Elsevier

Atherosclerosis

Volume 239, Issue 2, April 2015, Pages 629-633
Atherosclerosis

The association of nonalcoholic fatty liver disease, obesity, and metabolic syndrome, with systemic inflammation and subclinical atherosclerosis: The Multi-Ethnic Study of Atherosclerosis (MESA)

https://doi.org/10.1016/j.atherosclerosis.2015.02.011Get rights and content

Highlights

  • NAFLD is associated with inflammation and subclinical atherosclerosis independent of obesity and metabolic syndrome.

  • The association between NAFLD, inflammation and subclinical atherosclerosis differs according to gender and race.

  • With increasing burden of NAFLD, obesity and metabolic syndrome, there is a stepwise increase in the prevalence of inflammation and subclinical atherosclerosis.

Abstract

Introduction

We characterized the association of 3 metabolic conditions – obesity, metabolic syndrome, and nonalcoholic fatty liver disease (NAFLD) – with increased inflammation and subclinical atherosclerosis.

Methods

We conducted cross-sectional analysis of 3976 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) with adequate CT imaging to diagnose NAFLD. Obesity was defined as BMI ≥ 30 kg/m2, metabolic syndrome by AHA/NHLBI criteria, and NAFLD using non-contrast cardiac CT and a liver/spleen attenuation ratio (L/S) < 1. Increased inflammation was defined as high sensitivity C-reactive protein (hsCRP) ≥2 mg/L and subclinical atherosclerosis as coronary artery calcium (CAC) > 0. We studied the association of a stepwise increase in number of these metabolic conditions (0–3) with increased inflammation and CAC, stratifying results by gender and ethnicity.

Results

Mean age of participants was 63 (±10) years, 45% were male, 37% white, 10% Chinese, 30% African American, and 23% were Hispanic. Adjusting for obesity, metabolic syndrome and traditional risk factors, NAFLD was associated with a prevalence odds ratio for hsCRP ≥2 mg/L and CAC >0 of 1.47 (1.20–1.79) and 1.37 (1.11–1.68) respectively. There was a positive interaction between female gender and NAFLD in the association with hsCRP ≥2 mg/L (p = 0.006), with no interaction by race. With increasing number of metabolic conditions, there was a graded increase in prevalence odds ratios of hsCRP ≥2 mg/L and CAC >0.

Conclusion

NAFLD is associated with increased inflammation and CAC independent of traditional risk factors, obesity and metabolic syndrome. There is a graded association between obesity, metabolic syndrome, and NAFLD with inflammation and CAC.

Introduction

Nonalcoholic fatty liver disease (NAFLD) is an important condition with an estimated worldwide prevalence of 20% [1]. There is increasing recognition that NAFLD is associated with cardiovascular disease (CVD). Cross-sectional epidemiologic studies have shown NAFLD to be linked to a higher prevalence of CVD independent of traditional risk factors [2]. NAFLD has also been associated with an increased risk of CVD events in patients with type 2 diabetes independent of obesity, other metabolic syndrome components, and traditional risk factors [3]. Indeed, the most common cause of death among individuals with NAFLD is CVD [1].

In addition to manifest CVD, NAFLD has been associated with increased inflammation [4], [5], [6], [7] and subclinical atherosclerosis [8], [9], [10], [11], [12] both of which are well known predictors of CVD in asymptomatic patients [13], [14], [15], [16], [17], [18], [19]. NAFLD has also been closely associated with obesity and metabolic syndrome – two conditions known to be associated with CVD, subclinical atherosclerosis, and systemic inflammation [20], [21], [22], [23], [24]. The associations of these metabolic conditions with inflammation and subclinical atherosclerosis have not been well characterized. As a result, some investigators have contended that NAFLD is an epiphenomenon as opposed to a mediator in the development of CVD [25]. The relationship between NAFLD, obesity, metabolic syndrome, and CVD is further complicated by the known ethnic differences in the prevalence of both NAFLD and metabolic risk factors [26].

We hypothesized that NAFLD would be associated with high sensitivity C-reactive protein (hsCRP) as well as coronary artery calcium (CAC) independent of obesity and metabolic syndrome, and that this relationship would be similar across ethnic groups. Furthermore, we hypothesized that there would be a graded association between the number of these metabolic conditions present and the prevalence of high hsCRP and CAC.

Section snippets

Study design

MESA is an observational cohort of 6814 men and women aged 45–84 years without known CVD at the time of enrollment. White, Black, Chinese, and Hispanic individuals were enrolled at six different US field centers (Baltimore City and Baltimore County, Maryland; Chicago, Illinois; Forsyth County, North Carolina; Los Angeles County, California; New York City, New York; and St. Paul, Minnesota) from July 2000 through September 2002. The MESA study design has been described in detail previously [27].

Results

There were 670 (16.9%) individuals with NAFLD. Baseline characteristics according to presence/absence of NAFLD are shown in Table 1. Mean age differed slightly, 61 (±9.6) years for those with NAFLD and 63 (±10.5) years for those without. Gender distribution was similar in each group (46% male). The ethnic makeup of the two groups differed significantly, with a predominance of Hispanics in the NAFLD group. Individuals with NAFLD were more likely to be obese and meet criteria for metabolic

Discussion

The results of our cross-sectional analysis from this multi-ethnic cohort demonstrate that the presence of NAFLD is associated with systemic inflammation and subclinical atherosclerosis. This relationship remained significant after adjusting for traditional risk factors, obesity, and metabolic syndrome. We have also shown that there is a gradient response relationship with increasing number of these metabolic conditions suggesting a possible graded relationship of obesity, metabolic syndrome,

Conflict of interest

There is no conflict of interest to be declared.

Acknowledgments

This research was supported by R01 HL071739 and contracts N01-HC-95159 through N01-HC-95165 and N01 HC 95169 from the National Heart, Lung, and Blood Institute. The authors thank the other investigators, the staff, and the participants of the MESA study for their valuable contributions. A full list of participating MESA investigators and institutions can be found at http://www.mesa-nhlbi.org.

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    Drs. Al Rifai and Silverman contributed equally to this work.

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