Stacey S. Hickson

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 (R2=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.

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.

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.

Evaluation of the Vicorder, a novel cuff-based device for the noninvasive estimation of central blood pressure.

Objectives: The Vicorder is a new brachial cuff-based device that estimates central blood pressure (cBP) using a brachial-to-aortic transfer function. The aim of this study was to evaluate cBP estimated by the Vicorder. Methods: During cardiac angiography, cBP estimated by the Vicorder and the SphygmoCor was evaluated against simultaneous invasive cBP in 50 patients. The two devices were also compared noninvasively in a separate group of 90 healthy individuals. Results: Central SBP (cSBP) obtained with each device satisfied the American Association for the Advancement of Medical Instrumentation accuracy criteria when peripheral waveforms were calibrated to invasive mean arterial pressure (MAP)/DBP: estimated − invasive cSBP difference, −4.0 ± 7.4 mmHg, Vicorder, P < 0.001; −1.4 ± 7.9 mmHg, SphygmoCor, P = 0.21. When oscillometric brachial SBP/DBP was used for peripheral waveform calibration, cSBP was underestimated by Vicorder (&Dgr; −6.4 ± 7.4 mmHg, P < 0.001 versus invasive) and more so by SphygmoCor (&Dgr; −11.9 ± 7.2 mmHg, P < 0.001 versus invasive). Conversely, cSBP was more closely estimated by SphygmoCor when waveforms were calibrated to brachial MAP/DBP (&Dgr; −2.8 ± 9.4 mmHg, P = 0.04 versus invasive). In the noninvasive study, Vicorder cSBP correlated well with SphygmoCor cSBP when SphygmoCor waveforms were calibrated to brachial MAP/DBP (121 ± 16 versus 121 ± 17 mmHg, P = 0.2) but not when brachial SBP/DBP was used for calibration (115 ± 19 mmHg, P < 0.001). Conclusion: The Vicorder and SphygmoCor devices provide reliable estimates of cSBP when calibrated to invasive pressure. When calibrated to brachial BP, both devices underestimated cSBP, although this was attenuated when SphygmoCor was calibrated to brachial MAP/DBP. Vicorder may be a simple alternative to tonometry-based methods for noninvasive assessment of cBP.

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.

Use of the oral contraceptive pill is associated with increased large artery stiffness in young women: the ENIGMA study.

Background The oral contraceptive pill (OCP) is widely prescribed throughout the world. Although it is associated with a small but significant increase in blood pressure, the influence of the OCP on large artery stiffness and wave reflection is unclear. The aim of this study was to determine the relationship between use of the OCP and aortic stiffness and wave reflections in a young, healthy cohort of women. Methods Participants were drawn from the ENIGMA study, which examines the natural history of blood pressure in young adults. A detailed medical history and lifestyle questionnaire, including OCP details were taken. Blood pressure was measured according to the British Hypertension Society guidelines. Aortic pulse wave velocity (aPWV) was measured together with augmentation index (AIx). Stroke volume (SV) and cardiac output (CO) were also assessed. Results Women taking the OCP (n = 225) had a higher SBP and pulse pressure compared with nonusers (n = 660; 112 ± 12 vs. 110 ± 11 and 43 ± 8 vs. 42 ± 8 mmHg, respectively, P < 0.05 for both). CO and SV were also higher (6.6 ± 1.5 vs. 6.3 ± 1.5 l/min, P < 0.01 and 81 ± 16 vs. 78 ± 19 ml, P < 0.05) as was aPWV (5.5 ± 0.7 vs. 5.4 ± 0.7 m/s, P < 0.05). However, there was no difference in DBP (68 ± 9 vs. 69 ± 9 mmHg), mean arterial pressure (81 ± 10 vs. 81 ± 10 mmHg) or AIx (2 ± 12 vs. 3 ± 13%) between the groups. Conclusion Use of the OCP is associated with elevated pulse pressure and SV and a small increase in aPWV in young women. The longer term implications of these effects require further investigation.

Age-related changes of regional pulse wave velocity in the descending aorta using Fourier velocity encoded M-mode

Aortic pulse wave velocity (PWV) is an independent determinant of cardiovascular risk. Although aortic stiffening with age is well documented, the interaction between aging and regional aortic PWV is still a debated question. We measured global and regional PWV in the descending aorta of 56 healthy subjects aged 25–76 years using a one‐dimensional, interleaved, Fourier velocity encoded pulse sequence with cylindrical excitation. Repeatability across two magnetic resonance examinations (n = 19) and accuracy against intravascular pressure measurements (n = 4) were assessed. The global PWV was found to increase nonlinearly with age. The thoracic aorta was found to stiffen the most with age (PWV [thoracic, 20–40 years] = 4.7 ± 1.1 m/s; PWV [thoracic, 60–80 years] = 7.9 ± 1.5 m/s), followed by the mid‐ (PWV [mid‐abdominal, 20–40 years] = 4.9 ± 1.3 m/s; PWV [mid‐abdominal, 60–80 years] = 7.4 ± 1.9 m/s) and distal abdominal aorta (PWV [distal abdominal, 20–40 years] = 4.8 ± 1.4 m/s; PWV [distal abdominal, 60–80 years] = 5.7 ± 1.4 m/s). Good agreement was found between repeated magnetic resonance measurements and between magnetic resonance PWVs and the gold‐standard. Fourier velocity encoded M‐mode allowed to measure global and regional PWV in the descending aorta. There was a preferential stiffening of the thoracic aorta with age, which may be due to progressive fragmentation of elastin fibers in this region. Magn Reson Med, 2010.

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 aging, central stiffness increases with little change in peripheral stiffness, resulting in a reversal of the normal stiffness gradient. This reversal may reduce the wave reflection amplitude due to the movement of the major ‘effective’ reflection site further from the heart. To test this phenomenon, we investigated the relationship among arterial stiffness gradients (normal and reversed), wave reflection amplitude and reflection site distance. Subjects aged ⩾50 years 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 pulse wave velocity) and, in Study 2, in the leg (femoral-dorsalis pedis). Reflection site distance was calculated from cfPWV and the reflected wave Tr. Subjects were dichotomized into those with a normal stiffness gradient (peripheral >central PWV) or a reversed gradient (peripheral <central PWV). In Study 1, the reflection site distance was greater in subjects with a reversed gradient (P<0.01), whereas time-to-reflection was lower (P<0.001). Both the augmentation pressure (P<0.001) and augmentation index (P<0.05) were greater in subjects with a reversed gradient. In Study 2, the 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 an increased reflection site distance, and a paradoxical increase in reflected wave amplitude and augmentation index.

Using magnetic resonance imaging measurements for the determination of local wave speed and arrival time of reflected waves in human ascending aorta

Wave speed is one of the key factors describing wave propagation in arteries [1]. Local wave speed is directly related to the arterial wall properties [2]. With aging, arterial wave speed increases due to the stiffening of arterial wall, and also related to arterial disease.

Surrogate markers of cardiovascular risk and chronic obstructive pulmonary disease

Cardiovascular disease is a common comorbidity and cause of mortality in chronic obstructive pulmonary disease. A better understanding of mechanisms of cardiovascular risk in chronic obstructive pulmonary disease patients is needed to improve clinical outcomes. We hypothesized that such patients have increased arterial stiffness, wave reflections, and subclinical atherosclerosis compared with controls and that these findings would be independent of smoking status and other confounding factors. A total of 458 patients with a diagnosis of chronic obstructive pulmonary disease and 1657 controls (43% were current or ex-smokers) with no airflow limitation were matched for age, sex, and body mass index. All individuals underwent assessments of carotid–femoral (aortic) pulse wave velocity, augmentation index, and carotid intima–media thickness. The mean age of the cohort was 67±8 years and 58% were men. Patients with chronic obstructive pulmonary disease had increased aortic pulse wave velocity (9.95±2.54 versus 9.27±2.41 m/s; P<0.001), augmentation index (28±10% versus 25±10%; P<0.001), and carotid intima–media thickness (0.83±0.19 versus 0.74±0.14 mm; P<0.001) compared with controls. Chronic obstructive pulmonary disease was associated with increased levels of each vascular biomarker independently of physiological confounders, smoking, and other cardiovascular risk factors. In this large case-controlled study, chronic obstructive pulmonary disease was associated with increased arterial stiffness, wave reflections, and subclinical atherosclerosis, independently of traditional cardiovascular risk factors. These findings suggest that the cardiovascular burden observed in this condition may be mediated through these mechanisms and supports the concept that chronic obstructive pulmonary disease is an independent risk factor for cardiovascular disease.