Abstract
Inflammation, which plays a critical role in atherosclerosis and the occurrence of acute cardiovascular events, may be a new target for treatment of coronary artery disease (CAD) to reduce residual cardiovascular risk. Recently, Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease (CANTOS), the largest scale clinical trial that targeted inflammation but not lipids, has affirmed for the first time the inflammatory hypothesis of artherosclerosis and marked the advent of an exciting era of targeting inflammation for the prevention and treatment of cardiovascular diseases. Chinese medicine (CM) is a promising adjuvant therapy for CAD in light of its safety and pleiotropic effect of anti-inflammation, anti-platelet, lipid-regulating, endothelium-protection, microcirculation-improving, etc. In recent years, exploration of anti-inflammatory treatment of CAD with CM has been going on from theory to practice. Taking CANTOS as an example, the design strategy to combine CM and Western medicine to inhibit inflammation were discussed in this paper, which might provide a new perspective for CM intervention on CAD.
Similar content being viewed by others
References
Grundy SM, Cleeman JI, Merz CN, Brewer HB Jr, Clark LT, Hunninghake DB, et al. Coordinating Committee of the National Cholesterol Education Program. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel Guidelines. Circulation 2004;110:227–239.
European Association for Cardiovascular Prevention and Rehabilitation, Reiner Z, Catapano AL, De Backer G, Graham I, Taskinen MR, Wiklund O, et al. ESC/EAS Guidelines for the management of dyslipidaemias: the task force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS). Eur Heart J 2011;32:1769–1818.
Montalescot G, Sechtem U, Achenbach S, Andreotti F, Arden C, Budaj A. 2013 ESC guidelines on the management of stable coronary artery disease. Eur Heart J 2013;34:2949–3003.
Jellinger PS, Handelsman Y, Rosenblit PD, Bloomgarden ZT, Fonseca VA, Garber AJ, et al. American Association of Clinical Endocrinologists and American College of Endocrinology guidelines for management of dyslipidemia and prevention of cardiovascular disease. Endocr Pract 2017;23:479–497.
Cannon CP, Blazing MA, Giugliano RP, McCagg A, White JA, Theroux P, et al. Ezetimibe added to statin therapy after acute coronary syndromes. N Engl J Med 2015;372:2387–2397.
Sabatine MS, Giugliano RP, Keech AC, Honarpour N, Wiviott SD, Murphy SA, et al. Evolocumab and clinical outcomes in patients with cardiovascular disease. N Engl J Med 2017;376:1713–1722.
Li JJ, Fang CH. Atheroscleritis is a more rational term for the pathological entity currently known as atherosclerosis. Med Hypotheses 2004;63:100–102.
Ross R. Atherosclerosis—an inflammatory disease. N Engl J Med 1999;340:115–126.
Hansson GK. Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med 2005;352:1685–1695.
Libby P, Ridker PM, Hansson GK; Leducq Transatlantic Network on Atherothrombosis. Inflammation in atherosclerosis: from pathophysiology to practice. J Am Coll Cardiol 2009;54:2129–2138.
Alexander RW. Inflammation and coronary artery disease. N Engl J Med 1994;331:468–469.
Libby P, Ridker PM, Hansson GK. Progress and challenges in translating the biology of atherosclerosis. Nature 2011;473:317–325.
Ridker PM. Rosuvastatin in the primary prevention of cardiovascular disease among patients with low levels of low-density lipoprotein cholesterol and elevated highsensitive C-reactive protein: rationale and design of the JUPITOR trial. Circulation 2003;108:2292–2297.
Li JJ, Li YS, Fang CH, Hui RT, Yang YJ, Cheng JL, et al. Effects of simvastatin within two weeks on anti-inflammatory cytokine interleukin-10 in patients with unstable angina. Heart 2006;92:529–530.
Li JJ. Inflammation and atherosclerosis. Chin J Front Clin Sci (Elect version, Chin) 2011;3:4–6.
Nissen SE, Tuzcu EM, Schoenhagen P, Crowe T, Sasiela WJ, Tsai J, et al. Statin therapy, LDL cholesterol, C-reactive protein, and coronary artery disease. N Engl J Med 2005;352:29–38.
Ridker PM, Cannon CP, Morrow D, Rifai N, Rose LM, McCabe CH, et al. C-reactive protein levels and outcomes after statin therapy. N Engl J Med 2005;352:20–28.
Kaptoge S, Di Angelantonio E, Lowe G, Pepys MB, Thompson SG, Collins R, et al. C-reactive protein concentration and risk of coronary heart disease, stroke, and mortality: an individual participant meta-analysis. Lancet 2010;375:132–140.
Musunuru K, Kral BG, Blumenthal RS, Fuster V, Campbell CY, Gluckman TJ, et al. The use of high sensitivity assays for C-reactive protein in clinical practice. Nat Clin Pract Cardiovasc Med 2008;5:621–635.
Ridker PM, Rifai N, Rose L, Buring JE, Cook NR. Comparison of C reactive protein and low-density lipoprotein cholesterol levels in the prediction of first cardiovascular events. N Engl J Med 2002;347:1557–1565.
Koenig W. High-sensitivity C-reactive protein and atherosclerotic disease: from improved risk prediction to risk-guided therapy. Int J Cardiol 2013;168:5126–5134.
Kaptoge S, Seshasai SR, Gao P, Freitag DF, Butterworth AS, Borglykke A, et al. Inflammatory cytokines and risk of coronary heart disease: new prospective study and updated meta-analysis. Eur Heart J 2014;35:578–589.
Ridker PM. Clinical application of C-reactive protein for cardiovascular disease detection and prevention. Circulation 2003;107:363–369.
Ridker, P. M, Danielson E, Fonseca FA, Genest J, Gotto AM Jr, Kastelein JJ, et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med 2008;359:2195–2207.
Ridker PM, Everett BM, Thuren T, MacFadyen JG, Chang WH, Ballantyne C, et al. Anti-inflammatory therapy with canakinumab for atherosclerotic disease. N Engl J Med 2017;377:1119–1131.
Peter Libby. Interleukin-1 beta as a target for atherosclerosis therapy: biological basis of CANTOS and beyond. J Am Coll Cardiol 2017;70:2278–2289.
Chen KJ, Shi DZ, Xu H, Yin HJ, Zhang JC. The criterion of syndrome differentiation and quantification for stable coronary heart disease caused by etiological toxin of Chinese medicine. Chin J Integr Tradit West Med (Chin) 2011;31:313–314.
Wen C, Xu H, Huang QF, Chen KJ. Effect of drugs for promoting blood circulation on blood lipids and inflammatory reaction of atherosclerotic plaques in ApoE gene deficiency mice. Chin J Integr Tradit West Med (Chin) 2005;25:345–349.
Wen C, Xu H, Huang QF, Chen KJ, Li P, Sheng X. Effects of herbs of activation blood on atherosclerotic plaque morphology in ApoE gene-deficient mice. Chin J Pathophysiol (Chin) 2005;21:864–867.
Li SS, Zhao HY, Guo ZL. Study on the effective component API0134 of Andrographis paniculata to prevent reocclusion after coronary artery thrombolysis in dogs (Abstract). Chin Circ J (Chin) 1999;14:5–6.
Wu M, Zhang WG, Liu LT. Red yeast rice prevents atherosclerosis through regulating inflammatory signaling pathways. Chin J Integr Med 2017;23:689–695.
Huang Y, Yin HJ, Ma XJ, Wang JS, Liu Q, Wu CF, et al. Correlation between Fc γ R a and aortic atherosclerotic plaque destabilization in ApoE knockout mice and intervention effects of effective components of Chuanxiong rhizome and red Peony root. Chin J Integr Med 2011;17:355–360.
Wang Y, Cheng WL, Wang Y, Peng JP, Yuan J, Chen L, et al. Qingre Quyu Granule stabilizes plaques through inhibiting the expression of tenascin-C in patients with severe carotid stenosis. Chin J Integr Med 2015;21:339–345.
Liu JH, Muo GH, Tang L. Clinical study of Danhong Injection on coronary heart disease with angina pectoris. J Chin Physici (Chin) 2006;8:1715–1719.
Lin P, Ren QY. Effect of Safflower Yellow Injection on the inflammatory factor and blood lipids of old patients with coronary heart disease. Chin Hosp Pharm J (Chin) 2009;29:652–653.
Liu JG, Xu H, Dong GJ, Shi DZ, Zhou GH, Zhu JH, et al. Xuefu Zhuyu Oral Liquid on vascular endothelium function and hemorrheologic influence in patients with angina pectoris and blood-stasis syndrome. Chin J Integr Med Cardio Cerebrovasc Dis (Chin) 2006;4:659.
Zheng F, Zhou MX, Xu H, Chen KJ. Effects of herbs with function of activating blood circulation and detoxication on serum inflammatory markers and blood lipids in stable patients with coronary heart disease. China J Tradit Chin Med Pharm (Chin) 2009;24:1153–1157.
Zhou MX, Xu H, Chen KJ, Pan L, Wen C, Liu JG. Effects of some active ingredients of Chinese drugs for activating blood circulation and detoxicating on blood lipids and atherosclerotic plaque inflammatory reaction in ApoE-gene knockout mice. Chin J Integr Med Cardio-/Cerebrovasc Dis (Chin) 2007;5:1202–1205.
Gao S, Liu Z, Li H, Little PJ, Liu P, Xu S. Cardiovascular actions and therapeutic potential of tanshinone A. Atherosclerosis 2012;220:3–10. 40.
Li HZ, Lu YH, Huang GS, Chen Q, Fu Q, Li ZL. Tanshinone II A inhibits dendritic cell-mediated adaptive immunity: potential role in anti-atherosclerotic activity. Chin J Integr Med 2014;20:764–769.
Robertson AL, Holmes GR, Bojarczuk AN, Burgon J, Loynes CA, Chimen M, et al. A zebrafish compound screen reveals modulation of neutrophil reverse migration as an anti-Inflammatory mechanism. Sci Transl Med 2014;6:225ra29.
Shang QH, Wang H, Li SM, Xu H. The effect of sodium tanshinone A sulfate and simvastatin on elevated serum levels of inflammatory markers in patients with coronary heart disease: a study protocol for a randomized controlled trial. Evid Based Complement Alternat Med 2013;2013:756519.
Buckley DI, Fu R, Freeman M, Rogers K, Helfand M. C-reactive protein as a risk factor for coronary heart disease: a systematic review and meta-analyses for the U.S. Preventive Services Task Force. Ann Intern Med 2009;151:483–495.
Li SM, Jiao Y, Wang H, Shang Q, Lu F, Huang L, et al. Sodium tanshinone A sulfate adjunct therapy reduces high-sensitivity C-reactive protein level in coronary artery disease patients: a randomized controlled trial. Sci Rep 2017:17451.
Gao X. Clinical Study of Qing-Xin-Jie-Yu Decoction on elevated serum levels of inflammatory markers in patients with stable coronary heart disease [dissertation]. Beijing: Chin Academy of Chinese Medical Sciences; 2017.
Li SY, Guo M, Mao HM, Gao ZY, Xu Hao, Shi DZ. Qing-Xin-Jie-Yu Granules in addition to conventional treatment for patients with stable coronary artery disease (QUEST Trial): study protocol for a randomized controlled trial. Trials 2016;17:451.
White HD, Held C, Stewart R. Darapladib for preventing ischemic events in stable coronary heart disease. N Engl J Med 2014;370:1702–1711.
O'Donoghue ML, Braunwald E, White HD, Lukas MA, Tarka E, Steg PG, et al. Effect of darapladib on major coronary events after an acute coronary syndrome: the SOLID-TIMI 52 randomized clinical trial. JAMA 2014;312:1006–1015.
Newby LK, Marber MS, Melloni C, Sarov-Blat L, Aberle LH, Aylward PE, et al. Losmapimod, a novel p38 mitogenactivated protein kinase inhibitor, in non-ST-segment elevation myocardial infarction: a randomised phase 2 trial. Lancet 2014;384:1187–1195.
Morton AC, Rothman AM, Greenwood JP, Gunn J, Chase A, Clarke B, et al. The effect of interleukin-1 receptor antagonist therapy on markers of inflammation in non-ST elevation acute coronary syndromes: the MRC-ILA Heart Study. Eur Heart J 2015;36:377–384.
Koenig W, Khuseyinova N. Lipoprotein-associated and secretory phospholipase A2 in cardiovascular disease: the epidemiological evidence. Cardiovasc Drugs Ther 2009;23:85–92.
Nicholls SJ, Kastelein JJ, Schwartz GG, Bash D, Rosenson RS, Cavender MA, et al. Varespladib and cardiovascular events in patients with an acute coronary syndrome: the VISTA-16 randomized clinical trial. JAMA 2014;311:252–262.
Padfield GJ, Din JN, Koushiappi E, Mills NL, Robinson SD, Cruden NM, et al. Cardiovascular effects of tumour necrosis factor alpha antagonism in patients with acute myocardial infarction: a first in human study. Heart 2013;99:1330–1335.
Author information
Authors and Affiliations
Corresponding author
Additional information
Supported by the Beijing Municipal Science and Technology Commission (No. Z151100004015090)
Rights and permissions
About this article
Cite this article
Li, Sm., Li, Jg. & Xu, H. A New Perspective for Chinese Medicine Intervention for Coronary Artery Disease: Targeting Inflammation. Chin. J. Integr. Med. 25, 3–8 (2019). https://doi.org/10.1007/s11655-018-2995-1
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11655-018-2995-1