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ENDOTOXINEMIA IN ANTIVIRAL THERAPY
FOR CHRONIC HEPATITIS C AND ITS POTENTIAL
PHARMACOLOGIC CORRECTIONS
GEYVANDOVA N. I., YAGODA A. V.,
BONDARENKO E. M.
Serum levels of endotoxin were detected in 101 patients with CHC. All the patients received combined antiviral therapy (AVT): 83 of them got PEG-IFN-a-2a (Pegasys) and another 18 - short-acting IFNa.
The total number of leukocytes, neutrophils as well as the endotoxin levels in blood prior to AVT was normal. Through the course of AVT, 62 patients developed grade 2 neutropenia (54 patients on Pegasys and 8 receiving short-acting iFNa). Given the developing neutropenia, starting from Week 8 on, there was an increase in the blood endotoxin observed in all the patients, while those with neutropenia had their blood endotoxin higher if compared with those with no neutropenia. There was an inverse relationship found between the endotoxin levels and the number of neutrophils. Filgrastim (Neupo-max) was administered in 28 patients with neutro-penia<1.0x109/l. Against the Filgrastim treatment the endotoxinemia indices got down significantly (p<0.05), while the patients were demonstrating an improved well-being status. Introduction of Filgrastim allowed maintaining the neutrophil level at no lower than 1.0-1.5x109/l thus preventing the need to reduce the doses of interferon.
Key words: chronic hepatitis C, neutrophils, endotoxin, antiviral therapy, granulocyte colony-stimulating factor
ЭНДОТОКСИНЕМИЯ ПРИ ПРОТИВОВИРУСНОЙ ТЕРАПИИ ХРОНИЧЕСКОГО ВИРУСНОГО ГЕПАТИТА С И ВОЗМОЖНОСТИ ЕЕ ФАРМАКОЛОГИЧЕСКОЙ КОРРЕКЦИИ
Н. И. ГЕЙВАНДОВА, А. В. ЯГОДА, Е. М. БОНДАРЕНКО
У 101 больного с ХВГС определяли содержание эндотоксина в сыворотке крови. Всем пациентам проводилась комбинированная противовирусная терапия (ПВТ): 83 больных получали ПегИФН-а2а (Пегасис) и 18 - препараты ИФН-а короткого действия.
Общее количество лейкоцитов, число нейтро-филов и уровни в крови эндотоксина до начала ПВТ были нормальными. В ходе ПВТ нейтропе-ния II степени развилась у 62 больных (54 пациента, получавших Пегасисе, и 8 - ИФН-а короткого действия). На фоне развития нейтропении начиная с 8 недели отмечалось увеличение содержания в крови эндотоксина у всех пациентов. При этом у больных с нейтропенией уровень эндотоксина был выше, чем у пациентов без ней-тропении. Была выявлена обратная связь между уровнем эндотоксина и числом нейтрофилов. Филграстим (Нейпомакс) был применен у 28 пациентов с нейтропенией <1,0х109/л. На фоне назначения филграстима достоверно уменьшался уровень эндотоксинемии (р<0,05) и улучшалось самочувствие пациентов. Введение филграсти-ма позволило сохранять уровень нейтрофилов не ниже 1,0-1,5х109/л и тем самым предотвращать необходимость снижения дозы интерферонов.
Ключевые слова: хронический вирусный гепатит С, нейтрофилы, эндотоксин, противовирусная терапия, гранулоцитарный колониести-мулирующий фактор
© Group of authors, 2014 UDC 616-053.5:616.1
DOI - http://dx.doi.org/10.14300/mnnc.2014.09046 ISSN - 2073-8137
FEASIBILITY OF ALLOCATION OF PERSONS WITH SIGNS PREHYPERTENSION IN PREVENTIVE MEDICAL INVESTIGATION OF STUDENT YOUTH
Evsevyeva M. E., Mistchenko E. A., Rostovtseva M. V., Sergeeva O. V., Galkova I. Yu., Smirnova T. A.
Stavropol State Medical University, Russian Federation
Evsevyeva Maria, MD, PhD, Professor, Honored Doctor
of the Russian Federation, Head of the Student Health Center, Head
of Department of Internal Illnesses, Stavropol
State Medical University;
tel.: 8(928)3154687; e-mail: [email protected]
Mistchenko Elena, PhD, Assistant of Department of Internal Illnesses, Stavropol State Medical University; tel.: 8(926)3167244; e-mail:[email protected]
Rostovtseva Maria, Postgraduate of Department of Internal Illnesses, Stavropol State Medical University; tel.: 8(926)1919513; e-mail: [email protected]
Sergeeva Oksana, PhD, Docent of Department of Internal
Illnesses, Stavropol State Medical University;
tel.: 8(918)7412289; e-mail: [email protected]
Galkova Ilona, Postgraduate of Department of Internal Illnesses,
Stavropol State Medical University;
tel.: 8(928)2933574; e-mail:[email protected]
Arterial hypertension (AH) remains one of the most acute problems of modern health care because of the high incidence and significant contribution to the overall structure of mortality and disability population [1, 2, 3]. However, its detection in the early stages in young adults remains unsatisfactory [4, 5]. In this regard, adequate assessment of high normal blood pressure (HNAD), which relates in accordance with the classification of the Joint National Committee on Detection, Evaluation and Treatment of hypertension USA (ONC 7) prehypertension should call special attention to professionals. Current data
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indicate that its presence increases the risk of cardiovascular (CV) complications [6, 7, 8]. For example, the population register NHANES III [9] has demonstrated that prehypertension is associated with a significantly increased risk of death of CV diseases in 1.41 times (p<0.05) compared with persons with BP<120/80 mm Hg.
Development of these aspects of problem of prehypertension will create the basis for a more rational formation of groups of cardiovascular risk in young adults and will contribute to a more individualized preventive programs among the younger population.
Aim - to explore a circadian blood pressure profile in young adults with hypertension and HNAD to justify the formation of active young people identify with signs prehypertension and their inclusion in the number of persons subject to further medical examination.
Material and Methods. The study was conducted in two stages. In the first phase surveyed 147 boys aged 18 to 25 years (mean age 20.69±0.25 years) of the number of recruits with the presence of newly diagnosed hypertension according to office measurements > 140/90 mmHg (36 people - the main group) compared with the control group formed of the number of peers with office blood pressure of < 139/89 mmHg (111 people). The study group did not include individuals with the secondary hypertension according results of the fulfilled survey. In the second stage among the boys in the control group isolated persons with a pressure between 130/85-139/89 mmHg. Thus, the second phase examined the same 147 people, but under the new monitoring groups: 1gr. - Individuals with optimal and normal blood pressure (81 pers.) 2gr. - Persons with high normal blood pressure (30 pers.) And 3gr. - Persons with hypertension (36 pers.).
Office measurement was performed by standard procedure twice with a 5 minute interval on each arm. If the difference in blood pressure > 5 mmHg produced an extra dimension. In a finite minimum value was taken from three measurements. Blood pressure was measured with an accuracy of 2 mmHg BP values interpreted in accordance with the classifications recommended by ESC in 2013 [10]. At the level of blood pressure > 140/90 mmHg AH was recorded.
Ambulant monitoring (AM) the BP was spent on device BPLab Vasotens-24 (P. Telegin, Russia) with an interval of measurements of 30 minutes during the day and 60 minutes at night. More than 20 parameters - average means of the systolic (S) BP and diastolic (D) BP for a 24-hours, day, night, pulse pressure, variability the SBP and DBPD, a daily index, the maximal and minimal values the SBP and DBP for 24-hours, day, night and others - were analyzed.
Obtained data are processed by means of the software package «Statistica 6.0» ( StatSoft Inc.). Reliability of differences in parameters between
students I and VI courses was evaluated using the Pearson x2 test (significance of the differences of relative values). As practically all analyzed quantitative indicators of office and ambulatory BP had improper distribution according to method Sha-piro-Wilka, the statistical analysis of these indicators was based on non-parametric methods. The results are presented as medians and quartiles [68]. The differences were statistically significant at p<0.05.
Results and Discussion. The results of the analysis of indicators AMBP initial two comparable groups indicate the presence of significant differences between them for a variety of indicators of daily profile. And such indicators as the average mean SBP, DBP in the daytime reach a statistically significant level. This applies to the load indices elevated BP - time indices of systolic blood pressure (IVSAD) and diastolic BP (IVDAD) per night, day, night.
Showed higher numbers of SBP and DBP for all periods monitoring of young people with the original AH. And SBP readings per day in hypertensive patients exceeded the recommended limits and accounted for 128 (118.25-131.25) mm Hg compared with 116 (112-124) mm Hg in the group with unraised blood pressure (p=0.005). The daily average systolic Bp in the group was also slightly higher than the normative values and amounted to 135.5 (130.25-138) mm Hg at the upper boundary of the allowable 130-135 mm Hg [10].
Time indexes of SBP for the night and day in the group with hypertension exceed the allowed values and constitute 28.1 % and 23.55 %, respectively. Time indices DBP for the night and the day in a group of AH also were above the «norm» and constitute 43.35 % and 20 %, respectively (at a rate of < 25 % and < 15 %). Also revealed a significant difference in magnitude of the morning rise of systolic BP in group of AH.
Thus, a subdivision of young people according office BP above and below 140/90 mmHg looks at first glance quite convincing, since office hypertension is consistent with the increase of majority indicators of performanced ABPM. The validity of this approach is confirmed by the data obtained by us earlier [12,13]. They showed the presence of a number of differences in young people with hypertension compared with their peers with unraised BP.
However, the emergence of new data indicated to the predictive value of high-normal blood pressure, makes it worthwhile to study the peculiarities of circadian blood pressure profile in young carriers of this pressure [14, 15]. Therefore, the next stage of the study included three groups of observations with release of persons with high normal BP. Materials of Table allow to comparison between patients with hypertension and «true» normotensive persons, as well as with high-normal blood pressure carriers.
Notes: * - p1-2<0,05; ** - p1-3<0,05; # - p2-3<0,05.
BP - blood pressure, BP24-h,d,n. blood pressure average 24-h, per day, respectively, per night; Var - variability; TI. - time index; DI - daily index; MRV - morning rise in value; SMS BP - speed morning Systolic/ Diastolic BP surge; HR24,d,n. - heart rate average 24-h, per day, respectively, per night.
Table
ABPM indicators in groups with different levels of office BP (Ме, V0,25-0,75)
Indicators Normal BP group (n = 81) HN BP group (n = 30) Hypertension group (n = 36)
Office systolic BP (mm Hg) 120 (118-122) 132 (131-134.5) 143 (141.8-143.3)
Office diastolic BP (mm Hg) 76 (72-80.5) 82.5 (80.5-86) 92 (89.8-93)
Systolic BP24-h (mm Hg) 114 (111-119)* 125.5 (124-129.3) 128 (118.3-131.3)**
Systolic BPd (mm Hg) 118 (114-122)* 132.5 (127.5-138.3) 135.5 (130.3-138)**
Systolic BPn (mm Hg) 104 (101-109.3)* 115.5 (108.3-119.3) 115 (112.5-121.3)**
Diastolic BP24-h (mm Hg) 69 (65-73)* 77 (73.5-84.3) 78.5 (71-83.3)**
Diastolic BPd (mm Hg) 73 (70-78)* 84 (78.3-87.5) 83 (81-88)**
Diastolic BPn (mm Hg) 57.5 (54.8-63.3)* 67 (60.8-68) 63 (57.8-67)**
Var Systolic BPd. (mm Hg) 12 (10-14) 13.31 (10.2-14.7) 14.66 (10-18.2)
Var Diastolic BPd (mm Hg) 12 (9.3-15.1) 11.93 (11-13.5) 13.5 (11-16.5)
TI Systolic BP24-h. % 1.45 (0.2-5.5) 3.8 (1.8-9.4)# 28.1 (19.5-59.7)**
TI Systolic BPd. % 2.2 (0.3-4.3)* 23.95 (8.6-42.1) 23.55 (10.4-47.8)**
TI Systolic BPn. % 0 (0-0)* 17.35 (0-32.6) # 6.5 (0-34)*
TI Diastolic BP24-h. % 5.65 (2.2-12.6)* 21.55 (17.5-29.8) # 43.35 (31.5-56.9)**
TI Diastolic BPd. % 4.6 (2.5-11.9)* 28.9 (14.8-49) 20 (17-54.2)**
TI Diastolic BPn. % 0 (0-7.4)* 9.35 (0.5-19.6) 4.15 (0-21.1)**
DI Systolic BP. % 12 (8-14.1) 13.5 (10.6-14.5) 15.7 (12.1-18)
DI Diastolic BP. % 19 (15.9-25) 21.3 (15-25.1) 23.2 (19.5-28.3)
MRV Systolic BP. mm Hg 40 (35-49) 42.5 (33.3-49.3) 55 (50-62)**
MRV Diastolic BP. mm Hg 40 (30-48) 48.5 (22.3-55.8) 57 (34-63)
SMS Systolic BP. mm Hg/h 13 (9-22) 14.95 (2-21.2) 20 (12.4-43.5)
SMS Diastolic BP. mm Hg/h 11.7 (6-17.1) 13.5 (5.3-18.4) 11.3 (6.7-19)
HR24-h 75 (70-83)* 84.5 (81.3-90.5) 78 (74-81.3)
HRd 80 (75-86)* 90.5 (85.5-95.8) 85 (80-88)
HRn 62 (57.8-67.5)* 69.5 (63.3-74.3) 63 (61.8-70.3)
Var HRd 12 (9.3-15.1) 12.07 (10.3-13.7) 12.5 (10.7-14.6)
DI HR. % 18.4 (14.9-22.8) 20 (13.7-22.7) 23.75 (21.3-25)
The data in this table show that between the first and the third group was far more differences than before. So, if previously it has been presented significant differences on nine indicators, it is now revealed differences in thirteen parameters. Earlier differences concerned indicators such as average SBP, DBP in the daytime, time indexes of SBP and DBP day, night, now this number included another indicators - average night SBP and DBP, level of diastolic blood pressure at night. But it is also important that in the first group, there are differences not only with explicit hypertensive in the third group, but also with the second group of persons with HNBP. By some measures, they also reach significant levels. These indicators include the average SBP, DBP for all the monitoring period, as well as indicators of elevated blood pressure load (time index) and frequency of heart rhythm.
In other words, a more differentiated allocation among the young contingent of the group of persons with office high normal BP is justifiablied, since results of AMBP show presence of clear differences between this group and persons with normal and optimal blood pressure. Often
these differences reach severity similar circadian changes in individuals with hypertension and even exceed them. It is also noteworthy that more than half of young men with signs HNBP - 63 % - in result of the active questioning imposed various CV complaints. They show a more frequent occurrence of heredity, burdened by early CV disease - 80 % versus 59 % in comparison with their normotensive peers. These findings point to the need for more attention from doctors of the medical commissions of military committees to young men - HNBP carriers. Meanwhile, among the admitted ones to hospital for examination of the vast majority were young people with the unique presence of hypertension according to office BP assessment.
This approach coincides with the results of other authors about the increased risk of development in period 2-4 years the persistent arterial hypertension in young persons with initial prehypertension symptoms [14]. In another study authers show the emergence of new cases of hypertension during the 7-year follow-up in 10.5 % of men with high- normal blood pressure. In the female population, the Figures were 7.2 %
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[17]. Also it has been found that high normal systolic blood pressure was accompanied with an increased risk of hypertension in 2.43 times, high normal diastolic pressure - in 2.33 times
[18]. But while most of the studies have carried out on a more mature cohort aged 35 years
[19]. These data, combined with the results of epidemiological studies, about quite widespread of prehypertension in the general population [20, 21] indicate the need for further research on the characteristics of the course of cardio-vascular diseases on their prenosological stage. Youth age corresponds to this stage. These data indicate, on the one hand, the presence of a whole range of clinical and instrumental changes in young people with signs of high normal blood pressure, and on the other hand, provide a basis for optimizing the dispensary system of keeping the young population. The realisation of this approach is necessary to counteract the emergence of real atherosclerotic cardio-vascular diseases at the early stages of their development.
Conclusion
1. Among young patients, who are sent by the medical board military offices to hospitals about high blood pressure, most ones are characterized by pressure above 140/90 mm Hg. Young people with high-normal blood pressure (HNBP) are not regarded as noteworthy in terms of the continuation
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10. 2013 ESH/ESC Guidelines for the management of arte-
of the survey even if they have the appropriate complaints and negative family history.
2. In the general population of young men, who is characterized by the presence of hypertension in about 12 %, the number of subjects with high normal blood pressure is almost 20 %. More than half of the last ones have family history of early development of cardiovascular disease, as well as the presence of cardiac and cerebral complaints similar to hypertension.
3. Young people with high normal blood pressure are characterized by a number of reliable negative differences in terms of blood pressure monitoring compared with their peers with normal and optimal blood pressure. However, these changes are similar to those in patients with symptoms of hypertension, but their expression is less significant. Among such changes, relate primarily mean values of systolic blood pressure, diastolic blood pressure, high indices of load of systolic and diastolic blood pressure, the magnitude of morning rise in blood pressure.
4. Individuals with not only the presence of hypertension, but also with high normal blood pressure (HNBP) must be included in the group of cardiovascular risk according results of preventive examinations of young contingent. It is necessary for the implementation of early and effective preventive measures in this group of risk.
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12. Evsevyeva M., Rostovtseva M., Galkova I., Rusidi A., Andreeva E. About correlation of socio-psychological status and factors of cardiovascular risk at young men. EUSUHM Congress 2013: Breaking down the Barriers: reducing health inequalities for Europe's children and young people. London, 2013, 37-38.
13. Evsevyeva M., Mishchenko E., Sergeeva O., Galkova I., Smirnova T. Newly diagnosed arterial hypertention and prehypertention in young men: parameters of hemodynamic status and mental health. The 3rd International Conference on Prehypertension, Hypertension and Cardio Metabolic Syndrome, Warsaw. 2013. P. 27-28.
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22. McGill H., McMahan C. Pathology of Atherosclerosis in Youth and the Cardiovascular Risk Factors. In: Pediatric Prevention of Atherosclerotic Cardiovascular Disease. Eds. R.M. Lauer, T.L. Burns, S.R. Daniels. Oxford, 2006; P. 3-26.
FEASIBILITY OF ALLOCATION OF PERSONS WITH SIGNS PREHYPERTENSION IN PREVENTIVE MEDICAL INVESTIGATION OF STUDENT YOUTH
EVSEVYEVA M. E., MISTCHENKO E. A., ROSTOVTSEVA M. V., SERGEEVA O. V., GALKOVA I. Yu., SMIRNOVA T. A.
The study was performed to investigate the characteristics of circadian profile of blood pressure (BP) in young men, which demonstrate the office signs of high normal pressure (HNAD) and arterial hypertension (AH) for the setting of effective system of medical examination of the young population. Total number of recruits and students surveyed 147 younkers: with optimal and normal blood pressure - 81, high normal blood pressure - 30 and AH - 36. Ambulatory BP monitoring (ABPM) performed in the «typical working day» of 24±1,5 hours with intervals between the measurements of 15-30 minutes during the day and night respectively. Analyzed more than 30 indicators. Results: Young people with signs HNAD characterized by a number of significant negative differences in terms of ABPM compared with peers-carrier of normal and optimal blood pressure. However, the sechanges are similar to those inpatients with evidence of hypertension, but their expression is less important. Examples of such changes are the mean values of systolic and diastolic blood pressure, variability indexes BP, value and speed of its morning rise . Young men with HNAD are also characterized by the presence of family history of the development of early cardiovascular (CV) disease and the presence of cardio-cerebral complaints, frequency, similar to AH. Conclusion. The young people with HNAD must be timely included in the dispensary group of CV risks likely those ones with definite AG. It is necessary to perform among them effective prevention programmes in good time.
Key words: high-normal blood pressure, hypertension, boys, daily blood pressure profile
О ЦЕЛЕСООБРАЗНОСТИ ВЫДЕЛЕНИЯ ЛИЦ С ПРИЗНАКАМИ ПРЕДГИПЕРТЕНЗИИ В ПРОЦЕССЕ ДИСПАНСЕРИЗАЦИИ МОЛОДОГО КОНТИНГЕНТА
М. Е. ЕВСЕВЬЕВА, Е. А. МИЩЕНКО, М. В. РОСТОВЦЕВА, О. В. СЕРГЕЕВА, И. Ю. ГАЛЬКОВА, Т. А. СМИРНОВА
Изучены особенности суточного профиля АД у лиц молодого возраста с высоким нормальным (ВН) давлением и артериальной гипертензией (АГ) для обоснования необходимости формирования системы активного выявления молодых людей с признаками предгипертензии и их включения в число лиц, подлежащих дальнейшей диспансеризации. Обследовано 147 человек: с оптимальным и нормальным АД - 81, высоким нормальным АД - 30 и АГ - 36 человек. Суточное мониторирование АД (СМАД) выполнялось ам-булаторно в режиме «типичного рабочего дня» продолжительностью 24±1,5 часа с интервалами между измерениями 15-30 минут днем и ночью соответственно. Анализировали более 30 показателей. В основу статистического анализа положены непараметрические методы, данные представлены в виде медиан и 25, 75 перцентилей.
Молодые люди с признаками высокого нормального АД (ВНАД) характеризуются рядом достоверных негативных отличий в показателях СМАД по сравнению со сверстниками-носителями нормального и оптимального АД. Вместе с тем указанные изменения сходны с таковыми у лиц с признаками АГ но выраженность их менее значима. К подобным нарушениям относятся в первую очередь изменения средних значений САД и ДАД, а также индексов времени САД и ДАД, величины утреннего подъёма САД и ДАД. Юноши с наличием ВНАД характеризуются присутствием отягощённой наследственности по развитию ранних сердечно-сосудистых заболеваний и наличием кардио-церебральных жалоб, по частоте сходных с носителями АГ По результатам офисного измерения АД в процессе диспансеризации молодёжи в группы сердечно-сосудистого риска необходимо включать лиц не только с явной АГ, но также носителей ВНАД для осуществления среди них ранних и эффективных профилактических мероприятий.
Ключевые слова: артериальная гипертония, высокое нормальное артериальное давление, молодой возраст, мужская популяция, суточный профиль АД
