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      Coronary Microvascular Function and Cardiovascular Risk Factors in Women With Angina Pectoris and No Obstructive Coronary Artery Disease: The iPOWER Study

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          Abstract

          Background

          The majority of women with angina‐like chest pain have no obstructive coronary artery disease when evaluated with coronary angiography. Coronary microvascular dysfunction is a possible explanation and associated with a poor prognosis. This study evaluated the prevalence of coronary microvascular dysfunction and the association with symptoms, cardiovascular risk factors, psychosocial factors, and results from diagnostic stress testing.

          Methods and Results

          After screening 3568 women, 963 women with angina‐like chest pain and a diagnostic coronary angiogram without significant coronary artery stenosis (<50%) were consecutively included. Mean age ( SD) was 62.1 (9.7). Assessment included demographic and clinical data, blood samples, questionnaires, and transthoracic echocardiography during rest and high‐dose dipyridamole (0.84 mg/kg) with measurement of coronary flow velocity reserve ( CFVR) by Doppler examination of the left anterior descending coronary artery. CFVR was successfully measured in 919 (95%) women. Median ( IQR) CFVR was 2.33 (1.98–2.76), and 241 (26%) had markedly impaired CFVR (<2). In multivariable regression analysis, predictors of impaired CFVR were age ( P<0.01), hypertension ( P=0.02), current smoking ( P<0.01), elevated heart rate ( P<0.01), and low high‐density lipoprotein cholesterol ( P=0.02), but these variables explained only a little of the CFVR variation ( r 2=0.09). CFVR was not associated with chest pain characteristics or results from diagnostic stress testing.

          Conclusion

          Impaired CFVR was detected in a substantial proportion, which suggests that coronary microvascular dysfunction plays a role in the development of angina pectoris. CFVR was associated with few cardiovascular risk factors, suggesting that CFVR is an independent parameter in the risk evaluation of these women. Symptom characteristics and results from stress testing did not identify individuals with impaired CFVR.

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          Most cited references22

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          Stable angina pectoris with no obstructive coronary artery disease is associated with increased risks of major adverse cardiovascular events.

          Patients with chest pain and no obstructive coronary artery disease (CAD) are considered at low risk for cardiovascular events but evidence supporting this is scarce. We investigated the prognostic implications of stable angina pectoris in relation to the presence and degree of CAD with no obstructive CAD in focus. We identified 11 223 patients referred for coronary angiography (CAG) in 1998-2009 with stable angina pectoris as indication and 5705 participants from the Copenhagen City Heart Study for comparison. Main outcome measures were major adverse cardiovascular events (MACE), defined as cardiovascular death, myocardial infarction, stroke or heart failure, and all-cause mortality. Significantly more women (65%) than men (32%) had no obstructive CAD (P< 0.001). In Cox's models adjusted for age, body mass index, diabetes, smoking, and use of lipid-lowering or antihypertensive medication, hazard ratios (HRs) associated with no obstructive CAD were similar in men and women. In the pooled analysis, the risk of MACE increased with increasing degrees of CAD with multivariable-adjusted HRs of 1.52 (95% confidence interval, 1.27-1.83) for patients with normal coronary arteries and 1.85 (1.51-2.28) for patients with diffuse non-obstructive CAD compared with the reference population. For all-cause mortality, normal coronary arteries and diffuse non-obstructive CAD were associated with HRs of 1.29 (1.07-1.56) and 1.52 (1.24-1.88), respectively. Patients with stable angina and normal coronary arteries or diffuse non-obstructive CAD have elevated risks of MACE and all-cause mortality compared with a reference population without ischaemic heart disease.
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            Coronary microvascular reactivity to adenosine predicts adverse outcome in women evaluated for suspected ischemia results from the National Heart, Lung and Blood Institute WISE (Women's Ischemia Syndrome Evaluation) study.

            We investigated whether coronary microvascular dysfunction predicts major adverse outcomes during follow-up among women with signs and symptoms of ischemia. Altered coronary reactivity occurs frequently in women evaluated for suspected ischemia, and the endothelium-dependent component is linked with adverse outcomes. Possible links between endothelium-independent microvascular coronary reactivity and adverse outcomes remain uncertain. As part of the National Heart, Lung and Blood Institute-sponsored WISE (Women's Ischemia Syndrome Evaluation), we investigated relationships between major adverse outcomes and baseline coronary flow reserve (CFR) after intracoronary adenosine in 189 women referred to evaluate suspected ischemia. At a mean of 5.4 years, we observed significant associations between CFR and major adverse outcomes (death, nonfatal myocardial infarction, nonfatal stroke, or hospital stay for heart failure). An exploratory receiver-operator characteristic analysis identified CFR or=2.32 event rate 12.2%; p = 0.01). Lower CFR was associated with increased risk for major adverse outcomes (hazard ratio: 1.16, 95% confidence interval: 1.04 to 1.30; p = 0.009). This held true among the 152 women without obstructive coronary artery disease (CAD) (hazard ratio: 1.20, 95% confidence interval: 1.05 to 1.38; p = 0.008). The CFR significantly improved prediction of adverse outcomes over angiographic CAD severity and other risk conditions. Among women with suspected ischemia and atherosclerosis risk factors, coronary microvascular reactivity to adenosine significantly improves prediction of major adverse outcomes over angiographic CAD severity and CAD risk factors. These findings suggest that coronary microvessels represent novel targets for diagnostic and therapeutic strategies to predict and limit adverse outcomes in women. (Women's Ischemia Syndrome Evaluation [WISE]; NCT00000554). Copyright (c) 2010 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
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              Effects of sex on coronary microvascular dysfunction and cardiac outcomes.

              Coronary microvascular dysfunction (CMD) is a prevalent and prognostically important finding in patients with symptoms suggestive of coronary artery disease. The relative extent to which CMD affects both sexes is largely unknown.
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                Author and article information

                Journal
                J Am Heart Assoc
                J Am Heart Assoc
                10.1002/(ISSN)2047-9980
                JAH3
                ahaoa
                Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
                John Wiley and Sons Inc. (Hoboken )
                2047-9980
                15 March 2016
                March 2016
                : 5
                : 3 ( doiID: 10.1002/jah3.2016.5.issue-3 )
                : e003064
                Affiliations
                [ 1 ] Department of Cardiology Bispebjerg HospitalUniversity of Copenhagen Denmark
                [ 2 ] Department of Cardiology RigshospitaletUniversity of Copenhagen Denmark
                [ 3 ] Department of Cardiology Gentofte HospitalUniversity of Copenhagen Denmark
                [ 4 ] Department of Cardiology Hvidovre HospitalUniversity of Copenhagen Denmark
                [ 5 ] Department of Cardiology Odense University HospitalUniversity of Southern Denmark OdenseDenmark
                [ 6 ] Barbra Streisand Women's Heart CenterCedars‐Sinai Heart Institute Los Angeles CA
                Author notes
                [*] [* ] Correspondence to: Naja Dam Mygind, MD, Department of Cardiology, Bispebjerg Hospital, Copenhagen University Hospital, Bispebjerg Bakke 23, København, NV 2400. E‐mails: naja.dam.mygind@ 123456regionh.dk , ndmygind@ 123456dadlnet.dk
                [†]

                Dr Mygind and Dr Michelsen contributed equally to the study as shared first authors.

                Article
                JAH31390
                10.1161/JAHA.115.003064
                4943278
                27068634
                6947ed3f-5bab-4d6a-b709-8cba5429faa8
                © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

                This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                History
                : 16 December 2015
                : 02 February 2016
                Page count
                Pages: 11
                Funding
                Funded by: Danish Heart Foundation
                Award ID: 11‐10‐R87‐B‐A3628‐22678
                Funded by: University of Copenhagen
                Categories
                Original Research
                Original Research
                Coronary Heart Disease
                Custom metadata
                2.0
                jah31390
                March 2016
                Converter:WILEY_ML3GV2_TO_NLMPMC version:4.8.9 mode:remove_FC converted:05.05.2016

                Cardiovascular Medicine
                angina pectoris,coronary artery disease,echocardiography,microvascular dysfunction,women,risk factors

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