Opinion statement
Microvascular coronary dysfunction (MCD) is an increasingly recognized cause of cardiac ischemia and angina that is diagnosed more commonly in women. Patients with MCD present with the triad of persistent chest pain, ischemic changes on stress testing, and no obstructive coronary artery disease on cardiac catheterization. Data from the National Heart, Lung, and Blood Institute–sponsored Women’s Ischemia Syndrome Evaluation (WISE) study show that the diagnosis of MCD is not benign, with a 2.5% annual risk of adverse cardiac events including myocardial infarction, stroke, congestive heart failure, and death. The gold standard diagnostic test for MCD is the invasive coronary reactivity test (CRT), which uses acetylcholine, adenosine, and nitroglycerin to test endothelial-dependent and -independent microvascular and macrovascular coronary function. The CRT allows for diagnostic and treatment options as well as further risk stratification of patients for future cardiovascular events. Treatment of angina and MCD should be aimed at ischemia disease management to reduce the risk of adverse cardiac events, ameliorate symptoms to improve quality of life, and decrease morbidity from unnecessary and repeated cardiac catheterization in patients with open coronary arteries. A comprehensive treatment approach aimed at risk factor management, including lifestyle counseling regarding smoking cessation, nutrition, and physical activity, should be initiated. Current pharmacotherapy for MCD may include treatment of microvascular endothelial dysfunction (with statins, angiotensin-converting enzyme inhibitors, or low-dose aspirin), as well as treatment for angina and myocardial ischemia (with β-blockers, calcium channel blockers, nitrates, or ranolazine). Additional symptom management techniques may include tricyclic medication, enhanced external counterpulsation, hypnosis, and spinal cord stimulation. Although our current therapies are effective in treating angina and MCD, large randomized outcome trials are needed to optimize strategies to improve morbidity and mortality.
Similar content being viewed by others
References and Recommended Reading
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
Sharaf BL, Pepine CJ, Kerensky RA, et al.: Detailed angiographic analysis of women with suspected ischemic chest pain (pilot phase data from the NHLBI-sponsored Women’s Ischemia Syndrome Evaluation [WISE] Study Angiographic Core Laboratory). Am J Cardiol 2001, 87:937–941.
Likoff W, Segal BL, Kasparian H: Paradox of normal selective coronary arteriograms in patients considered to have unmistakable coronary heart disease. N Engl J Med 1967, 267:1063–1066.
Pasternak RC, Thibault GE, DeSanctis RW, Hutter AM: Chest pain with angiographically insignificant coronary arterial obstruction: clinical presentation and long-term follow up. Am J Med 1980, 68:813–817.
Reis SE, Holubkov R, Conrad Smith AJ, et al.: WISE Investigators: Coronary microvascular dysfunction is highly prevalent in women with chest pain in the absence of coronary artery disease: results from the NHLBI WISE study. Am Heart J 2001, B141(5):735–741.
Johnson BD, Shaw LJ, Buchthal SD, et al.: Prognosis in women with myocardial ischemia in the absence of obstructive coronary disease. Results from the National Institutes of Health–National Heart, Lung, and Blood Institute–sponsored Women’s Ischemia Syndrome Evaluation (WISE). Circulation 2004, 109:2993–2999.
Johnson BD, Shaw LJ, Pepine CJ, et al.: Persistent chest pain predicts cardiovascular events in women without obstructive coronary artery disease: results from the NIH-NHLBI-sponsored Women’s Ischaemia Syndrome Evaluation (WISE) study. Eur Heart J 2006, 27:1408–1415.
Cannon R: Microvascular angina and the continuing dilemma of chest pain with normal coronary angiograms. J Am Coll Cardiol 2009, 54:877–887.
Shaw LJ, Merz CN, Pepine CJ, et al.: Women’s Ischemia Syndrome Evaluation (WISE) Investigators: The economic burden of angina in women with suspected ischemic heart disease: results from the National Institutes of Health–National Heart, Lung, and Blood Institute–sponsored Women’s Ischemia Syndrome Evaluation. Circulation 2006, 114(9):894–904.
Asbury EA, Slattery C, Grant A, et al.: Cardiac rehabilitation for the treatment of women with chest pain and normal coronary arteries. Menopause 2008, 15:454–460.
Kayikcioglu M, Payzin S, Yavuzgil O, et al.: Benefits of statin treatment in cardiac syndrome-X1. Eur Heart J 2003, 24:1999–2005.
Kaski JC, Rosano G, Gavrielides S, et al.: Effects of angiotensin-converting enzyme inhibition on exercise-induced angina and ST segment depression in patients with microvascular angina. J Am Coll Cardiol 1994, 23:652–657.
Pizzi C, Manfrini O, Fontana F, Bugiardini R: Angiotensin-converting enzyme inhibitors and 3-hydroxy-3-methylglutaryl coenzyme A reductase in cardiac Syndrome X: role of superoxide dismutase activity. Circulation 2004, 109(1):53–58.
Jadhav S, Ferrell W, Greer IA, et al.: Effects of metformin on microvascular function and exercise tolerance in women with angina and normal coronary arteries: a randomized, double-blind, placebo-controlled study. J Am Coll Cardiol 2006, 48(5):956–963.
Roque M, Heras M, Raig E, et al.: Short-term effects of transdermal oestrogen replacement therapy on coronary vascular reactivity in postmenopausal women with angina pectoris and normal results on coronary angiograms. J Am Coll Cardiol 1998, 31:139–143.
Hsia J, Langer RD, Manson JE, et al.: for the Women’s Health Initiative Investigators: Conjugated equine estrogens and coronary heart disease. Arch Intern Med 2006, 166:357–365.
Kronhaus KD, Lawson WE: Enhanced external counterpulsation is an effective treatment for syndrome X. Int J Cardiol 2009, 135(2):256–257.
National Cholesterol Education Program (NCEP) Expert Panel on Detection: Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III): Third Report of the NCEP Expert Panel on Detection, Evaluation, Treatment, of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation 2002, 106(25):3143–3421.
Parikh P, McDaniel MC, Ashen MD, et al.: Diets and cardiovascular disease: an evidence based assessment. J Am Coll Cardiol 2005, 45:1379–1387.
Baigent C, Blackwell L, Collins R, et al.: Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Lancet 2009, 373:1849–1860.
Fraker Jr TD, Fihn SD, Gibbons RJ, et al.: American College of Cardiology; American Heart Association; American College of Cardiology/American Heart Association Task Force on Practice Guidelines Writing Group: 2007 chronic angina focused update of the ACC/AHA 2002 Guidelines for the management of patients with chronic stable angina: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines Writing Group to develop the focused update of the 2002 Guidelines for the management of patients with chronic stable angina. Circulation 2007, 116(23):2762–2772.
Kaski JC, Rodriguez-Plaza L, Brown J, et al.: Efficacy of carvedilol (BM14, 190), a new beta-blocking drug with vasodilating properties, in exercise-induced ischemia. Am J Cardiol 1985, 56(1):35–40.
Matsuda Y, Akita H, Terashima M, et al.: Carvedilol improves endothelium-dependent dilation in patients with coronary artery disease. Am Heart J 2000, 140(5):753–759.
Sen N, Tavil Y, Erdamar H, et al.: Nebivolol therapy improves endothelial function and increases exercise tolerance in patients with cardiac syndrome X. Anadolu Kardiyol Derg 2009, 9(5):371–379.
Lanza GA, Colonna G, Pasceri V, et al.: Atenolol versus amlodipine versus isosorbide-5-mononitrate on anginal symptoms in syndrome X. Am J Cardiol 1999, 84:854–856.
Bugiardini R, Borghi A, Biagetti L, Puddu P: Comparison of verapamil versus propranolol therapy in syndrome X. Am J Cardiol 1989, 63(5):286–290.
Bairey Merz CN, Eteiba W, Pepine CJ, et al.: Cardiac syndrome X: relation to microvascular angina and other conditions. Curr Cardiovasc Risk Rep 2007, 1:167–175.
Kaski JC, Rosano GM, Collins P, et al.: Cardiac syndrome X: clinical characteristics and left ventricular function. Long-term follow-up study. J Am Coll Cardiol 1995, 25:807–814.
Chapman BR: Ranolazine for the treatment of chronic angina and potential use in other cardiovascular conditions. Circulation 2006, 113:2462–2472.
Chaitman BR: Ranolazine for the treatment of chronic angina and potential use in other cardiovascular conditions. Circulation 2006, 113(20):2462–2472.
Caliskan M, Erdogan D, Gullu H, et al.: Effects of atorvastatin on coronary flow reserve in patients with slow coronary flow. Clin Cardiol 2007, 30(9):475–479.
Chen JW, Hsu NW, Wu TC, et al.: Long-term angiotensin-converting enzyme inhibition reduces plasma asymmetric dimethylarginine and improves endothelial nitric oxide bioavailability and coronary microvascular function in patients with syndrome X. Am J Cardiol 2002, 90(9):974–982.
Higuchi T, Abletshauser C, Nekolla SG, et al.: Effect of the angiotensin receptor blocker Valsartan on coronary microvascular flow reserve in moderately hypertensive patients with stable coronary artery disease. Microcirculation 2007, 8:805–812.
Cannon 3rd RO, Quyyumi AA, Mincemoyer R, et al.: Imipramine in patients with chest pain despite normal coronary angiograms. N Engl J Med 1994, 330:1411–1417.
Asbury EA, Kanji N, Ernst E, et al.: Autogenic training to manage symptomology in women with chest pain and normal coronary arteries. Menopause 2009, 16:60–65.
Valeriani M, Sestito A, Le Pera D, et al.: Abnormal cortical pain processing in patients with cardiac syndrome X. Eur Heart J 2005, 26:975–982.
Sestito A, Lanza GA, Le Pera D, et al.: Spinal cord stimulation normalizes abnormal cortical pain processing in patients with cardiac syndrome X. Pain 2008, 139:82–89.
Radovits T, Bomicke T, Kokeny G, et al.: The phosphodiesterase-5 inhibitor vardenafil improves cardiovascular dysfunction in experimental diabetes mellitus. Br J Pharmacol 2009, 156:909–919.
Piatti P, Fragasso G, Monti LD, et al.: Acute intravenous L-arginine infusion decreases endothelin-1 levels and improves endothelial function in patients with angina pectoris and normal coronary arteriograms: correlation with asymmetric dimethylarginine levels. Circulation 2003, 107(3):429–436.
Schulman SP, Becker LC, Kass DA, et al.: L-Arginine therapy in acute myocardial infarction. JAMA 2006, 295:58–64.
Acknowledgments
This work was supported by contracts from the National Heart, Lung, and Blood Institute, nos. N01-HV-68161, N01-HV-68162, N01-HV-68163, and N01-HV-68164; General Clinical Research Center grant MO1-RR00425 from the National Center for Research Resources; and grants from the Gustavus and Louis Pfeiffer Research Foundation, Denville, NJ, The Women’s Guild of Cedars-Sinai Medical Center, Los Angeles, CA, The Ladies Hospital Aid Society of Western Pennsylvania, Pittsburgh, PA, the Edythe L. Broad Women’s Heart Research Fellowship, Cedars-Sinai Medical Center, and the Barbra Streisand Women’s Cardiovascular Research and Education Program, Cedars-Sinai Medical Center.
Disclosure
No potential conflicts of interest relevant to this article were reported.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Samim, A., Nugent, L., Mehta, P.K. et al. Treatment of Angina and Microvascular Coronary Dysfunction. Curr Treat Options Cardio Med 12, 355–364 (2010). https://doi.org/10.1007/s11936-010-0083-8
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11936-010-0083-8