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      Coronary microvascular function and myocardial fibrosis in women with angina pectoris and no obstructive coronary artery disease: the iPOWER study

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          Abstract

          Background

          Even in absence of obstructive coronary artery disease women with angina pectoris have a poor prognosis possibly due to coronary microvascular disease. Coronary microvascular disease can be assessed by transthoracic Doppler echocardiography measuring coronary flow velocity reserve (CFVR) and by positron emission tomography measuring myocardial blood flow reserve (MBFR). Diffuse myocardial fibrosis can be assessed by cardiovascular magnetic resonance (CMR) T1 mapping. We hypothesized that coronary microvascular disease is associated with diffuse myocardial fibrosis.

          Methods

          Women with angina, a clinically indicated coronary angiogram with <50 % stenosis and no diabetes were included. CFVR was measured using dipyridamole (0.84 mg/kg) and MBFR using adenosine (0.84 mg/kg). Focal fibrosis was assessed by 1.5 T CMR late gadolinium enhancement (0.1 mmol/kg) and diffuse myocardial fibrosis by T1 mapping using a modified Look-Locker pulse sequence measuring T1 and extracellular volume fraction (ECV).

          Results

          CFVR and CMR were performed in 64 women, mean (SD) age 62.5 (8.3) years. MBFR was performed in a subgroup of 54 (84 %) of these women. Mean native T1 was 1023 (86) and ECV (%) was 33.7 (3.5); none had focal fibrosis. Median (IQR) CFVR was 2.3 (1.9; 2.7), 23 (36 %) had CFVR < 2 indicating coronary microvascular disease, and median MBFR was 2.7 (2.2; 3.0) and 19 (35 %) had a MBFR value below 2.5. No significant correlations were found between CFVR and ECV or native T1 ( R 2  = 0.02; p = 0.27 and R 2  = 0.004; p = 0.61, respectively). There were also no correlations between MBFR and ECV or native T1 ( R 2  = 0.1; p = 0.13 and R 2  = 0.004, p = 0.64, respectively). CFVR and MBFR were correlated to hypertension and heart rate.

          Conclusion

          In women with angina and no obstructive coronary artery disease we found no association between measures of coronary microvascular disease and myocardial fibrosis, suggesting that myocardial ischemia induced by coronary microvascular disease does not elicit myocardial fibrosis in this population. The examined parameters seem to provide independent information about myocardial and coronary disease.

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          Most cited references33

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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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              • Article: not found

              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

                Contributors
                +45 2066 1820 , naja.dam.mygind.02@regionh.dk
                Journal
                J Cardiovasc Magn Reson
                J Cardiovasc Magn Reson
                Journal of Cardiovascular Magnetic Resonance
                BioMed Central (London )
                1097-6647
                1532-429X
                4 November 2016
                4 November 2016
                2017
                : 18
                : 76
                Affiliations
                [1 ]Department of Cardiology, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark
                [2 ]Department of Cardiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
                [3 ]Department of Cardiology, Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark
                [4 ]Department of Cardiology, Hvidovre Hospital, University of Copenhagen, Copenhagen, Denmark
                [5 ]Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Rigshospitalet and University of Copenhagen, Copenhagen, Denmark
                Article
                295
                10.1186/s12968-016-0295-5
                5096323
                27809867
                8aa17a4c-6a31-4cec-a791-10023b2b6322
                © The Author(s). 2016

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 11 June 2016
                : 12 October 2016
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100006442, Det Sundhedsvidenskabelige Fakultet, Københavns Universitet;
                Funded by: FundRef http://dx.doi.org/10.13039/501100006442, Det Sundhedsvidenskabelige Fakultet, Københavns Universitet;
                Funded by: Hjerteforeningen (DK)
                Award ID: 11-10-R87-B-A3628-22678
                Award Recipient :
                Categories
                Research
                Custom metadata
                © The Author(s) 2016

                Cardiovascular Medicine
                microvascular dysfunction,women,angina pectoris,t1 mapping,coronary flow velocity reserve,cardiovascular magnetic resonance,doppler echocardiography,positron emission tomography,diffuse fibrosis,extracellular volume

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