Aging, Atherosclerotic Risk Factors and Coronary Flow Reserve
Aging, Atherosclerotic Risk Factors and Coronary Flow Reserve
The study population was divided into quartiles of age: 1 quartile = < 55 years, 2 quartile = ≥ 55 and 62 years, 3 quartile = between ≥ 63 years and 69 years, 4 quartile = ≥ 70 years. Table 1 reports the clinical characteristics and main echocardiographic parameters according to age quartiles. As expected, body mass index and BP increased significantly with age. Heart rate was not significantly different among the various age groups. LV mass index significantly increasedwith aging. The prevalence of LV hypertrophy in the pooled population was 44% (150/345). The frequency of anti-hypertensive and/or anti-ischemic therapy at time of testing (not discontinued) was significantly higher in the 4 quartile (p < 0.0001). Table 2 reports the prevalence of the main ARFs for age quartiles. Arterial hypertension had the greatest prevalence in the pooled population (54.8%), followed by hypercholesterolemia (46.7%), smoking habit (24.3%) and diabetes (20.3%) The frequency of arterial hypertension, hypercholesterolemia and, with a lower extent, diabetes mellitus increased with aging.
Table 3 summarizes the data of the CFR test according to age quartiles. Mean CFR was 2.63 ± 0.71. In the whole population CFR was gradually reduced with increasing age, showing the lowest value in the fourth quartile of age (p < 0.0001). This reduction was accounted for an increase of resting coronary flow velocities while the hyperemic coronary flow velocities remained unaffected in the several age classes (p = 0.08, NS).
We also analysed the data excluding the 116 patients with objective signs of ischemia at study entry (by ECG criteria and/or perfusion abnormalities) in order to rule out microvascular angina as a potential confounder. In the subset of 219 patients with no objective signs of ischemia, CFR was also gradually reduced with increasing age (p < 0.001).
In the pooled population age was correlated positively with coronary flow velocity at rest (r = 0.20, p < 0.0001) and negatively with hyperemic coronary flow velocity (r = −0.13, p < 0.02) (Figure 1). Age was negatively correlated with CFR (r = −0.41, p < 0.0001) (Figure 2) and was also related with systolic BP (r = 0.34), diastolic BP (r = 0.37) and mean BP (r = 0.39) (all p < 0.0001), with total blood cholesterol (r = 0.27) (p < 0.0001), fasting blood glucose (r = 0.18) (p < 0.001), body mass index (r = 0.12, p = 0.03) and LV mass index (r = 0.43, p < 0.0001).
(Enlarge Image)
Figure 1.
Upper panel: Correlation between age and Doppler velocities at rest. Lower panel: Correlation between age and Doppler velocities at hyperemic flow. Resting velocities progressively decrease with age, whereas hyperemic flow velocities remain unaffected.
(Enlarge Image)
Figure 2.
Correlation between CFR and age. CFR decreases progressively with aging.
A multiple linear regression analysis was performed to identify the independent associations of CFR, by including continuous variables (body mass index, heart rate, diastolic BP, total blood cholesterol, fasting blood glucose, LV mass index), categorical variables (male gender, cigarette smoking) and age quartiles as potential contributors (Table 4). CFR was independently associated with both the third (standardized β coefficient = −0.16, p < 0.005) and fourth (β = −0.22, p < 0.0001) age quartile. Among ARFs, elevated diastolic BP (p < 0.001) and high total cholesterol (p < 0.002) showed the best independent associations with CFR reduction, while the contribution of fasting blood glucose was lower (p < 0.01) and that of cigarette smoking did not achieve the statistical significance (p = 0.06). LVM index was a strong determinant of CFR (β = −0.32, p < 0.0001). Of note, by analyzing the impact of ARFs on hyperemic coronary flow velocity after adjusting for the same confounders analyzed in Table 4, only total blood cholesterol (standardized β coefficient = −0.126, diastolic BP (β = −0.134) and LV mass index (β = −0.130) (all p < 0.02) were independently associated with the hyperemic coronary flow velocity.
Results
The study population was divided into quartiles of age: 1 quartile = < 55 years, 2 quartile = ≥ 55 and 62 years, 3 quartile = between ≥ 63 years and 69 years, 4 quartile = ≥ 70 years. Table 1 reports the clinical characteristics and main echocardiographic parameters according to age quartiles. As expected, body mass index and BP increased significantly with age. Heart rate was not significantly different among the various age groups. LV mass index significantly increasedwith aging. The prevalence of LV hypertrophy in the pooled population was 44% (150/345). The frequency of anti-hypertensive and/or anti-ischemic therapy at time of testing (not discontinued) was significantly higher in the 4 quartile (p < 0.0001). Table 2 reports the prevalence of the main ARFs for age quartiles. Arterial hypertension had the greatest prevalence in the pooled population (54.8%), followed by hypercholesterolemia (46.7%), smoking habit (24.3%) and diabetes (20.3%) The frequency of arterial hypertension, hypercholesterolemia and, with a lower extent, diabetes mellitus increased with aging.
Table 3 summarizes the data of the CFR test according to age quartiles. Mean CFR was 2.63 ± 0.71. In the whole population CFR was gradually reduced with increasing age, showing the lowest value in the fourth quartile of age (p < 0.0001). This reduction was accounted for an increase of resting coronary flow velocities while the hyperemic coronary flow velocities remained unaffected in the several age classes (p = 0.08, NS).
We also analysed the data excluding the 116 patients with objective signs of ischemia at study entry (by ECG criteria and/or perfusion abnormalities) in order to rule out microvascular angina as a potential confounder. In the subset of 219 patients with no objective signs of ischemia, CFR was also gradually reduced with increasing age (p < 0.001).
In the pooled population age was correlated positively with coronary flow velocity at rest (r = 0.20, p < 0.0001) and negatively with hyperemic coronary flow velocity (r = −0.13, p < 0.02) (Figure 1). Age was negatively correlated with CFR (r = −0.41, p < 0.0001) (Figure 2) and was also related with systolic BP (r = 0.34), diastolic BP (r = 0.37) and mean BP (r = 0.39) (all p < 0.0001), with total blood cholesterol (r = 0.27) (p < 0.0001), fasting blood glucose (r = 0.18) (p < 0.001), body mass index (r = 0.12, p = 0.03) and LV mass index (r = 0.43, p < 0.0001).
(Enlarge Image)
Figure 1.
Upper panel: Correlation between age and Doppler velocities at rest. Lower panel: Correlation between age and Doppler velocities at hyperemic flow. Resting velocities progressively decrease with age, whereas hyperemic flow velocities remain unaffected.
(Enlarge Image)
Figure 2.
Correlation between CFR and age. CFR decreases progressively with aging.
A multiple linear regression analysis was performed to identify the independent associations of CFR, by including continuous variables (body mass index, heart rate, diastolic BP, total blood cholesterol, fasting blood glucose, LV mass index), categorical variables (male gender, cigarette smoking) and age quartiles as potential contributors (Table 4). CFR was independently associated with both the third (standardized β coefficient = −0.16, p < 0.005) and fourth (β = −0.22, p < 0.0001) age quartile. Among ARFs, elevated diastolic BP (p < 0.001) and high total cholesterol (p < 0.002) showed the best independent associations with CFR reduction, while the contribution of fasting blood glucose was lower (p < 0.01) and that of cigarette smoking did not achieve the statistical significance (p = 0.06). LVM index was a strong determinant of CFR (β = −0.32, p < 0.0001). Of note, by analyzing the impact of ARFs on hyperemic coronary flow velocity after adjusting for the same confounders analyzed in Table 4, only total blood cholesterol (standardized β coefficient = −0.126, diastolic BP (β = −0.134) and LV mass index (β = −0.130) (all p < 0.02) were independently associated with the hyperemic coronary flow velocity.