ACUPUNCTURE AND THE CARDIOVASCULAR SYSTEM:
A SCIENTIFIC CHALLENGE
By Soren Ballegaard, M.D., Cardiologist, Hellerup, Denmark

ABSTRACT
    Acupuncture research must address two main issues. Does the needle have a biological effect of its own? Is acupuncture helpful to patients in their daily lives?
    Acupuncture is a complex form of treatment in which the needles aim to modulate the physiological mechanisms of the body; the physician supports the patient in achieving a complimentary lifestyle. Forty-nine angina pectoris patients were included in evaluating the biological effect of needling; cardiac, neurophysiological, and psychological observations were made in a mutually independent manner. Needling was found to improve the working capacity of the heart. Additionally, acupuncture was ascertained to activate cardiovascular autoregulatory mechanisms in 24 healthy individuals.
    Judging the effectiveness of acupuncture in daily life involved following 69 patients with severe angina pectoris for two years after treatment. The incidence of cardiac death or myocardial infarction was 7%; invasive treatments, 15%-2 1 %. Surgery was postponed in 61 % of the patients due to clinical improvement. The annual number of in-hospital days was reduced by 90%, leading to a $12,000 saving for each patient.

KEYWORDS
    Angina Pectoris, Cardiovascular, Acupuncture, Clinical Trials

INTRODUCTION
    Dr. Mehmet Oz, a, leading heart surgeon at Columbia University, recently presented a puzzling scientific observation. Among the 1,000 patients who annually receive a bypass operation at the hospital, one-third return to the hospital within six months after surgery with major depression. The angiographic examination revealed open grafts. Viewed surgically, the patients were regarded as cured but apparently, not heated.
    Descartes, the philosopher, postulated the separation between mind and body 400 years ago. This approach has led to great technological achievements within all aspects of human life. The bypass operation is such an achievement. It is based on the scientific pathophysiological interpretation of angina pectoris; the consequence of an insufficient ratio between oxygen demand and supply to the myocardium. Thus, improved blood supply to the myocardium by the new vessels should cure the disease and accordingly, heal the patient. When the operation fails to meet this aim, one may ask, does this scientific interpretation represent the full picture of angina pectoris? Furthermore, is the heart more than just a pump? Hence, reflecting upon these questions in evaluating the effects of acupuncture on the cardiovascular system, further answers may be necessary:
1) Scientifically, does the needle have a biological effect of its own?
2) Clinically, does acupuncture aid patients in their daily life?
    Scientists study effects of manipulations of nature under the assumption that we control all factors that may influence the outcome of our manipulation; the one we study is excluded. This creates a highly artificial situation far away from daily life in the doctor-patient relationship; perhaps, wrongly assuming that we may eliminate this situation influencing the outcome of treatment. However, in a strictly scientific sense, acupuncture equals needling; in this respect, the scientific concept helps us to understand the specific biological effect of needling.
    The above scientific discussion of acupuncture takes into account only one part of the problem in daily life. Apart from needling, acupuncture includes a social interaction between patient and physician. In this respect, acupuncture is utilized according to traditional Chinese theory; acupuncture activates homeostatic mechanisms of the body, and the physician then assists the patient in developing a lifestyle supportive of this effort. The patient's primary interest is the outcome of this more complex treatment, rather than the specific biological effects of needling. Furthermore, the possibility exists to obtain a fair estimate of the degree and duration of treatment effects on quality of life. The challenges of studying the effects of acupuncture on the cardiovascular system, from both the scientist and the patient's vantage points, are addressed in this article.

STUDY DESIGN IN SCIENTIFIC
ACUPUNCTURE TRIALS
    The double-blind randomized trial is the landmark of the Western scientific world in assessing effects of a new treatment. The purpose of such a design is to study the effects of a treatment; eliminating all possible influences and factors other than the one being tested (1). The validity of this test is based on two main assumptions:
1. The groups compared are identical with regard to all factors that may influence the result.
2. The treatments compared appear identical to both the patients and to the observers.
    Much of the criteria for the double-blind randomized clinical trial cannot be fulfilled in acupuncture studies. In this paper, the essential considerations imposed by this fact are discussed. Many trials are cited to indicate the great variety of attempts that are made to overcome the methodological problems in acupuncture trials, rather than to detail results of the individual trials.

COMPLEXITY OF THE CHALLENGE
Placebo, Nocebo and Specific Effects
    Placebo has been defined as the non-specific, positive therapeutic effect of the entire patient-physician relationship (1, 2); nocebo is the opposite. The specific effect is the therapeutic influence attributed solely to the therapy being rendered (2). The term, "placebo," has been used for centuries. "Nocebo" was introduced in recent years by Kennedy (3) to describe those stimuli which may have a negative effect on the healing process: fear, anxiety, and mistrust.
    Many studies have been carried out; no special personality characteristics have been found to be related to either effect. On the contrary, the same person may react differently under different conditions. Basic to the placebo effect is the conclusion that the disease or symptoms change over time, or from patient-to-patient. The placebo effect is enhanced as the need for help increases.
    The suggestion is relative that the placebo/nocebo effect is allied to expectations from the patient, observer, and attending physician; and combined with conditioned Pavlovian response, activated by positive or negative anticipation of healing (4, 5, 6, 7). A reciprocal inhibition is exerted at the brainstem level: the placebo effect, through activation of the endogenous opioidsteroto-nergic, pain-inhibitory descending system. The nocebo effect is wielded through inducement of noradrenergic neurons in locus coeruleus (6, 8).
    The placebo effect may vary according to the disease or condition being treated (9). It is generally agreed that the influence of the placebo effect may be negligible on the death rates for cancer or liver cirrhosis. However, in conditions such as angina pectoris, impact of the placebo effect is known to be pronounced (10, 11, 12). Placebo, nocebo, and specific effects will influence the result of any treatment. Daily clinical practice may find the physician routinely using placebo effect to benefit the patient. In scientific studies aimed at elucidating the specific effects of acupuncture, the presence of placebo and nocebo effects impose a bias * Eliminating the influence of these effects requires certain factors to be addressed:
1) Choice of control group and control treatment.
2) Sample size.
3) Bias from the observer.
4) Bias from the acupuncturist.
5) Bias from the patient/subject.
6) Influence from psychosocial factors.

Choice of Control Group and Control Treatment
    In a double-blind randomized clinical trial, effect of the active treatment is compared with that of inactive preparation, placebo; the placebo appears identical to the active one for both patient and attending physician. Acupuncture trials permit no similar control treatment. Genuine acupuncture entails penetration of the skin at specific sites related to the condition of the patient, repeated physical contact involving the hands of the acupuncturist and skin of the patient, and a unique physical sensation when the needle impacts the acupuncture point. This sensation is described as soreness, aching, or burning; not to be confused with the sensation related to penetration of the skin. Furthermore, since the whole body can be regarded as one large acupuncture point, any insertion of an acupuncture needle may have both a specific local and general effect on the body.
    Consequently, a true non-active control treatment of the patient identical to genuine acupuncture is not possible. Many attempts have been made to solve this problem (13, 14, 15, 16). Previous trials have dealt with the selection of a proper control treatment, focusing on the penetration of the skin as well as the unique physical sensation.
    No penetration nor physical sensation were chosen as control treatment when the control group received no treatment (17), or a placebo pill (18).
    Some physical sensation, (but differing from that caused by a needle), was elicited during mock Trancutaneous Electrical Nerve Stimulation (19). Electrodes attached to the surface of the skin were connected to a dummy electric stimulator. Rubbing the skin creates another form of physical sensation (20).
    In sham (non-standard) acupuncture, the skin is penetrated; the needle is inserted at a site different from that of tranditional (standard) treatment. Needles may be inserted far from the genuine treatment point: lower instead of upper limb (2 1), in the adjacent dermatome (22), or, within the same dermatome, but outside the Chinese Meridian System (23).
    Superficial acupuncture inserts the needle at the same site as in genuine treatment, but, superficially: 2-4 mm, compared with up to 10 mm (24). The needle may be inserted without stimulation (23), or, with stimulation similar to traditional acupuncture (22). Injection of medicine at an acupuncture site is yet another control treatment (25).
    Some trials use more than one control group. In shoulder pain, acupuncture is compared with injection therapy, physiotherapy, and placebo medication (26). Traditional acupuncture is compared with dummy acupuncture, and no treatment, in testing the antiernetic effect (27).
    Instead of comparing the effects of acupuncture between groups receiving different treatment forms, the crossover design has been used to compare genuine and sham acupuncture (28); or, genuine acupuncture and treatment with a placebo pill (18). This design may be useful in measuring effects with a duration far shorter than the observation period.

Sample Size
     Sample size has no specific bearing on acupuncture trials, but may be worth considering. The assumption is that genuine acupuncture helps 70% of patients, sham acupuncture, 50%, and placebo, 30%. Study results comparing genuine acupuncture and placebo, with 20 patients in each group, result in a 25% probability of identifying differences in effects between the two treatments, on a 5% significance level. Thusly, a 75% probability of false negative results ensue; i.e., a treatment rendered ineffective, although it may have proven effective in a larger scale study. Studies comparing genuine and sham acupuncture, with 20 patients in each group, reflect a 13% probability of identifying a significant between-group difference; with 85 patients in each group, the probability is 75 %.

Bias from the Observer
     The blinding of the observer is easily done in both traditional pharmaceutical clinical trials and acupuncture trials. The patients are randomized, one group to genuine acupuncture and one to control treatment, and the observer is blinded as to treatments. Excluding bias, the observer must believe that the trial is testing an active against a non-active treatment, or two equally active treatments. Furthermore, this person must not bring up issues or reflect statements that would basically affect the patient emotionally. Both intentional and non-intentional observer expectancy has shown similar influences: the performance of a test (6); the effect of placebo pills (29); and, pain tolerance in experimentallyinduced pain (30).
    The impact of this effect, "The Rosenthal Effect," is illustrated by this diary entry from a patient: "Right after the initiation of acupuncture, a pronounced improvement appeared, but when I was told at the final exercise test that I ought to have a coronary bypass operation, I was knocked-out and felt terrible. For a long period afterwards, I had chest pain several times daily and needed to take nitroglycerin, which caused an unpleasant pressure in my head. Months later, I consulted another cardiologist who said that an operation was not needed right now. My mood improved right away, so did my general well-being, and the chest pain declined" (33).
     This agrees with findings that in patients who respond clinically well to the pain-relieving effect of acupuncture, a subjective period of mental stress will likely reverse experimentallyinduced acupuncture analgesia (32). Furthermore, in dogs conditioned to a stressful test situation, the electric stability of the heart was found to be decreased due to an increase in sympathetic activity (33). Similarly, the coronary circulation was found to be responsive to a conditioning procedure in which the animals "learned" voluntarily to decrease coronary blood flow to escape stress (34). In humans, verbal conditioning is found to influence exercise-testing in patients with angina pectoris (35).

Bias from the Acupuncturist
     When compared with surgery and pharmacological treatment, the risk of inducing bias is far greater in acupuncture treatment due to the extensive and prolonged contact between patient and doctor; 10- 12 times for 45 minutes, within a three-week period, in angina pectoris cases. Accordingly, it is of major importance to address the possible bias from the "Rosenthal Effect" induced by the acupuncturist. Owing to the very nature of acupuncture, and irrespective of the control treatment chosen, the acupuncturist can never be blinded. An experienced acupuncturist must administer the genuine treatment; otherwise, the treatment might not be properly performed. During training as an acupuncturist, one is exposed to a positive bias towards acupuncture, which will most likely be displayed during the trial.
     A special challenge in choosing a control treatment is in dealing with the possible physiological effects of human touch, distinct in acupuncture. Af ew examples illuminate the problem. Rats receiving a high-cholesterol diet and a one-to-one relationship with the investigator, including touch three times daily, showed a 60% reduction in diet-induced arteriosclerosis when compared with an untouched group (36). Premature infants in incubators increased their weight faster when touched daily, than did non touched infants in the same condition (37). In unconscious arrhythmic heart patients, manual pulse-taking had a normalizing effect on the heart rhythm (38, 39).

Bias from the Patient
     Effective patient blinding in an acupuncture trial is difficult to achieve. In the Western world, the amount of acupuncture information disseminated during the last decade has increased. The general population, therefore, has some knowledge of results and the way acupuncture may be experienced. Any control treatment differing from these perceptions may change the patient's expectations. Patients attending acupuncture trials will often have a positive or neutral attitude towards acupuncture; otherwise, ambivalent feelings toward the study may result. Compared to a pharmaceutical treatment, acupuncture is time-consuming and requires commitment. Hence, initial patient attitudes may create a positive bias towards acupuncture.

Influence from Psychosocial
     Factors Possible influences of patient psychosocial states on clinical trials is generally believed to be eliminated by the use of the double-blind randomized trial (1). However, unless the factors are identified and a stratification of the patients is performed, it is unknown whether the distribution of these characteristics is between the compared groups. Use of a crossover design, if possible, may solve this problem.
     The complexity of this issue was already apparent in 1958 when S. Wolf (40) wrote, "It is probable that most adaptive functions of the cardiovascular system are responsive to stimuli that owe their force to their special significance to the individual." Contemporary research confirms this theory. During experimentally-induced emotions such as anger, fear, and sadness, human blood pressure increases significantly. Response to exercise changes significantly with regard to heart rate, blood pressure, and exercise-performance (41). Anger increases heart rate and finger skin temperature more than happiness (42). Anger decreases the pumping function of the heart, measured as the ejection fraction, in patients with ischernic heart disease (43).
     Compared with non-depressed persons, individuals suffering depression are found to have 58% increased risk of a first myocardial infarction, as well as death from all factors (44). Depression is also a significant predictor of the 18-month, post-myocardial infarction cardiac mortality (45). The initial perception of illness in the patient suffering from an acute infarction is found to be an important determinant in returning to previous social life (46).
     The influences of psychosocial factors (personality, social support system, and life situation) are widely recognized in the pathogenesis of coronary heart disease (47). Treatment outcomes of these patients are similarly affected (48, 49, 50, 5 1).

Obvious Conclusions
     The conclusion can then be reached that the conditions of the traditional double-blind, randomized trials cannot be met in acupuncture studies because:
1) The patient cannot be truly blinded.
2) The acupuncturist cannot be truly blinded.
3) Psychological and social factors influence any treatment in heart patients.
     Consequently, it is mandatory to develop new methodological designs in order to eliminate the influences from these sources of bias.

A POSSIBLE SCIENTIFIC
ACUPUNCTURE STUDY DESIGN
Angina Pectoris Patients
     The first step in the present work was to evaluate the effect of needling in patients with angina pectoris. Subsequently, an investigation of the effects of needling on the cardiovascular system in healthy people became desirable.
     In order to eliminate the above-mentioned sources of bias, a triple-design was chosen: three individual tests were performed by three separate research teams, each unknown to the outcome of the other tests.
     The patients initially experienced a psychosocial test, including the patients' treatment outcome expectations for angina pectoris (52). The hypotheses tested were established through a retrospective testing of the patients participating in an initial study (53).
     Secondly, patients were randomized to genuine or sham acupuncture (54) for their angina pectoris. This afforded confidentiality of the observers. By correlating the results of this trial with the psychosocial testing, it was possible to detect whether such factors influenced the outcome of acupuncture used to treat an illness. The genuine acupuncture was performed according to traditional Chinese medicine, each patient receiving 10 treatments in a supine position within 3 weeks. The needles used were Chinese stainless steel, 30 gauge and 1.5 inch long. After obtaining needle sensation (or the arrival of Qi), the needles were left in place 20 minutes. No electrical or mechanical stimulation was given. In the control, needles were inserted superficially through the skin. No attempts were made to obtain needle sensation in points within the same spinal segments as the acupuncture points, outside the Chinese meridian system, or at trigger points. The needles were then left untouched.
     Thirdly (52, 55), the individuals then received traditional acupuncture from a different acupuncturist; the changes in skin temperature, pain threshhold (PT), and pain tolerance threshold (PTT) were recorded on the index finger (close to the acupuncture site), and on the hallux. The local effect of acupuncture was found to exceed the general one, in skin temperature (56), and pain threshold (57). This is in sharp contrast with the placebo effect; neither patient expectation nor conditioning is involved then (5, 6, 7).
     The patient study groups were told this experimental set-up was designed exclusively for the purpose of increasing our understanding of how acupuncture works, and thus, no accompanying therapeutic aim. In this respect, the trial examined the effect of acupuncture on skin temperature and pain thresholds. A computerized test program and automatic monitors were used to minimize the communication between acupuncturist and patient. Both were told not to discuss acupuncture during the procedure. The patient and acupuncturist were together for approximately one hour. It was assumed, however, that unexpressed acupuncturist expectancy was not likely to produce different effects on the index finger, when compared to the hallux. In this study, the needles were inserted in point Hegu (L1 4) bilaterally. Needles were stimulated electrically at 2 Hertz at an intensity sufficient to produce visible muscle contractions of musculus interosseus dorsalis 1, but well below pain threshold. The anode was connected to the left point Hegu (the measurement side). Later, however, Peter Nathan, M.D. (National Hospital for Neurology and Neurosurgery, London), pointed out that the two stimulation sites should, preferably, be on the same arm. Accordingly, this was changed in the study of healthy people (58).
     Skin temperature was used to reflect activity in the sympathetic nervous system, in order to examine the relationship between the anti-anginal effect and change in sympathetic tone. PT and PTT were included to examine their relationships to the anti-anginal effect of acupuncture; to elucidate the relationship between the pain-inhibitory and the anti-anginal effect of acupuncture.
     Correlating results from the two acupuncture trials resulted in acupuncturist bias being eliminated. The risk was considered that acupuncturist bias from two individually-blinded acupuncturists could interfere with results. Compared to the obvious known sources of errors, the anti-anginal effect that correlated to neurophysiological changes on the index finger (but not the hallus), was considered insignificant. Further-more, we believed that acupuncturist bias would have a general effect. Thus, no difference between hallux and index finger would be observed. The design helped to blind the patients as far as possible; patient expectation was already accounted for in the psychosocial questionnaire. Excluding patients who had previously received acupuncture treatment for their angina pectoris, eliminated the development of any conditioning response. This study had the potential for differentiating between a placebo effect, the specific effect due to needling, and the specific effect of traditional acupuncture.

RESULTS
     No significant influence from patient expectation and psychosocial factors on the anti-anginal effect of acupuncture was observed (52). No significant difference was noted between effects of the genuine, and sham acupuncture, on angina pectoris. Both noted daily activity with less nitroglycerin consumption and fewer angina attacks. Thus, it was concluded that the clinical improvement was due to a specific effect of both methods, or it was a placebo effect (54).
     In a neurophysiological trial, it was denoted that genuine acupuncture increased the pain thresholds locally but not distantly (55). This supports the findings by Andersson (57). Accordingly, it was concluded that effects observed during a neurophysiological trial were due to acupuncture itself and not acupuncturist bias.
     A significant relationship was observed between changes in skin temperature locally and the anti-anginal effect, and distant skin temperature was not affected. These findings supported the effects observed during a neurophysiological trial that acupuncture, rather than acupuncturist bias, was the key factor. Furthermore the findings suggested that a mutual mechanism was underneath the anti-angina effect of acupuncture, and a local increase in skin temperature. One such mechanism could be a decrease in sympathetic tone.
     Acupuncture was found to increase pain thresholds locally; this effect was not significantly correlated with the anti-anginal effect. Accordingly, an acupuncture-induced increase in pain threshold, and pain tolerance, was not found to play any significant role in the anti-anginal effect. Testing the validity of these findings, the change in exercise tolerance during an exercise test was related to the change in time. Myocardial ischemia was measured as time with ST-depression (as an indicator of an increase in pain threshold); with the change in Delta PRP (as an indicator of the oxygen consumption of the myocardium). The correlation was significant only as to an increase in Delta PRP. It was found to be significantly greater than that to time with ST-depression. Accordingly, these findings suggest that the anti-anginal effects may be due to positive hemodynamic alterations, rather than to an increase in pain thresholds.
     The alliance between anti-angina effect and change in skin temperature on the index finger was found to be significant, both for the groups receiving sham acupuncture and genuine acupuncture. Both treatments were interpreted to have a specific effect.

Healthy Subjects
     According to traditional Chinese theory, acupuncture in enhances the homeostatic mechanisms of the body. The findings in the patients with angina pectoris did not contradict this hypothesis. The hypothesis, however, should be tested in healthy subjects. Suggestive of the effects of acupuncture as being three-directional, it induces an increase in low initial values, a decrease of high initial values, and does not change intermediate values.
     A methodological point of view suggests the situation is simpler than when testing the effect in diseased persons. Using healthy individuals with no past acupuncture experience, the influence from subject-expectation was eliminated. In this trial (58), the effect of acupuncture was compared with the effect of a placebo pill in a randomized crossover design. Participants were told that the effect of the pill was expected to be the same as that of acupuncture. The exact effects were not told both to prohibit inducing certain expectations, and influencing the results. The randomized crossover design helped to eliminate a possible influence of bias from the observer. Furthermore, this person was separated from the subject and the acupuncturist by a curtain; all measurements were done by automatic machinery, and there was no verbal contact between subject and observer, or between subject and acupuncturist. The electric stimulators' unavoidable noise was always turned on throughout all sessions. The acupuncturist stayed with the subject during the entire test procedure and always performed the same physical movements; finger touch was included, whether the subject was having a placebo pill or acupuncture.
     The influence of the acupuncturist's expectations was eliminated by the hypothesis of the study; the effects of acupuncture being determined by the pre-treatment physiological state of the subject. Since this information was not available to the acupuncturist, there was no chance of anticipating any direction from responses of a particular person on a particular day. Similarly, there was no possibility of the subject developing a conditioning response.
     Risk is always present that an observed modulating effect of acupuncture would reflect the well-known: "Regression towards the mean." This was eliminated by comparing the effect of acupuncture to that of a placebo pill; in this trial, this represented the natural regression towards the mean. Acupuncture treatment points, Hegu (LI 4) and Shousanli (LI 10), were used bilaterally. The needles were inserted to a depth of approximately 5mm, perpendicular to the skin into the underlying muscle. After obtaining needle sensation, needles were stimulated electrically by 1 . 6 Hertz for 20 minutes, at a level of intensity sufficient to produce macroscopically-visible muscle movements, but well below the pain threshold. The anode was connected to point Hegu.
     Compared with a placebo, acupuncture had a significantly n greater homeostatic power during treatment, i.e., involving local of skin blood flow and systolic blood pressure/heart rate product (PRP), a measure of myocardial oxygen consumption. The difference was insignificant as to heart rate. During the 30-minute posttreatment observation period, the difference was significant as to local skin blood flow only.
     Based on this background, it was concluded that needling had an enhancing effect on existing homeostatic mechanisms of myocardial oxygen consumption, and local skin blood flow. The findings support the result of the angina pectoris study (52). A significant effect of acupuncture on myocardial oxygen consumption/supply ratio (measured as PRP), and sympathetic tone (measured as local skin blood flow/skin temperature), was observed.

THE EVALUATION OF ACUPUNCTURE
IN DAILY CLINICAL LIFE
     A design that allows both the doctor and the patient to act and interact in a natural manner is a necessity to evaluate the effect of acupuncture in daily life. Daily clinical life involves more than mere needling; acupuncture is a complex form of treatment in which the doctor supports the patient in striving toward a life in balance. This may include instruction in stress-reducing techniques, relaxation exercises, physical exercise, acupressure to be performed at home, and diet. Measuring the effects of such a treatment complex should appropriately include a cost-benefit analysis or a quality control.

Angina Pectoris Study Patients
     Obtaining a fair estimate, for the size and duration of acupuncture treatment effects in daily life, involved following 69 patients with advanced angina pectoris up to 2 years after treatment. Patients received 12 acupuncture treatments in a 4-week period, according to traditional Chinese theory. Needles were inserted in a supine patient position; after obtaining needle sensation, the needles were left in place 20 minutes. No electrical or mechanical stimulation was given. The patients were instructed to perform acupressure twice daily, on the middle of the stemurn at the level of the fourth intercostal space: Shanzhong (CV 17). Acupressure was also encouraged on the back between the shoulder blades, 1.5 inch lateral to the spinal processes of fourth and fifth thoracic vertebra: Jueyinshu (BL 14), and Xinshu (BL 15). Furthermore, patients were informed about adjustments in lifestyle and attitudes, stressreducing techniques, daily relaxation exercises, daily physical exercise, diets rich in potatoes, vegetables, fruits, bread, nuts, fish, garlic, olive oil, and moderate intake of red wine (59).
     Among the 69 patients, 49 were candidates for a coronary artery bypass grafting (CABG); bypass grafting was rejected in the remaining 20 patients. We compared our endpoint findings with those of a large prospective randomized trial, comparing CABG with percutaneous transluminal coronary angioplasty (PTCA). During the 24-month observation period, the incidence of death or myocardial infarction was 21% among the patients undergoing CABG, 15% among those undergoing PTCA, and 7% among our patients. No significant differences were found relating to pain relief between the 3 groups. An invasive treatment was postponed in 61 % of our patients owing to clinical improvement. The annual number of in-hospital days was reduced by 90%, bringing about estimated savings of $12,000 for each of our patients.
     The results suggest that the combined effects of acupuncture, acupressure, and lifestyle adjustments may be highly cost-effective for patients with advanced angina pectoris.

CONCLUSIONS REACHED
1. The study suggests that the needles have a biological effect of their own. However, the effect is not exclusively related to the Chinese acupuncture points; random points within the same spinal segment may achieve the same results.
2. The anti-angina effects of the needles may be due to positive hemodynamic alterations, rather than an increase in pain thresholds. A local decrease in sympathetic tone may account for a part of this effect.
3. The influence of patient expectations, psychological, and social factors may not be so pronounced that it is demonstrated in a trial of this size and observation period.
4. Utilizing a triple-design approach, including psychological and social measures, appropriate neuro-physiological tests, and a clinical evaluation of effects, furthers evaluation of the biological effect of needling versus a pronounced placebo effect.
5. In order to get an understanding of the underlying physiological mechanism of needling in the treatment of disease, it may be worthwhile to study the effects of physiological variables in healthy individuals.
6. The presented studies suggest: a) needling has an enhancing effect on the existing homeostatic mechanism concerning the myocardial oxygen consumption/demand ratio. b) needling effects the local tone of the sympathetic nervous system. This effect helps the patient with angina pectoris by increasing the working capacity of the heart. Consequently, the patients experience fewer anginal attacks during their daily lives.
7. Providing an evaluation method for the potential daily clinical applications of acupuncture, it is suggested that quality controls may be useful. This design provides the possibility to measure effects in a situation that approximates the use in daily clinical practice. The presented work indicates that acupuncture, acupressure, and lifestyle adjustments, applied according to classical Chinese philosophy, may be cost-beneficial for patients with advanced angina pectoris.

     The questions are: does this work aid in answering the puzzle Dr. Mehmet Oz's observation poses in the introduction? And, why are one-third of the patients not healed, when impaired blood myocardial supply is restored by a coronary artery bypass operation? It may be suggested that apart from epicardial blood supply, the pathogenesis of angina pectoris is influenced by stimulation of sensoric, emotional, social, and psychological origin. Furthermore, a treatment strategy addressing these pathogenetic aspects appears to be equally as efficient as high technological, invasive procedures in restoring epicardial blood supply. These findings indicate that further research in this direction may reap dividends.
     The goal here has been to illustrate some of the challenges occurring when contemporary scientific methods are applied to the treatment modality, acupuncture. Complex study designs, including large research teams, are required to meet these challenges. Select, detailed trials may be conducted as quality controls; estimating expected clinical improvement for patients treated with acupuncture in daily clinical life is possible.
     In societies with public-paid health systems, it is especially prudent that efficient treatments be thoroughly tested and offered. Outcomes of treatments are most important from the patient's view. Hence, quality control is mandatory. Hopefully, connections to national and international databases will soon provide an important tool in providing optimal health service for the entire world population.

(*Presented at the ICMART VII World Congress, Copenhagen, Denmark, May 9,1996.)

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AUTHOR INFORMATION
Dr. Soren Ballegaard is a cardiologist in Hellerup, Denmark.

Soren Ballegaard, M.D.
Acupuncture Centre
Lemchesvej 1, DK-2900
Hellerup, Denmark
Phone: +45 39 40 4142 - Fax: +45 39 40 4152
Email: ballegaard@akupunktur.dk

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