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   Journal of Geriatric Cardiology March   2009 Vol 6 No 1 56  Review Article Chinese herbal medicine and acupuncture for the treatment of cardiovascular disease Jun Xu,  1  Haiyun Wu 2 1. American TCM Society, 14 East 34th Street, 5th Floor, New York, NY 10016, USA2. Institute of Geriatric Cardiology, Chinese PLA General Hospital, Beijing 100853, China Corresponding author: Dr. Haiyun Wu, Institute of GeriatricCardiology, Chinese PLA General Hospital, Beijing 100853, China;Email: Traditional Chinese medicine (TCM) is one of theworld’s oldest healing systems. TCM includes herbalmedicine, acupuncture, moxibustion, massage, food therapy,and physical exercise, such as shadow boxing. In modernChina, TCM is a fully institutionalised part of health careand widely used with Western medicine. In 2006, the TCMsector provided care for over 200 million outpatients and some 7 million inpatients, accounting for 10-20% of healthcare in China. 1  Numerous studies conducted in China and some in other countries have shown that TCM significantlyhelps patients with coronary heart disease, hyperlipidemia,hypertension, pericarditis, angina pectoris, tachycardia,atherosclerosis, heart failure, and other circulatoryconditions. Many doctors trained with Western medicinenow recognize that a combination of Western therapy and TCM has shown better results in improving overall healthin patients with cardiovascular disease (CVD) than havemodern medicine drugs or surgery alone. 2  In this review, we present a brief outline of TCM for the treatment of CVD,focusing on the two most used TCM therapeutic modalities,Chinese herbal medicine (CHM) and acupuncture. Thereare huge amounts of Chinese publications on the use of CHM and acupuncture for CVD, but only those published in English will be reviewed here. Traditional Chinese medicine TCM is both an art and a systemic theory of patient-centered healing with combined attention to body, mind,and spirit. Knowledge of TCM has been enriched for over 4,000 years of observation and clinical experience. The phi-losophy of TCM is rooted in Chinese cultures of Taoism (tofollow nature’s way) and Confucius (to nurture humanityand morality) and the religion of Buddhism (to free fromsuffering). Traditionally, TCM doctors are usually pharma-cists and pharmacologists who themselves identify and collect herbs, prepare formulation and follow up their  patients. 3 In literature, TCM is characterized by individualized treatments based on the differentiation of syndrome(Zheng). CHM is the major modality in TCM practice. A prescription for CHM usually refers to a compound recipe(Fu Fang) that consists of principal, assistant, adjuvant,and guiding herbs to maximize therapeutic effects and mini-mize toxic effects. Ingredients in a CHM prescription areindividualized and changed on a weekly basis to tailor for the patient’s age, gender, symptoms, anthropologicalcharacters, geological location and living environment. 4  Thecompounds extracted from Chinese herbal medicines includeflavonoids, xanthones, triterpenoids, alkaloids, glycosides,alkyldisulfides, aminobutyric acid derivatives, guanidine, polysaccharides, peptides, and minerals. 5  In TCM, treat-ment effects are described differently, e.g., improved qi and  blood flow; decrease in blood stasis and qi stagnation; de-creased stagnation of cold in the chest; decreased phlegm,fluid, and damp accumulation; supplemented and nourished heart yin; strengthened heart qi; draining of heart fire; har-monized heart connections to other organs (not just ana-tomically speaking) such as kidneys, lung, pericardium,spleen, gallbladder, and small intestine; and reinforced and invigorated heart yang.Acupuncture involves the insertion of needles and stimulation of acupoints that are located at lines of merid-ians that correspond to the flow of energy through the body.Modern acupuncture has evolved other methods of stimu-lating acupoints including the use of an electrical current, by applying pressure to the acupoint (acupressure) or us-ing a low intensity laser. Texts on acupuncture date back to206 BC, although the Yellow Emperor, Huang Di, the srci-nator of TCM lived in 2,697 BC. During the past decades,acupuncture has gained increasing acceptance by the lay public, partly as a result of increasing communication be-tween the U.S. and China since the early 1970s. 4,   6  The mecha-nism by which acupuncture is believed to benefit the sub- ject is through its ability to modulate neural activity in sev-eral regions of the brain and thus reduces sympathetic out-flow to the heart and vascular system. 7   Journal of Geriatric Cardiology March   2009 Vol 6 No 1 57 Chinese herbal medicine for the treatment of specific CVD Heart failure Although CHM has been widely used for the treat-ment of heart failure and thousands of studies have beenreported, only a few were published in English, most of them were on a compound recipe: Sheng-mai-san (SMS),which is comprised of Radix Ginseng, Radix Ophiopogonis,and Fructus Schisandrae Chinensis. SMS has been clini-cally used for more than 800 years in China. According toChinese medical theory, SMS is prescribed for replenishingvital energy, restoring the circulation, and sustaining bodyfluids. SMS is commonly used in patients suffering fromcoronary heart disease, cardiogenic shock, and congestiveheart failure. A recent review of 19 clinical trials found that,compared to usual treatment alone, SMS injection plus usualtreatment showed significant improvement in New York Heart Association classification of clinical status (RR 0.32;95% CI 0.25 to 0.40), mortality (RR 0.25; 95% CI 0.07 to 0.86),hemodynamic tests, and tumor necrosis factor-alpha (WMD-0.52; 95% CI -0.99 to -0.05). No adverse affects were re- ported in any of the included trials. The authors concluded that it is possible that Shengmai plus usual treatment may be beneficial compared to usual treatment alone for heartfailure, although the evidence is weak because of the poor quality of the included trials. 8 Hypertension TCM is widely used in the treatment of hypertensionin China, whether in fixed or individualized recipe. AmongCHMs, Stephania tetrandra, Lingusticum wallichii,Uncaria rhynchophylla , and  Evodia rutaecarpa  are morecommonly used as hypotensive medicine. Tetrandrine, analkaloid extract of S.   tetrandra , has been shown to be acalcium ion channel antagonist, paralleling the effects of verapamil. Tetrandrine blocks T and L calcium channels,interferes with the binding of diltiazem and methoxyverapamilat calcium-channel binding sites, and suppresses aldoster-one production. A parenteral dose (15 mg/kg) of tetrandrinein conscious rats decreases mean, systolic, and diastolic blood pressures for more than 30 minutes; however, an in-travenous 40 mg/kg dose killed the rats by myocardialdepression. In stroke-prone hypertensive rats, an oral doseof 25 or 50 mg/kg produced a gradual and sustained hy- potensive effect after 48 hours without affecting plasmarenin activity. 7  In addition to its cardiovascular actions,tetrandrine has reported antineoplastic, immunosuppressive,and mutagenic effects. 9 More recently, tetrandrine has been implicated in anoutbreak of rapidly progressive renal failure, termed Chi-nese herb nephropathy. Numerous individuals developed the condition after using a combination of several Chineseherbs as part of a dieting regimen. It has been hypothesized that the cause may be attributed to misidentification of S.tetrandra ; nonetheless, questions still remain as to the roleof S. tetrandra  in the development of this serious toxic effect. 10 The root of  L. wallichii  is used in TCM as a circula-tory stimulant, hypotensive drug, and sedative.Tetramethylpyrazine, the active constituent extracted from  L. wallichii , inhibits platelet aggregation in vitro and low-ers blood pressure by vasodilation in dogs. With its actionsindependent of the endothelium, tetramethylpyrazine’svasodilatory effect is mediated by calcium channel antago-nism and nonselective antagonism of -adrenergic receptors.Some evidence suggests that tetramethylpyrazine acts onthe pulmonary vasculature. Currently, there is insufficientinformation to evaluate the safety and efficacy of this herbalmedicinl. 11 U. rhynchophylla  is sometimes used in TCM to treathypertension. Its indole alkaloids, rhynchophylline and hirsutine, are thought to be the active principles of  U. rhynchophylla ’s vasodilatory effect. The mechanism of  U. rhynchophylla ’s actions is unclear. Some studies pointto an alteration in calcium ion flux in response to activation,whereas others point to hirsutine’s inhibition of nicotine-induced dopamine release. One in vitro study has shown U. rhynchophylla  extract relaxes norepinephrine- precontracted rat aorta through endothelium-dependent and -independent mechanisms. For the endothelium-dependentcomponent, U rhynchophylla extract appears to stimulateendothelium-derived relaxing factor and/or nitric oxide re-lease without involving muscarinic receptors. Also, in vitroand in vivo studies have shown that rhynchophylline caninhibit platelet aggregation and reduce platelet thrombosesinduced with collagen or adenosine diphosphate plusepinephrine. Safety and efficacy cannot be evaluated at thistime because of a lack of clinical data. 12  E. rutaecarpa  (wu-chu-yu) is a Chinese herbal drugthat has been used as a treatment for hypertension. It con-tains an active vasorelaxant component called rutaecarpinethat can cause endothelium-dependent vasodilation in ex- perimental models. 9 Coronary heart disease In TCM, most cases of angina are considered to becaused by Xueyu (blood stasis) and/or Tanzuo (phlegmstagnation). Dozens of recipes have been used for the treat-ment of angina during the past decades. Among them, suxiao jiuxin wan, which composed of  Ligusticum chuanxiong  Hort.(chuanxiong) and Borneolum syntheticum (bingpian), and more recently, Salvia droplet pill (fufang danshen diwan)are most widely prescribed fixed compounds. A systemicreview of 15 trials involving 1,776 patients showed thatsuxiao jiuxin wan improved ECG measurements (RR 1.16,95% CI 1.05 to 1.27), reduced symptoms (RR 1.09, 95% CI1.04 to 1.13), reduced the frequency of acute attacks of an-gina (difference in means -0.70, 95% CI -0.90 to -0.50), re-duced diastolic pressure (difference in means -3mmHg, 95%   Journal of Geriatric Cardiology March   2009 Vol 6 No 1 58 CI -5.73 to -0.27) and reduced the need for supplementarynitroglycerin in patients with angina pectoris. 13 Salvia miltiorrhiza  (dan-shen), a relative of the West-ern sage Salvia officinalis , is perhaps the most marketingCHM in China. The effects of dan-shen for the treatment of AMI and other CVD have been extensively reviewed recently. 13  In TCM, the root of S. miltiorrhiza  is used as acirculatory stimulant, sedative, and cooling drug. S.miltiorrhiza  may be useful as an antianginal drug becauseit has been shown to dilate coronary arteries in allconcentrations, similar to Panax notoginseng . Also, S.miltiorrhiza  has variable action on other vessels depend-ing on its concentration, so it may not be as helpful in treat-ing hypertension. In vitro, S. miltiorrhiza , in a dose-depen-dent fashion, inhibits platelet aggregation and serotoninrelease induced by either adenosine diphosphate or epinephrine, which is thought to be mediated by an increasein platelet cyclic adenosine monophosphate caused by S.miltiorrhiza ’s inhibition of cyclic adenosine monophos- phate phosphodiesterase. S. miltiorrhiza  appears to have a protective action on ischemic myocardium, enhancing therecovery of contractile force on reoxygenation. Morerecently, S. miltiorrhiza  has been shown to protect myo-cardial mitochondrial membranes from ischemia-reperfusioninjury and lipid peroxidation because of its free radical-scav-enging effects. Qualitatively and quantitatively, a decoc-tion of S. miltiorrhiza  was as efficacious as the more expen-sive isolated tanshinones. 14, 15 The root of P. notoginseng  is also often used in thetreatment of patients with angina and coronary arterydisease. Because of its resemblance to P. ginseng  (Asianginseng), P. notoginseng  has acquired the common nameof pseudoginseng, especially since it is often an adulterantof P. ginseng  preparations. P. notoginseng  has been de-scribed as a calcium ion channel antagonist in vascular tissue. More specifically, its pharmacological action may beas a novel and selective calcium ion antagonist that doesnot interact with the L-type calcium ion channel but rather may interact with the receptor-operated calcium ion channel. 16 Arrhythmia  Numerous Chinese herbal medicines are identified tohave antiarrhythmic effects, such as xin bao, ci zhu wan, buxin dan, and several others. 17  However, few clinical trialshave been conducted to study their effects and safety. Inone observational study, the effects of xin bao were docu-mented in 87 patients with sick sinus syndrome. Xin baowas administered orally 2 to 3 times per day for 2 months.Patients with major symptoms of sick sinus syndrome, whichincluded dizziness, palpitations, and chest pressure, im- proved significantly after treatment. 18  No serious adverseeffects were noted.Shensong Yangxin (SSYX) is one of the compound recipes of traditional Chinese materia medica including 12ingredients such as P. ginseng , dwarf lilyturf tuber,nardostachys root, etc. Clinical study showed that SSYXcould reduce the number of ventricular extrasystoles in pa-tients with or without structural heart disease. Animal modelshowed that SSYX significantly inhibited the arrhythmiasinduced by toxic chemical compounds or ischemia-reperfusion injury. One of the mechanisms underlyingSSYX’s antiarrhythmic effects may be related to it’s actionof blocking multiple ion channels such as INa, ICa,L, IK, Itoand IK1, which may change the action potential duration. 19 Acupuncture for the treatment of CVD The World Health Organization (WHO) has noted thatacute infection and inflammation, dysfunction of autonomicnervous system, pain, and peripheral and central neurologi-cal diseases each represent conditions for which acupunc-ture may be indicated. There are four areas of CVD for whichacupuncture eventually may be indicated. These includeischemic CVD, hypertension, heart failure, and arrhythmias. 20 Coronary heart disease Experimental studies indicate that acupuncture re-duces demand-induced myocardial ischemia in felines, cat-echolamine- or stress-induced hypertension, or geneticallyassociated hypertension. These studies also demonstratethat acupuncture limits myocardial ischemia by reducingmyocardial oxygen demand rather than by increasing coro-nary blood flow in a feline model. 21, 22  Studies from severalgroups have examined the role of acupuncture in treatmentof patients with stable angina. Ballegaard and colleagues 23,24 showed an acupuncture-related improvement in exercisecapacity and rate-pressure product, particularly when acu- puncture reduces sympathetic neural outflow. Separately,Richter et al. 25  observed that acupuncture exerted a benefi-cial effect in patients with severe stable angina who had  been aggressively treated with medical therapy. Manual acu- puncture reduced the number of anginal attacks per week,the severity of chest pain, electrocardiographic evidence of myocardial ischemia, and increased the workload required to provoke angina in patients with CAD and stable angina.The latter study used a tablet placebo control. These stud-ies involved small numbers of patients, were unblinded, and did not use the most appropriate sham controls. Hypertension The rationale for using acupuncture to treat myocar-dial ischemia, hypertension, and arrhythmias stems from itsability to inhibit sympathetic outflow. Several small trialssuggest that hypertension may be improved by acupuncture.The magnitude of the effect of acupuncture on blood pres-sure in patients with hypertension is small but significant;reductions of 5 to 10 mm Hg have been noted. These and    Journal of Geriatric Cardiology March   2009 Vol 6 No 1 59 other small studies from outside the U.S. have led to fund-ing of at least two ongoing clinical trials by the NCCAM totest the hypothesis that acupuncture can lower blood pres-sure in patients with hypertension. Although there are nowell-controlled studies in humans, there is a suggestionthat one to four courses of 10 days’ treatment with acu- puncture lowers blood pressure (5 to 25 mm Hg) in some (e.g., borderline and essential hypertension) but not in all typesof hypertension.  26 Two high-quality randomized controlled trials (RCTs)of acupuncture for hypertension have been recently published, but with conflict results. In the Stop Hyperten-sion With Acupuncture Research Program (SHARP) trialcomparing individualized (and standard) Chinese acupunc-ture with a sham procedure, blood pressure declined in eachgroup between randomization and the 10-week follow-up, but the differences in achieved blood pressure reduction between groups were not significant. Thus, the authorsconcluded that there was no evidence of benefit of acu- puncture for blood pressure lowering. 27 However,Flachskampf et al 28  report a single-institution, single-blind randomized controlled trial of 160 adult patients with grade1 or 2 hypertension on stable blood pressure-loweringtherapy or no therapy. Over a 6-week period involving atotal of 22 treatment sessions, blood pressure-specific acu- puncture was administered to intervention group subjectsand sham acupuncture to control group subjects by Chi-nese physicians trained and accredited in Chinese tradi-tional medicine. The authors report that the change in 24-hour ambulatory systolic blood pressure between baselineand 6 weeks (primary outcome) was significantly greater (-6mm Hg) in the intervention group compared with the con-trol group (1 mm Hg), although blood pressure in both groupsreturned to pretreatment levels within 12 weeks of treatmentcessation. The authors conclude that acupuncture may of-fer an alternative antihypertensive therapeutic option espe-cially in patients who want to avoid drug therapy or areattracted to the spiritual foundations of such a therapy. Heart failure In the first study to examine acupuncture in heartfailure, Chen and colleagues 29  studied patients with 1) hy- pertrophic cardiomyopathy (n=24), 2) congestive cardiomy-opathy (n=16), and 3) normal healthy control subjects (n=12).Acupuncture was compared at 2 sites bilaterally: 1) Neiguan(P6) and 2) Shaofu (H8). Electroacupuncture (EA) for 2 min-utes was followed by retention of the needles in place for 15minutes. Echocardiography, apex cardiography, and sys-tolic time interval were used to assess cardiac performance before and after acupuncture. In 2 patients, pulmonary cap-illary wedge pressure was recorded. In the hypertrophiccardiomyopathy group, acupuncture at Neiguan was asso-ciated with an overall worsened cardiac performance. Leftventricular outflow diameter was diminished, stroke volumeand cardiac output were diminished significantly, and the pulmonary capillary wedge pressure increased. In contrast,in the congestive cardiomyopathy group, acupuncture at Neiguan improved parameters of cardiac function, specifi-cally contractility. Left ventricular outflow diameter, strokevolume and cardiac output, and pulmonary capillary wedge pressure decreased. The opposite acute effects were seenafter stimulation at Shaofu. That is, left ventricular outflowtract diameter increased in hypertrophic cardiomyopathy but decreased in congestive cardiomyopathy; stroke vol-ume and cardiac output increased in hypertrophic but de-creased in congestive cardiomyopathy. Acupuncture had no significant effect in normal subjects. The investigatorsconcluded that acupuncture at the Neiguan point had anoverall acute sympathomimetic effect, which could beacutely beneficial in congestive cardiomyopathy, whereasShaofu appeared to be sympatholytic with similar effects to beta-blockers in hypertrophic cardiomyopathy. In a small,controlled but unblinded study, the acute effect of electroacupuncture at Neiguan or at an adjacent,nonacupoint site on the heart rate, blood pressure, and echocardiographic findings in 8 patients experiencing con-gestive heart failure was studied. After Neiguan stimulation, but not control stimulation, left ventricular end diastolicvolume and stroke volume increase significantly. Heart rate, blood pressure, and ejection fraction remained unchanged after each type of stimulation. The investigators concluded that acupuncture at Neiguan improved ventricular relaxation, but in contrast to Chen’s study, contractility was not af-fected by acupuncture at Neiguan.  30  In a study of a large,heterogeneous group of cardiac patients (n=107) and con-trol subjects (n=100) without cardiac disease, the effects of needling at the left Neiguan point on left ventricular func-tion was examined. 31  In normal subjects, heart rate decreased significantly after needling, but other parameters of cardiacfunction remained unchanged. In cardiac patients, heart ratedecreased, contractility increased, but ventricular relaxationremained unchanged. The explanations for the inconsistentfindings in these studies can be found in their limitations of size, inadequate or absent controls, and unblinded design.To date, there are no large randomized, controlled trials of acupuncture in heart failure in which investigators inter- preting echocardiographic and/or hemodynamic data are blinded and satisfactory acupuncture controls are used. Theeffects of chronic acupuncture in patients experiencing heartfailure have not been studied.More recently, Middlekauff et al. 32  reported the effectof acute acupuncture in patients experiencing chronic heartfailure. Ten patients with advanced heart failure underwentacute mental stress testing before and after “real” acupunc-ture at Neiguan (P6), Hegu (Li4), and Taichong (Liv3). Acu- puncture needles were inserted and manually stimulated toachieve the De Qi sensation of heaviness, fullness, or soreness, and then left in place for 15 minutes. Mental stress
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