Characteristics of Left Ventricular Remodeling and the Effectiveness of Antihypertensive Therapy in Men and Women with Arterial Hypertension

The dissertation is devoted to the study of sex-related features of left ventricular remodeling in patients with arterial hypertension. It examines the prevalence of myocardial hypertrophy, patterns of cardiac geometry, the state of diastolic function, and neurohumoral mechanisms in men and women, including postmenopausal women. Particular attention is paid to a comparative assessment of the influence of antihypertensive therapy with metoprolol and amlodipine on the structural and functional parameters of the heart and on autonomic regulation at rest and during cold and psychoemotional tests.

Arterial hypertension (AH), by its prevalence and consequences for cardiovascular morbidity and mortality, can be fully regarded as a socially significant disease. According to recent data, elevation of systolic arterial pressure (SAP) is observed in approximately 40% of women and 39% of men (Oganov R.G., 2002).

Numerous epidemiological studies have provided convincing evidence confirming the influence of AH on the incidence of atherosclerosis, coronary heart disease, and heart failure. A direct relationship has been established between the degree of AH and the risk of stroke (Chalmers J., Chapman N., 2001). Sex-related differences are observed in the development of complications: the relative frequency of stroke, compared with myocardial infarction, is higher in women than in men (AHA 2004; Mark J., 2005). Among stroke survivors, morbidity and mortality rates are higher in women than in men.

The pathophysiology, course, and therapy of AH exhibit sex-related features. A significant influence of age and sex on blood pressure (BP) level has been demonstrated (Zhukovskiy G.S. et al., 1997; Britov A.N., 2003; Kannel W.B., 2000). It has been noted that in women the incidence of AH is also determined by the development and duration of postmenopause (Podzolkov V.I. et al., 1999; Bart B.Ya., 1996; Malichenko S.B. et al., 2000; Veber V.R. et al., 1992; 2001; Posner B. et al., 1993; Artigao K., 1998).

It has been established that the prevalence of AH before the age of fifty is higher in men, but in individuals older than this an increase in the number of hypertensive cases is observed in women, and subsequently the frequency surpasses that in the male population (Oganov R.G., 1997; Britov A.N., Bystrova M.M., 2002; Belousov Yu.B. et al., 2004; Claude Lenfant, 2005). It should be noted that men and women differ not only in the incidence of AH but also in the course of the disease, which in turn depends on neurohormonal regulation during different periods of life. Published data on this issue are contradictory (Frolysis V.V. et al., 1984; Khramov O.A., Veber V.R., 1985; Goncharuk V.D., Bayus R.M., 2000; Rahn K.N. et al., 1999). Central hemodynamic parameters depend substantially on age and sex, a fact acknowledged by many authors, yet views on changes in stroke volume, total peripheral vascular resistance, and heart rate in patients according to sex differ (Chebotarev D.F., Korkushko O.V., 1982; Amery A. et al., 1978; Franke S., 1980).

The majority of studies devoted to the effectiveness of antihypertensive therapy are conducted in mixed groups, without accounting for sex-related features of hemodynamics, autonomic regulation, and cardiac remodeling. Recently, a number of works have addressed differential antihypertensive therapy in perimenopausal women (Maslova N.P. et al., 1997; Veber V.R. et al., 2001; Zadionchenko V.S. et al., 2001). The pharmacodynamic features of individual drugs in men and women are being actively studied (Minushkina L.O. et al., 2005; Kharkevich D.A., 2004), but recommendations on the differentiated use of medications according to sex were not found in the available literature. The question of the autonomic "cost" of achieving target blood pressure in men and women with AH also remains unresolved.

In this regard, the following issues are important for practical cardiology:

- what explains the differences in cardiac remodeling between men and women with AH;

- whether it is sufficient to monitor only BP and left ventricular myocardial mass during the treatment of patients with arterial hypertension;

- what changes occur in men and women with AH when target blood pressure is achieved and how these changes affect left ventricular remodeling.

AIM OF THE STUDY

To investigate the characteristics of left ventricular remodeling, its autonomic and hemodynamic mechanisms of development, and the effectiveness of antihypertensive therapy with metoprolol and amlodipine in men and women with arterial hypertension.

OBJECTIVES OF THE STUDY

1. To investigate sex-related features of central hemodynamics and patterns of cardiac remodeling in men and women with arterial hypertension, as well as in women with different states of the reproductive system.

2. To study the relationship between different hemodynamic types in men and women and patterns of cardiac geometry and changes in left ventricular diastolic function.

3. To evaluate the response of autonomic parameters and central hemodynamics to cold and psychoemotional tests and under the influence of amlodipine and metoprolol according to patient sex and left ventricular remodeling type.

4. Based on an assessment of the effectiveness of treatment with metoprolol and amlodipine, to develop recommendations for their differentiated use in men and women.

SCIENTIFIC NOVELTY OF THE STUDY

For the first time in men and women with grade II AH (WHO/ISH, 1999), a comprehensive study was carried out of the sex-related features of cardiac remodeling patterns, hemodynamic types, autonomic regulation, and the response of autonomic and hemodynamic parameters to cold and psychoemotional tests. It was shown that the eukinetic type of central hemodynamics is predominant in grade II AH, with normal left ventricular geometry prevailing in men and concentric left ventricular hypertrophy prevailing in women with AH.

In men with grade II AH, normal left ventricular geometry constitutes a remodeling variant. In 42.4% of cases, men with normal geometry exhibit pronounced left ventricular diastolic dysfunction (E/A<1).

For the first time it was demonstrated that in men and women with AH, hemodynamic and autonomic responses to cold and psychoemotional tests differ and depend on the baseline autonomic tone. The contribution of hemodynamic and autonomic parameters to the formation of the type of cardiac remodeling has been determined.

The features of action of metoprolol and amlodipine in men and women have been studied in relation to left ventricular remodeling pattern, central hemodynamic type, and autonomic regulation features during cold and psychoemotional tests.

PRACTICAL SIGNIFICANCE OF THE STUDY

Cardiac remodeling in men and women with AH has distinctive features. Men with grade II AH and normal left ventricular myocardial mass require no less careful monitoring than patients with increased LVMM, since 44.4% of them exhibit left ventricular diastolic dysfunction and have a high probability of rapid development of heart failure.

It was shown that antihypertensive therapy, in addition to achieving target BP, requires monitoring of left ventricular myocardial mass and the dynamics of diastolic function, especially in the group of men, since they develop left ventricular diastolic dysfunction 3.6 times more often, regardless of LVMM dynamics.

The autonomic effects of amlodipine and metoprolol are more pronounced in women with AH; therefore, additional monitoring of autonomic regulation during treatment and the performance of stress tests are required in this group.

STATEMENTS PUT FORWARD FOR DEFENSE

1. In men and women with AH, all variants of left ventricular remodeling develop. Normal geometry prevails in men, and in 42.4% of cases it is combined with pronounced diastolic dysfunction. In women, the leading remodeling variant is concentric left ventricular hypertrophy, and its proportion increases significantly in postmenopause.

2. In men and women with grade II AH, the eukinetic type of central hemodynamics is predominant. No relationship was found between remodeling variant and hemodynamic type in patients with AH, but a relationship exists between the variant of cardiac remodeling and the magnitude and direction of hemodynamic and autonomic parameters during cold and psychoemotional tests.

3. When selecting an antihypertensive drug in men and women with arterial hypertension, it is necessary to take into account the baseline autonomic profile and, during treatment, to monitor its changes, as well as the dynamics of the left ventricular myocardial mass index and diastolic function.