Biomedical subjects
J David Spence
Publications and source records attributed to J David Spence.
Ultrasound measurement of carotid plaque as a surrogate outcome for coronary artery disease.
Intima-media thickness (IMT) is commonly used as a surrogate marker for coronary artery disease (CAD). However, use of this parameter is a problem because (1) it assumes uniform thickness throughout the blood vessel, and (2) it detects changes primarily in the media, whereas atherosclerosis is a focal phenomenon that is confined to the intima. As an alternative to IMT, we have investigated the use of ultrasound measurements of plaque area and plaque volume as surrogate outcomes for CAD. Plaque area is a sensitive predictor of coronary disease progression and is closely associated with CAD. Clinical studies have shown that the sample size needed to detect atherosclerosis progression is sufficiently small to make this a useful assessment in clinical trials. Plaque volume, as measured by 3-dimensional ultrasound, may offer an even better means of assessing atherosclerosis. Plaque volume assessments are highly accurate and the data can be saved on a compact disc for central reading. Because of the high degree of accuracy and the increased size of plaque volume relative to plaque area or IMT, it is likely that only a small sample size will be required to detect clinically meaningful differences in plaque volume in a clinical trial.
Reconstruction of carotid bifurcation hemodynamics and wall thickness using computational fluid dynamics and MRI.
A thorough understanding of the relationship between local hemodynamics and plaque progression has been hindered by an inability to prospectively monitor these factors in vivo in humans. In this study a novel approach for noninvasively reconstructing artery wall thickness and local hemodynamics at the human carotid bifurcation is presented. Three-dimensional (3D) models of the lumen and wall boundaries, from which wall thickness can be measured, were reconstructed from black-blood magnetic resonance imaging (MRI). Along with time-varying inlet/outlet flow rates measured via phase contrast (PC) MRI, the lumen boundary was used as input for computational fluid dynamic (CFD) simulation of the subject-specific flow patterns and wall shear stresses (WSSs). Results from a 59-year-old subject with early, asymptomatic carotid artery disease show good agreement between simulated and measured velocities, and demonstrate a correspondence between wall thickening and low and oscillating shear at the carotid bulb. High shear at the distal internal carotid artery (ICA) was also colocalized with higher WSS; however, a quantitative general relationship between WSS and wall thickness was not found. Similar results were obtained from a 23-year-old normal subject. These findings represent the first direct comparison of hemodynamic variables and wall thickness at the carotid bifurcation of human subjects. The noninvasive nature of this image-based modeling approach makes it ideal for carrying out future prospective studies of hemodynamics and plaque development or progression in otherwise healthy subjects.
Carotid plaque area: a tool for targeting and evaluating vascular preventive therapy.
BACKGROUND AND PURPOSE: Carotid plaque area measured by ultrasound (cross-sectional area of longitudinal views of all plaques seen) was studied as a way of identifying patients at increased risk of stroke, myocardial infarction, and vascular death. METHODS: Patients from an atherosclerosis prevention clinic were followed up annually for up to 5 years (mean, 2.5+/-1.3 years) with baseline and follow-up measurements recorded. Plaque area progression (or regression) was defined as an increase (or decrease) of >/=0.05 cm(2) from baseline. RESULTS: Carotid plaque areas from 1686 patients were categorized into 4 quartile ranges: 0.00 to 0.11 cm(2) (n=422), 0.12 to 0.45 cm(2) (n=424), 0.46 to 1.18 cm(2) (n=421), and 1.19 to 6.73 cm(2) (n=419). The combined 5-year risk of stroke, myocardial infarction, and vascular death increased by quartile of plaque area: 5.6%, 10.7%, 13.9%, and 19.5%, respectively (P<0.001) after adjustment for all baseline patient characteristics. A total of 1085 patients had >/=1 annual carotid plaque area measurements: 685 (63.1%) had carotid plaque progression, 306 (28.2%) had plaque regression, and 176 (16.2%) had no change in carotid plaque area over the period of follow-up. The 5-year adjusted risk of combined outcome was 9.4%, 7.6%, and 15.7% for patients with carotid plaque area regression, no change, and progression, respectively (P=0.003). CONCLUSIONS: Carotid plaque area and progression of plaque identified high-risk patients. Plaque measurement may be useful for targeting preventive therapy and evaluating new treatments and response to therapy and may improve cost-effectiveness of secondary preventive treatment.
Quantitative measurement of carotid atherosclerosis in relation to levels of von Willebrand factor and fibrinolytic variables in plasma--a 2-year follow-up study.
BACKGROUND: It has been proposed that the mechanism of action of the new risk factors for myocardial infarction and stroke, von Willebrand factor (vWF), tissue plasminogen activator (tPA) and tissue plasminogen activator inhibitor-1 (PAI-1) could possibly be mediated via a primary effect on atherogenesis but there is little data to substantiate this. DESIGN: A prospective single-centre cohort study of progression of atherosclerosis. METHODS: Carotid plaque area was quantitated by two-dimensional (2D) ultrasound in 258 subjects at entry and after 1 and 2 years. Plasma and serum samples were drawn at baseline and serum lipids and plasma levels of haemostatic factors were measured. RESULTS: The traditional risk factors, smoking, total cholesterol, hypertension and male gender explained 51% of the variance in plaque area at baseline and 48% at 1-year follow-up. There were small positive associations of plaque area with vWF, tPA and tPA/PAI-1 complex and a tendency to negative associations with PAI-1 levels, independent from the traditional risk factors. The additional explanatory power of the haemostatic factors did not exceed 3%. CONCLUSION: The data accord with a marginal role in atherogenesis of vWF and tPA, and underline the major impact of smoking, hypertension and cholesterol on carotid plaque area progression.
Treatment options for renovascular hypertension.
Renovascular hypertension is usually caused by atherosclerotic narrowing of the origin of the renal artery and is much more common than is thought among patients with peripheral vascular disease, carotid stenosis or heart failure. Renovascular hypertension must be distinguished from renal artery stenosis. In true renovascular hypertension, the kidney takes charge of the blood pressure and will do what it takes to push blood pressure high enough to force blood through the blocked artery. This can be diagnosed with functional tests that measure glomerular filtration rate before and after blockade of the renin-angiotensin system with angiotensin converting enzyme inhibitors or antagonists of the AT(1) subtype of the angiotensin receptor. There is insufficient data on which to make evidence-based recommendations on the management of renovascular hypertension. Only two randomised trials exist of angioplasty versus medical therapy and of these the larger was severely contaminated by angioplasty among the group initially assigned to medical therapy. Only one trial exists of angiotensin converting enzyme inhibition versus alternative medical therapy. The drugs that are most effective in medical management of renovascular hypertension--angiotensin converting enzyme inhibitors and angiotensin receptor-1 blockers--tend to be avoided because of fear of a very rare complication (acute renal failure in patients with severe stenosis of both renal arteries, or the artery to a single remaining kidney). This fear is misplaced not only because it is rare (< 5% of patients with renovascular hypertension) but because it is reversible and treatable by revascularisation. Patients with renovascular hypertension should be evaluated by nuclear medicine differential glomerular filtration rate, enhanced by blockers of the renin-angiotensin system. If medical therapy is ineffective or causes severe impairment of renal function, revascularisation is required. Some experts favour surgical revascularisation because of occasional angioplasty failure and the risk of deterioration of renal function after angioplasty.