James D. Cameron

Intensive cholesterol reduction lowers blood pressure and large artery stiffness in isolated systolic hypertension

OBJECTIVES We sought to investigate the effects of intensive cholesterol reduction on large artery stiffness and blood pressure in normolipidemic patients with isolated systolic hypertension (ISH). BACKGROUND Isolated systolic hypertension is associated with elevated cardiovascular morbidity and mortality and is primarily due to large artery stiffening, which has been independently related to cardiovascular mortality. Cholesterol-lowering therapy has been efficacious in reducing arterial stiffness in patients with hypercholesterolemia, and thus may be beneficial in ISH. METHODS In a randomized, double-blinded, cross-over study design, 22 patients with stage I ISH received three months of atorvastatin therapy (80 mg/day) and three months of placebo treatment. Systemic arterial compliance was measured noninvasively using carotid applanation tonometry and Doppler velocimetry of the ascending aorta. RESULTS Atorvastatin treatment reduced total and low-density lipoprotein cholesterol and triglyceride levels by 36 +/- 2% (p < 0.001), 48 +/- 3% (p < 0.001) and 23 +/- 5% (p = 0.003), respectively, and increased high density lipoprotein cholesterol by 7 +/- 3% (p = 0.03). Systemic arterial compliance was higher after treatment (placebo vs. atorvastatin: 0.36 +/- 0.03 vs. 0.43 +/- 0.05 ml/mm Hg, p = 0.03). Brachial systolic blood pressure was lower after atorvastatin treatment (154 +/- 3 vs. 148 +/- 2 mm Hg, p = 0.03), as were mean (111 +/- 2 vs. 107 +/- 2 mm Hg, p = 0.04) and diastolic blood pressures (83 +/- 1 vs. 81 +/- 2 mm Hg, p = 0.04). There was a trend toward a reduction in pulse pressure (71 +/- 3 vs. 67 +/- 2 mm Hg, p = 0.08). CONCLUSIONS Intensive cholesterol reduction may be beneficial in the treatment of patients with ISH and normal lipid levels, through a reduction in large artery stiffness.

Arterial compliance increases after moderate-intensity cycling

Exercise training elevates arterial compliance at rest, but the effects of acute exercise in this regard are unknown. This study investigated the effects of a single, 30-min bout of cycling exercise at 65% of maximal oxygen consumption on indexes of arterial compliance. Whole body arterial compliance determined noninvasively from simultaneous measurements of aortic flow and carotid pressure was elevated (66 ± 26%) at 0.5 h postexercise ( P = 0.04), followed by a decline to baseline 1 h after exercise. Aortic pulse-wave velocity, which is inversely related to compliance, was reduced (4 ± 2%; P = 0.04) at 0.5 h postexercise. Pulse-wave velocity in the leg decreased by 10 ± 4% at this time ( P = 0.01). Mean arterial pressure was unchanged; however, central systolic blood pressure was reduced postexercise ( P = 0.03). Cardiac output was elevated after exercise ( P = 0.007) via heart rate elevation ( P = 0.001), whereas stroke volume was unchanged. Total peripheral resistance was therefore reduced ( P = 0.01) and would be expected to contribute to an elevation in arterial compliance. In conclusion, a single bout of cycling exercise increased whole body arterial compliance by mechanisms that may relate to vasodilation.Exercise training elevates arterial compliance at rest, but the effects of acute exercise in this regard are unknown. This study investigated the effects of a single, 30-min bout of cycling exercise at 65% of maximal oxygen consumption on indexes of arterial compliance. Whole body arterial compliance determined noninvasively from simultaneous measurements of aortic flow and carotid pressure was elevated (66 +/- 26%) at 0.5 h postexercise (P = 0.04), followed by a decline to baseline 1 h after exercise. Aortic pulse-wave velocity, which is inversely related to compliance, was reduced (4 +/- 2%; P = 0.04) at 0.5 h postexercise. Pulse-wave velocity in the leg decreased by 10 +/- 4% at this time (P = 0.01). Mean arterial pressure was unchanged; however, central systolic blood pressure was reduced postexercise (P = 0.03). Cardiac output was elevated after exercise (P = 0.007) via heart rate elevation (P = 0.001), whereas stroke volume was unchanged. Total peripheral resistance was therefore reduced (P = 0.01) and would be expected to contribute to an elevation in arterial compliance. In conclusion, a single bout of cycling exercise increased whole body arterial compliance by mechanisms that may relate to vasodilation.

Computed tomography stress myocardial perfusion imaging in patients considered for revascularization: a comparison with fractional flow reserve

AIMS Adenosine stress computed tomography myocardial perfusion imaging (CTP) is an emerging non-invasive method for detecting myocardial ischaemia. Its value when compared with fractional flow reserve (FFR), a highly accurate index of ischaemia, is unknown. Our aim was to determine the diagnostic accuracy of CTP and its incremental value when used with computed tomography coronary angiography (CTA) for detecting ischaemia compared with FFR. METHODS AND RESULTS Forty-two patients (126 vessel territories), who had at least one ≥50% angiographic stenosis on invasive angiography considered for non-urgent revascularization, were included and underwent FFR and CT assessment, including CTP, delayed contrast enhancement scan and CTA all acquired using 320-detector row CT, and prospective ECG gating. Fractional flow reserve was determined in 86 territories subtended by vessels with ≥50% stenosis upon visual assessment. Fractional flow reserve ≤0.8 was considered to indicate significant ischaemia. Computed tomography myocardial perfusion imaging correctly identified 31/41 (76%) ischaemic territories and 38/45 (84%) non-ischaemic territories. Per-vessel territory sensitivity, specificity, positive, and negative predictive values of CTP were 76, 84, 82, and 79%, respectively. The combination of a ≥50% stenosis on CTA and perfusion defect on CTP was 98% specific for ischaemia, while the presence of <50% stenosis on CTA and normal perfusion on CTP was 100% specific for exclusion of ischaemia. Mean radiation for CTP and combined CT was 5.3 and 11.3 mSv, respectively. CONCLUSION Computed tomography myocardial perfusion imaging is moderately accurate in identifying perfusion defects associated with ischaemia as assessed by FFR in patients considered for revascularization. In territories, where CTA and CTP are concordant, CTA/CTP is highly accurate in the detection and exclusion of ischaemia. This is achievable with acceptable radiation exposure using 320-detector row CT and prospective ECG gating.

Aerobic Exercise Training Does Not Modify Large-Artery Compliance in Isolated Systolic Hypertension

The present study characterized large-artery properties in patients with isolated systolic hypertension (ISH) and determined the efficacy of exercise training in modifying these properties. Twenty patients (10 male and 10 female) with stage I ISH and 20 age- and gender-matched control subjects were recruited, and large-artery properties were assessed noninvasively. Ten ISH patients (5 male and 5 female) were enrolled in a randomized crossover study comparing 8 weeks of moderate intensity cycling with 8 weeks of sedentary activity. Brachial and carotid systolic, diastolic, mean, and pulse pressures were higher in the ISH group than in the control group. Systemic arterial compliance (0.43±0.04 versus 0.29±0.02 arbitrary compliance units for the control versus ISH groups, respectively;P =0.01) was lower, and carotid-to-femoral pulse-wave velocity (9.67±0.36 versus 11.43±0.51 m · s−1 for the control versus ISH groups, respectively;P =0.007), input impedance (2.39±0.19 versus 3.27±0.34 mm Hg · s · cm−1 for the control versus ISH groups, respectively;P =0.04), and characteristic impedance (1.67±0.17 versus 2.34±0.27 mm Hg · s · cm−1 for the control versus ISH groups, respectively;P =0.05) were higher in the ISH group than in the control group. Training increased maximal oxygen consumption by 13±5% (P =0.04) and maximum workload by 8±4% (P =0.05); however, there was no effect on arterial mechanical properties, blood lipids, or left ventricular mass or function. These results suggest that the large-artery stiffening associated with ISH is resistant to modification through short-term aerobic training.

Gender differences in the timing of arterial wave reflection beyond differences in body height.

Objectives The timing of arterial wave reflection affects the shape of the arterial waveform and thus is a major determinant of pulse pressure. This study assessed differences in wave reflection between genders beyond the effect of body height. Methods From 1123 elderly (aged 71 ± 5 years) currently untreated hypertensives, we selected 104 pairs of men and women with identical body height (average 164 ± 4 cm). All subjects underwent echocardiography, including measurement of aortic arch expansion, automated blood pressure measurements, measurement of ascending aortic blood flow and simultaneous carotid artery tonometry. Results Women had higher pulse (80 ± 17 versus 74 ± 17 mmHg, P < 0.05) and lower diastolic pressure (79 ± 11 versus 82 ± 10 mmHg, P < 0.05). Whilst heart rate was similar, women had a longer time to the systolic peak (210 ± 28 versus 199 ± 34 ms, P < 0.01) and a longer ejection time (304 ± 21 versus 299 ± 25 ms, P < 0.001). Wave reflection occurred earlier in women (time between maxima 116 ± 55 versus 132 ± 47 ms, P < 0.05) and augmentation index was higher (36 ± 11 versus 28 ± 12%, P < 0.001). Aortic diameter was smaller in women and the aortic arch was stiffer (median Ep 386 versus 302 kN/m2, P < 0.05). Hence, systemic arterial compliance was less in women (0.8 ± 0.2 versus 1.0 ± 0.3 ml/mmHg). Conclusions We conclude that elderly hypertensive men and women have a different timing of both left ventricular ejection and arterial wave reflection when both genders are matched for body height. Women have smaller and stiffer blood vessels resulting in an earlier return of the reflected wave, which is likely due to an increased pulse wave velocity in women.

Women exhibit a greater age-related increase in proximal aortic stiffness than men.

Background Large artery mechanical properties are a major determinant of pulse pressure and cardiovascular outcome. Sex differences in these properties may underlie the variation in cardiovascular risk profile between men and women, in relation to age. Objective To investigate sex differences in the age-related stiffening of large arteries. Design Cross-sectional. Methods One hundred and twenty healthy men and women were recruited and divided equally into tertiles by age: young (mean ± SD, 23 ± 5 years), middle-age (47 ± 3 years) and older (62 ± 7 years). Lipids, mean arterial pressure and heart rate were matched within each tertile. Carotid tonometry and Doppler velocimetry were used to measure indices of large artery stiffness. Results There was no sex difference in systemic arterial compliance (SAC) in the young group (mean ± SEM, 0.61 ± 0.05 arbitrary compliance units (ACU) in women compared with 0.67 ± 0.04 ACU in men), but in the older population women had lower SAC than men (0.27 ± 0.03 ACU compared with 0.57 ± 0.04 ACU respectively;P < 0.001). Measures independent of aortic geometry (distensibility index and aortic impedance) indicated that stiffness was lower in young women than in men (P < 0.05), but the reverse was true in the older population (P < 0.01). This paralleled the brachial and carotid pulse pressures, which were lower in young (P < 0.01) and higher in older women compared with those in men (P < 0.05). Follicle stimulating hormone concentrations correlated strongly (r values 0.39–0.65) with all indices of central, but not peripheral, arterial function, whereas concentrations of luteinizing hormone, progesterone and oestradiol correlated less strongly. Conclusions In men and women matched for mean pressures, the age-related stiffening of large arteries is more pronounced in women, which is consistent with changes in female hormonal status.

Age-Related Deterioration in Arterial Structure and Function in Postmenopausal Women: Impact of Hormone Replacement Therapy

Epidemiological evidence suggests that hormone replacement therapy (HRT) reduces morbidity and mortality from cardiovascular diseases in postmenopausal women. In this study, indices of arterial function [total systemic arterial compliance (SAC) and carotid arterial distensibility coefficient (DC)], structure [carotid intima-media thickness (IMT)], and lipid profiles were compared in postmenopausal women on long-term HRT and aged-matched controls. One hundred nine women aged 44 to 77 years taking HRT and an age-matched group of 108 female controls were entered into the study. The two groups were similar for body mass index, smoking status, exercise level, alcohol intake, and blood pressure. Fasting cholesterol, low density lipoprotein, and lipoprotein(a) were reduced and high density lipoprotein increased in the HRT group. IMT increased with age; SAC and DC were reduced with age in both groups. The HRT group had a higher mean SAC (0.42+/-0.02 versus 0.34+/-0.02 U/mm Hg, P=0.0001) and a lower mean IMT (0.67+/-0.01 versus 0.74+/-0.02 mm, P=0.006) than did controls. Subgroup analysis for estrogen versus estrogen plus progestin revealed no differences for SAC and IMT; DC, however, was greater in estrogen-only users. Smokers on HRT had a higher mean SAC (0.41+/-0.02 versus 0.31+/-0.01 U/mm Hg, P=0.008) and a lower IMT (0.65+/-0.02 versus 0.75+/-0.03 mm, P=0.002) than did smokers not taking such therapy. A protective effect of long-term estrogen therapy on age-related changes in arterial structure and function in postmenopausal women was evident in smokers and nonsmokers alike. Progestin appeared to counteract the effects of estrogen on carotid compliance only. Long-term controlled trials are needed to determine the significance of these findings.

Effects of Blood Pressure, Smoking, and Their Interaction on Carotid Artery Structure and Function

In the present study, we examined the relationships among carotid blood pressure, arterial geometry, and wall stress and determined the impact of hypertension, smoking status, and their interaction on these relationships. The study involved 679 subjects aged 49 to 82 years: 372 smokers (190 men and 182 women) and 307 nonsmokers (110 men and 197 women). Blood samples were taken to determine total cholesterol levels. Central pulse pressure was derived from measured brachial artery pressure with a linear regression equation from data obtained in a subgroup of 276 subjects that related brachial and carotid pulse pressures; the latter was measured with applanation tonometry. Carotid intima-media thickness (IMT), lumen diameter (D), and stiffness index (SI) were determined with high-resolution B-mode ultrasound. Mean and pulsatile circumferential stress (&sfgr;C) was calculated according to the Laplace relationship. Indexes of arterial geometry and function were adjusted for age, height, and heart rate. Hypertension (treated and/or screening blood pressure of >140/90 mm Hg) was present in 71 nonsmokers and 186 smokers. Nonsmokers and smokers did not differ in blood pressure and cholesterol levels. Hypertension and smoking individually and interactively significantly increased adjusted IMT, D, and SI. The radius-to–wall thickness ratio (R/IMT) (where R=D/2) and &sfgr;C were increased in hypertensives. SI was correlated with IMT (r =0.56, P <0.001); radius-to–wall thickness ratio was inversely correlated with central pulse pressure (r =−0.38, P <0.001). Smoking did not influence these relationships. In conclusion, carotid artery wall remodeling appears to follow Laplace’s law but is insufficient to prevent an increase in circumferential stress in hypertensive subjects. Unlike hypertension, smoking does not influence the lumen-to-wall ratio but has a significant effect on wall stiffness.

Combined CT coronary angiography and stress myocardial perfusion imaging for hemodynamically significant stenoses in patients with suspected coronary artery disease: a comparison with fractional flow reserve

OBJECTIVES We sought to determine the accuracy of combined coronary computed tomography angiography (CTA) and computed tomography stress myocardial perfusion imaging (CTP) in the detection of hemodynamically significant stenoses using fractional flow reserve (FFR) as a reference standard in patients with suspected coronary artery disease. BACKGROUND CTP can be qualitatively assessed by visual interpretation or quantified by the transmural perfusion ratio determined as the ratio of subendocardial to subepicardial contrast attenuation. The incremental value of each technique in addition to coronary CTA to detect hemodynamically significant stenoses is not known. METHODS Forty symptomatic patients underwent FFR and 320-detector computed tomography assessment including coronary CTA and CTP. Myocardial perfusion was assessed using the transmural perfusion ratio and visual perfusion assessment. Computed tomography images were assessed by consensus of 2 observers. Transmural perfusion ratio <0.99 was used as the threshold for abnormal perfusion. FFR ≤0.8 indicated hemodynamically significant stenoses. RESULTS Coronary CTA detected FFR-significant stenoses with 95% sensitivity and 78% specificity. The additional use of visual perfusion assessment and the transmural perfusion ratio both increased the specificity to 95%, with sensitivity of 87% and 71%, respectively. The area under the receiver-operating characteristic curve for coronary CTA + visual perfusion assessment was significantly higher than both coronary CTA (0.93 vs. 0.85, p = 0.0003) and coronary CTA + the transmural perfusion ratio (0.93 vs. 0.79, p = 0.0003). Per-vessel and per-patient accuracy for coronary CTA, coronary CTA + the transmural perfusion ratio, and coronary CTA + visual perfusion assessment was 83% and 83%, 87% and 92%, and 92% and 95%, respectively. CONCLUSIONS In suspected coronary artery disease, combined coronary CTA + CTP identifies patients with hemodynamically significant stenoses with >90% accuracy compared with FFR. When interpreted with coronary CTA, visual perfusion assessment provided superior incremental value in the detection of FFR-significant stenoses compared with the quantitative transmural perfusion ratio assessment.

The relationship between arterial compliance, age, blood pressure and serum lipid levels.

Objective To investigate the association of serum lipids with non-invasively assessed systemic arterial compliance in a group of newly diagnosed coronary artery disease patients and their matched controls. Design Systemic arterial compliance is important in maintaining diastolic blood pressure and coronary perfusion, with decreased diastolic blood pressure in the presence of significant coronary artery disease suggested as contributing to increased morbidity. Decreased systemic arterial compliance is also associated with increased morbidity through its contribution to systolic hypertension. Despite the importance of arterial compliance, its association with biochemical factors is not certain. Patients and methods Twenty newly diagnosed coronary artery disease patients and disease-free controls were matched for age, sex, smoking status and total serum cholesterol level. Systemic arterial compliance was measured using applanation tonometry and Doppler velocimetry before instigation of treatment. Results There was no difference in group low-density lipoprotein or high-density lipoprotein cholesterol levels. Systemic arterial compliance was significantly less in the coronary artery disease group. For the groups combined, a significant negative correlation was demonstrated between systemic arterial compliance and low-density lipoprotein; however, on separate group analysis the correlation was confined to the coronary artery disease group. A significant difference was found in the association between systemic arterial compliance and diastolic blood pressure for the two groups. Conclusions Increasing low-density lipoprotein cholesterol levels are associated with decreasing systemic arterial compliance; however, the identified intergroup differences suggest that, presumably because of differences in lipid–vessel wall interactions, disease-free subjects exhibit relatively less alteration in aortic mechanical properties than those who develop coronary artery disease.