Analysis of Prevalence of Lower Extremity Varicose Vein Disease of in One of Major Regions of Central Federal District of Russian Federation Using Multi-Variant Approach

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LIST OF ABBREVIATIONS

CI — confidence interval

CRH — Central Regional Hospital

FE — fixed effect

HM — Health Ministry

LEVV — lower extremity varicose veins

МО — medical organization

RE — random effect

RF — Russian Federation

YaR — the Yaroslavl region

INTRODUCTION

According to the Health Ministry of the Russian Federation (RF), the total morbidity of adult population of the RF with varicose veins of the lower extremities in the period 2013–2017 was 1049.0–1074.3 per 100,000 population [1]. In Russian population-based studies, the prevalence of varicose veins among the adult population ranges from 12% to 26% [2, 3]. In foreign sources, there are various estimates of the prevalence of lower extremity varicose veins (LEVV): from 2% to 56% in men and from 1% to 73.2% in women [4, 5]. The average prevalence of LEVV, according to epidemiological studies, is 25%–33% among women and 10%–40% among men [6–8].

All this indicates the seriousness of the problem of LEVV and indicates significant socio-economic burden borne by modern society due to the high prevalence of LEVV among the working-age population of economically developed countries. Besides, of importance is the high total cost of diagnosis and treatment of both the disease itself and its associated complications, high expenditures associated with the probable disability of the population suffering LEVV [9, 10]. Despite the slowly progressing course of the disease [11], its high prevalence in the population may lead to a rapid accumulation of a significant number of patients with complicated forms of LEVV significantly affecting the quality of patients’ life [12].

Most of the currently known epidemiological studies on LEVV assess morbidity and other statistical parameters in short term and have a small coverage across the territory. There are mostly continuous cross-sectional studies, and the data on the morbidity with and the incidence of LEVV in such studies may differ greatly from the calculated parameters on which the state health system directs their resources. In our opinion, it is important to analyze the data on the prevalence of LEVV from a scientific and practical point of view, including a comparative analysis that should be conducted on large strata and in dynamics over a long period of time. In the available literature, no works were found that describe the problem of the epidemiology of LEVV in this aspect.

The aim of this study to determine changes in the prevalence of lower extremity varicose veins in various territories of the Yaroslavl region over 10 years (from 2011 to 2021).

MATERIALS AND METHODS

A retrospective study of statistical parameters of the work of state medical organizations (MOs) for 2011–2021 was conducted, namely of:

- the total number of attached adult population;

- the dynamics of the attached population;

- the total number and dynamics of the number of patients with established diagnosis of LEVV with the codes I83.0, I83.1, I83.2, I83.9 of the International Statistical Classification of Diseases and Health-Related Problems, 10th revision.

The results were presented in accordance with Cochrane recommendations [13].

The study includes the following state MOs of Yaroslavl:

- Central City Clinical Hospital;

- Clinical Hospitals No. 2–4 (merged with Clinical Hospital No. 9 in 2019), No. 8 (merged with Clinical Hospital No. 2 in 2019), No. 7 (merged with Clinical hospital No. 3 in 2019), No. 9, No. 10 (merged with Semashko Clinical Hospital in 2019);

- Semashko Clinical Hospital;

- Avtodiesel Medical and Sanitary Unit (merged with Clinical Hospital No. 9 in 2014);

- city polyclinic No. 2 (merged with Central City Clinical Hospital in 2019);

- state MO of Rybinsk: City Hospitals No. 1–6, City Polyclinics No. 1–3;

- Pereslavl, Rostov and Tutaev Central District Hospitals (CDH).

The data for meta-analysis were obtained from the main annual statistical reports presented by state MOs:

- statistical reports according to the registration form No. 025-12/у ‘Outpatient talon’, approved by the Order of the Ministry of Health and Social Development of the Russian Federation No. 255 of November 22, 2004 ‘On the procedure for providing primary health care to citizens entitled to receive a set of social services’;

- statistical reports according to the form No. 025-1/у ‘Talon of a patient receiving medical care on an outpatient basis’, approved by the Order of the Ministry of Health of the Russian Federation No. 834n of December 15, 2014 ‘On approval of unified forms of medical documentation used in the MO providing medical care on an outpatient basis, and the procedures for filling them out’ (Orders of the Ministry of Health of the Russian Federation No. 2n of January 09, 2018; No. 1186n of November 02, 2020);

- statistical reports according to the form No. 066/у-02 ’Statistical card of a person discharged from 24-hour stay hospital, a day patient facility at a hospital, a day hospital at an outpatient polyclinic institution, a hospital at home’, approved by Order of the Ministry of Health of the Russian Federation No. 413 of December 30, 2002 ‘On approval of accounting and reporting medical documentation’.

Statistical data were provided by the state budgetary healthcare institution Center for Public Health and Medical Prophylaxis of the YaR in accordance with request No. 01/15-68 of October 07, 2022.

The following parameters were extracted from the included data: quantitative and frequency characteristics of the population, prevalence (Table 1). At the first stage, a meta-analysis of the results of the prevalence of LEVV was performed at the end of each year in the period from 2011 to 2021, obtained from the annual reports of state MOs located in the territories of Yaroslavl, Rostov, Pereslavl, Tutaev districts and the city of Rybinsk. At the second stage, the analysis and synthesis of statistical data on the effects of the implementation of the LEVV in the same municipal districts, but in the interval of one year, was carried out.

Data analysis was performed using Review Manager 5.3.5. (Cochrane Collaboration, Oxford, UK, 2014). The weighted average value for continuous variables with 95% confidence interval (CI) was estimated. Statistically significant parameters were considered those with p < 0.05. Heterogeneity was estimated on the basis of the I² value. With this, a low degree of heterogeneity (I² ≤ 25%) implied a homogeneous data series, and a high heterogeneity (I² ≥ 75%), on the contrary, reflects a significant true variability of the data. To assess the data bias, statistical significance was assessed for each I2 parameter. Eggers and Begg tests, as well as funnel plot, were used to evaluate the data bias.

RESULTS

The total population weight of the sample for Yaroslavl for all periods of the study was 5,360,846 people. The static weighted average value of the prevalence of LEVV for Yaroslavl at the end of the year in the period 2011–2021 was 1.040% (95% CI: 1.031–1.049). Here, in 2011–2012 and 2017–2019, the frequency of the LEVV event was above the average value, in 2013–2016 and 2020–2021 — below (Table 2).

 

Table 1. Number of Patients Aged 18 and Above Living in 5 Municipal Entities of the Yaroslavl Region Diagnosed with Low Extremity Varicose Veins

Territory	Year	Number of Adult Population	Low Extremity Varicose Veins	Year	Number of Adult Population	Low Extremity Varicose Veins
Yaroslavl	2011	486 312	7 151	2012	482 437	5 729
Rybinsk		170 223	864		168 438	803
Pereslavl district		51 498	543		51 047	354
Rostov district		54 557	564		53 678	509
Tutaev district		45 903	370		46 080	405
Yaroslavl	2013	482 364	4 532	2014	484 965	4 722
Rybinsk		163 717	675		162 076	628
Pereslavl district		50 793	441		50 071	351
Rostov district		53 193	486		52 604	589
Tutaev district		45 775	315		45 937	289
Yaroslavl	2015	486 221	4 615	2016	488 429	5 028
Rybinsk		159 877	692		156 035	708
Pereslavl district		50 137	367		49 928	344
Rostov district		51 861	557		51 421	398
Tutaev district		45 417	279		45 112	256
Yaroslavl	2017	489 537	5 619	2018	490 054	5 833
Rybinsk		154 286	545		154 904	590
Pereslavl district		49 459	282		48 098	274
Rostov district		51 088	344		50 449	419
Tutaev district		–	–		44 446	284
Yaroslavl	2019	490 945	5 645	2020	489 757	3 683
Rybinsk		151 408	448		150 862	440
Pereslavl district		47 371	264		47 006	200
Rostov district		49 568	418		49 322	373
Tutaev district		43 707	208		43 485	144
Yaroslavl	2021	489 825	3 696
Rybinsk		146 022	461
Pereslavl district		45 251	266
Rostov district		48 771	313
Tutaev district		42 861	174

 

Table 2. Characteristics of Groups Included in Study in Territory of Yaroslavl

Studies	Sample Size	Prevalence		Fixed Effect, %	Random Effect, %
		%	95% CI
2011	486 312	1.470	1.437–1.505	9.07	9.09
2012	482 437	1.188	1.157–1.218	9.00	9.09
2013	482 364	0.940	0.913–0.967	9.00	9.09
2014	484 965	0.974	0.946–1.002	9.05	9.09
2015	486 221	0.949	0.922–0.977	9.07	9.09
2016	488 429	1.029	1.001–1.058	9.11	9.09
2017	489 537	1.148	1.118–1.178	9.13	9.09
2018	490 054	1.190	1.160–1.221	9.14	9.09
2019	490 945	1.150	1.120–1.180	9.16	9.09
2020	489 757	0.752	0.728–0.777	9.14	9.09
2021	489 825	0.755	0.731–0.779	9.14	9.09
In total, FE	5 360 846	1.040	1.031–1.049	100.00	100.00
In total, RE	5 360 846	1.040	0.921–1.167	100.00	100.00

Notes: CI — Confidence Interval, FE — Fixed Effect, RE — Random Effect

 

In the test for heterogeneity it was found that samples included in the meta-analysis, were heterogenic I² — 99.51% (95% CI: 99.42–99.59) at р < 0.0001. On the basis of heterogeneity of sample, the random effect of LEVV realization in the territory of Yaroslavl made 1.040% (95% CI: 0.921–1.167; Table 2).

The adult population size in Yaroslavl during the analyzed ten-year period, practically remained unchanged, despite the different true sizes of the effect in each particular year. At the same time, the forest plot indicates a significant variability in the average prevalence parameter over the years relative to the general average. Here, in periods where the presented data are to the right of the average value, the situation on the prevalence of LEVV among the adult population was more unfavorable. In general, according to statistical reports provided by the state MOs of Yaroslavl, there was a tendency for reduction of morbidity with LEVV within 10 years. The P-values of the results of Eggers and Begg tests and the visual data of the funnel plot indicate the normal distribution of the statistical data obtained relative to the total average of all studies (Figure 1).

 

Fig. 1. Forest plot (А) and funnel plot (B) of parameters of groups included in the study, on the basis of the data of the state medical organizations of Yaroslavl. Notes: CI — confidence interval, RE — random effect, FE — fixed effect.

 

It is worth noting that in Yaroslavl, only 2 periods of 2017 and 2019 with similar prevalence of LEVV were recorded by the end of the year. In the rest of the periods, this parameter was characterized by sufficient volatility by the end of the year. In general, high heterogeneity of factors that influence the annual record of prevalence of LEVV in the territory of Yaroslavl, is of high scientific and practical interest.

Despite the decrease in the size of the effect of the realization of the LEVV in the period 2011–2021, similar samples for Rostov, Pereslavl, Tutaev districts and the city of Rybinsk, have their own specificity. In contrast to the city of Yaroslavl, negative dynamics of the adult population was recorded in the areas studied according to the protocol. In the period 2011–2015 in these areas, as shown by the visual analysis of the forest plot, the values of the annual cumulative prevalence turned out to be to the right from the general average, and in the period 2017–2021, the situation of morbidity with LEVV changed towards decline. It is interesting to note that in 2017, 2018 and 2019 in Yaroslavl, the situation with respect to the average values of the prevalence of LEVV turned out to be unfavorable, while in Rostov, Pereslavl districts and Rybinsk, the sizes of the effects of realization of LEVV appeared to be smaller compared to the general average in the same territories (Figure 2).

 

Fig. 2. Forest plot (A) and funnel plot (B) of parameters for groups included in the study, according to the data of state medical organizations of Rostov, Pereslavl, Tutaev districts and of the city of Rybinsk. Notes: RE — random effect, FE — fixed effect

 

In the course of the analysis of the prevalence of LEVV at the end of the year in the selected municipalities of the Yaroslavl region, the following patterns were revealed. Thu,, in 2011, the total studied population was 808,493 people aged 18 years and older, of whom 1,134 (95% CI: 1,111–1,157) were diagnosed with LEVV. With this, only in Yaroslavl, the incidence of LEVV was above the average and amounted to 1,470 (95% CI: 1,437–1,505). In the remaining territories, the prevalence of LEVV was below the recorded average effect. The lowest prevalence of LEVV in 2011, according to the results of annual reports of state medical organizations in Rybinsk, was 0.508 (95% CI: 0.474–0.542). The heterogeneity test for this year showed that the studies included in the meta-analysis for individual districts turned out to be highly heterogeneous I2 — 99.70% (95% CI: 99.62–99.76) at p < 0.0001. Taking into account the heterogeneity of the sample, the random effect of realization of LEVV was 0.948 (95% CI: 0.548–1.456; Table 3; Figure 3).

 

Table 3. Characteristics of Groups Included in Study in 2011

Territory of Study	Sample Size	Prevalence		Fixed Effect, %	Random Effect, %
		%	95% CI
Yaroslavl	486 312	1.470	1.437–1.505	60.15	20.08
Rybinsk	170 223	0.508	0.474–0.542	21.05	20.05
Pereslavl district	51 498	1.054	0.968–1.146	6.37	19.96
Rostov district	54 557	1.034	0.951–1.122	6.75	19.97
Tutaev district	45 903	0.806	0.726–0.892	5.68	19.94
Total FE	808 493	1.134	1.111–1.157	100.00	100.00
Total RE	808 493	0.948	0.548–1.456	100.00	100.00

Notes: CI — confidence interval, RE — random effect, FE — fixed effect

 

Fig. 3. Forest plot (A) and funnel plot (B) of parameters of the groups included in the study in 2011. Notes: CI — confidence interval, RE — random effect, FE — fixed effect.

 

The forest plot shows a strong variance in the average prevalence of all studies relative to the general average. The presented data, namely, the results of Eggers and Begg tests, visual signs of the funnel plot, indicate the fact of existence of different true effect sizes in each specific territory, that, nevertheless, fully corresponded to the normal distribution relative to the total average of all studies with a standard error of less than 0.03.

From the data presented in Table 4, it can be seen that within one year, each specific location has its own incidence of LEVV among the adult population. The heterogeneity revealed in the samples located to the left or right of the average value is not accidental and suggests the existence of certain factors affecting the incidence of LEVV in these areas. For example, in Pereslavl and Rostov districts, these factors are more similar than in other districts, and vice versa.

In analysis of the data for 2011–2021, a trend is determined to reduction of the incidence of LEVV. At the end of 2021, the prevalence of LEVV in Yaroslavl decreased by 0.715%, in Pereslavl district — by 0.466%, in Tutaevsky district — by 0.4%, in Rostov district — by 0.392%, in Rybinsk — by 0.192% with high heterogeneity (I² 99.14; 95% CI: 98.81–99.39; Table 4).

 

Table 4. Characteristics of Groups Included in Study in 2021

Territory of Study	Sample Size	Prevalence		Fixed Effect, %	Random Effect, %
		%	95% CI
Yaroslavl	489825	0.755	0.731–0.779	63.39	20.24
Rybinsk	146022	0.316	0.288–0.346	18.90	20.15
Pereslavl district	45251	0.588	0.519–0.663	5.86	19.87
Rostov district	48771	0.642	0.573–0.717	6.31	19.90
Tutaev district	42861	0.406	0.348–0.471	5.55	19.85
Total FE	772730	0.621	0.603–0.639	100.00	100.00
Total RE	772730	0.530	0.339–0.762	100.00	100.00

Notes: CI — confidence interval, RE — random effect, FE — fixed effect

 

Here, a gradual shift of the total random effect to the left of the average value is recorded on the forest plot (Figure 4), as well as a shift of the data to the left in each location, which, except for Rostov district, formally indicates improvement of the epidemiological situation for LEVV in the given municipalities of the YaR. On the contrary, an opposite trend is observed in Rostov district, which rather conventionally may indicate impairment of the situation with LEVV in the given region.

 

Fig. 4. Forest plot (А) and funnel plot (B) of parameters of the groups included in the study in 2012–2022. Notes: RE — Random Effect, FE — Fixed Effect 

 

The assessment of absolute and relative values of LEVV among the adult population in Rostov region in 2011–2021 is presented as a plot resembling a declining sinusoid. Here, the incidence of LEVV per capita of the dult population for the same period of time shows stronger fluctuations (Figure 5). The lowest prevalence parameters were noted in 2013, 2017 and 2021. Peaks of LEVV incidence occurred in 3 periods: 2011, 2014–2015 and 2018–2019.

 

Fig. 5. Number of patients with (А) and prevalence (B) of LEVV in Rostov district from 2011 to 2021. Notes: LEVV — lower extremity varicose disease.

 

The dynamics of absolute and relative values of LEVV among the adult population of Yaroslavl for 2011–2021, presented in the form of a plot, also resembles a sinusoid with a downward trend. At the same time, the frequency of occurrence of LEVV per capita of the adult population for the same period of time has a more flat form (Figure 6). The lowest prevalence rates of LEVV were noted in 2013, 2015 and 2020, 2021. Peak incidence of LEVV occurred in 2 periods: 2011, 2018–2019.

 

Fig. 6. Number of patients with А) and prevalence (B) of LEVV in Yaroslavl from 2011 to 2021. Notes: LEVV — lower extremity varicose disease.

 

DISCUSSION

The epidemiological situation and its dynamics in Yaroslavl, Rybinsk, Rostov, Pereslavl, Tutaev districts of the YaR exclude the significant role of genetic, ethnic and national, demographic and other social factors. The natural and climatic conditions, the ecological situation in these periods in Yaroslavl also remained unchanged. Thus, the trend towards a decrease in the prevalence of LEVV in Yaroslavl can be explained by the influence, first of all, of medical and social factors.

On the one hand, this may be due to a decrease in the level of diagnosis of the disease, on the other, due to an increase in the amount of radical treatment of the disease. The factor of the increasing participation of non-state organizations in the system of providing assistance to the population should not be discounted either. In the last decade, minimally invasive technologies for the treatment of LEVV, primarily endovasal thermal obliteration, significantly changed approaches to radical treatment of LEVV, changing the conditions of care to outpatient ones. In the YaR, hospital-substituting technologies are practiced exclusively in non-state MOs, whose work has no territorial limitations and is focused on the same contingent that is serviced in the public health sector of the region. In this study, the cases of referral to private MOs for treatment of LEVV were not considered. These circumstances can also explain the identified trends in the dynamics of officially recorded epidemiological parameters of LEVV.

The analysis of epidemiological data, including the test for heterogeneity of factors determining the variance of the studied effect in different periods of observation in Rostov, Pereslavl, Tutaev districts of the YaR and in Rybinsk, has a low level of statistical significance, which is confirmed by Eggers and Begg tests (in all statistical models p < 0.01) and by the results of visual analysis of the funnel plot (Figure 2). The latter appeared to be asymmetric, with a shift to the left from the fixed effects and diagonal lines of 95% CI in all the studied areas, where low prevalence of LEVV was recorded at the end of the year. Thus, the distribution of true sizes of the effect differ from normal relative to the general average in Rostov, Pereslavl, Tutaev districts of the YaR and the city of Rybinsk.

Such dynamics of epidemiological parameters could be explained by the heterogeneity of conditions and the effect of different medical and social factors in each of the studied territories. That is, in each of the districts there were unique conditions affecting the trends of the morbidity with LEVV recorded at the end of the year within 10 years. This, in turn, may indicate the absence of uniform standards in the healthcare of the region both in the diagnosis and treatment of this disease and, in general, the low efficiency of the system dealing with this nosological group of diseases, or transfer of the burden of providing such care to the non-state healthcare sector.

CONCLUSION

Thus, based on the meta-analysis conducted with observance of all protocols of Cochrane Community, it was revealed that lower extremity varicose veins is a common vascular disease in the population aged 18 years and older living in Yaroslavl and Rybinsk, Rostov, Pereslavl and Tutaev districts of the Yaroslavl region.

The frequency of occurrence of lower extremity varicose veins, according to the annual statistical reports of state medical organizations in the specified municipalities of the Yaroslavl region over the past 10 years, has a downward trend in all studies. The revealed dynamics of the incidence of lower extremity varicose veins in the studied territories of the Yaroslavl region differs from the data of current population-based epidemiological studies, which have recently recorded an increase in the incidence of varicose veins of the lower extremities. This may indirectly indicate the existence of a share of patients in the study population who fall out of the attention of specialists, the ineffectiveness of the whole system of identifying patients with varicose veins of the lower extremities.

From the analysis of data on the prevalence of lower extremity varicose veins at the end of each of the periods over the past 10 years in the studied municipalities of the Yaroslavl region, statistical heterogeneity was also found in the territories and in dynamics for each year.

The reasons for the situation that has developed in the last decade may be lack of uniform standards in the healthcare of the region both in the diagnosis and treatment of varicose veins, and at the same time an increase in the share of the non-state healthcare sector in the system of providing medical care to patients with venous pathology.

These circumstances should be taken into account when planning and organizing medical care for the population with this pathology.

ADDITIONALLY

Funding. The authors declare that there is no funding for the study.

Conflict of interests. The authors declare no conflicts of interests.

Contribution of the authors: M. P. Potapov ― study concept and design, statistical analysis, data analysis and interpretation, text writing; I. N. Staroverov ― the concept and design of the study, checking the critical intellectual content of the work, final approval for publication of the manuscript. All authors made a substantial contribution to the conception of the work, acquisition, analysis, interpretation of data for the work, drafting and revising the work, final approval of the version to be published and agree to be accountable for all aspects of the work.

About the authors

Maksim P. Potapov

Yaroslavl State Medical University

Author for correspondence.
Email: mxp@mail.ru
ORCID iD: 0000-0002-4596-6517
SPIN-code: 2732-2232

MD, Cand. Sci. (Med.), Associate Professor

Russian Federation, Yaroslavl

Il'ya N. Staroverov

Yaroslavl State Medical University

Email: aspirant.ygmy@yandex.ru
ORCID iD: 0000-0001-9855-9467
SPIN-code: 8011-7176

MD, Dr. Sci. (Med.), Associate Professor

Russian Federation, Yaroslavl

References

Supplementary files