| Summary: |
Resistant hypertension (RH) is a major problem for patients, healthcare system and professionals. Presently, it is a medical problem without a solution, as the available treatment options to lower blood pressure in these patients, namely antihypertensive drugs and renal denervation, have reduced success.(1, 2) In this context, exercise training emerges as a promising therapy, as it is a polypill with several benefits including blood pressure reduction.(3-10) Exercise can be a cost effective treatment in the long run, when its
effects on blood pressure are extrapolated to a reduction in cardiovascular events with associated health gains and cost reductions.
Exercise also has potential to reduce lifetime multiple drug use, with associated savings and implications for quality of life. Although the benefits of exercise are increasingly recognized, it is only with great delay that it is being investigated as part of the management of RH.(11)
Despite promising, the evidence about the impact of exercise training in the control of blood pressure in RH is fragile. Only three studies exist(12-14); two(13, 14) used a water-based exercise intervention, which is difficult to implement due to staff and infrastructures requirements. The only land-based study(12) has several limitations, as it fails to provide crucial information, namely frequency, intensity, time, and type of exercise, as well as exercise adherence and the timing of the blood pressure measurements, which is a critical aspect as the evaluation should avoid the postexercise hypotension and the detraining effects. Additionally, the 3 studies did not control modifications in diet, physical activity, and body fat, hence not accounting their contribution to the changes in blood pressure, hence not observing the independent effect of exercise. Moreover, none of these studies provided any insight about the mechanisms of blood pressure reduction or did a follow-up evaluation to clarify whether the effects of exercise  |
Summary
Resistant hypertension (RH) is a major problem for patients, healthcare system and professionals. Presently, it is a medical problem without a solution, as the available treatment options to lower blood pressure in these patients, namely antihypertensive drugs and renal denervation, have reduced success.(1, 2) In this context, exercise training emerges as a promising therapy, as it is a polypill with several benefits including blood pressure reduction.(3-10) Exercise can be a cost effective treatment in the long run, when its
effects on blood pressure are extrapolated to a reduction in cardiovascular events with associated health gains and cost reductions.
Exercise also has potential to reduce lifetime multiple drug use, with associated savings and implications for quality of life. Although the benefits of exercise are increasingly recognized, it is only with great delay that it is being investigated as part of the management of RH.(11)
Despite promising, the evidence about the impact of exercise training in the control of blood pressure in RH is fragile. Only three studies exist(12-14); two(13, 14) used a water-based exercise intervention, which is difficult to implement due to staff and infrastructures requirements. The only land-based study(12) has several limitations, as it fails to provide crucial information, namely frequency, intensity, time, and type of exercise, as well as exercise adherence and the timing of the blood pressure measurements, which is a critical aspect as the evaluation should avoid the postexercise hypotension and the detraining effects. Additionally, the 3 studies did not control modifications in diet, physical activity, and body fat, hence not accounting their contribution to the changes in blood pressure, hence not observing the independent effect of exercise. Moreover, none of these studies provided any insight about the mechanisms of blood pressure reduction or did a follow-up evaluation to clarify whether the effects of exercise could be maintained.
Therefore, due to lack of success of the available treatments, the methodological limitations of the available evidence and the high burden of disease attributable to high blood pressure, we aim to test the hypothesis that aerobic exercise is an effective antihypertensive therapy in patients with RH; and, that the positive changes induced in the blood pressure control are mediated by exercise-induced increase in nitric oxide bioavailability. In this sense, the main objective is to assess in a randomized controlled trial whether exercise training reduces ambulatory blood pressure in patients with RH. As secondary objectives we aim to evaluate the effects of the exercise intervention on: the use of blood pressure lowering agents; risk factors, body composition, daily physical activity, dietary intake, quality of life, cardiorespiratory fitness; inflammatory biomarkers, autonomic function, arterial stiffness;
endothelial function, damage and repair/regeneration; nitric oxide bioavailability, endothelial Nitric Oxide Synthase (eNOS) and oxidative stress. Third, to evaluate the effect of exercise on blood pressure and the former parameters three months postintervention,
to clarify whether the effects of exercise could be maintained after the end of the training period.
To accomplish these goals 60 patients with RH will be recruited and randomized into exercise training or control groups and followed up for 6 months. The patients in the exercise group will participate in a 3-month outpatient program. The control group will receive
usual medical care. At baseline, |