Search

Background and Purpose — The long-term beneficial effects of stroke unit care have been proved in several randomized trials. However, there is a question of large-scale applicability in routine clinical practice of interventions used by dedicated investigators in small randomized trials. The objective of this study was to compare, 21/2 years after stroke, patients who had been treated in stroke units and those treated in general wards in routine clinical practice. Methods — This is a prospective cohort study based on 8194 patients who were included, during the first 6 months in 1997, in Riks-Stroke, the Swedish National Register for quality assessment of acute stroke. Two years after the event, 5189 patients were still alive and 5104 were followed up with a postal questionnaire to which 4038 responded. Results — Among the group of patients who were independent in activities of daily living (ADL) functions before the stroke, patients who were treated in stroke units were less often dependent in ADL functions, after adjustment for case mix (OR, 0.79; CI, 0.66 to 0.94). If they also lived at home before the stroke, then they had a lower case-fatality rate 2 years after the stroke (OR, 0.81; CI, 0.72 to 0.92). Conclusions — Long-term beneficial effects of treatment in stroke units were shown for patients who were independent in ADL functions before the stroke. No benefits were shown for patients who were dependent on help for primary ADL before the stroke. Further studies on this group of patients with more detailed outcome measures are needed.

Background The overall aim was to test whether low birthweight (LBW) in newborns is associated with the risk indicators for cardiovascular disease in early middle age, even in a welfare society. Further, a possible interaction of LBW and heredity for myocardial infarction or stroke was investigated. Methods Overall, subjects were identified as newborns in a local birth register, and as adult participants, in the Vasterbotten Intervention Program (n = 7876). Outcome measures such as systolic (SBP) and diastolic blood pressures (DBP), body mass index (BMI), cholesterol, triglycerides and anthropometrics were investigated (at age 29-41 years) in relation to LBW. Results Low birthweight was associated with increased SBP and DBP. Triglycerides were elevated among women with LBW and total cholesterol was elevated in men with LBW. Heredity for myocardial infarction or stroke interacted with LBW, and indicated a synergistic effect on the level of SBP. The BMI did not differ between LBW and normal birthweight subjects. Conclusions Our interpretation is that the 'fetal origins' hypothesis' is valid for middle-age subjects who grow up in a welfare society. The population attributable proportions that result from different exposures to LBW were relatively small overall; from a public health perspective, heredity was more important than LBW for elevated SBP.

Oxidative stress has been implicated in human illness such as cardiovascular and neurodegenerative disease. The genetic mechanisms involved are only poorly understood. Here we describe the determination of the allelic frequency and phenotype of a common polymorphism in Se-dependent glutathione peroxidase 1 (GPX1) in Finnish/Swedish populations. A proline/leucine variant occurs at position 197 close to the C-terminus of the protein. The more common allele encoding the Pro variant is present at 59% in a Finnish/Swedish population (n = 66) and at 73% in a Swedish population (n = 315). The genotypes encoding Pro/Pro, Pro/Leu, and Leu/Leu are distributed according to the Hardy–Weinberg relationship. The Swedish population consisted of 101 stroke cases and 214 controls. No significant association between allele frequency and risk to suffer from stroke was evident. Erythrocyte GPX activity was determined in the Finnish/Swedish population and no significant differences were obtained between the genotypes. It can be concluded that the Pro/Leu genetic variation does not appear to compromise the defense against oxidative stress in red blood cells nor to be associated with stroke.

Background and Purpose —Diabetic subjects have a 3- to 6-fold increased risk for stroke compared with nondiabetic subjects, and hyperinsulinemia shows strong and consistent associations with a cluster of cardiovascular risk factors. Methods separating proinsulin from (true) insulin have demonstrated proinsulin to be more strongly associated with cardiovascular disease than insulin. The present study evaluates the associations between first-ever stroke, proinsulin, and insulin. Methods —In this incident case-referent study of a nondiabetic population, 94 cases of first-ever stroke (59 men and 35 women) were individually age- and sex-matched to 178 referents. Blood sampling was collected before the stroke event. Proinsulin and insulin were measured with highly sensitive 2-site sandwich enzyme-linked immunosorbent assays. Results —In the study population, high proinsulin concentration more than tripled the risk for first-ever stroke after adjustments for total cholesterol, systolic blood pressure, smoking, body mass index, and insulin, with an odds ratio of 3.4 (95% CI, 1.4 to 8.4). In women the risk was even more pronounced, with an odds ratio of 13.7 (95% CI, 1.3 to 146). Synergy was found between proinsulin and systolic blood pressure. In women, synergy was also found between proinsulin and diastolic blood pressure as well as between insulin and both blood pressures. Conclusions —High levels of proinsulin may predict later occurrence of first-ever stroke in a nondiabetic population.

Background and Purpose —Stroke is declining in most of the western and northern European countries, whereas no such decline is seen in eastern Europe. The aim of this study was to investigate trends in stroke attack rates and 28-day case fatality and risk factor levels in Novosibirsk, Siberia, and northern Sweden during 1987–1994. Methods —Within the World Health Organization Multinational Monitoring of Trends and Determinants in Cardiovascular Disease (MONICA) Project, acute stroke events and 28-day case fatality were registered in a standardized way in men and women aged 35 to 69 years. Cardiovascular risk factors were monitored in randomly selected men and women in the group aged 35 to 64 years in 1985–1986 and 1994–1995. Results —Stroke attack rates increased significantly from 430 per 100 000 to 660 ( P =0.005) in men in Novosibirsk and from 298 to 500 ( P =0.02) in women. In northern Sweden, stroke attack rates varied between 244 and 303 per 100 000 in men and from 117 to 157 in women, with a small increasing trend in women ( P =0.03). The mortality rates were 5 times higher in Novosibirsk, and the case fatality was significantly lower in northern Sweden ( P =0.0001). The risk factor surveys showed significantly higher blood pressure, overweight, and more smoking men in Novosibirsk, while northern Sweden had higher cholesterol levels and more smoking women. Most risk factors showed stable or improving patterns over time. Conclusions —Large differences in both attack rates and case fatality account for the large and widening gap in stroke mortality between Russia and Sweden. A higher prevalence of hypertension in Russia may explain much of the differences in stroke occurrence. In Russia, a marked increase in attack rates has occurred despite stable or improving patterns of conventional cardiovascular risk factors.

Background and Purpose —Autoantibodies against oxidatively modified LDL have been shown to be associated with atherosclerosis. Their possible pathogenic role is not yet fully understood, and earlier published data are inconsistent. In this prospective study, we have investigated the association of these antibodies with future stroke. Methods —A prospective case-control study in which 44 725 men and women from the World Health Organization Multinational Monitoring of Trends and Determinants in Cardiovascular Disease (MONICA) project and the Västerbotten Intervention Program (VIP) were enrolled and followed from January 1, 1985, to August 31, 1996. One hundred nineteen cases of stroke (male 75, female 44) were noted and compared with 233 age- and sex-matched controls from the same population. Antibodies against oxidatively modified LDL (copper-oxidized LDL and malonaldehyde [MDA]-LDL) were analyzed by ELISA. Results —There was no difference in the levels or in the prevalence of IgG, IgA, and IgM autoantibodies against copper-oxidized LDL or MDA-LDL between patients and controls. Risk ratios for these antibodies, when adjusted for diabetes mellitus, hypertension, and smoking habits, did not confer a risk of stroke. Serum triglycerides (1.7 versus 1.4 mmol/L, P =0.01), fasting blood sugar, and systolic and diastolic blood pressures were significantly higher in the patient group than in the control group, as was the prevalence of hypertension (51.8% versus 27.4%, P P Conclusions —Autoantibodies against oxidatively modified LDL do not constitute a risk factor for stroke in an adult population.

Background and Purpose —An association between high lipoprotein(a) [Lp(a)] levels and positive Chlamydia pneumoniae IgG titers in coronary artery disease has been described. The possibility of predicting ischemic stroke by measurements of plasma Lp(a) and C pneumoniae antibodies was investigated. Methods —This incident case-control study included 101 case subjects (cases) who had suffered ischemic cerebral infarctions and 201 matched control subjects (controls). The study population was nested within the Västerbotten Intervention Program or the WHO MONICA project. Plasma samples were measured for C pneumoniae –specific IgG and IgA antibodies and Lp(a). Results —A significantly higher mean Lp(a) level was found in female cases than in female controls. However, plasma Lp(a) was unable to predict ischemic cerebral infarctions in either women or men. The proportion of individuals with positive C pneumoniae –specific IgG or IgA titers did not differ between cases and controls. Antibody titers were unable to predict a future stroke. The proportion of individuals with a positive C pneumoniae IgG titer in combination with a high Lp(a) level did not differ significantly between cases and controls. Conclusions —These data suggest that there is no association between baseline plasma Lp(a) levels, presence of C pneumoniae antibodies, and future ischemic cerebral infarctions. Furthermore, no evidence of an interactive effect between high Lp(a) levels and C pneumoniae IgG titers was found. However, selection bias and a recent C pneumoniae epidemic may have influenced the results.

Background and Purpose —Leptin, important for body weight regulation, may be involved in the pathogenesis of the insulin resistance syndrome, associated with cardiovascular disease. We tested to determine whether leptin is a risk marker for first-ever stroke in a nested case-referent study. Methods —We identified 113 patients with first-ever stroke (94 with ischemic and 19 with hemorrhagic stroke) who, before the stroke, had participated in population-based health surveys in northern Sweden. Referents were matched for sex, age, date and type of health survey, and geographic region. Blood pressure (BP), body mass index (BMI), and presence of smoking, diabetes, and hypertension were recorded. Total cholesterol, insulin, and leptin were analyzed in stored samples. Risk markers for first-ever stroke were analyzed by conditional logistic regression analysis. Results —Patients with hemorrhagic stroke had higher levels of BMI and systolic and diastolic BPs. Leptin levels were 72% and 59% higher in males and females, respectively, with hemorrhagic stroke versus referents. Patients with ischemic stroke more often had hypertension, diabetes mellitus, and higher fasting glucose and insulin levels. A diagnosis of hypertension and elevated systolic and diastolic BPs were significant risk markers for first-ever hemorrhagic stroke in univariate analysis. High leptin (OR=20.55; 95% CI, 1.12 to 376.7) levels together with hypertension (OR=16.28; 95% CI, 1.49 to 177.3) remained as significant risk markers in a multivariate model. The combination of high leptin and high systolic or diastolic BP were associated with a profoundly increased risk for hemorrhagic stroke (OR=22.11; 95% CI, 1.57 to 310.9). Diabetes, hypertension, and obesity (BMI ≥27), together with high levels of insulin, glucose, systolic and diastolic BP, were significant risk markers for first-ever ischemic stroke in univariate analysis. Hypertension (OR=2.10; 95% CI, 1.14 to 3.86) remained as an independent risk marker in a multivariate model. Conclusions —Plasma leptin is strongly associated with an increased risk for first-ever hemorrhagic stroke, independent of other risk markers for cardiovascular disease. Leptin may be an important link in the development of cardiovascular disease in obesity.

Background and Purpose —Stroke mortality rates and case fatality of stroke have declined since the beginning of the 1970s in Sweden, but the incidence of stroke has been stable. The aim of this study was to analyze trends in long-term survival after stroke. Methods —Within the framework of the population-based WHO Multinational Monitoring of Trends and Determinants in Cardiovascular Disease (MONICA) Project, all acute stroke events were recorded in the age group 25 to 74 years in northern Sweden during the period 1985 to 1994. All first-ever stroke patients were followed for information on vital status (minimum follow-up time was 1 year). Survival time was related to time period of stroke onset, stroke diagnosis, and concomitant diseases. Results —Survival times for a total of 6819 first-ever stroke patients (4057 men and 2762 women) were analyzed. Age-adjusted odds ratio for death within 1 year after stroke was 0.70 (95% confidence interval [CI], 0.55 to 0.88) in the period 1993 to 1994 as compared with the period 1985 to 1986 in men and 0.69 (95% CI, 0.53 to 0.90) in women. Corresponding odds ratios were 0.73 in men and 0.70 in women among those who survived the first 28 days. Similar improvements were seen for 3- and 5-year survival. Improvements in survival over time were most marked among patients with ischemic stroke. There was no improvement in survival over time among patients with the most severe deficits at onset. Conclusions —Gradually improved survival, both short and long term, was observed during the 10-year study period. The improvements are not explained by changes in known confounding prognostic factors.

Background and Purpose The aim of this study was to conduct a population-based epidemiological survey among young adults aged 18 to 44 years in Northern Sweden and furthermore to gain further insight into the etiology of ischemic stroke in this age group. Methods Two studies were done. In the first part, epidemiological data were collected to calculate incidence and mortality from 1991 through 1994. This was based on the World Health Organization Northern Sweden MONICA register of acute stroke events. Eighty-eight first-ever ischemic stroke patients were identified during that period. In the second part, 107 consecutive patients aged 18 to 44 years with ischemic stroke referred to a university hospital were studied prospectively during a 5-year period and were extensively evaluated according to a standardized protocol. On the basis of modified Trial of ORG 10172 in Acute Stroke Treatment (TOAST) criteria, the patients were classified into eight subtypes of ischemic stroke. Results The average population-based annual incidence rate for ischemic stroke (cases per 100 000 per year) was 11.3 (95% confidence interval, 6.7 to 16.1). The case-fatality rate was 5.7%. According to the modified TOAST criteria, a probable cause of ischemic stroke was identified in 36% and remained unexplained in 21% of cases. Spontaneous cervical arterial dissection was the leading probable etiology (13%). Patent foramen ovale or atrial septal aneurysm was a possible cause of stroke in 28% of cases. The percentages of ischemic stroke attributed to IgG anticardiolipin antibodies (4.7%), atherothrombotic vasculopathy (3.7%), oral contraceptive use (7%), and migraine (1%) were lower than reported in recent clinical series. Conclusions The incidence rate for ischemic stroke was higher than previously reported from most countries in Western Europe. The higher incidence was not explained by a higher prevalence of premature atherosclerotic vasculopathy. Without the additional diagnostic information derived from advanced cardiac imaging, the proportion of indeterminate cases would have constituted 37% of the patients.

Background and Purpose Modern treatment may have influenced the risk of stroke after myocardial infarction (MI). The purpose of this study was to examine the incidence of ischemic stroke during the first month after an acute MI in an unselected population, to identify predictors of MI-related stroke, and to investigate the secular trend in MI-related stroke incidence. Methods In this case-control study, from a population of approximately 310 000 25- to 74-year-old inhabitants, case subjects with a stroke within 1 month after an MI were prospectively recorded in the population-based Northern Sweden MONICA (Monitoring of Trends and Determinants in Cardiovascular Disease) study from 1985 to 1994. The same number of control subjects with an MI but without a stroke were matched for age, sex, and year when MI occurred. Results One hundred twenty-four case subjects were recorded. Fifty-one percent (63/124) of the strokes occurred within 5 days after onset of MI. The odds ratios (ORs) of an MI-related stroke were for a history of hypertension 1.7 (95% confidence interval [CI], 1.0 to 3.2), previous stroke 2.4 (CI, 1.0 to 6.1), chronic atrial fibrillation 3.0 (CI, 1.1 to 9.2), onset of atrial fibrillation during the hospital stay 3.5 (CI, 1.4 to 10.1), ST-segment elevation 2.4 (CI, 1.4 to 4.6), and anterior infarction 1.5 (CI, 0.9 to 2.6). In a conditional multiple logistic regression model, previous stroke (OR, 2.8; CI, 1.1 to 7.6), chronic atrial fibrillation (OR, 3.8; CI, 1.3 to 11.0), new-onset atrial fibrillation (OR, 4.6; CI, 1.6 to 12.8), and ST-segment elevation (OR, 3.4; CI, 1.6 to 7.4) were independent predictors of stroke. MIs preceding stroke were larger and in 51% were located anteriorly. There was a decrease in the incidence and event rate of MI-related stroke during the study period ( P P Conclusions The risk of stroke is highest the first 5 days after MI. Only approximately half of the strokes occurring the first month after an MI are preceded by an anterior MI. The most important predictors of MI-related stroke are atrial fibrillation (chronic or new onset), ST elevation, and a history of a previous stroke. There is a long-term trend toward a lower incidence of MI-related stroke. These findings have important implications concerning both the pathophysiology and prevention of MI-related stroke.

An enzyme-linked immunosorbent assay (ELISA) based on recombinant nucleocapsid protein (rN delta) (aa 1-117) of Hantaan, Seoul, Dobrava, Sin Nombre and Puumala hantaviruses was used to determine the prevalence of antibodies among randomized and stratified individuals from northern Sweden. In total, 137/1533 individuals (8.9%) had specific serum IgG antibodies to Puumala virus, the only hantavirus known to occur in the region. The prevalence of antibodies to Puumala virus (8.9%) was determined to be higher than previously reported (5.4%) in the same serum material, by use of immunofluorescence assay. As expected, sera reactive to Puumala virus rN delta did frequently cross-react with Sin Nombre virus protein. Unexpectedly, 21/1533 (1.4%) individuals recognized the Sin Nombre virus rN delta exclusively. Another 8 subjects showed reactivity in the ELISA to Hantaan, Seoul, or Dobrava virus-derived rN delta but not Puumala virus or Sin Nombre virus rN delta. The present demonstration in some individuals of antibodies specifically recognizing the Sin Nombre, Dobrava, Hantaan and Seoul virus protein justifies an awareness of the possibility that hantaviruses antigenically different from Puumala virus might occur in the region.

The occurrence of different life-style patterns, including marital status, educational level, nutrition, tobacco and alcohol use, and frequency of physical activity, in patients with oral lichenoid reactions (OLR) in total or partial contact with amalgam fillings was examined. When compared with an age- and sex-matched control group, the daily intake of carbohydrates, fibers, and iron was statistically significantly higher in the OLR patients. Regarding marital status, there was a statistically significant difference between the OLR patients and the control subjects, the former group containing more people who were divorced or whose spouse had died. The frequency of physical activity was also statistically significantly higher in the OLR patients than in the control group. Hypothetical mechanisms that may lie behind the results obtained are discussed.

ContextGeographic variations in cardiovascular disease (CVD) and associated risk factors have been recognized worldwide. However, little attention has been directed to potential differences in hypertension between Europe and North America.ObjectiveTo determine whether higher blood pressure (BP) levels and hypertension are more prevalent in Europe than in the United States and Canada.Design, Setting, and ParticipantsSample surveys that were national in scope and conducted in the 1990s were identified in Germany, Finland, Sweden, England, Spain, Italy, Canada, and the United States. Collaborating investigators provided tabular data in a consistent format by age and sex for persons at least 35 years of age. Population registries were the main basis for sampling. Survey sizes ranged from 1800 to 23 100, with response rates of 61% to 87.5%. The data were analyzed to provide age-specific and age-adjusted estimates of BP and hypertension prevalence by country and region (eg, European vs North American).Main Outcome MeasuresBlood pressure levels and prevalence of hypertension in Europe, the United States, and Canada.ResultsAverage BP was 136/83 mm Hg in the European countries and 127/77 mm Hg in Canada and the United States among men and women combined who were 35 to 74 years of age. This difference already existed among younger persons (35-39 years) in whom treatment was uncommon (ie, 124/78 mm Hg and 115/75 mm Hg, respectively), and the slope with age was steeper in the European countries. For all age groups, BP measurements were lowest in the United States and highest in Germany. The age- and sex-adjusted prevalence of hypertension was 28% in the North American countries and 44% in the European countries at the 140/90 mm Hg threshold. The findings for men and women by region were similar. Hypertension prevalence was strongly correlated with stroke mortality (r = 0.78) and more modestly with total CVD (r = 0.44).ConclusionsDespite extensive research on geographic patterns of CVD, the 60% higher prevalence of hypertension in Europe compared with the United States and Canada has not been generally appreciated. The implication of this finding for national prevention strategies should be vigorously explored.

Impaired fibrinolysis is found in impaired glucose tolerance and type 2 diabetes, associated with components of the metabolic syndrome. There are no data concerning fibrinolysis in subjects with normal glucose tolerance that convert to diabetes. We studied the activities of tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) and the levels of tPA antigen (a marker of endothelial dysfunction) in 551 subjects with normal glucose tolerance in 1990 in relation to incident diabetes during nine years of follow-up. Subjects with diabetes at follow-up (n = 15) had significantly lower baseline tPA activity and higher PAI-1 activity and tPA antigen than non-converters. The risk of diabetes increased linearly across quartiles of PAI-activity (p = 0.007) and tPA antigen (p < 0.001) and decreased across quartiles of tPA activity (p = 0.026). The risk of diabetes with low tPA activity or high PAI-1 activity persisted after adjustment for age and sex but diminished to a non-significant level after further adjustments. The odds ratio of diabetes for high tPA antigen was 10.4 (95% confidence interval 2.7–40) adjusted for age and sex. After further adjustment for diastolic blood pressure, waist circumference, insulin, triglycerides, fasting and post load glucose the odds ratio was 6.5 (1.3–33, p = 0.024). Impaired fibrinolysis and endothelial dysfunction are evident in subjects with normal glucose tolerance who later develop diabetes. High tPA antigen is predictive of future diabetes independent from the metabolic syndrome.

Human urine was studied in regard to precipitation of crystals under various experimental conditions. These included alkalization of the urine by adding NaOH or by inoculation with Proteus bacteria. The contents of calcium and magnesium in the urinary supernatant after incubation for 24 hours at 37 degrees C were significantly lower after inoculation with Proteus bacteria than in noninoculated urine. Microscopy of the sediments showed distinct crystalline aggregations after the bacterial inoculation. Inoculation with killed Proteus organisms did not lead to crystalline precipitation in otherwise identical experiments. The effect of other live bacteria was also studied. The mechanism of crystal formation in bacteria-inoculated urine is discussed.

Background Favorable dietary habits promote health, whereas unfavorable habits link to various chronic diseases. An individual's "sense of coherence" (SOC) is reported to correlate with prevalence of some diseases to which dietary habits are linked. However, understanding what determines an individual's dietary preferences and how to change his/her behavior remains limited. The aim of the present study was to evaluate associations between dietary intake and SOC in adults. Methods Diet intake was recorded by an 84-item semi-quantitative food frequency questionnaire and SOC was measured by the 13-item Antonovsky questionnaire in 2,446 men and 2,545 women (25–74 years old) from the population based northern Sweden MONICA screening in 1999. Results Intakes of energy, total and saturated fat, ascorbic acid, sucrose, and servings of fruits, vegetables, cereals, and sweets correlated with SOC among women, whereas intakes of total and saturated fat, ascorbic acid, fiber, and alcohol, and servings of fruits, vegetables, bread, bread and cereals, fish, and potatoes correlated with SOC among men. With a few exceptions, intakes of these nutrients/foods were significantly explained by SOC quartile scores in linear GLM models. Both women and men classified into the highest SOC quartile had significantly higher age-BMI-education standardized mean intakes of vegetables than those in the lowest quartiles. Women in the highest SOC quartile also had higher intake of fruits but lower intakes of energy, total and saturated fat, sucrose, and sweets. Projection to latent structures (PLS) multivariate modeling of intakes of the 84 food items and food aggregates simultaneously on SOC scores supported low SOC to coincide with a presumably less health promoting dietary preference, e.g. intake of pizza, soft drinks, candies, sausages for main course, hamburgers, mashed potato, chips and other snacks, potato salad, French fries, whereas men and women with high SOC scores were characterized by e.g. high intake of rye crisp whole meal bread, boiled potato, vegetables, berries, and fruits. Conclusion Both men and women in the highest, as compared with the lowest, SOC score quartile reported more "healthy" food choices. Dietary habits for individuals in the lowest SOC quartile therefore may render a higher risk for various endemic diseases.