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Page 2 of 9 Sobenin et al. Vessel Plus 2019;3:15 I http://dx.doi.org/10.20517/2574-1209.2019.09

and genetic risk factors (particularly, mutant variants of mitochondrial genome) may interplay in the formation of
susceptibility to atherosclerosis.

Keywords: Carotid atherosclerosis, high-risk patients, mitochondrial DNA mutations, air pollution, convenient
cardiovascular risk factors

INTRODUCTION
Early detection and treatment of patients with a high risk of atherosclerosis is an urgent medical problem.
[1]
Within this aspect, the identification of markers of subclinical atherosclerosis is an essential factor .
The thickness of the intima-media layer of the carotid arteries [carotid intima-media thickness (cIMT)],
determined by high-resolution ultrasonography, is considered to be a validated and conventionally accepted
non-invasive marker of subclinical atherosclerosis, that is used in clinical and epidemiological studies to
[2]
assess the effect of traditional and new cardiovascular risk factors on atherosclerosis . Since there is a
correlation between cIMT and the degree of development of coronary atherosclerosis, and this factor has
a prognostic significance in relation to the clinical manifestations of atherosclerosis, it is proposed as a
[3,4]
surrogate marker of systemic atherosclerosis, including coronary one . The classic cardiovascular risk
factors are weakly associated with the cIMT of the carotid arteries, thus suggesting the presence of other
factors that determine the risk of developing atherosclerosis. The results of a recent European multicenter
study [The Carotid Intima Media Thickness (IMT) and IMT-Progression as Predictors of Vascular Events
in a High Risk European Population Study, or IMPROVE Study] revealed the existence of a geographical
[5]
gradient of the cIMT, coupled with a known gradient of cardiovascular mortality . The detected south-
north geographic gradient of cIMT did not depend on interpopulation differences in the cumulative effects
of conventional cardiovascular risk factors. It has been suggested that other mechanisms play a role in
the origin of this gradient, including hereditary, socio-economic and environmental factors. In order to
verify this assumption, we conducted our own population-based cross-sectional study in Moscow, the
methodology of which could allow us to regard the results as a significant addition to the data from the
European IMPROVE study. In particular, we aimed to explore whether geographical location, genetic and
environmental factors are associated with carotid atherosclerosis in high-risk individuals, thus focusing on
the possibility of specific interplay of genetic and environmental factors.

METHODS
Patients
The study was performed at municipal outpatient clinics in Moscow, Russia. The study was organized
in accordance with international and domestic standards of quality clinical practice, namely, Helsinki
Declaration of 1975 as revised in 1983, 2008 and 2013, and was approved by the local ethics committee. The
study involved 470 subjects (200 men and 270 women) without clinical manifestations of atherosclerosis
randomly recruited from the visitors’ flow who have passed a routine screening for cardiovascular
risk factors, as a screening subpart of Atherosclerosis Monitoring and Atherogenicity Reduction Study
(ClinicalTrials.gov Identifier: NCT01734707) and Monocyte Activation in Preclinical Atherosclerosis Study
(ClinicalTrials.gov Identifier: NCT02126280). The criteria for inclusion and exclusion were designed from
those of IMPROVE Study, which allowed to form an observation group that is completely comparable with
samples from European populations.

We have recruited men and women aged 55-79 years old who had at least three conventional risk factors
for cardiovascular diseases. The latter included: hypercholesterolemia (low-density lipoprotein cholesterol
level >160 mg/dL, or prescribed to cholesterol-lowering medications), hypertriglyceridemia (triglycerides >
200 mg/dL, or prescribed to triglyceride-lowering drugs), low HDL-cholesterol (below 40 mg/dL), arterial