Integrative Therapies in Vascular Disease

Sara Warber

Complementary and alternative medicine (CAM) use is on the increase in America. The prevalence of CAM use among people with a diagnosis of cardiovascular disease (CVD) or with risk factors for such is significantly higher than in the general population. Patients who undergo cardiac surgery have been reported as using a number of CAM modalities including vitamins (54%), prayer (36%), nutritional approaches (17%), meditation (11%), massage (11%), chiropractic (11%), and herbs (10%). Qualitative studies have shown that people often become CAM users after an acute health event such as a new diagnosis of cancer or a myocardial infarction. Among post–heart attack patients, their stated goals include avoidance of a second heart attack, avoidance of surgery, and promotion of general health.

The predominant modalities embraced by CVD patients who use alternative therapies are either biologically active substances, such as herbs and supplements, and mind–body therapies that address stress reduction and quality of life. Understanding of alternative options and how they complement or interfere with conventional medical and surgical therapeutics is a strategy that will serve patients well.

An integrative plan for addressing peripheral vascular disease includes diet, exercise, smoking cessation, mind–body therapies, and the judicious use of natural products, such as herbs and supplements. An integrative approach emphasizes lifestyle modifications that are in line with conventional best practices.

Diet

A healthy cardiovascular diet should be high in fiber and antioxidant-rich foods, especially fruits and vegetables with intense colors, such as melons, berries, and squashes. Foods high in omega-3 fatty acids such as cold-water fish (e.g., salmon, herring, sardines), nuts, and flax seeds (three tablespoons finely ground per day) or flax seed oil (one tablespoon, or one or two 500-mg capsules twice daily) should be included. One clove of raw or very lightly cooked garlic may be beneficial each day. A low-fat or cholesterol-free diet, such as the Mediterranean-based diet or the Dean Ornish diet, is a good model for patients to follow. It is important to include six to eight glasses of water per day, but not in the form of tea, coffee, soda, or juice, to maintain hydration.

Exercise

Large observational studies show that lack of exercise is a risk factor in arterial disease and that moderate to high physical activity reduces coronary heart disease and stroke. Often, exercise is difficult or painful for people with peripheral arterial disease (PAD), so that other interventions discussed later, such as Ginkgo biloba extract, that increase pain-free walking distance, have additive effects by allowing greater exercise. In the case of chronic venous insufficiency (CVI), it is thought that the action of the leg muscles aids the return of blood toward the heart. This must be balanced with the fact that upright posture for exercise can exacerbate peripheral pooling. Supine bicycle exercise, rowing machines, or yoga, which uses many postures, may be good choices for people with CVI. An effective exercise program is flexible and enjoyable so patients will continue to exercise for the rest of their life. Activity goals should increase in a stepwise fashion to a final goal of 30 to 60 minutes a day combined with stretching before and after exercise.

Smoking Cessation

Smoking is a significant independent risk factor for vascular disease. Acupuncture for smoking cessation has been reviewed but does not show an increase in abstinence at 1 year. Two recent reviews of hypnosis for smoking cessation show evidence of similar effects when compared to other behavioral treatments. For selected patients, hypnosis and/or acupuncture may be well worth a trial in addition to the use of other proven treatments.

Mind–Body Connection

Meditation, hypnosis, biofeedback, yoga, qigong, tai chi, cognitive–behavior treatment, and music therapy have been studied as possible mind–body interventions for cardiovascular disease. Transcendental meditation decreases basal cortisol and lessens carotid atherosclerosis, a surrogate marker for coronary artery disease. Hypnosis and biofeedback are particularly useful for decreasing heart rate and blood pressure.

The increasingly popular practice of yoga, which includes focused control of the mind, breath, and body, decreases sympathetic tone, improves blood pressure, decreases heart rate, and decreases oxygen requirement without affecting work. Qigong, a traditional Chinese practice of breathing, meditation, and movement, has beneficial effects on hypertension, depression, anxiety, and CAD. Tai chi, another mind, breath, and movement discipline, improves exercise endurance, reduces stress, and enhances positive mood.

Cognitive–behavioral treatment has been applied to reducing risk factors such as obesity, blood pressure, exercise, and type A behavior. Music therapy, including singing, playing instruments, and listening to music, has the ability to directly alter heart rate, stress levels, and anxiety in heart patients.

Each of these approaches brings the mind, spirit, and emotions into balance with the body, thus enhancing a variety of mechanisms that promote optimal health. No one approach is good for all patients. It is important to work with individual patients to identify mind–body approaches that are consistent with their beliefs and interests.

Natural Products for Peripheral Arterial Disease

Natural products for peripheral arterial disease are listed in Table 1.

TABLE 1

Natural Products for Peripheral Arterial Disease

Natural Product	Indications	Dosage	Clinical Effect	Evidence	Evidence Grade∗	Comments
Ginkgo biloba extract	Fontaine’s IIb PAD and intermittent claudication	120–240 mg EGb761 (Tanakan, Tebonin Konzent)	Increased pain-free walking distance; decreased incidence of surgery or amputation in elderly	9 RCTs; Cochrane review	A	Bleeding risk if used with antiplatelet drugs or warfarin
Inositol nicotinate	Intermittent claudication and Raynaud’s syndrome	4 g divided bid–qid	Improved symptoms	Multiple studies support effects	B	Several weeks of treatment are needed before full benefit is seen
Propionyl-L-carnitine	Intermittent claudication	1–2 g/day, PO or IV	Increased walking distance and time	Multiple studies support effects	B	Trans-Atlantic Inter-Society Consensus II recommends use in combination with physical training
Padma 28	Stage II PAD	As directed	Improved maximum walking distance by 81 m	Five RCTs	B	Mixture of 22 herbs; includes Sida cordifolia, which contains ephedrine
Policosanol	Intermittent claudication	10–20 mg daily	Improved walking distance	Three studies	B	Also lowers lipids; avoid with antiplatelet drugs or warfarin
L-Arginine	Intermittent claudication	3.3 g bid to 24 g qd	Improved endothelial function, pain-free and total walking distance	Two studies	B	Avoid in kidney or liver failure; observe for decrease in blood pressure
Mesoglycan	Intermittent claudication	100 mg daily	Improved walking distance	Two studies; Grade B	B	Contains heparin, caution with other anticoagulants; discontinue 2 wk before surgery
Alpha lipoic acid	PAD and claudication	300 mg bid	Decreased pain with exercise; no increase in exercise tolerance	Single study	—	—
PUFAs plus folic acid plus vitamins B6 and E	Men with PAD and intermittent claudication	1 year of supplementation: Omega-3 Oleic acid Folic acid Vitamin B6 Vitamin E	Increased pain-free walking distance; improved ankle-to-brachial pressure index	Single study	—	Decreased total cholesterol
Vitamin C	Women	Vitamin C ± vitamin E	Decreased risk of PAD	Epidemiologic evidence	—	Effects inconsistent in other populations
Vitamin E	Intermittent claudication in male smokers	all-rac-α-Tocopherol (synthetic vitamin E)	No effect alone or in combination with β-carotene	Few studies	—	—
Chelation	Stage II PAD	IV EDTA plus vitamins 2×/wk × 20 wk	No benefit	Cochrane review of 5 RCTs	—	—
Garlic	Stage II PAD	Garlic × 12 wk	No improvement in walking distance	Cochrane review of 1 RCT	—	—
Omega-3 fatty acids	Intermittent claudication		No improvement in pain-free or maximum walking distance	Cochrane review of 4 RCTs	—	Decreases risk of major coronary events

EDTA, Ethylenediaminetetraacetic acid; PAD, peripheral arterial disease; PUFA, polyunsaturated fatty acids; RCT, randomized, controlled trial.

^∗Evidence grades: A, statistically significant evidence of benefit from randomized trials and/or meta-analysis; B, statistically significant evidence of benefit from randomized trials or nonrandomized studies.

Ginkgo biloba Leaf Extract

Ginkgo biloba leaf extract comes from the oldest living trees in the world, with fossil evidence dating back 200 million years. Ginkgo is one of the best-selling herbs in the United States and is also one of the most studied herbs, with evidence supporting its action as an inhibitor of platelet activating factor and as a vasodilator. According to the German Commission E and the World Health Organization monographs, ginkgo is approved for peripheral vascular occlusive disease and post-phlebitis syndrome, Raynaud’s disease, and acrocyanosis.

The evidence of its efficacy for intermittent claudication was assessed in a meta-analysis of multiple randomized, double-blinded, placebo-controlled trials in humans. The mean improvement in pain-free walking of the ginkgo group over the placebo group was 34 meters. In a head-to-head trial of Ginkgo biloba extract and pentoxifylline, each product caused a similar increase in pain-free walking distance and maximal walking distance.

There are case reports of bleeding complications, but recent randomized studies have shown that ginkgo does not interfere with coagulation parameters or warfarin. Caution is still advised when using it in patients on antiplatelet drugs or those undergoing surgical procedures.

Inositol Nicotinate

Inositol nicotinate consists of six molecules of nicotinic acid (niacin) chemically linked to an inositol molecule. Once in the blood stream, it is slowly hydrolyzed to free nicotinic acid and inositol. Because of this, inositol nicotinate has been marketed as a no-flush niacin. Several weeks of treatment may be necessary before the full beneficial effects are seen in peripheral vascular disorders such as Raynaud’s disease, suggesting that fibrinolysis, lipid lowering, and vasodilative action contribute to its beneficial effects. Inositol nicotinate has been used in conventional medical practice in Great Britain for improving symptoms of peripheral vascular disorders and treating hyperlipidemia for many years.

Propionyl-L-Carnitine

Carnitine is an amino acid metabolized from lysine or derived from eating meat and dairy products. Without carnitine, the carrier molecule for fatty acids, acyl-CoA, cannot cross the mitochondrial membrane, leading to decreased concentrations of fatty acids in the mitochondria and decreased energy production. In patients with peripheral artery disease, short-term therapy with propionyl-L-carnitine (LPC) significantly improved pain-free walking distance compared to placebo. L-Carnitine’s beneficial effect on the walking capacity of patients with intermittent claudication appears to be a result of improved energy metabolism within the muscle and not from improved blood flow in the lower limbs. Additionally, LPC administration improves the healing of ulcerative lesions, reduces the need for analgesic medication, and lessens the incidence of amputation.

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