Ukrainian break-through in the European and World strategy of individual prophylaxis of an ischemic stroke in patients with arterial hypertension

Causes of ischemic stroke. Assessment of individual risk for cardiovascular disease in humans. The development in patients of hypertension and coronary heart disease. Treatment in a modern hospital disorders biomarkers of coagulation and fibrinolysis.


Ukrainian break-through in the European and World strategy of individual prophylaxis of an ischemic stroke in patients with arterial hypertension

Tolstopyatov S.M.

Today without new laboratory technology and new tactics of individual primary and secondary prevention of an ischemic stroke it is impossible decrease death rate of people.

On the conclusion of prof. Marrku Kaste (Stroke, 2010, 41: 2449) death rate from a stroke above, than from a tuberculosis, AIDS and a malaria taken together.

In the USA stroke is registered everyone 40 sec (795000 in a year). Under assumption R.J. Gibbons et al. (Circulation, 2008, 118) mortality from an ischemic stroke in USA will increased by 100 % with 2000 to 2032. The negative statistics, confirming existing catastrophe in prevention and treatment (V. Hachinsky - Stroke, 2008, 39: 2409 - stroke: a preventable and treatable catastrophe), specifies also in that fact, that public health services not in a condition to offer a way and the program for decrease in strokes and their risk (D.C. Goff et al., 2007).

At the analysis information about traditional risk factors it has been established, that they do not allow to explain a cause of the general burden of strokes in population (A.J. Grau et al. - Arch. Neurol., 2010,67 (1): 16-17) and, possibly, therefore in last recommendations they are not applied to identification and therapeutic influence at low and moderate risk (F. Zannad et al. - Eur. J. of Preventive Cardiology, 2012, 19 (5): 5-6).

For the decision of the social problem a number of authors inform, that a cause of an ischemic stroke is formation of a clot of blood which blocks a blood-vesels in a brain (J.S. Paikin et al. - Circulation, 2012, 125: e439-e442), and a clinical predictor of a thrombosis is dysfunction of coagulation and anticoagulation systems of blood towards a hypercoagulable state and fibrinolysis depression (B. Siagerine et al.,-Circulation, 2010; A.I. Shafer et al. - Hematology, 2003 v. 2; B.M. Ridker et al. - Circulation, 2004, 109; C.D. Bushnell et al.-Stroke, 2002, 33; K.A. Bauer et al.-Hematology, 2002, 1:363; B.M. Coul - Stroke, 2004), and a key therapeutic principle of prevention of a stroke should be inhibition of coagulation (J. Steffel et al. - Eur. Heart. J., 2009, 30: 2832-2834).

Meanwhile a number of authors it is established, that the recommended markers of coagulation system seldom reveal a haemostatic risk factor even at acute coronary syndrome and an ischemic stroke (Boss M.J. et al - Circulation 2006, 114: 1591; Bushnell C.D. et al. - Stroke, 2000, 31: 3067; Cocho D. et al.-Stroke 2006, 37: 996; Derhasching F.E. et al. - Clinical Chemistry, 2002, 48: 1924; Leira E.C. et al. - Cerebrovasc. Disease, 2004, 18 (2: 139); Walenya J.M. et al, - Seminar Thromb. Haemost., 2004, 50: 683). Therefore Guy De Baccer et al.(Eur.Journ. of Preventive Cardiology, 2012; 19 (52): 114-117) wrote that estimation of an individuals cardiovascular risk remains approximate and the addition of new risk factors has disappointingly small effects.

Most often the stroke develops in patients with hypertension and ischemic heart disease. ischemic stroke heart hypertension

The ischemic stroke most often develops at an arterial hypertension (H) and ischemic heart disease. At XVI European conference on a hypertension (2006, Madrid) under the initiative prof. Thomas Giles (USA) the decision to consider H as a complex cardiovascular pathology at which urgency and aggression of treatment should be in a context of individual overall risk, instead of simple decrease the blood pressure (BP) was accepted. According to the literature at H not only the BP raises, but also is frequent (61,9 %- my data) develop Birmingham paradox which is connected with infringement of biomarkers of the coagulation cascade and system of the fibrinolysis, clinically shown in the form of transitory ischemic attack or an ischemic stroke. The key thesis of conference became the requirement to treat in a clinical practice earlier and more aggressively.

In 7 years became obvious, that experts have not developed effective pathogenetic indicators for revealing clinical overall risk, and tactics of treatment still has been directed only on decrease the BP. New concept about H and effective approaches to an individual prevention of ischemic stroke have not found reflection even in materials 2013 ESH/ESC Guidelines. The dramatic nature of a situation is burdened with the information, that traditional risk factors (blood pressure, total serum cholesterol, and smoking status) in short-term risk (0-10 years) and in long-term risk (0-35 years) can not effectively be used to predict of a stroke (Kok Wai Glang et al.-Eur. Heart J., 2013, 34 (14): 1068).

Considering a pathogenesis of an ischemic stroke, we have developed the qualitative program for identification of a clinical risk factor and a degree of its expressiveness. In a basis of this development is a process of formation of a blood clot, clinical predictor which is interfaced to hypercoagulation state. We have developed new laboratory technology which registers a condition of 36 integrated biomarkers of coagulation cascade and fibrinolysis of whole blood. Owing to this method it has been established, that at H hypercoagulation develops only in 61,9%, at other cases takes place hypocoagulation (22,0%) or is kept normocoagulation state 17,0%). At the analysis of data were have allocated X degrees of infringement of the coagulation cascade and have generated groups of patients with a various degree of a clinical risk factor. As at IX and X degrees the sharp ischemic stroke is demonstrated, VI-VIII degrees have been estimated as an attribute of a high risk factor. Opportunity of revealing of a various degree of a risk factor was the basis for additions and specifications of recommendations of 2013 XVI European conference Guidelines in aspect to what patients is necessary urgency and aggressive therapy and what there is a technique of such treatment..

At the analysis of results it has been ascertained, that urgency therapy should be applied intravenously or intramuscularly at a high clinical risk factor. As ntiplatelet drugs have been chosen acelysin. After development of a technique of calculation of individual dozes (on weight of a body and a degree of a risk factor) the program has been successfully approved in a clinical practice. For the first time it has been revealed, that for qualitative prevention of a stroke it is necessary intramuscular therapy, which allows quickly (within 4-6 days) to lower high coagulation potential on 300-400 % (i.e. from VIII item to II item) and to improve a clinical condition of the patient without occurrence any hemorrhage complications.

Thus, for optimization of individual treatment of patients with H the doctor should be guided by new concept about this pathology, and urgency and aggression of treatment for prevention of an ischemic stroke it is necessary to apply at presence of a high clinical risk factor. Hence, absence of such approach in 2013 ESH/ESC Guidelines will be reflected in preservation of high parameters of death rate and physical inability of the population from a stroke, and purpose Polypill without adequate diagnostics of a clinical-laboratory risk factor and monitoring of biomarkers of the coagulation cascade contradicts representation about pathogenetic qualitative treatment also that such treatment is counter-indicative at a hypocoagulation and a normocoagulation state of whole blood.

Because current stroke prevention guidelines do not provide adequate methodology information to permit assessment of their quality, potential bias and clinical applicability (R.G. Hart et al.- Neurology, 2012, 59: 977-82), and inadequate access to cardiovascular prevention (G. Saposnik et al.- Stroke, 2011, 42: 3336-3337), for the decision of a catastrophic social problem we have been invented new laboratory technology CoaguloscopeTS (the patent of the Ukraine). This device registers and calculates with help of the special computer program 36 new integrated biomarkers of the coagulation cascade and fibrinolysis system in a whole blood. High information tests it has been confirmed in investigation of patients at cardiology institute, in neurology department of hospitals 3 and 9, in medical centers "Consilium" and "Avizenna" of city Kiev (Ukraine). In total 818 people, including 120 healthy individuals (control group) and 404 patients with a high blood pressure, including of ischemic heart disease at 178 cases, have been surveyed. As inhibition of coagulation is the key therapeutic principle for stroke prevention (J. Steffel et al., 2009) for clinical practice two integrated tests (the coagulation module - CM and the fibrinolysis module- FM) have been offered. These biomarkers allows the doctor to identify patients with a clinical cardiovascular risk factor, to determine risk degree, to calculate an individual dose of the antiplatelet agent and to use antiplatelet agents only in the presence of laboratory signs of a hypercoagulable state. Except that CM and FM have signs + and - reflecting change of activity of hemostasis system accordingly towards increase or decrease. As CM and FM reflect process thrombus formation and, hence, are qualitative indicators of a clinical (pathogenetic) risk factor of an ischemic stroke, character of infringement of a hemostasis has been conditionally divided into X degrees. We have suggested to consider CM + I-II of degrees, as a low risk factor of thrombus formation, CM+ III-V of degrees - moderate risk, CM + VI-VIII of degrees- high risk and CM + IX-X of degrees - very high risk factor which usually take place in patients who were hospitalised with acute ischemic stroke..

As the subjective approach to treatment has led to stroke progressing, we have been developed a new program for of a calculation of an individual dose by results of degree HCM+ and weight of the patients. For decreased high coagulation potential it is necessary to begin prevention of thrombus formation with individual intramuscular using of new antiplatelet agent named acelysin (acetylsalicylate lysine). This therapy is necessary for applying once a day within 4-6 days. We estimated efficiency of new treatment at 89 patients (75,8 % had high blood pressure or ischemic heart disease) with HCM+ from I to X degree. In fig.1the concrete example of realisation of new strategy for prevention of an ischemic stroke at the patient with a hypertension and ischemic heart disease is presented.

Figure 1 In hypertensive patient for prevention of stroke new technology Coaguloscope-TS (the patent of Ukraine) provides qualitative identification of a clinical (pathogenetic) risk factor of a vascular thrombosis and its degree (in 1 day CM+ = VII degrees, for 30 day CM + =VIII degrees), and the use emerging therapy associated with treatment for rapidity (for 4-6 day) decrease of coagulation potential on 300-400% (CM + = 2 degrees) after intramuscular therapy of an individual dose of the antiplatelet agent (an acelisin - once a day within 4-6 days), and including antihypertensive and lipid-lowering agents.

At the analysis of results it has been revealed, that after emergency treatment degree of a clinical risk factor has authentically decreased and level of CM + has changed from VII degree to 2,150,25 degree (P <0,0001), clot substances levels from 115,84,72 mmol-eq/L to 84,513,76 mmol-eq/L (P < 0,0001), clot substances density from 1775,1943,76 eq.units to 1525,9250,11 eq.units (P < 0,0001), and ratio between anticoagulation system level and procoagulant system level has increased from 81,572,34 mmol-eq/L/min to 102,033,75 mmol-eq/L/min (P < 0,0001). In patients with a high clinical risk factor (CM+ VI-VIII degree) the coagulation potential often decreased to level of a low risk factor (CM+ I-II degree). Thanks to high efficiency of treatment the clinical condition of patients improved, and signs of haemorrhage complications were absent.

Thus, the received results of investigation confirm, that the new program of diagnostics of an individual clinical (pathogenetic) risk factor developed by us, identification of various degrees of risk and new tactics of urgent treatment of a high risk factor have a more potential for the statement, that existing high rate of disability and death of the population from strokes and occurrence of bleeding episodes after antiplatelet therapy are connected with absence in recommendations of experts of the pathogenetic approach for primary and secondary prevention of this killer. Meanwhile in guidelines the 2012 Canadian Hypertension Education Program Recommendation for the Management of Hypertension (Canad. J. of Cardiol., 2012, 28: 270) are presented the evidence-based recommendation for the diagnosis, assessment, prevention, and treatment of hypertension without any laboratory tests for the investigation of coagulation and fibrinolysis state. On page 280 it is noticed, that strong consideration should be given to the addition of low-dose acetylsalicylic acid therapy and in high-risk patients, when combination therapy is being used, choices should be individualized. Unfortunately anybody from 64 authors have not presented the qualitative program of prevention of a stroke for health care practitioners.

We have represent recommendations which are based on results of investigation which have been published in journal of the Ukrainian Medical Association of North America, 1994, v. XLI, N 3 (94), p. 155-160; in materials of scientifically-practical conference Modern aspects of military medicine, 1995, . 287-289 (Kiev, Ukraine); in Ukrainian journal Medical News, 1996, N 9, p. 9-13; in Ukrainian journal Vrachebnoe Delo, 1997, N5, p. 56-59 (; 2006, N8, p. 21-34; 2007, N 7, p. 60-67; 2007, N8, p. 47-60; in materials of I-st National Congress the Person and a Medicine - Ukraine (on March, 26-28-th, 2008, Kiev, Ukraine), 2008, p. 60; in Ukrainian journal Vrachebnoe Delo, 2009, N 7-8, p. 32-40; 2010, N 5-6, p. 3-21.

For realization of individual primary and secondary stroke prevention program and reduce the impact of stroke on the lives of people and their families the first key component of this purpose is the urgent beginning of manufacture as stated above laboratory technology Coaguloscope (the patent of Ukraine).

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