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Coronary Pathophysiology and Microcirculation

Position Papers and Consensus Documents from the ESC Working Group on Coronary Pathophysiology and Microcirculation



Position paper of the European Society of Cardiology–working group of coronary pathophysiology and microcirculation: obesity and heart disease

Authors: Lina Badimon, Raffaele Bugiardini, Edina Cenko, Judit Cubedo, Maria Dorobantu, Dirk J. Duncker, Ramón Estruch, Davor Milicic, Dimitris Tousoulis, Zorana Vasiljevic, Gemma Vilahur, Cor de Wit, Akos Koller

European Heart Journal (2017) 38 (25): 1951-1958; doi: 10.1093/eurheartj/ehx181; Published: 10 May 2017

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Coronary vascular regulation, remodelling, and collateralization: mechanisms and clinical implications

On behalf of the working group on coronary pathophysiology and microcirculation

Authors: Axel R. Pries, Lina Badimon, Raffaele Bugiardini, Paolo G. Camici, Maria Dorobantu, Dirk J. Duncker, Javier Escaned, Akos Koller, Jan J. Piek, Cor de Wit

European Heart Journal (2015); doi:10.1093/eurheartj/ehv100; First published online: 25 June 2015

Objective: To present a critical and integrated view on vascular adaptations that occur at different time scales, in response to physiological and pathological challenges occurring in the coronary microcirculation which is beyond the domain of catheter investigation and intravascular imaging.

Introduction: Histological specimen and textbook schematics evoke static pictures of vascular networks. However, the concept of a static system is grossly misleading as vessels and their arrangement into networks exhibit a high degree of adaptation in vessel tone and vessel wall structure. These adaptive responses include the fast adjustment of vessel diameter by changes in smooth muscle tone, the slower changes of structural vessel diameter, the addition or removal of vessels by angiogenesis (sprouting/splitting), or vascular pruning. It is relevant to distinguish physiological adaptation, maintaining an adequate state of perfusion as well as perfusion reserve, from mal-adaptation, which may occur in the context of pathological conditions, such as a persistent increase in blood pressure. There are also differences between regulatory mechanisms in larger vessels (e.g. remodelling at the site of epicardial stenosis) and those in the microcirculation. Even within the microcirculation vascular control mechanisms are highly dependent on vessel size and type and the extent of changes in vasomotor tone and structure seem to increase with decreasing vessel size. Adaptive processes in the microcirculation are increasingly emerging as being crucial for maintenance of physiological function and for the development of relevant pathological conditions. This part of the coronary circulation, exhibiting that functional and structural plasticity requires more attention in both basic and clinical science as the basis to develop improved diagnostic and therapeutic approaches. Consequently, the present review will focus on adaptive events occurring in the coronary microcirculation which is beyond the domain of catheter investigation and intravascular imaging.

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Presentation, management, and outcomes of ischaemic heart disease in women

Authors: Viola Vaccarino, Lina Badimon, Roberto Corti, Cor de Wit, Maria Dorobantu, Olivia Manfrini, Akos Koller, Axel Pries, Edina Cenko & Raffaele Bugiardini

Nature Reviews Cardiology; 10, 508-518 (September 2013); doi:10.1038/nrcardio.2013.93

Objective: To assess inequities and the evidence for sex-related differences in the clinical presentation, treatment, and outcome of Ischemic Heart Disease, and identify gaps that need to be addressed in future research efforts and sex-related differences in cardiovascular management

Highlights:

  • Issues concerning presentation and recognition of ischemic symptoms in women continue to raise questions regarding specificity/ sensitivity of symptoms in this population.
  • Younger women presenting without chest pain have greater hospital mortality than men
  • Environmental or behavioral causes of sex differences in outcomes may be more important than biological ones.
  • The assumption that prognosis of all women with angina and "minimal or no obstructive coronary artery disease" by angiography is benign should be discouraged.
  • Our traditional diagnostic strategy focusing on detection of severe coronary stenoses may be inadequate in women
  • Testing aimed at determining endothelial coronary dysfunction is required to assess risk stratification in women with chest pain and minimal or no obstructive coronary artery disease.

Abstract: Scientific interest in ischaemic heart disease (IHD) in women has grown considerably over the past 2 decades. A substantial amount of the literature on this subject is centred on sex differences in clinical aspects of IHD. Many reports have documented sex-related differences in presentation, risk profiles, and outcomes among patients with IHD, particularly acute myocardial infarction. Such differences have often been attributed to inequalities between men and women in the referral and treatment of IHD, but data are insufficient to support this assessment. The determinants of sex differences in presentation are unclear, and few clues are available as to why young, premenopausal women paradoxically have a greater incidence of adverse outcomes after acute myocardial infarction than men, despite having less-severe coronary artery disease. Although differential treatment on the basis of patient sex continues to be described, the extent to which such inequalities persist and whether they reflect true disparity is unclear. Additionally, much uncertainty surrounds possible sex-related differences in response to cardiovascular therapies, partly because of a persistent lack of female-specific data from cardiovascular clinical trials. In this Review, we assess the evidence for sex-related differences in the clinical presentation, treatment, and outcome of IHD, and identify gaps in the literature that need to be addressed in future research efforts.

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Ischemic Heart Disease in Women: Are There Sex Differences in Pathophysiology and Risk Factors?

Position Paper from the Working Group on Coronary Pathophysiology & Microcirculation of the European Society of Cardiology

Authors: Viola Vaccarino, Lina Badimon, Roberto Corti, Cor de Wit, Maria Dorobantu, Alistair Hall, Akos Koller, Mario Marzilli, Axel Pries, Raffaele Bugiardini

Cardiovascular Research Journal (2011) 90, 9–17; doi: http://dx.doi.org/10.1093/cvr/cvq394 9-17; First published online: 15 December 2010

Objective: To identify gaps in existing literature and make recommendations for future research in sex related ischemic heart disease pathophysiology, endothelial function, epidemiology and cardiovascular risk factors
Abstract: Cardiovascular disease (CVD) is the leading cause of death in women, and knowledge of the clinical consequences of atherosclerosis and CVD in women has grown tremendously over the past 20 years. Research efforts have increased and many reports on various aspects of ischaemic heart disease (IHD) in women have been published highlighting sex differences in pathophysiology, presentation, and treatment of IHD. Data, however, remain limited. A description of the state of the science, with recognition of the shortcomings of current data, is necessary to guide future research and move the field forward. In this report, we identify gaps in existing literature and make recommendations for future research. Women largely share similar cardiovascular risk factors for IHD with men; however, women with suspected or confirmed IHD have less coronary atherosclerosis than men, even though they are older and have more cardiovascular risk factors than men. Coronary endothelial dysfunction and microvascular disease have been proposed as important determinants in the aetiology and prognosis of IHD in women, but research is limited on whether sex differences in these mechanisms truly exist. Differences in the epidemiology of IHD between women and men remain largely unexplained, as we are still unable to explain why women are protected towards IHD until older age compared with men. Eventually, a better understanding of these processes and mechanisms may improve the prevention and the clinical management of IHD in women.

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Comments: Professor Viola Vaccarino comments the position paper "Ischemic Heart Disease in Women: Are There Sex Differences in Pathophysiology and Risk Factors?"

Viola Vaccarino, MD, PhD, Professor and Chair, Department of Epidemiology, Rollins School of Public Health, and Professor of Medicine, Division of Cardiology, Emory University, Atlanta, GA.

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A review of methods for assessment of coronary microvascular disease in both clinical and experimental settings

Authors: Axel R. Pries, Helmut Habazettl, Giuseppe Ambrosio, Peter Riis Hansen, Juan Carlos Kaski, Volker Schächinger, Harald Tillmanns, Giuseppe Vassalli, Isabella Tritto, Michael Weis, Cor de Wit, Raffaele Bugiardini

Cardiovascular Research (November 2008), 80 (2) 165-174; doi: 10.1093/cvr/cvn136; First published online: 29 May 2008

Objective: To evaluate the role of the microvasculature in the genesis of myocardial ischaemia and cardiac damage-in the presence or absence of obstructive coronary atherosclerosis and to translate current molecular, cellular, and physiological knowledge into new evolving diagnostics and therapeutic options.

Abstract: Obstructive disease of the large coronary arteries is the prominent cause for angina pectoris. However, angina may also occur in the absence of significant coronary atherosclerosis or coronary artery spasm, especially in women. Myocardial ischaemia in these patients is often associated with abnormalities of the coronary microcirculation and may thus represent a manifestation of coronary microvascular disease (CMD). Elucidation of the role of the microvasculature in the genesis of myocardial ischaemia and cardiac damage—in the presence or absence of obstructive coronary atherosclerosis—will certainly result in more rational diagnostic and therapeutic interventions for patients with ischaemic heart disease. Specifically targeted research based on improved assessment modalities is needed to improve the diagnosis of CMD and to translate current molecular, cellular, and physiological knowledge into new therapeutic options.

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