Characterization of the sample
For the analysis, we used data from the cross-sectional epidemiological study, Epidemiology of Cardiovascular Diseases in the Regions of the Russian Federation (ESSE-RF), conducted in 2013-2014. A total of 21,923 subjects 25-64 years of age in 13 regions of the Russian Federation participated in the study. When forming the sample, the Kish grid method was employed, ensuring a systematic multistage random sampling based on the territorial principle (on the basis of medical institutions). The response rate to the survey was approximately 80%, ranging across study regions.
The study was approved by the Ethics Committees of National Research Center for Therapy and Preventive Medicine (Moscow, Russian Federation) №07-03/12 (03.07.2012). The study was performed in compliance with Good Clinical Practice and the Declaration of Helsinki principles. Written informed consent was obtained from all participants prior to their enrollment in the study.
ECG was performed in 11 regions. St. Petersburg was excluded from the final sample, because it differed significantly in its regional characteristics from ten other regions. St. Petersburg is classified in the Russian Federation as a separate administrative territorial unit, while ten other regions are large territories, including both cities and rural areas.
For some individual indicators considered as covariates, there were missing or incomplete data: marital status (n=126 or 0.8% of the final sample), education (n=15 or 0.1%), employment (n=12 or 0.1%), income (n=264 or 1.6%), hypertension (n=441 or 2.7%), obesity (n=203 or 1.2%), hypercholesterolemia (n=633 or 3.9%), diabetes mellitus (n=738 or 4.5%), dietary pattern (n=1,876 or 11.4%), alcohol consumption (n=1,774 or 10.8%), and smoking (n=28 or 0.2%). For these indicators, the missing data was restored using the k-nearest neighbors’ algorithm according to the following input parameters: region, place of residence (urban/rural), gender, and age. Hence, the final sample included 16,400 subjects representing 10 regions, comprising 6,305 men and 10,095 women.
Major and minor ECG abnormalities
Recording of 12 ECG leads at rest was carried out according to the same protocol at a medical institution, in the supine position after a 5-minute rest, on a PADSY computer ECG complex (Medset Medizintechnik GmbH, Hamburg, Germany). ECG recordings from the regions were sent electronically to the National Medical Research Center for Therapy and Preventive Medicine of the Russian Federation Ministry of Healthcare. ECG coding of all study participants was carried out in a unified way sensu the Minnesota code, version of 2009 [33], by two trained specialists of the Center, with an involvement of the third expert in disputable cases. Coded ECG changes were grouped into two categories: Major ECG abnormalities and Minor ECG abnormalities. The criteria and algorithm matched the classification by Prineas RJ et al. [33]. They are presented in Table 1.
Individual covariates
Of individual variables, as covariates, we selected socioeconomic and demographic characteristics with the highest evidential level of their effect on the likelihood of cardiovascular disorders according to the published data sources. Gender, age, place of residence (urban vs. rural) of study subjects were identified from filled questionnaires, along with some other variables: educational level (not higher vs. higher education), marital status (has vs. does not have a family), employment status (employed vs. jobless), income level, medicine intake, dietary patterns, alcohol consumption, smoking status (never did, quit, currently smokes), diabetes mellitus, heredity (myocardial infarction in parents and or siblings: yes/no/ not aware of).
Income level was assessed indirectly by three questions characterizing the share of income spent on food, and opinions of respondents about their financial potentials and well-being as compared with other families. Each question had five response options, which were ranked from 1 pt. (the ‘poorest’ answer) to 5 pts. (the ‘richest’ answer). From sums of points, the tertiles were calculated, in accordance with the values of which the level of income was grouped into three categories: low, medium, and high.
Hypertension was defined as systolic blood pressure of 140 mm Hg or higher, and/or diastolic blood pressure of 90 mm Hg or higher, and/or an intake of antihypertensive medicines by the study participant within the last two weeks.
The presence of obesity was determined by body mass index: its values of 30.0 kg/m2 and above were classified as obese.
Diabetes mellitus was classified given the presence of at least one of the following three criteria: a history of diabetes mellitus type 1 or 2; fasting hyperglycemia (glucose level of 7.0 mmol/L or more); intake of medications to lower glucose level. Blood sampling to determine the concentration of glucose was carried out from the median cubital vein on an empty stomach, after 12 hours of fasting. The glucose level was identified via glucose oxidase method on Sapphire-400 automated biochemistry analyzer (Japan) using Human GmbH kits.
Hypercholesterolemia was classified given the following: blood level of total cholesterol of 5.0 mmol/L or more; and/or use of cholesterol-lowering medications in the past two weeks. Total cholesterol was determined by the enzymatic method on Abbott Architect c8000 analyzer using Abbott Diagnostic kits (USA).
The presence and level of alcohol consumption was assessed according to questionnaire data, by converting the frequency, volume and type of consumed alcoholic beverages into average daily values in grams of ethanol [34]. There was a group of subjects with zero alcohol consumption. Among those who drank alcohol, the values of the 25th and 75th percentiles were calculated, according to which a grouping was performed into the following categories of alcohol consumption: small, moderate and excessive.
An assessment of dietary patterns was performed sensu empirical models, allowing to integrally analyze the diets of respondents according to the actual consumption frequency of food groups. A detailed description of the selection procedure via using the method of principal component analysis, along with an analysis of Russian dietary patterns (DP), was presented in our earlier publication [35]. Overall, four DP were identified: reasonable (dairy products, sweets and confectionery, fruits and vegetables, cereals and pasta), salty foods (Vienna sausages, sausages, offal, pickles and pickled products), meat-based (red meat, fish and seafood, poultry), and mixed (legumes, pickles and pickled products, fish and seafood). According to the quantitative value of individual adherence to each of four DP, the sample was grouped into four quartiles with a higher quartile characterizing a higher adherence to the particular DP.
Regional variables
To describe regional living conditions, an integral index assessment was employed, which was previously performed using the methodology of principal component analysis [36]. In short, to identify regional indices, publicly available data from the official website of the Federal Statistics Service of Russia (www.gks.ru) for 2010-2014 were borrowed. In total, five regional indices were identified, which were quantitative indicators reflecting a negative (negative index values) or positive (positive index values) trend in a particular region.
The Sociogeographic Index combined 10 characteristics: (a) mean per capita consumption of vodka; (b) mean per capita consumption of wine; (c) mean per capita consumption of low alcohol drinks; (d) mean per capita consumption of cognac; (e) mean annual air temperature (negative impact on the factor); (f) forested area size in the region; (g) per capita number of crimes; (h) geographical latitude of the regional center location; (i) share of dilapidated housing; (j) shares of school students studying in the morning and afternoon shifts. In general, an increase in this index value characterizes the deterioration of the social environment. In a similar way, higher values of this index imply more northerly location of the region with correspondingly worse climatic conditions.
The Demographic Index is formed by five characteristics: (a) natural population growth (negative impact); (b) fertility rate (negative impact); (c) total mortality rate; (d) the proportion of people of retirement age among the population; (e) mortality caused by respiratory diseases. An increase in this index values implies aggravated demographic depression in the region with depopulation and population restructuring towards the dominance of older age groups.
The Industrial Index encompassed eight characteristics: (a) volume of mineral resource mining; (b) energy production; (c) mortality caused by tuberculosis; (d) mortality caused by infectious diseases; (e) mortality caused by external causes; (f) the proportion of people in the region working in hazardous working conditions; (g) population numbers in the region; (h) air emissions. An increase in this index values is indicative of an increase in the regional industrial development, primarily, due to mining and energy production, with a consequent exposure of the working and retired population to unfavorable anthropogenic factors.
There are five components forming the Mixed Index: (a) number of workers in fish farms; (b) mean per capita volume of paid services; (c) mean per capita number of cars; (d) ratio of men to women (negative impact); (e) geographical longitude of the regional center location. The values of mixed index are the most difficult to interpret. However, it could be assumed that with its growth, the region is characterized by a favorable socioeconomic increase in the mean per capita volume of paid services and number of cars.
The Economy Index is formed by five characteristics: (a) per capita volume of retail trade; (b) mean per capita household consumption; (c) Gini index value; (d) mean per capita income; (e) the level of development of manufacturing industries in the region. An increase in this index values implies the growth of economic development, income, and economic inequality of the population in the region.
Statistical data processing
We used Pearson’s chi-squared test to compare the frequencies of categorical variables in men vs. women, and Student’s t-test to compare mean age values. The studied variables are represented by a complex two-level sample with individual and regional characteristics; therefore, to measure associations, generalized estimating equations [37] with stable standard errors were used, taking into account the nested structure of the data (subjects in regions). Several sets of logistic models of the probability of major and minor ECG abnormalities were performed, with the calculation of the odds ratio (OR) and 95% confidence intervals (CI). Model 1 included only regional indices. In Model 2, individual socioeconomic characteristics were added to the regional indices: age, urban vs. rural residence, family status, educational level, employment status, and income category. Model 3, characterized as comprehensive, additionally included cardiovascular risk factors: hypertension, obesity, hypercholesterolemia, diabetes mellitus, smoking status, alcohol consumption, dietary pattern, and heredity risks. The preliminary analysis yielded some interactions of gender with regional indices; hence, we decided to perform all analyses separately for men and women. The critical level of statistical significance was assumed at p≤0.05. All statistical procedures were performed using the SPSS software platform, version 22 (IBM, USA).