Showing papers by "Bruce Neal published in 2005"
TL;DR: 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.
Abstract: 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.
814 citations
TL;DR: These results indicate that an active blood pressure–lowering regimen stopped or delayed the progression of white matter hyperintensities in patients with cerebrovascular disease.
Abstract: BACKGROUND: The prevalence of white matter hyperintensities (WMHs) detected on cerebral MRI is associated with hypertension, but it is not known whether blood pressure lowering can arrest their progression. We report here the results of an MRI substudy of PROGRESS (Perindopril Protection Against Recurrent Stroke Study), a randomized trial of blood pressure lowering in subjects with cerebrovascular disease. METHODS AND RESULTS: The substudy comprised 192 participants who had a cerebral MRI both at baseline and after a mean follow-up time of 36 months (SD=6.0 months). At the first MRI, WMHs were graded with a visual rating scale from A (no WMH) to D (severe WMH). Participants were assigned to a combination of perindopril plus indapamide (or their placebos; 58%) or to single therapy with perindopril (or placebo). At the time of the second MRI, the blood pressure reduction in the active arm compared with the placebo arm was 11.2 mm Hg for systolic blood pressure and 4.3 mm Hg for diastolic blood pressure. Twenty-four subjects (12.5%) developed new WMHs at follow-up. The risk of new WMH was reduced by 43% (95% CI -7% to 89%) in the active treatment group compared with the placebo group (P=0.17). The mean total volume of new WMHs was significantly reduced in the active treatment group (0.4 mm3 [SE=0.8]) compared with the placebo group (2.0 mm3 [SE=0.7]; P=0.012). This difference was greatest for patients with severe WMH at entry, 0.0 mm3 (SE=0) in the active treatment group versus 7.6 mm3 (SE=1.0) in the placebo group (P<0.0001). CONCLUSIONS: These results indicate that an active blood pressure-lowering regimen stopped or delayed the progression of WMHs in patients with cerebrovascular disease.
437 citations
TL;DR: Several prospective studies have shown significant associations between plasma fibrinogen, viscosity, C-reactive protein (CRP), Fibrin d-dimer, or tissue plasminogen activat...
Abstract: Background and Purpose— Several prospective studies have shown significant associations between plasma fibrinogen, viscosity, C-reactive protein (CRP), fibrin d-dimer, or tissue plasminogen activat...
115 citations
TL;DR: For most patients with atrial fibrillation, routine blood pressure-lowering is likely to provide protection against major vascular events additional to that conferred by anticoagulation.
Abstract: Background and Purpose—Patients with atrial fibrillation have a high risk of stroke and other vascular events even if anticoagulated. The primary objective here is to determine whether routine blood pressure–lowering provides additional protection for this high-risk patient group. Methods—This study was a subsidiary analysis of the Perindopril Protection Against Recurrent Stroke Study (PROGRESS)—a randomized, placebo-controlled trial that established the beneficial effects of blood pressure–lowering in a heterogeneous group of patients with cerebrovascular disease. A total of 6105 patients were randomly assigned to either active treatment (2 to 4 mg perindopril for all participants plus 2.0 to 2.5 mg indapamide for those without an indication for or a contraindication to a diuretic) or matching placebo(s). Outcomes are total major vascular events, cause-specific vascular outcomes, and death from any cause. Results—There were 476 patients with atrial fibrillation at baseline, of whom 51% were taking anticoagulants. In these patients, active treatment lowered mean blood pressure by 7.3/3.4 mm Hg and was associated with a 38% (95% confidence interval [CI], 6 to 59) reduction in major vascular events and 34% (95% CI, 13 to 61) reduction in stroke. The benefits of blood pressure–lowering in patients with atrial fibrillation were achieved irrespective of the use of anticoagulant therapy (P homogeneity0.8) or the presence of hypertension (P homogeneity0.4). Conclusions—For most patients with atrial fibrillation, routine blood pressure–lowering is likely to provide protection against major vascular events additional to that conferred by anticoagulation. (Stroke. 2005;36:2164-2169.)
109 citations
TL;DR: NT-proBNP and renin are independent predictors of MI risk after stroke or transient ischemic attack, providing information additional to that provided by classic risk factors, and may enable more effective targeting of MI prevention strategies.
Abstract: Background— B-type natriuretic peptide (BNP), C-reactive protein (CRP), and renin are elevated in persons at risk for cardiovascular disease. However, data that directly compare these markers in the prediction of myocardial infarction (MI) are limited. Methods and Results— N-terminal-proBNP (NT-proBNP), CRP, and renin were measured in baseline blood samples from a nested case-control study of the 6105 participants of the Perindopril Protection Against Recurrent Stroke Study (PROGRESS), a placebo-controlled study of a perindopril-based blood pressure-lowering regimen among individuals with previous stroke or transient ischemic attack. Each of 206 subjects who experienced MI, either fatal or nonfatal, during a mean follow-up of 3.9 years was matched to 1 to 3 control subjects. Most MI cases (67%) occurred in subjects without a history of coronary heart disease. NT-proBNP, CRP, and renin each predicted MI; the odds ratio for subjects in the highest compared with the lowest quarter was 2.2 (95% CI, 1.3 to 3.6...
82 citations
TL;DR: In both white and Asian populations, there is compelling epidemiological evidence of continuous associations between usual blood-pressure values and the risks of major cardiovascular diseases and the value of categorical systems for the classification of blood- pressure values is questionable.
60 citations
TL;DR: The ADVANCE trial as discussed by the authors is a 2 × 2 factorial randomized controlled trial, where participants were randomized to perindopril/indapamide (initially 2.0/0.625 mg daily, increasing to 4.0 /1.25 mg daily after 3 months) or matching placebo; and to an intensive gliclazide MR-based glucose control regimen aiming for a haemoglobin A1c (HbA1c) value of 6.5% or lower, or local standard therapy.
Abstract: Aims The primary aim of ADVANCE is to determine the effects on macrovascular and microvascular disease of blood pressure lowering (with an ACE inhibitor–diuretic combination), irrespective of initial blood pressure level; and of intensive glucose lowering, in high-risk individuals with Type 2 diabetes. Methods The study is a 2 × 2 factorial randomized controlled trial. Following 6 weeks on active perindopril–indapamide combination, eligible participants were randomized to perindopril/indapamide (initially 2.0/0.625 mg daily, increasing to 4.0/1.25 mg daily after 3 months) or matching placebo; and to an intensive gliclazide MR-based glucose control regimen aiming for a haemoglobin A1c (HbA1c) value of 6.5% or lower, or local standard therapy. The study is being conducted in 215 centres in 20 countries within Australasia, Asia, Europe and North America. Results Recruitment commenced in June 2001 and was completed in March 2003, with the inclusion of 11 140 randomized participants. Fifty-seven per cent of participants are male and the mean age at baseline was 66 years. On average, the diagnosis of diabetes was made 8 years before study entry. At baseline 32 and 10% of patients had a history of macrovascular and microvascular disease, respectively. The mean blood pressure at baseline was 145/81 mmHg; the mean HbA1c concentration was 7.5%. While blood pressure and HbA1c values were broadly similar, certain characteristics of randomized participants varied between countries. Conclusions With successful worldwide recruitment completed, ADVANCE should provide reliable and broadly generalizable results on the effects of routine blood pressure lowering and intensive glucose control in high-risk individuals with Type 2 diabetes.
57 citations
TL;DR: Lipid variables are associated with the risk of MI, but not recurrent stroke, in patients with established cerebrovascular disease.
Abstract: Aims To evaluate the role of plasma lipids in recurrent vascular events, including stroke, among individuals with established cerebrovascular disease.
Methods and results Plasma total cholesterol, HDL cholesterol, and triglycerides were measured at baseline among individuals participating in the Perindopril Protection Against Recurrent Stroke (PROGRESS) study, a randomized clinical trial of blood pressure lowering among patients with previous stroke or transient ischaemic attack. A series of nested case–control studies were used to investigate the association between each of these lipid variables and the risk of subsequent haemorrhagic stroke, ischaemic stroke, myocardial infarction (MI), and heart failure. A total of 895 patients were selected as cases (83 haemorrhagic stroke, 472 ischaemic stroke, 206 MI, and 258 heart failure) and each was matched with one to three controls. After adjustment for other major cardiovascular risk factors, none of the lipid variables was associated with the risk of either stroke subtype. There were significant positive and negative associations for total cholesterol and HDL, respectively, with the risk of MI; the odds ratio comparing the highest and lowest thirds of each of these lipid variables was 2.00 (95% CI: 1.30–3.09) for total cholesterol and 0.58 (95% CI: 0.37–0.90) for HDL. HDL was inversely associated with the risk of heart failure; however, this result was of borderline statistical significance ( P =0.05).
Conclusion Lipid variables are associated with the risk of MI, but not recurrent stroke, in patients with established cerebrovascular disease.
44 citations
TL;DR: It is concluded that NT-proBNP and CRP are independent predictors of CHF risk after stroke or TIA and may be markers of mechanisms ofCHF pathogenesis distinct from those responsive to angiotensin-converting enzyme inhibitor–based therapy.
Abstract: B-type natriuretic peptide (BNP) and C-reactive protein (CRP) are elevated in persons at risk for congestive heart failure (CHF). However, limited data are available directly comparing BNP-related peptides and CRP in persons at risk of CHF. To evaluate amino terminal-pro-BNP (NT-proBNP) and CRP, separately and together, for assessment of risk of CHF, we performed a nested case-control study of the 6105 participants of the Perindopril pROtection aGainst REcurrent Stroke Study (PROGRESS), a placebo-controlled study of a perindopril-based blood pressure-lowering regimen among individuals with previous stroke or transient ischemic attack (TIA). Each of 258 subjects who developed CHF resulting in death, hospitalization, or withdrawal of randomized therapy during a mean follow-up of 3.9 years was matched to 1 to 3 control subjects. NT-proBNP and CRP predicted CHF; the odds ratio for subjects in the highest compared with the lowest quarter was 4.5 (95% confidence interval, 2.7 to 7.5) for NT-proBNP and 2.9 (confidence interval, 1.9 to 4.7) for CRP, and each remained a predictor of CHF after adjustment for all other predictors. Screening for both markers provided better prognostic information than screening for either alone. Elevation of NT-proBNP above 50 pmol/L and CRP above 0.84 mg/L predicted CHF with sensitivity of 64% and specificity of 66%. NT-proBNP and CRP predicted CHF in subjects receiving perindopril-based therapy. We conclude that NT-proBNP and CRP are independent predictors of CHF risk after stroke or TIA. Moreover, NT-proBNP and CRP may be markers of mechanisms of CHF pathogenesis distinct from those responsive to angiotensin-converting enzyme inhibitor-based therapy.
43 citations
TL;DR: Waist circumference and WHR were more strongly associated with fasting plasma glucose and diabetes than were weight and BMI, and are likely to be more useful for assessing the obesity-related risk of cardiovascular diseases in Asian populations.
Abstract: Aims/hypothesis
Asian populations have high risks of disease at low levels of BMI and weight, possibly because of high rates of abdominal obesity. In such populations, waist circumference and WHR (measures of fat distribution) may better capture the effects of adiposity.
Journal Article•
TL;DR: Urgent strategies are required to prevent increasing levels of dyslipidaemia in Thailand, as well as to develop and promulgate treatment guidelines that incorporate locally-relevant risk prediction functions.
Abstract: The authors' objective was to describe the distribution of serum lipids and the prevalence of dyslipidaemia using US lipid-lowering guidelines in an adult Thai population. Fasting serum lipids were measured in a population-based survey that included 5305 rural and urban Thai adults aged 335 years. The US National Cholesterol Education Program (NCEP) guidelines were used to determine the eligibility of each individual for lipid-lowering therapy. Compared with urban residents, rural residents had lower mean levels of total cholesterol (men. 4.80 vs 5.54 mmol/L, women: 5.18 vs 5.71 mmol/L, both p < 0.001) and high density lipoprotein cholesterol (men: 1.06 vs 1.19 mmol/L, women: 1.13 vs 1.34 mmol/L, both p < 0.001). Mean triglyceride levels were higher in rural compared to urban populations, for both men (2.15 vs 1.88 mmol/L, p = 0.001) and women (1. 73 vs 1.51 mmol/L, p = 0.01). Direct application of the NCEP guidelines identified up to 37% of the adult population (or 10 million adult Thais) as eligible for lipid-lowering drug therapy, which is an unfeasibly high proportion of the population. Urgent strategies are required to prevent increasing levels of dyslipidaemia in Thailand, as well as to develop and promulgate treatment guidelines that incorporate locally-relevant risk prediction functions.
TL;DR: The authors imply that preventive measures in the elderly might reasonably be narrowed to focus on a few selected determinants of disease, with the specific clinical recommendation that ‘above all, the importance of regular physical exercise’ should be highlighted.
01 Jan 2005
TL;DR: Benetos et al. as mentioned in this paper report the findings of a cohort study performed in an older patient group and conclude that their study ‘demonstrates important changes in the role of certain major classical risk factors in older compared to younger individuals.
Abstract: With a progressively ageing global population [1], precise and reliable information about the determinants of death and disease in the elderly are of increasing consequence. In this issue of the journal Benetos et al. [2] report the findings of a cohort study performed in an older patient group and conclude that their study ‘demonstrates important changes in the role of certain major classical risk factors’ in older compared to younger individuals. The authors also imply that preventive measures in the elderly might reasonably be narrowed to focus on a few selected determinants of disease, with the specific clinical recommendation that ‘above all, the importance of regular physical exercise’ should be highlighted.