Elisabet Zia

Blood pressure in relation to the incidence of cerebral infarction and intracerebral hemorrhage. Hypertensive hemorrhage: debated nomenclature is still relevant.

Background and Purpose— Data regarding the association between blood pressure level and incidence of stroke subtype, especially primary intracerebral hemorrhage (PICH) subtypes, is sparse. This population-based study explored the relationship between blood pressure and the incidence of cerebral infarction, and PICH, with lobar and nonlobar location. Methods— Risk factors were assessed in 27 702 men and women without prior stroke from the city of Malmö, Sweden. Results— Mean age was 58.1 years. In all, 701 subjects had stroke (613 cerebral infarction and 88 PICH) during the follow-up period (mean, 7.5 years). The age- and sex-standardized incidences of cerebral infarction in subjects with hypertension grade 3 (≥180/110 mm Hg) and normal blood pressure (<140/90 mm Hg) were 6.8 and 1.7 per 1000 person-years, respectively. Compared with the normotensive group, the adjusted relative risk of cerebral infarction was 3.4 (95% CI: 2.6 to 4.5) in subjects with hypertension grade 3. The corresponding incidences of lobar PICH were 0.5 versus 0.08 per 1000 person-years, respectively (adjusted relative risk: 9.2, 95% CI: 2.6 to 32.6) and for nonlobar PICH 1.6 versus 0.09 per 1000 person-years, respectively (adjusted relative risk: 25.9, 95% CI: 8.2 to 82.3). Conclusions— The incidence of hemorrhagic and ischemic stroke increased progressively with increasing blood pressure. Although hypertension was associated with substantially higher incidence rates and absolute numbers of cerebral infarction, which is most important in the public health perspective, the relationship with nonlobar PICH was strongest in terms of relative risks.

Three-Year Survival and Stroke Recurrence Rates in Patients With Primary Intracerebral Hemorrhage

Background and Purpose— There are few studies on the prognosis after primary intracerebral hemorrhages, and they reported big differences in mortality rates. Our aim was to evaluate mortality and stroke recurrence rates in relation to hemorrhage characteristics, demographic and clinical factors, in a large unselected patient cohort. Methods— We analyzed consecutive cases of first-ever primary intracerebral hemorrhages from 1993 to 2000 in a prospective stroke register covering the Malmö region, Sweden (population approximately 250 000). Mortality rates during 28 days and 3 years of follow-up and recurrence rates were analyzed. Results— A total of 474 cases were identified (46% women). In patients <75 years of age, 20% of the women and 23% of the men died within 28 days (P=0.38). The corresponding figures in patients ≥75 years were 26% and 41%, respectively (P=0.02). Male sex was an independent risk factor both for 28-day (OR, 1.5; 95% CI, 1.008 to 2.2) and 3-year mortality (OR, 1.7; 95% CI, 1.3 to 2.3). Other independent predictors of death were high age, central and brain stem hemorrhage location, intraventricular hemorrhage, increased volume, and decreased consciousness level. The recurrence rate was 5.1 per 100 person-years, 2.3 per 100 person-years for intracerebral hemorrhage and 2.8 per 100 person-years for cerebral infarction. Only age >65 years was significantly related to recurrent stroke. Conclusion— Women had better survival than men after primary intracerebral hemorrhages. The difference is largely explained by a higher 28-day mortality in male patients >75 years. However, the underlying reasons are yet to be explored.

Marital Dissolution Is Followed by an Increased Incidence of Stroke

Background: Many studies have reported lower mortality in married people. The relation between marital status and incidence of haemorrhagic and ischaemic stroke is unclear. It is largely unknown whether the risk of stroke is increased the first years after divorce or death of spouse. Methods: Incidence of first-ever stroke (n = 6,184) was followed over 10 years in a cohort consisting of all 40- to 89-year-old inhabitants (n = 118,134) in the city of Malmö, Sweden. Marital dissolution (i.e. divorce or death of spouse) prior to the date of stroke was compared in a nested case-control design (3,134 initially married stroke cases, 9,402 initially married controls). Results: As compared to the married groups, the incidence of stroke was increased in divorced men and women (RR = 1.23, CI: 1.10–1.39 and RR = 1.26, CI: 1.12–1.41, respectively) and widowed men and women (RR = 1.13, CI: 0.99–1.28 and RR = 1.13, CI: 1.02–1.24, respectively) after adjustments for age, country of birth and socioeconomic indicators. The risk of stroke was not increased in never married men. Marital dissolution was followed by increased risk of stroke, which was significant for men (adjusted odds ratio: 1.23, CI: 1.03–1.5) and borderline significant for women below 65 years of age (odds ratio: 1.45, CI: 0.99–2.14). Conclusion: The incidence of stroke is increased in divorced and widowed individuals. Never married men do not have an increased incidence. The risk of stroke is elevated during the first years after divorce or death of spouse.

Risk Factors for Primary Intracerebral Hemorrhage. A Population-Based Nested Case-Control Study.

Purpose: In this population-based study, risk factors for primary intracerebral hemorrhage (PICH) and PICH subtypes were explored in a nested case-control design. Method: Risk factors were determined in 22,444 men and 10,902 women (mean age 47 years) who participated in a health-screening programme between 1974 and 1991. 147 subjects with CT or autopsy-verified first-ever PICH during the follow-up period (mean 14 years) were compared with 1,029 stroke-free controls, matched for age, sex and screening-year. Results: As compared to controls, PICH cases had significantly higher blood pres- sure (135/91 vs. 127/85 mm Hg), triglycerides (1.7 vs. 1.4 mmol/l), BMI (25.5 vs. 24.8) and shorter stature (1.73 vs. 1.74 m). Diabetes (6.9 vs. 2.8 %) and history of psychiatric morbidity (19.7 vs. 11.0 %) were more common in PICH cases and more of them were living alone (35.4 vs. 25.5%). After adjustment in a backward logistic regression model, high systolic blood pressure, diabetes, high triglycerides, short stature and psychiatric morbidity remained significantly associated with PICH. As compared to the control group, high systolic blood pressure was significantly associated both with nonlobar and lobar PICH. Diabetes and psychiatric morbidity were associated with nonlobar PICH. Smoking doubled the risk for lobar PICH, but was unrelated to nonlobar PICH. Conclusion: In this prospective population-based study, hypertension, diabetes, height, triglycerides and psychiatric morbidity were risk factors for PICH. Smoking was a risk factor for lobar PICH only.

Changes in Functional Outcome Over the First Year After Stroke: An Observational Study From the Swedish Stroke Register

Background and Purpose— Large longitudinal studies on stroke outcome are scarce. The aim of this study was to analyze predictors and changes in functional outcome during the first year poststroke. Methods— Data on patients who were independent in activities of daily living (ADL) and hospitalized for acute stroke in 2008 to 2010 were obtained from the Swedish Stroke Register. Case fatality was assessed by linkage to the Swedish Population Register. ADL was defined by independence or dependence in dressing, toileting, and indoor mobility and assessed at 3 and 12 months. Predictors of ADL dependency were assessed through multivariate analysis. Results— In total, 64 746 patients were included. Case fatality at 3 months was 13.1% (men 11.6% versus women 14.8%; P<0.0001) and at 12 months 18.2% (men 16.4% versus women 20.3%; P<0,0001). In the 35 064 followed-up survivors, ADL dependency rates at 3 and 12 months were 16.2% (men 15.9% versus women 19.2%; P<0.0001) and 28.3% (men 22.7% versus women 34.9%, P<0.0001), respectively. Factors predicting deterioration to ADL dependency between 3 and 12 months were female sex (relative risk [RR]=1.56; 95% confidence interval [CI], 1.50–1.70), diabetes mellitus (RR=1.50; 95% CI, 1.05–1.60), comatose at admittance (RR=2.34; 95% CI, 1.79–3.05), previous stroke (RR=1.52; 95% CI, 1.43–1.61), hemorrhagic or unspecified stroke (RR=1.14; 95% CI, 1.05–1.25), and atrial fibrillation (RR= 1.11; 95% CI, 1.04–1.17). Conclusions— Transition from ADL independence to dependence was observed in a high proportion of patients between 3 and 12 months, challenging the common belief that functioning after stroke is stable beyond 3 months. Deterioration occurred more commonly in women, among whom 1/6 converted to dependency.

Swirl sign in intracerebral haemorrhage: definition, prevalence, reliability and prognostic value

BackgroundSwirl sign has previously been described in epidural hematomas as areas of low attenuation, radiolucency or irregular density. The aims of this study were to describe swirl sign in ICH, study its prevalence, study the reliability of the subjective evaluation on computed tomography (CT), and to explore its prognostic value.MethodsCTs of 203 patients with ICH were retrospectively evaluated for the presence of swirl sign. Association between swirl sign and different clinical and radiological variables was studied.ResultsInter- and intraobserver agreement with regard to the occurrence of swirl sign was substantial (К 0.80) and almost perfect (К 0.87), respectively. Swirl sign was found in 30% of the study population. 61% of patients with swirl sign were dead at one month compared with 21% of those with no swirl sign (p < 0.001). Only 19% of patients with swirl sign exhibited favorable outcome at three months compared with 53% of those with no swirl sign (p < 0.001). Patients with swirl sign exhibited larger ICHs with average ICH-volume 52 ± 50 ml (median 42 ml) compared with 15 ± 25 ml (median 6) in patients whose CT did not show swirl sign (p < 0.001). Swirl sign was independent predictor of death at one month (p = 0.03; adjusted odds ratio 2.6, 95% CI 1.1 – 6), and functional outcome at three months (p = 0.045; adjusted odds ratio 2.6, 95% CI 1.02 – 6.5).ConclusionsAs swirl sign showed to be an ominous sign, we recommend identification of this sign in cases of ICHs.

Total and differential leucocyte counts in relation to incidence of stroke subtypes and mortality: a prospective cohort study

Abstract.  Zia E, Melander O, Björkbacka H, Hedblad B, Engström G (Lund University, Malmö; Institute of Clinical Sciences, Lund University, Malmö; Skåne University Hospital, Malmö; and Astra Zeneca R&D, Malmö, Sweden). Total and differential leucocyte counts in relation to incidence of stroke subtypes and mortality: a prospective cohort study. J Intern Med 2012; 272: 298–304.

Early do-not-resuscitate orders in intracerebral haemorrhage; frequency and predictive value for death and functional outcome. A retrospective cohort study

IntroductionIn former studies from North America early Do-Not–Resuscitate orders (DNR orders) in patients with intracerebral haemorrhage (ICH) had negative prognostic impact on mortality. The influence of DNR orders on functional outcome and whether DNR orders are grounded on relevant patient characteristics is unknown. We aimed to determine the frequency and predictive factors of DNR-orders and its association to prognosis, in ICH patients, in Scandinavia.MethodsIn 197 consecutive ICH patients admitted to Skåne University Hospital, Malmö, Sweden, between January 2007 and June 2009, information of the presence of DNR orders within 48 hours, clinical and radiological characteristics was retrieved by review of patient medical journal and computed tomography scans. Determinants of DNR-orders, one-month case fatality and bad functional outcome (modified Rankin Scale, grade 4–6) were assessed by logistic regression analysis.ResultsDNR orders were made in 41% of the cases. After adjustment for confounding factors, age ≥ 75 years (Odds Ratio (95% confidence interval) 4.2(1.8-9.6)), former stroke (5.1(1.9-3.1)), Reaction Level Scale grade 2–3 and 4 (7.0(2.8-17.5) and (4.1(1.2-13.5), respectively) and intraventricular haemorrhage (3.8(1.6-9.4)) were independent determinants of early DNR orders. Independent predictors of one-month case fatality was age ≥ 75 years (3.7(1.4-9.6)) volume ≥ 30 ml (3.5(1.3-9.6)) and DNR orders (3.5(1.5-8.6)). Seizure (6.0(1.04-34.2) and brain stem hemorrhage (8.0(1.1-58.4)) were related to bad functional outcome, whereas early DNR order was not (3.5(0.99-12.7)).ConclusionsWell known prognostic factors are determinants for DNR orders, however DNR orders are independently related to one-month case fatality. In addition to improvements of the local routines, we welcome a change of attitude with an enhanced awareness of the definition of, and a more careful approach with respect to DNR orders.

Lung Function as a Risk Factor for Subarachnoid Hemorrhage: A Prospective Cohort Study

Background and Purpose— The etiology of subarachnoid hemorrhage (SAH) is poorly understood. Reduced lung function, expressed as low forced expiratory volume in 1 second (FEV1) and low forced vital capacity (FVC), is a predictor of cardiovascular disease, but whether reduced lung function is a risk factor for SAH is not known. The association between lung function and incidence of SAH was investigated in a prospective cohort study. Methods— Between 1974 and 1992, 20 534 men and 7237 women (mean age, 44 years) were examined in a health screening program including spirometry. The incidence of SAH was studied during a mean follow-up of 26 years in relation to age- and height-standardized FEV1, FVC, and FEV1/FVC. Results— One hundred forty-five subjects had a SAH (18.3 per 100 000 person-years in men and 26.5 per 100 000 person-years in women). The hazard ratio for SAH in the lowest compared to the highest quartile of FEV1 and FEV1/FVC was 2.24 (95% CI, 1.32–3.81; P for trend=0.014) and 1.92 (95% CI, 1.14–3.23; P for trend=0.003), respectively, after adjustment for several confounding factors including smoking and hypertension. The results persisted when analysis was restricted to nonsmokers. FVC showed no significant association with incidence of SAH. Conclusions— Baseline lung function, expressed as low FEV1 or FEV1/FVC, is a risk factor for SAH, independently of smoking.

Plasma Natriuretic Peptides and Incidence of Subtypes of Ischemic Stroke

Background and Purpose: Natriuretic peptides predict poor outcomes in cardiovascular disease. However, the knowledge of their relationship to stroke is limited and prospective studies from the general population are few. The purpose of this study was to explore the relationship between N-terminal pro-brain natriuretic peptide (NT-proBNP) and midregional pro-atrial natriuretic peptide (MR-proANP) plasma levels and the risk for ischemic stroke and its subtypes. Methods: NT-proBNP and MR-proANP were measured in fasting blood samples from 4,862 subjects (40.2% men, mean age 57.5 ± 6.0 years) without cardiovascular disease from the Malmö Diet and Cancer Study, a prospective, population-based study in Sweden. Incidence of ischemic stroke was monitored over a mean follow-up of 14.9 ± 3.0 years. Stroke cases were etiologically classified according to the TOAST classification. Cox proportional-hazards regression was used to study the incidence of stroke in relationship to NT-proBNP and MR-proANP. Results: During follow-up, 227 had a first-ever ischemic stroke (large-artery atherosclerosis, n = 35; cardioembolic stroke, n = 44; small-artery occlusion, n = 80; undetermined cause, n = 68). In the age- and sex-adjusted model, only NT-proBNP was associated with total ischemic stroke. This association was completely explained by an increased incidence of cardioembolic stroke. Adjusted for cardiovascular risk factors (age, sex, hypertension, diabetes, smoking, body mass index and low-density lipoprotein cholesterol), the hazard ratios (HRs, 95% confidence interval, 95% CI) for cardioembolic stroke were 1.00 (reference), 1.42 (0.34-6.00), 2.79 (0.77-10.12) and 5.64 (1.66-19.20), respectively, for the 1st, 2nd, 3rd and 4th quartiles of NT-proBNP. The corresponding HRs (95% CIs) for quartiles of MR-proANP were 1.00 (reference), 1.83 (0.55-6.14), 1.20 (0.33-4.34) and 3.96 (1.31-11.99), respectively. In total, 335 (6.9%) subjects were diagnosed with atrial fibrillation during follow-up. Among the cardioembolic stroke cases, 30% were diagnosed with atrial fibrillation before the stroke event and another 36% within 6 months after the stroke. Of the cardioembolic stroke cases with atrial fibrillation, 59% were in the top quartile of NT-proBNP, 69% in the top quartile of MR-proANP and 79% were either in the top quartile of NT-proBNP or in the top quartile of MR-proANP. Conclusion: High plasma levels of NT-proBNP and MR-proANP are associated with a substantially increased risk of cardioembolic stroke, but not with other subtypes of ischemic stroke. The results suggest that assessment of stroke risk, including electrocardiography, is warranted in subjects with high NT-proBNP or MR-proANP.