Aging, Atherosclerotic Risk Factors and Coronary Flow Reserve
Aging, Atherosclerotic Risk Factors and Coronary Flow Reserve
Age may affect coronary flow reserve (CFR) especially in subjects with atherosclerotic risk factors (ARFs). The aim of this prospective, multicenter, observational study was to determine the effects of aging on CFR in patients with normal epicardial coronary arteries and ARFs. Three-hundred-thirty-five subjects (mean age = 61 years) with at least one ARF but normal coronary angiography underwent high-dose dipyridamole stress-echo with Doppler evaluation of left anterior descending artery. CFR was calculated as the ratio between hyperemic and resting coronary diastolic peak velocities. Patients were divided in age quartiles. CFR was progressively reduced with aging (1 quartile: 3.01 ± 0.69, 4 quartile: 2.39 ± 0.49, p < 0.001). This was mainly due to a gradual increase of resting velocities (1 quartile = 26.3 ± 6.1 cm/s, 4 quartile = 30.2 ± 6.4 cm/s, p < 0.001) while the reduction of hyperemic velocities remained unaffected (1 quartile = 77.7 ± 18.9 cm/s, 4 quartile = 70.9 ± 18.4 cm/s, NS). When age quartiles and ARFs were entered into a regression model, third and fourth age quartile (p < 0.0005 and p < 0.0001 respectively), left ventricular mass index (p < 0.0001), diastolic blood pressure (p < 0.001), total cholesterol (p < 0.002), fasting blood glucose (p < 0.01) and male gender (p < 0.05) were independent determinants of CFR in the whole population. Aging reduces coronary flow reserve in patients with angiographically normal coronary arteries due to a gradual increase of resting coronary flow velocity. CFR is also affected by atherosclerotic risk factors and left ventricular hypertrophy.
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. Conceptually, CFR is the difference between the basal, autoregulated coronary flow and the maximal flow, at any given perfusion pressure. 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. 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). TTE derived CFR of LAD has an excellent concordance with invasive Doppler flow wire and optimal reproducibility 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. The reduction of CFR can reflect a reduction in maximal flow with stable resting flow, stable maximal flow with increase in resting flow or a combination of reduction in maximal and increase in resting flow. The primary end-point of the present study was to elucidate the most likely mechanism for the known decrease in CFR with age. Our hypothesis was that age and composite risk factors had differential impact on resting versus maximal coronary flow velocity.
Abstract and Introduction
Abstract
Age may affect coronary flow reserve (CFR) especially in subjects with atherosclerotic risk factors (ARFs). The aim of this prospective, multicenter, observational study was to determine the effects of aging on CFR in patients with normal epicardial coronary arteries and ARFs. Three-hundred-thirty-five subjects (mean age = 61 years) with at least one ARF but normal coronary angiography underwent high-dose dipyridamole stress-echo with Doppler evaluation of left anterior descending artery. CFR was calculated as the ratio between hyperemic and resting coronary diastolic peak velocities. Patients were divided in age quartiles. CFR was progressively reduced with aging (1 quartile: 3.01 ± 0.69, 4 quartile: 2.39 ± 0.49, p < 0.001). This was mainly due to a gradual increase of resting velocities (1 quartile = 26.3 ± 6.1 cm/s, 4 quartile = 30.2 ± 6.4 cm/s, p < 0.001) while the reduction of hyperemic velocities remained unaffected (1 quartile = 77.7 ± 18.9 cm/s, 4 quartile = 70.9 ± 18.4 cm/s, NS). When age quartiles and ARFs were entered into a regression model, third and fourth age quartile (p < 0.0005 and p < 0.0001 respectively), left ventricular mass index (p < 0.0001), diastolic blood pressure (p < 0.001), total cholesterol (p < 0.002), fasting blood glucose (p < 0.01) and male gender (p < 0.05) were independent determinants of CFR in the whole population. Aging reduces coronary flow reserve in patients with angiographically normal coronary arteries due to a gradual increase of resting coronary flow velocity. CFR is also affected by atherosclerotic risk factors and left ventricular hypertrophy.
Introduction
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. Conceptually, CFR is the difference between the basal, autoregulated coronary flow and the maximal flow, at any given perfusion pressure. 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. 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). TTE derived CFR of LAD has an excellent concordance with invasive Doppler flow wire and optimal reproducibility 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. The reduction of CFR can reflect a reduction in maximal flow with stable resting flow, stable maximal flow with increase in resting flow or a combination of reduction in maximal and increase in resting flow. The primary end-point of the present study was to elucidate the most likely mechanism for the known decrease in CFR with age. Our hypothesis was that age and composite risk factors had differential impact on resting versus maximal coronary flow velocity.