Elsevier

Atherosclerosis

Volume 241, Issue 1, July 2015, Pages 145-150
Atherosclerosis

Advanced fibrosis associates with atherosclerosis in subjects with nonalcoholic fatty liver disease

https://doi.org/10.1016/j.atherosclerosis.2015.05.002Get rights and content

Highlights

  • We explored the association between advanced fibrosis and subclinical atherosclerosis in NAFLD patients.

  • Advanced fibrosis was positively associated with subclinical atherosclerosis parameters in the NAFLD patients.

  • The positive association was independent of conventional cardiometabolic risk factors and insulin resistance.

  • NFS might be useful to assess future CVD risk of NAFLD patients.

  • Early prevention of CVD should be valued in NAFLD patients with NFS > 0.676.

Abstract

Objective

Nonalcoholic fatty liver (NAFLD) with advanced fibrosis usually has a deteriorated prognosis, which was mainly attributed to cardiovascular cause. We investigated whether advanced fibrosis assessed by noninvasive fibrosis markers was associated with subclinical atherosclerosis in NAFLD patients.

Methods

A total of 2550 participants with ultrasound confirmed NAFLD from a community based population study were included in the present analysis. NAFLD fibrosis score (NFS) derived from available parameters was calculated to assess severity of fibrosis of the NAFLD patients. The NAFLD patients with a NFS > 0.676 indicated of presence of advanced fibrosis. The carotid intima-media thickness (CIMT), carotid plaques and brachial-ankle pulse wave velocity (ba-PWV) were used as the indicators of early atherosclerosis.

Results

NAFLD patients with advanced fibrosis had higher CIMT and ba-PWV, compared with those without fibrosis (CIMT: 0.65 versus 0.57 mm; ba-PWV: 1884 versus 1535 cm/s, both p < 0.0001). Participants with advanced fibrosis were more likely to have higher homeostasis model assessment of insulin resistance index (HOMA_IR, 3.28 versus 2.45, p < 0.0001). After adjusting the confounders, participants with advanced fibrosis associated with 1.98-folds increased risk for elevated CIMT, 2.28-folds increased risk for present carotid plaque and 2.68-folds increased risk for arterial stiffness, respectively, as compared to participants without fibrosis. After further adjustment for HOMA_IR, the positive associations did not appreciably change.

Conclusion

Advanced fibrosis indicated by NFS was positively associated with CIMT, presence of carotid plaque and arterial stiffness in the NAFLD patients, independent of conventional cardiometabolic risk factors and insulin resistance.

Introduction

Nonalcoholic fatty liver disease (NAFLD) indicates a spectrum of liver diseases that encompass simple steatosis, fatty infiltration plus inflammation (NASH), fibrosis and ultimately cirrhosis. With an increase presence of NAFLD global widely, it has posed great burden on public health. Fatty liver has been considered as a risk factor of cardiovascular events, and currently the grade of NAFLD determines the progressive cardiovascular risk [1], [2]. Simple steatosis is fairly benign and reversed [3], [4], however, NAFLD progressing to NASH or advance fibrosis has a deteriorated prognosis [5]. The gold standard to confirm presence and severity of NAFLD fibrosis depends on the utilization of liver biopsy, which was not universally accepted by patients in clinic practice.

Recently, a growing number of studies were performed trying to explore the clinic value of the non-invasive scores for NAFLD fibrosis [6]. NAFLD fibrosis score (NFS) has been validated in 13 studies with more than 3000 patients [7], and it incorporates age, body mass index (BMI), hyperglycemia, blood platelet count, serum albumin and aspartate aminotransferase/alanine aminotransferase ratio (AST/ALT), which presents great accuracy for diagnosis of advanced fibrosis [8]. This score has been recommended to be applied in clinical practice with 97% specificity for confirming advanced fibrosis at the cut-off point of 0.676 [9]. Results derived from the National Health and Nutrition Examination Survey (NHANES) have shown that advanced fibrosis determined by non-invasive fibrosis panels is a significant predictor of mortality caused by cardiovascular disease (CVD) in patients with NAFLD, independent of other known risk factors [10]. To our best knowledge, studies exploring the association between NAFLD fibrosis and subclinical arterial vascular disease in community-based ultrasonography-confirmed NAFLD patients are limited. This study aims to evaluate the association of advanced fibrosis assessed by NFS with markers of subclinical arterial vascular disease such as carotid intima-media thickness (CIMT), presence of carotid plaques and arterial stiffness measured by brachial-ankle pulse wave velocity (ba-PWV).

Section snippets

Subjects and study design

The participants were from a community-based cross-sectional survey, which was conducted in Jiading district, Shanghai, China, from March to August, 2010. The details of the study, including design, sampling extracting, eligibility criteria, items detected, information collected, have been described elsewhere [11]. A total of 10,375 inhabitants aged 40 years or older were recruited to take part in this survey. All participants were undergone abdominal ultrasonic examination. Of those,

Characteristics of NAFLD participants

A total of 2550 participants were confirmed as NAFLD patients by ultrasonography, accounting for 30.8% of all participants. Demographic and clinical characteristics of participants with NAFLD were summarized in Table 1. According to the cut-off points of NFS at −1.455, 0.676 separately, 103 participants had advanced fibrosis, and 1226 participants were excluded to have advanced fibrosis. As expected from the component variables of the score, advanced fibrosis was associated with older age.

Discussion

In the present study, we found that NAFLD patients with advanced fibrosis related to a high risk of having elevated CIMT, presence of carotid plaque and arterial stiffness, independent of conventional metabolic factors and prior CVD history and insulin resistance.

NAFLD is well regarded as the manifestation of metabolic syndrome in liver. Due to a fast conversation of lifestyle occurred in the past decades, the prevalence of NAFLD is increasing sharply [14]. Abdominal ultrasonography is

Conflicts of interest

The authors declare that they have no competing interests.

Acknowledgments

The authors thank the field workers for their contribution and the participants for their cooperation. This work is supported by grants from the Key Laboratory for Endocrine and Metabolic Diseases of Ministry of Health (1994DP131044), the National Clinical Research Center for Metabolic Diseases of Ministry of Health (2013BAI09B13), the National Key New Drug Creation and Manufacturing Program of Ministry of Science and Technology (2012ZX09303006-001), the National High Technology Research and

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    Ying Chen and Min Xu contributed equally to this article.

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