Complementary and alternative medicine

Author : Dr Stephen Bent University of California, San Francisco

2008-06-10

I. What is Complementary and Alternative Medicine?

Complementary and Alternative Medicine (CAM) is variably defined but generally refers to medical therapies and practices that are not commonly taught at medical schools or available at major hospitals and clinics in the United States^{1, 2} (in contrast to “traditional” or “conventional” medicine, which refers to therapies that are provided in most hospitals and clinics). 

Sometimes complementary medicine is described as non-traditional therapies that are used in conjunction with traditional therapies (to complement their action), while alternative medicine is used to describe non-traditional therapies that are used in place of (as an alternative to) traditional therapies. Practically speaking, most non-traditional therapies are simply classified under the general rubric: CAM therapies. A related term used in some settings is integrative medicine, which highlights the belief that CAM therapies are best used when integrated with (rather than replacing) conventional medical care.

II. What are the major types of CAM?

There are many different ways to categorize CAM therapies. The National Center for Complementary and Alternative Medicine (NCCAM – see: http://nccam.nih.gov/) is the scientific branch of the National Institutes of Health that provides research funding for CAM. It outlines four “domains” of CAM and also describes “whole medical systems,” which refers to different theories of medical practice (such as Traditional Chinese Medicine or Homeopathic Medicine) that may involve several domains of CAM treatments.

A. The Four NCCAM domains of CAM:

1) Mind-Body Medicine – techniques used to “enhance the mind’s capacity to affect bodily functions and symptoms,” including meditation, prayer, mental healing, and therapies that use creative outlets such as art, music, and dance.

2) Biologically-Based Practices – products found in nature, such as herbs and vitamins, which may act similarly to drugs by affecting some biological pathway.

3) Manipulative and Body-Based Practices – practices such as chiropractic and massage that involve the manipulation of body parts.

4) Energy Medicine – practices that are designed to affect proposed “energy fields” surrounding the body (examples include qi gong, Reiki, and Therapeutic touch), as well as the use of conventional electromagnetic fields to affect diseases or symptoms.

Whole medical systems may involve different types of therapies – for example, Traditional Chinese Medicine (TCM) may involve the use of herbs, a change in diet or routine, and acupuncture. 

B. Passive vs. Active Therapies:

CAM therapies may also be categorized by the “level of involvement” of the patient into three main groups:

1) Dietary supplements: which are taken in a similar fashion to drugs (for example, chondroitin for knee pain or Echinacea for the common cold).

2) Passive therapies: require the patient to visit a provider and receive some form of treatment (examples include acupuncture, massage, chiropractic, and certain forms of energy healing).

3) Active therapies: require the patient to learn a technique or skill and practice that on their own. Examples include diet, exercise, yoga, meditation, and stress reduction techniques.

In many ways, the “active” therapies are the most desirable, because they provide the patient with a tool or skill that they can use indefinitely and at low cost. Interestingly, although diet, exercise, meditation, and stress reduction are sometimes viewed as CAM therapies, there is strong scientific evidence that many of these “common sense” and “lifestyle interventions” lead to marked improvements in the outcomes of many conditions. However, they are often still viewed as CAM therapies, as many hospitals and clinics do not provide programs that teach these techniques.

III. Why do patients use CAM therapies?

Although the use of CAM has likely been common for decades, the issue received widespread media attention after the publication of two national surveys (conducted in 1990 and 1997) that found that 33.8% of the population (1990) and 42.1% of the population (1997) reported using a CAM therapy in the past year.^{1, 2} Perhaps even more surprising was the fact that the total visits to CAM providers in 1997 numbered 629 million, which exceed the number of visits to all US primary care physicians; in other words, the population at large was seeing CAM providers more commonly than traditional physicians! Also, the out-of-pocket expenditures for CAM therapies in 1997 were estimated to be $27 billion, which was comparable to the out-of-pocket expenditures for all physician services in the US. These landmark studies shed light on the fact that almost half of the population was using CAM therapies, and that patients were contributing similar amounts of their own financial resources to CAM and traditional care. These studies were a major factor in the rising public interest and awareness of CAM, reflected by the Congressional action to establish the National Center for Complementary and Alternative Medicine at the National Institutes of Health in October of 1998. NCCAM was charged with conducting research into the safety and efficacy of CAM, providing training for scientists to conduct research, and disseminating information about CAM to the public.

A separate national survey, conducted in 1998, sought to determine why people use CAM.³ Interestingly, this study found that most patients do not use CAM due to dissatisfaction with conventional care, but rather because CAM was more “congruent with their own values.” Use of CAM was more common in persons with:

            1) more education

            2) poorer health status

            3) a self-described holistic orientation to health

4) a prior “transformational experience” that changed the person’s worldview

5) any of the following health problems: anxiety, back problems, chronic pain, urinary tract infections

6) classification in a cultural group identifiable by their commitment to environmentalism, feminism, or interest in spiritual and personal growth psychology.

This study and others have borne out the conclusion that the use of CAM is particularly common among patients who have disorders that have not responded well to traditional medical therapies. Examples include such problems as chronic pain, psychiatric illness (anxiety, depression, insomnia), gastrointestinal disease (abdominal pain, constipation, diarrhea), or generalized complaints (fatigue, malaise) where a significant percentage of patients have unsatisfactory outcomes. After exhausting traditional options (for example, pain medicines, steroid injections, or surgery for chronic back pain), many patients seek CAM treatments to relieve symptoms.

IV. Which CAM therapies are most commonly used?

The most recent and extensive national survey of CAM use was released in 2004 and involved a national sample of 31,044 interviews of adults over the age of 18 in 2002.⁴ The most commonly used CAM therapies are shown in the attached figure (double-click figure for a larger view of the text).

When prayer used specifically for health reasons was excluded, the study found that 36% of adults had used some form of CAM therapy in the past year. The most commonly used CAM therapy was natural products (18.9%), which includes herbal medicines, functional foods (such as garlic), and animal-based products (such as glucosamine). Deep breathing (11.6%), meditation (7.5%), chiropractic (7.5%), yoga (5.1%), and massage (5.0%) were among the most commonly used CAM therapies.

The overall use of CAM (36%, excluding prayer) was lower than in the national survey conducted in 1997 (which concluded that 42.1% of adults had used CAM).¹ This may reflect a true decline in the use of CAM, or may be due to differences in survey design (including the use of different definitions of specific CAM practices and differences in the group of patients that were surveyed). Regardless, it is clear the use of CAM is still very common in the United States.

V. Which CAM therapies are effective?

 As with any medical therapy, a determination of the efficacy of a specific CAM therapy is based on a review of scientific evidence, which may come in several different forms

A. Background on evaluating scientific evidence:

 The highest-quality scientific study for evaluating the efficacy of any intervention (CAM or traditional) is the double-blind, placebo-controlled, randomized trial. These studies create groups of patients with similar characteristics (similar age, similar socioeconomic status, similar severity of medical conditions such as diabetes, heart disease, etc) by randomly assigning patients to a treatment or control group. The use of double-blinding indicates that neither the patient nor the persons conducting the study know whether any given patient is receiving the “real” treatment or an identical, inactive placebo treatment. Therefore, patients and study personnel should not be influenced when judging whether they have improved (because they do not know whether they are taking the active or the placebo treatment). Once the study is completed, the investigators “unblind” the data, and determine if patients in the active group improved more or less than patients in the placebo group.

Unfortunately, there have been few high quality randomized controlled trials conducted on the vast majority of CAM interventions. A review of studies examining the efficacy of CAM therapies concluded that most randomized controlled trials in this field are of poor quality.⁵

Most of the evidence regarding the efficacy of CAM interventions comes from anecdotal reports (also known as case reports when they are published in the medical literature). These reports generally describe a patient (who for example, might have had severe back pain) who was given a CAM treatment (such as acupuncture) and who improved. These reports provide preliminary evidence that a therapy might be effective, but they are extremely limited for several reasons:

1)      Case reports have no comparison group, so it is not clear whether similar patients (or the same patient) would have improved without the intervention (this problem is sometimes referred to as a lack of information about the “natural history of the disease”).

2)      Case reports are not blinded, so both the patient and the person assessing the outcome are aware of the treatment. This may lead to a biased interpretation of the effect (for example, an acupuncturist might firmly believe in the efficacy of the intervention, and might tend to overestimate the effect). Also, the lack of blinding can lead to a placebo effect, where the observed benefit is not due to the intervention, but to an expectation of benefit (though one can certainly argue that there is nothing wrong with a good placebo effect!).

3)      Case reports often involve one or just a few patients, and it is not clear if they are representative of the larger group of patients who suffer from similar conditions.

There are many examples in traditional medicine where widely held medical beliefs (based on case reports or other similar “observational studies”) were later proven incorrect by the higher-quality randomized controlled trials. For example, for decades it was well established medical practice that when post-menopausal women were given estrogen, they seemed to have less heart disease. It was not until several large randomized controlled trials were conducted that it was discovered that estrogen had no beneficial effects on heart disease.⁶ The original observations of benefit were likely due to the fact that women who went to the doctor to get estrogen were more health-conscious and did other things that reduced their risk of heart disease.

However, it should also be mentioned that many of the most important scientific discoveries originally came from case reports, and the value of case reports to suggest important possibilities should not be underestimated. For example, the phenomenon of a group of 11 men (who were either homosexual or intravenous drug users) becoming immune deficient was originally described in a case series.⁷ This “anecdotal” observation or case series led to the discovery of the AIDS virus.

Historical use is often mentioned as an important consideration regarding the efficacy of CAM interventions, many of which have been used for hundreds or thousands of years. Unfortunately, historical use does not provide strong evidence of efficacy, as it is essentially just a “very large case series” and suffers from the same problems noted above.

For the vast majority of CAM therapies, there is little or no evidence to document efficacy. However, the lack of evidence should NOT be equated with a conclusion that a therapy is ineffective. In the absence of scientific evidence, there is an equal chance that any therapy will be beneficial or harmful.

Also, each CAM therapy must be evaluated for efficacy for a specific indication or medical problem. For example, it is too broad to ask the question, “Is acupuncture effective?” and scientific evidence must be more narrowly focused to answer a question such as, “Is acupuncture effective for the treatment of chronic low back pain?”

B. Brief review of the evidence for efficacy for the most commonly used CAM therapies:

Herbs and other dietary supplements: Herbs and other natural products are the most commonly employed CAM therapies, used by 18.9% or roughly 1 in 5 adults in the US.⁴ The vast majority of these natural products are orally ingested, although a small percentage is applied topically. A recent review article examined the evidence of herbs’ efficacy from systematic reviews (which are extensive reviews of all studies of a particular agent for a particular indication). The results are summarized in the table below.⁸

Herb	Herbal Sales, 2001*	Common Use	Efficacy
1. Echinacea	6.5%	Common Cold	Inconclusive
2. Garlic	6.1%	Lowering Cholesterol	Likely effective, reducing cholesterol by 4-6%
3. Ginkgo biloba	4.2%	Dementia	Likely effective, with small benefit
4. Saw palmetto	4.2%	Urinary problems from enlarged prostate	Inconclusive
5. Ginseng	3.4%	Physical performance	Not effective
6. Grape seed	3.2%	Venous insufficiency	No evidence
7. Green tea	3.1%	Cancer	Limited evidence
8. St. John’s wort	3.0%	Depression	Likely effective for mild-moderate depression but not major depression
9. Bilberry	3.0%	Vision impairment	No evidence
10. Aloe	2.9%	Wound healing	Limited evidence

*Herbal sales refers to the percent of all herbal products sold in retail natural product stores in 2001.

Concerns with the use of herbal products:

• It has been estimated that there are approximately 20,000 herbal products available in the United States.⁹ The evidence for efficacy is very limited for the ten most commonly used herbs, and is extremely limited or non-existent for the remainder of the 20,000 herbal products.
• Consistency of the content of herbal products has been problematic. Herbs contain many different organic chemicals, and it is difficult to know which, if any of these components, have important biological effects. Even when specific active ingredients are identified, many studies have shown that the contents of these herbal products vary widely.⁸
• Safety studies of herbal products are also very limited (see safety, below). There have been many case reports of severe adverse effects, possibly due to active ingredients in the herbs, contaminants in the product, or resulting from interactions with drugs.
• The Food and Drug Administration has very limited oversight of herbs and other dietary supplements. Herbal products can be produced and marketed without FDA approval, and the manufacturer, not the FDA, is responsible for ensuring the safety of a dietary supplement. As a result, there are many herbal products that are contaminated with heavy metals, drugs, incorrectly labeled herbs, or incorrect doses of active ingredients.
• False and misleading marketing information is common with dietary supplements,¹⁰ which may give consumers unrealistic expectations of safety or efficacy.

Commonly used non-herb dietary supplements:

1. Glucosamine and Chondroitin sulfate – there is ongoing controversy regarding the possible efficacy of glucosamine and chondroitin sulfate for the treatment of osteoarthritis of the knee. A recent systematic review concluded that the symptomatic benefit of chondroitin is minimal or non-existent.¹¹ A large, high-quality randomized controlled trial found that the combination of glucosamine and chondroitin sulfate was not effective for the overall group of patients with knee pain, but that it was likely effective in the subgroup of patients with moderate-to-severe pain.¹² Ongoing studies may shed more light on the question of efficacy for this supplement.
2. Omega-3 fatty acids - there is strong scientific evidence from randomized controlled trials that the regular intake of omega-3 fatty acids (either from a diet high in fish or from the use of supplements) reduces the risk of heart disease. The American Heart Association now recommends that patients with heart disease take about 1 gm of long-chain omega-3 fatty acids per day.¹³ Dietary content of omega-3 fatty acids varies substantially. Fish is a major source, and a 3 gram serving of an “oilier” fish (such as tuna, sardines, salmon, mackerel, and herring) contains roughly 1 gm of omega-3 fatty acids. Plant sources of omega-3 fatty acids include flaxseed oil, canola oil, soybean oil, and certain nuts including walnuts. Numerous available supplements contain 1 gm of omega-3 fatty acids.

Bottom-line for herbs and other dietary supplements:There are certainly many herbs that have active ingredients that are potentially beneficial for treating certain disorders. It is estimated that 1/3 of currently used drugs originally came from plants. However, the current problems of poor consistency, safety concerns, scant data to support efficacy, and inadequate oversight limit the usefulness of herbal products. Certain non-herb dietary supplements such as omega-3 fatty acids have strong data to support efficacy. These products are often simpler than herbs (and therefore easier to study), because they have only one or a few components.

Passive therapies:

Acupuncture

1. Acupuncture –

• Acupuncture is a component of Traditional Chinese Medicine that dates back over 2,000 years and involves the insertion of small needles at specific points in the body. The use of acupuncture is based on the theory that there are patterns of energy flow through the body (known as Qi – pronounced “chee”), and that disease states are due to impaired flow of this energy. The use of acupuncture is believed to improve disease states and symptoms by restoring the normal flow of Qi.
• There is controversy regarding the efficacy of acupuncture for specific conditions. Some studies and reviews have concluded that acupuncture is effective for:

1. post-operative and chemotherapy-induced nausea and vomiting
2. post-operative dental pain
3. other pain syndromes including menstrual cramps, tennis elbow, fibromyalgia, and back pain

·        However, a recent review of systematic reviews re-examined prior evidence, and set a “higher bar” for establishing efficacy of acupuncture (requiring at least 4 randomized controlled trials with valid outcome measures and a total of at least 200 patients). This study concluded that there is currently no robust evidence that acupuncture works for any indication.¹⁴

·        A recent, large-scale, high-quality randomized controlled trial in 1162 patients with chronic low  back pain found that both acupuncture and a “sham” or fake acupuncture led to a much larger percentage of patients improving compared with standard treatment (47.6% of patients with “real acupuncture” and 44.2% of patients with “sham acupuncture” improved compared to only 27.4% of patients in the conventional therapy group).¹⁵

·        Similarly, a study in 1007 patients with osteoarthritis of the knee found that both acupuncture and sham acupuncture led to higher success rates than conventional therapy (53.1% success with acupuncture, 51.0% with sham acupuncture, and 29.1% with conventional therapy).¹⁶  Conventional therapy refers to the use of anti-inflammatory pain medicines.

·        Bottom line: Acupuncture is almost certainly effective for back pain, knee pain from osteoarthritis, and probably for other syndromes of chronic pain. The mechanism of this benefit (and whether it is a placebo effect or a physiological effect of the needle placement) is unknown.

2. Chiropractic –

• Although there are mentions of certain forms of spinal manipulations dating back centuries, modern chiropractic care began in the United States in 1895 when Dr. David Palmer established the profession and soon after founded the first school. Chiropractic practice grew in popularity, and chiropractors are now the third largest group of health professionals in the United States (after physicians and dentists). Chiropractors are licensed in all 50 states, and 45 states have state-mandated benefits for chiropractic care.¹⁷
• Chiropractic care is believed to act through corrections of malalignments of the spine (termed subluxations) through the use of spinal manipulation (called spinal adjustments). Chiropractic care may also involve advice about exercise, nutrition, and lifestyle changes.
• A systematic review of the efficacy of chiropractic care (spinal manipulation) for low back pain found that it was no more effective than general practitioner care, analgesics, physical therapy, or exercises.¹⁸
• Other reviews have found that there is insufficient evidence to support the efficacy of chiropractic care for asthma and menstrual cramps.^{19, 20}
• One review found that chiropractic care may be effective for the prevention of migraine headaches.²¹
• Bottom Line: Despite the widespread popularity of chiropractic care, there is limited high-quality scientific evidence that it leads to improved outcomes for specific disorders.

3. Massage –

• Massage is commonly used by patients with disabling, painful, or terminal conditions, and has one of the highest physician referral rates of all CAM therapies. Research into the effectiveness of massage for specific indications is limited and complicated by the difficulties of designing appropriate control or placebo groups.
• There is strong scientific evidence that massage is effective for the relief of chronic back pain, and the benefit is greater than that found with relaxation, self-care, or acupuncture.²²
• In pregnant women, massage of the perineal region 1-2 times per week has been shown to reduce the frequency of perineal trauma during childbirth. ²²
• Massage of pre-term or low birth weight infants improves daily weight gain and may improve weight and reduce post-natal complications at 4-6 months. ²²
• Current evidence is insufficient to determine if massage is effective for a variety of other indications, including cancer, asthma, fecal incontinence and constipation associated with neurological disorders, neck pain, tendonitis, and work-related upper extremity pain.
• Bottom Line – massage has been shown to be effective for chronic back pain, weight gain in low-weight infants, and prevention of perineal trauma during childbirth. Evidence for the efficacy of massage for other indications is limited.

4. Energy healing –

• Research investigating the use of therapies that are believed to modify energy fields surrounding the body (such as Reiki, Therapeutic Touch, and Healing Touch) is preliminary. These therapies are commonly used to treat anxiety, improve relaxation, achieve stress reduction, enhance wound healing, and to reduce pain.
• Bottom Line: Currently, there is insufficient scientific evidence to make conclusions regarding the efficacy of these interventions.

Active therapies:

1. Meditation –

• Meditation has been practiced for centuries in many different cultures throughout the world. While there are many different styles and practices of meditation, a recent review of all styles found the common theme of “achieving a well-defined state of thoughtless awareness focusing attention to the present moment and away from the unchangeable past or the undetermined future…”²³
• There is promising, though not definitive evidence, that meditation may be helpful for epilepsy, menstrual cramping, menopausal symptoms, mood and anxiety disorders, autoimmune diseases, and emotional disturbances in patients with cancer.²³  Further research is needed to define the potential benefits of this therapy.

2. Yoga –

• Yoga is an ancient practice that originated in India and literally means “union” in Sanskrit, referring to a union between the mind, body, and spirit. While the ancient practice of yoga involves many aspects of mental and spiritual well being, the modern practice of yoga often refers to the physical postures or poses designed to improve strength, flexibility, and balance. These are often coupled with deep breathing and relaxation or meditative techniques.
• There is strong scientific evidence that yoga is more effective than self-care for chronic low back pain, resulting in improved function and reduced pain.²⁴
• There is preliminary evidence that yoga may be helpful for improving stress-related symptoms and quality of life in patients with cancer.²⁵ Some evidence also suggests that yoga may be effective for the treatment of depression and anxiety.^{26, 27}

3.   Diet and Exercise –

• There are numerous studies documenting the health benefits of diet and exercise for a variety of conditions from reductions in death and disability from diabetes and heart disease to improvements in mood and overall quality of life. While these therapies may not be considered “complementary and alternative,” the traditional care environments (most clinics and hospitals) often do a poor job of providing access to these therapies and assisting patients to develop healthy diet and exercise practices. Therefore, many CAM practitioners devote more time and energy to emphasizing and implementing diet and exercise strategies. Hence, these therapies are often included in the CAM “umbrella” of services. There are many different forms of diet and exercise, and an analysis of particular strategies is beyond the scope of this review.

VI. Are CAM therapies safe?

There are significant concerns about the safety and efficacy of herbs and other dietary supplements and their potential to interact with prescription medications. Many severe, life-threatening, and fatal side effects to dietary supplements have been reported in the medical literature. The unresolved problems of limited regulation, difficulty creating consistent products, contamination, and little or no safety testing for most dietary supplements creates great potential for side effects from these products.⁸

There is little information regarding the safety of most other CAM therapies as well, though most appear to be relatively safe. Acupuncture is widely used, but there have been only rare reports of any side effects, and most of these are minor (fainting, minor bleeding, worsening of symptoms). The standard use of disposable needles in this country has reduced the concern over the risk of infection or disease transmission.²⁸ Similarly, there are few concerns regarding the safety of massage, although some patients will report pain or discomfort or worsening of symptoms, particularly with more forceful treatments. Serious complications of chiropractic care have also been reported only rarely, and have been generally attributed to improper technique.²⁸

One of the greatest safety concerns with all CAM therapies is that the use of CAM may delay the diagnosis or traditional treatment of a disorder (which could ultimately worsen the outcome for some patients). For this reason, patients are always encouraged to discuss CAM treatments (and the symptoms or reasons that prompted their use) with their regular clinical care provider. Unfortunately, only a minority of patients discuss their use of CAM with the traditional care providers. This is a complex problem that involves perceptions from patients that doctors will not support their use of CAM as well as a lack of openness to discuss and support the use of CAM therapies on the part of some care providers.

VII. Resources to learn more and help decide whether to use a CAM therapy

1. National Center for Complementary and Alternative Medicine (NCCAM) –is the Federal Government's lead agency for scientific research on CAM, and is 1 of the 27 institutes and centers that make up the National Institutes of Health (http://nccam.nih.gov/). NCCAM supports research and training and disseminates information to the public.

2. Natural Standard – is a Web-based information service (subscription required) that conducts extensive reviews of the safety and efficacy of CAM therapies and provides summaries for both patients and clinical providers (www.naturalstandard.com/).

3. Natural Medicines Comprehensive Database – is a Web-based information service (subscription required) that also conducts extensive searches of the medical literature and summarizes information about natural products (dietary supplements) for patients and clinical providers (www.naturaldatabase.com/).

4. Consumerlab.com – is a Web-based information service (subscription required) that analyzes the content of dietary supplements to determine if the label correctly reports the actual ingredients and whether the products meet current accepted standards for contents of specific products (www.consumerlab.com).

References:

1.         Eisenberg DM, Davis RB, Ettner SL, et al. Trends in alternative medicine use in the United States, 1990-1997: results of a follow-up national survey. JAMA. Nov 11 1998;280(18):1569-1575.

2.         Eisenberg DM, Kessler RC, Foster C, Norlock FE, Calkins DR, Delbanco TL. Unconventional medicine in the United States. Prevalence, costs, and patterns of use. N Engl J Med. Jan 28 1993;328(4):246-252.

3.         Astin JA. Why patients use alternative medicine: results of a national study. JAMA. May 20 1998;279(19):1548-1553.

4.         Barnes PM, Powell-Griner E, McFann K, Nahin RL. Complementary and alternative medicine use among adults: United States, 2002. Adv Data. May 27 2004(343):1-19.

5.         Linde K, Jonas WB, Melchart D, Willich S. The methodological quality of randomized controlled trials of homeopathy, herbal medicines and acupuncture. Int J Epidemiol. Jun 2001;30(3):526-531.

6.         Hulley S, Grady D, Bush T, et al. Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. Heart and Estrogen/progestin Replacement Study (HERS) Research Group. JAMA. Aug 19 1998;280(7):605-613.

7.         Masur H, Michelis MA, Greene JB, et al. An outbreak of community-acquired Pneumocystis carinii pneumonia: initial manifestation of cellular immune dysfunction. N Engl J Med. Dec 10 1981;305(24):1431-1438.

8.         Bent S, Ko R. Commonly used herbal medicines in the United States: a review. Am J Med. Apr 1 2004;116(7):478-485.

9.         Winslow LC, Kroll DJ. Herbs as medicines. Arch Intern Med. Nov 9 1998;158(20):2192-2199.

10.       Morris CA, Avorn J. Internet marketing of herbal products. JAMA. Sep 17 2003;290(11):1505-1509.

11.       Reichenbach S, Sterchi R, Scherer M, et al. Meta-analysis: chondroitin for osteoarthritis of the knee or hip. Ann Intern Med. Apr 17 2007;146(8):580-590.

12.       Clegg DO, Reda DJ, Harris CL, et al. Glucosamine, chondroitin sulfate, and the two in combination for painful knee osteoarthritis. N Engl J Med. Feb 23 2006;354(8):795-808.

13.       Harris WS. Fish oil supplementation: evidence for health benefits. Cleve Clin J Med. Mar 2004;71(3):208-210, 212, 215-208 passim.

14.       Derry CJ, Derry S, McQuay HJ, Moore RA. Systematic review of systematic reviews of acupuncture published 1996-2005. Clin Med. Jul-Aug 2006;6(4):381-386.

15.       Haake M, Muller HH, Schade-Brittinger C, et al. German Acupuncture Trials (GERAC) for chronic low back pain: randomized, multicenter, blinded, parallel-group trial with 3 groups. Arch Intern Med. Sep 24 2007;167(17):1892-1898.

16.       Scharf HP, Mansmann U, Streitberger K, et al. Acupuncture and knee osteoarthritis: a three-armed randomized trial. Ann Intern Med. Jul 4 2006;145(1):12-20.

17.       Shekelle PG. What role for chiropractic in health care? N Engl J Med. Oct 8 1998;339(15):1074-1075.

18.       Assendelft WJ, Morton SC, Yu EI, Suttorp MJ, Shekelle PG. Spinal manipulative therapy for low back pain. A meta-analysis of effectiveness relative to other therapies. Ann Intern Med. Jun 3 2003;138(11):871-881.

19.       Hondras MA, Linde K, Jones AP. Manual therapy for asthma. Cochrane Database Syst Rev. 2005(2):CD001002.

20.       Proctor ML, Hing W, Johnson TC, Murphy PA. Spinal manipulation for primary and secondary dysmenorrhoea. Cochrane Database Syst Rev. 2006;3:CD002119.

21.       Bronfort G, Nilsson N, Haas M, et al. Non-invasive physical treatments for chronic/recurrent headache. Cochrane Database Syst Rev. 2004(3):CD001878.

22.       Ezzo J. What can be learned from Cochrane systematic reviews of massage that can guide future research? J Altern Complement Med. Mar 2007;13(2):291-295.

23.       Arias AJ, Steinberg K, Banga A, Trestman RL. Systematic review of the efficacy of meditation techniques as treatments for medical illness. J Altern Complement Med. Oct 2006;12(8):817-832.

24.       Sherman KJ, Cherkin DC, Erro J, Miglioretti DL, Deyo RA. Comparing yoga, exercise, and a self-care book for chronic low back pain: a randomized, controlled trial. Ann Intern Med. Dec 20 2005;143(12):849-856.

25.       Bower JE, Woolery A, Sternlieb B, Garet D. Yoga for cancer patients and survivors. Cancer Control. Jul 2005;12(3):165-171.

26.       Kirkwood G, Rampes H, Tuffrey V, Richardson J, Pilkington K. Yoga for anxiety: a systematic review of the research evidence. Br J Sports Med. Dec 2005;39(12):884-891; discussion 891.

27.       Pilkington K, Kirkwood G, Rampes H, Richardson J. Yoga for depression: the research evidence. J Affect Disord. Dec 2005;89(1-3):13-24.

28.       Cherkin DC, Sherman KJ, Deyo RA, Shekelle PG. A review of the evidence for the effectiveness, safety, and cost of acupuncture, massage therapy, and spinal manipulation for back pain. Ann Intern Med. Jun 3 2003;138(11):898-906.

Heart attack

Author : Edward J McNulty Kaiser Permanente San Francisco Medical Center

2008-11-06

Heart Attack : Background, Diagnosis and Treatment

Heart attacks are a leading killer in both developed and developing nations. They are caused when part of the heart does not receive enough blood, usually because of a blockage in a coronary artery. This knol explains what is meant by a heart attack, how they are caused, and how this condition is diagnosed.

What is a heart attack?

     A heart attack occurs when there is a blockage of blood flow to the heart muscle, causing an area of the heart muscle to die.  This most commonly occurs due to a blockage of a coronary artery (see “coronary arteries”).  If there is a complete blockage in one of the three main coronary arteries, a large heart attack may occur, during which the part of the heart muscle fed by the artery dies.   If the blockage is not complete, bits of blood clot can travel downstream and clog smaller arteries, causing a smaller heart attack.  Both large and small heart attacks are serious and potentially fatal, and both require urgent attention.  Heart attacks are also called “myocardial infarctions” and often abbreviated as “MIs.”

How common are heart attacks?

     It is estimated that one half of men in the US and one third of women will develop angina (pain from a blocked artery in the heart) or suffer a heart attack in their lifetimes (2).   Fatal complications of coronary artery disease (primarily heart attack) are the most common cause of death in the United States, killing approximately half a million people per year.  There are approximately 8 million heart attacks per year in the United States (3).  While heart attacks have long been a leading killer in most developed countries, they have rapidly grown as a problem in developing nations and are now the leading cause of death in lower income countries (4).

Types of Heart Attacks

     There are two main types of heart attacks.  The large heart attacks that result when one of the main coronary arteries become blocked usually cause distinct changes on an electrocardiogram (“see Diagnosis of Heart Attack – ECG”) and are often referred to as “ST Elevation myocardial infarctions.”  (see Figure 1) Smaller heart attacks caused by bits of blood clot traveling downstream into smaller arteries usually cause different findings on an electrocardiogram and are called “non-ST Elevation myocardial infarctions.”

Figure 1.  ECG of an “ST segment elevation myocardial infarction”

What causes heart attacks?

the role of plaque

     The most common disease that affects coronary arteries and leads to heart attacks is “atherosclerosis” (literally meaning hardening of arteries due to plaque formation).  In atherosclerosis, plaque (consisting of cholesterol and other materials) is deposited within the wall of the arteries.  Not only does this plaque cause the arteries to become hardened, but the insides become narrowed.  Once plaque has grown large enough, blockage to the flow of blood may occur.  This can obstruct the flow of blood if the plaque becomes large enough (see Figure 2a), resulting in what is commonly referred to as a “blockage” or “clogged artery,” similar to a kitchen pipe becoming clogged with debris that prevents water from flowing through it.  If there is obstruction to flow through a coronary artery, there may not be enough blood for the heart muscle beyond the obstruction.   As noted above, this becomes a heart attack when the obstruction is complete and the heart muscle fed by the artery dies.

Figure 2.

   

     Over the past few decades a greater understanding of the role of plaque in causing heart attacks has emerged.   Sometimes the plaque can rupture into the inside of the artery, resulting in a blood clot forming on the plaque that completely obstructs the flow of blood and causes a heart attack (see Figure 2b).  While plaques associated with severe blockages can rupture and lead to heart attacks, there are often many less severe plaques scattered throughout the arteries, often not associated with severe narrowing, that may also rupture  and lead to obstruction of blood and also cause heart attacks (see Figure 2c).

Traditional Risk Factors
(See Table 1)

Table 1.  Traditional Risk Factors for Heart Attack

Age

Male gender

Tobacco Use

High Blood Pressure

Diabetes

High LDL (“bad”) cholesterol

Low HDL (“good”) cholesterol

Family History of early heart attack

     "Risk factors" are things that make it more likely that someone will develop a certain condition.  Over the past half a century, there have been tremendous efforts in identifying the risk factors for heart attacks.  Most patients with heart attacks have high blood pressure, abnormal cholesterol, diabetes, or a history of tobacco use (5,6).  These risk factors – along with older age, male gender, and a family history of premature coronary artery disease – comprise the “traditional” risk factors for having a heart attack and are discussed below.

Gender
     Heart attacks are more common in men, but become more common in women following menopause.  One explanation for this has been that the female hormone “estrogen” provides some protection from coronary disease.  However, taking estrogen after menopause does not appear to protect women from heart attacks and may in fact increase the risk (7).

Age
     Since plaque in coronary arteries forms over time, heart attacks are more common later in life.

High blood pressure
     The higher the systolic blood pressure (the higher of the two blood pressure readings) and the higher the diastolic blood pressure (the lower of the two readings) the greater the risk of having a heart attack.  Guidelines for treatment usually define elevated systolic blood pressure as above 140 mm Hg, and elevated diastolic blood pressure as above 90 mm Hg.  Studies including hundreds of thousands of people have shown that lower blood pressure (systolic and diastolic) indicates a reduced risk of suffering a heart attack (8,9).  The risk of dying from a heart attack is reduced by roughly half for every 20 mm Hg decrease in the systolic blood pressure or 10 mm Hg decrease in diastolic blood pressure (10).

Tobacco use 
     Tobacco use is considered the strongest potentially “modifiable” risk factor for having a heart attack (a modifiable risk factor is one that can be changed, unlike age or gender).  Cigarette smoking increases ones risk of dying from complications of coronary artery disease, primarily heart attack, by two to three times (11).  Furthermore, an estimated 35,000 nonsmokers die in the United States from complications of coronary artery disease each year as a result of exposure to “second hand” tobacco smoke (12).

Link to CDC tobacco factsheet:
http://www.cdc.gov/tobacco/data_statistics/fact_sheets/health_effects/tobacco_related_mortality/

Cholesterol

     The higher one’s total cholesterol level is, the greater the risk of having a heart attack (13).  When total cholesterol is greater than 200 mg/dl it is considered elevated.  There are many types of cholesterol, and modern guidelines rely upon looking at the various components of cholesterol. The higher one’s low density lipoprotein (LDL) cholesterol (often referred to as “bad” cholesterol) the greater the chance of developing plaque in the coronary arteries and dying as a result of a heart attack.  On the other hand, high density lipoprotein (HDL) cholesterol (often referred to as “good” cholesterol”) seems to protect individuals from heart attacks.  HDL levels tend to be higher in women than in men.  A low HDL cholesterol level (less than 40 mg/dl) therefore is not a good thing and is considered a risk factor for heart attack in current guidelines.  An HDL cholesterol of greater than 60 mg/dl is considered a “negative” risk factor; that is, having a high HDL level protects one from having a heart attack. Triglycerides are another type of cholesterol that appear to increase the risk of heart attack, especially in women.  Normal triglyceride levels are less than 150 mg/dl.  Whether other types of cholesterol, as well as ratios of various components, are more useful to measure is a subject of much current research and debate.
   
Diabetes

     Diabetes is considered a “coronary artery disease equivalent,” meaning that adults with diabetes have similar risks of dying from complications of coronary artery disease, primarily heart attacks, as do individuals with established coronary artery disease.

Family History of Premature Coronary Artery Disease

     Heart attacks are common, especially as ones get older, so the majority of individuals have a blood relative who has had a heart attack.  Early or premature coronary artery disease (including heart attack) refers to women having complications of coronary artery disease (a heart attack, angina, or a coronary procedure such as an angioplasty or bypass surgery) before the age of 65 or a man before the age of 55.  A “family history of premature coronary artery disease” means that one has a first degree relative (mother, father, brother or sister) with premature coronary artery disease, and this increases one’s risk for developing a heart attack (14).

Traditional Risk Scores

     The risk factors above are considered “traditional” risk factors.  Much of the work in identifying these factors came from following the population of Framingham, Massachusetts for many years (14).  A limitation of this work was that most of the population studied was Caucasian.  Subsequent studies have confirmed the role of these same risk factors in more diverse populations (15,16).  There are many “risk scores” that can be used to calculate an individual’s risk of having a heart attack or dying from complications of coronary artery disease.  One commonly used calculator is the Framingham Risk Calculator.

Link to Framingham risk calculator:   http://hp2010.nhlbihin.net/atpiii/calculator.asp?usertype=pub
Other Risk Factors for Heart Attack

     While there is abundant evidence linking the above risk factors to coronary artery disease, many (up to 20%) of individuals can develop complications of coronary artery disease, including heart attacks, without any of the identified traditional risk factors.  Therefore there has been much effort at identifying other risk factors for coronary artery disease and heart attacks.

Peripheral Artery Disease

     As with diabetes, individuals with peripheral artery disease (severe plaque in arteries in the neck or extremities) or abdominal aortic aneurysms have similar risks of developing complications from coronary artery disease as do individuals with established coronary artery disease, and therefore are treated as if they have coronary artery disease.

Physical inactivity/lack of exercise 

     Physical activity appears to reduce the risk of heart attack and death from coronary artery disease.  Conversely, physical inactivity and poor conditioning increases the risk of these complications (16).  Among its beneficial effects, exercise reduces weight (and the risk of developing diabetes) and blood pressure – and improves cholesterol.
Obesity 
     Obesity increases blood pressure, lowers “good” (HDL) cholesterol, raises “bad” (LDL) cholesterol and triglycerides, and increases the risks of diabetes.  In other words, obesity causes many of the other known risk factors for coronary artery disease and heart attack.  Obesity also appears to increase the risk of suffering complications of coronary artery disease in and of itself, independent of these other risk factors (17).  Furthermore, the location of adipose tissue (fat) appears to be important, with having abdominal obesity (fat in the truck or “belly”) being worse than having fat more spread out through the body.  Obesity is usually defined as having a body mass index or BMI of greater than 30.
Link to BMI calculator:
http://www.nhlbisupport.com/bmi/

The metabolic syndrome

     The metabolic syndrome refers to individuals who have three of the following: abdominal obesity, elevated fasting blood sugar (a precursor to diabetes), high blood pressure, low good (HDL) cholesterol, and elevated triglycerides.  Whether this syndrome confers a risk for coronary artery disease and heart attack beyond the additive risks of the individual risk factors is a subject of controversy and current research.

Diet

     Coronary artery disease and heart attacks are more common in countries with diets higher in animal fat and processed sugar (so called “Industrial” or “Western Diets”) (18).  Even among western countries there is considerable variation in the rates of coronary artery disease and heart attack from country to country.  In general, countries with a very high intake of animal fat have correspondingly high rates of coronary artery disease and heart attacks.  Additional evidence for the role of diet in developing coronary artery disease comes from studying individuals migrating from areas where coronary artery disease is uncommon to areas where it is very common.  For example, studies of Japanese immigrants revealed dramatic increases in the rates of coronary artery disease once individuals moved to western countries and adopted western diets.  Finally, as countries develop and adopt western diets, the incidence of coronary artery disease and heart attacks increases.

     While the evidence linking diet to coronary artery disease and heart attacks is compelling, there is also much about this relationship that is poorly understood.  Some fats appear to be harmful (saturated and “trans” fatty acids) while others seem to be protective (polyunsaturated and monounsaturated fats).  Studies have shown lower rates of coronary artery disease and heart attack in countries with diets rich in omega-3 fatty acids, part of the so called “Mediterranean Diet” (19).

Alcohol use

     Moderate alcohol intake (one drink per day for women and one to two drinks per day for men) appears to be protective against death from coronary artery disease and heart attack (16).  While some studies have suggested that substances in red wine could account for this protective effect, it appears that any alcohol intake is protective.  It should be noted that this finding refers to individuals who have established moderate patterns of alcohol intake, not individuals who begin drinking to prevent the development of coronary artery disease. At least part of the beneficial effect of alcohol intake is due to increasing levels of good cholesterol.

Stress and Depression

     Anxiety, depression, and having “type A” personality have all been shown to increase the risk of developing complications of coronary artery disease and heart attack (20).

Drugs

     Certain medications and illicit drugs can also cause heart attacks, including cocaine and methamphetamine.

What are the symptoms of a heart attack?

     The typical symptom of a heart attack is chest discomfort,  usually described as a sensation of pain or pressure over the middle or left side of the chest.  However many people having heart attacks have different symptoms such as neck pain, arm or shoulder pain (usually but not always on the left side), or pain in the upper abdomen (above the umbilicus or "belly button").  Other less "typical" symptoms that patients having heart attacks experience include nausea or a feeling of fullness in the upper abdomen.  In addition to these symptoms, people having heart attacks also have other "associated" symptoms, such as sweating and a feeling of breathlessness.  Typical symptoms occur in only about a half of individuals with heart attack, and occur more often in men than women.  Some people experience little in the way of symptoms despite having major heart attacks, especially those with diabetes. 
     Often people having heart attacks feel tired with less energy in the days leading up to heart attacks.  Sometimes patients with angina develop worsening symptoms in the days leading up to a heart attack.  If you or someone you know thinks that they may be having a heart attack, it is vital that they seek medical attention right way (in other words, call 911).  The sooner heart attack victims get treated, the more lives are saved and the more heart muscle is saved.

Complications of heart attacks

     The most dreaded complication of heart attacks is death, and up to one half of patients experiencing heart attacks die before they can receive medical attention.  Those surviving until they reach the hospital do better, but many still die.  There are two main ways that heart attacks can result in death, either through causing fatal irregular heart beats or by causing so much of the heart to die that the patient goes into “shock” and dies.  Earlier recognition and treatment can reduce these complications and improve survival.  Even if an individual survives the heart attack, the heart can be left weakened and “congestive heart failure” can result.

How is a Heart Attack Diagnosed?

1.  Electrocardiogram (“ECG”)

     If a heart attack is suspected, an electrocardiogram (ECG) is performed.  This test entails placing electrodes (simple adhesive strips) on the patient to measure the electrical activity of the heart, and can be useful in detecting signs of an ongoing or imminent heart attack as well as a prior heart attack (see figure 1).  It is quick, easy to perform and relatively inexpensive and is therefore useful as an initial tool in the diagnosis of suspected heart attack.  However, individuals with a normal ECG can still have a heart attack.

2.  Blood tests

     Certain substances are released into the blood in patients having a heart attack and can be detected by blood tests.  These tests, especially measurement of the creatine phosphokinase (“CPK”) and troponin, are useful in determining if an individual is having a heart attack.

3.  Coronary Angiography (“Cardiac Catheterization”)

     Currently, the most accurate method to detect blockages in the coronary arteries is invasive angiography.  This is an invasive test, because it requires temporarily placing objects into the body and is performed in a facility called a catheterization laboratory.   It is usually recommended in patients with a suspected major heart attack (an “ST Segment Elevation MI) and in many patients with smaller heart attacks.  It is performed by placing a hollow tube (called a sheath) into an artery in the groin or wrist and then threading small “catheters” (hollow, plastic tubes 2-3 mm in diameter) through the arteries to the coronary arteries.  This is performed using X-ray guidance, so the procedure does require exposure to radiation.  Once the catheters are placed into the beginnings of the coronary arteries, a substance called “contrast” is injected into the arteries while X-ray movies are taken.  The contrast contains iodine so that X-rays will not penetrate it; therefore arteries with contrast inside appear dark on the X-ray picture.  In this way a picture of the inside of the coronary arteries is obtained, usually from multiple positions, and blockages detected. (See figure 3). 

Figure 3.  Angiography

Blockages can sometimes be treated at the same time with angioplasty and stents (see figure 4).


Figure 4.  Angiogram showing complete blockage in right coronary artery, before (top) and after (bottom) treatment with a stent.  Arrow in top panel points to blood clot at blockage in the artery.

Treatment of heart attacks:  “Time is muscle”

     It cannot be overemphasized how important prompt treatment is in reducing the risk of death in heart attacks.  Even if it is not possible to perform an angiogram right away, clot dissolving medicines can be administered which are also effective in treating heart attacks.  The more time that elapses when there is a complete blockage in an artery in the heart, the less likely it becomes that the heart muscle can be saved and the more likely fatal complications become.

     Initial treatments for heart attack include aspirin, oxygen, nitroglycerin and sometimes morphine.  This should be done by experienced medical personnel and in a setting where the patient can be monitored.  Other medicines that are given early in heart attacks to certain patients are beta blockers and other blood thinning medicines including aspirin. 

     For larger heart attacks, or so called "ST segment elevation heart attacks," patients are taken as quickly as possible to a cardiac catheterization laboratory for a "coronary angiogram."  If a completely blocked or seriously blocked artery is found, it can usually be opened with a balloon and a stent.  Sometimes the blockages are in locations that require open heart bypass surgery.  If patients cannot be taken quickly for a cardiac catheterization, then powerful clot dissolving medicines called "thrombolytics" are given.

     For smaller heart attacks, patients are also treated with medications including beta blockers and blood thinning medications including aspirin.  Depending on how serious the heart attack is, patients may have a stress test or be sent for a coronary angiogram where blockages can be treated with balloons and stents.

     During the recovery from a heart attack, patients are usually treated with cholesterol lowering medications (especially a type called "statins") and also given medications including aspirin (or other similar blood thinning medicines), beta blockers, and ACE inhibitors.  Also important is adopting a healthy diet and lifestyle.

Other Links

National Heart Lung and Blood Institute

American Heart Association

References
1. Roger VL, Weston SA, Killian JM et al  Time Trends in the Prevalence of Atherosclerosis: A Population-based Autopsy Study Am Journal Med 2001 110:267-273.

2. Jones DM, Larson MG, Beiser A Levy D , Lifetime Risk of Developing Coronary Heart Disease Lancet 1999; 353:89-92.

3.  American Heart Association/American Stroke Association Heart Disease and Stroke Statistics, 2008.

4.  World Heath Organization Global Burden of Disease Statistics 2002 (http://www.who.int/healthinfo/bodestimates/en/index.html).
     
5.  Greenland, P, Knoll, MD, Stamler, J, et al. Major risk factors as antecedents of fatal and nonfatal coronary heart disease events. JAMA 2003; 290:891.

6.  Khot UN, Khot MB, Bajzer CT, Sapp SK et al Prevalence of Conventional Risk Factors in Patients With Coronary Heart Disease JAMA 2003; 290:891.

7.  NIH Women’s Health Initiative (www.nhlbi.nih.gov/whi/)

8.  S. MacMahon, R. Peto and J. Cutler et al., Blood pressure, stroke and coronary heart disease: Part I. Prolonged differences in blood pressure: Prospective observational studies corrected for the regression dilution bias, Lancet 335 (1990), pp. 765–774.

9.  W.B. Kannel, M.J. Schwartz and P.M. McNamara, Blood pressure and the risk of coronary heart disease: The Framingham study, Crit Rev Dis Chest 56 (1969), p. 43.

10.  Prospective Studies Collaberation Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies The Lancet 2002 360:1903-1913.

11.  Centers for Disease Control and Prevention, Tobacco-related Mortality Fact Sheet.  Sept 2006.  www.cdc.gov/tobacco/factsheets/Tobacco_Related_Mortality_factsheet.htm

12.  Annual Smoking-Attributable Mortality, Years of Potential Life Lost, and Productivity Losses – United States, 1997-2001, Morbidity and Mortality Weekly Report 2005;54:625-628.

13.  Third Report of the Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults (ATP III Final Report) National Heart Lung and Blood Institute.
www.nhlbi.nih.gov/guidelines/cholesterol/atp3_rpt.htm

14.  Anderson KM, Odell PM, Wilson PWF and Kannel WB Cardiovascular disease risk profiles, Am Heart J 121 (1991), pp. 293–298.

 15.  Ramachandran SV, Sullivan LM, Wilson PWF, Sempos CT, Sundstrom J et al Relative Importance of Borderline and Elevated Levels of Coronary Heart Disease Risk Factors Annals Int Med 2005;142:393-402.

16.  Yusuf S, Hawken S, Ounpuu, Dans T, Avezum A et al  Effect of Potentially Modifiable Risk Factors Associated with Myocardial Infarction in 52 countries (the INTERHEART Study): a case control study.  Lancet 2004 364:937-52.

17.  Yan et al Midlife BMI and Hosp and Mortality in Older Age JAMA 2006; 295:190-198.

18.  Yusuf S, Reddy S, Ounpuu and S Anand, Global burden of cardiovascular diseases: part I: general considerations, the epidemiologic transition, risk factors, and impact of urbanization, Circulation 104 (2001): 2746–2753.

19.  Anderson CAM and Appel LJ Dietary Modification and CVD Prevention: A Matter of Fat JAMA 2006; 295(6): 693 – 695


20.  Rosengren A, Hawken S and Ôunpuu S et al., Association of psychosocial risk factors with risk of acute myocardial infarction in 11 119 cases and 13 648 controls from 52 countries (the INTERHEART study): case-control study, Lancet 364 (2004), pp. 953–962