Differential association of diabetes mellitus and female sex with impaired myocardial flow reserve across the spectrum of epicardial coronary disease.

Aims Diabetes mellitus (DM) affects the macro- and microvasculature, leading to impairment in coronary vascular reactivity. Microvascular dysfunction is more prevalent in females compared to males, leading to increased cardiovascular risk in women. The purpose of this study was to quantify the association between diabetes and female sex on myocardial flow reserve (MFR) across the spectrum of epicardial coronary artery disease (CAD). Methods and results In 222 patients with known or suspected CAD (63.7 +/- 10.7 years, 66 females, 85 with diabetes) who had rubidium- 82 positron emission tomography (PET) and invasive coronary angiography within 6 months, a multiple linear regression model was developed to predict MFR based on clinical risk factors and imaging results across a spectrum of regional epicardial disease. A significant interaction effect suggested that impairment of MFR is accelerated in diabetics with increasing severity of epicardial disease. Furthermore, female sex (-13%), decade of age (-6%), ischaemia on electrocardiogram (-10%), resting rate-pressure product (-3%), and rest end-diastolic volume (-0.2%) were associated with reductions in MFR independent of the combined extent and severity of epicardial disease. Conclusion In the presence of significant obstructive epicardial disease, MFR decreases more rapidly in patients with DM compared to those without. Additional patient demographics and risk factors such as female sex and older age, and stress PET functional parameters should also be considered in the clinical interpretation of MFR. This has implications for the diagnosis and management of CAD patients with these and other risk factors for microvascular disease.