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      Angina in Women without Obstructive Coronary Artery Disease

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          Abstract

          Angina in the absence of obstructive coronary artery disease, sometimes referred to as cardiac syndrome X (CSX), is a debilitating condition that disproportionately affects women. More than 50% of women evaluated for angina have non-obstructive disease by cardiac catheterization, although the total numbers of women affected by CSX are unknown. Varying clinical definitions and the lack of large scale epidemiologic studies focusing on this illness have resulted in limited knowledge about its risk factors, although there appears to be an association with black race, estrogen deficiency, and insulin resistance. Contrary to prior beliefs about the benign nature of this entity, these women suffer considerable morbidity with costly economic implications that approach the lifetime costs of healthcare utilization for those with obstructive coronary disease. Two prevailing hypotheses have emerged to explain CSX: the ischemic hypothesis detailing abnormal coronary microvascular function and the non-ischemic hypothesis describing altered pain perception and myocardial hypersensitivity. Treatment strategies have focused on both of these pathways with the main goal of improving symptoms. Beta blockers provide the most convincing evidence for benefit, with other antianginals having secondary roles. Other promising pharmacologic therapies include xanthine derivatives, estrogen replacement therapy, ACE inhibitors, and statin medications, among other emerging treatment options. Neurostimulation and lifestyle factors including exercise can also be beneficial in reducing symptoms. However, managing patients with CSX can be frustrating for both patients and physicians, as there is a lack of data regarding an optimal treatment algorithm including few large-scale randomized controlled trials to clarify effective therapies.

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          Long-term follow-up of patients with mild coronary artery disease and endothelial dysfunction.

          Coronary endothelial dysfunction is characterized by vasoconstrictive response to the endothelium-dependent vasodilator acetylcholine. Although endothelial dysfunction is considered an early phase of coronary atherosclerosis, there is a paucity of information regarding the outcome of these patients. Thus, this study was designed to evaluate the outcome of patients with mild coronary artery disease on the basis of their endothelial function. Follow-up was obtained in 157 patients with mildly diseased coronary arteries who had undergone coronary vascular reactivity evaluation by graded administration of intracoronary acetylcholine, adenosine, and nitroglycerin and intracoronary ultrasound at the time of diagnostic study. Patients were divided on the basis of their response to acetylcholine into 3 groups: group 1 (n=83), patients with normal endothelial function; group 2 (n=32), patients with mild endothelial dysfunction; and group 3 (n=42), patients with severe endothelial dysfunction. Over an average 28-month follow-up (range, 11 to 52 months), none of the patients from group 1 or 2 had cardiac events. However, 6 (14%) with severe endothelial dysfunction had 10 cardiac events (P<0.05 versus groups 1 and 2). Cardiac events included myocardial infarction, percutaneous or surgical coronary revascularization, and/or cardiac death. Severe endothelial dysfunction in the absence of obstructive coronary artery disease is associated with increased cardiac events. This study supports the concept that coronary endothelial dysfunction may play a role in the progression of coronary atherosclerosis.
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            Effect of exercise on coronary endothelial function in patients with coronary artery disease.

            Studies of the cardioprotective effects of exercise training in patients with coronary artery disease have yielded contradictory results. Exercise training has been associated with improvement in myocardial perfusion even in patients who have progression of coronary atherosclerosis. We therefore conducted a prospective study of the effect of exercise training on endothelial function in patients with coronary artery disease. We randomly assigned 19 patients with coronary endothelial dysfunction, indicated by abnormal acetylcholine-induced vasoconstriction, to an exercise-training group (10 patients) or a control group (9 patients). To reduce confounding, patients with coronary risk factors that could be influenced by exercise training (such as diabetes, hypertension, hypercholesterolemia, and smoking) were excluded. In an initial study and after four weeks, the changes in vascular diameter in response to the intracoronary infusion of increasing doses of acetylcholine (0.072, 0.72, and 7.2 microg per minute) were assessed. The mean peak flow velocity was measured by Doppler velocimetry, and the diameter of epicardial coronary vessels was measured by quantitative coronary angiography. In the initial study, the two groups had similar vasoconstrictive responses to acetylcholine. After four weeks of exercise training, coronary-artery constriction in response to acetylcholine at a dose of 7.2 microg per minute was reduced by 54 percent (from a mean [+/-SE] decrease in the luminal diameter of 0.41+/-0.05 mm in the initial study to a decrease of 0.19+/-0.07 mm at four weeks; P<0.05 for the comparison with the change in the control group). In the exercise-training group, the increases in mean peak flow velocity in response to 0.072, 0.72, and 7.2 microg of acetylcholine per minute were 12+/-7, 36+/-11, and 78+/-16 percent, respectively, in the initial study. After four weeks of exercise, the increases in response to acetylcholine were 27+/-7, 73+/-19, and 142+/-28 percent (P<0.01 for the comparison with the control group). Coronary blood-flow reserve (the ratio of the mean peak flow velocity after adenosine infusion to the resting velocity) increased by 29 percent after four weeks of exercise (from 2.8+/-0.2 in the initial study to 3.6+/-0.2 after four weeks; P<0.01 for the comparison with the control group). Exercise training improves endothelium-dependent vasodilatation both in epicardial coronary vessels and in resistance vessels in patients with coronary artery disease.
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              Adverse cardiovascular outcomes in women with nonobstructive coronary artery disease: a report from the Women's Ischemia Syndrome Evaluation Study and the St James Women Take Heart Project.

              Women with clinical findings suggestive of ischemia but without findings of obstructive coronary artery disease (CAD) on angiography represent a frequent clinical problem; predicting prognosis is challenging. The Women's Ischemia Syndrome Evaluation (WISE) study examined symptomatic women referred for clinically indicated coronary angiography and followed up for a mean 5.2 years. The St James Women Take Heart (WTH) Project enrolled asymptomatic, community-based women with no history of heart disease who were followed up for 10 years. We compared cardiovascular events (ie, myocardial infarction, stroke, and hospitalization for heart failure) and death in 540 WISE women with suspected ischemia but no angiographic evidence of obstructive CAD with those from a cohort of 1000 age- and race-matched WTH women. Compared with the WISE women, asymptomatic WTH women had a lower prevalence of obesity, family history of CAD, hypertension, and diabetes mellitus (P < .001). Five-year annualized event rates for cardiovascular events were 16.0% in WISE women with nonobstructive CAD (stenosis in any coronary artery of 1%-49%), 7.9% in WISE women with normal coronary arteries (stenosis of 0% in all coronary arteries), and 2.4% in asymptomatic WTH women (P < or = .002), after adjusting for baseline CAD risk factors. The cardiovascular events were most frequent in women with 4 or more cardiac risk factors, with the 5-year annualized cardiovascular event rate being 25.3% in women with nonobstructive CAD, 13.9% in WISE women with normal coronary arteries, and 6.5% in asymptomatic women (P = .003). Women with symptoms and signs suggestive of ischemia but without obstructive CAD are at elevated risk for cardiovascular events compared with asymptomatic community-based women.
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                Author and article information

                Journal
                Curr Cardiol Rev
                CCR
                Current Cardiology Reviews
                Bentham Science Publishers Ltd.
                1573-403X
                1875-6557
                February 2010
                : 6
                : 1
                : 71-81
                Affiliations
                [1 ] From the Donald W. Reynolds Cardiovascular Clinical Research Center, the University of Texas Southwestern Medical Center, Dallas TX
                [2 ] From the Division of Cardiology, the University of Texas Southwestern Medical Center, Dallas TX
                [3 ] From the Department of Internal Medicine, the University of Texas Southwestern Medical Center, Dallas TX
                Author notes
                [* ]Address correspondence to this author at the Division of Cardiology, UT Southwestern Medical Center, 5909 Harry Hines Blvd., Rm. HA9.133, Dallas, TX 75390-9047; Tel: 214-645-7500; Fax: 214-645-7501; E-mail: amit.khera@ 123456utsouthwestern.edu
                [#]

                Drs. Banks and Lo contributed equally to the preparation of this manuscript.

                Article
                CCR-6-71
                10.2174/157340310790231608
                2845797
                21286281
                927ed1d1-8cd8-4a80-8ebc-2b2605f27b11
                © Bentham Science Publishers Ltd.

                This is an open access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.5/), which permits unrestrictive use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 1 August 2009
                : 31 September 2009
                : 8 October 2009
                Categories
                Article

                Cardiovascular Medicine
                syndrome x,angina,women.
                Cardiovascular Medicine
                syndrome x, angina, women.

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