Exercise training in the treatment of hypertension in the metabolic syndrome; exercise type and interactions with antihypertensive medication

Laburpena

GENERAL SUMMARY Background The metabolic syndrome (MetS) is an accumulation of multiple related risk factors such as abdominal obesity, insulin resistance, hypertension and high levels of lipids and glucose in blood. This condition is associated with an increased risk for cardiovascular disease and all-cause mortality. MetS has become a major public health problem worldwide with a prevalence of ~31% of the adult population in countries like Spain and the United States. One of the most frequent factors of this syndrome is arterial hypertension, with a prevalence of 80% in MetS individuals. Hypertension besides of a key component in MetS, is the leading factor contributing to cardiovascular disease and mortality. Thus, reducing hypertension is one important clinical goal that would reduce the cardiovascular risk factors in this population. The first line of therapy for MetS are lifestyle changes involving hypocaloric diet and increasing the levels of energy expenditure through physical activity and structured exercise training. Aerobic exercise training has a favorable effect on most cardiovascular risk factors associated with MetS. Especially, high blood pressure is highly responsive to aerobic exercise. In fact, guidelines for the management of high blood pressure in America and Europe list exercise as a non-pharmacological intervention of paramount importance. The benefits of exercise appear after only one bout of exercise, in a phenomenon named post-exercise hypotension (PEH), characterized by a transient reduction in blood pressure below the values observed either immediately prior to exercise or on a control day. In addition to this acute response that can lasts 24-h, if exercise sessions are systematically repeated over time (i.e. exercise training), a chronic adaptation is achieved, and blood pressure is lowered significantly over time. This reduction could be maintained for 3 years in MetS individuals if they devote only one-third of the year to aerobic training. The benefits of exercise training are not only limited to this BP reduction but improve cardiorespiratory fitness as well, which is an independent predictor of mortality inversely correlated with MetS. Justification The post-exercise hypotension observed after one bout of exercise is a consistent response in both in normotensive and hypertensive people. However, the exercise training duration, mode and intensity that produces the largest reduction in hypertension is not well known. High-intensity interval training (HIIT) has emerged as a time-efficient approach to exercise with larger improvements in cardiorespiratory fitness and cardiovascular risk factors than the traditional moderate-intensity continuous training. However, it is unclear if HIIT is superior to continuous moderate-intensity aerobic training to specifically lower hypertension. Habitually, hypertensive MetS individuals combine antihypertensive medication with non-pharmacological interventions since their increased cardiovascular risk require a multi-component approach. The interactions between the current antihypertensive medications and lifestyle interventions (i.e. aerobic exercise) have not been fully described, making difficult to tailor the optimal combined treatment. Finally, hypertensive MetS people are encouraged to engage in exercise training regularly over time. However, there are critical dates during the year characterized by low levels of physical activity combined by repeated periods of overeating (i.e. Christmas holidays). Therefore, we think that these uncertainties in the integrated pharmacological and non-pharmacological treatment of hypertensive MetS individual requires clarification. Aims of the dissertation This dissertation encompasses six studies aimed to gain knowledge to improve the efficacy of exercise and medication on lowering hypertension in MetS patients. We tried to determine the most effective type of aerobic exercise on the acute blood pressure response that follows a bout of exercise. We also aimed to study the interactions between a bout of exercise and the pharmacological treatment on the acute and mid-term (i.e., 24 h) blood pressure responses. We also studied how an aerobic training program (4 months long) interacts with their pharmacological treatment to lower blood pressure. Finally, we studied the effects of interrupting aerobic training during the most critical part of the year for weight gaining (Christmas holidays). Main findings The effectiveness of exercise to lower blood pressure may depend on the type and intensity of exercise. In study 1 we aimed to determine if a single bout of HIIE has a larger effect on lowering blood pressure compared to an isocaloric bout of moderate-intensity continuous exercise (MICE) using ambulatory monitoring to follow the blood pressure response during 14-h after exercise. We found that normotensive MetS did not reduce its ambulatory blood pressure after any type of exercise. However, hypertensive MetS individuals reduced systolic ambulatory blood pressure by 6 mmHg only after HIIE. Our results suggest that the ambulatory blood pressure reduction of a bout of exercise depends on the intensity and type of exercise. A morning session of HIIE may serve as a non-pharmacological aid in the treatment of the hypertension associated with MetS. Hypertensive MetS patients frequently combine pharmacologic therapy while engaging in exercise training regimes at the same tame. However, the interactions between their most habitual antihypertensive medication (i.e. angiotensin receptor blockers; ARBs) and exercise are not well described. In study 2 a group of hypertensive individuals with MetS chronically medicated with ARBs underwent two exercise trials in a blind randomized order. One trial was conducted after taking their habitual dose of ARBs and another after 48 h of placebo medicine. Exercise reduced systolic blood pressure by 7 mmHg but those effects were added on top of another 5 mmHg when taking ARB’s. Apparently, some of the ARB effects resided in the microcirculation. The results show that ARBs and a bout of intense exercise have an additive effect on lowering blood pressure in hypertensive individuals. A bout of exercise is very effective at acutely reducing hypertension. However, the question that arises is, what is more effective at reducing hypertension over a 24-h period, one dose of antihypertensive medication or one bout of intense aerobic exercise? In study 3 we analyzed a hypertensive MetS sample chronically medicated with angiotensin receptor blockers (ARBs). Participants underwent 24-hr monitoring in four separated days in a randomized order; (a) after taking their habitual dose of antihypertensive medicine, (b) substituting their medicine by placebo medicine, (c) placebo medicine with a morning bout of intense aerobic exercise and (d) combining exercise and antihypertensive medicine. We found that one bout of intense aerobic exercise in the morning could substitute the effects of antihypertensive medicine in lowering blood pressure but only during the day up to 10 hours after the exercise bout, but the effects fade out at night. During those hours, combining exercise and ARBs medication resulted in longer reductions in SBP than exercise alone. Lack of time is one of the main reasons for not exercising. Thus, low volume high-intensity interval exercise approaches have emerged as an option to fight hypertension. Inspired by the large differences in PEH when increasing exercise intensity from continuous to HIIE of our study 1, we speculated that shorter bouts of higher exercise intensity (supramaximal exercise) could be even more efficacious lowering blood pressure in the mid-term (i.e., in the 24-h post-exercise). In study 4 we analyzed the post-exercise hypotension response to a supramaximal bout of aerobic interval exercise performed alone or in combination with subjects’ habitual ARB medication. The results showed that the blood pressure-lowering effect of a morning exercise bout alone lasts 19-h. Conversely, when exercise was conducted with ARB medicine, the blood pressure-lowering effect was larger in magnitude and duration than with exercise alone, lasting at least 21-h after exercise. It is unclear if aerobic exercise training can chronically lower blood pressure in MetS individuals already taking antihypertensive medicine. In study 5, MetS chronically medicated with blockers of the renin-angiotensin-aldosterone system (RAAS), underwent an aerobic training program during 4-months. Before and after training, 24-h ambulatory BP was monitored under 2 conditions in a double-blind, placebo randomized design: a) PLAC trial substituting for 3 consecutive days AHM by placebo, and b) AHM trial, taking their prescribed antihypertensive medicine. We found that aerobic training reduces blood pressure and increases the daytime efficacy of antihypertensive medication in treated MetS people. The parallel reduction in plasma aldosterone elicited by antihypertensive medication after training suggests that a better blockade of the RAAS could be behind that improvement in blood pressure. There are periods during the year in which exercise programs are discontinued and improper dietary habits reappear (e.g., Christmas holidays). The purpose of study 6 was to assess the effects of continue or discontinue exercise training during Christmas holidays on body weight, cardio-metabolic health parameters and exercise performance in MetS individuals. The main finding was that exercise-training during Christmas prevented the deterioration in body weight, blood pressure, waist circumference, insulin sensitivity, cardiorespiratory fitness and the capacity to oxidize fat during exercise. Given that body weight is the most important risk factor for MetS, only nine bouts of training during Christmas can prevent that increase in body weight and its associated deleterious effects on the hypertension of MetS individuals.