Biomedical subjects
Publications and source records attributed to James D Cameron.
Explore the source record for details and available documents.
Central arterial waveforms and related indices of large artery properties can be determined with relative ease. This would make them an attractive adjunct in the risk stratification for cardiovascular disease. Although they have been associated with some classical risk factors and the presence of coronary disease, their prospective value in predicting cardiovascular outcomes is unknown. The present study determined the relative predictive value for cardiovascular disease-free survival of large artery properties as compared with noninvasive brachial blood pressure alone in a population of elderly female hypertensive subjects. We measured systemic arterial compliance, central systolic pressure, and carotid augmentation index in a subset of female participants in the Second Australian National Blood Pressure Study (untreated blood pressure 169/88+/-12/8 mm Hg). There were a total of 53 defined events during a median of 4.1 years of follow-up in 484 women with complete measurements. Although baseline blood pressures at the brachial artery predicted cardiovascular disease-free survival (hazard ratio [HR], 2.3; 95% CI, 1.3 to 4.1 for pulse pressure > or =81 versus <81 mm Hg; P=0.01), no such relation was found for carotid augmentation index (HR, 0.80; 95% CI, 0.44 to 1.44; P value not significant) or systemic arterial compliance (HR, 1.25; 95% CI, 0.72 to 2.16; P value not significant). Blood pressure, but not noninvasively measured central arterial waveforms, predict outcome in the older female hypertensive patient. Thus, blood pressure measurement alone is superior to measurement of arterial waveforms in predicting outcome in this group.
Evidence suggests that flavonoid-containing diets reduce cardiovascular risk, but the mechanisms responsible are unclear. In the present study, we sought to determine the effect of flavanol-rich cocoa on vascular function in individuals with CAD (coronary artery disease). Forty subjects (61+/-8 years; 30 male) with CAD were recruited to a 6-week randomized double-blind placebo-controlled study. Subjects consumed either a flavanol-rich chocolate bar and cocoa beverage daily (total flavanols, 444 mg/day) or matching isocaloric placebos daily (total flavanols, 19.6 mg/day) for 6 weeks. Brachial artery FMD (flow-mediated dilation) and SAC (systemic arterial compliance) were assessed at baseline, 90 min following the first beverage and after 3 and 6 weeks of daily consumption. Soluble cellular adhesion molecules and FBF (forearm blood flow) responses to ACh (acetylcholine chloride; 3-30 microg/min) and SNP (sodium nitroprusside; 0.3-3 microg/min) infusions, forearm ischaemia and isotonic forearm exercise were assessed at baseline and after 6 weeks. FMD, SAC and FBF responses did not differ between groups at baseline. No acute or chronic changes in FMD or SAC were seen in either group. No difference in soluble cellular adhesion molecules, FBF responses to ischaemia, exercise, SNP or ACh was seen in the group receiving flavanol-rich cocoa between baseline and 6 weeks. These data suggest that over a 6-week period, flavanol-rich cocoa does not modify vascular function in patients with established CAD.
Positive coronary artery remodeling is associated with unstable coronary syndromes. Serum inflammatory markers, including high-sensitivity CRP (hsCRP), can predict future risk of acute coronary events in patients with stable coronary artery disease. We sought to elucidate the relationship of specific serum inflammatory markers with intravascular ultrasound (IVUS) estimation of coronary artery remodeling in patients with stable coronary artery disease. Thirty-one sequential patients at our institution undergoing IVUS-assisted percutaneous coronary intervention (PCI) with stable coronary artery disease were enrolled. Automated IVUS pullback and offline analysis were performed in all patients. Images were analyzed for vessel wall area (VWA) and lumen area (LA), at the culprit lesion and at a proximal reference site, and the remodeling index (RI) was calculated. Positive and negative remodeling were defined as a RI of > 1.05 and < 0.95, respectively. ELISA essays were performed for soluble VCAM-1, ICAM-1 and E-selectin. The distribution of data followed a lognormal distribution. By defining arterial remodeling as simply positive or negative, significant differences were identified for log E-selectin only (1.80 +/- 0.04 versus 1.62 +/- 0.05, respectively; p = 0.02). The RI correlation coefficient was 0.38 (p = 0.04) for log sVCAM-1 and 0.42 (p = 0.02) for log sICAM-1. The log E-selection and RI correlation coefficient, although weaker at 0.32, showed a trend toward significance (p = 0.08). There was no significant correlation between log hsCRP and RI (p = 0.42). Using step-wise multivariate analysis, log sVCAM-1 only remained an independent predictor of the RI (p = 0.03). Positive coronary artery remodeling correlates with serological markers of inflammation in patients with stable coronary artery disease.
We examined the hypothesis that a stiff aorta is associated with reduced coronary blood flow (CBF) and CBF response to percutaneous coronary intervention (PCI). Aortic mechanical properties are thought to affect CBF, with increased stiffness associated with decreased coronary perfusion. Animal studies are conflicting, and human evidence is lacking. Even less is known about the effects of aortic stiffness on the CBF response to successful PCI. In 18 subjects undergoing elective PCI, a Doppler velocity guidewire was positioned proximal to a severe coronary stenosis to measure resting and adenosine-induced hyperemic CBF before and after PCI. Stenosis severity was assessed with Doppler velocity and pressure guidewires. Aortic mechanical indexes measured included central pulse-wave velocity (cPWV) and central pulse pressure (cPP). PCI was successful in all subjects (diameter stenosis: 88 +/- 9% to 2 +/- 7%; coronary flow velocity reserve: 1.8 +/- 0.6 to 3.0 +/- 0.8; fractional flow reserve: 0.57 +/- 0.19 to 0.92 +/- 0.06; all P < 0.001). With the adjustment for age and gender, resting and hyperemic CBF were inversely related to cPWV irrespective of the presence of stenosis (resting: before PCI, r2 = 0.452, P < 0.01; after PCI, r2 = 0.261, P = 0.043; hyperemic: before PCI r2 = 0.503, P = 0.005; after PCI r2 = 0.500, P = 0.002), whereas they were related to cPP in absence of stenosis (resting: r2 = 0.368, P = 0.022; hyperemic: r2 = 0.370, P = 0.016). Hyperemic CBF response (P = 0.005) and hyperemic CBF improvement from PCI (P = 0.025) were less marked in a stiff aorta than a compliant aorta. A stiff aorta is associated with a reduction in CBF, a lower hyperemic CBF response, and may reduce the improvement in hyperemic CBF after successful PCI.
The objective of this study was to investigate the determinants of aortic pressure waveform morphology in the thoracoabdominal aorta with specific reference to features of potential prognostic value for cardiovascular disease. In particular, we aimed to determine the location of major pressure wave reflection sites within the aorta. Aortic pressure waveforms were acquired with 2-Fr Millar Mikro-tip catheter transducers in 40 subjects (26 men, 14 women), and repeated in 10 subjects, at five predetermined points within the aorta: aortic root, transverse arch, and at the levels of the diaphragm, renal arteries, and aortic bifurcation. Waveforms were analyzed for augmentation index (AI), time to inflection point (Ti), and pressure parameters. AI decreased progressively between the aortic root and bifurcation (P < 0.001), and Ti increased (P < 0.01). There was the expected progressive peripheral amplification of systolic and pulse pressures and fall in time to peak pressure (all P < 0.001). There was no difference on repeat pullback or between sexes. These data are at variance with the concept that central AI results solely from pressure wave reflection, when Ti would be expected to decrease and AI increase with distal progression. Pressure wave propagation phenomena may contribute, and the potential role of frequency dispersion merits investigation.
BACKGROUND: Evidence for statin therapy in prevention of coronary artery disease is overwhelming. In spite of theoretical benefits, any additional advantage of its early introduction in the management of acute coronary syndrome is, however, uncertain. We therefore investigated differences between plasma levels of the systemic inflammatory markers intercellular adhesion molecule-1, vascular cell adhesion molecule-1, E-selectin, C-reactive protein and interleukin-6 in patients presenting with unstable angina or acute myocardial infarction, and assessed whether the 30-day levels of these markers are influenced by early instigation of the HMG-CoA reductase inhibitor pravastatin. MATERIALS AND METHODS: 170 (134 male) patients presenting with acute coronary syndrome, but without previous statin therapy, participated. Blood was taken within 24 h of onset of ischaemic pain and again at 30 days. In all, 87 (71 male) participants were treated with pravastatin (20-40 mg daily) and 83 (63 male) with a matched placebo. RESULTS: At presentation, interleukin-6 was higher in males than in females (P=0.008) and lower in those with a pre-existing history of myocardial infarction (P=0.038). C-reactive protein and interleukin-6 were greater in myocardial infarction, but this difference was lost at 30 days. Thirty-day changes in all parameters were inversely related to level at presentation but not to treatment with pravastatin. Hypertension (P=0.011) and smoking (P=0.042) were associated with elevation of C-reactive protein with no difference between unstable angina or acute myocardial infarction. The effect of these individual factors was cumulative. CONCLUSIONS: Interleukin-6 was greater in acute myocardial infarction than in unstable angina; E-selectin was positively associated with a previous myocardial infarction and inversely related to age. We found no effect of early introduction of pravastatin on systemic inflammatory markers 30 days after acute coronary syndrome.
Explore the source record for details and available documents.
OBJECTIVE: Previous studies have demonstrated a prognostic role of large artery stiffness in hypertensive subjects and increased stiffness in subjects with coronary artery disease. Although plasma cholesterol is an established risk factor for cardiovascular disease, its relationship with large artery properties in a hypertensive population is unclear. METHODS AND RESULTS: Plasma cholesterol and large artery properties were measured at baseline in a subset of participants of a randomized controlled trial (ANBP2) evaluating hypertension treatment in older (65 to 84 years) subjects. Noninvasive measures of large artery behavior were central augmentation index (AI), systemic arterial compliance (SAC), and transverse expansion of the aortic arch (aortic distensibility). Arterial waveforms acceptable for analysis were obtained in approximately 80% of cases yielding valid measurements of AI in 868, SAC in 846, and aortic distensibility in 680 subjects. Mean total and high-density lipoprotein (HDL) concentrations were 5.5+/-1.0 and 1.4+/-0.5 mmol L(-1). Total and HDL cholesterol and AI were greater in females than males, whereas SAC and aortic distensibility were greater in males. In multiple regression analyses there were no significant associations between stiffness parameters and total or HDL cholesterol. Significant independent associations in such analyses were found for mean arterial blood pressure, gender, age, height, and heart rate, in keeping with previous findings. CONCLUSIONS: In the largest cohort of elderly hypertensive subjects studied to date, plasma cholesterol per se was not associated with large artery stiffness. Such independence from cholesterol increases the potential for artery stiffness measurements to additionally contribute to cardiovascular risk assessment in this population.
OBJECTIVE: Venous disease was evaluated in relation to post-thrombotic syndrome 5 years after deep venous thrombosis (DVT) in patients treated with a regimen of low-molecular-weight heparin (LMWH) and warfarin in a Hospital-in-the-Home program. METHODS: The presence of flow, reflux and compressibility in 51 patients (102 limbs, 54 with DVT and 48 without DVT) was assessed by duplex ultrasound scanning. Blood tests were carried out for prothrombotic screening. Venous disease was related to pathologic severity of post-thrombotic syndrome, characterized by the CEAP (clinical, etiologic, anatomic, pathophysiologic) classification on a scale of 0 to 6. RESULTS: In the 102 limbs studied, 30 patients (59%) had an underlying thrombophilic disorder. The most common cause of DVT was postoperation and prolonged immobilization not related to postoperation. The most common thrombophilic abnormalities were anticardiolipin antibody and a deficiency of protein C or S, or both. Twenty-six limbs (48%) had proximal involvement (proximal and proximal plus distal DVT); resolution (recanalization or normal vein) in these limbs was seen in 85% at 6 months and 96% at 5 years. After 5 years, 25 of these proximal DVT limbs (96%) developed reflux and there were 4 limbs in CEAP class 0, 8 in classes 1 to 3, and 14 in classes 4 to 6. All of the 28 limbs (52%) with distal DVT showed DVT resolution by 6 months. After 5 years, 10 limbs (36%) developed reflux, and 13 limbs were in class 0, 12 in classes 1 to 3, and 3 limbs in classes 4 to 6. No DVT was detected in the 48 contralateral limbs, but reflux was detected in 25 limbs (52%), predominately in the superficial veins (16 limbs, 64%). CONCLUSIONS: The resolution of thrombus was more rapid and complete in patients with distal DVT than in those with proximal DVT. Patients with proximal DVT developed a more severe form of post-thrombotic syndrome that was likely related to the development of deep venous reflux. An important finding of this study was an unexpectedly high incidence of venous reflux in the apparently unaffected limb. Although these non-DVT limbs were not investigated at presentation, our data is consistent with the hypothesis that DVT may result in a more systemic disorder of venous function.
Transfer function techniques are increasingly used for non-invasive estimation of central aortic waveform characteristics. Non-invasive radial waveforms must be calibrated for this purpose. Most validation studies have used invasive pressures for calibration, with little data on the impact of non-invasive calibration on transfer-function-derived aortic waveform characteristics. In the present study, simultaneous invasive central aortic (Millar Mikro-tip catheter transducer) and non-invasive radial (Millar Mikro-tip tonometer) pressure waveforms and non-invasive brachial pressures (Dinamap) were measured in 42 subjects. In this cohort, radial waveforms were calibrated to both invasive and non-invasive mean and diastolic pressures. From each of these, central waveforms were reconstructed using a generalized transfer function obtained by us from a previous cohort [Hope, Tay, Meredith and Cameron (2002) Am. J. Physiol. Heart Circ. Physiol. 283, H1150-H1156]. Waveforms were analysed for parameters of potential clinical interest. For calibrated radial and reconstructed central waveforms, different methods of calibration were associated with differences in pressure (P<0.001), but not time parameters or augmentation index. Whereas invasive calibration resulted in little error in transfer function estimation of central systolic pressure (difference -1+/-8 mmHg; P=not significant), non-invasive calibration resulted in significant underestimation (7+/-12 mmHg; P<0.001). Errors in estimated aortic parameters differed with non-invasively calibrated untransformed radial and transfer-function-derived aortic waveforms (all P<0.01), with smaller absolute errors with untransformed radial waveforms for most pressure parameters [systolic pressure, 5+/-16 and 7+/-12 mmHg; pulse pressure, 0+/-16 and 4+/-12 mmHg (radial and derived aortic respectively)]. When only non-invasive pressures are accessible, analysis of untransformed radial waveforms apparently produces smaller errors in the estimation of central aortic systolic pressure, and other waveform parameters, than using a generalized transfer function.
OBJECTIVES: Monitoring of brachial blood pressure during exercise-electrocardiogram (ECG) testing is mandatory and changes in blood pressure (BP) can provide critical management evidence. Patient movement, mechanical vibration, artifactual sounds and observer variability make standard manual techniques problematic. This was an investigator-initiated study to assess an automated auscultatory technique of BP assessment [Tango exercise blood pressure monitor (SunTech Medical Instruments, NC, USA)] to adequately measure BP during stress-ECG testing. METHODS: Initially five fit young male volunteers underwent invasive right brachial artery BP recording using a low-compliance fluid-filled catheter with simultaneous manual and automated assessment. Secondarily, during exercise-ECG testing, the system was assessed against beat-to-beat brachial blood pressures obtained from a catheter-tip solid-state pressure manometer positioned in the ipsilateral brachial artery. RESULTS: In the supine study overall mean difference (+/-SEM) between invasive and manual blood pressures was 3.26 (1.53) and 3.89 (1.90) mmHg for diastolic BP (DBP) and systolic BP (SBP) respectively. Corresponding differences between invasive and automated results, and manual and automated were 3.68 (0.84) and -7.31 (1.83) mmHg, and -0.64 (+/-1.43) and -11.42 (+/-1.59) mmHg. During treadmill exercise-ECG testing the combined mean difference (+/-SEM) between invasive and automated SBP and DBP was 4.79 (+/-0.14) and 6.33 (+/-0.10) mmHg, respectively. CONCLUSION: Automated BP assessment during exercise-ECG testing is feasible with the use of appropriate automatic devices likely to be at least as accurate as manual BP registration. The Tango device is tolerant to exercise and provides reliable automatic BP assessment with absolute differences within an acceptable clinical range.
OBJECTIVES: To determine whether sex differences in large-artery stiffness contribute to the greater prevalence of systolic hypertension in elderly women than in elderly men. DESIGN: During a single visit arterial stiffness was assessed in the unmedicated state using four parameters. PARTICIPANTS: Three hundred seventy-four women with a mean age+/-standard deviation of 72+/-5 and 296 men aged 71+/-5 participated. SETTING: Hypertensive patients were recruited from general practice as part of the second Australian National Blood Pressure Study in Melbourne, Australia. MEASUREMENTS: Large-artery stiffness was assessed using multiple methodologies, including aortic arch stiffness (beta-index) using M-mode ultrasound and arterial compliance and augmentation index using noninvasive carotid pressure and aortic flow measurements. RESULTS: Women had greater carotid and brachial pulse pressure (PP) than men (P<.001), despite higher mean arterial pressure in men. Mean arterial compliance was lower in women (0.20+/-0.12 vs 0.28+/-0.16 mL/mmHg, P<.001) even after correction for aortic area, and aortic arch stiffness was higher (30+/-36 vs 23+/-22; P<.01). Consistent with both a stiffer proximal circulation and a shorter distance to reflection sites, women had higher augmentation index (38+/-11% vs 29+/-12%, P<.001). In multivariate analysis, sex was an independent determinant of all arterial stiffness indices. CONCLUSION: Independently of known confounders, elderly hypertensive women have stiffer large arteries, greater central wave reflection, and higher PP than elderly men. Stiffer large arteries likely contribute to the greater prevalence of systolic hypertension in elderly women and may partly explain the acceleration in postmenopausal cerebrovascular and cardiac complications.
OBJECTIVE: Optimal blood pressure control in subjects with diabetes reduces cardiovascular complications. There is theoretical benefit in the assessment of central aortic waveforms including the augmentation index, which is taken as a putative index of stiffness. Transfer functions may be used to reconstruct aortic from radial pressure waveforms; however, a single generalized transfer function may not be appropriate for all patients. We aimed to evaluate the technique in subjects with diabetes. RESEARCH DESIGN AND METHODS: Simultaneous invasive central aortic and noninvasive radial waveforms were acquired in 19 subjects with type 2 diabetes, and a diabetes-specific transfer function was derived. Similar data were acquired from 38 age- and sex-matched subjects without diabetes. Central waveforms were reconstructed using a generalized transfer function in all patients and the diabetes-specific transfer function in individuals with diabetes. RESULTS: There was no difference between groups in measured central pressures. The error in generalized transfer function-derived systolic pressure was greater in individuals with diabetes (6 +/- 7 mmHg) (mean +/- SD) than without diabetes (2 +/- 8 mmHg) (P<0.05). Errors in other parameters were no different. The diabetes-specific transfer function reduced the error in derived systolic pressure to 0 +/- 7 mmHg in individuals with diabetes--no different than that with the generalized transfer function in individuals without diabetes. The central augmentation index reconstructed by either transfer function was unrelated to that directly measured. CONCLUSIONS: A generalized transfer function is inappropriate for the derivation of central waveforms in subjects with type 2 diabetes. Errors in subjects with diabetes might be reduced with a diabetes-specific transfer function.
Explore the source record for details and available documents.
OBJECTIVE: To investigate the utility and accuracy of radial-aortic arterial transfer functions for the derivation of central blood pressure waveforms. DESIGN Prospective measurement of central and peripheral waveforms in patients undergoing coronary angiography or percutaneous coronary intervention. METHODS: Simultaneous invasive central aortic and non-invasive radial pressure waveforms were recorded in 78 subjects (61 male : 17 female). Data were applied to a single-input/single-output model for the calculation of a transfer function (TF). Individual TFs were derived by two methods and ensemble averaged TFs obtained for the group. Reverse transformation was performed using each averaged TF applied to the radial data of each subject. RESULTS: There was close linear correlation between measured aortic parameters and both radial and TF-derived aortic systolic and diastolic pressures (P < 0.001) and most other waveform parameters. However, despite small mean differences between measured and most TF-derived aortic parameters (systolic pressure 0.8-2.9 mmHg, augmentation index 4.3-5.6%), individual scatter was marked, with 95% limits of agreement of +/- 14.6 mmHg (systolic pressure) and +/- 24.4% [augmentation index (AI)]. Indeed, scatter for AI was so marked that measured and derived values were not statistically significantly correlated. CONCLUSIONS: Transfer functions may be valid for the derivation of some central aortic waveform characteristics. However, in providing neither improved reproducibility nor data on parameters not obtainable from the radial waveform, transfer function techniques may offer no additional clinical benefit. The absence of correlation between measured and TF-derived aortic AI and wide limits of agreement of other parameters should be considered if this technique is utilized in clinical practice.
OBJECTIVE: To compare age-related changes in the mechanical properties of different arterial segments in normal volunteers and subjects with type 2 diabetes. RESEARCH DESIGN AND METHODS: In 169 subjects (diabetic n = 57 and nondiabetic n = 112), we assessed the mechanical properties of three arterial segments of differing wall composition. Pulse wave velocity (PWV) was measured noninvasively in a thoraco-abdominal segment (carotid femoral PWV [PWV(cf)]), in an upper limb muscular artery (carotid radial PWV [PWV(cr)]), and from the aorta to the finger (PWV from the aorta to the finger [PWV(fin)]). Central aortic compliance (CAC) was also measured. RESULTS: Average CAC was lower (0.662 vs. 0.850, P < 0.05) and all measures of PWV tended to be faster in diabetic subjects despite the fact that they were, on average, 10 years younger. However, these measures were not related to age in diabetic subjects. After correcting for blood pressure, only PWV(cf) was associated with age in nondiabetic subjects (P < 0.001). Expressing results as ratios of nonelastic to elastic arterial segments (i.e., PWV(cr)-to-PWV(cf) and PWV(fin)-to-PWV(cf)) improved the relationship with age. Both PWV(cr)-to-PWV(cf) and PWV(fin)-to-PWV(cf) were significantly associated with age in nondiabetic subjects (r = -0.59, P < 0.001; r = -0.57, P < 0.001) but not in diabetic subjects (r = -0.15, P = 0.302; r = -0.24, P = 0.129). Multivariate analysis showed that the ratios were not associated with systolic blood pressure. CONCLUSIONS: There are significant differences in the rate of age-related decline in vascular stiffness in elastic arteries of nondiabetic compared with diabetic arteries. Diabetic arteries appear to age at an accelerated rate at an earlier age and then reach a functional plateau.
Explore the source record for details and available documents.