Acupuncture, a promising adjunctive therapy for essential hypertension: a double-blind, randomized, controlled trial

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ChangShik Yin*, ByungKwan Seo, Hi-Joon Park, Miran Cho1,

WooSang Jung", Ryowon Choue1, ChangHwan Kim, Hun-Kuk Park,

Hyejung Lee and HyeongGyun Koh

*Department of Acupuncture, CHA Biomedical Center, College of Medicine, Pochon CHA University, Seoul 135-081, Korea

Department of Acupuncture and "Department of Cardiovascular and Neurologic Diseases (Stroke Center), Kyung Hee University Hospital, Seoul 130-702, Korea
TKM Research Group, Kyung Hee University, Seoul 130-701, Korea

1Department of Medical Nutrition, Graduate School of East-West Medical Science, Research Institute of Clinical Nutrition, Seoul 130-702, Korea

 

Background: This study assessed effects of acupuncture as an add-on to conventional antihypertensive managements such as medication or lifestyle modification for hypertensive or pre-hypertensive subjects.

Methods: A randomized, double-blind, placebo-controlled trial was conducted at Kyung Hee University Hospital. Forty-one hypertensive or pre-hypertensive (systolic BP>120 mmHg or diastolic BP>80 mmHg) volunteers were recruited and randomly assigned into real or sham acupuncture groups. The hypertensive subjects on antihypertensive medication continued their medication. Acupuncture point prescriptions were partially individualized, based on the Saam acupuncture theory. Park's sham needle method was adopted for the sham procedure. Measurements were performed at baseline, weeks 4 and 8. BP, scales of overall health and pain, and anticipation or satisfaction for the treatments, were recorded.

Results: Thirty subjects completed the intervention, all of whom were on antihypertensive medication. The sham acupuncture group showed no significant change in mean BP, while the real acupuncture group showed a significant (p,0.01) decrease in mean BP after 8 weeks of intervention from 136.8/83.7 to 122.1/76.8 mmHg. Other factors showed no difference between the groups throughout the study.

Conclusion: Acupuncture seems to offer an additional benefit to the treatment of hypertensive patients. [Neurol Res 2007; 29: S98-S103]

Keywords: Acupuncture; blood pressure; clinical trials; hypertension

INTRODUCTION[1]
Hypertension affects approximately one billion indivi-duals worldwide, and the prevalence of hypertension tends to rise with age. Hypertensive blood pressure (BP)

is also a significant independent risk factor for heart attack, heart failure, stroke end kidney disease1. Hypertension is more than a problem of high BP alone.

It is a syndrome of metabolic and cardiovascular changes, and it is clear that clinicians are still confronting problems and unmet needs in the manage- ment of hypertension2. The need for lifelong management, and the poor compliance with or adverse effects of, antihypertensive medication, often result in low control rates of ,25%, especially in older people. Individuals within pre-hypertensive BP category of the report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure VII are not candidates for drug therapy, but require health-promoting lifestyle modifications to prevent the progressive rise in BP

Acupuncture has long been used in Korea, China and Japan, and its acceptance in the West is rapidly increasing. Increasing evidence suggests that acupuncture is useful for treating patients with neurological disease, including disorders of the autonomic nervous system, hypertension, heart insufficiency, stroke and other forms of cardiovas- cular disease. However, there is still insufficient evidence that acupuncture produces better results than conventional treatments. Recently, a large-scale study of acupuncture in hypertension, designed to gather preliminary data on the efficacy of acupuncture in treating hypertension without the use of pharmacologic therapy, was started.

To assess the potential benefit of acupuncture as an adjunctive therapy to conventional antihypertensive management of drug therapy or lifestyle modification. We conducted a double-blind, randomized, controlled trial, which showed promising results.

METHODS

Subjects
The study received approval from the institutional review board at Kyung Hee University Hospital of Oriental Medicine, Seoul, Korea, where this study was conducted from January 1 to May 31, 2004. Volunteers with hypertensive or pre-hypertensive BP were recruited through a public notice on the internet homepage of Kyung Hee University Hospital and articles in several local newspapers.

The subjects with systolic BP>120 mmHg or diastolic BP>80 mmHg were included. The subjects with systolic BP>140 mmHg or diastolic BP>90 mmHg were included only when they were already on anti-hypertensive medication. Subjects with systolic BP>180 mmHg or diastolic BP>100 mmHg were excluded to avoid any serious problem during the study. This study was aimed to investigate acupuncture as an adjunctive antihypertensive therapy; therefore, taking antihypertensive medication or BP within pre-hypertension category did not preclude a volunteer from joining, provided that his or her BP had been stable on the same medication or lifestyle modification without significant adverse reactions for at least 1 month to the study.

The exclusion and dropout criteria were as follows: secondary hypertension, manifest or unstable risk factors related to hypertension, a weight-reduction program or any change in antihypertensive medication 1 month before or during 8 weeks of the intervention period, history of a severe injury or psychologic disorder, a current severe painful condition and other uncontrolled medical problems such as atrial fibrillation or renal insufficiency. Current severe pain was an exclusion criterion when the severity of the current pain exceeded 50 on a 100 mm visual analogue scale (VAS). Subjects with systolic BP>140 mmHg or diastolic BP>90 mmHg and not on antihypertensive medication were excluded.

The estimated sample size was 15.68 based on a two- sample t-test (normal approximation) using the change in diastolic BP as the primary endpoint10-12. Practical considerations, such as a possible dropout rate of 40%, led us to recruit at least 23 subjects for each group. When allocated into two equal groups, the total estimated number of subjects needed was 46.

Blinding and randomization
The assessor and subjects were blinded to the infor- mation as to which group a subject belonged to throughout the study. A single assessor made the measurements including BP, psychologic factors and lifestyle throughout the study. The acupuncture treatment effect was controlled using Park's sham needle, a new non-penetrating sham acupuncture device13. The subjects were randomized using computerized random allocation.

Intervention
Acupuncture treatment, together with breathing and easy-walking exercises14,15, was adopted as adjunctive therapy in the management of hypertension. Seventeen sessions starting on the day of the study were performed with 3-4 day intervals between sessions, for 8 weeks. The acupuncture formula for a given subject was selected from four pre-made acupuncture prescriptions, which were based on and modified from the Saam acupuncture theory of Korean acupuncture after the constitutional energy traits of the subject was considered. The four formulas are as follows: (1) ST36, LI11 and BL25 for tonification of the large intestine (LI) meridian energy; (2) SP3, LU9 and BL13 for the lung (LU); (3) KI7, KI2 and CV4 for the kidney (KI); (4) LI1, GV14 and GB20 for the bladder (BL). LI, LU, KI or BL energy is typically considered deficient when a body is in a state of dampness, dryness, cold or hot, respectively. Optionally, PC6 and HT7 were added when a psychologic factor was considered of importance. The physician who performed the acupuncture treatment selected the prescription, and the selected prescription was not changed during the intervention period. In the real acupuncture group, the needle punctured the skin and was twisted slowly by, 90u, every 2 seconds, within a range of 180u, to search for the Deqi sensation. In the sham acupuncture group, the needle did not penetrate the skin, but was twisted slowly to imitate real acupuncture. After the Deqi sensation was detected, the needle was withdrawn immediately, as in the classic style of acupuncture.

On each acupuncture session, any adverse effect related to acupuncture was recorded using a checklist of adverse reactions, which included bleeding, hematoma, infection, neurological symptoms, fainting, dizziness, nausea, persistent Deqi sensation, aggravation of pain and others. The answers to the question on adverse reaction of acupuncture also served to find out if the blinding for the subjects was being successfully maintained. If the subject gave an answer implying that the acupuncture session they received was not a usual one considering their previous experience of acupuncture treatment or the acupuncture needle did not penetrate the skin, the subject was planned to be dropped out. Subjects were encouraged to follow the instructions for 10 minute deep, slow breathing exercise and to walk for 30 minutes a day at an easy pace during the 8 week period; they were also required to keep a record of compliance by filling out an exercise diary.

Measurements
The measurements consisted of the baseline measurements and outcome measurements made after 4 and 8 weeks of intervention. The measurements were carried out roughly at the same time of day for each measurement. The main outcome measurement was BP. BP was measured on the right upper arm using an automated sphygmomanometer (model T4, Omron, Japan) after 5 minutes in supine positions19. Average of 3 readings with a 5 minutes interval in supine positions was recorded. BP was taken six times for the baseline measurement and three times for the outcome measurements.

On every measurement day, the subject filled out a symptom list form and was asked an open question about subjective symptom changes and feeling about acupuncture sessions. In addition, lifestyle factors were recorded: preference for salty food, smoking and drinking, together with psychologic factors such as Beck's depression index, degree of the anticipation or satisfaction for the effectiveness of the treatment, overall health status and overall pain severity. The self-assessed overall health status, overall pain and anticipation/satisfaction with the effectiveness of the study intervention were measured on 100 mm VAS. Patient compliance with the breathing and walking exercises was assessed using the number of days when the exercise was carried out properly, as recorded in the exercise diary.

Statistical analysis
This study was designed as a per-protocol analysis. For the baseline measurements, an independent sample t-test and chi-squared analysis were used to examine differences between the two groups. Paired sample t-test was used to assess the temporal change 4 and 8 weeks after baseline in each group. Independent sample t-test was performed to assess any difference between the two groups. All the statistical analyses were performed using the SPSS 11.0 statistical package. p50.05 was used.

RESULTS

Subjects
Forty-one subjects gave informed consent and were registered and randomly allocated into two groups: 21 subjects in the real acupuncture group and 20 subjects in the sham group. All subjects were indigenous Korean. Four individuals in the sham acupuncture group had medical history: hepatitis C, angina, a fatty liver and gallstones, as did five in the real acupuncture group, herniated lumbar disks in two subjects, uterine cyst, hypothyroidism and bronchiectasis. The randomization was successful in that the baseline characteristics of the two groups did not differ significantly when compared using the independent sample t-test or chi-squared test for the items in Table 1.

Table 1: Comparison of the baseline characteristics between the two groups

[1] *Values are given as mean (95% CI). Numbers of subjects are given as n (%). All subjects were indigenous Korean. An independent sample t-test and chi-squared analysis were used to examine differences between the two groups. No significant difference was observed between the two groups (NS: no significant).

[2] The four acupuncture formulas, C2, Cz, D2 and Dz, indicate the following: (1) LI1, GV14 and GB20 for tonification of the bladder (BL) meridian energy; (2) KI7, KI2 and CV4 for the kidney (KI); (3) SP3, LU9 and BL13 for the lung (LU); (4) ST36, LI11 and BL25 for the large intestine (LI), respectively.

Table 2: Temporal changes of blood pressure 4 and 8 weeks after baseline

[1] Values are given as mean (95% CI).
*p,0.01 by paired sample t-test versus baseline and versus 4 weeks.

By the end of 4 weeks, nine subjects had dropped out: four (three; number in the real acupuncture group in parentheses) for job-related reasons, two (one) because of the distance to the hospital, one (zero) for severe gonalgia, one (one) for uncertainty about the effectiveness of the treatment and one (zero) forpersonal reasons. One subject in the real acupuncture group dropped out for job-related reasons and one subject dropped out in the sham acupuncture group for personal reasons after 8 weeks. The overall dropout rate was 27%. Six subjects in the real acupuncture group and five in the sham group did not complete the intervention, and measurement data were not obtained. Measurement data at week 4 were available for 32 subjects, while data were available for 30 subjects who completed the 8 week intervention. The data for the 30 subjects were analysed. All 30 subjects were on antihypertensive medication. The baseline characteris- tics of the 30 subjects in the two groups such as age, gender and others did not differ significantly (Table 1).

Changes in BP
The values of the systolic and diastolic BP at baseline, weeks 4 and 8, in the sham acupuncture group, did not change significantly, while those in the real acupunc- ture group showed a significant (p,0.01) decrease in BP during the second half of the intervention (Table 2).

The temporal change of the values of the systolic and diastolic BP showed a significant (p,0.05) difference between the two groups, during the second half of the intervention (Table 3).

Other changes in outcome measures
Paired sample t-test was performed for the scales of overall health, overall pain and anticipation / satisfaction. In the sham acupuncture group, the overall health scale increased during the second half of the intervention, while in the real acupuncture group, it increased during both parts of the intervention. The overall pain scale did not change significantly in the sham acupuncture group, while it decreased after the 8 week intervention in the real acupuncture group. The anticipation / satisfaction scale for the effectiveness of the treatment increased only in the real acupuncture group, during the second half of the intervention (data not shown).

Other factors that might affect BP showed no change, including alcohol consumption, smoking, daily breathing exercises, easy-walking exercises, tendency to use salt when cooking or eating, and body mass index (BMI).

Compliance, blinding and adverse effects
Of the 30 subjects who completed the entire intervention, acupuncture sessions were performed a mean of 16.2 times in the sham group (95% CI: 15.8- 16.6) versus 15.9 times in the real acupuncture group (15.4-16.4). The difference was not significant. Subject compliance was generally good, as reflected in the exercise diary. Subjects recorded that they performed the walking exercise a mean of 86.6 (78.3-92.9) and 84.6% (76.6-92.7) of days in the intervention period in the sham and real acupuncture groups, respectively. Similarly, breathing exercises were performed for a mean of 92.7 (89.1-96.4) and 93.1% (88.7-97.5) of days, respectively.

Blinding was successful in that no subject was dropped out by reason of finding out the sham nature of their acupuncture sessions.

The only adverse effect recorded was spot-bleeding, which occurred in 5% of all the real acupuncture sessions. The spot-bleeding was observed in eight subjects in the real acupuncture group, averaging 1.6 times per subject.

Table 3: Comparison of the temporal changes of blood pressure between the two groups

[1] *Values are given as mean (95% CI).
{p,0.05 by independent sample t-test.

DISCUSSION
Hypertension is an increasingly important medical and public health issue, and the benefits of lowering BP, such as reductions in the incidence of stroke (average reduction, 35-40%), myocardial infarction (20-25%) and heart failure (.50%), are significant. High pre-valence of hypertension which occurs in more than half of people aged 60-69 years old, in ,75% of those aged 70 years or more, and poor control in an estimated two- thirds of hypertensive patients, call for the advanced management of hypertension. Acupuncture has long been a therapeutic modality in East Asia, and is being increasingly accepted in the west5. Physiologic stimula- tion due to acupuncture is effective in many conditions, including neurological disorders.

The autonomic nervous system is involved in the development of hypertension, and chronic imbalance of the autonomic nervous system is a prevalent, potent risk factor for adverse cardiovascular events. Both increased sympathetic nerve firing rates and reduced neuronal norepinephrine reuptake contribute to sympathetic activation in hypertension. The possible mechanisms underlying the effect of acupuncture on cardiovascular disorders have been reported to include neurological influences, primarily via modulation of the autonomic nervous system. Acupuncture stimulation seems to reduce sympathetic nervous system activation via activation of the cholinergic system and opioid receptors in the rostral ventrolateral medulla, which is in agreement with a previous report of the naloxone-reversible cardiovascular depression effect of acupunc- ture25. The influence of acupuncture on the autonomic nervous system is reflected in heart rate variability, depending on the site of stimulation.

As the researchers of the ‘Stop Hypertension with the Acupuncture Research Program', now in progress, have pointed out that previous studies on acupuncture therapy for hypertension had serious methodological limitations8. According to an analysis of previous randomized controlled trials, acupuncture was no more effective than sham acupuncture or the antihypertensive drug reserpine, and the methods to control for the effect of acupuncture were to insert needles at incorrect acupuncture points, to use a group of acupuncture points not selected in accordance with traditional Chinese medicine principles and diagnosis, and not to perform acupuncture. Recent reports, have noted contradictory results after 4-8 weeks of intervention, and did not include proper methods of control, blinding or randomization. It is important to use proper control and blinding methods in acupuncture research. Park's sham needle, adopted in this study as a method of control and blinding, is reported to be an effective method.

This study was a double-blind, randomized, controlled clinical trial with an 8 week intervention period. Acupuncture, together with lifestyle management involving easy-walking and breathing exercises, was studied as an adjunctive to conventional pharmaceutical therapy. In this study, randomization and blinding should preclude election and measurement bias.

Attrition bias was negligible, considering the similar dropout rates. Nevertheless, a confounding bias such as performance bias might have affected the result. Sample size, follow-up period and standardization of the acupuncture formulas should be considered in future studies.

The acupuncture formula in this study was modified from the basic formulas in Saam acupuncture theory, a form of Korean acupuncture based on the diagnosis of imbalance in the constitutional meridian-energy traits. This study tried to imitate the real practices of Korean acupuncture and was not expected to involve per-acupuncture formula analysis. Therefore, the selection of the acupuncture formula was up to the physician who conducted the acupuncture. A real or sham needle was used for the respective acupuncture groups. Chisquared analysis of the distribution of the selected acupuncture prescriptions showed no difference between the two groups, at both randomization and completion, which suggest that the possible effect of selection of a different acupuncture formula was probably controlled between the two groups.

All the subjects whose data were analysed were those on antihypertensive medication. Acupuncture sessions were an adjunctive treatment to the subjects. On completion of the 8 week intervention period, the systolic and diastolic BP decreased 14.8 (mean, 95% CI: 9.2-20.3) and 6.9 (3.1-10.6) mmHg respectively in the real acupuncture group which was significant by pairedsample t-test. In the sham acupuncture group, the systolic and diastolic BP were 4.0 (22.7-10.7) and 1.1 (23.7-5.8) mmHg decreased, which was not significant by paired sample t-test. The only minor adverse effect observed was occasional temporary spot-bleeding at the skin-puncture site.

A subjective measure of overall health status tended to increase in both groups, and symptomatic improvement, such as improved digestion and decreased headache or backache, was often observed. The overall pain scale decreased only in the real acupuncturegroup. The subjects' belief in or anticipation of the effectiveness of acupuncture may affect the result of acupuncture treatment. We assessed this using a subjective measurement with a VAS. The values on the anticipation/satisfaction scale increased only in the real acupuncture group, during the second half of the intervention, which corresponded to the period when the down-regulating effect of acupuncture on BP was prominent.

Psychosocial factors play a role in the pathogenesis of hypertension30. The down-regulating effect of acupuncture seen in this study might be related to the neurological influences of acupuncture, which might be reflected in psychologic factors, such as subjective measures of overall health and pain, and a belief in its effectiveness or a feeling of satisfaction.

In conclusion, this study reports promising results from a double-blind, randomized, controlled trial of acupuncture in the management of hypertension. Considering hypertension is one of the significant risk factors for stroke, acupuncture might contribute to the decrease in the incidence of such disease. Further research should lead to the development and validation of a new strategy for the management of hypertension that integrates acupuncture and other physiologic therapeutics.

 

ACKNOWLEDGEMENT
This study was supported by the SRC program of KOSEF (R11-2005-014), Korea.

 

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Correspondence and reprint requests to: Hyeong Gyun Koh, KMD, PhD, Department of Acupuncture, Kyung Hee University Hospital, 1 Hoegi-dong, Dongdaemun-gu, Seoul 130-702, Korea. [acuyin@shinbiro.com]