Cardiac Syndrome X: Background, Pathophysiology, Epidemiology

Sections

Overview

Background

Cardiac syndrome X (CSX) is typical anginalike chest pain with evidence of myocardial ischemia in the absence of ﬂow-limiting stenosis on coronary angiography.^[1]Cannon et al termed this entity, characterized by a decrease in coronary flow reserve without epicardial artery stenosis, microvascular angina.^[2]Cardiac syndrome X is a heterogeneous entity, both clinically and pathophysiologically, involving various pathogenic mechanisms.

Pathophysiology

Many mechanisms have been proposed to result in cardiac syndrome X, including the following:

Endothelial dysfunction (microvascular angina)
Myocardial ischemia
Insulin resistance
Abnormal autonomic control
Altered cardiac sensitivity
Estrogen deficiency

Endothelial dysfunction

Endothelial dysfunction in cardiac syndrome X appears to be multifactorial and linked to risk factors such as smoking, obesity, hypercholesterolemia, and inflammation.^[3]Low levels of high-density lipoprotein cholesterol (HDL-C) appears to be associated with systemic inflammation in cardiac syndrome X^[4]; elevated plasma C-reactive protein levels, a marker of inflammation, have been shown to correlate with disease activity and endothelial dysfunction.^[5]

Endothelial dysfunction, with reduced bioavailability of endogenous nitric oxide and increased plasma levels of endothelin-1 (ET-1), may explain, at least in part, the abnormal coronary microvasculature in cardiac syndrome X.^{[6, 7, 8]}

Insulin resistance

Several studies support the presence of hyperinsulinemia in many patients with cardiac syndrome X.^{[9, 10, 11]}Additionally, metformin has been shown to improve vascular function and decrease myocardial ischemia in nondiabetic women with chest pain and angiographically normal coronary arteries.^[12]

Abnormal autonomic control

Abnormalities of the autonomic nervous system characterized by adrenergic hyperactivity and baroreceptor dysfunction have been demonstrated by several investigators.^{[13, 14, 15, 16]}In patients with cardiac syndrome X, Camici et al showed improvement of coronary flow reserve by α-adrenergic blockade with doxazosin.^[17]

Altered cardiac sensitivity

Multiple studies have suggested that abnormalities in pain perception are the principal abnormality in patients with chest pain and normal findings on coronary angiography. Altered central neural handling of afferent signals may contribute to the abnormal pain perception in these patients.^[18]

Estrogen deficiency

Cardiac syndrome X frequently occurs in perimenopausal or postmenopausal women, supporting a pathogenic role for estrogen deﬁciency.^[19]In postmenopausal women with cardiac syndrome X, estrogen replacement therapy improves coronary endothelial function, decreases anginal frequency, and improves exercise-induced angina.^{[20, 21, 22]}

Epidemiology

Approximately 20%-30% of patients undergoing coronary angiography for evaluation of anginalike chest pain may have nonobstructive coronary artery disease.^{[23, 24]}

Cardiac syndrome X is more common in women than in men.^[25]

Cardiac syndrome X frequently occurs in perimenopausal and postmenopausal women.

Prognosis

Patients with angina and normal coronary arteries at angiography, fulfilling the diagnostic criteria of cardiac syndrome X, have an excellent prognosis.^{[26, 27, 28, 29, 30]}However, an increased coronary atherosclerotic burden at 10-year follow-up was specifically observed in a group of women with cardiac syndrome X who also displayed coronary endothelial dysfunction.^[31]The Women’s Ischemic Syndrome Evaluation study, the largest and most thoroughly investigated cohort of middle-aged women with cardiac syndrome X, showed that these patients often have atherosclerosis on intravascular coronary ultrasound and face a 2.5% annual rate adverse cardiac events.^[32]

Clinical Presentation

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Media Gallery

Coronary blood ﬂow in response to nitroglycerine (NTG) and acetylcholine (ACH) infusion.
Cardiac magnetic resonance imaging.

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Author

Subodh Raja Devabhaktuni, MD Resident Physician, Department of Internal Medicine, University of Nevada School of Medicine

Disclosure: Nothing to disclose.

Coauthor(s)

Nirmal Sunkara, MD Chief Resident, Department of Internal Medicine, University of Nevada School of Medicine

Nirmal Sunkara, MD is a member of the following medical societies: American College of Physicians, American Medical Association

Disclosure: Nothing to disclose.

Kartika Shetty, MD, FACP Program Director, Internal Medicine Residency Program, Sunrise GME; Facility Medical Director, TEAMHealth, Mountain View Hospital

Kartika Shetty, MD, FACP is a member of the following medical societies: American College of Physicians, Association of Program Directors in Internal Medicine, Medical Council of India

Disclosure: Nothing to disclose.

Kasaiah Makam, MD Resident Physician, Department of Internal Medicine, University of Nevada School of Medicine

Kasaiah Makam, MD is a member of the following medical societies: American College of Physicians

Disclosure: Nothing to disclose.

Chowdhury H Ahsan, MD, PhD, MRCP, FSCAI Clinical Professor of Medicine, Director of Cardiac Catheterization and Intervention, Marlon Cardiac Catheterization Laboratory, Director of Cardiovascular Research, University Medical Center, University of Nevada School of Medicine

Chowdhury H Ahsan, MD, PhD, MRCP, FSCAI is a member of the following medical societies: American College of Cardiology, American College of Physicians, American Heart Association, Society for Cardiovascular Angiography and Interventions, American Stroke Association

Disclosure: Received consulting fee from sanofi for consulting; Received honoraria from astra zeneca for speaking and teaching; Received honoraria from BI for speaking and teaching.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

Richard A Lange, MD, MBA President, Texas Tech University Health Sciences Center, Dean, Paul L Foster School of Medicine

Richard A Lange, MD, MBA is a member of the following medical societies: Alpha Omega Alpha, American College of Cardiology, American Heart Association, Association of Subspecialty Professors

Disclosure: Nothing to disclose.

Cardiac Syndrome X

Background

Pathophysiology

Endothelial dysfunction

Insulin resistance

Abnormal autonomic control

Altered cardiac sensitivity

Estrogen deficiency

Epidemiology

Prognosis

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Cardiac Syndrome X

Background

Pathophysiology

Endothelial dysfunction

Insulin resistance

Abnormal autonomic control

Altered cardiac sensitivity

Estrogen deficiency

Epidemiology

Prognosis

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