Weight management in PAD can be divided into several interrelated areas. For patients with intermittent claudication and obesity, the first consideration (and sometimes the sole expectation) is to prevent further weight gain. Maintenance of a stable body weight in an obese patient with claudication represents an effort to effect a positive change; the behavior is a “discouragement of weight gain” and is evidence of the patient’s willingness to modify his or her lifestyle. Reducing the onset of claudication distance resultant from further weight gain is another measure of success.
Most patients with peripheral arterial disease (PAD) have flow-limiting atherosclerosis in the aortoiliac or femoral arteries. A common comorbidity in these patients is obesity. When treating patients with aortoiliac-femoral PAD and obesity, the clinician’s primary objective is to encourage weight reduction. Although this would seem to be straightforward, weight management in PAD with obesity is challenging. This review will address the specific issues surrounding weight management in PAD and identify the obstacles that must be overcome to be successful.
Causes and Risk Factors
The most commonly suggested underlying mechanisms may be the atherosclerotic effects of several metabolic, inflammatory, and hormonal disorders which are associated with obesity and damage the arterial walls. This area is particularly important because if specific pathways can be identified which lead to atherosclerosis in obese individuals, this may provide future therapeutic targets to prevent and treat PAD.
Several possible mechanisms have been suggested to explain the obesity-PAD relationship. Ambulatory venous hypertension, which occurs as a result of obese individuals spending long periods sitting down, is considered to lead to muscle pump impairment, decreased circulation in the microvasculature, and ultimately result in structural and functional changes in the arteries in the lower limbs. High blood pressure and increased arterial pulse pressure are more common in obese individuals, and these too are thought to cause structural arterial changes in the peripheral vasculature.
Obesity is a systemic disorder often associated with diabetes, hypertension, and hyperlipidemia, all of which are well-known risk factors for PAD. However, even after these comorbid conditions are accounted for, obesity still seems to be an independent risk factor for the development and progression of PAD. This therefore indicates that there may be an aspect of PAD pathogenesis susceptibility related to the obese state which is not yet understood.
Obesity is one of the most prevalent causes of PAD and has been shown to be an independent risk factor for this disease, even after other cardiovascular diseases and risk factors, such as diabetes or hypertension, have been controlled. Epidemiological studies have shown an increased factor of 2 to 4 in obese individuals to develop clinically apparent PAD and a higher degree of atherosclerosis using non-invasive testing compared with non-obese individuals.
Obesity and its Impact on Arterial Health
Obesity has been recognized as a significant health hazard and a major independent risk factor for the onset of PAD. The Framingham Heart Study reported the development of intermittent claudication in 5,209 men and 6,073 women between 1952 and 1974. It was found that obesity was a strong predictor of intermittent claudication. The relative risk of intermittent claudication was 2.04 in men with a weight of 120-129% of the desirable weight and 3.65 in men with a weight greater than 130% of the desirable weight. Similarly, women had a relative risk of 2.28 for a weight of 120-129% of desirable weight and 3.98 for weights greater than 130% of desirable weight. The Physicians’ Health Study prospectively analyzed 21,414 US male physicians with a mean age of 53 years over a 5-year period. Stepwise increase in BMI was positively associated with the development of symptomatic PAD. The relative risk of PAD in men who were overweight was 1.4, and in men who were obese, it was 2.53, compared to men with a normal BMI.
Multiple terms are used to describe a person who is overweight or obese. A BMI index over 30 kg/m2 is considered overweight, and an index over 25 is considered obese. The risk of obesity is assessed by waist circumference as well as the BMI. The distribution of body fat is also considered as a determinant of the health risk of body weight. Higher waist circumference has been related to higher morbidity, particularly related to cardiovascular disease and diabetes.
2.2. The Role of Sedentary Lifestyle in Peripheral Arterial Disease
Effective diagnosis of a person’s activity levels can be established using the Baecke questionnaire. This is a 16-part simple and practical self-administered questionnaire which provides information on habitual physical activity patterns in epidemiological studies. It is calculated using work index scores (8 types of jobs, range 1-5), sport index scores (score for sport activity which includes intensity, frequency, and type), leisure index scores (based on 6 types of leisure activities), total physical activity index (sum of work, sport, and leisure scores), and a physical activity index which uses work, sport, and total scores to stratify to low, moderate, and high activity levels. Step counting is also an effective method of assessing activity levels as daily step count is inversely associated with peripheral artery disease.
Sedentary lifestyle is defined as not taking part in enough daily physical activity, i.e., doing less than 30 minutes of moderate exercise on five or more days of the week. A person is also considered to have a sedentary lifestyle if they are taking enough exercise on a weekly basis, but that exercise does not counteract the effects of their occupation, which would commonly give a person a level of physical activity equivalent to sedentary. Evidence that physical inactivity is a risk factor for all-cause and cardiovascular mortality is now available from many different studies and is in line with healthy living messages.
Effects of Peripheral Arterial Disease and Obesity
Obesity has a major impact on the factors that influence the development of PAD. It has been shown to cause a prothrombotic state with increased platelet aggregation and fibrin formation. Obesity is also associated with increased levels of plasminogen activator inhibitor-1, which impairs fibrinolysis. High cholesterol levels, notably low-density lipoprotein cholesterol, are almost universal in obesity, and Type IIa and IIb hyperlipidemias are very prevalent. It is estimated that a 1% reduction in LDL cholesterol will reduce the risk of PAD by 2%. High total cholesterol and lipoprotein (a) levels are predicted to double the risk of PAD, and with the increasing prevalence of obesity, the impact on PAD incidence is likely to rise.
The term Peripheral Arterial Disease (PAD) refers to atherosclerotic occlusive disease of the lower extremities. This is a common manifestation of generalized atherosclerosis and is associated with a marked increase in cardiovascular events. Most patients with PAD do, in fact, die of cardiovascular disease (CVD), with myocardial infarction as the most common cause of death. The prevalence of PAD is increased in obesity, with activation of both the insulin and endothelin systems, leading to increased vasoconstriction and reduced blood flow to the lower limbs. Functional impairment is a frequent consequence of PAD and can result in loss of employment and premature retirement.
Cardiovascular Complications
The mechanisms by which obesity contributes to PAD are still unclear, but several physiological changes associated with obesity may be involved. Obesity causes insulin resistance, which is a major factor in the development of type II diabetes. Diabetes greatly increases the risk of developing PAD by damaging the blood vessels and nerves. High cholesterol and hypertension are also common in overweight individuals. These factors are also risk factors for PAD by causing atherosclerosis and worsening hypertension. It is likely that the cumulative effect of these risk factors on the development of PAD is greater than that of each individual risk factor. This may partially explain why a study on elderly obese women showed that they had a high prevalence of PAD even in the absence of other risk factors.
Recent investigations have shown that overweight and obese individuals are at increased risk for all forms of cardiovascular disease. The Framingham study showed that being overweight at age 40 greatly increases one’s risk of developing coronary heart disease. Obese individuals have a 70% increase, and overweight individuals have a 30% increase in developing coronary artery disease compared to those with a healthy body weight. Obesity is also a major risk factor for the development of peripheral arterial disease (PAD). A 10-year prospective cohort study of 38,000 men age 40-75 showed a strong association between increasing body weight and the development of symptomatic PAD. Compared to men with a body mass index of 21-23, those with a BMI of 24-25 had a 26% increase in risk, those with a BMI of 26-27 had a 63% increase in risk, and those with a BMI greater than 27 had an 81% increase in risk of developing PAD.
Impaired Quality of Life
Impairment in the QOL of patients with PAD occurs primarily because of the symptom of intermittent claudication. This functionally disabling symptom dramatically limits physical activity and the ability to exercise. It is established that claudicants have a lower functional capacity and increased rates of physical disability compared with those without PAD. The disease prevents many patients from being able to perform simple tasks of daily living. In more severe cases of PAD, ischemic rest pain and ulceration/gangrene of the lower extremities can lead to functional impairment and even amputation of the affected limb.
Quality of life is a broad multidimensional concept that usually includes subjective evaluations of both positive and negative aspects of life. The WHO has defined health as a state of complete physical, mental, and social well-being, and not merely the absence of disease or infirmity. This definition of health aligns with the definition of QOL. QOL is the ultimate endpoint of medical care, and in recent years it has become of increasing interest in the field of medicine. Using standardized instruments to measure one’s QOL, a strong inverse association between increasing severity of PAD and worsening QOL has been demonstrated in numerous studies.
Increased Mortality Risk
This method of assessment was performed by noting weights and changes in body weights over 26 weeks following removal of silastic implants containing testosterone or estradiol. Reduced male life span was the most sensitive endpoint. Eleven studies were performed on C57BL/6J or UM-HET3 mice. The male survival curves in control groups from all 11 studies were averaged. The resulting composite male survival curve was used as a standard against which to compare the effects of sex hormone manipulation on male survival. The effect of testosterone in males was first assessed by combining and comparing data from the 5 C57BL/6J and the 6 UM-HET3 studies. The combined male survival curve for all studies utilizing the higher dose testosterone implant was shifted to the left indicating reduced survival of testosterone treated males compared to controls (P < 0.05, Log-rank test of trend). Estimated median survival time was reduced by as much as 2.4% (P < 0.01). Testosterone treatment had similar effects in females. Data for the 5 C57BL/6J and the 6 UM-HET3 studies utilizing the higher dose testosterone implant were combined and then compared to the female control composite curve. The combined female curve was also shifted to the left, indicating reduced survival of testosterone treated females compared to controls (P < 0.05, Log-rank test of trend). Estimated median survival time was reduced by as much as 3.5%. Therefore, testosterone reduced life span in both genders and strains. Any observed effects of estradiol on survival were secondary to toxicity of the implant and not due to the hormone and are not presented here. These findings indicate that physiologic sex hormone concentrations have substantial effects on life span in mice of both genders.
Breaking the Cycle: Prevention and Treatment Strategies
Upon recognizing the strong epidemiologic association of PAD and obesity, the interdisciplinary team of the Vascular Disease Academic Award Program, consisting of experts in vascular medicine, endovascular intervention, vascular surgery, lipid research, exercise physiology, nutrition, and behavioral science, embarked on an ambitious program of scientific investigation to improve our understanding of the pathophysiology of the association and to develop effective methods of intervention. This manuscript summarizes their findings. To combat PAD in the obese patient, it is essential to break the vicious cycle of inactivity, weight gain, and progressive atherosclerosis. This requires strategies to induce and sustain weight loss while simultaneously improving functional capacity. We have found that the combination of diet and exercise produces a substantial acceleration of the expected improvement in walking performance due to medical therapy alone, which may be a powerful motivator for patients – which aids their success in long-term adherence to these lifestyle changes. Our work has potential wide significance, as nearly 75% of PAD patients are either overweight or obese. In this regard, the most effective diet and exercise recommendations for these patients are not known, yet formulating such recommendations is an essential first step towards changing behavior and reducing the large public health burden of obesity-related PAD. The following are our data-based conclusions in an attempt to provide a clearer direction for future research and public health policy.
Healthy Diet and Weight Management
Research has consistently shown that excessive weight and obesity have been associated with higher rates of PAD. In addition, those with increased body weight are more likely to experience symptoms associated with PAD. Being overweight increases the mechanical load on the lower extremity arteries and is associated with arterial disease in the legs. Numerous population-based epidemiological studies have consistently shown an association between excess weight or obesity and higher rates of symptomatic peripheral arterial disease (PAD). Compared to those at their recommended weight, the risk of experiencing symptoms due to PAD is 1.5 times higher in those who are overweight and 3 times higher in those classified as obese. The increase in risk continues as weight increases, so those who are classified as severely obese are 6 times more likely to have symptoms related to PAD. This is an important issue because the degree of the pain and limitation experienced from intermittent claudication is directly related to the patient’s functional status and their perception of quality of life.
Regular Physical Activity and Exercise
Given that PAD is underdiagnosed and undertreated, exercise programs can also be an effective non-invasive way to improve functional status for patients with atypical leg symptoms. A recent paper by Gardner et al. suggests that a home treadmill exercise program without PST supervision is also successful, with improvements in treadmill walking performance, walking distance, and quality of life, serving as a less resource-intensive alternative.
Physician-supervised exercise training (PST) has proven to be significantly effective in the diagnosis and treatment of peripheral arterial disease (PAD), improving claudication onset time and quality of life for patients. An exercise program led by a physical therapist, which includes walking exercise and lower extremity resistance training, is a class I recommendation for PAD patients with claudication. This is useful for patients at all levels of function. The therapist-led setting provides a safe environment for patients to exercise in and can provide immediate care if an adverse event occurs. Sessions lasting up to 12 weeks have produced lasting effects on walking performance and functional status.
Patients should be aware of the signs or symptoms that may delay or stop exercise, understand that it is not harmful to walk with mild or intermittent claudication, and learn to differentiate between muscle ischemia and neurogenic pain.
Changes should be made to increase usual activity levels through formal exercise or physical activity (e.g., walking, stair climbing) each week. The duration of exercise should be increased, aiming for three to five sessions of exercise per week and progressing to 45 minutes per session. A combination of moderate and supervised exercise is recommended with a goal of walking to near-maximum pain. However, current fitness levels and co-existing conditions such as claudication, fatigue, or intermittent rest pain must be taken into consideration. High-intensity exercise work may aggravate symptoms and is not recommended.
First, the benefits and risks of exercise in PAD must be explained to the patient, indicating the reasons why an increase in physical activity is necessary and the improvements that can be expected. Suggestions from the American College of Sports Medicine for action by the patient on the findings are to set specific, short-term, and long-term goals related to an increase in physical activity and to understand the risks and benefits of increased physical activity.
Regular physical activity and exercise are essential factors in promoting weight loss and improving PAD symptoms. Patients with peripheral arterial disease (PAD) may face initial challenges to their mobility, confidence, and independence. In order to prescribe an effective exercise program for PAD patients, several points need to be considered.
Medications and Medical Interventions
A supervised exercise program has been shown to be beneficial for patients with symptomatic PAD. Smoking cessation, control of diabetes and hypertension, and the initiation of a structured exercise program are ways in which patients can improve the symptoms of their PAD. In more severe cases, invasive treatment may be necessary. Angioplasty or bypass surgery may be required to revascularize an affected limb. Although this can provide significant symptom relief and improve walking distance, it is not a cure for the systemic nature of the disease and symptoms may return. These patients should pay particular attention to secondary prevention strategies.
Medications are generally the first step in medical intervention for PAD. The antiplatelet agents pentoxifylline and cilostazol have been shown to be beneficial in patients with intermittent claudication. The use of statins to control cholesterol levels has been recommended to improve lipid profiles and cardiovascular outcomes in patients with PAD. Angiotensin converting enzyme (ACE) inhibitors are helpful in controlling blood pressure and possibly reducing the cardiovascular event rate. Although these medications provide many benefits in patients with PAD, the real challenge lies in motivating patients to make long-term positive changes in their health and lifestyle. This is the most effective way to slow down the progression of PAD and improve quality of life.
Lifestyle Modifications for Long-Term Success
Management of PAD is complex and should be approached with a plan to prevent its progression. This can be best achieved through lifestyle modification and risk factor reduction aimed at reducing the atherosclerotic burden which is driving the disease. Avoiding the cardiovascular morbidity and mortality associated with symptomatic PAD is an important goal: patients with intermittent claudication have a mortality from cardiovascular events of 4% per year. This is a similar 10-year risk to that of patients with myocardial infarction but is not widely appreciated, therefore patients with PAD often do not receive aggressive intervention to reduce their cardiovascular risk. A recent study has shown that patients with symptomatic PAD and a sedentary lifestyle have a six-fold increase in cardiovascular mortality compared to patients with symptomatic PAD who habitually engage in regular exercise. Therefore, it is important to provide education for patients with PAD about their increased cardiovascular risk and to promote a healthier lifestyle as an effective strategy to improve their overall cardiovascular prognosis. Smoking cessation is the most effective and cost-effective intervention in reducing the risk of cardiovascular events in patients with symptomatic PAD. In patients with intermittent claudication, smoking cessation can lead to improvements in walking distances that are comparable to those achieved with invasive revascularization, as well as reducing the risk of lower limb amputation. Unfortunately, smoking is also the most difficult risk factor to modify, often requiring multiple attempts with both medical and psychological interventions before achieving long-term cessation. Therefore, it is important to provide continuous support for PAD patients in their efforts to quit smoking and a recent study suggests that referral to a specialized smoking cessation service can be effective in this patient group.