Abstract
Hypertension is the leading risk for cardiovascular morbidity and mortality worldwide. It has been known for decades that lowering elevated blood pressure with antihypertensive medication has a beneficial effect on mortality. All major classes of antihypertensive medications lower brachial blood pressure effectively. Beta-adrenoceptor blockade (beta-blockade) has been a mainstay of antihypertensive treatment in the past but other classes of antihypertensive medications have shown better effect on lowering central blood pressure and on prevention of stroke.
Traditionally blood pressure is measured at rest, in the sitting or supine position with a brachial sphygmomanometer. The hemodynamic status, however, is considerably different in the upright position as numerous physiological changes are necessary to compensate for the gravitational shift of blood in the body. Resting blood pressure measurements lack the ability to give information about this adaptational state. Since humans spend most of their active time upright, the traditional way of monitoring blood pressure does not necessarily represent the most prevalent hemodynamic state. In addition, as the human heart on average goes through over 90000 cycles a day, a couple of blood pressure readings provide only a fraction of information about the multitude of systolic and diastolic pressures.
The aim of this thesis was to study the hemodynamic effects of beta-blockade in hypertensive men both supine and during upright challenge and to analyze different hemodynamic phenotypes of central blood pressure in the upright position. A non- invasive hemodynamic measurement protocol with continuous tonometric pulse wave analysis and whole-body impedance cardiography was utilized to achieve a comprehensive examination of the cardiovascular system during pharmacological and positional challenges.
In study I the effect of a three-week course of beta-blocker bisoprolol (5mg / day) was examined in 16 never-treated men with grade I to II hypertension in a double-blind randomized placebo-controlled cross-over fashion. In supine measurements bisoprolol decreased blood pressure both peripherally and centrally without effects on central wave reflection. Bisoprolol also decreased pulse pressure amplification which indicates better peripheral than central blood pressure
reduction.
The second study (II) included an orthostatic challenge in addition to the protocol of the first study (I). In the upright position bisoprolol induced a marked reduction of heart rate and cardiac output which resulted in a more pronounced rise in peripheral resistance than during placebo. This resulted in pronounced central wave reflection and increased pulse pressure. Hence, central systolic blood pressure was not reduced with bisoprolol in the upright position.
In the third study (III) different phenotypes of central blood pressure change during upright position were studied. In 613 participants both central and finger systolic blood pressures were decreased from supine levels when assuming the upright position. However, when participants were divided into tertiles according to the supine-to-upright change in central systolic blood pressure, only two thirds of them exhibited a decrease in central systolic blood pressure. Instead, one third of participants presented with a rise in central systolic blood pressure, some of which could be classified to be hypertensive only in the upright, but not supine position. The primary explanatory factor for this was the difference in systemic vascular resistance regulation.
In conclusion, resting blood pressure measurements can provide only limited information about human hemodynamics. Upright position presents a remarkable challenge for the cardiovascular system. The adverse effects of beta-blockade to central hemodynamics are uncovered in the upright position, which is detrimental to the central antihypertensive effect of the compound. Moreover, the compensation mechanisms to positional challenge are not uniform but can vary considerably between individuals.
Traditionally blood pressure is measured at rest, in the sitting or supine position with a brachial sphygmomanometer. The hemodynamic status, however, is considerably different in the upright position as numerous physiological changes are necessary to compensate for the gravitational shift of blood in the body. Resting blood pressure measurements lack the ability to give information about this adaptational state. Since humans spend most of their active time upright, the traditional way of monitoring blood pressure does not necessarily represent the most prevalent hemodynamic state. In addition, as the human heart on average goes through over 90000 cycles a day, a couple of blood pressure readings provide only a fraction of information about the multitude of systolic and diastolic pressures.
The aim of this thesis was to study the hemodynamic effects of beta-blockade in hypertensive men both supine and during upright challenge and to analyze different hemodynamic phenotypes of central blood pressure in the upright position. A non- invasive hemodynamic measurement protocol with continuous tonometric pulse wave analysis and whole-body impedance cardiography was utilized to achieve a comprehensive examination of the cardiovascular system during pharmacological and positional challenges.
In study I the effect of a three-week course of beta-blocker bisoprolol (5mg / day) was examined in 16 never-treated men with grade I to II hypertension in a double-blind randomized placebo-controlled cross-over fashion. In supine measurements bisoprolol decreased blood pressure both peripherally and centrally without effects on central wave reflection. Bisoprolol also decreased pulse pressure amplification which indicates better peripheral than central blood pressure
reduction.
The second study (II) included an orthostatic challenge in addition to the protocol of the first study (I). In the upright position bisoprolol induced a marked reduction of heart rate and cardiac output which resulted in a more pronounced rise in peripheral resistance than during placebo. This resulted in pronounced central wave reflection and increased pulse pressure. Hence, central systolic blood pressure was not reduced with bisoprolol in the upright position.
In the third study (III) different phenotypes of central blood pressure change during upright position were studied. In 613 participants both central and finger systolic blood pressures were decreased from supine levels when assuming the upright position. However, when participants were divided into tertiles according to the supine-to-upright change in central systolic blood pressure, only two thirds of them exhibited a decrease in central systolic blood pressure. Instead, one third of participants presented with a rise in central systolic blood pressure, some of which could be classified to be hypertensive only in the upright, but not supine position. The primary explanatory factor for this was the difference in systemic vascular resistance regulation.
In conclusion, resting blood pressure measurements can provide only limited information about human hemodynamics. Upright position presents a remarkable challenge for the cardiovascular system. The adverse effects of beta-blockade to central hemodynamics are uncovered in the upright position, which is detrimental to the central antihypertensive effect of the compound. Moreover, the compensation mechanisms to positional challenge are not uniform but can vary considerably between individuals.
| Original language | English |
|---|---|
| Place of Publication | Tampere |
| Publisher | Tampere University |
| ISBN (Electronic) | 978-952-03-3515-1 |
| ISBN (Print) | 978-952-03-3514-4 |
| Publication status | Published - 2024 |
| Publication type | G5 Doctoral dissertation (articles) |
Publication series
| Name | Tampere University Dissertations - Tampereen yliopiston väitöskirjat |
|---|---|
| Volume | 1052 |
| ISSN (Print) | 2489-9860 |
| ISSN (Electronic) | 2490-0028 |