The impact of aging and atherosclerotic risk factors on transthoracic coronary flow reserve in subjects with normal coronary angiography

Coronary flow reserve (CFR) represents the maximal increase in coronary flow above its resting level for a given perfusion pressure when coronary vasculature is maximally dilated [1,2]. Conceptually, CFR is the difference between the basal, autoregulated coronary flow and the maximal flow, at any given perfusion pressure [3,4]. In the clinical setting, however, CFR is measured in dimensionless units by dividing maximal by autoregulated flow, that is the CFR ratio.CFR can be measured by several - invasive or non invasive - techniques, which quantify coronary blood flow in absolute terms (e.g., positron emission tomography [PET]) or measure coronary blood flow velocity (Doppler) and calculate coronary flow velocity reserve [5]. Among these techniques, transthoracic echocardiography (TTE) allows the recording of flow velocities with a high feasibility for the mid-distal left anterior descending artery (LAD) [6]. TTE derived CFR of LAD has an excellent concordance with invasive Doppler flow wire and optimal reproducibility [6,7] and has now entered the stress echo laboratory for its clinical routine use during vasodilator stress testing.A reduction in coronary flow reserve can be associated to a significant epicardial coronary artery stenosis, but also to coronary microvascular disease or to factors increasing extravascular resistance and endoluminal compressive forces with normal coronary arteries, as it happens in left ventricular (LV) hypertrophy, dilated or hypertrophic cardiomyopathy, aortic valve stenosis. Previous studies have suggested that CFR may be impaired in individuals with atherosclerotic risk factors (ARFs). Also aging induces similar effects and it is likely that CFR might be attenuated in elderly subjects free of coronary artery stenosis. An age-dependent reduction of CFR has been previously reported by PET in limited sample size of healthy volunteers [8,9]. The reduction of CFR can reflect a reduction in maximal flow with stable resting flow, stable m