The impact of cardiovascular risk factors on aortic stiffness and wave reflections depends on age: The Anglo-Cardiff Collaborative Trial (ACCT III)

Ageing exerts differential effects on arterial stiffness and wave reflections. However, the impact of cardiovascular risk factors on arterial stiffness and wave reflections and, particularly, how such effects are influenced by ageing has not been assessed within a single large population, covering a sufficiently wide age range. Therefore, we determined the extent to which age alters the impact of traditional cardiovascular risk factors on arterial stiffness and wave reflections. Aortic stiffness and wave reflections were assessed in 4421 individuals (age range 18 to 92 years). When treated as continuous variables, clinic systolic, diastolic, and pulse pressures and glucose levels were independently associated with stiffness, and, with the exception of diastolic pressure, these associations were more marked in older individuals. In contrast, clinic systolic and diastolic pressures and smoking were independently associated with wave reflections, with stronger associations observed in younger individuals. The impact of traditional cardiovascular risk factors on arterial stiffness and wave reflections is strongly dependent on age and is largely driven by blood pressure. Additional studies are required to assess the impact of these arterial measures on cardiovascular outcome within a single population

Aortic calcification is associated with aortic stiffness and isolated systolic hypertension in healthy individuals

Arterial stiffening is an independent predictor of mortality and underlies the development of isolated systolic hypertension (ISH). A number of factors regulate stiffness, but arterial calcification is also likely to be important. We tested the hypotheses that aortic calcification is associated with aortic stiffness in healthy individuals and that patients with ISH exhibit exaggerated aortic calcification compared with controls. A total of 193 healthy, medication-free subjects (mean age+/-SD: 66+/-8 years) were recruited from the community, together with 15 patients with resistant ISH. Aortic pulse wave velocity (PWV) was measured noninvasively, and aortic calcium content was quantified from high-resolution, thoraco-lumbar computed tomography images using a volume scoring method. In healthy volunteers, calcification was positively and significantly associated with aortic PWV (r=0.6; P<0.0001) but was not related to augmentation index or brachial PWV. Calcification was significantly higher in treatment-resistant and healthy subjects with ISH compared with controls (mean [interquartile range]: 1.92 [1.14 to 3.66], 0.84 [0.35 to 1.75], and 0.19 [0.1 to 0.78] cm3, respectively; P<0.0001 for both). In a multiple regression model, aortic calcium was independently associated with aortic PWV along with age, mean arterial pressure, heart rate, and estimated glomerular filtration rate (R(2)=0.51; P<0.0001). Only age, calcium phosphate product, and aortic PWV were independently associated with calcification. These data suggest that calcification may be important in the process of aortic stiffening and the development of ISH. Calcification may underlie treatment resistance in ISH, and anticalcification strategies may present a novel therapy

Influence of the central-to-peripheral arterial stiffness gradient on the timing and amplitude of wave reflections

In individuals with compliant aortas, peripheral muscular artery stiffness exceeds central elastic artery stiffness. With ageing, central stiffness increases, with little change in peripheral stiffness, resulting in a reversal of the normal stiffness gradient. This reversal may reduce wave reflection amplitude, due to movement of the major “effective” reflection site further from the heart. To test this, we investigated the relationship among arterial stiffness gradients (normal and reversed), wave reflection amplitude and reflection site distance. Subjects aged ≥50years were recruited from the Anglo-Cardiff Collaborative Trial. Central stiffness was assessed by carotid-femoral pulse wave velocity (cfPWV). In study 1, peripheral PWV was also measured in the arm (carotid-radial, crPWV), and in study 2 in the leg (femoral- dorsalis pedis, fpPWV). Reflection site distance was calculated from cfPWV and reflected wave travel time. Subjects were dichotomized into those with a normal stiffness gradient (peripheral>central PWV), or a reversed gradient (peripheral<central PWV). In study 1, reflection site distance was greater in subjects with a reversed gradient (P<0.01), whereas time to reflection was lower (P<0.001). Both augmentation pressure (P<0.001) and augmentation index (P<0.05) were greater in subjects with a reversed gradient. In study 2, augmentation pressure, augmentation index and reflection site distance were greater in subjects with a reversed stiffness gradient (P<0.01, P<0.05 and P<0.01, respectively), and time to reflection was not different between groups. A reversed arterial stiffness gradient is associated with increased reflection site distance and a paradoxical increase in reflected wave amplitude, and augmentation index

Stiffening and ventricular-arterial interaction in the ascending aorta using MRI: ageing effects in healthy humans

OBJECTIVES: The aim of this study was to investigate the effect of age and sex on nPWV and ndI in the ascending aorta of healthy humans. BACKGROUND: Local pulse wave velocity (nPWV) and wave intensity (ndI) in the human ascending aorta have not been studied adequately, because of the need for invasive pressure measurements. However, a recently developed technique made the noninvasive determination of nPWV and ndI possible using measurements of flow velocity and arterial diameter. METHODS: Diameter and flow velocity were measured at the level of the ascending aorta in 144 healthy participants (aged 20-77 years, 66 men), using MRI. nPWV, ndI parameters; forward (FCW); backward (BCW) compression waves, forward decompression wave (FDW), local aortic distensibility (nDs) and reflection index (nRI) were calculated. RESULTS: nPWV increased significantly with age from 4.7 ± 0.3 m/s for those 20-30 years to 6.4 ± 0.2 m/s for those 70-80 years (P < 0.001) and did not differ between sexes. nDs decreased with age (5.3 ± 0.5 vs. 2.6 ± 0.2 10 1/Pa, P < 0.001) and nRI increased with age (0.17 ± 0.03 vs. 0.39 ± 0.06, P < 0.01) for those 20-30 and 70-80 years, respectively. FCW, BCW and FDW decreased significantly with age by 86.3, 71.3 and 74.2%, respectively (P < 0.001), all compared to the lowest age-band. CONCLUSION: In healthy humans, ageing results in stiffer ascending aorta, with increase in nPWV and decrease in nDs. A decrease in FCW and FDW indicates decline in left ventricular early and late systolic functions with age in healthy humans with no differences between sexes. nRI is more sensitive than BCW in establishing the effects of ageing on reflected waves measured in the ascending aorta

Validity and repeatability of the Vicorder apparatus : a comparison with the SphygmoCor device

Aortic stiffness, an independent predictor of cardiovascular risk and all-cause mortality, can be estimated non-invasively by measuring carotid to femoral (aortic) pulse wave velocity (aPWV). The Vicorder device has been developed to measure aPWV with little operator training in a non-intrusive manner. The aim of this study was to assess the repeatability of aPWV measured with the Vicorder device and to compare aPWV values with those obtained using the SphygmoCor system. Vicorder and SphygmoCor aPWV was assessed in 122 subjects (5318 years, 46 male) using both the manufacturers' and a standardized approach. Vicorder aPWV measurement proved to be highly repeatable (within-subject coefficient of variation 2.8%). Transit time differed significantly between the two devices (mean difference 229 ms, P<0.001), independent of the different algorithms used to calculate transit time. However, aPWV was similar between the two devices (mean difference 0.311.54 m s-1, P<0.001) though with an inherent bias toward lower Vicorder aPWV values at high values of SphygmoCor aPWV. Bias was reduced by subtracting the additional femoral artery segment measured by the Vicorder device, also bringing the measure of transit time in closer agreement to SphygmoCor values (mean difference 59 ms, P<0.001). Transit time values significantly differed between the two devices and the Vicorder device reported lower aPWV values at higher SphygmoCor values of aPWV. This difference in transit time and inherent bias was reduced when adjustment for the additional femoral artery segment measured by the Vicorder device was made.7 page(s

The Relationship of age with regional aortic stiffness and diameter

Objectives: The purpose of this study was to determine the impact of age on regional aortic pulse wave velocity (aPWV). Background: aPWV is an independent predictor of cardiovascular risk and increases exponentially with age. However, it is unclear whether such changes occur uniformly along the length of the aorta or vary by region. Methods: A total of 162 subjects, aged 18 to 77 years and free of cardiovascular disease and medication, were recruited from the Anglo-Cardiff Collaborative Trial. Cine phase contrast magnetic resonance imaging was performed at 5 aortic levels. Systolic diameter and average blood flow were measured at each level and regional aPWV (regional aPWV measured by cine phase contrast magnetic resonance imaging) determined in 4 aortic segments: the arch (R1), the thoracic-descending aorta (R2), mid-descending aorta (R3), and the abdominal aorta (R4) and across the entire aorta. Results: Regional PWV measured by cine phase contrast magnetic resonance imaging values increased from the valve to the bifurcation in the 4 segments (PWV-R1- PWV-R4: 4.6 ± 1.5 m/s, 5.5 ± 2.0 m/s, 5.7 ± 2.3 m/s, 6.1 ± 2.9 m/s, respectively) and did not differ between genders. The greatest age-related difference in stiffness occurred in the abdominal aorta (+0.9 m/s per decade, p < 0.001) followed by the thoracic-descending region (+0.7 m/s, p < 0.001), the mid-descending region (+0.6 m/s, p < 0.001) and aortic arch (+0.4 m/s, p < 0.001). The average systolic diameters decreased moving distally (L1-5: 3.1 ± 0.4 cm, 2.3 ± 0.3 cm, 2.1 ± 0.3 cm, 1.9 ± 0.2 cm, and 1.7 ± 0.2 cm, respectively). The greatest variation in systolic diameter as a function of age occurred in the ascending region (+0.96 mm/decade, p < 0.001). Values of aPWV measured across the entire aorta were strongly correlated with PWV-tonometry (R = 0.71, p < 0.001), although they were significantly lower (mean difference 1.7 ± 1.6 m/s, p < 0.001). Conclusions: The greatest difference in aortic stiffness occurs in the abdominal region, whereas the greatest difference in diameter occurs in the ascending aorta, which may help offset an increase in wall stiffness.9 page(s

The Accuracy of central SBP determined from the second systolic peak of the peripheral pressure waveform

Background: Recent evidence suggests that central aortic blood pressure may be a better predictor of cardiovascular risk than peripheral blood pressure. The central SBP (cSBP) can be estimated from the late systolic shoulder of the radial pulse waveform. We compared the second systolic peak of the radial waveform (pSBP2) with the central systolic pressure derived by a generalized transfer function in a large cohort, across a wide age range, of patients from the Anglo-Cardiff Collaborative Trial. We also compared pSBP2 with the true cSBP measured by cardiac catheterization [invasively measured cSBP (cSBPi)]. Methods: Noninvasive measurements were made by applanation tonometry using the SphygmoCor device. The aortic pressure waveform was derived from the radial waveform using a validated transfer function. Invasive measures of cSBPi were carried out in a group of 38 patients undergoing diagnostic cardiac angiography, and radial artery pressure waveforms were simultaneously recorded using the SphygmoCor device. Results: Overall, there was a strong correlation (r = 0.99, P < 0.001) and good agreement between pSBP2 and the derived cSBP (mean difference ± SD 1 ± 4 mmHg). However, there was a systematic bias with a greater difference between these measures at lower average pressures. There was also a strong correlation and good agreement between the invasively measured cSBPi and pSBP2 (r = 0.92, P < 0.001, mean difference 2 ± 6 mmHg). Conclusion: The second systolic shoulder of the peripheral pressure waveform approximates the cSBP in a large cohort of patients across a wide age range, but this may be inaccurate at low SBP values.5 page(s