Comorbidity profile in chronic brain ischemia on the background of multifocal atherosclerosis.

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Abstract. Comorbidity profile in chronic brain ischemia on the background of multifocal atherosclerosis. Dzyak L.А., Rosytska О.А. Aim to evaluate the comorbidity profile in patients with chronic cerebral ischemia on the background of multifocal atherosclerosis. The study included 137 patients aged 40 to 84 years with chronic cerebral ischemia (CСI) on the background of multifocal atherosclerosis, which were divided into three clinical groups depending on the localization of vascular lesions by stenosing atherosclerosis. The co-morbidity profile and severity were evaluated using the Charlson's index in modification of R. A. Deyo (1992). In CCI patients, regardless of the combination of vascular basins affected by atherosclerosis, a severe degree of comorbidity prevailed -the Charlson's comorbidity index (IC) was predominantly > 5 points (84.7% of cases). In the analysis of IC in age categories, depending on the combination of atherosclerotic lesions of the vascular basins, it was found that comorbidity of severe degree (IC> 5) was predominantly represented by patients of the older age group (60-74 years), and comorbidity of moderate severity (IC≤5) -patients of middle age group (45-59 years). A median difference of 3 points in assessing the mean value of age-matched comorbidity index showed that age, as a non-modifiable risk factor, in 1/3 cases determines the comorbidity index, which depends on the number of vascular basins affected by atherosclerosis. In  The number of patients suffering from several diseases increases every year [1]. Comorbidity is the coexistence of two and / or more syndromes or diseases in one patient, pathogenetically interacting with each other or coinciding in time. Both conditions are the result of a single pathological process, and the differences in their course are due to the influence of external behavioral factors [3].
Comorbidity not only acts as a global medical problem and determines an individual prognosis for each patient (functionality, duration and quality of life, disability and mortality), but also has largescale social consequences at the population level. Especially it affects the determination of the diagnostic and therapeutic approach for patient management [4]. Often, it is comorbid lesions that worsen the course of the underlying disease and / or lead to chronicity, cause disability and premature death of the working population. The presence of comorbid diseases significantly worsens the course of each disease separately [1] Most patients, especially the elderly and senile, have a combined pathology: damage to the brain, cardiovascular system and kidneys, as well as metabolic syndrome. On average, examination of elderly and senile patients reveals from 4 to 8 leading diseases. With age, there is an increase in the number of patients with coronary heart disease, arterial hypertension (and their complicationsmyocardial infarction and heart failure), chronic На умовах ліцензії CC BY 4.0 kidney disease, diabetes mellitus (and its complications -primarily diabetic nephropathy, retinopathy and polyneuropathy), anemic syndrome. Each of the diseases is an independent risk factor for death in elderly patients. It has been established that risk factors for cerebrovascular diseases are simultaneously risk factors for cardiovascular diseases. The development and progression of cerebrovascular diseases, as well as cardiovascular diseases, is closely associated with modifiable risk factors (smoking, unhealthy diet, physical inactivity, psychosocial factors, hypertension, dyslipidemia, diabetes mellitus, metabolic syndrome, microalbuminuria, hyperhomocysteinemia, endothelial dysfunction and other factors (age, gender, adverse heredity) [5].
It was found that multidimensional indices, including the degree of severity (measured by functional constraint) for assessing comorbidity, correlate well with health outcomes, including quality of life and mortality. However, there are much fewer studies evaluating the severity or functional limitation of comorbidity [9, 11. For example, comorbidity prevents rehabilitation after a stroke [10], increases the number of complications after surgery, and increases the likelihood of falls in the elderly. Thus, the effect of comorbidity on the clinical manifestations, diagnosis, prognosis and treatment of many diseases is multifaceted and individual [2]. High comorbidity is an independent predictor of poor prognosis for survival [8] and can lead to mortality not associated with the underlying disease [11].
The possibility of the development and progression of cerebrovascular diseases, including chronic cerebral ischemia, increases with an increase in the number of compatibility and severity of behavioral factors and comorbid conditions. Comorbidity and potentially interacting vascular risk factors associated with the prevalence of atherosclerosis, which determine its heterogeneity, occupy an important place in the study of chronic brain ischemia. In domestic literature, such studies are not adequately covered, which determines the relevance of this work.
The purpose of the study: to evaluate the profile of comorbidity in patients with chronic brain ischemia on the background of multifocal atherosclerosis.

MATERIALS AND METHODS OF RESEARCH
The study included 137 patients aged 40 to 84 years, with multifocal vascular lesions. Of these, 107 (78.1%) patients are male and 30 (21.9%) are female. The average age of patients was (63.6±0,8) years.
Depending on the location of the lesion of vascular beds with stenosing atherosclerosis, all patients were divided into three clinical groups: I group -30 (21.9%) patients with vascular lesions of the brain, heart and lower extremities; II group -87 (63.5%) patients with vascular lesions of the brain and heart; III group -20 (14.6%) patients with vascular lesions of the brain and lower extremities. The distribution of patients depending on the course of chronic cerebral ischemia (CCI) were as follows: CCI no episodes of acute ischemia of the disease in anamnesis (23 patients), CCI with TIA in anamnesis (15 patients), CCI with a single cerebral infarction in the anamnesis (59 patients), with repeated infarcts of the brain in history (40 patients).
Neurological status was assessed with the identification of leading clinical symptoms and the establishment of a form of cerebral circulation disorder. The nature of vascular lesions was refined by ultrasound Doppler ultrasound of the extra-and intracranial arteries on the device HP SONOS-1000 HP made by Hewlett Packard (USA), as well as selective cerebral angiography (according to indications). Structural lesions and their extent were determined using a brain MRI on the apparatus of "General Electric" (USA).
Assessment of the comorbidity profile was performed using the Charlson's index in the modification of R.A. Deyo (1992) 10,11, which is a point system for estimating age, presence and number of comorbid diseases and allows to determine the severity of comorbidity: moderate -Charlson's comorbidity index ≤5 and severe -Charlson's 5 comorbidity index (Table 1).
Statistical analysis of the obtained data was performed using the licensed program Statistica v.6.1® (StatSoft, USA) (serial number AGAR909E415822FA). Mean values are presented as arithmetic mean with standard error (M±m) in cases of normal distribution law (Shapiro-Wilk test) or as median and quartile -Me (25-75%) in other cases. When comparing the relative indicators Fisher's two-way exact test (FTWET), was used for medium -the Mann-Whitney test.

RESULTS AND DISCUSSIONS
The analysis of the comorbid profile of patients with ССI in clinical groups showed heterogeneity of risk factors and concomitant diseases that contribute to the development and progression of vascular damage to the brain ( Table 2).
It was found that hypertension in 92.7% of cases and ischemic heart disease in 85.4% of cases predominanted among pathogenetically related comorbid diseases. In 22.6% of cases, patients with gastrointestinal tract pathology were identified, which we attributed to pathogenetically unrelated comorbid diseases. However, the term "pathogenetically unrelated diseases" is very conditional, given the concept of uniform behavioral factors that can lead to the development of atherosclerotic lesions of the 19/ Том XXIV / 4 vascular system and ischemic events. In the presented study, among the behavioral modifiable risk factors, the leading ones were identified: eating disorders (94.9%), physical inactivity (63.5%) and smoking (57.7%), and an unmodifiable factor -age (60 years and older -66.4%) Considering the large number of combinations of comorbid diseases in patients with CCI, we eva-luated the severity of comorbidity in selected clinical groups (Table 3). The analysis of the comorbidity profile in the selected clinical groups showed the heterogeneity of its severity associated with number of vascular basins affected by atherosclerosis. It was found that in patients with CCI, regardless of the combination of vascular beds affected by atherosclerosis, a severe degree of comorbidity prevailed -Charlson's comorbidity index (CI) was predominantly> 5 points (84.7% of cases). Thus, if in the first clinical group with combined atherosclerotic lesions of the vessels of the brain, heart and lower extremities, a severe degree of comorbidity was observed in 100% of cases, then in the II and III groups it was 80.5% and 80.0%, respectively (p<0.05 compared with group I), and a moderate degree of comorbidity in these groups was 19.5% and 20.0% of cases, respectively.

The prevalence of comorbid conditions and risk factors in patients with CCI in clinical groups
It was found that the severity of comorbidity, which means an increase in the number of comorbid conditions, affects not only the number of vascular basins affected by atherosclerosis, but also the nature (severity) of clinical manifestations of vascular brain lesions in patients with CСI (Table 4). Thus, if patients with a history of TIA had a severe degree of comorbidity -66.7% of cases, then in patients with a history of stroke, it was already 79.7% of cases, and in patients with a history of relapses -90% of cases.
To clarify the factors that determine the severity of comorbidity in clinical groups the comorbidity index was evaluated, taking into account age categories (Table 5).
In the analysis of the comorbidity index (IC) in age categories in selected clinical groups depending on a combination of the atherosclerotic lesion of the vascular beds it was established that severe comorbidity (IC>5) was represented mainly by the older age group (60-74 years) and comorbidity of moderate severity (IC≤5) -middle-age group (45-59 years). In individuals aged over 75 years only severe comorbidity was established (IC>5).

T a b l e 4
Characteristics of the degree of comorbidity severity in patients with CСI, taking into account the nature of the disease Assessment of IC in clinical groups, taking into account the nature of the disease (Table 6) (p<0,05), showed a relationship between the number of vascular pools affected by atherosclerosis, the severity of the clinical course of ССI and the severity of comorbidity. Thus, at atherosclerotic lesions of the vessels of all three basins (brain, heart and lower extremities), the highest values of the mean IC value (10 points) were established. That is, patients in the first clinical group with atherosclerotic lesions of the vessels of the brain, heart and lower extremities had the highest number of the ones with a greater number of comorbid conditions than in the second and third clinical groups with the damage of two basins -vessels of the brain and heart and vessels of brain and lower extremities, respectively. To assess the effect of modifiable and non-modifiable risk factors on the severity of comorbidity, an analysis of the Charlson comorbidity index in R.A. Deyo excluding age estimates (Table 7).

T a b l e 7
Characteristics of the comorbidity index without taking into account age in clinical groups, taking into account age categories Analysis of the characteristics of comorbidity severity without taking into account age showed a decrease in its severity in the selected clinical groups (Table 7). So, if age was taken into account when assessing IC, then in the І clinical group only a severe degree of comorbidity was established, and if age was not taken into account, then in this group a moderate degree of comorbidity was established, and severe -in only 60% of cases. These data confirm the concept of the effect of age on comorbidity severity and on the number of vascular basins affected by atherosclerosis in patients with CCI.

T a b l e 8
The average value of the comorbidity index without taking into account age in the clinical groups, taking into account the nature CCI