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Page 6 of 9 Sobenin et al. Vessel Plus 2019;3:15 I http://dx.doi.org/10.20517/2574-1209.2019.09

smoking status, LDL cholesterol, HDL cholesterol, serum triglycerides, menopausal status for women,
family history of myocardial infarction) as independent variables. It was found that the total burden of these
risk factors explains 21% of the cIMT variability. Since conventional risk factors do not fully explain the
variability of cIMT in the samples from European populations and the Moscow high-risk group, it should be
assumed that other factors play a role in the formation of atherosclerosis predisposition.

One of these factors may be the adverse effects of the external environment. As a possible characteristic of
the environmental situation, we used the mean annual integrated air pollution index. It was calculated as the
sum of the ratios of the concentrations of the five major pollutants (nitrogen oxide, nitrogen dioxide, carbon
monoxide, ozone and formaldehyde) to the maximum permissible concentration in the atmosphere. It was
found that standardized mortality from coronary heart disease tends to correlate with the atmospheric
pollution index: the correlation coefficient was 0.742 with P = 0.056. At the same time, the air pollution index
correlated with the mean cIMT: the correlation coefficient was 0.812 with P = 0.026.

The other acting non-beneficial factor may be the genetic background. In our study, we have assessed the
mutation burden of mitochondrial DNA by those heteroplasmic variants that have been previously shown
to be associated with atherosclerotic lesions in human aorta and also with carotid atherosclerosis [9-11] . As it
was shown in linear regression model, 5 of 10 mutations, for which the level of heteroplasmy was measured,
2
independently provided the explanatory level of 23% for cIMT variation by adjusted R at P < 0.001 (Fisher’s
exact test 11.21; P < 0.001); these were m.652delG, m.3256C>T, m.13513G>A, m.14459G>A, and m.15059G>A.
The combined model, which included conventional risk factors and the above mutations provided
significantly better explanatory level (36%, Fisher’s exact test 8.28; P < 0.001).

DISCUSSION
In this study, we used one of the generally accepted methods for assessing susceptibility to atherosclerosis,
namely, non-invasive ultrasound scanning of the carotid arteries in high-resolution mode. This approach
allowed to obtain direct quantitative estimate of the degree of development of subclinical atherosclerosis in
individuals with a high risk of CHD. The criteria used for inclusion in the study allowed us to form a sample
well comparable to the European samples in the IMPROVE Study on the cumulative effects of traditional
cardiovascular risk factors. A direct comparison of the measurement of cIMT with European data showed
that in spite of the same cumulative risk, the Moscow population-derived sample was more prone to
atherosclerosis.

We were able to expand significantly the hypothesis on the existence of a geographic gradient of the
variability of cIMT, and this gradient was associated not only with geographical latitude, as it was
demonstrated in the IMPROVE Study, but also with geographical longitude. The association of the cIMT
gradient with the gradient of cardiovascular mortality was confirmed, thus allowing to describe cIMT as the
risk factor for atherosclerotic disease and its clinical manifestations.

It was confirmed that the variability of cIMT is not sufficiently explained by the cumulative effect of
conventional risk factors: the explanatory nature of the used models for assessing the association of risk
factors with cIMT was 21%. Therefore, it was rather logical to assume that previously unexplored (or
insufficiently studied) mechanisms of susceptibility to atherosclerosis may be of importance. The latter may
include hereditary, socio-economic and environmental factors. The cross-sectional study in the sample from
Moscow population, the methodology of which allowed it to be regarded as an addition to the data from
the IMPROVE Study, showed that the ecological situation can be one of the factors associated with both the
development of subclinical atherosclerosis and its clinical manifestations and complications.

The hypothesis on the possible role of the damage of mitochondrial DNA in atherosclerosis development has
raised relatively recently but gains more and more experimental and clinical background. It is known that