Biomedical subjects

Neil Chapman

Publications and source records attributed to Neil Chapman.

13 recordsLinked to original sources

PubMed2006

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↗

PubMed2005

Effects of different blood pressure-lowering regimens on major cardiovascular events in individuals with and without diabetes mellitus: results of prospectively designed overviews of randomized trials.

BACKGROUND: Blood pressure (BP) level is a major determinant of cardiovascular morbidity and mortality in individuals with diabetes mellitus. Several guidelines recommend lower BP goals and specific drug classes for these patients. The overviews reported herein were performed to formally compare the effects on cardiovascular events and death of different BP-lowering regimens in individuals with and without diabetes. METHODS: Twenty-seven randomized trials (N = 158 709 participants) that included 33 395 individuals with diabetes and 125 314 without diabetes contributed to these analyses. For each outcome and each comparison summary, estimates of effect and 95% confidence intervals were calculated for patients with and without diabetes using a random-effects model. The constancy of the effects of each treatment regimen in participants with and without diabetes was examined using chi(2) tests of homogeneity. RESULTS: Total major cardiovascular events were reduced to a comparable extent in individuals with and without diabetes by regimens based on angiotensin-converting enzyme inhibitors, calcium antagonists, angiotensin receptor blockers, and diuretics/beta-blockers (P > .19 for all by chi(2) test of homogeneity). There was limited evidence that lower BP goals produced larger reductions in total major cardiovascular events in individuals with vs without diabetes (P = .03 by chi(2) test of homogeneity). CONCLUSIONS: These overviews showed that the short- to-medium-term effects on major cardiovascular events of the BP-lowering regimens studied were broadly comparable for patients with and without diabetes. Different effects of regimens on intermediate renal outcomes not evaluated in these overviews may still provide a rationale for using specific drug classes in patients with diabetes.

Aged↗

PubMed2004

Effects of an angiotensin-converting enzyme inhibitor-based regimen on pneumonia risk.

Observational studies conducted among Asian populations suggest that the risk of pneumonia is substantially reduced among users of angiotensin-converting enzyme (ACE) inhibitors but not other blood pressure-lowering agents. We conducted analyses of the effects of ACE inhibitor therapy on pneumonia in 6,105 patients with a history of stroke or transient ischemic attack enrolled in a randomized trial conducted in Australasia, Europe, and Asia. Patients were randomly assigned perindopril-based active treatment or placebo. The effects of ACE inhibitors on pneumonia (fatal or nonfatal) were determined from Cox models fitted according to the principle of intention to treat. During a median follow-up of 3.9 years, 261 patients developed pneumonia. Overall, active treatment was associated with a nonsignificant 19% lower risk of pneumonia (95% confidence interval, -3 to 37; p = 0.09) compared with placebo. Active treatment significantly reduced the risk of pneumonia among participants of Asian ethnicity (47%, 14-67%; p = 0.01), with no significant effect among non-Asian participants (5%, -27 to 29%; p = 0.7) (p for homogeneity = 0.04). These findings substantially add to the body of evidence about the effects of these drugs on pneumonia but do not provide the definitive information required to inform clinical decisions about the prevention of pneumonia with ACE inhibitors.

Aged↗

PubMed2004

Association of mean platelet volume with risk of stroke among 3134 individuals with history of cerebrovascular disease.

BACKGROUND AND PURPOSE: Mean platelet volume (MPV) is positively associated with measures of platelet activity and may be a useful indicator of the risk of vascular events in a variety of patient groups. METHODS: The association of MPV with the risk of stroke was assessed in the Perindopril Protection Against Recurrent Stroke Study (PROGRESS). All participants had a history of cerebrovascular disease at baseline, and analyses were adjusted for the effects of potential confounders. RESULTS: The study followed 3134 individuals for an average of 3.9 years (mean age, 65 years; 71% male; average MPV, 10.0 fL). Three hundred eighty-three individuals had 402 stroke events, and 160 had major coronary events. MPV was positively associated with the risk of stroke, with an 11% increased relative risk (95% CI, 3% to 19%) of stroke per femtoliter greater MPV. There was no clear association of MPV with the risk of major coronary events (9% decreased relative risk; 95% CI, -23% to 7%). Perindopril did not alter MPV. CONCLUSIONS: MPV is an independent predictor of the risk of stroke among individuals with a history of stroke or transient ischemic attack. The measurement of MPV may add useful prognostic information for clinicians managing patients with a history of cerebrovascular disease.

Aged↗

PubMed2004

Perindopril-based blood pressure lowering in individuals with cerebrovascular disease: consistency of benefits by age, sex and region.

OBJECTIVE: To assess the consistency of the benefits of blood pressure lowering on secondary stroke risk by age, sex and geographic region of recruitment. DESIGN: Randomized, placebo-controlled trial. Participants were randomized to the angiotensin-converting enzyme (ACE) inhibitor perindopril (plus the diuretic indapamide if not indicated or contraindicated) or to placebo(s) over a mean follow-up of 3.9 years. Main analyses used Cox proportional hazards models on an intention-to-treat basis. Subgroup results were standardized for the proportion (42%) taking single-drug therapy. SETTING: A total of 172 centres in Asia, Australia, New Zealand and Europe. PARTICIPANTS: Patients (n = 6105) with a history of stroke or transient ischaemic attack, of whom 50% were aged over 65 years at baseline, 30% were women and 39% were from Asia. MAIN OUTCOME MEASURES: Stroke, coronary heart disease and major vascular events. RESULTS: Overall, treatment reduced stroke by 28% [95% confidence interval (CI) 17-38%] and major vascular events by 26% (16-44%), with separately significant reductions across subgroups defined by age (< or > or = 65 years), sex and region (Asia or not). Treatment was safe and well tolerated, and the absolute benefits were large; 5 years' treatment would be expected to avert at least one major vascular event among every 20 patients in all age, sex and region subgroups. There was some evidence of particularly large benefits among younger participants and those from Asia. CONCLUSIONS: Blood pressure lowering reduces secondary stroke risk, with large absolute benefits across groups defined by age, sex and geographic region.

Age Distribution↗

PubMed2003

The ACE gene I/D polymorphism is not associated with the blood pressure and cardiovascular benefits of ACE inhibition.

The insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene might have consequences for the risks of vascular diseases. We examined the ACE genotype and the effects of a perindopril-based blood pressure-lowering regimen on macrovascular events, dementia, and cognitive decline among hypertensive and nonhypertensive patients with a history of cerebrovascular disease. ACE I/D genotypes were measured in 5688 of 6105 individuals with previous stroke or transient ischemic attack who participated in the PROGRESS trial. The DD genotype was significantly (P<0.0001) less frequent in Asian subjects (Chinese and Japanese, 14.7%) than in non-Asian subjects (32.0%). Controlling for racial background, there were no associations between ACE genotypes and cerebrovascular disease history or cardiovascular risk factors, including baseline blood pressure. The ACE genotype was not associated with the long-term risks of stroke, cardiac events, mortality, dementia, or cognitive decline; neither did the ACE genotype predict the blood pressure reduction associated with the use of the ACE inhibitor perindopril. Similarly, there was no evidence that the ACE genotype modified the relative benefits of ACE inhibitor-based therapy over placebo. This study provides no evidence that in patients with cerebrovascular disease, knowledge of ACE genotype is useful for predicting either the risk of disease or the benefits of perindopril-based blood pressure-lowering treatment.

Adult↗

PubMed2003

Effects of blood pressure lowering with perindopril and indapamide therapy on dementia and cognitive decline in patients with cerebrovascular disease.

BACKGROUND: High blood pressure and stroke are associated with increased risks of dementia and cognitive impairment. This study aimed to determine whether blood pressure lowering would reduce the risks of dementia and cognitive decline among individuals with cerebrovascular disease. METHODS: The Perindopril Protection Against Recurrent Stroke Study (PROGRESS) was a randomized, double-blind, placebo-controlled trial conducted among 6105 people with prior stroke or transient ischemic attack. Participants were assigned to either active treatment (perindopril for all participants and indapamide for those with neither an indication for nor a contraindication to a diuretic) or matching placebo(s). The primary outcomes for these analyses were dementia (using DSM-IV criteria) and cognitive decline (a decline of 3 or more points in the Mini-Mental State Examination score). RESULTS: During a mean follow-up of 3.9 years, dementia was documented in 193 (6.3%) of the 3051 randomized participants in the actively treated group and 217 (7.1%) of the 3054 randomized participants in the placebo group (relative risk reduction, 12% [95% confidence interval, -8% to 28%]; P =.2). Cognitive decline occurred in 9.1% of the actively treated group and 11.0% of the placebo group (risk reduction, 19% [95% confidence interval, 4% to 32%]; P =.01). The risks of the composite outcomes of dementia with recurrent stroke and of cognitive decline with recurrent stroke were reduced by 34% (95% confidence interval, 3% to 55%) (P =.03) and 45% (95% confidence interval, 21% to 61%) (P<.001), respectively, with no clear effect on either dementia or cognitive decline in the absence of recurrent stroke. CONCLUSIONS: Active treatment was associated with reduced risks of dementia and cognitive decline associated with recurrent stroke. These findings further support the recommendation that blood pressure lowering with perindopril and indapamide therapy be considered for all patients with cerebrovascular disease.

Aged↗

PubMed2003

Twelve-year changes in vascular risk factors and their associations with mortality in a cohort of 3499 Thais: the Electricity Generating Authority of Thailand Study.

BACKGROUND: Vascular mortality is increasing in economically developing countries such as Thailand but reliable data about the determinants of these changes are few. METHODS: In 1985, male and female employees of the Electricity Generating Authority of Thailand took part in a cardiovascular risk factor survey. In 1997, a follow-up survey was conducted and causes of death were determined for those subjects known to have died. Changes in levels of vascular risk factors over 12 years, and the associations of baseline risk factors with vascular mortality, were calculated. RESULTS: The 1985 survey recruited 3499 volunteers (average age 43 years) of whom 23% were female. In 1997, vital status was determined for 3318 (95%) and 2967 (85%) of the study participants were resurveyed. Mean levels of systolic blood pressure (SBP) and diastolic blood pressure (DBP), body mass index, total cholesterol and high density lipoprotein (HDL) cholesterol all increased over the 12-year follow-up period. Over the same time, the prevalence of diabetes also rose but the proportion of current smokers decreased. Vascular diseases were the most frequent cause of death during follow-up (n = 46), were positively associated with baseline age, SBP, DBP, smoking, diabetes, male sex, and total cholesterol, and were negatively associated with HDL cholesterol. CONCLUSIONS: Levels of most vascular risk factors worsened over the 12-year period between 1985 and 1997. The associations between baseline risk factor levels and vascular mortality were consistent with those observed in other populations. Interventions that control vascular risk factors have the potential to avert much premature vascular disease in Thailand.

Adult↗

PubMed2003

International Society of Hypertension (ISH): statement on blood pressure lowering and stroke prevention.

The ISH Statement on blood pressure lowering and stroke prevention was finalized after presentation and discussion at the World Health Organization and International Society of Hypertension (WHO-ISH) Meeting on Stroke and Blood Pressure, held in Melbourne Australia, 5-7 December 2002. The meeting was conducted under the auspice of the Austin Hospital Medical Research Foundation, Melbourne.

Anticoagulants↗

PubMed2002

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↗

PubMed2002

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↗

PubMed2002

Retinal vascular tree morphology: a semi-automatic quantification.

A semi-automatic method to measure and quantify geometrical and topological properties of continuous vascular trees in clinical fundus images is described. Measurements are made from binary images obtained with a previously described segmentation process. The skeletons of the segmented trees are produced by thinning,ff branch and crossing points are identified and segments of the trees are labeled and stored as a chain code. The operator selects a tree to be measured and decides if it is an arterial or venous tree. An automatic process then measures the lengths, areas and angles of the individual segments of the tree. Geometrical data and the connectivity information between branches from continuous retinal vessel trees are tabulated. A number of geometrical properties and topological indexes are derived. Vessel diameters and branching angles are validated against manual measurements and several derived geometrical and topological properties are extracted from red-free fundus images of ten normotensive and ten age- and sex-matched hypertensive subjects and compared with previously reported results.

Adult↗

PubMed2002

Is carotid artery intima-media thickening a reliable marker of early atherosclerosis?

BACKGROUND: It is widely believed that carotid artery intima-media thickening represents an early marker for the development of atheroma. However, carotid intima-media thickening might also be expected to occur in response to an increased tensile stress and decreased wall shear stress which may accompany physical exercise. DESIGN, METHODS, AND RESULTS: In order to test this hypothesis 24 athletes (professional footballers) were compared to 14 age and sex matched control subjects. Each subject underwent carotid and femoral ultrasonography and echocardiography. The athletes had a greater left ventricular mass index compared with the controls: 135 (127-143) vs. 104 (91-116) g/m2, p < 0.001. In addition, they had a greater carotid intima-media thickness (IMT): 0.55 (0.52-0.57) vs. 0.51 (0.48-0.54) mm, p < 0.05. However, carotid artery diameters, femoral IMT and femoral artery diameters were similar: 6.0 (5.9-6.2) vs. 5.8 (5.6-6.1) mm, 0.43 (0.42-0.45) vs. 0.43 (0.41-0.45) mm and 8.3 (8.0-8.6) vs. 8.4 (8.0-8.7) mm, respectively. CONCLUSIONS: The increased carotid IMT of the athletes may result from intermittent exposure to markedly elevated systemic arterial pressures during exercise, resulting in intermittent elevations in carotid wall tensile stress. The lack of a disparity between athletes and controls for femoral IMT may be explained by the intermittent elevation of femoral wall tensile stress being accompanied by increased femoral artery blood flow and wall shear stress, which would tend to reduce any wall thickening. This is an important observation, since it suggests that an increased carotid IMT cannot be relied on solely as a marker of early atherosclerosis.

Adolescent↗