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Simon A McG Thom

Publications and source records attributed to Simon A McG Thom.

11 recordsLinked to original sources

Rationale and design of the AdRem study: evaluating the effects of blood pressure lowering and intensive glucose control on vascular retinal disorders in patients with type 2 diabetes mellitus.

The ADVANCE Retinal Measurements (AdRem) Study is a large intervention study evaluating the effects of target driven intensive glucose control and placebo controlled blood pressure lowering on retinal vascular changes. AdRem is a sub-study of the ADVANCE Study (Action in Diabetes and Vascular disease), a 2x2 factorial randomized controlled trial with an ACE inhibitor-diuretic combination (perindopril-indapamide) and a gliclazide MR-based regimen in patients with type 2 diabetes mellitus. The AdRem study is based on seven-field stereoscopic retinal photographs of both eyes. These are taken within 3 months after randomization in ADVANCE (baseline), at the biennial and at the final visit. The primary outcome is progression of two or more steps in ETDRS classification. Secondary outcomes include progression of retinal vascular lesions and distortion of retinal vascular geometry. Retinal photographs are made on film and digitized at a central laboratory. The AdRem study uses fully digitized quality control and grading. Between August 2002 and January 2004 1978 patients were included in the AdRem study, from 39 centers in 14 countries. Approximately 85% comply with the strict AdRem quality requirements. Publication of the results is expected in early 2008. The AdRem study is designed to provide reliable evidence on the effects of intensive glucose control and blood pressure lowering on both diabetic retinopathy and abnormalities of retinal vasculature in patients with type 2 diabetes mellitus.

Antihypertensive Agents↗

Indian Asian men have less peripheral arterial disease than European men for equivalent levels of coronary disease.

OBJECTIVES: Indian Asians have high rates of heart disease and stroke, but risks of peripheral arterial disease appear to be low. This paradox, and reasons for it, have not been explored. We compared ethnic differences in peripheral arterial disease for a given level of coronary disease. METHODS: We studied 83 European and 84 Indian Asian men with a range of coronary disease. Extent of coronary atheroma was quantified by coronary artery calcification score on multislice CT. Femoral intima-media thickness (IMT) was measured by ultrasound. RESULTS: Femoral IMT was 1.58, 2.06, 2.12, and 2.69 mm in Europeans, and 0.61, 1.41, 1.81 and 2.29 in Indian Asians by increasing categories of coronary atheroma (p=0.003 for ethnic difference, adjusted for age and lumen diameter). Adjustment for smoking and systolic blood pressure, the only risk factors adversely distributed in Europeans, only partly accounted for this ethnic difference (p=0.05). Other risk factors, including lipids, obesity, insulin and glycaemic status, more adversely distributed in Indian Asians, could not account for ethnic differences. Prevalence of abnormal ankle brachial index and lower limb atherosclerotic plaque was also greater in Europeans. CONCLUSIONS: For a given level of coronary disease, Indian Asians have less lower limb atherosclerosis than Europeans, unexplained by established risk factors. Further study of these populations would help tease out relative contributions of risk factors to atherosclerosis in different vessel beds.

Aged↗

Abnormalities of retinal microvascular structure and risk of mortality from ischemic heart disease and stroke.

Abnormalities of the retinal microcirculation are found in hypertension and diabetes and predict cardiovascular mortality. This study examined the relationship between abnormalities of the retinal microvasculature and death from ischemic heart disease (IHD) and stroke. A population-based, nested case-control study was undertaken within the Beaver Dam Eye Study. Subjects (43 to 74 years) who died of IHD (n=126) or stroke (n=28) over a 10-year period were age and gender matched with controls subjects (n=528; case:control matching, approximately 1:4). Retinal photographs of cases and controls were digitized and analyzed using a computer-based technique. Increased risk of IHD death was associated with a suboptimal relationship of arteriolar diameters at bifurcation (P=0.02 unadjusted) and decreased retinal arteriolar tortuosity (P=0.011 unadjusted). These associations remained significant after adjustment for age, sex, past history of cardiovascular disease, and other known cardiovascular risk factors. Increased arteriolar length:diameter ratio, a measure of generalized arteriolar narrowing, was associated with increased stroke mortality (P=0.02 unadjusted). This association was independent of age and gender but was attenuated by adjustment for systolic blood pressure (P=0.15). Other quantitative measures of the retinal microvascular network (eg, venular tortuosity and arteriolar and venular bifurcation angle) were not associated with death from IHD or stroke. Retinal microvascular abnormalities are predictive of death from IHD and stroke. A detailed assessment of the retinal microvascular network from digitized photographs may be useful in the noninvasive assessment of target organ damage and cardiovascular risk.

Aged↗

Quantification of topological changes in retinal vascular architecture in essential and malignant hypertension.

OBJECTIVE: Grading of hypertension severity by fundoscopic appearance is difficult and inaccurate. We investigated whether essential hypertension (EHT) and malignant phase hypertension (MHT) were associated with quantifiable abnormalities of the topology and architecture of the retinal circulation. METHODS: The topology and architecture of the retinal microvasculature were compared in images from 20 normotensive subjects, 20 patients with EHT and 20 patients with MHT. Digitized retinal photographs were analysed by a novel multiscale image analysis method using a semi-automated program to quantify geometrical and topological properties of arteriolar and venular trees. RESULTS: EHT was associated with an increase in the arteriolar length-to-diameter ratio (P < 0.01). There were also alterations in arteriolar topology indicative of rarefaction, including a marked reduction in the number of terminal branches in EHT (P < 0.01). These changes in the arteriolar network were exaggerated in MHT and there was also increased venular tortuosity and venular rarefaction in MHT compared with normotensive subjects. CONCLUSIONS: Hypertension is associated with marked topological alterations in the retinal vasculature, and quantification of these changes may be a useful novel approach to the assessment of target organ damage in hypertension.

Adult↗

Comparison between three-dimensional volume-selective turbo spin-echo imaging and two-dimensional ultrasound for assessing carotid artery structure and function.

PURPOSE: To compare a volume-selective three-dimensional turbo spin echo (TSE) technique with ultrasound (US) for assessing carotid artery wall structure and function. MATERIALS AND METHODS: A three-dimensional volume-selective TSE technique was used to image the carotid artery in 10 healthy subjects and five hypertensive subjects (each of whom were scanned three times while they received different hypertension treatments). Lumen and wall area were measured on MR images. Two-dimensional US measurements of the intima-media thickness (IMT) and lumen diameter were taken in three orientations through a single cross section. The lumen area change over the cardiac cycle was used to determine distension. For validation, a Bland-Altman analysis was used to compare the vessel wall and lumen areas measured by three-dimensional MRI volumes with those obtained by US scans. RESULTS: Agreement between the two methods was found. The mean difference in distension between US and MRI was 1.2% (+/-5.1%). For the wall area measurements, good agreement was shown, but there was a systematic difference due to the visualization of the adventitia by MRI. Both techniques offer an easy way to objectively measure lumen indices. MRI can provide the complete circumference over the length of a vessel, while US is flexible and relatively inexpensive. The application of US is limited, however, when subjects are poorly echogenic. A difference between hypertensive and healthy subjects was found. CONCLUSION: There was a good agreement between MRI and the clinically established two-dimensional US method. The MRI method has the advantage of providing increased vessel coverage, which permits one to assess localized abnormalities without assuming vessel uniformity.

Adult↗

Effects of vasoactive agents on intracellular calcium and force in myometrial and subcutaneous resistance arteries isolated from preeclamptic, pregnant, and nonpregnant woman.

OBJECTIVE: Preeclampsia is a common and serious complication of pregnancy, characterized by maternal hypertension and proteinuria, placental insufficiency, and fetal growth restriction. The purpose of this study was to investigate whether intracellular Ca 2+ ([Ca 2+ ] i ) and contractile responses of vascular smooth muscle to vasoactive agents are altered in preeclampsia compared with normal pregnancy and the nonpregnant state. STUDY DESIGN: Subcutaneous and myometrial resistance arteries from women who had preeclampsia, normal pregnancy, and nonpregnant women were obtained at the time of cesarean section or hysterectomy. Arteries were mounted on an isometric myograph and loaded with the Ca 2+ indicator, fura-2AM, to permit simultaneous measurement of force and [Ca 2+ ] i . Reponses to endothelium-dependent relaxants (acetylcholine and substance P) and vasoconstrictors (depolarizing potassium solution, phenylephrine, and angiotensin II) were examined. RESULTS: The fall in [Ca 2+ ] i and relaxation in response to acetylcholine was significantly inhibited in both myometrial and subcutaneous arteries from preeclamptic women compared with arteries from nonpregnant or normal pregnant women. However, responses to substance P did not differ between the 3 groups. There were no significant differences in [Ca 2+ ] i or force responses to high potassium, phenylephrine, or angiotensin II in myometrial and subcutaneous resistance vessels in women with preeclampsia compared with normal pregnant women. However, force, but not [Ca 2+ ] i responses to angiotensin II, in subcutaneous vessels from normal pregnant and preeclamptic women were reduced compared with subcutaneous arteries from nonpregnant women, indicating that pregnancy is associated with a reduction in Ca 2+ sensitization in this tissue. A similar effect was not seen in myometrial arteries. CONCLUSION: Endothelial function is altered in preeclampsia, with loss of effect of acetylcholine, but not substance P. Vasoconstrictor reactivity is not increased in preeclampsia compared with uncomplicated normal pregnancy, and this is unlikely to be an explanation for the increased peripheral vascular resistance seen in preeclampsia.

Adult↗

Operator dependence of 3-D ultrasound-based computational fluid dynamics for the carotid bifurcation.

The association between vascular wall shear stress (WSS) and the local development of atherosclerotic plaque makes estimation of in vivo WSS of considerable interest. Three-dimensional ultrasound (3DUS) combined with computational fluid dynamics (CFD) provides a potentially valuable tool for acquiring subject-specific WSS, but the interoperator and intraoperator variability associated with WSS calculations using this method is not known. Here, the accuracy, reproducibility and operator dependence of 3DUS-based computational fluid dynamics were examined through a phantom and in vivo studies. A carotid phantom was scanned and reconstructed by two operators. In the in vivo study, four operators scanned a healthy subject a total of 11 times, and their scan data were processed by three individuals. The study showed that with some basic training, operators could acquire accurate carotid geometry for flow reconstructions. The variability of measured cross-sectional area and predicted shear stress was 8.17% and 0.193 N/m2 respectively for the in vivo study. It was shown that the variability of the examined parameters was more dependent on the scan operators than the image processing operator. The range of variability of geometrical and flow parameters reported here can be used as a reference for future in vivo studies using the 3DUS-based CFD approach.

Adult↗

Reconstruction and quantification of the carotid artery bifurcation from 3-D ultrasound images.

Three-dimensional (3-D) ultrasound is a relatively new technique, which is well suited to imaging superficial blood vessels, and potentially provides a useful, noninvasive method for generating anatomically realistic 3-D models of the peripheral vasculature. Such models are essential for accurate simulation of blood flow using computational fluid dynamics (CFD), but may also be used to quantify atherosclerotic plaque more comprehensively than routine clinical methods. In this paper, we present a spline-based method for reconstructing the normal and diseased carotid artery bifurcation from images acquired using a freehand 3-D ultrasound system. The vessel wall (intima-media interface) and lumen surfaces are represented by a geometric model defined using smoothing splines. Using this coupled wall-lumen model, we demonstrate how plaque may be analyzed automatically to provide a comprehensive set of quantitative measures of size and shape, including established clinical measures, such as degree of (diameter) stenosis. The geometric accuracy of 3-D ultrasound reconstruction is assessed using pulsatile phantoms of the carotid bifurcation, and we conclude by demonstrating the in vivo application of the algorithms outlined to 3-D ultrasound scans from a series of patient carotid arteries.

Algorithms↗

Midwall myocardial shortening in athletic left ventricular hypertrophy.

BACKGROUND: Patients with pathological left ventricular hypertrophy have depressed midwall systolic shortening in spite of normal indices of left ventricular chamber function and a reduced midwall function has been observed to be an independent predictor of cardiovascular risk. Whether midwall shortening is depressed in physiological hypertrophy is unknown. METHODS: Forty-two subjects, 27 athletes and 15 age- and sex-matched normal control subjects (group 1) were studied. The athletes were divided into those with eccentric hypertrophy (group 2) and those with concentric hypertrophy (group 3). Systolic left ventricular function was assessed at the midwall and endocardium using two-dimensional echocardiography in all subjects. RESULTS: Left ventricular mass index was significantly greater in both athletic groups than in controls (group 1, 101+/-5.8 g/m(2), group 2, 141+/-11.1*, group 3, 155+/-5.8*; *P<0.01 compared with group 1). Left ventricular systolic function assessed at the endocardium was similar among all three groups (ejection fraction: group 1, 66.2+/-2.38, group 2, 66.8+/-1.44, group 3, 63.7+/-1.66%; endocardial fractional shortening: group 1, 37.1+/-1.71, group 2, 37.6+/-1.13, group 3, 35.1+/-1.25%). However, fractional shortening at the midwall was reduced in the concentric hypertrophy athletes compared with the other two groups (midwall fractional shortening: group 1, 21.9+/-1.1, group 2, 21.9+/-0.86, group 3, 18.4+/-0.96*%; P<0.05 compared with groups 1 and 2). CONCLUSION: Subjects with physiological concentric hypertrophy have depressed midwall fractional shortening. This suggests that the observed discrepancy between midwall and endocardial shortening in patients with left ventricular hypertrophy is likely to be a function of the geometry and not necessarily a reflection of pathology within the myocardium.

Adult↗

Ethnic differences in carotid and left ventricular hypertrophy.

OBJECTIVES: Afro-Caribbean subjects have a higher prevalence of hypertension, a lower prevalence of ischaemic heart disease and a higher premature mortality compared to White Europeans. Left ventricular hypertrophy (LVH) is also more prevalent in Afro-Caribbeans even at similar levels of blood pressure. It is widely believed that carotid artery intima-media thickening (IMT) represents an early marker for the development of atheroma, and carotid IMT and LVH are associated in White populations. Whether the relationship between carotid IMT and LVH is similar in Black subjects is unknown. METHODS: Thirty-eight subjects were studied using carotid and femoral ultrasonography and echocardiography; 19 Afro-Caribbean and 19 White European subjects were matched for age, sex and mean 24 h systolic blood pressure. RESULTS: The Afro-Caribbean group had a significantly greater left ventricular mass index (LVMI) compared to the White European: 136.4 +/- 6.1 versus 112.4 +/- 6.2 g/m2, P < 0.01. However, carotid IMT, carotid diameter, femoral IMT and femoral diameter were similar between the groups: 0.75 +/- 0.02 versus 0.77 +/- 0.04 mm, 6.54 +/- 0.15 versus 6.56 +/- 0.16 mm, 0.66 +/- 0.03 versus 0.68 +/- 0.03 mm and 8.40 +/- 0.33 versus 8.25 +/- 0.23 mm, respectively. CONCLUSIONS: Afro-Caribbean subjects with similar blood pressures have similar mean carotid and femoral IMTs compared to White Europeans, in spite of marked differences in LVMI. Whether this reflects a discrepancy in the degree of cardiovascular risk for similar levels of LVMI or whether this is a reflection of an altered pattern of target organ damage associated with hypertension in Afro-Caribbean subjects is unclear.

Adult↗