Publications (3)14.46 Total impact

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    ABSTRACT: Background: Although all guidelines recommend initiation of drug treatment in all individuals with SBP>140 or DBP>90mmHg, it has recently been remarked that this recommendation is not evidence-based. A recent reappraisal of the European guidelines has recommended this matter should be approached by an adequate trial. We have attempted to get some information by a subanalysis of the FEVER study. Methods: The FEVER trial included 9711 hypertensive patients from China, all pretreated with 12.5 mg/day hydrochlorothiazide, and then randomized to addition of either felodipine (F) 5 mg/day or placebo(P). The F group with a mean on-treatment SBP/DBP137.5/82.5mmHg had a significant reduction(26 to 35%) of each of several major cardiovascular outcomes compared with the P group (SBP/DBP142.1/84.5mmHg). Cox regression models were used to assess differences between treatments in subgroups of patients with and without history or signs of cardiovascular events and diabetes. Results: There were 4850 patients without history and signs of cardiovascular events and diabetes. These patients could be defined as at an average low cardiovascular risk since incidence of total cardiovascular events in the P group was below the usual cut off of 15% in 10 years. In these “low” risk hypertensives reduction of SBP/DBP to138.1/82.8mmHg in the F group rather than 141.9/85.1 in the P group was accompanied by reductions of all cardiovascular events by 39% (17 to 55%, p = 0.0015) and of all deaths by 43% (14 to 61%, p = 0.0081). By contrast, in the equally large subgroup of patients having either cardiovascular disease or diabetes (n = 4861), who could therefore be defined as at “high” risk, reduction of SBP/DBP to 138.0/82.4 mmHg in the F group reduced all cardiovascular events by 20% (1 to 35%, p = 0.00431), strokes by 22% (p = 0.0571), cardiovascular deaths by 24% (p = 0.1518). Conclusions: This analysis of FEVER data clearly indicates significant benefits of small BP differences, as well as lowering SBP/DBP below 140/85 mmHg in hypertensive patients at relatively low risk because of absence of cardiovascular disease and diabetes.
    Journal of Hypertension 06/2010; 28. DOI:10.1097/01.hjh.0000378900.35954.9a · 4.22 Impact Factor
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    ABSTRACT: High and low blood pressure (BP) levels are common following acute stroke, with up to 60% of patients being hypertensive (SBP > 160 mmHg) and nearly 20% having relative hypotension (SBP < or = 140 mmHg), within the first few hours of ictus, both conditions being associated with an adverse prognosis. At present, the optimum management of blood pressure in the immediate post-stroke period is unclear. The primary aim of the Controlling Hypertension and Hypotension Immediately Post-Stroke (CHHIPS) Pilot Trial is to assess whether hypertension and relative hypotension, manipulated therapeutically in the first 24 h following acute stroke, affects short-term outcome measures. The CHHIPS Pilot Trial is a UK based multi-centre, randomized, double-blind, placebo-controlled, titrated dose trial. Acute stroke and medical units in teaching and district general hospitals, in the UK. The CHHIPS Pilot Study aims to recruit 2050 patients, with clinically suspected stroke, confirmed by brain imaging, who have no compelling indication or contraindication for BP manipulation. The primary outcome measure will be the effects of acute pressor therapy (initiated < or = 12 h from stroke onset) or depressor therapy (started < or = 24 h post-ictus) on death and dependency at 14 days post-stroke. Secondary outcome measures will include the influence of therapy on early neurological deterioration, the effectiveness of treatment in manipulating BP levels, the influence of time to treatment and stroke type on response and a cost-effectiveness analysis.
    Journal of Hypertension 03/2005; 23(3):649-55. · 4.22 Impact Factor
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    ABSTRACT: Genetic influences are important in multifactorial cerebral small-vessel disease (SVD) and may act via endothelial dysfunction. Nitric oxide (NO) synthesized by endothelial nitric oxide synthase (eNOS) is a key mediator of endothelial function. We determined the role of 3 potentially functional eNOS polymorphisms (T-786C, intron 4ab, G894T) located toward the 5' flanking end of the gene as risk factors for SVD and different SVD subtypes: isolated lacunar infarction (n=137) and ischemic leukoaraiosis (n=160). Three hundred patients with SVD and 600 community controls were studied. Genotypes were determined through polymerase chain reaction with or without restriction fragment digestion. Nitrate (NO(x)) levels were determined in a subgroup by use of a Griess method. Polymorphisms were tested individually and in combination with haplotype analysis. The intron 4a variant was protective against SVD. This effect was confined to isolated lacunar infarction (odds ratio, 0.55; 95% confidence interval, 0.35 to 0.86; P=0.01). Haplotypes encountered were significantly different in this subtype compared with controls (P=0.001), with the -786C promoter/intron 4a combination particularly underrepresented. NO(x) levels were associated with the T-786C locus (P=0.03) but only in the presence of the intron 4a allele (P=0.07 for interaction). The intron 4ab insertion/deletion genotype was associated with isolated lacunar infarction. Haplotype and functional studies suggested that the protective effect of the 4a variant could be mediated through changes in eNOS promoter activity and increased NO levels. The specific association with isolated symptomatic lacunar infarction and not ischemic leukoaraiosis may reflect different etiopathogeneses of the 2 subtypes. Lack of NO could predispose to localized microatheroma in proximal arterioles rather than diffuse arteriosclerosis affecting distal perforating vessels.
    Stroke 04/2004; 35(3):654-9. DOI:10.1161/01.STR.0000117238.75736.53 · 6.02 Impact Factor