE disclosure forms for further details. The following are the supplementary data to this article: Download .pdf (.19 MB) Help with pdf files Multimedia component 1