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