Abstract
BackgroundThe risk of liver fibrosis in non-alcoholic fatty liver disease (NAFLD) can be easily evaluated by noninvasive scoring systems, of which the NAFLD fibrosis score (NFS) is the most commonly used. Proprotein convertase subtilisin/kexin type 9 (PCSK9), a new predictor of cardiovascular events, has been reported to be associated with cardiovascular outcomes and NAFLD. However, the relationship of NFS with PCSK9 and their prognostic abilities in cardiovascular risks are unknown.MethodsA total of 2008 hospitalized subjects who had chest pain without lipid-lowering therapy were consecutively included. Baseline clinical data were collected, and the NFS was calculated. The circulating PCSK9 concentration was determined by enzyme immunoassay. The major adverse cardiovascular event (MACE) occurrences were recorded in the follow-up period. Associations of PCSK9 concentration with NFS were examined. All of the participants were categorized into three groups according to NFS levels and were further stratified by PCSK9 tertiles to evaluate the MACEs.Results158 (7.87%) MACEs were observed during a mean of 3.2 years of follow-up. NFS levels were independently related to higher PCSK9 levels according to multivariable linear regression analysis. Furthermore, elevated PCSK9 and NFS concentrations were respectively associated with increased MACE incidence in multivariable Cox regression models. When combining NFS status with PCSK9 tertiles as a stratifying factor, patients with intermediate-high NFS and high PCSK9 levels had higher risks of events than those with low NFS and low PCSK9 levels.ConclusionsThis study revealed for the first time that NFS is positively related to PCSK9 and that the combination of NFS and PCSK9 greatly increased the risk of MACEs in patients with chest pain, providing a potential link between NFS and PCSK9 for predicting cardiovascular events.
Highlights
Non-alcoholic fatty liver disease (NAFLD) has been acknowledged as a major public health concern, with an estimated prevalence of 25% in adults, and it shows a continuously increasing trend [1, 2]
Higher NAFLD fibrosis score (NFS) and Proprotein convertase subtilisin/kexin type 9 (PCSK9) concentrations were observed in individuals with events than in those without, while the proportions of male sex, hypertension, blood pressure, smoking and drinking status; Body mass index (BMI), and triglyceride, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), platelet count, Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), albumin, fasting plasma glucose (FPG), Hemoglobin A1c (HbA1c) levels were not significantly different in patients with and without
NFS, non-alcoholic fatty liver disease fibrosis score Model 1 was unadjusted model Model 2 was adjusted for gender Model 3 was adjusted for model 2 covariates plus body mass index Model 4 was adjusted for model 3 covariates plus smoking and drinking Model 5 was adjusted for model 4 covariates plus hypertension and family history of coronary artery disease Model 6 was adjusted for model 5 covariates plus triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, fasting plasma glucose and hemoglobin A1c P < 0.05 suggests significant difference
Summary
Non-alcoholic fatty liver disease (NAFLD) has been acknowledged as a major public health concern, with an estimated prevalence of 25% in adults, and it shows a continuously increasing trend [1, 2]. Several noninvasive scoring systems derived from routinely accessible biochemical and clinical parameters have been used as more available and safe alternatives to the preliminary estimation of individuals with advanced liver fibrosis, especially for patients without symptoms or a history of liver diseases [5]. The NAFLD fibrosis score (NFS), as the most common noninvasive marker for assessing fibrosis severity in NAFLD, has been demonstrated to be related to liver disease risks and total cause mortality [4]. The risk of liver fibrosis in non-alcoholic fatty liver disease (NAFLD) can be evaluated by noninvasive scoring systems, of which the NAFLD fibrosis score (NFS) is the most commonly used. The relationship of NFS with PCSK9 and their prognostic abilities in cardiovascular risks are unknown
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