Long-term risk factors of recurrent stroke, myocardial infarction and death in patients leaving hospital with a diagnosis of ischemic stroke or TIA.

Objectives. The prevalence of patients with prior stroke is increasing globally. Accordingly, there is a need for up-to-date evidence of patient-related prognostic factors for stroke recurrence, post stroke myocardial infarction (MI) and death based on long-term follow-up of stroke survivors. For this purpose, the RIALTO study was established in 2004. Design. A prospective cohort study in which patients diagnosed with ischemic stroke (IS) or transient ischemic attack (TIA) in three Copenhagen hospitals were included. Data were collected from medical records and by structured interview. Data on first stroke recurrence, first MI and all-cause death were extracted from the Danish National Patient Registry and the Danish Civil Registration System. Results. We included 1215 patients discharged after IS or TIA who were followed up by register data from April 2004 to end of 2018 giving a median follow-up of 3.5-6.9 years depending on the outcome. At the end of follow-up 406 (33%) patients had been admitted with a recurrent stroke, 100 (8%) had a MI and 822 (68%) had died. Long-term prognostic predictors included body mass index, diabetes, antihypertensive and lipid lowering treatment, smoking, a sedentary lifestyle as well as poor self-rated health and psychosocial problems. Conclusions. Long-term risk of recurrent stroke and MI remain high in patients discharged with IS or TIA despite substantial improvements in tertiary preventive care in recent decades. Continued attention to the patient risk profile among patients surviving the early phase of stroke, including comorbidities, lifestyle, and psychosocial challenges, is warranted.

Effects of candesartan in acute stroke on vascular events during long-term follow-up: results from the Scandinavian Candesartan Acute Stroke Trial (SCAST).

BACKGROUND: Randomized-controlled trials have shown no beneficial short-term effects of blood pressure lowering treatment in the acute phase of stroke. AIM: We aimed to see whether blood pressure lowering treatment with candesartan in the acute phase can lead to benefits that become apparent over a longer period of follow-up. METHODS: The Scandinavian Candesartan Acute Stoke Trial was a randomized- and placebo-controlled trial of candesartan in 2,029 patients with acute stroke and systolic blood pressure ≥140 mmHg. Trial treatment was given for seven-days, and the primary follow-up period was six-months. We have used the national patient registries and the cause of death registries in the Scandinavian countries to collect data on vascular events and deaths up to three-years from randomization. The primary end-point was the composite of stroke, myocardial infarction, or vascular death, and we used Cox proportional hazards regression model for analysis. RESULTS: Long-term data were available for 1,256 of the 1,286 patients (98%) from Scandinavia. The risk of the primary composite end-point did not differ significantly between the groups (candesartan 178/632 events, placebo 203/624 events, hazard ratio = 0·87, 95% confidence interval 0·71-1·07). There were also no statistically significant differences for the secondary end-points stroke and all-cause death, or in any of the pre-specified subgroups. CONCLUSIONS: Treatment with candesartan in the acute phase of stroke was not associated with clear long-term clinical benefits. This result supports the conclusion from trials with short-term follow-up, that blood pressure lowering treatment with candesartan should not be given routinely to patients with acute stroke and raised blood pressure.

Specific antismoking advice after stroke.

INTRODUCTION: Many stroke survivors would benefit from modification of their lifestyle in order to reduce their risk of recurrent stroke. We investigated if tailored smoking cessation advice would yield a higher smoking cessation rate and a higher rate with sustained abstinence in ex-smokers in the intervention group than among controls. MATERIAL AND METHODS: Patients admitted with an acute stroke or a transient ischaemic attack were included in a randomised controlled trial focusing on control of lifestyle risk factors and hypertension. Here, we report the intervention focused on smoking cessation. We used multiple logistic regression analysis to identify patient characteristics associated with smoking cessation. Analyses were by intention to treat excluding those who died or suffered severe disease. RESULTS: We included 254 patients with a history of smoking. Two years after inclusion, 15 of 57 (26%) baseline smokers in the intervention group had stopped smoking versus eight of 56 (14%) among controls (p = 0.112). Living with a partner (p = 0.012), having at least ten years of education (p = 0.012), and not being exposed to smoking at home (p = 0.036) were independent predictors of smoking cessation. CONCLUSION: We did not achieve our aim of higher smoking cessation rates in the intervention group. Future smoking cessation interventions should be more intensive, focus on patients' social circumstances and, if possible, involve patients' relatives. FUNDING: This study was supported by the Ludvig and Sara Elsass Foundation, the Lundbeck Foundation and The Danish Heart Foundation (Grant 07-4-B703-A1378-22384F). TRIAL REGISTRATION: This protocol is registered with Clinical Trials.gov (NCT 00253097).

The angiotensin-receptor blocker candesartan for treatment of acute stroke (SCAST): a randomised, placebo-controlled, double-blind trial.

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.

Blood pressure 1 year after stroke: the need to optimize secondary prevention.

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.

Angiotensin receptor blockade in acute stroke. The Scandinavian Candesartan Acute Stroke Trial: rationale, methods and design of a multicentre, randomised- and placebo-controlled clinical trial (NCT00120003).

BACKGROUND: Elevated blood pressure following acute stroke is common, and yet early antihypertensive treatment is controversial. ACCESS suggested a beneficial effect of the angiotensin receptor blocker candesartan in the acute phase of stroke, but these findings need to be confirmed in new, large trials. AIMS AND DESIGN: The Scandinavian Candesartan Acute Stroke Trial is an international randomised, placebo-controlled, double-blind trial of candesartan in acute stroke. We plan to recruit 2500 patients presenting within 30 h of stroke (ischaemic or haemorrhagic) and with systolic blood pressure ≥140 mmHg. The recruited patients are randomly assigned to candesartan or placebo for 7-days (doses increasing from 4 to 16 mg once daily). Randomisation is performed centrally via a secure web interface. The follow-up period is 6-months. Patients are included from the following nine North-European countries: Norway, Sweden, Denmark, Belgium, Germany, Poland, Lithuania, Estonia and Finland. STUDY OUTCOMES: There are two co-primary effect variables: • Functional status at 6-months, measured by the modified Rankin Scale, and • vascular death, myocardial infarction or stroke during the first 6-months. Secondary outcome variables: Secondary effect variables include • the Barthel index (functional status) • EuroQol (quality of life) and • Mini-mental state examination (cognition) at 6-months • Health economic costs during the first 6-months FUNDING: The Scandinavian Candesartan Acute Stroke Trial receives basic funding from Norwegian health authorities. AstraZeneca supplies the trial drugs, and AstraZeneca and Takeda support the trial with limited, unrestricted grants. SUMMARY: The Scandinavian Candesartan Acute Stroke Trial is the first large trial of angiotensin receptor blockers in patients with elevated blood pressure and acute stroke, and aims to answer whether treatment with angiotensin receptor blockers is beneficial for this indication.

Little change of modifiable risk factors 1 year after stroke: a pilot study.

BACKGROUND: Recurrent stroke accounts for about 25% of admissions for acute stroke. For the prevention of recurrent cerebro and cardiovascular disease, stroke patients are advised to change modifiable stroke risk factors before discharge from stroke units. AIMS: To investigate the change in modifiable risk factors 1 year after stroke and to explore the feasibility of a preventive programme aimed at stroke patients discharged from hospital. METHODS: From April 2004 to February 2005, 173 patients admitted to hospital with a diagnosis of stroke were consecutively included and interviewed about their medical history and modifiable risk factors before stroke. One-year follow-up with measurement of blood pressure was performed in 92% of surviving and able participants. RESULTS: One year after discharge, 121 participants were reinterviewed and 118 had their blood pressure measured. We found uncontrolled hypertension in 43 of 65 patients (66% of those receiving antihypertensive medication) and unknown hypertension in 30 of 53 patients (57% of those without antihypertensive medication). There was a reduction in the prevalence of excessive consumption of alcohol from 24 of 121 patients (20%) to 16 of 121 patients (13%) (P<0.05). The frequency of cigarette intake remained unchanged: 57 of 121 patients (47%) 1 year after stroke. The proportion of patients who were physically inactive increased from 36% (43 of 121 patients) before stroke to 59% (71 of 121) 1 year later (P<0.0001). CONCLUSIONS: The change in modifiable risk factors was inadequate 1 year after stroke. The pilot study indicated that a preventive programme should focus on hypertension, smoking and physical inactivity.

Vital exhaustion increases the risk of ischemic stroke in women but not in men: results from the Copenhagen City Heart Study.

BACKGROUND: Several studies have indicated an association between depression and the development of stroke, but few studies have focused on gender differences, although both depression and stroke are more common in women than in men. The aim of the present study was to describe whether vital exhaustion, a measure of fatigue and depression, prospectively predicts ischemic and hemorrhagic strokes in a large cohort, with particular focus on gender differences. METHODS: The cohort was composed of 5219 women and 3967 men without cardiovascular disease who were examined in the Copenhagen City Heart Study in 1991-1994. Subjects were followed for 6-9 years. Fatal and nonfatal strokes were ascertained from the Danish National Register of Patients. Cox proportional hazards model was used to describe vital exhaustion as a potential risk factor for stroke. RESULTS: Four hundred nine validated strokes occurred. A dose-response relationship between vital exhaustion score and the risk of stroke was found in women reaching a hazard ratio (HR) of 2.27 (95% confidence interval: 1.42-3.62) for the group with the highest score. HR was only slightly attenuated by multivariate adjustment. There was no association between vital exhaustion score and stroke in men. HR was strongest for ischemic stroke, whereas no association was seen for hemorrhagic stroke. CONCLUSION: Vital exhaustion, a measure of fatigue, conveyed an increased risk of ischemic stroke in women, but not in men, in this study sample.

Major life events increase the risk of stroke but not of myocardial infarction: results from the Copenhagen City Heart Study.

BACKGROUND: More attention has been paid to psychosocial conditions as possible risk factors for cardiovascular disease (CVD) and the impact of accumulated major life events (MLE) on the development of CVD has received little attention. DESIGN: The aim of this study was to explore the influences of MLE on CVD risk in a large cohort study. METHODS: The study population consisted of 9542 randomly selected adults free of CVD examined in the Copenhagen City Heart Study in 1991-1994 and followed up for CVD defined as myocardial infarction or ischaemic stroke until 2001. MLE were analysed using an 11-item questionnaire and hazard ratios (HR) were calculated using the Cox proportional hazards model. RESULTS: During follow-up there were 443 myocardial infarctions (MI) and 350 ischaemic strokes. Financial problems in both childhood and adulthood were associated with risk of stroke with an HR of 1.71 (95% CI: 1.29-2.26) and 1.60 (1.12-2.30), respectively. Accumulation of MLE was also associated with risk of stroke with HR reaching a maximum of 1.41 (95% CI: 1.06-1.90) for more than one event in childhood and 1.49 (95% CI: 1.09-2.04) for more than one event in adulthood. MLE accumulated over a life course showed a dose-response relationship with stroke. Associations were somewhat attenuated by adjustment for vital exhaustion suggesting a mediating role, but not by adjustment for behavioural risk factors. There were no associations between MLE and MI. CONCLUSION: In this population-based cohort study, we found that MLE conveyed a moderately increased risk of stroke partly mediated through vital exhaustion. We found no association between MLE and the risk of MI.

ExStroke Pilot Trial of the effect of repeated instructions to improve physical activity after ischaemic stroke: a multinational randomised controlled clinical trial.

OBJECTIVES: To investigate if repeated verbal instructions about physical activity to patients with ischaemic stroke could increase long term physical activity. DESIGN: Multicentre, multinational, randomised clinical trial with masked outcome assessment. SETTING: Stroke units in Denmark, China, Poland, and Estonia. PARTICIPANTS: 314 patients with ischaemic stroke aged >or=40 years who were able to walk-157 (mean age 69.7 years) randomised to the intervention, 157 (mean age 69.4 years) in the control group. INTERVENTIONS: Patients randomised to the intervention were instructed in a detailed training programme before discharge and at five follow-up visits during 24 months. Control patients had follow-up visits with the same frequency but without instructions in physical activity. MAIN OUTCOME MEASURES: Physical activity assessed with the Physical Activity Scale for the Elderly (PASE) at each visit. Secondary outcomes were clinical events. RESULTS: The estimated mean PASE scores were 69.1 in the intervention group and 64.0 in the control group (difference 5.0 (95% confidence interval -5.8 to 15.9), P=0.36. The intervention had no significant effect on mortality, recurrent stroke, myocardial infarction, or falls and fractures. CONCLUSION: Repeated encouragement and verbal instruction in being physically active did not lead to a significant increase in physical activity measured by the PASE score. More intensive strategies seem to be needed to promote physical activity after ischaemic stroke. TRIAL REGISTRATION: Clinical Trials NCT00132483.

Long-term survival after stroke: 30 years of follow-up in a cohort, the Copenhagen City Heart Study.

BACKGROUND AND PURPOSE: Only few have studied long-term survival after stroke. Such knowledge is essential for the evaluation of the current and future burden of stroke. The present study presents up to 30 years of follow-up of patients after a first-ever stroke. METHODS: Participants in the Copenhagen City Heart Study who experienced a first-ever stroke from 1978 to the end of 2001 were followed to the end of 2007. Stroke events were validated using the World Health Organization's definition of stroke. Linkage to the Danish Civil Registration System enabled identification of participants who died before the end of 2007. The National Register of Causes of Death provided cause of death. Survival in stroke patients was compared with survival in participants in the Copenhagen City Heart Study who did not suffer a stroke, and with survival in the general Danish population. Cox regression analyses adjusting for age and gender were used to compare survival in six consecutive 4-year periods starting with 1978-1982. RESULTS: Of 2,051 patients with first-ever stroke 1,801 died during follow-up. Causes of death were cerebrovascular disease in 37%, other cardiovascular diseases in 28%, cancer in 12%, and other causes in 23%. The most important determinant for long-term survival was age at time of stroke. In the 65- to 72-year age group 11% survived 15 years after stroke. In the age group <65 years 28% survived 15 years. For all age groups survival was poorer in stroke patients than in non-stroke controls. Long-term survival improved steadily over time. Life expectancy after stroke increased up to 4 years from 1978 to the end of 2001, exceeding the increase of life expectancy in the general population. Slightly longer survival was found in women than in men when adjusted for age at stroke onset. CONCLUSION: In this cohort long-term survival after stroke gradually improved over three decades from 1978. The gain in remaining lifetime after stroke exceeded that of the general population.