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.

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.

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.

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.

Effects of microplasmin on recovery in a rat embolic stroke model.

OBJECTIVES: The purpose of the present study was to examine the effects of microplasmin on behavioral performance and infarct volume after middle cerebral artery occlusion (MCAO) in rats. Some experiments support that microplasmin may have neuroprotective and thrombolytic properties. METHODS: Eighty rats underwent surgery and were embolized in the right carotid territory with a fibrin-rich embolus and randomly assigned into three groups: 5 mg/kg microplasmin, 10 mg/kg microplasmin or saline (control). Groups treated with microplasmin received 50% bolus injection 10 minutes after embolization and 50% continuous infusion during the following hour. Animals from all groups were trained to obtain high baseline scores in Montoya's staircase test before embolization and were retested during 7-14 days after surgery. RESULTS: When pre-maturely dead animals were excluded, no differences were observed among groups regarding infarct volumes. Furthermore, mortality was significantly lower in Group 1 than in Group 2 (p<0.05) and when performances were evaluated 7-14 days after surgery, Group 1 was significantly better than Group 2 concerning fine motor performance (p<0.05) and also achieved more normal bodyweight (p<0.05). DISCUSSION: Among surviving animals, 5 mg/kg microplasmin treatment had no effect compared to saline-treated control animals; 5 mg/kg microplasmin reduced mortality and improved both behavioral rehabilitation and bodyweight compared to 10 mg/kg microplasmin treatment, while saline-treated animals did not differ from animals treated with 10 mg/kg microplasmin. Overall, these results indicate a potential beneficial effect of 5 mg/kg microplasmin treatment, while 10 mg/kg may worsen outcomes.

Sex differences in quality of life in stroke survivors: data from the Tinzaparin in Acute Ischaemic Stroke Trial (TAIST).

BACKGROUND AND PURPOSE: Female sex is predictive of poor functional outcome in stroke, even after correction for prognostic factors. Poor quality of life (QoL) is observed in stroke survivors with lower scores seen in the most disabled patients. We used data from the Tinzaparin in Acute Ischaemic Stroke Trial (TAIST) to assess the relationship between sex and QoL after ischemic stroke. METHODS: TAIST was a randomized, controlled trial assessing the safety and efficacy of tinzaparin versus aspirin in 1484 patients with acute ischemic stroke. QoL was measured at 180 days postrandomization using the Short Form-36 health survey, which assesses QoL across 8 domains. The relationship between sex and each domain was assessed using ordinal regression, both unadjusted and adjusted for key prognostic factors. RESULTS: Of the 1484 patients randomized into TAIST, 216 had died at 180 days postrandomization. A total of 1268 survivors were included in this analysis, 694 males (55%) and 574 females (45%). Females tended to score lower than males across all QoL domains (apart from general health); statistically significant lower scores were seen for physical functioning (OR: 0.58, 95% CI: 0.47 to 0.72), vitality (OR: 0.79, 95% CI: 0.64 to 0.98), and mental health (OR: 0.75, 95% CI: 0.61 to 0.93). The results for physical functioning and mental health remained significant after adjustment for prognostic variables (OR: 0.73, 95% CI: 0.58 to 0.92; OR: 0.76, 95% CI: 0.60 to 0.95, respectively). CONCLUSIONS: QoL, in particular physical function and mental health domains, is lower in female patients after stroke. This difference persists even after correction for known prognostic factors such as age and stroke severity.

Validity of stroke diagnoses in a National Register of Patients.

BACKGROUND: Many registers containing routine medical information have been developed for research and surveillance purposes. In epidemiological research assessment of endpoints is often conducted via registers. In the present study we validated stroke and transient ischemic attack (TIA) diagnoses in the Danish National Register of Patients (DNRP). METHODS: Subjects from a Danish cohort study, the Copenhagen City Heart Study (n = 19,698), were crosslinked with the DNRP. The following International Classification of Disease 10th revision codes were used to identify possible strokes and TIAs: I60-I69 and G45. Two independent raters reviewed all cases. Positive predictive values of stroke, TIA and stroke subtypes were estimated by dividing the confirmed cases by the total number of cases located in the DNRP. Interrater reliability was tested using kappa statistics. RESULTS: Of 236 possible cerebrovascular events, 1 in 6 stroke diagnoses did not meet study criteria. The majority of events in the DNRP were registered as unspecified stroke (I64), n = 105 (44%), of which two thirds were diagnosed as ischemic stroke events by the raters. Intracerebral hemorrhage and ischemic stroke had a positive predictive value from 74 to 97%, respectively. CONCLUSION: Our results show that the DNRP tends to overestimate the number of cerebrovascular events, while ischemic stroke is underestimated.

Stroke severity, early recovery and outcome are each related with clinical classification of stroke: data from the 'Tinzaparin in Acute Ischaemic Stroke Trial' (TAIST).

INTRODUCTION: Baseline severity and clinical stroke syndrome (Oxford Community Stroke Project, OCSP) classification are predictors of outcome in stroke. We used data from the 'Tinzaparin in Acute Ischaemic Stroke Trial' (TAIST) to assess the relationship between stroke severity, early recovery, outcome and OCSP syndrome. METHODS: TAIST was a randomised controlled trial assessing the safety and efficacy of tinzaparin versus aspirin in 1484 patients with acute ischaemic stroke. Severity was measured as the Scandinavian Neurological Stroke Scale (SNSS) at baseline and days 4, 7 and 10, and baseline OCSP clinical classification recorded: total anterior circulation infarct (TACI), partial anterior circulation infarct (PACI), lacunar infarct (LACI) and posterior circulation infarction (POCI). Recovery was calculated as change in SNSS from baseline at day 4 and 10. The relationship between stroke syndrome and SNSS at days 4 and 10, and outcome (modified Rankin Scale at 90 days) were assessed. RESULTS: Stroke severity was significantly different between TACI (most severe) and LACI (mildest) at all four time points (p<0.001), with no difference between PACI and POCI. The largest change in SNSS score occurred between baseline and day 4; improvement was least in TACI (median 2 units), compared to other groups (median 3 units) (p<0.001). If SNSS did not improve by day 4, then early recovery and late functional outcome tended to be limited irrespective of clinical syndrome (SNSS, baseline: 31, day 10: 32; mRS, day 90: 4); patients who recovered early tended to continue to improve and had better functional outcome irrespective of syndrome (SNSS, baseline: 35, day 10: 50; mRS, day 90: 2). CONCLUSIONS: Although functional outcome is related to baseline clinical syndrome (best with LACI, worst with TACI), patients who improve early have a more favourable functional outcome, irrespective of their OCSP syndrome. Hence, patients with a TACI syndrome may still achieve a reasonable outcome if early recovery occurs.

Early recovery and functional outcome are related with causal stroke subtype: data from the tinzaparin in acute ischemic stroke trial.

INTRODUCTION: Baseline severity and causal subtype are predictors of outcome in ischemic stroke. We used data from the Tinzaparin in Acute Ischemic Stroke Trial (TAIST) to further assess the relationship among stroke subtype, early recovery, and outcome. METHODS: Patients with ischemic stroke (<48 hours ictus) and enrolled into TAIST were included. Severity was measured prospectively as the Scandinavian Neurological Stroke Scale (SNSS) at days 0, 4, 7, and 10. Causal subtype as large artery atherosclerosis (LAA), cardioembolism (CE), or small vessel occlusion (SVO) was assigned after standard investigations. The rate of recovery was calculated as the change in SNSS at each time point. Functional outcome was assessed using the modified Rankin Scale (mRS) and Barthel Index at day 90. RESULTS: Analyses were performed on the 1190 patients in TAIST who met criteria for LAA, CE, and SVO. The largest change in SNSS score occurred between baseline and day 4 and was greatest in SVO (median improvement 4 U), compared with LAA (median improvement 2 U) and CE (median improvement 2 U) (P < .0001). If no improvement in SNSS had occurred by day 4, irrespective of subgroup, then early recovery (median SNSS improvement by day 10: 2) and functional outcome (mRS 4) tended to be limited; patients who recovered early tended to continue to improve (median SNSS improvement by day 10: 11) and had a better outcome at day 90 (median, mRS 2). CONCLUSIONS: Recovery is related to causal subtype. In all subtypes most recovery occurred by day 4, and was predictive of longer-term functional outcome.

Relationship between outcome and baseline blood pressure and other haemodynamic measures in acute ischaemic stroke: data from the TAIST trial.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Abnormalities on ECG and telemetry predict stroke outcome at 3 months.

BACKGROUND: ECG is a useful tool in monitoring vital functions in patients with acute stroke; however, fairly little evidence is available concerning the prevalence and the prognostic impact of ECG findings in patients with acute cerebral infarction and acute intracerebral haemorrhage (ICH). METHODS: This analysis was based on data from 692 patients with acute cerebral infarction, 155 patients with intracerebral haemorrhage (ICH), and 223 patients with transient ischaemic attack (TIA), who were admitted to hospital within 6 h of symptom onset. A 12 lead ECG was obtained on admission, and the patient was on telemetry for the first 12-24 h of hospitalisation. RESULTS: ECG abnormalities were observed in 60% of patients with cerebral infarction, 50% of patients with ICH, and 44% of patients with TIA. In multivariate analyses 3-month mortality in patients with ischaemic stroke was predicted by atrial fibrillation OR 2.0 (95% CI 1.3-3.1), atrio-ventricular block OR 1.9 (95% CI 1.2-3.9), ST-elevation OR (2.8, 95% CI 1.3-6.3), ST-depression OR 2.5 (95% CI 1.5-4.3), and inverted T-waves OR 2.7 (95% CI 1.6-4.6). This was independent of stroke severity, pre-stroke disability and age. In patients with ICH, sinus tachycardia OR 4.8 (95% CI 1.7-14.0), ST-depression OR 5.2 (95% CI 1.1-24.9), and inverted T-wave 5.2 (95% CI 1.2-22.5) predicted poor outcome. None of the changes reached significance in patients with TIA. In patients with severe cerebral infarction or ICH, heart rate did not decrease within the first 12 h after admission, which was the case in patients with mild to moderate stroke. Rapid heart rate predicted 3-month mortality in multivariate testing OR 1.7 (95% CI 1.02-2.7). CONCLUSIONS: ECG abnormalities are frequent in acute stroke and may predict 3-month mortality.

Compression stockings and the prevention of symptomatic venous thromboembolism: data from the Tinzaparin in Acute Ischemic Stroke Trial.

BACKGROUND: Venous thromboembolism (VTE) is a well-recognized and preventable complication of acute stroke. Although graduated compression stockings reduce the risk of VTE for patients undergoing operation, their benefit in acute stroke remains uncertain. METHODS: The relationship between symptomatic VTE (sVTE) and use of stockings using observational data from the Tinzaparin in Acute Ischemic Stroke Trial, which compared 10 days of treatment with tinzaparin (175 IU/kg(-1) or 100 IU/kg(-1)) with aspirin (300 mg), was assessed using logistic regression adjusted for known VTE risk factors and treatment. RESULTS: sVTE Occurred in 28 patients (1.9%; 18 with deep vein thrombosis and 13 with pulmonary embolism) within 15 days of enrollment in 1479 patients. Patients wearing one or two stockings for any period of time during the first 10 days (n = 803) had a nonsignificant increase (odds ratio 2.45, 95% confidence interval 0.95-6.32) in the risk of sVTE. In contrast, those wearing bilateral stockings for 10 days (n = 374) had a nonsignificant reduction in the odds of sVTE as compared with those who wore no stockings or wore them for less than 10 days (odds ratio 0.65, 95% confidence interval 0.26-1.65). Mild stroke and treatment with tinzaparin were associated with a reduced risk of VTE. CONCLUSIONS: Bilateral graduated compression stockings may reduce the incidence of VTE by one third for patients with acute ischemic stroke. However, the uncertainty in this finding, low frequency of sVTE, potential for stockings to cause harm, and cost of stockings highlight the need for a large randomized controlled trial to examine the safety and efficacy of stockings in acute stroke.

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.

Self-reported stress and risk of stroke: the Copenhagen City Heart Study.

BACKGROUND AND PURPOSE: Lay people often mention stress as one of the most important risk factors for stroke. Stress might trigger a cerebrovascular event directly or could be associated with higher levels of blood pressure or an unfavorable lifestyle. To examine these possibilities, we analyzed the association between self-reported stress frequency and intensity and risk of stroke. METHODS: Data from the second examination, 1981 to 1983, of participants in the Copenhagen City Heart Study were analyzed with Cox regression after a mean of 13 years of follow-up. A total of 5604 men and 6970 women were included, and 929 first-ever strokes occurred, of which 207 (22%) were fatal within 28 days after onset of symptoms. The stress frequency categories were never/hardly ever, monthly, weekly, or daily. The stress intensity categories were never/hardly ever, light, moderate, or high. RESULTS: Subjects with high stress intensity had almost a doubled risk of fatal stroke compared with subjects who were not stressed (relative risk [RR], 1.89; 95% CI, 1.11 to 3.21). Weekly stress was associated with an RR of 1.49 (95% CI, 1.00 to 2.23). There was no significant effect of stress in analyses of nonfatal strokes. Subjects who reported to be stressed often were more likely to have an adverse risk factor profile. CONCLUSIONS: Self-reported high stress intensity and weekly stress were associated with a higher risk of fatal stroke compared with no stress. However, there were no significant trends, and the present data do not provide strong evidence that self-reported stress is an independent risk factor for stroke.