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Nutrition and Peripheral Arterial Disease: Dietary Approaches for Prevention

Importance of nutrition in preventing peripheral arterial disease

A hypothetical statement is presented on what might be the cause of peripheral arterial disease (PAD). There is a growing body of evidence to suggest an association between nutrition and the incidence of peripheral artery disease (PAD). McGee, Nihill, Smith, and Schlant surveyed patients undergoing cardiac catheterization and found that those with PAD were more likely to be hypercholesterolemic and hypertriglyceridemic, and this was independent of their lipid status. They found that dietary fat may be a causal risk factor in the development of PAD, and suggested that a therapeutic low-fat diet may prevent the progression of the disease. Leng and Dy also found that hypertriglyceridemia caused by a high carbohydrate and low-fat diet was associated with PAD versus hypertriglyceridemia caused by insulin resistance in non-diabetics. This is consistent with studies showing that compared to diabetics, non-diabetics with PAD have less lower extremity functional impairment and evidence of occlusive disease in angiograms. Finally, Hiatt et al found that a low ankle/brachial index, a nonspecific marker of PAD, is associated with a high dietary intake of n-6 and low intake of n-3 polyunsaturated fatty acids. Despite these findings, there are few studies to date which have specifically examined the effects of dietary interventions on the prevention of PAD. This may be because the pathobiology of PAD is multifactorial, atherosclerosis is a systemic disease, and intermittent claudication is a chronic and often subtle condition which is difficult to study. An understanding of the year-to-year incidence of PAD is also difficult because patients often use alternative ways of referring to intermittent claudication when speaking to their physician. For example, patients may refer to leg pain as tiredness or arthritic pain, thus making the diagnosis of PAD in epidemiologic studies less accurate. These factors have likely made investigators less inclined to try and prevent a disease which may be difficult to diagnose, or a condition which patients do not find bothersome enough to seek medical care. Despite these obstacles, nutrition holds potential as a simple, cost-effective, and safe technique that may prevent the development of PAD in high-risk populations such as diabetics and patients with cardiovascular disease.

Overview of peripheral arterial disease

It is important to accurately diagnose PAD in order to implement appropriate secondary prevention measures. The ankle-brachial index (ABI) is a simple, non-invasive test used to diagnose PAD. It is calculated by dividing the systolic blood pressure at the ankle by the systolic blood pressure in the arm. An ABI of less than 0.90 is indicative of PAD. According to the American College of Cardiology/American Heart Association guidelines, measurement of the ABI is a Class I recommendation for patients with exertional leg symptoms, patients over 50 with a history of smoking or diabetes, and patients with known atherosclerosis. High cardiovascular risk associated with PAD and the ABI criteria for diagnosis suggest that PAD is a manifestation of systemic atherosclerosis. This is an important concept that will be revisited when discussing the role of diet in managing PAD.

Peripheral arterial disease (PAD) is a condition characterized by atherosclerosis in the arteries supplying the lower extremities. It affects 8-12 million people in the United States and is responsible for significant morbidity resulting from functional impairment and limb loss. Intermittent claudication, commonly known as leg pain with exertion, is the classic symptom of PAD. However, up to 50% of patients with PAD are asymptomatic. Patients with PAD have a substantially increased risk of cardiovascular events and mortality. Patients with intermittent claudication have a 20% chance of having a myocardial infarction or stroke and a 30% risk of cardiovascular death over a 5-year period. Among patients with non-healing foot ulcers or amputation as a result of PAD, the cardiovascular event and mortality rates approach 70% at 5 years. Because of the high cardiovascular risk and substantial decrease in functional capacity associated with PAD, aggressive secondary prevention is paramount. Modifiable risk factors for PAD include smoking, diabetes, dyslipidemia, and hypertension.

Role of diet in managing peripheral arterial disease

Although atherosclerosis, the principal underlying process in PAD, involves systemic risk factors, there are features specific to the arteries of the legs. Dietary investigators have been interested in the possibility that nutritional factors might influence atherosclerosis at specific sites and might thereby exert site-specific effects on manifestations of PAD. In order for atherosclerosis to cause disease in the arteries of the legs, there needs to be a sufficient degree of atheroma to impair blood flow. Epidemiological studies have failed to find strong associations with specific nutrients or foods and the development of intermittent claudication but have given some pointers regarding factors influencing atheroma burden and the extent of systemic atherosclerosis. High saturated fat intake has been associated with faster progression of atherosclerosis in the aorta and legs. In a small cohort of male smokers, vitamin C and E intake was associated with less progression of atherosclerosis in the legs over a follow-up of 2-3 years. Read more about the need for a diet plan for this.

Peripheral arterial disease (PAD) is the restriction of blood vessels in the legs, usually due to furred arteries. It may also be a sign of more widespread arterial disease. The main symptoms are usually pain in the legs when walking, which stops when the person rests. Poor circulation can also lead to leg ulcers, infection, and in severe cases, gangrene. In its most severe form, critical ischaemia, there is a dramatic increase in the risk of amputation. In recent years, there has been increasing awareness of the possible involvement of nutritional factors in the development of PAD.

 Key Nutrients for Prevention

Fruit, vegetables, and their derivative products are the major sources of antioxidant nutrients in the diet. Vitamins A, C, and E are classic examples of dietary antioxidants. They are commonly found in fruits and vegetables and are widely available as supplements. Numerous studies have shown that individuals with low dietary intake or low blood levels of antioxidants have an increased risk for atherosclerosis and cardiovascular disease. All conclusive evidence suggests that an antioxidant-rich diet will help prevent atherosclerosis, thus preventing PAD. Different antioxidants have different roles and impacts on health. There is no published study specifically investigating the effect of any one antioxidant on PAD. This is an area in need of research.

Antioxidants are substances that protect against cell damage from free radicals, which are byproducts of oxygen metabolism that can damage cell structure. Any substance that prevents or repairs damage caused by free radicals is an antioxidant. Free radical damage is the initiation process of atherosclerosis. Being that atherosclerosis is the predominant cause of PAD, it is very important to fight against it. Studies suggest that antioxidants may prevent the oxidation of LDL cholesterol, which can lead to the formation of atherosclerotic plaque. Antioxidants may achieve this by preventing free radicals from damaging the arterial wall. One animal study found that antioxidant therapy inhibited the development of atherosclerosis by 40-70%. There are many varieties of antioxidants and they can be found in a large selection of plant foods.

Antioxidants and their role in preventing peripheral arterial disease

Currently, there is no research that specifically targets antioxidant vitamin supplements as a method of preventing PAD. In diabetics, however, there is an ongoing randomized control trial which will conclude next year, focusing on high-dose vitamin E supplementation and its effect on cardiovascular health, including PAD. The results of this trial will be of high interest. As it currently stands, the use of antioxidant vitamin supplements is not recommended for the prevention of cardiovascular disease as a whole. The American Heart Association has previously stated that it is not sufficient to make a distinction based on antioxidant treatments, and a guideline subsequent to this has indicated that the use of vitamin E and C supplements, and multivitamins, is not useful in preventing cardiovascular disease. Given that the evidence for PAD is weak and sporadic compared to other cardiovascular diseases, it can be surmised that antioxidants will not be used in the widespread prevention of PAD in the near future. This may change with further research showing the specific effects on PAD and a clear understanding of the mechanisms involved in oxidative stress in atherogenesis.

Various theories have developed about the role of oxidative stress in atherosclerosis. Smith and colleagues have described the oxidative modification hypothesis whereby low-density lipoprotein (LDL) is oxidatively modified by the removal of antioxidant vitamins. They state that only oxidatively damaged LDL is atherogenic and the resulting modified lipoprotein fosters atherosclerosis. The other theories state that the oxidation of LDL is an initiating factor in atherosclerosis and later oxidative stress from various sources perpetuates the state. It is clear, however, that oxidative stress is increased in the presence of cardiovascular risk factors such as hypertension. It is through these mechanisms that antioxidants may influence the development of PAD. Women with high dietary vitamin E intake had a lower prevalence of PAD in the Women’s Health Study. A diet high in vegetables, which are high in antioxidant vitamins, has also shown a decreased prevalence of PAD. Thus, it seems that increased dietary intake of vitamins E and C, either through diet or supplements, may protect against the development of PAD.

Omega-3 fatty acids and their impact on peripheral arterial disease

Fatty acid molecules are classified, based on their biochemical structure, into three groups: saturated, monounsaturated, and polyunsaturated. Of these, the polyunsaturated fatty acids (PUFA) are the most potent fatty acids affecting atherosclerotic disease. The PUFA can be divided into two main groups, the n-6 and n-3 fatty acids. The n-6 fatty acids are readily converted to arachidonic acid and thus produce the 2 series prostaglandins (PGs) and thromboxanes (TXs). These have been shown to be pro-thrombotic and produce vasoconstriction and thus exacerbate many cardiovascular pathologies. The n-3 fatty acids are a far less homogeneous group. The main fatty acid group is that of the fish oils eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). These are essential fatty acids and cannot be synthesized by humans. It is these fish oils that have been shown to have a beneficial effect on atherosclerotic disease. Dietary supplementation with fish oils has been shown to reduce blood pressure and triglyceride levels. EPA has also been shown to inhibit the biosynthesis of the 2 series PGs and TXs from arachidonic acid. This change in eicosanoid metabolism may actually reduce the predisposition to thrombotic events and produce a vasodilatory effect. The fish oils have also been shown to reduce platelet aggregation and perhaps most interestingly have a direct inhibitory effect on atheroma formation. The mechanism of this effect is complex and involves a decreased production of endothelial adhesion molecules and thus a reduction in macrophage migration into an atheroma accompanied with an increased rate of its degradation. A recent double-blind, controlled trial involving 124 participants with intermittent claudication showed that a 300 mg capsule of fish oil could increase maximal walking distance and improve systemic and calf muscle hemodynamics.

Fiber and its importance in reducing the risk of peripheral arterial disease

Fiber is the indigestible part of plant food. It has two main types: soluble and insoluble. Each of these has different benefits in terms of health. Soluble fiber is believed to be more effective in lowering blood cholesterol and LDL-cholesterol than insoluble fiber. Soluble fiber has also been implicated in lowering blood pressure and reducing inflammation, all of which are risk factors for PAD. There is a significant inverse association between fiber intake and the incidence of coronary heart disease. One study showed the use of dietary fiber enhanced insulin sensitivity in people with type 2 diabetes. Considering that diabetes is a potent risk factor for PAD, a condition that showed to increase cardiovascular event risk and decrease the effectiveness of antiplatelet therapy in patients with PAD, making secondary prevention even more important. Fiber intake was also attributed to a reduced risk of cardiovascular disease and all-cause mortality in patients with type 2 diabetes. In conclusion, based on the current study, sufficient evidence of an increased risk of peripheral artery disease is present in those with a poor diet. Data on previous attempted improvements in diet are limited due to questionnaire reliance. Although limited in current evidence, general associations found between certain foods and nutrients suggest good reason for potential encouragement of dietary changes. High cholesterol is associated with narrowed peripheral arteries. Should dietary encouragement in the prevention of intermittent claudication and current peripheral artery disease focus on replicated dietary changes that benefit those with or at risk of hyperlipidemia?

Micronutrients and their contribution to preventing peripheral arterial disease

Vitamin E is a fat-soluble antioxidant found in vegetable oils, seeds, and green leafy vegetables. It functions in inhibiting an oxidative reaction which converts LDL to oxidized-LDL by donating a hydrogen molecule. A study done in Japan on over 40,000 patients without a history of cerebral, cardiac or peripheral artery disease were followed over a 17-year span to test the relationship of vitamin E and incidence of peripheral arterial disease. The study concluded that individuals who consumed higher amounts of vitamin E had a decreased risk of developing peripheral arterial disease. A similar study concluded that vitamin E supplementation has the ability to reduce the progression of atherosclerosis in individuals with type 2 diabetes by means of carotid intima-media thickness.

There are many published studies on the health effects of a variety of vitamins and minerals that are contained within fruits and vegetables and how they may contribute to reducing the risk of developing peripheral arterial disease. This section will review studies on the many types of vitamins and minerals that are not covered in the above sections including vitamin E, vitamin C, and some carotenoids (alpha-carotene, beta-carotene, and astaxanthin), thiamine, potassium, and magnesium.

Dietary Approaches

Mediterranean diet and its benefits for peripheral arterial disease prevention

DASH diet and its impact on reducing the risk of peripheral arterial disease

Plant-based diet and its role in managing peripheral arterial disease

Low-sodium diet and its effect on peripheral arterial disease prevention

Other dietary approaches for preventing peripheral arterial disease

Lifestyle Modifications

Importance of regular physical activity in preventing peripheral arterial disease

Smoking cessation and its impact on peripheral arterial disease prevention

Weight management and its role in reducing the risk of peripheral arterial disease

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