Acupuncture for the Treatment of Cardiovascular Diseases: A Systematic Review

Journal of Acupuncture and Meridian Studies Available online 27 July 2018 open access In Press, Uncorrected ProofWhat are Uncorrected Proof articles? Journal of Acupuncture and Meridian Studies Review Article Author links open overlay panelRodrigode Lima Pimentel1Alice P.Duque1Beatriz R.Moreira2Luiz F.RodriguesJunior12 1 Laboratory of Cardiovascular Biophysics, Department of Physiological Sciences, Biomedical Institute, Federal University of the State of Rio de Janeiro, Rio de Janeiro, RJ, Brazil 2 Physiotherapy Service, National Institute of Cardiology, Rio de Janeiro, RJ, Brazil Received 16 May 2018, Revised 16 July 2018, Accepted 23 July 2018, Available online 27 July 2018. Show less https://doi.org/10.1016/j.jams.2018.07.005Get rights and content Open Access funded by International Pharmacopuncture Institute Under a Creative Commons license Abstract Acupuncture, for the westerns countries, is an innovative and low-cost therapy for treatment and prevention of cardiovascular diseases (CVDs). However, most of its effects and mechanisms are poorly understood. Thus, the objective of this work was to systematically review the literature regarding the clinical effects of acupuncture for the treatment and prevention of CVDs. A search for papers published in English or Portuguese in the past 20 years was conducted at PubMed, SciELO, and PEDro databases. Clinical trials conducted on the effects of acupuncture were included in this review. Two reviewers extracted the data independently from the remaining 17 articles after screening. The most used acupoint was PC6 (10 studies, 64.7%), followed by ST36 (6 studies, 35.3%) and auricular acupoints (4 studies, 23.5%). Among the clinical applications, hypertension was the most studied CVD, with acupuncture being the most reported method among the studies (70.6%). Only three articles reported no benefit in the treatment of CVDs for the methodology used. We conclude that although several studies indicated an improvement in the response of the cardiovascular system in CVDs by acupuncture, electroacupuncture, or electrostimulation treatment, the heterogeneity of the studies does not allow a standardization of its application for each specific disease, making further studies necessary for its use to become a reality. Previous articleNext article Keywords acupuncturecardiovascular diseaseelectroacupuncture (EA)transcutaneous electrical acupoint stimulation (TEAS) Introduction The World Health Organization estimates that 17.5 million people died of cardiovascular diseases (CVDs) in 2012, representing 31% of all deaths worldwide [1]. The coronary artery disease (CAD) is the leading cause of death, followed by cerebral vascular disease. Together, both are responsible for 7.4 and 6.7 million of deaths, respectively [2]. The global number of deaths caused by CVDs increased by 12.5% during the last decade [3]; in the last 2 decades, the prevalence of CVDs has been particularly high in low and middle-income countries, which account for 80% of the deaths caused by CVDs [4]. The estimated annual cost of interventions for prevention and treatment of CVDs in those countries is just over US$8 billion [5]. In Brazil, it is estimated that approximately U$ 3.2 billion was spent in the health sector with direct costs for cases of severe CVDs in 2004; combined with the indirect cost of retirements and incapacity benefits incurred by CVDs, the effect on the economy was around U$12 billion [6]. The scenario described above favors the applying of innovative and low-cost therapies, such as most alternative and complementary therapies, for treatment and prevention of CVDs. Traditional medicine methods, including acupuncture, electroacupuncture (EA), and transcutaneous electrical acupoint stimulation (TEAS), have been increasingly adopted by health-care professionals despite the lack of evidences on its effects on CVDs [7]. Acupuncture is a traditional therapeutic method from East Asia, dating back more than 2000 years [8]. It is based on peripheral neural stimulation by the introduction of needles into specific regions of the body surface, called acupuncture points or acupoints, with the intention of promoting organic and functional changes for therapeutic purposes or simple neuromodulation [9]. The occidental scientific community has been studying acupuncture effectiveness and its physiological mechanisms of action on the relief of pain, revealing it to be a powerful mode of sensorial stimulation. Recently, the number of studies publishing about acupuncture effects on a wide spectrum of pathologies and etiologies, such as infection, inflammation, dysfunction of the autonomic, peripheral, and central nervous system, metabolic disorders, and CVDs has increased [10], [11]. EA is an acupuncture method in which acupoints are stimulated by a pulsating electric current applied through metallic needles from an electrostimulation device [12]. One of the main advantages of EA, from a clinical or research perspective, is its capacity to define the intensity objectively and quantifiably by altering the amplitude of wave and frequency [13]. Transcutaneous electrical acupoints stimulation (TEAS) is another acupuncture method [12]. It is based on the application of a pulsating electric current to the surface of the skin, above the regions corresponding to acupoints, using electrodes. Studies performed with rats have demonstrated that the efficacy and mechanisms of the analgesic response induced by TEAS are similar to those induced by EA and acupuncture. In addition, it has been demonstrated that electrical stimulation at an acupoint with the use of electrodes can reach deeper tissues and induce the intended effects without the need for needles [12], [14], thereby, reducing intercurrences caused by needles such as discomfort by perforation, risk of future infections [15], and localized argyria [16]. Currently, the effects of acupuncture, EA, and TEAS for the treatment of CVDs remains poorly understood, and most of its mechanisms have not yet been completely elucidated. So, the purpose of the current study was to review the literature on the effects of acupuncture, EA, and TEAS in CVDs. Methods This systematic review followed the recommendations in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses [17] as well as the tutorial for writing systematic reviews [18]. We performed literature searches with the PubMed, SciELO, and PEDro databases, using concomitant and alternating combinations of the following English descriptors: “acupuncture,” “electrostimulation,” and “electroacupuncture” with “hypertension,” “cardiovascular disease,” “coronary artery” and “heart” as Medical Subject Headings (MeSH, http://www.nlm.nih.gov/mesh/meshhome.html); and the following are Portuguese descriptors: “acupuntura”, “eletroestimulação” and “eletroacupuntura” with “hipertensão”, “doenças cardiovasculares”, “doença coronariana,” and “válvula cardíaca.” Two reviewers extracted the data independently. Clinical trials published between January 1997 and September 2017, in English or Portuguese, which provided the full text in the aforementioned databases and indicated results regarding the association of one of the relevant techniques for treatment and/or prevention of CVDs, were included in this study. Reviews, observational, and experimental studies using animal models were excluded from the study. The methodological quality of the studies was analyzed based on the score on the Physiotherapy Evidence Database scale provided in the PEDro database (Table 1). This analysis was performed independently by two evaluators, and disagreements were resolved by discussion and consensus. If a selected study was not scored in this database, the authors ranked it using the Portuguese (Brazilian) version of the scale [19]. Table 1. Methodological quality assessment by the Physiotherapy Evidence Database (PEDro) Scale. PEDro scale items Author, date 1 2 3 4 5 6 7 8 9 10 11 Score Abdi et al, 2017 Yes Yes Yes Yes Yes No No Yes No Yes Yes 7/10 Carpenter et al, 2010 Yes Yes Yes Yes Yes No No Yes Yes Yes Yes 8/10 Ho et al, 1999 Yes No No Yes No No No Yes Yes Yes Yes 5/10 Jiang, 2003 Yes Yes No Yes No No No No No Yes Yes 4/10 Kim et al, 2012 Yes Yes Yes Yes Yes No Yes No Yes Yes Yes 8/10 Kurono et al, 2002 Yes Yes Yes Yes No No No Yes Yes Yes Yes 7/10 Li et al, 2015 Yes Yes Yes Yes Yes No No Yes Yes Yes Yes 8/10 Liu et al, 2015 Yes Yes Yes Yes No Yes Yes Yes Yes Yes Yes 9/10 Lomuscio et al, 2011 Yes Yes No Yes No No Yes Yes Yes Yes Yes 7/10 Park et al, 2010 Yes Yes Yes Yes Yes No Yes Yes Yes Yes Yes 9/10 Severcan et al, 2012 Yes No No No No No Yes Yes Yes Yes No 4/10 Wang et al, 2015 Yes Yes No Yes No No No Yes Yes Yes Yes 6/10 Yang et al, 2010 Yes Yes No Yes Yes No Yes Yes Yes Yes Yes 8/10 Yeh et al, 2015 Yes Yes Yes Yes No No No Yes Yes Yes Yes 7/10 Yilmaz et al, 2017 Yes Yes No Yes Yes No No Yes Yes Yes Yes 7/10 Yin et al, 2007 Yes Yes No Yes Yes Yes Yes Yes Yes Yes Yes 9/10 Zamotrinsky et al, 1997 Yes Yes Yes Yes No No No Yes Yes Yes Yes 7/10 1 = eligibility criteria; 2 = random allocation; 3 = concealed allocation; 4 = baseline comparability; 5 = blind patients; 6 = blind therapists; 7 = blind assessors; 8 = adequate follow-up; 9 = “intention-to-treat” analysis; 10 = between-group comparisons; 11 = point estimates and variability. Eligibility criteria item does not contribute to total score. Results A total of 506 articles were selected, of which 120 were excluded based on the date of publication, 316 were excluded because they were not clinical trials, 37 were excluded because they were not available in English or Portuguese (29 in Chinese, 2 in Spanish, 2 in German, 1 in Russian, 1 in Japanese, 1 in Korean, and 1 in Persian), and 16 were excluded for not directly associating one of the techniques with at least one CVD. Finally, 17 studies were included in the present review (Fig. 1) and are summarized in Table 2. Figure 1 Download high-res image (486KB)Download full-size image Figure 1. PRISMA flow diagram. PRIMSA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Table 2. Study characteristics. Author, year Technique Application points Study type Sampling (number of individuals) Duration Related cardiovascular disease Main results Abdi et al, 2017 [27] Acupuncture Abdominal (ST25, GB28, RN12, RN9, RN4, and SP6). Auricular (TF4, CO1, CO4, CO17, and HX1) Controlled; randomized Auricular: 204 (102C 102T); Abdominal: 196 (98C 98T) 2 times per week for 6 weeks Hypertension Significant time-dependent improvement in systolic blood pressure (SBP) measurements in the abdominal intervention group, a significant increase in SBP level in the auricular intervention group. Carpenter et al, 2010 [43] Acupuncture Back Shu, PC6, EX12, urinary bladder (15, 17, 18, 20, 23), and auricular. Cross-over; single-blind 12T 1 time Vasovagal syncope and Hypertension Significant decrease in sympathetic balance (low frequency: high frequency and SBP at rest). Ho et al, 1999 [38] Acupuncture PC6 Controlled 22C, 22T 1 time Coronary disease Mean values of left ventricular ejection fraction increased significantly at baseline, during, and after 15 minutes of acupuncture but became insignificant at one week. Jiang, 2003 [9] Acupuncture LI11, ST40, and LR3 Controlled; randomized 30T, 30C 1 time per day; 6 days Hypertension There was no difference in BP and plasma levels of ET-1 between the treated group and the control group. Kim et al, 2012 [23] Acupuncture ST36 and PC6 Placebo-controlled; randomized; double-blind 12T, 16P 2 times per week, 8 weeks Hypertension Increased diastolic blood pressure (DBP) at night and increased number of dippers. Kurono et al, 2002 [39] Acupuncture PC6 Randomized 16T (10 LN, 6 SPM) 1 time Coronary disease There was an increase in the diameter of the coronary artery in some patients after acupuncture but coronary narrowing in other patients. Li et al, 2015 [22] Electroacupuncture PC5, PC 6, ST36, and ST37 Two-arm parallel randomized; blinded for participants and for researcher 65T (33 in points PC5-6 + ST 36 + 37/in LI 6-7 + GB 37-39) 1 time per week; 8 weeks Hypertension Peak decrease and median SBP and DBP; decreased plasma concentrations of norepinephrine, renin and aldosterone. Liu et al, 2015 [21] Acupuncture LI11, SP4, ST36, LT3, and PC6 Controlled; randomized; blinded for assessors and for statistician 48T, 13C 8 weeks Hypertension Decrease only of DBP and reduction of heart rate variability (HRV) of HF in the 4th and 8th week of treatment of the treated group. Lomuscio et al, 2011 [40] Acupuncture PC6, C7, and BL15 Controlled; randomized; single-blind 17T, 13P, 24C, 26R 1 time per week; 10 weeks Atrial fibrillation Decreased recurrence rate of arrhythmias in the intervention group. Park et al, 2010 [20] Acupuncture ST36 and PC6 Placebo-controlled; randomized; double-blind; cross-over 15T, 15P 7 times; 1 week Hypertension Significant improvement of flow-mediated dilatation of the brachial artery in acupuncture ST 36 and ST 36 + PC6. Severcan et al, 2012 [28] Acupuncture EX-HN3, KI3, LIV3, SP9, LI4, HT7, ST36, and SP6 Randomized 32T 1 time per week, 10 weeks Hypertension Reduction of SBP and DBP values and increase of nitric oxide concentration during the 10 sessions. Wang et al, 2015[36] Electroacupuncture PC6 and PC4 Controlled; randomized 102T, 102C 1 time Coronary disease Significant improvement in cardiac function and reduction of adverse cardiovascular and cerebrovascular events in the treated group. Yang et al, 2010 [37] Electroacupuncture PC6, LU7, and LU2 Controlled; randomized 30T, 30C 1 time per day; 5 days Heart valve disease Pretreatment with electroacupuncture resulted in a cardioprotective effect in patients undergoing valve replacement heart surgery. Yeh et al, 2015 [32] Acupuncture Auricular Controlled; randomized 63T, 60C 10 weeks Hypertension There were no significant differences in HRV parameters, heart rate, BP, and quality of life. Yilmaz et al, 2017 [42] Electrostimulation Peroneal nerve Controlled; randomized 11T, 11C 1 time Critical ischemia No significant difference was observed between the treated group and the control group. Yin et al, 2007 [24] Acupuncture ST36, LI11, BL25, SP3, LU9, BL13, KI7, KI2, CV4, LI1, GV14, GB20, HT7, and PC6 Placebo-controlled; randomized; double-blind 15T, 15P 17 times; 8 weeks Hypertension Decreased mean BP after 8 weeks of intervention. Zamotrinsky et al, 1997 [33] Electroacupuncture Auricular Controlled; randomized 10T, 10C 1 time Coronary disease Relief of angina symptoms; decrease in certain biochemical signs of myocardial damage, and increase in heart tolerance to operative reperfusion injury. C = individuals in the control group; P = individuals in the placebo group; T = individuals in the treated group; R = individuals in the reference group; LN = leaving needle method; SPM = sparrow pecking method. Discussion In the studies analyzed in this review, the most used acupoint among the different techniques was the PC6 (Neiguan) acupoint (10 studies, 64.7%), followed by ST36 (Zu San Li) acupoint (6 studies, 35.3%) and auricular acupoints (4 studies, 23.5%). The simultaneous use of acupoints PC6 and ST36 was also observed in five clinical studies for the treatment of hypertension [20], [21], [22], [23], [24]. Anatomically, the heart is innervated by lower thoracic and upper cervical nerve segments, which also innervate the somatic area around PC6 acupoint. Moreover, the PC6 acupoint is located on the forearm surface in a region corresponding to the anatomical path of the median nerve [25], [26], which may corroborate the relationship between the point stimulus and the physiological changes observed in the cardiovascular system. Among the CVDs, to which the analyzed techniques were clinically applied, the most common was hypertension, totaling 10 studies. Of these, nine were related to acupuncture and only one to EA, with 80% reporting positive results in the modulation of the disease through the reduction of blood pressure (BP). Abdi et al [27] performed a double-blind randomized controlled clinical trial in which obese and hypertensive patients (not receiving drug therapy) were submitted to auricular acupuncture or abdominal EA, at Tianshu (ST25), Weidao (GB28), Zhongwan (RN12), Shuifen (RN9), Guanyuan (RN4), and Sanyinjiao (SP6) acupoints, during 6 weeks, showing a more expressive decrease in systolic blood pressure (SBP) and diastolic blood pressure (DBP) by abdominal EA compared to auricular acupuncture. In a randomized clinical trial, blinded for assessors and for statistician, conducted by Liu et al [21], 15 primary moderate hypertensive patients were submitted to acupuncture at LI11, SP4, ST36, LT3, and PC6 acupoints twice a week for 8 weeks; a reduction was observed in DBP but not in SBP, despite the improvement observed in parasympathetic tonus. Yin et al [24], in another double-blind randomized controlled clinical trial, submitted 21 hypertensive or prehypertensive patients for 8 weeks treatment with acupuncture in several acupoints, including ST36 and PC6, observing a decrease in SBP and DBP at the end of 17 treatment sessions compared to sham acupuncture group. Interestingly, in a study, blinded for participants and for statisticians, conducted by Li et al. [22], 65 moderate hypertensive patients (not receiving antihypertensive medication) were treated with EA at PC5, PC6, ST36, and ST37 once a week for 8 weeks, evidencing a reduction in SBP and DBP, accompanied by a significant reduction in plasma norepinephrine and renin levels at the end of the follow-up, suggesting a physiological modulation by EA. Severcan et al [28] reported an increase on plasma nitric oxide (NO) concentration with a decrease in SBP and DBP observed after 10 weeks of treatment of hypertensive patients with acupuncture at EX-HN3 (Yintang), KI3, LIV3, SP9, LI4, HT7, ST36, and SP6 acupoint. NO is a potent vasodilator produced in vascular endothelial cells by the conversion of the amino acid arginine into citruline, by enzymatic action of NO synthase, and plays a critical antihypertensive role in the homeostasis of BP [29]. EA, also, inhibits sympathetic stimulus by regulating the expression of NO synthase in the central nervous system [30], [31]. The depressant effect of EA on BP occurs mainly through vasodilation of mesenteric vessels caused by the inhibition of sympathetic tonus, which is responsible for vasoconstriction [29]. Unlike the aforementioned studies, Yeh et al [32], in a randomized clinical trial, observed no effects on BP and sympathovagal balance after 10 weeks of auricular acupuncture for the treatment of patients with primary hypertension. Also, Jiang [9], in a randomized controlled trial with 60 hypertensive patients, treated the intervention group daily with acupuncture at the LI11 (Quchi), ST40 (Fenglong), and LR3 (Taichong) acupoints for 30 minutes, during 6 days, observing no differences in BP between intervention and control groups after the follow-up. This may be explained by the fact that some patients are usually low-respondents to acupuncture for BP reduction [22], evidencing the necessity for understanding those involved mechanisms for a more precise prescription of acupuncture with this objective. The CAD was another important application of acupuncture among CVDs, observed in five studies. Zamotrinsky et al [33], in a randomized controlled trial, submitted 10 patients with CAD with inability to perform any activity without angina or angina at rest to auricular EA. After 10 procedures, the EA exerted a vagotonic/sympatholytic effect with a decrease of angina threshold, with patients' no longer developing angina either at rest or after a moderate physical load. Moreover, their dependence on treatment with vasodilators had decreased considerably. Also, EA improved stress-induced proteins, such as the thermal shock protein (HSP70i), which participates in the elimination of damaged or defective proteins [34] directly inhibiting apoptosis [35]. Interestingly, Wang et al [36] showed, in a randomized controlled trial with 60 patients, that 30 minutes of EA administered at PC6 acupoint prior to heart valve replacement surgery leads to cardioprotection, evidenced by post operatory reduced serum levels of cardiac troponin I, a critical marker of myocardial injury [37], a lower usage of inotropic drugs and a shortened intensive care unit stay time. The cardioprotective action of EA was also studied by Wang et al [36] in a randomized controlled trial with 204 patients. The EA was performed 30-minute at Antiguan (PC6) and Ximen (PC4) acupoints 1 to 2 hours prior to percutaneous coronary intervention, resulting in a lower incidence of acute myocardial infarction, improvement in cardiac function, and fewer adverse events such as sudden death, arrhythmias, heart failure, acute thrombosis, myocardial infarction, and stroke after percutaneous coronary intervention. Ho et al [38] stimulated the EH6 acupoint of 22 patients who had angiographically proven CAD (>50% diameter stenosis) for 30 minutes, demonstrating that acupuncture improved cardiac function in these but not on control patients. Although the previously described, Kurono et al [39] demonstrated that in patients with vasospastic angina, the acupuncture at EH6 acupoint could be deleterious, leading to vasospasm of coronary artery. According to Lomuscio et al [40], acupuncture treatment at PC6, HT7, and BL 15 acupoints leads to similar benefits as amiodarone, an antiarrhythmic agent which is the most effective drug used worldwide for treatment of atrial fibrillation [41], reducing the recurrence of atrial fibrillation after electrical cardioversion therapy. Transcutaneous electrostimulation for peripheral limb ischemia was studied by Yilmaz et al [42]. Electrostimulation of the peroneal nerve produced a substantial increase in blood velocity in anterior tibialis artery, associated with better clinical outcomes, in terms of longer walking distance. The two last studies did not suggest any mechanism for the observed effects. In conclusion, this review demonstrates that acupuncture may be a viable alternative as a complementary therapy for CVD, particularly for hypertension and CAD. However, the heterogeneity of the studies does not allow a standardization of its application for each specific disease, making further studies necessary for its use to become a reality. Financial support There was no financial support. Acknowledgments The authors thank the researchers from the Undergraduate Program in Cardiovascular Sciences of the National Institute of Cardiology for the intellectual support. Appendix A. Supplementary data The following is the supplementary data related to this article: Research data for this article ACUPUNCTURE, ELETROACUPUNCTURE, AND TRANSCUTANEOUS ELECTROSTIMULATION OF ACUPUNCTURE POINTS IN THE TREATMENT OF CARDIOVASCULAR DISEASES: A SYSTEMATIC REVIEW Original Data The information stored in this repository refers to the tools used to search for articles for this systematic review. The criteria of selection and exclusion can be found, as well as the analysis of the quality of the articles selected. Get data from Open Science Framework About research data References [1] World Health Organization (WHO) Global Status Report on noncommunicable diseases in 2010 (2010) Geneva [2] S. Mendis, P. Puska, B. 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