Evaluation of early atherosclerosis markers in patients with
nonalcoholic fatty liver disease
Metin Kucukazman
a
, Naim Ata
b
, Bunyamin Yavuz
c
, Kursat Dal
b
, Omer Sen
c
,
Onur S. Deveci
c
, Kadir Agladioglu
d
, Abdullah O. Yeniova
a
, Ya ¸ sar Nazligul
a
and Derun T. Ertugrul
b
Objectives Nonalcoholic fatty liver disease (NAFLD) is
characterized by the excessive accumulation of fat in the
liver cells. It is strongly associated with cardiovascular risk
factors for atherosclerosis. Flow-mediated dilation (FMD)
and carotid intima-media thickness (CIMT) are noninvasive
methods for the evaluation of endothelium. They are
considered early markers of atherogenesis. The aim of this
study was to evaluate early atherosclerosis markers in
patients with NAFLD.
Methods We examined 161 patients. All the patients
underwent hepatic ultrasonography, transthoracic
echocardiography, and brachial artery and carotid artery
imaging. Fasting blood samples were drawn from all
patients for the determination of lipids, insulin, C-peptide,
and fasting blood glucose. HOMA-IR was calculated.
Results Among the 161 patients, 44 had normal
hepatic ultrasonography, 42 had stage 1 hepatosteatosis,
53 had stage 2 hepatosteatosis and 22 had stage 3
hepatosteatosis. FMD was reduced in patients with
NAFLD as compared with the healthy controls
(5.9±3.1 vs. 9.6±2.7%, P < 0.001). There was a
significant negative moderate correlation between
ultrasonographic hepatosteatosis grade and FMD
(r = – 0.556, P < 0.001). The mean CIMT was significantly
increased in patients with NAFLD as compared
with the controls (0.40±0.19 vs. 0.27±0.18, P < 0.001).
There was a significant positive weak correlation
between ultrasonographic hepatosteatosis grade
and mean CIMT (r = 0.376, P < 0.001).
Conclusion This study showed that NAFLD is associated
with impaired CIMT and FMD, which are early markers of
atherosclerosis. These findings may play a crucial role in
understanding the pathophysiology of the atherosclerotic
process in patients with NAFLD. Eur J Gastroenterol
Hepatol 25:147–151 c 2013 Wolters Kluwer Health |
Lippincott Williams & Wilkins.
European Journal of Gastroenterology & Hepatology 2013, 25:147–151
Keywords: atherosclerosis, carotid intima-media thickness, flow-mediated
dilation, nonalcoholic fatty liver disease
a
Department of Internal Medicine, Division of Gastroenterology, Departments of
b
Internal Medicine,
c
Cardiology and
d
Radiology, Kecioren Teaching and Research
Hospital, Ankara, Turkey
Correspondence to Metin Kucukazman, MD, Department of Internal Medicine,
Division of Gastroenterology, Kecioren Teaching and Research Hospital,
06380 Ankara, Turkey
Tel: + 90 312 3569000; fax: + 90 312 3569002;
e-mail: drmetingastromd@gmail.com
Received 24 July 2012 Accepted 12 September 2012
Introduction
Nonalcoholic fatty liver disease (NAFLD) is a common
condition worldwide. It is characterized by the excessive
accumulation of fat in the liver cells [1,2]. Patients with
NAFLD have higher morbidity and mortality rates [3].
It is also strongly associated with risk factors for athero-
sclerosis, such as obesity, dyslipidemia, hypertension,
type 2 diabetes mellitus, and insulin resistance [4]. The
increased risk of atherosclerosis in patients with NAFLD
is because of the coexistence of this entity with metabolic
syndrome. NAFLD has been accepted recently as a
hepatic component of metabolic syndrome [5].
Brachial artery flow-mediated dilation (FMD) is a non-
invasive method for the determination of endothelial
function in humans. Endothelial dysfunction is a char-
acteristic of most conditions associated with athero-
sclerosis and thus it is considered as an early marker for
atherogenesis. When endothelial dysfunction is present,
lower levels of FMD are detected [6,7]. Carotid intima-
media thickness (CIMT), which is another early athero-
sclerotic marker, was positively related to the severity of
coronary artery and cardiovascular events [8].
There are several papers on the association between
NAFLD and subclinical atherosclerosis in patients with
a low cardiovascular risk. However, the literature is
controversial about it. The aim of this study was to
evaluate endothelial function in patients with NAFLD
using FMD.
Methods
We examined 161 patients who were referred to the
outpatient clinic of the Division of Gastroenterology for
the determination of hepatic function. According to the
hepatic ultrasonographic findings, we divided the patients
into four groups: those with normal hepatic ultrasono-
graphy (USG), those with stage 1 hepatosteatosis, those
with stage 2 hepatosteatosis, and those with stage 3
hepatosteatosis [9]. The study protocol was in accordance
Original article 147
0954-691X c 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins DOI: 10.1097/MEG.0b013e32835a58b1
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.