Elsevier

Clinical Biochemistry

Volume 43, Issue 18, December 2010, Pages 1399-1404
Clinical Biochemistry

The severity of non-alcoholic fatty liver disease correlates with high sensitivity C-reactive protein value and is independently associated with increased cardiovascular risk in healthy population

https://doi.org/10.1016/j.clinbiochem.2010.09.003Get rights and content

Abstract

Objectives

We aimed to investigate the correlation between non-alcoholic fatty liver disease (NAFLD) and risk of cardiovascular disease (CVD).

Design and methods

We analyzed 724 subjects without CVD according to presence or absence of NAFLD. Logistic regression model was used to determine if NAFLD was an independent risk factor of CVD.

Results

Subjects with NAFLD had increased percentage of 10-year cardiovascular risk ≧ 10% compared to those without NAFLD (p < 0.001). The severity of NAFLD significantly correlated with increasing Framingham risk score and C-relative protein (CRP) value. After adjusting for conventional CVD risk factors, the presence of NAFLD was an independent predictor for future CVD risk ≧ 10% [odds ratio: 1.89, p = 0.004]. Subgroup analysis showed the predictive value of NAFLD was significant among aged subjects and those with increased baseline hsCRP level.

Conclusions

NAFLD is independently associated with increased CVD risk, especially among elderly subjects and those with increased CRP level.

Introduction

Non-alcoholic fatty liver disease (NAFLD) is hepatic infiltration by fat tissue. NAFLD has a wide spectrum, ranging from simple steatosis to more severe manifestation such as non-alcoholic steatohepatitis, which may lead to cirrhosis and hepatic failure [1]. The prevalence of NAFLD has been estimated at 10% to 39% in various populations [2], [3], [4], [5], [6], and increasing incidence worldwide was also observed. Subjects with fatty liver usually present variable degree of liver damage and variable cardiovascular (CV) risk factors such as obesity [7], type 2 diabetes, insulin resistance [8], hypertension [9] and metabolic syndrome (MtS) [10], [11]. Recently, Hamaguchi et al. demonstrated that coexistence of the CV risk factors may correlate with the severity of NAFLD [12] and suggested that non-alcoholic fatty liver disease (NAFLD) acts as the hepatic presentation of metabolic syndrome. Although NAFLD has been reported to be associated with cardiovascular risk factors and is considered an independent factor in determining cardiovascular events [13], [14], [15], there is still argument about whether NAFLD is an independent risk factor or merely a bystander of accumulating multiple cardiovascular disease risk factors [16], [17]. Is NAFLD a consequence of, or a contributor to, the dysmetabolic cascade leading to CVD? Does NAFLD promote atherosclerosis, or is it a simple epiphenomenon? In the conclusions of McKimmie and coauthors' study, NAFLD is less likely a direct mediator of cardiovascular disease (CVD) and may best be described as an epiphenomenon [18]. In addition, the connections between NAFLD and CVD were not consistent [19], and the independent association of fatty liver and CV risk may persist or disappear after adjusting for cardiovascular risk factors such as diabetes, or hypertension, suggesting the unclear role of fatty liver in cardiovascular disease. Therefore, our current study aimed to investigate the association between NAFLD and cardiovascular risk. We also investigate the association between NAFLD and other traditional CV risk factors.

Section snippets

Study subjects

A total of 833 subjects (733 men and 60 women) who received health examination at Taipei Veterans General Hospital between January 2007 and December 2007 were screened in this study. Subjects with major cardiovascular disease like stroke, myocardial infarction, coronary artery disease, or peripheral artery disease were excluded from the study. In addition, subjects were also excluded if they fulfilled the following criteria: (1) presence of serological markers of hepatitis B virus infection

Results

The baseline characteristics of study subjects are shown in Table 1. Compared with subjects without NAFLD, NAFLD subjects had significantly higher blood pressure, higher body mass index, increased waist circumference, and higher incidence of hypertension and diabetes as well as metabolic syndrome. In addition, NAFLD subjects had higher serum triglyceride and cholesterol levels, and lower HDL-C level. Subjects with NAFLD had higher hsCRP than those without NAFLD (1.9 mg/L vs. 1.4 mg/L, p = 0.047).

Discussion

Our study demonstrates non-obese and relatively healthy subjects with NAFLD have an increased risk of developing cardiovascular events. In addition, NAFLD is an independent risk factor for CVD. The severity of NAFLD correlates with increasing CV risks as well as underlying inflammatory status. Our study further demonstrates the risk-predictive value of NAFLD is most significant in aged subjects and in subjects with increased baseline hsCRP level, suggesting its novel value in identifying

Conclusion

Our study demonstrates that nonalcoholic liver disease is significantly associated with increased CV risk, especially among elderly subjects and subjects with increased baseline value of CRP.

References (41)

  • L.M. Araujo et al.

    Liver and biliary ultrasonography in diabetic and non-diabetic obese women

    Diab Metab

    (1998)
  • A.Y. el-Hassan et al.

    Fatty infiltration of the liver: analysis of prevalence, radiological and clinical features and influence on patient management

    Br J Radiol

    (1992)
  • H. Nomura et al.

    Prevalence of gallstone disease in a general population of Okinawa, Japan

    Am J Epidemiol

    (1988)
  • A.A. Patel et al.

    Effect of weight loss on nonalcoholic fatty liver disease

    J Clin Gastroenterol

    (2009)
  • E. Bugianesi et al.

    Insulin resistance in non-diabetic patients with non-alcoholic fatty liver disease: sites and mechanisms

    Diabetologia

    (2005)
  • G. Donati et al.

    Increased prevalence of fatty liver in arterial hypertensive patients with normal liver enzymes: role of insulin resistance

    Gut

    (2004)
  • G. Tarantino et al.

    Non-alcoholic fatty liver disease: further expression of the metabolic syndrome

    J Gastroenterol Hepatol

    (2007)
  • T. Kogiso et al.

    Clinical significance of fatty liver associated with metabolic syndrome

    Hepatol Res

    (2007)
  • M. Hamaguchi et al.

    The metabolic syndrome as a predictor of nonalcoholic fatty liver disease

    Ann Intern Med

    (2005)
  • M. Akahoshi et al.

    Correlation between fatty liver and coronary risk factors: a population study of elderly men and women in Nagasaki, Japan

    Hypertens Res

    (2001)
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