Exercise‐induced benefits in metabolic syndrome

Metabolic syndrome (MetS) is a modern pandemic comprised of several cardiovascular risk factors that coexist and promote cardiovascular morbidity and mortality.1 Accumulating data point towards the beneficial role of aerobic exercise on promoting individual risk factor control of conditions such as diabetes mellitus and essential hypertension.2, 3 However, studies, particularly randomized trials, regarding the effects of aerobic exercise in MetS are limited. In this issue of the Journal of Clinical Hypertension, Mora‐Rodriguez and colleagues4 present their randomized study on the effects of 6‐month high‐intensity aerobic interval training on arterial stiffness and microvascular dysfunction in patients with MetS and hypertension.

Arterial stiffness parallels structural changes in the medial layer of the elastic arteries (aorta and major arterial conduits) and is produced mainly by the progressive elastic fiber degeneration. An increase in stiffness occurs with aging and is accelerated in patients with hypertension.4, 5 It is also seen in patients with end‐stage renal disease, diabetes6, 7 and other cardiovascular risk factors.8 Aortic pulse wave velocity (PWV) constitutes the most accurate and reliable noninvasive method to determine arterial stiffness.9 In addition, augmentation index, which was also measured in this study, has been suggested as a more sensitive marker of arterial stiffness in younger individuals.10 PWV predicts cardiovascular and all‐cause mortality in healthy individuals but also in patients with hypertension11 and provides a useful tool of risk stratification in patients with cardiovascular risk factors when its measurement is available.12

Cross‐sectional studies have documented the beneficial effects of regular physical activity on indices of arterial stiffness in healthy men and women.13, 14, 15, 16 However, the optimal duration, intensity, and type of exercise interventions remain to be clarified.17 Notably, it seems that high‐intensity exercise may have an advantage over light to moderate exercise in improving arterial stiffness, although results of individual studies are not comparable because of the heterogeneity in exercise modules and study populations. In addition, intervention studies that focus on patients with increased cardiovascular risk are scarce. In postmenopausal women, both moderate‐ and high‐intensity aerobic exercise interventions improved arterial stiffness.18 However, in older adults with hypertension, diabetes mellitus and dyslipidemia PWV presented a significant reduction only after a 3‐month vigorous aerobic exercise program compared with the nonaerobic group.19 In contrast to the effect in a healthy population, moderate‐intensity aerobic exercise did not reduce PWV in patients with hypertension.20, 21 In accordance with these data, a recent meta‐analysis failed to show an improvement in arterial stiffness in obese adults following moderate‐intensity aerobic exercise.22 In this meta‐analysis, however, arterial stiffness improved in the subgroup of patients who presented with a significant reduction in blood pressure (BP) levels. These results are in line with the study by Mora‐Rodriguez and colleagues, who found a reduction in BP levels as well as arterial stiffness indices (PWV and augmentation index) following high‐intensity aerobic exercise training.

Endothelial dysfunction is recognized as an impairment of endothelium‐dependent vasodilation and is considered a precursor of clinical detectable atherosclerosis.23 Endothelial dysfunction has been associated with all of the established cardiovascular risk factors, such as essential hypertension and MetS.24 Flow‐mediated dilatation is considered the gold standard noninvasive imaging method to estimate endothelial function.25 By estimating the reactivity of the brachial artery after occlusion ischemia is induced, flow‐mediated dilatation is the most robust marker of endothelial function in the medium arteries where the principal mediator of vasodilation is endothelium‐derived nitric oxide.26 Novel established biochemical markers of endothelial dysfunction include asymmetric dimethylarginine and endothelial microparticles.27 In the present study, Mora‐Rodriguez and colleagues utilized peripheral postocclusion reactive hyperemia, which is a measurement of microvascular reactivity, in patients with MetS.28

The composition of the arterial wall changes along the arterial tree. While large arteries are the main elastic arteries in the human body, small arteries (<350 μm diameter) and the arteriole (<100 μm diameter) wall consist mainly of smooth muscle cells and the capillary (<7 μm diameter) wall is covered only by a single layer of endothelial cells. Likewise, BP differs along the arterial tree. Pulsatile flow is highest in the large arteries, decreases towards the small arteries, and begins to disappear in the arterioles, with the flow being almost constant at the level of the capillaries. Therefore, the effect of high BP on the arterial wall cannot be the same. On the contrary, it differs according to the structure of the arterial wall and the hemodynamic parameters.29 This is one of the main reasons why different methods have evolved in order to investigate vascular function in the human body. The method that Mora‐Rodriguez and colleagues used is noninvasive and easy to perform, while it investigates vascular reactivity at the level of cutaneous vessels, consisting mainly of capillaries covered by a single layer of endothelial cells. At this level of microcirculation, other mediators apart from nitric oxide, such as prostaglandins and endothelium‐derived hyperpolarizing factor, contribute to vasodilation.30

Aerobic exercise has been shown to be beneficial on endothelial dysfunction measured mainly by flow‐mediated dilatation in healthy individuals and patients with increased cardiovascular disease.3 Improvement in flow‐mediated dilatation has also been shown in obese patients with insulin resistance syndrome.31 To our knowledge, Mora‐Rodriguez and colleagues were the first to show an improvement in microvascular reactivity following randomized exercise intervention in MetS. As also acknowledged by the authors, there is no gold standard method for the measurement of microvascular function, but several methods are available. Another method of microvascular function is near‐infrared spectroscopy, which very recently has been shown to be impaired in patients with essential hypertension.32 Furthermore, it is not yet known and remains to be proven whether microvascular dysfunction/reactivity is associated with endothelial dysfunction in medium arteries. It is also under investigation whether any microvascular damage observed in patients with cardiovascular risk factors reflects a more generalized endothelial dysfunction in the vascular bed. In this respect, this study does not provide insights into the effect of exercise on endothelial function in MetS. Nevertheless, it demonstrates important innovative data regarding the effect of exercise on microvascular function. Last, although a significant improvement on vascular parameters was observed after high‐intensity exercise, this study was not designed to investigate whether this improvement was the result of BP lowering per se or of other parameters associated with exercise.

The authors also measured high‐sensitivity C‐reactive protein, fibrinogen, platelets, leukocytes, and erythrocytes in their effort to understand the effects of high‐intensity aerobic exercise in this population. A recent small study of women with MetS showed a reduction in high‐sensitivity C‐reactive protein and monocyte chemotactic protein‐1 levels following a 6‐month lifestyle modification program.33 However, these markers are not sensitive prothrombotic markers and were not expected to improve following training. More sensitive markers that have been found to change following exercise include markers of platelet activation, such as monocyte‐platelet aggregates,34 or markers of coagulation and fibrinolysis, such as thrombin‐antithrombin complexes and human plasminogen activator inhibitor‐1.35 Molecular mechanisms by which exercise exerts its beneficial effects on the cardiovascular system need to be further investigated. Several mechanisms have been implicated including oxidative stress reduction, changes in vasoactive compounds, and anti‐inflammatory and antiapoptotic effects.3

In conclusion, high‐intensity aerobic exercise training seems to be beneficial to the cardiovascular system by promoting BP control and macrovascular and microvascular function in patients with MetS. A better understanding of the role of exercise intensity and duration in this process is warranted to interpret this knowledge into clinical practice. In addition, risks and benefits should be carefully investigated in specific subgroups. Further well‐designed studies are needed in patients with MetS to clarify the pathophysiology and possible favorable effect of pharmacological treatment on exercise‐induced effects.

CONFLICTS OF INTEREST

The authors have no conflicts of interest to declare.

Gkaliagkousi E, Gavriilaki E, Douma S. Exercise‐induced benefits in metabolic syndrome. J Clin Hypertens. 2018;20:19–21. 10.1111/jch.13124