Summary Background Raised blood pressure is common in acute stroke, and is associated with an increased risk of poor outcomes. We aimed to examine whether careful blood-pressure lowering treatment ...with the angiotensin-receptor blocker candesartan is beneficial in patients with acute stroke and raised blood pressure. Methods Participants in this randomised, placebo-controlled, double-blind trial were recruited from 146 centres in nine north European countries. Patients older than 18 years with acute stroke (ischaemic or haemorrhagic) and systolic blood pressure of 140 mm Hg or higher were included within 30 h of symptom onset. Patients were randomly allocated to candesartan or placebo (1:1) for 7 days, with doses increasing from 4 mg on day 1 to 16 mg on days 3 to 7. Randomisation was stratified by centre, with blocks of six packs of candesartan or placebo. Patients and investigators were masked to treatment allocation. There were two co-primary effect variables: the composite endpoint of vascular death, myocardial infarction, or stroke during the first 6 months; and functional outcome at 6 months, as measured by the modified Rankin Scale. Analyses were by intention to treat. The study is registered, number NCT00120003 ( ClinicalTrials.gov ), and ISRCTN13643354. Findings 2029 patients were randomly allocated to treatment groups (1017 candesartan, 1012 placebo), and data for status at 6 months were available for 2004 patients (99%; 1000 candesartan, 1004 placebo). During the 7-day treatment period, blood pressures were significantly lower in patients allocated candesartan than in those on placebo (mean 147/82 mm Hg SD 23/14 in the candesartan group on day 7 vs 152/84 mm Hg 22/14 in the placebo group; p<0·0001). During 6 months' follow-up, the risk of the composite vascular endpoint did not differ between treatment groups (candesartan, 120 events, vs placebo, 111 events; adjusted hazard ratio 1·09, 95% CI 0·84–1·41; p=0·52). Analysis of functional outcome suggested a higher risk of poor outcome in the candesartan group (adjusted common odds ratio 1·17, 95% CI 1·00–1·38; p=0·048 not significant at p≤0·025 level). The observed effects were similar for all prespecified secondary endpoints (including death from any cause, vascular death, ischaemic stroke, haemorrhagic stroke, myocardial infarction, stroke progression, symptomatic hypotension, and renal failure) and outcomes (Scandinavian Stroke Scale score at 7 days and Barthel index at 6 months), and there was no evidence of a differential effect in any of the prespecified subgroups. During follow-up, nine (1%) patients on candesartan and five (<1%) on placebo had symptomatic hypotension, and renal failure was reported for 18 (2%) patients taking candesartan and 13 (1%) allocated placebo. Interpretation There was no indication that careful blood-pressure lowering treatment with the angiotensin-receptor blocker candesartan is beneficial in patients with acute stroke and raised blood pressure. If anything, the evidence suggested a harmful effect. Funding South-Eastern Norway Regional Health Authority; Oslo University Hospital Ullevål; AstraZeneca; Takeda.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Lowering blood pressure (BP) in stroke survivors reduces the risk of recurrent stroke. We tested the hypothesis that a nurse-led nonpharmacologic intervention would lower the BP of participants in an ...intervention group compared with a control group. A total of 349 patients who had sustained acute stroke or transient ischemic attack were randomly assigned to either usual care or to 4 home visits by a nurse. During the visits, the nurse measured and recorded BP and provided individually tailored counseling on a healthy lifestyle. A total of 303 patients completed the 1-year follow up. No change in systolic BP was noted in either the intervention group or the control group. Because of an increase in diastolic BP in the control group ( P = .03), a difference in mean diastolic BP between the 2 groups was found at follow-up ( P = .007). Mean BP at follow-up was 139/82 mm Hg in the intervention group and 142/86 mm Hg in the control group. Linear regression analysis demonstrated that BP at the point of discharge was the strongest predictor of BP 1 year later ( P < .0001). The proportion of patients on antihypertensive medication increased in the intervention group ( P = .002). Patients were compliant with antihypertensive therapy, and 92% of the hypertensive patients in the intervention group followed the advice to see a general practitioner (GP) for BP checkups. At follow-up, 187 patients (62%) were hypertensive, with no difference in the rate of hypertension seen between the groups. Our data indicate that home visits by nurses did not result in a lowering of BP. Patients complied with antihypertensive therapy and GP visits in the case of hypertension. Nonetheless, the majority of patients were hypertensive at the 1-year follow up.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Background: The adrenal glucocorticoid stress response in humans causes catabolism, increasing blood glucose and heart rate, and possibly potentiates ischaemic damage to neurons. These effects could ...induce secondary brain damage in acute stroke.
Materials and Methods: This prospective study was based on a single determination of s-cortisol in 172 patients included within 24 h of stroke onset, 50% within 12 h of stroke onset. All patients were admitted to hospital within 6 h of stroke onset. We investigated the relations of s-cortisol to neurological deficit measured by Scandinavian Stroke Scale (SSS), lesion volume on CT-scan, blood glucose on admission, pulse rate, blood pressure, body temperature, deteriorating stroke, cytokines and cytokine receptors, and outcome.
Results: In a multivariate logistic regression analysis, s-cortisol was independently related to death within 7 days of stroke onset, odds ratio (OR) Cortisol
+100 nmol/l 1.9 (95% CI 1.01–3.8); serum-cortisol was, however, not a predictor of death or dependency within 3 months. S-cortisol correlated to SSS (
ρ=−0.45,
p<0.001), body temperature (
ρ=0.27,
p<0.001), pulse rate (
ρ=0.26,
p<0.001), and lesion volume (
ρ=0.33,
p<0.001). S-cortisol was related to the presence of insular damage.
Conclusion: Acute stroke mortality related to increasing serum-cortisol levels. S-cortisol was associated with stroke severity and markers reflecting stroke severity.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The goals of this work were to investigate whether elevated total homocysteine (tHcy) measured within 24 hours of acute stroke was an independent risk factor for recurrent stroke and to compare ...levels of tHcy in groups of patients with diagnoses of ischemic and hemorrhagic cerebrovascular events.
We performed a longitudinal study of 1039 stroke patients (mean age, 75 years). Fasting tHcy was measured the morning after primary admission. Patients were followed up for 15 months.
Serum homocysteine was significantly higher in the 105 patients who experienced a recurrent stroke during the follow-up period than in patients without recurrence. The geometric mean+/-SD was 13.4+/-10.7 versus 11.8+/-7.1 micromol/L (P=0.008), and the mean difference was 1.2 micromol/L 95% confidence interval (CI), 1.05 to 2.3. In a multiple logistic regression model, tHcy was an independent explanatory variable of recurrent stroke within 15 months (odds ratio, 1.3; 95% CI, 1.1 to 1.5) for each increase in tHcy of 10 micromol/L. At the index event, serum homocysteine was significantly higher in 909 patients with ischemic cerebrovascular events than in 130 patients with intracerebral hemorrhage (geometric mean, 12.1+/-7.3 versus 10.4+/-5.2 micromol/L; P<0.001).
The data in this study indicate that elevated tHcy is an independent risk factor for recurrent stroke.
Levels of C-reactive protein (CRP) and white blood cell count (WBC) in acute stroke may reflect the stroke lesion itself or pre-existing factors such as infections, smoking or atherosclerosis. The ...aim of this study was to investigate the relation between CRP and WBC levels and time from onset of stroke, stroke severity and outcome.
The analyses were based on 719 patients in whom WBC test material was obtained within 9 h of stroke onset and CRP test material within 24 h of stroke onset. Stroke severity was assessed by the Scandinavian Stroke Scale Score on admission and outcome by death 7 days, 3 months and 1 year after symptom onset as well as modified Rankin Scale 3 months after stroke onset.
CRP and WBC levels correlated significantly with time from symptom onset as well as with stroke severity and outcome. Levels of CRP and WBC were higher in later determinations in severe stroke. In multivariate logistic regression analysis, CRP(+10 mg/l) was independently related to 1-year mortality (OR 1.1, 95% CI 1.02-1.2).
Levels of WBC and CRP increase within the first 24 h in patients with severe stroke. CRP but not WBC is related to long-term mortality possibly by reflecting the vascular risk profile.
A poor outcome after stroke is associated independently with high blood pressure during the acute phase; however, relationships with other haemodynamic measures heart rate (HR), pulse pressure (PP), ...rate-pressure product (RPP) remain less clear.
The Tinzaparin in Acute Ischaemic Stroke Trial is a randomised, controlled trial assessing the safety and efficacy of tinzaparin versus aspirin in 1484 patients with acute ischaemic stroke. Systolic blood pressure (SBP), diastolic blood pressure (DBP) and HR measurements taken immediately prior to randomization were averaged, and the mid-blood pressure (MBP), PP, mean arterial pressure (MAP), pulse pressure index, and RPP were calculated. The relationship between these haemodynamic measures and functional outcome (death or dependency, modified Rankin Scale > 2) and early recurrent stroke, were studied with adjustment for baseline prognostic factors and treatment group. Odds ratios (OR) and 95% confidence intervals (CI) refer to a change in haemodynamic measure by 10 points.
A poor functional outcome was associated with SBP (adjusted OR; 1.11; 95% CI, 1.03-1.21), HR (adjusted OR; 1.15; 95% CI, 1.00-1.31), MBP (adjusted OR; 1.15, 95% CI, 1.03-1.29), PP (adjusted OR; 1.14; 95% CI, 1.02-1.26), MAP (adjusted OR; 1.15; 95% CI, 1.02-1.31) and RPP (adjusted OR; 1.01; 95% CI, 1.00-1.02). Early recurrent stroke was associated with SBP, DBP, MBP and MAP.
A poor outcome is independently associated with elevations in blood pressure, HR and their derived haemodynamic variables, including PP and the RPP. Agents that modify these measures may improve functional outcome after stroke.
Background Reduced lung function has been shown to be a significant predictor of non-fatal ischaemic heart disease, and of mortality due to cardiovascular disease. Fewer studies have analysed the ...relationship between lung function and risk of fatal or non-fatal stroke. The present study presents results on the relation between forced expiratory volume in one second (FEV1) and risk of incident and fatal first-ever stroke. Subjects and Methods The analyses are based on prospective cohort data from 12 878 eligible men and women aged 45–84 years, who participated in the first health examination of the Copenhagen City Heart Study in 1976–1978. The subjects were followed from day of entry until 31 December 1993. During that period 808 first-ever strokes occurred of which 153 were fatal within 28 days. Risk of incident and fatal stroke was estimated by means of Cox hazard regression. The analyses included adjustment for potential confounders: sex, age, smoking, inhalation, body mass index, systolic blood pressure, triglycerides, physical activity in leisure time, education, diabetes mellitus, and antihypertensive treatment. Results We found an inverse association between FEV1 and risk of first-time stroke. For each 10% decrease in FEV1 in percentage of expected, the relative risk (RR) increased 1.05 (95% CI : 1.00–1.09, P = 0.03). This represents an approximately 30% higher risk of stroke in the group of people with the lowest lung function as compared to the group with the highest lung function. The association between lung function and risk of fatal stroke resembled that of risk of incident stroke (fatal and non-fatal). The RR was 1.11 (95% CI : 1.03–1.19) for each 10% decrease in FEV1 in percentage of expected. This represents approximately a doubling of the risk between the highest and lowest lung function groups. Conclusions This study shows that reduced lung function measured in percentage of predicted FEV1 is a predictor of first-time stroke and fatal stroke independent of smoking and inhalation. The high risk of fatal first-ever stroke in the group of people with low lung function may be of significance in both the design and interpretation of clinical trials.
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