Outcome of coronary heart disease differs by gender with the most pertinent difference being that women referred to angiography for angina or myocardial infarction twice as often as men have no significant coronary vessel disease. It has been estimated that approximately 40.000 women in Denmark suffer from this condition. Contrary to previous understanding, these patients have a poor prognosis in terms of continued chest pain, reduced quality of life and increased risk of adverse cardiovascular outcomes. Coronary microvessel dysfunction has emerged as a novel target for diagnostic and therapeutic strategies. Concordantly, there is a growing international call for action to test the value of including measures of coronary flow reactivity to guide treatment on subgroups with demonstrated microvessel disease. A main obstacle in this, however, is the lack of clinically applicable easily available methods to diagnose microvascular disease.
The aim of the ongoing iPower study is dual: to improve our diagnostic capabilities of diagnosing coronary microvascular dysfunction and to determine whether routine assessment of microvascular dysfunction identifies women at risk of later cardiovascular events. The study is conducted in a strategic collaboration between five department of cardiology in Denmark with the majority of examinations taking place at Bispebjerg Hospital. We aim at examining 2000 women with chest pain but no obstructive coronary disease and have currently included approximately 1100. Microvessel disease will be defined by non-invasive echocardiography Doppler measurement of coronary flow reserve (CFR) and by peripheral endothelial function assessed digitally. In sub-studies, patients are further characterized by advanced imaging (echocardiography, CT- and MR perfusion scan and PET-CT) to further optimize diagnostic testing for ischemic heart disease in the absence of epicardial stenosis. In addition, utility of a number of inflammatory and non-inflammatory biomarkers will be tested for diagnostic and prognostic value and a biobank will be established to screen for potential relevant genotypes associated with microvascular dysfunction. The cohort of women will be followed for symptoms and cardiovascular endpoints to establish optimal risk stratification in women with angina. In small substudies effect of interventions on CFR and symptoms is tested in randomized trials.
The study is funded by the Danish Heart Foundation after winning a nationwide competition, and by grants from the University of Copenhagen and from the Danish Council of Independent Research. The study is conducted by 5 ph.d. students and a number of research year graduates (medical students).
Both nationally and internationally experience with diagnosing and treating microvessel disease is limited. Developing and improving clinically applicable methods to diagnose microvessel disease will not only have impact on patients with angina but is of relevance as a diagnostic and research tool to follow sub clinical coronary heart disease and will expand our knowledge on the role of microvessel function in coronary heart disease.
We anticipate that this comprehensive research project will result in optimized diagnostic testing for ischemic heart disease in the absence of epicardial stenosis, improved risk stratification in women with angina and better knowledge on evidence based treatment. The study will have considerable scientific impact and has the potential to improve clinical practice for this large group of patients.