Heat Therapy as a Viable Treatment for Peripheral Artery Disease: A Mini Review Free

Peripheral artery disease (PAD) is an atherosclerotic disease predominantly in the peripheral lower extremities. PAD prevalence has significantly increased worldwide and is projected to become an even greater global burden [1, 2]. PAD is a multifactorial disease that originates from various causes such as hypertension, obesity, and aging which contribute to the development of plaque in the conduit arteries in the lower limbs [3, 4]. The accumulation of plaque buildup in the arteries results in arterial stiffness, restricted blood flow, and impaired oxygen delivery, thereby attenuating skeletal muscle function in the lower limbs [5, 6]. Moreover, severe PAD has commonly shown critical limb ischemia and has the potential to block arteries across the body, leading to stroke and myocardial infarction [7‒9]. Although the specific pathophysiological mechanisms of PAD have not been shown yet, targeting skeletal muscle mitochondrial and microcirculatory dysfunction has been suggested as an effective strategy to treat symptoms of PAD [10‒13]. These were further supported by recent studies which reported that mitochondrial-targeted antioxidant therapy improves mitochondrial function and exercise tolerance in the patients with PAD [14‒17]. In order to improve skeletal muscle mitochondrial function, peripheral vascular function, and walking performance, supervised exercise/walking has been used as the first-line treatment for PAD. In vitro studies suggested that supervised exercise/walking may improve endothelial function [18] and mitochondrial respiratory capacity in patients with PAD [19]. Additionally, supervised exercise/walking training has shown improvement in walking performance and quality of life compared to pharmacological and surgical treatment in patients with Fontaine stage II [20‒22].

Although supervised exercise/walking therapies showed beneficial clinical outcomes, the adherence rate of supervised exercise/walking is relatively low due to the leg pain (claudication), cramps, fatigue, and pain during walking which is the most common symptom of PAD and acts as a major barrier for participating in exercise-based therapies [23, 24]. The intermittent claudication is associated with exercise-induced ischemia and is attributed to inflammation and oxidative stress in the leg muscles [25, 26]. Additionally, weight-bearing during walking in the lower limbs has been considered a potential contributor to exercise-induced skeletal muscle ischemia [27]. As a result, the fear of leg pain discourages participation in exercise therapy, inducing deviation from the treatment and poor quality of life [28]. To address this challenge, alternative therapies have been suggested and, interestingly, heat therapy has shown promising results. Recent studies examined the applicability of heat therapy for PAD and reported clinically meaningful outcomes such as delaying ulcers in early-stage PAD [29]. Interestingly, Akerman and colleagues reported that heat therapy could stimulate not only higher adherence rates but also similar functional and cardiovascular improvements to supervised exercise therapies [30]. Likewise, Park and colleagues’ previous study showed that conducting heated water-based walking exercise in PAD was able to significantly improve the cardiovascular function, physical function, and adherence rates, compared to traditional exercise therapy [31, 32].

Although the effects of heat therapy on vascular function, pain, and physical function seem promising, the mechanisms of heat therapy have not yet been well documented (Fig. 1). Considering that patients with PAD are commonly accompanied by diverse comorbidities [33], it is imperative to conduct mechanistic studies of heat therapies in patients with PAD. Furthermore, current and previous heat therapies have utilized inconsistent forms of experimental protocols such as varied temperatures, durations, and heat application locations. Therefore, it will be imperative to document and optimize a standardized protocol for heat therapy with greater mechanistic knowledge, specifically considering thermal conductivity, safety, obesity, age, and dehydration. Thus, the aim of this review was to identify and compare numerous consequences of interventions for PAD treatment, focusing on heat, to document both experimental and clinical considerations, and also to develop optimal protocols for heat therapies in patients with PAD.

This mini review was conducted to summarize the effects of heat therapy in patients with PAD. Studies included in this review were identified through comprehensive searches in PubMed, Scopus, and Web of Science databases. The search strategy included keywords such as “heat therapy,” “peripheral artery disease,” “vascular function,” and “exercise therapy.” We included studies that (1) evaluated passive or active heat therapy as an intervention for PAD, (2) included outcome measures related to vascular function, pain relief, or walking performance, and (3) were published in peer-reviewed journals. Studies specifically targeting patients with intermittent claudication, primarily classified as Fontaine stage II or III, were included. No restrictions were placed on the type, application method, frequency, or duration of heat therapy. Although this is not a systemic review, effort was made to incorporate the most relevant on this topic.

Recently, heat therapy has emerged as a potential therapeutic intervention for PAD symptoms, particularly in patients who struggle with the physical demands and pain associated with traditional exercise/walking therapies (Table 1). Interestingly, most research using heat therapy on patients with PAD has shown improved symptoms including walking capacity and vascular health. Passive heat therapy, only heat application, has been reported to provide similar enhancements in vascular function and health outcomes compared to traditional exercise/walking therapies [30]. Active heat therapy, heat with walking exercise, has revealed even greater improvements in walking capacity and cardiovascular health than traditional exercise/walking therapy [32]. Both passive and active heat therapies have demonstrated higher adherence rates than traditional exercise/walking therapy, showing promise to address the limitation of traditional therapies [30, 32]. Although recently the heat therapy as a therapeutic strategy for PAD has been noticeably studied, there are still numerous components such as forms, a wide range of applied temperatures, and multiple combinations should be studied to provide a general guideline. This lack of standardization makes it challenging to comprehensively interpret the benefits of heat therapy. Therefore, it is important to explore and consider specific factors that influence the effectiveness and safety of these interventions.

Common passive heat therapy such as far-infrared-ray sauna therapy, known as Waon therapy, utilized a wide wave spectrum of electromagnetic frequencies (3–25 μm) for PAD treatment [34]. This spectrum allows for deeper tissue penetration, reaching muscles and even the blood vessels in the deeper layers, making it suitable for treating PAD symptoms. These passive heat therapies utilizing a wide wave consists of dry sauna for 15 min at 45–60°C without hydration pressure, followed by supine rest with blankets for an additional 30 min. These therapies recommended to undergo 5 days per week for 10 weeks. Waon therapy has shown favorable effects across various PAD classifications (from Fontaine II to Fontaine IV). Treatment at 60°C significantly improved pain score, walking distance, ankle-brachial index, blood flow in patients with intermittent claudication and pain at rest, and even facilitated the healing of toe ulcers [34]. Treatment at 45°C also was effective in healing digital ulcer [53]. However, the heat therapies using a wide wave reported some mild adverse effects, such as leg pain during sauna sessions [35], along with mild claustrophobia and bronchitis, which led to dropouts in some cases [54]. Another passive heat therapy option is short-wave or microwave diathermy, which penetrates deep tissues. This therapy produces heat and is primarily used for topical application. The therapy typically requires 2 to 3 times per week at 37–43°C. The effectiveness of diathermy remains debated. Some studies indicated that it can immediately and chronically improve pulsation in patients with arterial disturbances in the lower extremities [36], while others suggested that it does not reduce blood flow velocity in patients with PAD compared to active exercise or shock wave therapy, which stimulates blood flow supply by causing a small amount of inflammation rather than generating heat [37]. Additionally, diathermy carries a higher risk of burn injuries due to direct heating of deep tissue [55], and precautions should be taken to remove any metallic materials near the treatment area [56]. Finally, therapeutic ultrasound, which uses acoustic waves, has promoted angiogenesis in clinically relevant animal models, including type 2 diabetic mice, hypertensive rats with PAD, and rats with hindlimb ischemia [57‒59]. A clinical study involving 30-min sessions, 3 days per week for 6 weeks at 250 kHz, showed increased walking performance in patients with PAD, but ankle-brachial index did not significantly increase [38].

Passive heat therapy using thermal garments (90 min per session, more than 3 times per week for at least 6 weeks at 41–48°C) reported a significant improvement in vascular function in patients with PAD. Neff and colleagues found that a single bout of passive heat therapy with thermal garment could lower serum endothelin-1 concentration and blood pressure while increasing blood flow in patients with PAD [39]. Similarly, Monroe and colleagues, using the same protocol, found improvements in endothelin-1 and blood pressure, along with extended peak walking tolerance, but muscle oxygenation and onset time of claudication showed no improvement compared to the sham treatment group [41]. These findings are consistent with their other studies which induced chronic heat application with thermal garment for 6 weeks, and they found a decrease in endothelin-1 and improved perceived physical function without improvement in walking performance [40]. Although the practicality of thermal garments have been demonstrated by showing higher adherence rates [40, 42, 43], the inconsistent findings regarding its effects on walking capacity and hemodynamic responses [39‒43] warrant further investigation.

Passive heat therapy with water immersion involving sessions at the water temperature of 39–42°C for 30–45 min, and the therapy has shown both acute and chronic benefits for patients with PAD. Thomas and colleagues reported that waist-level water immersion at 42°C for 30 min significantly improved blood flow in the lower limbs [44]. Similarly, Pellinger and colleagues observed increases blood flow in the lower limbs and walking distance with shallow water immersions (40 cm depth) for a shorter duration of 15 min at 42°C as well as for 45 min duration [45]. Furthermore, applying waist-level water immersion at 40.5°C for 60 min over 36 sessions across 8 weeks to sedentary individuals who are at potential risk for PAD [60] showed an enhanced nitric oxide dependent vasodilatory function in forearm and arterial compliance in lower limbs, and reduced pulse wave velocity [61, 62]. In addition, passive heat therapy with warm/hot water immersion showed better thermal comfort compared to heated air-based therapy. For example, heated air-based therapy, such as the Finnish sauna [63], has been conducted in patients with other cardiovascular diseases like hypertension and heart failure and healthy individuals, but not yet in patients with PAD. Despite similar increases in plasma anti-inflammatory cytokine levels at matched core temperatures, forced air heating caused higher thermal discomfort than warm/hot water immersion [64]. Despite greater than 90% of adherence, completion and positive consequences associated with passive heat therapy with water immersion [44], multiple variation in protocols, and the limited number of studies makes it challenging to comprehensively interpret the results.

The Bohr effect is a phenomenon that describes how hemoglobin’s affinity for oxygen is reduced in the presence of increased carbon dioxide, CO₂, facilitating the release of oxygen (O₂) to tissues and increase O₂ perfusion and tissue oxygenation. In CO₂ bathing, this effect is induced artificially, with optimal bath conditions maintained at an approximately 1,000 ppm CO₂ concentration and temperatures of 34–41°C for 10–20 min per session. These baths are usually administered more than 5 times a week for at least 4 weeks. At higher temperatures, the binding affinity of oxygen to hemoglobin further decreases, shifting the oxygen dissociation curve to the right. Given these characteristics, CO₂ baths are often combined with thermal gas or water therapy to enhance therapeutic effects. Like other heat therapies, both acute and chronic improvement in pain relief and vascular function were induced by CO₂ bath. Acute CO₂ bath with thermal gas and water were effective in local vasomotor function and oxygen availability in the muscle tissues in patients with Fontaine stage II PAD [46, 47], repeated CO₂ baths alleviated pain and plasma free radical, and elevated blood flow and antioxidant levels by increased oxygenation in patients with stage II of PAD [48, 49]. Increased frequency, duration, and temperature of CO₂ baths even protected ulcer or gangrene limbs from amputation in patients with stage IV of PAD via raise of blood flow in the peripheral tissues in the limbs [50]. Interestingly, an animal study suggested that there is a CO₂ bath temperature dependent positive effects appeared in the rats with hindlimb ischemia [65]. For example, CO₂ baths with 34°C caused higher blood flow in ischemic limbs compared to 41°C, but CO₂ bath with 41°C resulted in higher vascular density compared to 34°C. Despite the promising results, there was no available report/data on adherence rates in patients with PAD, making it unclear whether it has the potential to overcome the limitation of traditional exercise/walking therapies.

Aquatic exercise in the heated water, allows patients with PAD to benefit from both the effects of heat therapy and exercise. The buoyancy provided by water reduces weight-bearing stress, enabling patients with PAD to participate without the fear or burden of pain. At the same time, the water-induced drag imposes the intensity of movement. The combination of internal heat generated by exercise and external heat from the heated water may induce potential synergistic effects in mitigating PAD symptoms. Indeed, previous studies investigated aquatic exercise in patients with PAD and have reported positive health outcomes. Aquatic exercise in the heated water typically involves waist-to-chest depth immersion at 28–39°C for 30 min, 3 times per week for 12 weeks [31, 32, 51]. These active therapies have been shown to lower arterial stiffness and ameliorate cardiorespiratory fitness, exercise tolerance, and physical function [32, 51]. Aquatic exercise has also demonstrated a greater efficacy in improving cardiovascular and physical functions compared to supervised exercise/walking therapies [32]. Even when conducted in shallower water (50–60 cm depth), aquatic exercise resulted in better walking capability and vascular reactivity compared to supervised exercise/walking therapies [52]. Additionally, studies have generally reported positive adherence rates except for one study. Al-Jazzar and colleagues observed low adherence to aquatic exercise, with only 7 out of 20 patients completing the entire program. They speculated that it might be due to inconveniences such as the need to change into specialized equipment and the distance of the facility [51]. Their protocol included supplemental devices like hydro-tone boots and water cycling, which may have contributed to the discomfort. In contrast, Quarto and colleagues reported that aquatic exercise in the heated water was safe and well tolerated by patients with PAD, though they did not provide specific adherence data [52]. Additionally, Park and colleagues’ previous studies identified high adherence to aquatic exercise in the heated water, which were higher than those of supervised exercise/walking therapies [31, 32]. These studies suggest that heat therapy with aquatic exercise can overperform traditional exercise/walking therapy in terms of effectiveness and adherence, along with the relatively identical protocol. However, further research is needed due to the limited number of accessible studies.

Several active heat therapies have recently been explored for cardiovascular benefits, though not specifically targeted toward patients with PAD. These therapies were often integrated with pre-, during-, and post-exercise interventions. For instance, Akerman and colleagues used 30-min sessions with immersion up to the xiphoid process and shoulders in 39°C water, followed by 15–30 min of warm clothing and calisthenic exercises. The results showed significant improvements in cardiovascular health and walking distance after 12 weeks of heated water therapy in patients with PAD. Additionally, this study reported that the heated water therapy showed relatively higher adherence rates compared to other types of heat therapies [30].

Yoga with heat application, commonly known as hot yoga, has been shown to improve endothelial function, arterial stiffness, cholesterol levels, blood pressure, and overall physical functional capacity in healthy adults across various age groups [66, 67]. Hot yoga in healthy young adults induced cellular and neural adaptations, such as increased expression of heat shock protein 70 in peripheral blood mononuclear cells and serum brain-derived neurotrophic factor [68]. It has also demonstrated beneficial effects in overweight and obese individuals. For instance, Guo and colleagues reported improvements in lipid profiles, body fat percentage, and blood pressure among overweight women [69]. Additionally, insulin resistance and arterial stiffness improvements were observed in older obese adults and young overweight adults, respectively [70]. Similarly, aerobic exercise with sauna suit has showed improvement in cardiorespiratory fitness and cardiometabolic risk factors in physically active young to middle-aged adults [71]. Endurance exercise with sauna bathing showed significant improvement in blood pressure compared to an acute strength exercise with sauna bathing and sauna alone in healthy and prehypertensive men [72]. Moreover, 8 weeks of cycling exercise with sauna bathing provided supplemental benefits for cardiorespiratory fitness, systolic blood pressure, and total cholesterol levels compared to cycling exercise alone in middle-aged adults with sedentary lifestyles [73].

Passive heat therapy with thermal garments has been shown to effectively reduce arterial stiffness; however, aerobic exercise performed in a hot environment has been found to increase arterial stiffness in middle-aged adults [74]. Furthermore, even short-term exercise in hot environments significantly increased heat loss capacity and produced heat stress [75, 76]. Therefore, the application of the heat therapy should take into account environmental factors such as humidity and temperature.

No matter how effective therapies are, participation is the most critical in determining the degree of effects. Adherence rates depend on various factors such as the appeal and accessibility of the protocols. Passive heat therapies generally have higher adherence rates (Table 1) and might be due to their less physically demanding nature. For instance, wave frequency, thermal garments, and water immersion therapy have shown adherence rates above 90%. In contrast, active therapies, such as aquatic exercise, may have lower adherence due to the effort required. However, adherence rates were available in only few studies of heat therapy. In order to conclude whether heat therapy is optimal therapy to overcome the limitation of traditional therapies, further investigation is needed on adherence rates.

In other disease conditions, heat therapy exerts its therapeutic effects through multiple physiological mechanisms. First, it enhances endothelial function by increasing nitric oxide bioavailability, leading to improved vasodilation and perfusion in ischemic tissues [61, 77, 78]. Second, heat exposure upregulates heat shock protein and heat shock factor 1, which protect against oxidative stress [79, 80] and inflammation-induced endothelial dysfunction [81]. Additionally, repeated heat exposure has been shown to modulate pro-inflammatory cytokines such as tumor necrosis factor-a while increasing anti-inflammatory mediators [82, 83], thereby modulating the chronic inflammatory state observed in patients with PAD. Furthermore, heat therapy can enhance mitochondrial biogenesis [84] and oxidative capacity in skeletal muscle [85, 86], which may contribute to improved walking endurance and physical function in patients with PAD. These mechanisms collectively support the potential of heat therapy as an alternative or complementary treatment for PAD (Fig. 1).

In order to overcome the limitations of traditional walking therapies, various alternative trials have been examined to increase exercise compliance. Although both passive and active heat therapies reported significant health benefits to patients with PAD, there are a number of factors to consider for the heat applications. First, aging is positively correlated with the prevalence of PAD [87]. Aging can cause abnormal thermal sensitivity [88], which may suppress the effects of heat therapy in patients with PAD. During local heating, endothelial nitric oxide synthase (eNOS) was blunted in middle-aged and elderly individuals [89, 90]. Second, obesity has known to be associated with a higher prevalence of PAD [1]. Likewise, obesity can induce an abnormal thermal threshold [91], and Stephens and colleagues previously demonstrated that thermal responses to hot water immersion varied and dependent upon body composition such as body fat mass and fat percentage [92]. Consequently, aging and obesity-induced dysfunction of thermal sensitivity may require higher and longer heat application to achieve beneficial effects in patients with PAD [93, 94]. However, patients with PAD are more susceptible to burns or other skin problems, due to age-mediated hair loss and skin atrophy [95]. Indeed, some studies reported non-perceived skin or tissue injury can occur and the skin irritation/injury can be a cause of dropout during heat therapy [40, 42]. Therefore, it is imperative to find a proper heat temperature ranges to maximize the health benefits in patients with PAD.

Additionally, perspiration is also a crucial consideration when applying heat therapy to patients with PAD. Heat exposure naturally increases sweat production as the body attempts to regulate its temperature, and even local heat application can increase skin temperature and accentuate sweating [96]. Likewise, patients with PAD may have attenuated function of perspiration due to the attenuated blood flow to the peripheral extremities which impairs normal sweating and further increasing the risk of overheating with significant fluid loss, resulting in dehydration in patients with PAD. Lowe and colleagues suggested that dehydration can increase blood viscosity, thereby placing additional stress on the cardiovascular system and exacerbating PAD symptoms such as pain and cramping [97]. Moreover, the rise in blood viscosity heightens the risk of coagulation, particularly in patients with PAD who are already susceptible to blood clot formation due to impaired circulation [97]. This combination of dehydration and increased coagulation risks require careful monitoring and management during heat therapy to avoid potential complications. Therefore, proper hydration and careful adjustment of heat therapy protocols are essential to manage these risks effectively.

Heat therapy presents a compelling alternative to traditional exercise/walking therapies for the treatment of PAD. The higher adherence rates and promising clinical outcomes make it an attractive option, particularly for patients who struggle with the physical demands of exercise due to pain or other limitations. However, the lack of standardized protocols and mechanistic understanding of its benefits highlight the need for further research. Studies should focus on optimizing heat therapy protocols, considering variables such as temperature, duration, and patient characteristics like age and obesity. By addressing these gaps, heat therapy could become a key treatment strategy in improving vascular function, reducing pain, and enhancing overall quality of life for patient with PAD.

No conflicts of interest, financial or otherwise, are declared by the authors.

This article was supported by the Dong-A University research fund, and University of Nebraska at Omaha.

M.-H.J.: writing – review and editing, writing – original draft, visualization, methodology, and conceptualization. S.-Y.P.: writing – review and editing, writing – original draft, supervision, project administration, and conceptualization. S.D.K.: writing – review and editing and visualization. S.H.L.: writing – review and editing, supervision, project administration, and conceptualization.

Min-Hyeok Jang and Song-Young Park contributed equally to this work.