Arterial Hypertension and Carotid Atherosclerosis: Features of Circadian and Cerebral Haemodynamics

The dissertation is devoted to studying the features of circadian and cerebral haemodynamics in patients with arterial hypertension combined with carotid atherosclerosis. The work considers the epidemiological significance of arterial hypertension as a leading risk factor for cardiovascular complications, including myocardial infarction and cerebral stroke, and analyses the contribution of atherosclerotic lesions of the main arteries of the head to cerebral circulatory disorders. Based on ambulatory blood pressure monitoring data and ultrasound examination of the carotid arteries, a comparative analysis of the circadian blood pressure profile, the state of cerebral haemodynamics, and the blood lipid spectrum was carried out depending on the degree and duration of hypertension and on the type of circadian profile. Using multivariate regression analysis, a clinical-haemodynamic model was developed and verification predictors of atherosclerotic lesion of the common carotid arteries were determined, which makes it possible to clarify the prognostic role of the circadian blood pressure profile in the pathogenesis of atherosclerosis.

It is known that arterial hypertension (AH) is one of the most widespread cardiovascular diseases in highly developed countries (Oganov R.G., 1997; Kryukov N.N., 2002; Kuznetsov G.P., 2007). The frequency of AH in the adult population exceeds 40% (Shalnova S.A., 2001; Kotovskaya Yu.V., 2004; Belenkov Yu.N., 2005). Its epidemiological significance increases because AH is one of the main risk factors for the development of cardiovascular diseases and mortality from them. In persons with elevated blood pressure (BP), starting from the age of 45, life expectancy is on average 10 years shorter than in people without AH, which is associated with the earlier development of atherosclerosis and, as a consequence, myocardial infarction and cerebral stroke (Lazebnik L.B., Komissarenko I.A., 2006). The share of AH in the structure of overall mortality reaches 50% (Blacher J. et al., 2000). The diseases closely associated with AH — coronary heart disease and cerebrovascular pathology — account for almost 80% of mortality from cardiovascular causes (Kotovskaya Yu.V., Kobalava Zh.D., 2004). In Russia, cerebrovascular diseases constitute almost 40% of all deaths from circulatory system diseases (Kharakoz O.S. et al., 2001). According to combined data of a 19-year prospective follow-up of 8,000 men aged 40–59 years, AH increases the risk of death from coronary heart disease by a factor of three, and from stroke (haemorrhagic and ischaemic) by a factor of six (Britov A.N. et al., 2002). Many authors note a strong direct correlation between the risk of stroke development and BP level (Kobalava Zh.D., Tolkacheva V.V., 2003). Systematic antihypertensive therapy reduces the frequency of strokes by 20–50% (Skvortsova V.I. et al., 2002). The risk of stroke development increases significantly when AH is combined with occlusive-stenotic lesions of the carotid arteries (Glynn R.G. et al., 1997; Lee A.J., 2000). In the pathogenesis of cerebral circulatory disorders, an important role is played by atherosclerotic lesions of the main arteries of the head (MAH), which occur in 30–50% of patients with AH and with which, in 40% of cases, the development of acute cerebrovascular accident (ACVA) is associated (Denisova G.A. et al., 2000; Vasan R.S. et al., 2001). At the same time, atherothrombotic strokes in 21% of cases are caused by thrombosis of extracranial or intracranial vessels, and in 13% — by artery-to-artery emboli, mainly from "unstable" atherosclerotic plaques of the internal carotid arteries (ICA) (Vereshchagin N.V. et al., 2004). Thus, with carotid artery (CA) stenosis of less than 50% of the diameter, the frequency of subsequent neurological complications amounts to 3.0–4.8% (Lipovetsky B.M., 2005). And if CA stenosis occupies more than 70% of the diameter and clinical manifestations are present, the frequency of ipsilateral stroke averages 10% per year (Van Bortel L.M. et al., 2001). With CA stenosis exceeding 75% of the diameter, the frequency of such complications rises to 15–46% (Lipovetsky B.M., 2005). In addition, stenoses and deformations of these arteries are one of the necessary components of haemodynamic stroke (Vereshchagin N.V. et al., 2004).

In the pathogenesis of target organ damage in AH, many mechanisms participate (both cellular and humoral), as well as dysfunction of the vascular system at its various levels. Over the last 10 years, a clearer understanding has emerged of the fact that AH is accompanied by a specific vascular lesion, and that this may represent an important pathophysiological problem and serve as a potential therapeutic target (Struijker-Boudier H.A. et al., 1992; Dudko V.A., 2003; Lipovetsky B.M., 2005).

Thus, hypertensive disease appears in a new light as a pathological process that remodels not only the heart but also the entire network of peripheral, cerebral, visceral, and coronary vessels (Verdecchia P. et al., 2001; Belousov Yu.B., 2004; Agafonov A.V., 2005). Arterial hypertension performs the function of a triggering mechanism with respect to a whole range of pathological changes in the circulatory system that determine human life expectancy: atherosclerosis, ischaemic and sclerotic changes in organs, and the development of cerebrovascular and cardiac insufficiency (Rodgers A. et al., 1996; Kumar C.A., Das U.N., 2000).

At present, a relationship has already been established between the parameters of ambulatory blood pressure monitoring (ABPM) and target organ changes in AH (Zelveyan P.A. et al., 2001; Kobalava Zh.D., Kotovskaya Yu.V., 2002; Gapon L.I. et al., 2003; Ripp T.M. et al., 2006). It is known that target organ damage and, consequently, the development of cerebrovascular and cardiac complications in AH are associated with the degree of BP elevation as well as with disturbances of the circadian rhythm and variability of BP (Geraskina L.A. et al., 2006). It remains unclear whether there is a single parameter characterizing the circadian BP profile that is equally associated with the formation and progression of carotid atherosclerosis. In addition, the question of whether changes in the structure of the arterial wall play a primary role in the disturbance of the circadian BP profile or are its consequence has not been answered. The currently available data on the influence of the disturbed circadian BP rhythm on the state of target organs are sometimes contradictory and require further investigation in this area.

The above provided the basis for conducting this study.

The aim of the dissertation is to assess the state of circadian and cerebral haemodynamics in patients with arterial hypertension and carotid atherosclerosis.

To achieve this aim, the following tasks were set and solved:

1. To investigate the circadian BP profile in patients with AH and carotid atherosclerosis.

2. To study the state of cerebral circulation in patients with different degrees of AH.

3. To perform a correlation analysis between the parameters of circadian and cerebral haemodynamics in patients with AH and carotid atherosclerosis.

4. To develop a clinical-haemodynamic model and to determine verification predictors of atherosclerotic lesion of the common carotid arteries in patients with arterial hypertension.

Scientific novelty of the study

The revealed changes in the circadian blood pressure profile have been analysed depending on the stage, degree, and duration of arterial hypertension and on atherosclerotic lesions of the main arteries of the brain.

New relationships have been established between the circadian blood pressure profile and the degree of atherosclerotic lesion of the carotid arteries.

For the first time, using multivariate regression analysis, a mathematical model has been developed that allows predicting the probability of atherosclerotic change of the vascular wall based on the clinical and haemodynamic characteristics of the patient.

The independent influence of the altered circadian BP profile on the formation of atherosclerotic lesion of the carotid artery wall has been proved, which makes it possible to assess from new positions the clinical significance and prognostic role of the circadian blood pressure profile in the pathogenesis of atherosclerosis.

Practical significance of the study

The data obtained as a result of the study supplement modern understanding of the role of arterial hypertension in the development of atherosclerosis.

For the practical use of the study results, it is possible to recommend the regression model for predicting the probability of atherosclerotic lesion of the CA based on the values of age, AH duration, nocturnal BP dipping, and blood triglycerides of the patient.

The widely used method of ambulatory BP monitoring, using the parameter of nocturnal blood pressure fall, allows cardiologists to perform risk stratification at early preclinical stages in patients with an elevated risk of cerebrovascular complications.

On the basis of the analysis of the data obtained on the state of cerebral haemodynamics in the presence of a disturbed circadian BP profile, practical recommendations have been developed for the rational management of patients with unfavourable changes in the circadian BP rhythm.

Main propositions defended:

1. In patients with AH, carotid atherosclerosis is the cause of an increase in the number of cases of insufficient nocturnal BP fall. The duration and degree of AH statistically significantly increase the intima-media thickness of the carotid arteries in patients with AH and carotid atherosclerosis.

2. In patients with a disturbed circadian BP profile, higher values of intima-media thickness of the carotid arteries are noted than in persons with an unchanged circadian BP profile, which reveals the independent role of the circadian BP rhythm in the pathogenesis of atherosclerosis.

3. Disturbance of the circadian BP profile in patients with arterial hypertension occurs at the first stage of AH and precedes the increase in intima-media thickness of the carotid arteries.

4. Vascular remodelling in AH and carotid atherosclerosis is reflected in statistically significant relationships between structural changes in the CA (intima-media thickness), clinical parameters (patient age, duration of the disease, degree of AH, cholesterol and triglyceride levels in the blood), and systemic haemodynamic parameters (degree of nocturnal fall of diastolic BP).

Approbation of the work. The materials of the dissertation were reported at the V Scientific Conference of Young Scientists "Postgraduate Readings — 2004" (Samara, 2004) and at the XII All-Russian Congress "Ecology and Human Health" (Samara, 2007).

The approbation of the dissertation was carried out at a joint meeting of the Department of Faculty Therapy and the Department of Internal Diseases of the State Educational Institution of Higher Professional Education SamSMU.

Publications. On the topic and materials of the dissertation, 11 printed works have been published (including 2 articles in journals reviewed by the Higher Attestation Commission of the Russian Federation), reflecting the main propositions of the dissertation.

Volume and structure of the dissertation. The dissertation is presented on 114 pages of typewritten text and consists of an introduction, a review of the literature, a chapter on material and methods, 3 chapters of results of original research, a chapter of discussion, a conclusion, conclusions, and practical recommendations. The text of the dissertation is illustrated with 20 tables and 14 figures. The bibliography includes 223 sources, of which 115 are domestic and 108 are foreign authors.