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UDC 616.12-07:616-08-07
FEATURES OF CIRCADIAN BLOOD PRESSURE MONITORING (BEFORE TREATMENT AND ON THE BACKGROUND OF EFFECTIVE ANTIHYPERTENSIVE AMLODIPINE TREATMENT) AND THE REACTION TO PHYSICAL STRESS IN HYPERTENSIVE WOMEN WITH NORMAL EMOTIONALBACKGROUND AND WITH SUBCLINICAL DEPRESSION
A.I.Vinogradov, I.A.Suhenko, A.S.Dyakov
Yaroslav-the-Wise Novgorod State University, zhmailova.svetlana@yandex.ru
Effective therapy with amlodipine reduces the load on the target organs by elevated systolic blood pressure, which also increases the load by lowered blood pressure, especially diastolic BP at night, and to a greater extent in hypertensive patients with subclinical depression. BP variability is higher in hypertensive women with subclinical depression during the day. We revealed inadequate hemodynamic support of physical stress in hypertensive women with subclinical depression.
Keywords: hypertension, daily blood pressure monitoring, hypertension load, hypotension load, the normal psycho-emotional background, subclinical depression
При эффективной терапии амлодипином уменьшается нагрузка на органы-мишени повышенным систолическим АД, но при этом нарастает нагрузка пониженным АД, особенно диастолическим АД в ночные часы, причем в большей степени у больных АГ с субклинической депрессией. Вариабельность АД выше у больных АГ женщин субклинической депрессией на протяжении суток. Выявлено неадекватное гемодинамическое обеспечение физической нагрузки у больных АГ женщин с субклинической депрессией. Ключевые слова: артериальная гипертензия, суточное мониторирование АД, нагрузка гипертензией, нагрузка гипотензией, нормальный психоэмоциональный фон, субклиническая депрессия
Recent years a great attention has been paid to study the effect of depression on the course and prognosis of cardiovascular disease, including hypertension (HT). A number of studies [1] has shown that almost in half of hypertensive patients is detected subclinical depression. However, question of the effect of subclinical depression on the variability of the circadian rhythm remains poorly understood.
In our prior studies [2-5] was shown that the autonomic response to stress (cold test) in hypertensive patients with normal psycho-emotional background (PEB) is accompanied mainly by activation of sympathoadrenal system, and in hypertensive patients with of subclinical depression occurs, by contrast, more often with increase of vagotonic activity, accompanied by a reduction of blood pressure and decrease o heart rate, which indicates the paradoxical autonomic and hemodynamic responses to stress in this group of hypertensive patients.
Objective: to study the dynamics of ambulatory blood pressure monitoring (ABPM) before treatment and on the background of effective antihypertensive treatment with amlodipine in hypertensive women with normal PEB and with subclinical depression, as well as to investigate the reaction of BP on physical activity in these groups of patients.
Materials and methods
We examined two groups of patients: Group I included 15 women with AH stage II (ESC / ESH 2007), average age 45,4 ± 1,7 years with normal psycho-emotional background, the second group consisted of 14 women with AH stage II, matched by age (46,7 ± 1,3 years).
To assess the psycho-emotional background (PEB) we used psychometric scales: a) the depression
scale CES-D (Central for Epidemiologic Studies-Depression); b) Scale of Beck (Beck Depression Inventory); c) The hospital anxiety and depression scale — HAD S. The second study group included hypertensive patients in whom was revealed subclinical depression by testimony of two of the three scales. All the patients underwent daily BP monitoring, we analyzed the dynamics of indicators: time index (TI), and the index of measurement (IM) by elevated and by lowered systolic blood pressure (SBP) and diastolic blood pressure (DBP), reflecting the load by hypertension and by hypotension on the target organs.
Patients were examined before the start of the regular antihypertensive therapy and in one month of treatment with amlodipine. The dose of amlodipine was adjusted by double-blind, individually and was 5-10 mg/day. The study included only those patients who according to office measurements and data of self-control of BP has achieved target blood pressure level.
Before starting the regular antihypertensive therapy in all hypertensive patients as aprobe with physical activity was conducted a standard bicycle stress study using the bicycle ergometer «Tunturi» E3.
Before the study (before landing on the ergome-ter) was conducted three times measurement of blood pressure, was taken the average value, then blood pressure was measured again when landing on the ergometer (reactivity test), further — in the last minute of each stage of the load (25 W, 50 W, at the height of the load) and 1 minute after the cessation of pedaling. We defined levels of SBP, DBP and pulse pressure (PP). The criteria for termination of the test with physical exercise were muscle fatigue, shortness of breath, submaximal HR and increase of blood pressure above 230/110mm Hg.
Fig.1. TI and elevated systolic and diastolic blood pressure both day and night inhypertensive women with normal PEB (I group) and with subclinical depression (II group)
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Fig.2. Change of TI and elevated systolic and diastolic blood pressure both day and night in hypertensive women with normal PEB (I group) and with subclinical depression(II group) during therapy with amlodipine
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Fig.3. Change of TI by lowered SAD during the day and night at the hypertensivewomen with normal PEB (I group) and subclinical depression (II group) beforetreatment and after 1 month of therapy with amlodipine
Statistical analysis was performed using the program «Statistica 6,0». Among the methods of nonpara-metric statistics, we used the most conservative method of comparing data on the median — the criterion of Friedman and concordance of Kandell. To visualize the results of research we used graphical and analytical method.
The results
The results showed that in patients with hypertensive women with subclinical depression indicators TI and IM and elevated blood pressure during the day did not significantly differ from the parameters of TI and IM and elevated blood pressure in patients with normal PEB
(Fig-1).
During therapy with amlodipine indicators TI and IM and elevated SBP during the dayin the total group of patients did not change significantly, but significantly in-creasedrates of TI and IM and elevated diastolic blood pressure, especially at night in bothgroups, but to a greater degree in patients with subclinical depression (Fig.2 ).
If during the day was a tendency to increase TI by elevated diastolic blood pressure in patients with with sub-clinical depression under the influence of amlodipine (x2 = 3,6; p= 0.058) and patients with normal PEB (%2 = 3,0; p = 0.083), then increase of the load by elevated blood pressure in patients with subclinical depression was more significant (increase in high blood pressure in both groups can be represented by the ratio 2:6). That is to say, compared with the first group (with normal PEB) patients of the second group (with subclinical depression) have more pronounced load by elevated DBP on the target organs.
Analysis of TI by lowered blood pressure during the day (Fig.3) showed that therapy with amlodipine in both groups increased significantly by lowered systolic pressure during the day (in the first group, yl = 8,33; p = 0.0039, the second group, y2 = 10, 00, p = 0.0016) and by lowered SBP at night (in the first group, y2 = 8,33; p =
0.0039, in the second group, y2 = 10,00; p = 0.0016), and to a greater degree in the group of hypertensive women with subclinical depression (rise of median of TI by low-
ered SBP during the day on the the background of therapy with amlodipine in patients of the second groupin 1,7 times more than in the group with normal PEB).
Variability of SAD during the day, in patients with subclinical depression was slightly higher (p = 0.057) than patients with normal PEB. After a month of treatment with amlodipine in hypertensive women with subclinical depression (Fig.4) noted upward trend in SBP variability at night (%2 = 3,6; p = 0.058) and authentic increase in the variability of DBP during the night (x2 = 6,9; p = 0.011). In hypertensive women with normal PEB (Fig.5) noted only a tendency of increase of the index of variability of DBP at night (%2 = 3,0; p = 0.083).
In hypertensive women with subclinical depression after a month of treatment with amlodipine noted increase in subclinical depression of points on HADS scale. In hypertensive women with normal PEB during therapy with amlodipine in nearly half ofcases also noted an increase scores on the HADS scale, but within normal area of points of PEB. In both groups, this was accompanied by an increase in variability of DBP during the night, and most significantly in patients with subclinical depression (Fig.4).
The results showed that, despite the exceptional pharmacokinetic and pharmacodynamic properties of a calcium channel blocker amlodipine generation III, and in hypertensive patients with normal PEB, as in some patients (16,7% of the total examined) BP variability, especially at night DBP becomes excessively high for the first time. In both groups of patients, this leads to an increased workload on the target organs and, above all, the heart and brain vessels, but in a group of hypertensive patients with subclini-cal depression, this effect is more pronounced.
Such a load with low blood pressure limits the use of the drug in elderly patients with hypertension and in patients with concomitant coronary artery disease, with cerebrovascular accidents. This significant increase in workload by low blood pressure during therapy with am-lodipine makes more strict and selective approach to the appointment of the drug. The results of this study demonstrate the need for ABPM in hypertensive patients receiving amlodipine, to avoid excessive and prolonged nocturnal BP reduction, which is dangerous in terms of acute cardiac and vascular episodes.
Fig.4. Variability of SBP and DBP during the day and night in hypertensive women with subclinical depression before treatment and on the background of antihypertensive therapy with amlodipine
Fig.5. Variability of SBP and DBP during the day and night in hypertensive women with normal PEB before treatment and on the background of antihypertensive therapy with amlodipine
Despite the fact that some calcium channel blockers, particularly verapamil, used in psychiatry for the treatment of depression [6], in amlodipine also described the development of depression as one of the side effects. The results of our studies have shown that the appointment of amlodipine increases the severity of subclinical depression (points on HADS depression scale increase in 90% of patients), and in 88,9% cases it is associated with increased BP variability. Such an unusual increase in points on HADS depression scale also requires understanding the reasons for such changes in PEB and requires further research on the dynamics of changes in PEB during treatment with the drug.
One possible reason for this change in PEB, in spite of the effectiveness of antihypertensive therapy may be just the increased load by low blood pressure, that in a part of hypertensive patients may be accompanied by a deterioration of cerebral perfusion. Furthermore, increased variability in of the daily blood pressure also leads to a significant load on the system of autoregulation of cerebral blood vessels that may contribute to the de-
velopment or growth of the level of subclinical depression.
Study of the dynamics of blood pressure at different levels of stress during cycle ergometry in women with AH normal PEB and with subclinical depression showed that if, before landing on the ergometer by the level of SBP between the two groups of patients the differences were not detected, then landing on the ergometer (reactivity test) in women with normal PEB SBP increases whereas in hypertensive women with subclinical depression, by contrast, is reduced compared with baseline. Later during the velo-ergometry-study at all levels of load (25 W, 50 W and at the height of the load — the maximum load when the test was stopped) and within the first minute after the cessation of pedaling SBP in hypertensive patients with subclinical depression was significantly lower than SAD in hypertensive patients with normal PEB(Fig.6).
On the degree of the load equal to 50 W level of SBP 160 mm Hg and below was observed in 60% of hypertensive women with normal PEB and only 25% of patients with subclinical depression (%2 = 3,83; p = 0,05).
Fig.6. The reaction of SBP to physical exercise during cycle ergometry in hypertensive patients with normal PEB (I group) and subclinical depression (II group) before treatment
Thus, the reaction of SBP to exercise hemodynamic indicates on inadequate provision of physical activity in hypertensive women with subclinical depression.
During bicycle exercise at a load of 50 watts and at the height of the load level of DBP in patients with sub-clinical depression was significantly lower then values of DBP in patients with normal PEB (x2 = 5,760; p = 0.016).
Thus, the dynamics of DBP in hypertensive patients with subclinical depression also differs significantly from the dynamics of DBP in patients with normal PEB.
Result of changes in SBP and DBP during the veloergometry is a change in pulse pressure (PP) in both groups. In hypertensive women with subclinical depression when landing on the ergometer, the load of 25 W, 50 W and at the height of the load PP was lower than in patients with normal PEB. The level of PP 60 mmHg and below was found in 22,2% of hypertensive patients of the first group and in 43.3% of the patients of the second group (x2 = 4,879; p =0.027).
Authentically lower PP on the load 25 W, 50 W and at a height of the load in patients with subclinical depression is a poor prognostic sign, since the lack of adequate growth of PP during the performance of exercise hampers further the load.
Conclusions
1. With effective antihypertensive therapy with amlodipine decreases the load on the target organs by elevated SBP, but it increases the load by lowered blood pressure, especially by lowered DBP at night in both groups, but in hypertensive women with subclinical depression to a greater extent.
2. Variability of blood pressure in hypertensive women with subclinical depression during the day higher than in hypertensive women with normal psycho-emotional background. Besides, in most of hypertensive women with subclinical depression in 1 month of effective antihypertensive treatment with amlodipine increases points of subclinical depression on psychometric HADS scale and grows daily BP variability.
3. The reaction of systolic BP and diastolic BP and pulse pressure during cycle ergometry indicates on inadequate hemodynamic support of physical stress in hypertensive women with subclinical depression, compared with hypertensive women with normal psycho-emotional background. Lower level of pulse pressure during cycle ergometry in patients with AH during the presence of subclinical depression is an unfavorable hemodynamic change for the further implementation of increasing workload.
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