The therapeutic role of exercise training in vascular diseases

Lanzi Stefano, Pedrazzoli Kaliska, Mazzolai Lucia
Division of Angiology, Heart and Vessel Department, Lausanne University Hospital, UNIL, Switzerland

Abstract

It is well known that regular exercise training reduces the risk of developing cardio-vascular diseases. Therefore, along with cardiovascular risk factor management and pharmacological treatment, exercise training is considered a cornerstone of therapeutic care in patients with cardio-vascular diseases. The role of supervised exercise training in improving walking performance and quality of life in patients with symptomatic chronic peripheral artery disease is well documented. On the other hand, the therapeutic role of exercise training in the management of patients with venous, lymphatic, or rare vascular diseases is still poorly investigated. Recent evidence highlighted the potential role of exercise training in improving general mobility and quality of life in patients with venous, lymphatic, or rare vascular diseases. This suggests that exercise training should be part of the overall management of patients with vascular disease. However, more research is needed to provide more solid evidence and to standardize practice.  

Résumé

Il est bien connu que l’exercice physique régulier réduit le risque de développer des maladies cardiovasculaires. Avec un strict contrôle des facteurs de risque cardiovasculaire, l’exercice physique est considéré comme un élément capital de la prise en charge thérapeutique des patient.e.s atteints de maladies cardio-vasculaires. Chez les patient.e.s avec une maladie artérielle périphérique chronique des membres inférieurs, il est bien documenté que les programmes d’entraînement supervisés améliorent les capacités de marche et la qualité de vie. En revanche, le rôle thérapeutique de l’exercice physique dans la prise en charge des patient.e.s avec des maladies veineuses, lymphatiques ou des maladies vasculaires rares reste encore peu étudié. Des données récentes ont mis en évidence le rôle potentiel de l’exercice physique dans l’amélioration de la mobilité générale et de la qualité de vie des patient.e.s avec des maladies veineuses, lymphatiques ou des maladies vasculaires rares. Cela suggère que l’exercice physique devrait faire partie de la prise en charge globale des patient.e.s avec des maladies vasculaires. Cependant, des investigations supplémentaires sont nécessaires pour fournir des évidences plus solides et pour standardiser la pratique.

Introduction

Cardio-vascular (CV) diseases (CVDs) include conditions affecting the heart and vessels. CVDs are the leading cause of death globally and therefore, management of CVDs is of major public health interest. Controlling CV risk factors is recommended including pharmacological treatment, lifestyle changes, and increasing regular physical activity.
In this article, we will focus on the therapeutic role of exercise training in the management of arterial, venous, and lymphatic vessel diseases. The role of exercise in rare vascular diseases will also be discussed.

Exercise training for patients with lower extremity ­peripheral artery disease 

Lower extremity peripheral artery disease (PAD) is a chronic atherosclerotic vascular disease characterized by a narrowing or occlusion of one or more arteries in the lower limbs [1,2]. The hallmark symptom of PAD is intermittent claudication (IC), defined as a discomfort, fatigue or cramping appearing in the lower limbs (calf, buttock, thigh or foot) during exercise and forcing the patient to stop [1,2]. IC symptoms are usually relieved within 5-10 min of rest. It has been well shown that patients with PAD have decreased walking abilities [3], impaired muscle strength and muscle power [4], gait abnormalities [5], and balance impairments [6]. As a consequence, patients with PAD show decreased functional performance (defined as the ability to perform daily life tasks) and quality of life [7,8].
Along with CV risk factor control and pharmacological treatment, supervised exercise training (SET) is the first-line therapeutic option in patients with symptomatic PAD [1,3,9]. The goal of SET is to improve walking performance, physical function, and quality of life. It has been shown that SET programs significantly improve treadmill pain-free and maximal walking distance in patients with symptomatic PAD [10]. The improved walking performance following SET are similar to those observed after endovascular revascularization [11]. SET programs also improve functional walking performance (assessed by a six-minute walking test) and quality of life (assessed by dedicated questionnaires) [3,12]. It is interesting to note that improvements in six-minute walking distance following SET are predictive of improvements in quality of life in patients with PAD [13]. Finally, SET programs also showed gait pattern changes during treadmill and overground walking in these patients [14,15]. Notably, the changes in gait pattern are significantly related to changes in walking distance [14,15]. 
Walking is the most common training mode in patients with PAD. However, some patients are unwilling/unable to perform walking sessions, especially because of high pain levels leading to short walking bouts and long resting periods during. In those cases, alternative training modalities should be proposed with regard to maximizing the dose of exercise accumulated during the training sessions [16]. The effectiveness of other training modalities (such as resistance training, cycling, arm-cranking) in improving walking performance has been recently observed in patients with PAD [17]. For optimal results, exercise training program duration should be at least three months, with at least three exercise sessions per week, with a duration between 30 to 60 min [3,9,12].
Although international guidelines clearly recommend exercise training among first line treating modality in symptomatic chronic PAD, SET programs remain underused and their availability and adherence is low [18-20]. It has recently been shown that SET programs exist only in 59% of the European countries and that costs of SET are covered by the health insurance only in 41% of the European countries [21]. In this context, home-based programs with remote observation (logbook, phone call, activity trackers) may be an effective alternative, especially if delivered in a structured manner and considering the FITT (Frequency, Intensity, Time, Type) principles of exercise training prescription [22].
Although the therapeutic role of exercise training in the management of PAD has been widely investigated for several decades, the recommendations for other vascular diseases are currently less well established.

Exercise training in patients with rare vascular diseases

Among rare vascular diseases the most frequently observed ones are: connective tissue disorders such as vascular Ehlers-Danlos syndrome, Marfan syndrome and Marfan-like syndromes; Buerger’s disease, primary lymphedema, autoimmune vasculitis, and some vascular malformations. The therapeutic management in these situations is multimodal and complex due to the generally multisystemic involvement. In addition to condition-specific drug or surgical treatments, the therapeutic management generally includes blood pressure control and early detection of vascular damage.
As for the general population, exercise training in patients with rare vascular disease is a key component to maintain physical and psychological well-being. However, particular attention should be given to some specific exercise training parameters, such as the modality and the intensity of exercise [23,24]. In patients with rare vascular diseases the risks of inadequate exercise training monitoring are vascular injuries such as dissections or ruptures. For these reasons, patients with some specific rare vascular diseases (such as connective tissue disorders) should not engage in high-intensity exercise activities or resistance training (especially if performed under isometric conditions), high-contact and competitive activities. Because of these cautionary recommendations, exercise training prescription for these patients is very difficult, especially in the absence of clearly established protocols [23,24]. 
However, the sedentary lifestyle and consequent physical inactivity usually observed in these patients increases the risk of further vascular complications, including the risk of developing/increasing hypertension, which may contribute to the increased risk of vascular lesions. Therefore, the sedentary lifestyle is one of the cardiovascular risk factors that must be actively addressed in patients with rare vascular diseases. The few studies (mostly performed on animals) on exercise and Marfan have recently shown the potential benefits of exercise training on cardiorespiratory and muscular capacity [23]. A recent study showed beneficial effects of low-to-moderate intensity (55-65% of the maximal oxygen uptake) exercise training on aortic wall structure and function, but also showed deleterious effects when exercise training was conducted at high intensity (75-85% of the maximal oxygen uptake) [25]. In the only study conducted in humans, the exercise training protocol consisted in a combination of daily 30-min ergometer training, gymnastics for 60 min four times per week, fitness training during 60 min three times per week, and Nordic walking 30 min three times per week [26]. In addition, patients were asked to participate twice weekly in a psychological group therapy and muscle relaxation [26]. The training duration was three weeks. The authors observed significant improvements in the exercise capacity assessed by the increased maximum power developed on an ergometer and increased walking performance [26]. Significant improvements in psychological wellbeing (assessed by questionnaires) were also observed [26]. Notably, these improvements persisted through one-year follow-up [26].

To date, exercise training modalities performed at low-to-moderate exercise intensity, such as walking, hiking, swimming or cycling should be recommended in patients with rare vascular diseases. A personalized approach should also be recommended for these patients. 

Exercise training in patients with venous diseases

The most common diseases affecting venous system are the venous insufficiency and venous thromboembolic diseases [27,28].
Venous insufficiency results in peripheral venous stasis and hyperpressure that causes trophic changes in the muscles, subcutaneous tissues, and skin, through a chronic inflammatory process. This has a considerable impact on functional capacities and quality of life. The spectrum of clinical manifestations is wide: heaviness, pain, cramps, stasis dermatitis and eczema, tissue atrophy and skin ulceration [27,28]. Elastic compression and classic lifestyle measures, including regular exercise training, are the most common conservative treatments for the management of venous insufficiency [27,28]. Drug or interventional treatments are also considered depending on the stage of the disease [27,28]. A 6-week exercise training program combined with compression therapy has been shown to be more effective in improving quality of life, muscular strength, pain perception and functional ability than compression therapy alone [29]. The exercise training program comprised twice weekly aerobic exercise with cycle ergometer followed by calf muscles strengthening and stretching exercises [29]. 
For venous thromboembolic disease, short- and medium-term complications include extension of thrombosis, pulmonary embolism and recurrence of thrombosis [27,28]. The most common long-term complication is post-thrombotic syndrome, defined as the appearance of chronic venous symptoms and/or signs secondary to thrombosis. Current evidence indicates that regular exercise training is not contraindicated in the management of acute thromboembolic disease. On the contrary, it has previously been shown that early walking was associated with reduced incidence and severity of post-thrombotic syndrome [30]. Also, treadmill exercise did not worsen venous symptoms (heaviness and swelling) and improved calf flexibility in patients with post-thrombotic syndrome [31]. In addition, it has been shown that a 6-month supervised training program significantly improved quality of life (assessed by the Venous Insufficiency Epidemiological and Economic Study Quality of Life questionnaire) and reduced (although not significantly) the severity of post-thrombotic syndrome (assessed by the Villalta scale) compared to standard of care [32]. Moreover, the physical component summary score of the SF-36 questionnaire, leg strength and quadriceps flexibility were significantly improved following the training program [32]. In that study [32] the supervised training program consisted of a combination of strengthening, stretching, and aerobic ­exercises. 
Taken together, these data indicate that early mobilization (endurance activities and lower limb strengthening) after an acute event should be considered in these patients.  

Exercise training in patients with lipedema

Lipedema is a chronic, progressive and under-diagnosed disease characterized by an abnormal distribution of adipose tissue resulting in a disproportionate increase in volume in both lower and upper limbs [33]. Lipedema mainly affects women [33]. Although the physiopathological mechanisms are not yet fully elucidated, studies suggest the involvement of a polygenic susceptibility associated with hormonal, microvascular and lymphatic disorders [33]. Lipedema is associated with chronic pain, functional limitation and psychosocial distress [33]. Body fat excess may also have a huge impact on walking pattern. The gait abnormalities and knee pain usually reported by these patients drastically reduce the desire and the ability to move and perform daily life tasks. This may lead to an increased sedentary behavior and/or physical inactivity and an associated risk of obesity. In the absence of etiological treatment, the current management of lipedema aims to reduce symptoms, improve functional limitations, and prevent disease progression. Therefore, a multidisciplinary approach is needed including patient education, weight control, exercise training, lymphatic drainage, elastic compression, psychological support and, in selected cases, surgical management [33].
Aquatic exercise interventions seem to be effective because of a draining effect induced by the water pressure and an unloading of the joints avoiding further orthopaedic complications. It is recommended that elastic compression should always be worn during and after exercise training sessions for activities such as walking or resistance training. Although rehabilitation programs are under-investigated in these patients, a recent study showed that a 6-week (nine training sessions) rehabilitation program combining manual therapy, tailored exercise guidance, education and compression improved lower limb pain perception and quality of life in patients with early stage lipedema [34]. 

Exercise training in patients with lymphatic diseases

Lymphedema is a vascular disease characterized by an accumulation of fluid in the subcutaneous soft tissues secondary to dysfunction of the lymphatic system [35,36]. The primary lymphoedema occurs as a result of a congenital malformation of the lymphatic vessels [35]. The secondary lymphoedema occurs as a result of damage or obstruction of the lymphatic vessels caused by venous stasis, surgery, trauma or infection. Lymphedema mainly affects the upper and lower limbs and one of the most frequent complication is infection. This may lead to heaviness and pain in the limbs and have a negative impact on daily life functional performance and quality of life. The current treatment of lymphedema consists of monitoring oedema to prevent infection and hypomobility through manual lymphatic drainage, elastic compression and exercise training. In selected cases, surgical management may also be considered.
Although the role of exercise training in patients with lymphoedema has been poorly investigated, recent evidence suggests that exercise training appears to be safe and effective in controlling oedema and disease-related symptoms. A recent review of the literature has shown the potential relevance of aquatic exercise interventions [37]. This training modality has been shown to improve general mobility, quality of life and pain perception in these patients [37]. In addition, some studies reported a reduction in limb volume, especially in the short term period [37]. Notably, a high degree of adherence is usually observed during water-based treatment [37]. However, the role of exercise training in the therapeutic care of patients with lymphedema remains to be confirmed by future investigations. Indeed, the existing protocols are very heterogeneous and usually combine lymphatic drainage, elastic compression, and aquatic exercise interventions [37].

Conclusions

Exercise training is effective in improving general mobility and quality of life and should therefore be part of the overall management of patients with vascular disease.

Declaration of conflicting interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding 

The authors received no financial support for the research, authorship, and/or publication of this article.

Corresponding author

Stefano Lanzi, PhD
Division of Angiology, Heart and Vessel Department
Lausanne University Hospital (CHUV)
Ch. de Mont-Paisible 18, 1011 Lausanne, Switzerland
Tél. +41 079 556 49 11, stefano.lanzi@chuv.ch
https://orcid.org/0000-0003-1089-6309
@ste_lanzi 

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