CC BY
19
х1ж journal of clinical medicine of Kazakhstan
Озын, Макала / Оригинальная Статья / Original Article
DOI: 10.23950/1812-2892-JCMK-00337
Platelet aggregation and von Willebrand factor in patients with artherial hypertension combined with osteoarthritis
Abstract
Objective: To investigate the platelet aggregation and level of von Willebrand factor in patients with hypertension and knee osteoarthritis.
Methods: The study involved 102 people: 29 patients with hypertension stage II combined with osteoarthritis stage II - main group; 29 patients with hypertension stage II - first group of comparison, 24 patients with osteoarthritis stage II - second group of comparison. The control group consisted of 20 almost healthy persons. Methods: ambulatory blood pressure monitoring, optical platelet aggregation test (inducers of platelet aggregation - adenosine diphosphate, collagen, thrombin, ristocetin (2 micromole)).
Results: Von Willebrand factor was higher in patients with hypertension combined with osteoarthritis and in patients with isolated hypertension (182.6 [171.6 - 201.7] %, 184.8 [171.6 - 207.7] % respectively), compared to patients with osteoarthritis (167 [144.6 - 181.6] %) and the control group (163.4 [151.7 - 172.3] %) (p<0.05). The degree of platelet aggregation with adenosine diphosphate in patients with hypertension combined with osteoarthritis and in patients with hypertension had significant correlations with level of total cholesterol and daily index of systolic blood pressure (p <0.05)).
Conclusion: Von Willebrand factor, degree platelet aggregation induced by adenosine diphosphate, collagen and thrombin were higher in patients with hypertension combined with osteoarthritis and in patients with hypertension compared to both the group of patients with osteoarthritis and control group (p <0.05). The degree of platelet aggregation with adenosine diphosphate was influenced by the level of total cholesterol and daily index of systolic blood pressure, the degree of platelet aggregation with collagen was influenced by daily index of systolic blood pressure and daily index of diastolic blood pressure (p<0.05).
Keywords: hypertension - osteoarthritis - platelet aggregation - von Willebrand factor - ambulatory blood pressure monitoring.
ОСТЕОАРТРОЗБЕН ЦОСАРЛАНГАН АРТЕРИАЛДЫ ГИПЕРТЕНЗИЯСЫ БАР НАУЦАСТАРДАГЫ ТРОМБОЦИТТЕР АГРЕГАЦИЯСЫ ЖЭНЕ ВИЛЛЕБРАНД ФАКТОРЫ Родионова В.В.1, Хмель Е.С.1
^емлекеттш мекеме «Украина Денсаульщ са^тау министрлтнщ Днепропетровск медицинальщ академиясы», Кэшби аурулар жэне клиникальщ иммунология кафедрасы, Днепр, Украина.
Т¥ЖЫРЫМДАМА
Максаты: TÍ3e буындарыныц остеоартрозыменен косарланган артериалды гипертензиясы бар наукастардагы тромб TY3my кызметш жэне тамыр эндотелшнщ жагдайын тромбоциттер агрегациясы децгей мен Виллебранд факторына байланысты багалау.
Зерттеудщ эдютерк 102 адам зерттелген:остеоратроздыц II дэрежеамен косарланган артериалды гипертензияныц II стадиясы, 2 дэрежеамен 29 наукас - негiзгi топ; артериалды гипертензияныц II стадиясымен 29 наукас - салыстыратын бiрiншi топ, остеоартроздыц II дэрежесiмен 24 наукас - салыстыратын ешшл топ. Бакылау тобы - жастары бойынша сэйкес келетЫ 20 сау адамдар. Артериалды кысымныц тэулiктiк мониторингi, тромбоциттер агрегациясыныц индукторларын колданумен оптикалык агрегатометрия - аденозиндифос-фат, коллаген, тромбин, ристомицин (2 мкмоль).
Viktoriya Rodionova1, Olena Khmel1
'Department of occupational diseases and clinical immunology, State establishment «Dnipropetrovsk medical academy of Health Ministry of Ukraine», Dnipro, Ukraine
© ®
This work is licensed under a Creative Commons Attribution 4.0 International License
Received: 16-02-2017 Accepted: 29-03-2017 uDC: 615.038;616-08-035
J Clin Med Kaz 2017; 1(43):34-41
Corresponding author: Olena Khmel. Department of Occupational Diseases and Clinical Immunology of the State Institution «Dnepropetrovsk Medical Academy of the Ministry of Health of Ukraine» Address: 49044 Ukraine, Dnipro, Str. Vladimir Vernadsky, 9. Tel.: +38 (056) 713-52-57. E-mail: [email protected]
Нэтижелерк Остеоартрозбен косарланган артериалды гипертензиясы бар наукастарда жэне артеиалды гипертензиясы бар наукастарда аденозинфосфатпен тромбоциттер агрегациясыныц дэрежес жалпы холестерин кврсеткшнщ жогарлауына жэне систолалык артериалды кысымныц TYHгi уакытта твмендеу (р<0,05) дэрежесiне байланысты. Остеоартрозбен косарланган артериалды гипертензиясы бар наукастарда жэне окшауланган артериалды гипертензиясы бар наукастарда Виллебарнд факторы (182,6 [171,6 - 201,7] %, 184,8 [171.6 - 207.7] % тшанше) остеоартрозы бар нуакастарга (167 [144.6 - 181.6] %) жэне бакылау тобына 163.4 [151.7 - 172.3]%) (р<0,05) караганда жогары.
Корытынды: Остеоартрозбен косарланган артериалды гипертензиясы бар наукастарда жэне косарланган патологиясы жок артериалды гипертензиясы бар наукастарда Виллебранд факторы, индукторлармен тромбоциттер агрегациясы децгешнщ кврсеткш осеора-трозбен наукастардыц жэне бакылау тобыныц кврсеткiштерiмен салыстырганда айтарлыктай жогары (р<0,05). Аденозиндифосфатпен тромбоциттердщ агрегациясыныц дэрежесiне жалпы холесеринннщ жогары децгей жэне систолалык артериалды кысымныц TYHгi уакытта томендеу децгеш, коллагенмен тромбоциттердщ агрегация дэржеанщ жогарлауына систолалык артериалды кысымныц TYHгi уакытта твмендеу децгей жэне диастолалык артериалды кысымныц TYHгi уакытта твмендеу децгеш эсер еткен.
Мацызды свздер: артериалды гипертензия - остеоартроз - артериялды кысымныц тэулктк мониторингi - тромбоцит тер агрегациясы - Виллебранд факторы.
агрегация тромбоцитов и фактор виллебранда у вольных артериальной гипертензией в сочетании с остеоартрозом
родионова В.В.1, Хмель Е.С. 1
Тосударственное учреждение «Днепропетровская медицинская академия МОЗ Украины», кафедра профессиональных болезней и клинической иммунологии, Днепр, Украина.
РЕЗЮМЕ
Цель исследования: оценить функцию тромбообразования и состояние сосудистого эндотелия у больных артериальной гипертензией в сочетании с остеоартрозом коленных суставов по уровню агрегации тромбоцитов и фактора Виллебранда.
Методы: Обследовано 102 человека: 29 больных артериальной гипертензией II стадии, 2 степени, в сочетании с остеоартрозом II ст. - основная группа; 29 пациентов с артериальной гипертензией II стадии - первая группа сравнения, 24 пациента с остеоартрозом II ст. - вторая группа сравнения. Группа контроля - 20 практически здорових лиц сопоставимых по возрасту. Проводилось суточное мониторирование артериального давления, оптическая агрегатометрия с применением индукторов агрегации тромбоцитов - аденозиндифосфат, коллаген, тромбин, ристомицин (2 мкмоль).
Результаты: Степень агрегации тромбоцитов с аденозиндифосфатом у больных артериальной гипертензией в сочетании с остеоартрозом и у больных артериальной гипертензией достоверно связана с повышением показателя общего холестерина и степенью ночного снижения систолического артериального давления (р<0,05)). Фактор Виллебранда был повышен у больных артериальной гипертензией в сочетании с остеоартрозом и у больных с изолированной артериальной гипертензией (182,6 [171,6 - 201,7] %, 184,8 [171.6 - 207.7] % соответственно), по сравнению с больными остеоартрозом (167 [144.6 - 181.6] %) и с группой контроля (163.4 [151.7 - 172.3]%) (р<0,05).
Выводы: У больных артериальной гипертензией в сочетании с остеоартрозом и у больных с больных с артериальной гипертензией без сочетанной патологии фактор Виллебранда, показатель степени агрегации тромбоцитов с индукторами были достоверно выше по сравнению с показателями как в группе больных остеоартрозом, так и в группе контроля (р<0,05). На повышение степени агрегации тромбоцитов с аденозиндифосфатом влиял повышенный уровень общего холестерина и степень ночного снижения систолического артериального давления, на повышение степени агрегации тромбоцитов с коллагеном влияли степень ночного снижения систолического артериального давления и степень ночного снижения диастолического артериального давления (р<0,05).
Ключевые слова: артериальная гипертензия - остеоартроз - суточное мониторирование артериального давления - агрегация тромбоцитов - фактор Виллебранда.
Introduction
Hypertension remains the most prevalent and preventable cause of cardiovascular and cerebrovascular disease. [1]. The presence of high blood pressure enlarges probability of myocardial infarction in 2 times, heart failure in 4 times, stroke in 3.7 times [2]. The World Health Organization (WHO) defines hypertension as "the leading global risk of increasing of death from cardiovascular disease in the world" [3, 4]. According to the WHO, 1.5 billion people, including 30-45% of European population, have high blood pressure (BP) for today [5].
Cardiovascular diseases are the reason of about 17 million death cases in a year at the global level, it is nearly one third of total number of deaths [3]. Complications of HT causes 9.4 million deaths worldwide each year [4]. Not less than 45% of the deaths caused by heart troubles and 51% of the cases of death caused by a stroke fall to the share of HT [6].
In Ukraine, every third adult suffers from HT [7]. Thus, in 2012 in Ukraine there were 12286.8 cases, while the prevalence of HT was 32780.9 per 100 thousand of population [8].
Ukraine ranks first in mortality due to complications of HT among the European countries [5]. Also, there causes concern the fact that mortality from cardiovascular diseases in working age people in Ukraine is 3-5 times higher than those in other European countries, with a tendency to increase of mortality [7].
It is necessary to mark that the frequency of HT origin increases with age, at the same time HT even more often is accompanied by associated diseases, first of all - joint pathology [9]. So, in Europe where exist a problem of aging of the population (25.6% are people >55 years), osteoarthritis (OA) is one of the most frequent forms ofjoints diseases, which accounts for 60-70% of all diseases of the joints [9, 10]. European researchers pay attention to the high incidence of HT in patients with diseases of the joints [11]. And it is noted that joint disease in combination with HT is the most common chronic condition in the elderly persons, because about 36% of patients with HT suffer from joint diseases and 50% of patients with diseases of the joints have concomitant cardiovascular disease [12].
About 20% of elderly population need to take analgetic drugs because of chronic pain, often non-steroidal anti-inflammatory drugs (NSAIDs) at high doses and without any control, which can cause the development of multiple side effects and, in particular, creates pathogenic conditions for progression and complication of HT because promotes reducing the synthesis of prostaglandin E2 and prostacyclin, which have vasodilatative effect, while the synthesis of thromboxane A2, which causes vasoconstriction, doesn't change [13].
Lots of clinical trials, such as ALLHAT, ACCOMPLISH, ASCOT-LLA, APOLLO, CHHIPS are aimed to find out the
most appropriate, safe and effective therapy for hypertension and prediction of the development of cardiovascular disorders, in which not the least role is played by thrombosis and endothelial dysfunction [5]. Hemodynamic changes that lead to the disturbance of hemostasis and thrombolysis occur in the early stages of HT. Inflammation and subsequent intake of NSAIDs in patients with OA also contribute to the imbalance between thromboxane synthesis in platelets, which have prothrombogenic action and "antithrombogenic" eicosanoids (prostacyclin), which ultimately leads to increased risk of thrombosis [14]. This problem necessitates studying the platelet aggregation and level of von Willebrand factor in patients with HT combined with OA [14].
Objectives: to investigate the platelet aggregation induced by adenosine diphosphate, collagen and thrombin, and level of von Willebrand factor in patients with HT combined with knee OA.
Materials and methods
Our prospective study included 102 people. They were divided in 3 groups: main group included 29 male patients with HT stage II, 2nd degree combined with knee OA stage II according to Kellgren-Lawrence, with dysfunction of joints (JDF) of the 1-2 degree, age 40-65 years (mean age - 54.33±1.82 years). The first comparison group consisted of 29 patients with HT stage II, degree 1-2, the second comparison group consisted of 24 patients with OA stage II according to Kellgren-Lawrence, with JDF 1-2 degree (mean age - 53.64±1.71 years and 55.81±1.67 years respectively). The average duration of the HT in patients with HT combined with OA was 10.08±0.72 years, in patients with isolated HT - was 10.17±0.61 years. The duration of OA - in patients with HT combined with OA was 7.64±0.83 years, in patients with isolated OA was 8.31±0.91 years. Control group included 20 almost healthy individuals. This study was a part of the PhD research, which was approved by the ethics committee of SE "Dnipropetrovsk medical academy of Health Ministry of Ukraine" protocol № 1 from 18.01.2015.
All patients of all groups were comparable with the main group in age, sex, duration of diseases. Diagnosis of "Arterial hypertension" was put according to the recommendations of the Ukrainian Association of Cardiology (2012), the Order of the Ministry of Health of Ukraine № 384 from 24.05.2012 [15, 16]. Diagnosis "Osteoarthritis" was put according to clinical and radiological criteria of the American College of Rheumatology, EULAR recommendations from 2009 and formulated as required by the Ministry of Health of Ukraine according to the Order № 676 "On approving the protocols of care in specialty «Rheumatology»" from 12.10.2006 [17, 18, 19].
Criteria for inclusion in research: presence of verified diagnosis of HT of the II stage, 2nd degree, combined with verified diagnosis of knee OA of the II stage with JDF 1-2 degree; age of patients is 40-65 years; receiving the voluntary informed consent to participation in research.
Exclusion criteria: age less than 40 years and more than 65 years; established and verified diagnosis of ischemic heart disease; HT of the III stage and/or 3rd degree; chronic heart failure of the III-IV functional class; cardiac arrhythmia that causes a violation of hemodynamics and requires correction with the use of antiarrhythmic drugs; diabetes mellitus; hyperand hypothyroidisms; chronic renal insufficiency (glomerular filtration rate (GFR) <60 ml / min / 1,73 m2); obesity of the III-IV degree; tuberculosis, cancer, any chronic disease exacerbation.
Body mass index, waist size was defined in all patients, also there were held general clinical studies (complete blood count, urinalysis, blood chemistry, including total cholesterol, uric acid, C-reactive protein).
To confirm the presence and nature of HT, patients had 24-hour ambulatory blood pressure monitoring with "AVR-01" («Solveig», Ukraine). Measurements were carried out every 15 minutes during daytime activity and every 30 minutes during the night.
We analyzed the average values of systolic and diastolic blood pressure (SBP and DBP). Data were assessed daily and in day and night time. Previous calculations of average values for blood pressure in night time sleep and daytime hours were used in order to reveal the adequacy of daily (circadian) rhythm of blood pressure, which was estimated according to the degree of reduction of SBP and DBP at night.
According to the degree of nocturnal BP reduction there were distinguished the following groups of patients and types of daily blood pressure curves: patients with normal blood pressure reduction at night (degree of reduction = 10-20%) - type «dippers», patients with insufficient nocturnal reduction of blood pressure (degree of reduction <10%) - «non-dippers», patients with nocturnal increase of blood pressure (degree of reduction has a negative value) - «night-peakers», patients with excessive nocturnal reduction of blood pressure (degree of reduction > 20%) - «over-dippers».
In order to assess the platelet aggregation properties there was held optical platelet aggregation test with determination of degree, time and velocity of platelet aggregation. There were used adenosine diphosphate (ADP), collagen, thrombin (2 micromole) as inducers of platelet aggregation. Also, level of von Willebrand factor was determined using platelet aggregation with ristocetin (2 mM) (platelet aggregation analyzer AR 2110, SEC "Solar").
For confirming the diagnosis of OA there were used data of anamnesis, physical examination and x-ray examination of joints.
Statistical analysis of the research results was performed using the software package STATISTICA (6.1). There were analyzed a type of quantitative data distribution using W-test of Shapiro-Wilk. Average values were determined with averages (M) and standard error (± m) for normal type of distribution and median (Me) with upper and lower quartiles ([25% - 75%]) for abnormal type of distribution. Authenticity of differences between the determined data was carried out with t-criterion of Student for normal type of distribution and U-Mann-Whitney criterion for abnormal type of distribution and number of patients less than 30 in each group. Dependence between variables was estimated using Spearman correlation coefficient (R). The results were considered as statistically significant at p <0.05.
Results
Patients with HT mostly complained about periodical headache - 58 (100%), dizziness, flickering flies in front of the
eyes - 8 (13.8%), periodical blood pressure increase - 36 (62 %).
Patients with OA most often complained about joint pains - 53 (100%), impaired walking - 34 (64.2%), limitation of movement in knee joints - 36 (68%). On examination, there were also determined: pain in the joint projection - in 33 patients (62.2%), limiting flexion - in 29 (54.7%), crunching and crackling during movement - in 21 (39.6%). X-ray examination determined exacerbation and prolongation of intercondylar
tuberosity in 40 patients (75.5%), sclerosis of the articular surfaces -in 25 patients (47.2%), joint space narrowing - in 18 patients (34%), osteophytes - in 7 patients (13.2%).
The average body mass index in patients with HT in combination with OA was 31.2 [26.18 - 35.1] kg/m2, in patients with HT was 26.6 [23.2 - 31.2] kg/m2, in patients with OA was 29.88 [27.4 - 35] kg/m2. Waist size in main group was 94 [85 -104] cm, in patients with HT - 87 [80 - 99] cm, in patients with OA - 92 [86 - 100] cm.
Average daily pressure level in patients with HT in combination with OA was 144.3 [131.4 - 154.8] / 98.5 [91.7 -106.5] mm Hg, in patients with HT - 142 [138.4 - 148.8] / 94.8 [85.0 - 102.8] mm Hg, in patients with OA was 121.6 [106.4 -138.2] / 74 [65.2 - 83.3] mm Hg.
While analyzing the circadian rhythm of blood pressure in patients with HT combined with OA there was found that in 4 (13.8 %) patients a sufficient level of nocturnal reduction of blood pressure (normal type of BP daily curve - dippers) was determined, in 16 (55.2 %) patients was identified insufficient degree of blood pressure reduction (non-dippers), in 6 (20.7 %) was revealed an excessive blood pressure reduction at night
The tendency to increase of C-RP in OA patients in remission may indicate the presence of indolent inflammation that requires continuing treatment with NSAIDs and may increase the risk of further defeats of cardiovascular system in
(over-dippers), and in 3 (10.3 %) patients - increased blood pressure at night (night-peakers). SBP daily index was 8 [6 -17], DBP daily index was 6 [0 - 18].
While analyzing the circadian rhythm of blood pressure in patients with isolated HT there was found that in 7 (24.1 %) patients was determined a sufficient level of nocturnal reduction of blood pressure (normal type of daily curve - dippers), in 14 (48.3 %) patients was identified insufficient degree of BP reduction (non-dippers), in 6 (20.7 %) was revealed an excessive blood pressure reduction at night (over-dippers). SBP daily index was 11 [5 - 19], DBP daily index was 11 [6 - 19].
While analyzing the circadian rhythm of blood pressure in patients with OA there was found that in 16 (66.7 %) patients was determined a sufficient level of nocturnal blood pressure reduction (normal type of BP daily curve - dippers), in 7 (29.2 %) patients was identified insufficient degree of blood pressure reduction (non-dippers). SBP daily index was 15 [6 - 21], DBP daily index was 14 [5 -20].
When analyzing biochemical parameters, attention was paid to the indicators of total cholesterol, uric acid and C-RP (Table 1).
patients of this group.
When comparing the platelet aggregation induced by ADP, collagen and thrombin there were obtained the following data: (Table 2)
Table 1
Average values of platelet adhesion and aggregation induced by ADF, collagen and thrombin (Med [25% - 75%])
Indicator Main group (Hypertension in combination with Osteoarthritis), n=29 1st group of comparison (Hypertension), n=29 2nd group of comparison (Osteoarthritis), n=24 Control group, n=20 p
Degree of aggregation with adenosine diphosphate,% 66.9 [57.9 - 79.4]» 63.5 [53.2 - 70.3] » 44.5 [39.7 - 52.9] 41.2 [35.0 - 48.0] p1-2 = 0.19 p1-3 = 0.001 p2-3 = 0.002
Response time of aggregation, sec 386 [330 - 446] 426 [354 - 518] 451[346 - 544] 462 [244 - 498] p1-2 = 0.12 p1-3= 0.07 p2-3 = 0.86
Velocity of aggregation in 30 seconds 52.4 [42.4 - 66.4]» 54.9 [44.6 - 66.7]» 37.1 [25.1 - 43.8] 33.1 [25.9 - 42.1] p1-2 = 0.84 p1-3 = 0.004 p2-3= 0.018
Degree of aggregation with collagen,% 63.4 [54.8 - 73.1]» 61.8 [55.7 - 70.8]» 44.9 [33.0 - 45.7] 42.7 [33.0 - 45.7] p1-2 = 0,98 p1-3 = 0.007 p2-3=0,002
Response time of aggregation, sec 384 [324 - 446] 415 [349 - 498] 385 [313 - 484] 347 [283 - 431] p1-2 = 0,27 p1-3 = 0,76 p2-3= 0,19
Velocity of aggregation in 30 seconds 39.4 [29.4 - 49.0] 41.6 [40.8 - 55.7] 44.0 [33 - 58.0] 35.5 [28.3 - 41.6] p1-2 = 0.68 p1-3 = 0.37 p2-3=0.33
Degree of aggregation with thrombin, % 70,9 [59.8 - 86.7]» 70,3 [50.6 - 92.4]» 58.8 [44.5 - 76.4]» 38.3 [35.6 - 45.3] p1-2 = 0,9 p1-3 = 0,019 p2-3= 0,049
Response time of aggregation, sec 448 [340 - 551] 458 [355 - 551] 521 [282 - 579]» 436 [322 - 519] p1-2 = 0.85 p1-3 = 0.36 p2-3= 0.36
Velocity of aggregation in 30 seconds 49.8 [42.6 - 56.8]» 51 [36 - 68.8]» 42.4 [29.2 - 47.2] 36.5 [21.8 - 43.8] p1-2 = 0.58 p1-3 = 0.028 p2-3=0.022
Von Willebrand Factor, % 182.6 [171.6 - 201.7]» 184.8 [171.6 - 207.7]» 167 [144.6 - 181.6] 163.4 [151.7 - 172.3] p1-2 = 0,72 p1-3 = 0,01 p2-3= 0,004
Note: * - reliability of distinctions between results in comparison with group of control < 0.05
Table 1
Average values of total cholesterol, uric acid and C-RP (Med [25% - 75%])
Indicator Main group (Hypertension in combination with Osteoarthritis), n=29 1st group of comparison (Hypertension), n=29 2nd group of comparison (Osteoarthritis), n=24 Control group, n=20
Total cholesterol, mmol/l 5,54 [4,46 - 6,14] 5,44 [4,54 - 6,28] 5,17 [4,47 - 6,02] 4,44 [4,14 - 4,83]
Uric acid, |ikmol/l 368 [319 - 434] 344 [261 - 351] 344 [301 - 368] 336 [282 - 379]
C-reactive protein, g/l less than 6,0 less than 6,0 less than 12,0 less than 6,0
Von Willebrand factor, as an indirect indicator of vascular endothelium damage, was significantly higher in patients with HT combined with OA and increased in patients with isolated HT (182.6 [171.6 - 201.7] %, 184.8 [171.6 - 207.7] % respectively) in comparison with OA patients (167 [144.6 - 181.6] %) and the control group (163.4 [151.7 - 172.3] %), which may indicate more expressed endothelial damage with further development of its dysfunction (p<0.05).
At the same time, patients with HT combined with OA and patients with isolated HT had significantly higher degree of platelet aggregation with ADP (66.9 [57.9 - 79.4] %, 63.5 [53.2 - 70.3] % respectively) in comparison with OA patients (44.5 [39.7 - 52.9] %) and the control group (41.2 [35.0 - 48.0] %) (p<0.05). Also these patients had increased velocity of platelet aggregation with ADP for 30 sec (patients with HT combined with OA - 52.4 [42.4 - 66.4], patients with isolated HT - 54.9 [44.6 - 66.7]) in comparison with OA patients (37.1 [25.1 - 43.8] %) and the control group (33.1 [25.9 - 42.1] %) (p<0.05). So, it is possible to consider that increased initiation of irreversible aggregation of circulating platelets takes place.
Also, patients with HT combined with OA and patients with isolated HT had significantly higher degree of aggregation with collagen (63.4 [54.8 - 73.1] %, 61.8 [55.7 - 70.8] % respectively) comparing to patients with OA and control group (44.9 [33.0 - 45.7] %, 42.7 [33.0 - 45.7] % respectively), what indicates an increased adhesion of platelets to collagen of the
injured vascular endothelium (p<0.05).
Also, a significant increase in degree of thrombin aggregation in all groups of patients was observed (HT combined with OA - 70.9 [59.8 - 86.7%, HT - 70.3 [50.6 - 92.4] %, OA
- 58.8 [44.5 - 76.4] % in comparison with the group of control
- 38.3 [35.6 - 45.3]. But patients with HT combined with OA and patients with isolated HT also had a significantly increased velocity of aggregation with thrombin in 30 seconds (49.8 [42.6
- 56.8] %, 51 [36 - 68.8] % respectively) comparing to patients with OA and control group (42.4 [29.2 - 47.2] %, 36.5 [21.8
- 43.8] % respectively). These data indicate the stimulation of endothelin-1 synthesis with subsequent disturbance of procoagulants and anticoagulants ratio and can promote further endothelial dysfunction in vessels (p<0.05).
When determining the correlative relationships according to Spearman there was revealed that degree of platelet aggregation with ADP in patients with HT combined with OA and in patients with HT had reliable connections with level of total cholesterol (r = 0.44; p <0.05) and SBP daily index (r = -0.53; p<0.05).
At the same time, there was found a significant correlation between the degree of platelet aggregation with collagen and SBP daily index (r = -0.58; p<0.05) and DBP daily index (r = -0.56; p <0.05). Also, in patients with isolated HT was found correlative relationship between values of von Willebrand factor and level of total cholesterol (r = 0.49; p<0.05) (Figure 1).
Scatterplot of Von Willebrand factor % against Tatat cholesterol mmol/1 Spreadsheet 10v*32c Von Willebrand factor, %= 163,9026t6 9286'*. 0,95 Conf.lnt
260 ......................
o
240 -
j? °
t- 220 -
0
Jo
1 200 - °
-Q .........
...... .......;...........
J 180 - ______-— ......~
> __—--- c
O ■>**■'
0
160 -"" °°
140 -1-1-1-1-
3,0 3,5 4,0 4,5 5.0 6,5 6.0 6,5 7.0 7,5
Total cholesterol mmol/l
Figure 1- Correlation between the degree of von Willebrand factor and level of total cholesterol in hypertensive patients.
Discussion
In our study we revealed, that patients with HT combined with OA and patients with isolated HT mostly had insufficient degree of blood pressure reduction (non-dippers), but patients with HT combined with OA have more decreased SBP daily index and DBP daily index. In 29.1 % of patients with OA, despite the fact of absence of complains which are characteristic for HT, was identified insufficient degree of blood pressure reduction (non-dippers) and in 4.1 % was identified an excessive blood pressure reduction at night (over-dippers), which indicates the further possible occurrence of cardiovascular disease in these patients.
The tendency to increase of C-RP in OA patients in remission may indicate the presence of indolent inflammation
that requires continuing treatment with NSAIDs and may increase the risk of further injury of cardiovascular system in patients of this group.
Von Willebrand factor, as an indirect indicator of vascular endothelium damage, was significantly higher in patients with HT combined with OA and increased in patients with isolated HT compared to patients with OA, which may indicate more expressed endothelial damage with further development of its dysfunction. At the same time, patients with HT combined with OA and patients with isolated HT had significantly higher degree and velocity of platelet aggregation with ADP. So, it is possible to consider that increased initiation of irreversible platelet aggregation takes place. Also, patients with HT combined with OA and patients with isolated HT had significantly higher degree of aggregation with collagen, what indicates an increased adhesion of platelets to collagen of the injured vascular endothelium. Also, a significant increase in degree of thrombin aggregation was observed in all groups of patients, but patients with HT combined with OA and patients with isolated HT also had a significantly increased velocity of aggregation with thrombin in 30 seconds. These data indicate the stimulation of endothelin-1 synthesis with subsequent disturbance of procoagulants and anticoagulants ratio and can promote further endothelial dysfunction in vessels.
When determining the correlative relationships according to Spearman there was revealed that degree of platelet aggregation with ADP in patients with HT combined with OA and in patients with HT had reliable connections with the level of total cholesterol. At the same time, there was found a significant correlation between the degree of platelet aggregation with collagen and SBP daily index. Also, there was found correlative relationship between values of von Willebrand factor and level of total cholesterol.
In modern references there is discussed a question of the cardiovascular complications increased risk, which appears
when platelet dysfunction exists, so the study of platelet aggregation degree inducted by ADP, collagen, thrombin, and von Willebrand factor in patients with HT is quite relevant [16, 20, 21]. Authors Medvedev I.N.,Skoryatina I.A. (2013) indicates that one of the most common causes of death in the developed countries are cardiovascular diseases, which are often caused by thrombotic events in the vessels of vital organs [20].
HT is one of the most widespread among all cardiovascular diseases, and it is often combined with dyslipidemia. This combinationvery actively violates platelet function with the subsequent development of thrombosis, and it is confirmed in article of Medvedev I.N. in coauthorship with Gromnatsky N. I. and Skoryatina I. A. [21, 22].
BMI and waist size were increased in all groups of patients. Despite the lack of a reliable difference between groups, these indicators were high exactly in group with the combined pathology of HT and OA. According to the data which were received by Belovol A.N. (2007), Hromylev A.V. (2015), obesity has a significant negative impact not only on endothelial function causing induction of expression of TNF-alpha, IL-8 and cell adhesion molecules, but also affects platelet function by decreasing the production of adiponectin thereby contributing to increasing the risk of cardiovascular complications development [23, 24].
At the same time Shanchenko S.A., Lipatova T.E. pay attention to the fact that when BMI is above normal characteristic, there appears a decrease in the elasticity of the vascular wall, more expressed in patients with elevated blood pressure [25]. Depression of endothelium function in arteries of small muscular type is characteristic feature of patients with obesity [26]. An important indicator of growing thrombotic danger in patients with HT is activation of platelet adhesion and aggregation [26]. At the same time, these authors point out that the mechanism of platelet hemostasis disorders in hypertensive patients is not enough studied and that it is especially important to develop tactics of its correction [25].
In patients with OA the above stated indicators significantly didn't differ from indicators in persons of control group, most likely due to the fact that a week before starting of the study in patients were canceled NSAIDs, which negative effect was determined by a decrease in synthesis of prostaglandin (PG) E2 and prostacyclin, that have antithrombotic and vasodilatative effect according to observations of Eliseev MS, Barskova VG. [14].
Also, the likely explanation is that studied patients were diagnosed with isolated osteoarthritis of the knee, not polyosteoarthritis, which, according to Alekseenko E.Y., Zwinger S.M. increasingly provides effects on platelet function
[27].
At the same time despite normal levels of von Willebrand factor and degree of platelet aggregation inducted by ADP and collagen, in patients with OA was revealed a significant prolongation of platelet aggregation time with ADP, which indicates increased propensity for initiating of irreversible aggregation of circulating platelets. There is also noted the increase in degree of platelet aggregation induced by thrombin, which is consistent with the literature. So, Kurkina I.A. points at the fact that when there is an activation of thrombogenesis, thrombin forms a blood clot, even with low level of procoagulants
[28]. According to Drobysheva V.A., Egorova E.A., Logacheva G.S., Filatov O.M. increase in thrombin levels is associated with increased membranous activation of platelets and intracellular
synthesis of endogenic proagregants that leads to the stimulation of the endothelin-1 synthesis with the subsequent disturbance of procoagulant and anticoagulant ratio and promotes further endothelial dysfunction [29].
The revealed dependence of platelet aggregation from indicators of ambulatory blood pressure monitoring is confirmed with data obtained by Kislyak O. A., Postnikova S. L., Kopelev A. A., and also Delyagina V M. and coauthors though they point only to an indirect role of the increased platelet aggregation in development of cardiovascular accidents. The data, obtained by authors, confirms the need of further studying in problem of platelet function change [26, 30].
The limitations of study were: age (40-65 years), stage and degree of HT and OA (stage, 2nd degree, combined with verified diagnosis of knee OA of the II stage with JDF 1-2 degree), patients shouldn't receive NSAID's and antihypertensive drugs during 10 days before studying, they shouldn't have established and verified diagnosis of ischemic heart disease; HT of the third stage and/or 3rd degree; chronic heart failure of the III-IV functional class; cardiac arrhythmia that causes a violation of hemodynamics and requires correction with the use of antiarrhythmic drugs; diabetes mellitus; hyper- and hypothyroidism; chronic renal insufficiency (glomerular filtration rate (GFR) <60 ml / min / 1,73 m2); obesity of the III-IV degree, tuberculosis, cancer, any chronic disease exacerbation, pregnancy, lactation, receiving the voluntary informed consent to participation in research.
Conclusions
Excessive body mass was revealed in all groups of the examined patients, which is one of the basic risk factors in the development of endothelial dysfunction and diseases of the cardiovascular system, which, if there is a presence of comorbidities (including OA), may lead to increased platelet aggregation and development of cardiovascular accidents. The analysis of blood pressure circadian rhythm showed that despite the lack of significant differences, circadian rhythm indexes -SBP and DBP were closer to normal in the group of patients with isolated HT in comparison with group of patients with HT combined with OA; in 26,7% of patients with OA was identified insufficient degree of blood pressure lowering (non-dippers). In patients with HT combined with OA and in patients with isolated HT degree of platelet aggregation induced by ADP and collagen were significantly higher in comparison with group of patients with OA and the control group, what confirms an increased initiation of irreversible aggregation of circulating platelets and an increased adhesion of platelets to the injured collagen of vascular endothelium in these patients. In patients with HT combined with OA and in patients with isolated HT was significantly increased von Willebrand factor, which testifies to the affection of endothelium with following dysfunction (p<0.05). The degree of platelet aggregation with thrombin was increased in all three study groups, indicating the probable stimulate of endothelin-1 synthesis with subsequent disturbance of procoagulant and anticoagulant ratio and contributes to endothelial dysfunction (p<0.05).
References
1. Neal B. Blood Pressure Lowering Treatment Trials' Collaboration: Effects of ACE inhibitors, calcium antagonists, and other blood pressure-lowering drugs: result of prospectively designed over views of randomized trails. Lancet. 2000;355:1955-64.
2. Pharmacotherapy of arterial hypertension in accordance with the guidance of the joint national committee for the prevention, recognition and treatment of hypertension in 2014 (review of literature). Y. V Verkhovodova, I.V. Kireev, M.G. Bakumenko, etc. Drugs - for people. Modern problems of pharmacotherapy and prescribing of drugs. Materials of the XXX All-Ukrainian scientific and practical conference, Kharkiv, 2014. H.: NFaU. 2014; 163-171.
3. Guideline for hypertension ed. by VM. Kovalenko, E.P. Svischenko, Y.M. Sirenko. Kyiv . MORION, 2010; 491 p.
4. Svintsitsky I.A. Modern aspects of management in patients with hypertension. Practicing doctor. 2013; 3:63-69.
5. Mancia G, Fagard R, Narkiewicz K, Redon J, Zanchetti A, Böhm M, Christiaens T, Cifkova R, De Backer G, Dominiczak A, Galderisi M. 2013 ESH/ESC guidelines for the management of arterial hypertension: The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Blood pressure. 2013; 1;22(4):193-278.
6. A global brief on Hypertension. Silent killer, global public health crisis[Electronic resource] // WHO. - 2013. - access mode to the resource: http://apps.who.int/iris/bitstream/10665/7905/1/WH0_DC0_WHD_2013.2_eng.pdf.
7. Blikhar VE. Treatment of patients with arterial hypertension and concomitant pathology. Medicine and education in Siberia. 2014; 1: 41-48.
8. Vizir M.O. Home blood pressure monitoring in clinical practice. M.A. Vizir, O.A. Kochubyey. The role and place of medicine in ensuring of human health in modern society: a collection of abstracts of scientific papers participants of the international scientific conference, Lviv, 31 January - 1 February 2014 - Lviv medical community. - 2014. - P. 16-17.
9. Rebrov A.P., Magdeeva I.A., Romanova VV Features of endothelial dysfunction in arterial hypertension in combination with gout or osteoarthritis. Bulletin of modern clinical medicine. 2011: 1(4):6-8.
10. Differentiated approach in the treatment of Gonarthrosis with anti-inflammatory drugs, depending on the mineral density of bone tissue. N.M. Shuba, T.M. Tarasenko. Ukrainian rheumatological journal. 2015; 1: 42 - 49.
11. Flurbiprofen in the treatment of osteoarthritis T.S. Silantieva, G.P. Ivanova, T.M. Kostyuchenko et all. Ukrainian rheumatological journal. 2013; 1: 26 - 32.
12. Rodionov A.V Non-steroidal anti-inflammatory drugs and arterial hypertension: the urgency of the problem and the tactics of patient management. Therapist. 2013; 2: 25-31.
13. Use of non-steroidal anti-inflammatory drugs in elderly people. VB. Shatilo, L.A. Stadnyuk, E.A. Asanov, VY. Prikhodko. Distance learning. 2010; 2:14-19.
14. Eliseev MS, Barskova VG, Eliseyev MS. MELOXICAM: WHAT DO WE KNOW ABOUT CARDIOVASCULAR SAFETY?. Modern Rheumatology Journal. 2010; 14(1):79-83.
15. Recommendations of Ukrainian Association of Cardiology on prevention and treatment of hypertension. Guide to the National Programme for prevention and treatment of hypertension. Kyiv. 2011.
16. Arterial hypertension. Updated and adapted clinical guidelines based on evidence. Annex to the Order of the MOH Ukraine On approval and introduction of medical and technological documents for standardization of medical care in hypertension from May, 24, 2012 №384. Retrieved from www.moz.gov.ua/ua/portal/dn_20120524_384.html.
17. Altman R, Asch E, Bloch D, Bole G, Borenstein D, Brandt K, Christy W, Cooke TD, Greenwald R, Hochberg M, Howell D. Development of criteria for the classification and reporting of osteoarthritis: classification of osteoarthritis of the knee. Arthritis & Rheumatology. 1986; 1;29(8):1039-49.
18. Zhang W, Doherty M, Peat G, Bierma-Zeinstra SM, Arden NK, Bresnihan B, Herrero-Beaumont G, Kirschner S, Leeb BF, Lohmander LS, Mazieres B. EULAR evidence based recommendations for the diagnosis of knee osteoarthritis. Annals of the rheumatic diseases. 2009; 17:8-18.
19. Annex to the Order of the MOH Ukraine On approval and introduction of medical and technological documents for standardization of medical care in rheumatology from October, 12, 2006 № 676. [in Ukrainian]. Retrieved from http://www.moz.gov.ua/ua/ portal/dn_20061012_676.html
20. Medvedev I.N. Rosuvastatin in reducing the risk of thrombotic danger in patients with arterial hypertension and dyslipidemia. Medical almanac. 2013; 4:105-108.
21. McManus DD, Freedman JE. MicroRNAs in platelet function and cardiovascular disease. Nature Reviews Cardiology. 2015; 1;12(12):711-7. http://www.nature.com/nrcardio/journal/v12/n12/full/nrcardio.2015.101.html
22. Medvedev I.N. Dynamics of platelet hemostasis activity in patients with arterial hypertension and dyslipidemia as a result of atorvastatin intake. Fundamental research. 2013; 9:84-88.
23. Khromylev A.V Pathogenetic aspects of atherothrombotic risk in obesity and thrombophilia. Obstetrics, gynecology and reproduction. 2015; 3:45-52.
24. 24. Belovol AN Tactics of management of patients with arterial hypertension: a view through the prism of cardiometabolic risk. Ukrainian Journal of Cardiology. 2007; 6:8-12.
25. Shanchenko S.A., Lipatova T.E. BMI and blood pressure level as factors influencing the elasticity of the vascular wall and endothelium-dependent dilatation in pregnant women [Electronic resource]. Cardiology. 2016. Mode access to the resource: http://medconfer.com/node/6481.
26. Delyagin VM., Novikova T.A., Olimpieva S.P. Evidence-based analysis of the results of daily monitoring of blood pressure in children and adolescents. Systemic hypertension. 2011: 2: 60-66.
27. Alexenko E.Y., Govorin A.V., Zwinger S.M. Nitroxide-producing endothelial function and platelet aggregation in patients with primary osteoarthritis. Bulletin of the East Siberian Scientific Center of the Siberian Branch of the Russian Academy of Medical Sciences. 2011; 1; 21-24.
28. Kurkina I.A. Hypercoagulation and thrombosis in patients with cirrhosis. Gastroenterology. 2015; 3:20-25.
29. Drobyshev VA., Egorova E.A., Logachova G.S., Filatov O.M. Low-energy electromagnetic fields and radiation in correction of vascular and haemostasiological changes in patients with arterial hypertension with cervical dorsopathies [Electronic resource]. Medicine and Education in Siberia. 2015. - Mode access to the resource: http://ngmu.ru/cozo/mos/article/text_full.php?id=1757.
30. Kislyak O.A. Combined therapy: the key to successful control of hypertension for a practical physician. Consilium medicum. 2011; 13:90-93.
How to cite this article: Rodionova V, Khmel O. Platelet aggregation and von Willebrand factor in patients with artherial hypertension combined with osteoarthritis. J Clin Med Kaz 2017;1(43):34-41
