Резюме

Железнякова Н.М. Фактори інтенсифікації кардіоваскулярного ризику в умовах коморбідності ХОЗЛ та хронічного панкреатиту.

У статті представлені результати дослідження генетичних маркерів кардіоваскулярного ризику у пацієнтів з ізольованим ХОЗЛ та при його поєднанні з хронічним панкреатитом. Показано, що при коморбідній патології достовірно частіше спостерігається носійство патологічного генотипу D/D гена АПФ. Виявлено асоціацію даних генних мутацій з тяжкістю перебігу коморбідної патології, а саме ступенем бронхіальної обструкції та зовнішньосекреторної недостатності підшлункової залози, рівнями С-РБ та гомоцістеїну. Отримані дані дозволяють припустити наявність підвищеного кардіоваскулярного ризику у даної категорії хворих.

Ключові слова: ХОЗЛ, хронічний панкреатит, I/D поліморфізм гена АПФ, С-РБ, гомоцистеїн.

Резюме

Железнякова Н.М. Факторы интенсификации кардиоваскулярного риска в условиях коморбидности ХОЗЛ и хронического панкреатита.

В статье представлены результаты исследования отдельных генетических, воспалительных и тромботических маркеров кардиоваскулярного риска у пациентов с изолированным ХОЗЛ и при его сочетании с хроническим панкреатитом. Показано, что при коморбидной патологии достоверно чаще наблюдается носительство патологического генотипа D/D гена АПФ. Выявлена ассоциация данных генных мутаций с тяжестью течения коморбидной патологии, а именно степенью бронхиальной обструкции и внешнесекреторной недостаточности поджелудочной железы, уровнями С-РБ и гомоцистеина. Полученные данные позволяют предположить наличие повышенного кардиоваскулярного риска у данной категории больных.

Ключевые слова: ХОЗЛ, хронический панкреатит, I/D полиморфизм гена АПФ, С-РБ, гомоцистеин.

Summary

Zhelezniakova N.M. Factors of cardiovascular risk intensification in a comorbidity of COPD and chronic pancreatitis.

The article presents the results of a study of certain genetic, inflammatory and thrombotic cardiovascular risk markers in patients with isolated COPD and when it is combined with chronic pancreatitis. It was shown that in case of comorbidity were significantly more often revealed pathological genotypes D/D of I/D polymorphism of ACE gene. It was revealed an association between these gene mutations and degree of bronchial obstruction, severity of exocrine pancreatic insufficiency, levels of C-PR and homocysteine. These data indicate the presence of increased cardiovascular risk in these patients.
Key words: COPD, chronic pancreatitis, I/D polymorphism of ACE gene, C-RP, homocysteine.

Рецензент: д.мед.н., проф. Я.А. Соцька

UDC 616.24-007.272-036.12+616.37-002]:616.1

Харьковский национальный медицинский университет

Kharkiv National Medical University,

nmz25@mail.ru

According to modern concepts, COPD is considered a disease, not limited with the involvement in the pathological process, only the respiratory tract and is a systemic disease. This systemic inflammation leads to the formation of lesions and complications of other vital organs, especially the cardiovascular events that in most cases are the direct cause of death of patients.

The aim of the study was to determine the prevalence of gene polymorphisms of angiotensin-converting enzyme in patients with comorbidity of COPD and chronic pancreatitis (CP), and to determine their association with the pathological process and the risk of cardiovascular events.

Materials and methods. A 148 patients with COPD were examined, including 76 patients with a combined course of COPD and CP (study group) and 72 patients with isolated course of COPD (group of comparison). The work involved patients with I and II degree of bronchial obstruction: 25 patients with COPD and CP were I degree, 51 patients - II degree of bronchial obstruction; in the comparison group data value was - 25 and 47, respectively were studied insertion-deletion (I/D) polymorphism of the gene of angiotensin converting enzyme (ACE), the value of C-reactive protein (CRP) and homocysteine.

Results and discussion. In the group of healthy individuals phenotypical row of I/D polymorphism of the ACE gene was as follows: genotype I/I were recorded in 8 patients, genotype I/D - in 27 and pathological genotype D/D - in 15 people. In patients with isolated COPD, the distribution of genotypes had the following picture: 13, 33 and 26patients, respectively. Thus, in patients with isolated COPD pathological D/D genotype was observed more frequently in comparison with a group of healthy individuals, but the statistical analysis showed no significant differences in the distribution of genotypes (df=2, χ2=0,801, р=0,669).

In case of comorbidity of COPD and CP genotypic ratio I/D polymorphism of the ACE gene had a somewhat different picture that was shown: a decrease in the number of patients with normal I/I genotype to 9 patients and increased pathological mutations (D/D genotype) - 43 patients. At the same genotype I/D was established in 24 cases. Statistical analysis showed significant differences in the distribution of genotypes of I/D polymorphism of the ACE gene between patients with comorbidity and isolated COPD (df=2, χ2=6,233, р=0,044).

In the group with comorbidity in most cases (39 people)pathological D/D genotype was characteristic of patients with II degree of severity of airflow obstruction, which had an average severity of exocrine pancreatic insufficiency.Also, the proportion of these patients had 8 patients observation of I/D genotype, whereas genotype I/I had not met in these patients. Pathological genotype D/D significantly more often met in men - 29 cases than in women - 14, which gave significant differences for this indicator (df=1, χ2=7,259, р=0,007).

It has been found authentic increase of homocysteine in relation to the values of healthy individuals 9,6±0,5 mmol/l in the group with isolated COPD (t=2,145, p=0,038), and when it is combined with chronic pancreatitis (t=4,395, p<0,001). So in the patients of the study group, the figure reached 16,9±1,4 mmol/l in the comparison group 13,8±1,2 mmol/l (t=2,591, p=0,013).

Content of CRP in patients with combined course of COPD and chronic pancreatitis was higher in 4,3 times compared to reference values - 1,43±0,06 mg/l, and reached 6,2±0,25 mg/l (t=5,148, p<0,001), while in the comparison group - 4,1±0,22 mg/l (t=4,085, p<0,001). When comparing the indicators of basic and group comparison revealed that the content of CRP in patients with comorbidity was exceeded than the similar value of patients with isolated course of COPD 1,7 times (t=2,049, p=0,040).In the study of oscillations of CRP and homocysteinelevels based on ACE gene polymorphism was determined that the pathological mutant genotype D/D positively associated with statistically more pronounced deviation as CRP level (Q=+0,543), as homocysteine (Q= 0,423).

Summary. The development and course of COPD and its combination with CP occurs in a redistribution of genotypes I/D polymorphism of the ACE gene, characterized by a predominance of pathological variants indicates the presence of an increased risk of cardiovascular events in these patients.It should be noted that the presence of concomitant chronic pancreatitis brings significant credible changes in the distribution of genotypes of I/D polymorphism of the ACE gene by increasing the frequency of occurrence of abnormal genotype D/D (56,6%).

In patients with comorbid diseases the presence of pathological genotype D/D ACE gene in the majority of cases are associated with more severe airflow obstruction and exocrine pancreatic insufficiency, indicating a significant pathogenetic role of these genetic deviations in the development and progression of both COPD and chronic pancreatitis.Also it was revealed positive statistical association between the presence of abnormal genotype D/D of ACE gene and a more marked increase in the concentrations of homocysteine and CRP.