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J David Spence

Publications and source records attributed to J David Spence.

At least 37 records · Page 2Linked to original sources
PubMed2005

Variation in the carotid bifurcation geometry of young versus older adults: implications for geometric risk of atherosclerosis.

BACKGROUND AND PURPOSE: Retrospective analysis of clinical data has demonstrated major variations in carotid bifurcation geometry, in support of the notion that an individual's vascular anatomy or local hemodynamics may influence the development of atherosclerosis. On the other hand, anecdotal evidence suggests that vessel geometry is more homogenous in youth, which would tend to undermine this geometric risk hypothesis. The purpose of our study was to test whether the latter is indeed the case. METHODS: Cross-sectional images of the carotid bifurcations of 25 young adults (24+/-4 years) and a control group of 25 older subjects (63+/-10 years) were acquired via MRI. Robust and objective techniques were developed to automatically characterize the 3D geometry of the bifurcation and the relative dimensions of the internal, external, and common carotid arteries (ICA, ECA, and CCA, respectively). RESULTS: Young vessels exhibited significantly less interindividual variation in the following geometric parameters: bifurcation angle (48.5+/-6.3 degrees versus 63.6+/-15.4 degrees); ICA angle (21.6+/-6.7 degrees versus 29.2+/-11.3 degrees); CCA tortuosity (0.010+/-0.003 versus 0.014+/-0.011); ICA tortuosity (0.025+/-0.013 versus 0.086+/-0.105); ECA/CCA diameter ratio (0.81+/-0.06 versus 0.75+/-0.13), ICA/CCA (0.81+/-0.06 versus 0.77+/-0.12) diameter ratio, and bifurcation area ratio (1.32+/-0.15 versus 1.19+/-0.35). CONCLUSIONS: The finding of more modest interindividual variations in young adults suggests that, if there is a geometric risk for atherosclerosis, its early detection may prove challenging. Taken together with the major interindividual variations seen in older vessels, it suggests a more complex interrelationship between vascular geometry, local hemodynamics, vascular aging, and atherosclerosis, the elucidation of which now calls for prospective studies.

Adult↗
PubMed2005

Absence of microemboli on transcranial Doppler identifies low-risk patients with asymptomatic carotid stenosis.

BACKGROUND AND PURPOSE: Carotid endarterectomy clearly benefits patients with symptomatic severe stenosis (SCS), but the risk of stroke is so low for asymptomatic patients (ACS) that the number needed to treat is very high. We studied transcranial Doppler (TCD) embolus detection as a method for identifying patients at higher risk who would have a lower number needed to treat. METHODS: Patients with carotid stenosis of > or =60% by Doppler ultrasound who had never been symptomatic (81%) or had been asymptomatic for at least 18 months (19%) were studied with TCD embolus detection for up to 1 hour on 2 occasions a week apart; patients were followed for 2 years. RESULTS: 319 patients were studied, age (standard deviation) 69.68 (9.12) years; 32 (10%) had microemboli at baseline (TCD+). Events were more likely to occur in the first year. Patients with microemboli were much more likely to have microemboli 1 year later (34.4 versus 1.4%; P<0.0001) and were more likely to have a stroke during the first year of follow-up (15.6%, 95% CI, 4.1 to 79; versus 1%, 95% CI, 1.01 to 1.36; P<0.0001). CONCLUSIONS: Our findings indicate that TCD- ACS will not benefit from endarterectomy or stenting unless it can be done with a risk <1%; TCD+ may benefit as much as SCS if their surgical risk is not higher. These findings suggest that ACS should be managed medically with delay of surgery or stenting until the occurrence of symptoms or emboli.

Age Factors↗
PubMed2005

3D ultrasound measurement of change in carotid plaque volume: a tool for rapid evaluation of new therapies.

BACKGROUND AND PURPOSE: New therapies are being developed that are antiatherosclerotic but that lack intermediate end points, such as changes in plasma lipids, which can be measured to test efficacy. To study such treatments, it will be necessary to directly measure changes in atherosclerosis. The study was designed to determine sample sizes needed to detect effects of treatment using 3D ultrasound (US) measurement of carotid plaque. METHODS: In 38 patients with carotid stenosis >60%, age+/-SD 69.42+/-7.87 years, 15 female, randomly assigned in a double-blind fashion to 80 mg atorvastatin daily (n=17) versus placebo (n=21), we measured 3D plaque volume at baseline and after 3 months by disc segmentation of voxels representing carotid artery plaque, after 3D reconstruction of parallel transverse duplex US scans into volumetric 3D data sets. RESULTS: There were no significant differences in baseline risk factors. The rate of progression was 16.81+/-74.10 mm3 in patients taking placebo versus regression of -90.25+/-85.12 mm3 in patients taking atorvastatin (P<0.0001). CONCLUSIONS: 3D plaque volume measurement can show large effects of therapy on atherosclerosis in 3 months in sample sizes of approximately 20 patients per group. Sample sizes of 22 per group would be sufficient to show an effect size of 25% that of atorvastatin in 6 months. This technology promises to be very useful in evaluation of new therapies.

Aged↗
PubMed2005

A comparison of ultrasound measurements to assess carotid atherosclerosis development in subjects with and without type 2 diabetes.

BACKGROUND: Subjects with type 2 diabetes are at an increased risk of vascular complications. The use of carotid ultrasound remains an attractive, non-invasive method to monitor atherosclerotic disease progression and/or response to treatment in patients with type 2 diabetes, with intima-media thickness routinely used as the gold standard to detect pathology. However, alternative measurements, such as plaque area or volume, may represent a potentially more powerful approach. Thus, the objective of this study was to compare the traditional intima-media thickness measurement against the novel total plaque volume measurement in analyzing carotid atherosclerosis development in individuals with type 2 diabetes. METHODS: The case-control study included 49 Oji-Cree adults with diabetes or impaired glucose tolerance, aged 21-69, and 49 sex- and age-matched normoglycemic subjects. At baseline, metabolic variables were measured, including body mass index, waist circumference, total cholesterol: high density lipoprotein ratio, plasma triglycerides, plasma glucose, and serum insulin. Carotid ultrasound measurements, 7 years later, assessed carotid arterial intima-media thickness and total plaque volume. RESULTS: At baseline, the two groups were well matched for smoking habits, hypertension, body mass index, and waist circumference. Differences were noted in baseline measurements of total cholesterol:high density lipoprotein (P = 0.0006), plasma triglycerides (P < 0.0001) and fasting glucose (P < 0.0001). After seven years, carotid ultrasound scans revealed that total plaque volume measurements (P = 0.037), but not intima-media thickness measurements, were higher in subjects with diabetes/impaired glucose tolerance compared to the normoglycemic controls. Correlation between intima-media thickness and total plaque volume was moderate. Based on our study findings, to achieve power levels > 0.70 when comparing intima-media thickness measurements for diabetics versus non-diabetics, thousands of study subjects are required. For comparing total plaque volume measurements, only hundreds of study subjects are required. CONCLUSION: The development of atherosclerotic plaque is greater in subjects with diabetes/impaired glucose tolerance. Total plaque volume appears to capture the atherosclerotic disease burden more effectively in subjects with type 2 diabetes, and would be an appropriate outcome measure for studies aimed at changing the diabetic milieu.

Adult↗
PubMed2005

Vitamin B12, homocysteine and carotid plaque in the era of folic acid fortification of enriched cereal grain products.

BACKGROUND: Carotid plaque area is a strong predictor of cardiovascular events. High homocysteine levels, which are associated with plaque formation, can result from inadequate intake of folate and vitamin B12. Now that folic acid fortification is widespread in North America, vitamin B12 has become an important determinant of homocysteine levels. We sought to determine the prevalence of low serum levels of vitamin B12, and their relation to homocysteine levels and carotid plaque area among patients referred for treatment of vascular disease since folic acid fortification of enriched grain products. METHODS: We evaluated 421 consecutive new patients with complete data whom we saw in our vascular disease prevention clinics between January 1998 and January 2002. We measured total carotid plaque area by ultrasound and determined homocysteine and serum vitamin B12 levels in all patients. RESULTS: The patients, 215 men and 206 women, ranged in age from 37 to 90 years (mean 66 years). Most were taking medications for hypertension (67%) and dyslipidemia (62%). Seventy-three patients (17%) had vitamin B12 deficiency (vitamin B12 level < 258 pmol/L with homocysteine level > 14 mumol/L or methylmalonic acid level > 271 nmol/L). The mean area of carotid plaque was significantly larger among the group of patients whose vitamin B12 level was below the median of 253 pmol/L than among those whose vitamin B12 level was above the median: 1.36 (standard deviation [SD] 1.27) cm2 v. 1.09 (SD 1.0) cm2; p = 0.016. CONCLUSIONS: Vitamin B12 deficiency is surprisingly common among patients with vascular disease, and, in the setting of folic acid fortification, low serum vitamin B12 levels are a major determinant of elevated homocysteine levels and increased carotid plaque area.

Adult↗
PubMed2005

Anthropometric data for magnetic resonance imaging of the carotid bifurcation.

PURPOSE: To provide anthropometric data applicable to the design of protocols for high-resolution magnetic resonance imaging (MRI) of the carotid bifurcation, particularly those aimed at elucidating the role of local factors in carotid atherogenesis. MATERIALS AND METHODS: Axial black-blood MR images of the carotid bifurcation were acquired from 25 young, healthy volunteers and 25 older, asymptomatic patients, from which were measured a variety of quantities related to the orientation and placement of the bifurcation within the neck. RESULTS: Descriptive statistics were obtained for the following quantities: separation of the bifurcation apices within (57.8+/-6.7 mm) and between (4.9+/-4.1 mm) axial slices; orientation of the bifurcation within the axial plane (31.7+/-26.9 degrees ), and of the common carotid artery (CCA) relative to the sagittal (7.5+/-7.1 degrees ) and coronal (7.9+/-7.8 degrees ) planes; depth of the bifurcation from the skin surface (29.5+/-7.2 mm); and neck width (125.9+/-14.4 mm). CONCLUSION: In most cases, both carotid arteries may be captured, without aliasing, within a 12-cm field-of-view axial image; however, the two apices will rarely be captured within the same axial slice. The CCA is significantly oblique to the body axis, but at angles sufficiently acute to permit the use of axial slices. Finally, a significant linear relationship between neck width and carotid depth may be used to inform radio frequency (RF) coil selection prior to scanning a subject, and hence facilitate optimal imaging in light of the wide anatomic variations observed.

Adult↗
PubMed2005

Differences between carotid wall morphological phenotypes measured by ultrasound in one, two and three dimensions.

Ultrasound measurements are both surrogate markers and risk factors for atherosclerosis end points. Carotid intima-media thickness (IMT) is most commonly used, but ultrasound can also define structures in higher spatial dimensions, such as total plaque area (TPA) and total plaque volume (TPV). Because there are minimal data regarding the relationship between IMT, TPA and TPV, we measured these variables in 272 Oji-Cree subjects. We found pairwise correlations for IMT:TPA, IMT:TPV and TPA:TPV of 0.507, 0.588 and 0.846, respectively (transformed variables, all P <0.0001). In a subset of 168 subjects with complete cardiovascular risk factor data, we performed multivariate regression analysis to identify sources of variation for IMT, TPA and TPV. We found that the ultrasound traits showed different correlations with individual cardiovascular risk factors. In particular, IMT was significantly associated with hypertension, TPA with smoking and plasma cholesterol, and TPV with diabetes. Therefore, these ultrasound measures of carotid artery morphology, while somewhat correlated, likely represent distinctive quantitative traits with different biological determinants, as underscored by different risk factor associations in the multivariate regression analysis. Because the measurements have different implications and determinants, investigators might need to be selective about the particular measurements they choose for specific applications.

Adult↗
PubMed2005

Quantification of carotid plaque volume measurements using 3D ultrasound imaging.

An accurate and reliable technique used to quantify carotid plaque volume has practical importance in research and patient management. In this study, we develop and investigate a theoretical description of carotid plaque volume measurements made using three-dimensional (3D) ultrasound (US) images and compare it with experimental results. Multiple observers measured 48 3D US patient images of carotid plaque (13.2 to 544.0 mm(3)) by manual planimetry. Coefficients of variation in the measurement of plaque volume were found to decrease with increasing plaque size for both inter- (90.8 to 3.9%) and intraobserver (70.2 to 3.1%) measurements. Plaque volume measurement variability was found to increase with interslice distance (ISD), while the relative measurement accuracy remained constant for ISDs between 1.0 and 3.0 mm and then decreased. Root-mean-square (RMS) difference between our theoretical description of plaque volume measurement variance and the experimental results was 5.7%. Thus, our results support the clinical utility of measuring carotid plaque volume by manual planimetry noninvasively using 3D US.

Aged↗
PubMed2005

Intra-arterial thrombolysis of embolic middle cerebral artery using collateral pathways.

BACKGROUND AND PURPOSE: Cervical internal carotid artery (ICA) occlusion associated with middle cerebral artery (MCA) embolic occlusion requires prompt revascularization to prevent devastating stroke. With the advent of endovascular techniques for chemical and mechanical thrombolysis, the clinical outcome of patients with major arterial occlusions will improve. Finding the most expedient pathway to the site of end organ occlusion for thrombolysis is important. METHODS: We present two cases of acute stroke secondary to thrombotic occlusion of the cervical ICA associated with MCA embolic occlusion treated with intra-arterial thrombolysis via catheter navigation through the posterior communicating artery to the site of MCA arterial occlusion. No attempt was made to transverse the occluded ICA. RESULTS: Near complete restoration of flow was achieved in one patient and minimal vessel reopening was observed in the other patient. Both patients had good outcomes. CONCLUSION: Intra-arterial thrombolysis via Circle of Willis collaterals such as the posterior communicating artery for the treatment of acute thrombotic occlusion of the cervical internal carotid artery associated with embolic occlusion of the middle cerebral artery is a therapeutic option. This treatment option avoids the potential complications of navigating through an occluded proximal internal carotid artery and may expedite reopening of the MCA.

Aged↗
PubMed2005

Point: uses of carotid plaque measurement as a predictor of cardiovascular events.

Vascular prevention is most cost-effective in high-risk patients, but secondary prevention misses many opportunities. The high-risk strategy- identifying patients with high levels of risk factors-is problematic because traditional risk factors predict only half of vascular events. In multiple regression, traditional risk factors explained only half of carotid atherosclerosis. New strategies are being explored, such as electron-beam computerized tomographic measurement of coronary calcification, to identify high-risk patients. Carotid plaque is a powerful tool for identifying and managing high-risk vascular patients, as it explains twice as much of unexplained vascular risk as coronary calcium by electron beam computerized tomography, and it has significant advantages compared with intimal-medial thickness. After adjustment for risk factors, patients in the highest quartile of baseline plaque area have 3.5 times the risk of stroke, death, or myocardial infarction compared with those in the lowest quartile. Those with regression or stable plaque have half the risk of those with progression after adjustment for the same panel of risk factors. The therapeutic target is plaque regression or stabilization, not just control of traditional risk factors. Trying to treat arteries without measuring plaque is like trying to treat hypertension without measuring the pressure, or hyperlipidemia without measuring the lipids.

Cardiovascular Diseases↗
PubMed2004

Genetic variation in PPARG encoding peroxisome proliferator-activated receptor gamma associated with carotid atherosclerosis.

BACKGROUND AND PURPOSE: Peroxisome proliferator-activated receptor gamma is a crucial molecule in atherogenesis because it is associated with metabolic risk factors such as obesity and diabetes and also plays a key role in subcellular metabolism of arterial wall macrophage foam cells. Genetic variation in PPARG has been associated with metabolic and cardiovascular end points. METHODS: We investigated the relationship between 2 common PPARG polymorphisms, namely P12A and c.1431C>T, and carotid atherosclerosis in a sample of 161 Canadian aboriginal people. Dependent variables were carotid intima media thickness (IMT), assessed using B-mode ultrasonography, and total carotid plaque volume (TPV), assessed using 3D ultrasound. RESULTS: Using multivariate analysis, we found that subjects with > or =1 PPARG A12 allele had less carotid IMT than others (0.72+/-0.03 versus 0.80+/-0.02 mm; P=0.0045), with no between-genotype difference in TPV. In contrast, subjects with the PPARG c.1431T allele had greater TPV than others (124+/-18.4 versus 65.1+/-23.7 mm3; P=0.0079), with no between-genotype difference in IMT. CONCLUSIONS: The findings show an association between PPARG genotypes and carotid arterial phenotypes, and further reflect the prevailing view that the PPARG A12 allele protects against deleterious phenotypes. Also, whereas IMT and TPV are somewhat correlated with each other, they might also represent distinct traits with discrete determinants representing different stages of atherogenesis.

Adult↗
PubMed2004

Measurement of carotid plaque volume by 3-dimensional ultrasound.

BACKGROUND AND PURPOSE: Measurement of carotid plaque volume and its progression are important tools for research and patient management. In this study, we investigate the observer variability in the measurement of plaque volume as determined by 3-dimensional (3D) ultrasound (US). We also investigate the effect of interslice distances (ISD) and repeated 3D US scans on measurement variability. Materials and Methods Forty 3D US patient images of plaques (range, 37.43 to 604.1 mm3) were measured by manual planimetry. We applied ANOVA to determine plaque volume measurement variability and reliability. Plaque volumes were measured with 9 ISDs to determine the effect of ISD on measurement variability. Additional plaque volumes were also measured from multiple 3D US scans to investigate repeated scan acquisition variability. Results Intraobserver and interobserver measurement reliabilities were 94% and 93.2%, respectively. Plaque volume measurement variability decreased with increasing plaque volume (range, 27.1% to 2.2%). Measurement precision was constant for ISDs between 1.0 and 3.0 mm, whereas plaque volume measurement variability increased with ISD. Repeated 3D US scan measurements were not different from single-scan measurements (P=0.867). Conclusions The coefficient of variation in the measurement of plaque volume decreased with plaque size. The volumetric change that must be observed to establish with 95% confidence that a plaque has undergone change is approximately 20% to 35% for plaques <100 mm3 and approximately 10% to 20% for plaques >100 mm3. Measurement precision was unchanged for ISDs <3.0 mm, whereas measurement variability increased with ISD. Repeated 3D US scans did not affect plaque volume measurement variability.

Aged↗
PubMed2004

Noninvasive phenotypes of atherosclerosis: similar windows but different views.

BACKGROUND AND PURPOSE: Noninvasive measures of atherosclerosis, such as carotid intima-media thickness, total carotid plaque area, and carotid stenosis, probably represent different phenotypes with distinct determinants. For instance, total carotid plaque area may reflect atherosclerotic lesion size more closely than carotid stenosis, which instead may reflect hemodynamic compromise within the arterial lumen. METHODS: In 1821 patients from a Premature Atherosclerosis Clinic, we studied determinants of total carotid plaque area and carotid stenosis as measured by ultrasound using multivariate regression analysis with traditional risk factors and some emerging risk factors. RESULTS: Regression modeling showed that (1) traditional atherosclerosis risk factors were more strongly associated with total carotid plaque area than with carotid stenosis (R=0.53 and 0.13, respectively), and (2) individual risk factors had different relationships with total carotid plaque area and carotid stenosis. For instance, age accounted for 53% and 26% of the explained variance of total carotid plaque area and carotid stenosis, respectively. Female sex was inversely associated with total carotid plaque area but positively associated with carotid stenosis. Nontraditional risk variables such as plasma homocysteine had different associations with the 2 analytes. CONCLUSIONS: Total carotid plaque area and carotid stenosis had different associations with specific atherosclerosis risk factors. Thus, for future studies of the determinants of atherosclerosis, it is important to distinguish between different phenotypes and to appreciate that they will not necessarily have the same determinants.

Aryldialkylphosphatase↗
PubMed2004

Lowering homocysteine in patients with ischemic stroke to prevent recurrent stroke, myocardial infarction, and death: the Vitamin Intervention for Stroke Prevention (VISP) randomized controlled trial.

CONTEXT: In observational studies, elevated plasma total homocysteine levels have been positively associated with ischemic stroke risk. However the utility of homocysteine-lowering therapy to reduce that risk has not been confirmed by randomized trials. OBJECTIVE: To determine whether high doses of folic acid, pyridoxine (vitamin B6), and cobalamin (vitamin B12), given to lower total homocysteine levels, reduce the risk of recurrent stroke over a 2-year period compared with low doses of these vitamins. DESIGN: Double-blind randomized controlled trial (September 1996-May 2003). SETTING AND PARTICIPANTS: 3680 adults with nondisabling cerebral infarction at 56 university-affiliated hospitals, community hospitals, private neurology practices, and Veterans Affairs medical centers across the United States, Canada, and Scotland. INTERVENTIONS: All participants received best medical and surgical care plus a daily multivitamin containing the US Food and Drug Administration's reference daily intakes of other vitamins; patients were randomly assigned to receive once-daily doses of the high-dose formulation (n = 1827), containing 25 mg of pyridoxine, 0.4 mg of cobalamin, and 2.5 mg of folic acid; or the low-dose formulation (n = 1853), containing 200 microg of pyridoxine, 6 microg of cobalamin and 20 microg of folic acid. MAIN OUTCOME MEASURES: Recurrent cerebral infarction (primary outcome); coronary heart disease (CHD) events and death (secondary outcomes). RESULTS: Mean reduction of total homocysteine was 2 micromol/L greater in the high-dose group than in the low-dose group, but there was no treatment effect on any end point. The unadjusted risk ratio for any stroke, CHD event, or death was 1.0 (95% confidence interval [CI], 0.8-1.1), with chances of an event within 2 years of 18.0% in the high-dose group and 18.6% in the low-dose group. The risk of ischemic stroke within 2 years was 9.2% for the high-dose and 8.8% for the low-dose groups (risk ratio, 1.0; 95% CI, 0.8-1.3) (P =.80 by log-rank test of the primary hypothesis of difference in ischemic stroke between treatment groups). There was a persistent and graded association between baseline total homocysteine level and outcomes. A 3- micromol/L lower total homocysteine level was associated with a 10% lower risk of stroke (P =.05), a 26% lower risk of CHD events (P<.001), and a 16% lower risk of death (P =.001) in the low-dose group and a nonsignificantly lower risk in the high-dose group by 2% for stroke, 7% for CHD events, and 7% for death. CONCLUSIONS: In this trial, moderate reduction of total homocysteine after nondisabling cerebral infarction had no effect on vascular outcomes during the 2 years of follow-up. However, the consistent findings of an association of total homocysteine with vascular risk suggests that further exploration of the hypothesis is warranted and longer trials in different populations with elevated total homocysteine may be necessary.

Adult↗