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Kjell Asplund

Publications and source records attributed to Kjell Asplund.

At least 19 recordsLinked to original sources
PubMed2006

Genome-wide linkage scan of common stroke in families from northern Sweden.

BACKGROUND AND PURPOSE: Taking advantage of low genetic variations in northern Sweden, we performed a genome-wide linkage scan to investigate the susceptibility loci for common forms of stroke. METHODS: Fifty-six families, containing multiple cases of stroke and whose data had been previously used to replicate linkage to the phosphodiesterase 4D locus on chromosome 5q, were genotyped in a genome-wide scan. Fine mapping was performed, and subsequently 53 additional families from the same region were genotyped over the candidate regions. RESULTS: Linkage calculations were performed by using 3 different disease models, from a very broad (all stroke cases defined by World Health Organization MONICA criteria) to a narrower (ischemic stroke only) stroke phenotype. With all models, nonparametric multipoint linkage analysis yielded allele-sharing log of the odds (LOD) scores >1.2 at 9 locations: 1p34, 5q13, 7q35, 9q22, 9q34, 13q32, 14q32, 18p11, and 20q13. The highest allele-sharing LOD scores were obtained on chromosomes 5q (previously reported), 1p (LOD=2.09), and 18p (LOD=2.14). Fine mapping resulted in increased allele-sharing LOD scores for chromosome 5q (previously reported) and 9q22 (LOD=1.56), but all others decreased. Combining these initial results with a subsequent analysis of 53 additional families, we obtained the highest allele-sharing LOD scores on chromosomes 5q, 13q, and 18p, although none reached the initial genome-wide allele-sharing LOD scores. CONCLUSIONS: Genetic analysis of stroke in families from northern Sweden did not identify any new major stroke loci. This indicates that multiple minor susceptibility loci in addition to the previously known locus on chromosome 5 could contribute to the disease.

Aged↗
PubMed2006

Age, hypertension, and lacunar stroke are the major determinants of the severity of age-related white matter changes. The LADIS (Leukoaraiosis and Disability in the Elderly) Study.

BACKGROUND: Age-related white matter changes (ARWMC), seen on neuroimaging with high frequency in older people, are thought to be consequent to the effect of vascular risk factors and vascular diseases including hypertension and stroke. Among the proofs conventionally required for a factor to be considered a risk factor for a definite pathology, there is the demonstration of a trend in risk exposure related to disease severity. We sought whether such a trend existed in the association of vascular risk factors or comorbidities with the severity of ARWMC aiming particularly at further elucidating the relative roles of hypertension and stroke in this regard. METHODS: The LADIS (Leukoaraiosis and Disability) Study is evaluating the role of ARWMC as an independent determinant of the transition to disability in the elderly. Six hundred and thirty-nine nondisabled subjects (mean age 74.1+/-5.0, M/F: 288/351) with ARWMC of different severity grades on MRI (mild, moderate, or severe according to the Fazekas scale) were assessed at baseline for demographics, vascular risk factors, and comorbidities, and are being followed up for 3 years. RESULTS: Age, frequency of hypertension and history of stroke increased along with increasing ARWMC severity independently of other factors. For hypertension, however, this occurred only in subjects without a stroke history, while for stroke history, it mainly depended on lacunar stroke. The amount of cigarettes smoked and the interaction between hypercholesterolemia and smoking predicted only the most severe ARWMC grade. CONCLUSIONS: The LADIS Study confirms that age, hypertension and lacunar strokes are the major determinants of ARWMC. Smoking and hypercholesterolemia provide additional risk.

Age Factors↗
PubMed2005

Linkage of ischemic stroke to the PDE4D region on 5q in a Swedish population.

BACKGROUND AND PURPOSE: Recent Icelandic studies have demonstrated linkage for common forms of stroke to chromosome 5q12 and association between phosphodiesterase4D (PDE4D) and ischemic stroke. Using a candidate region approach, we wanted to test the validity of these findings in a different population from northern Sweden. METHODS: A total of 56 families with 117 affected individuals were included in the linkage study. Genotyping was performed with polymorphic microsatellite markers with an average distance of 4.5 cM on chromosome 5. In the association study, 275 cases of first-ever stroke were included together with 550 matched community controls. Polymorphisms were tested individually for association of PDE4D to stroke. RESULTS: Maximum allele-sharing lod score in favor of linkage was observed at marker locus D5S424 (lod score=2.06; P=0.0010). Conditional logistic regression calculations revealed no significant association of ischemic stroke to the defined at-risk allele in PDE4D (odds ratio, 1.1; 95% confidence interval, 0.84 to 1.45). A protective effect may though be implied for 2 of the polymorphisms analyzed in PDE4D. CONCLUSIONS: Using a candidate region approach in a set of stroke families from northern Sweden, we have replicated linkage of stroke susceptibility to the PDE4D gene region on chromosome 5q. Association studies in an independent nested case-control sample from the same geographically located population suggested that different alleles confer susceptibility/protection to stroke in the Icelandic and the northern Swedish populations.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed2005

Plasminogen activator inhibitor-1 4G/5G polymorphism and risk of stroke: replicated findings in two nested case-control studies based on independent cohorts.

BACKGROUND AND PURPOSE: Impaired fibrinolytic function secondary to elevated plasminogen activator inhibitor-1 (PAI-1) levels has been implicated in ischemic stroke. PAI-1 levels are determined by genetic factors and environmental factors, triglyceride levels in particular. The aim of this study was to investigate the common functional 4/5 guanosine (4G/5G) polymorphism in the promoter region of the PAI-1 gene and the risk of stroke. METHODS: A nested case-control study design was applied, using baseline data for 2 independent cohorts obtained at population-based surveys in northern Sweden. In study A, there were 113, and in study B, there were 275 individuals without major concomitant disease at baseline who later experienced a first-ever stroke. Blood samples obtained at baseline were analyzed for potential risk factors, including the 4G/5G polymorphism of the PAI-1 gene. RESULTS: The 4G allele of the PAI-1 polymorphism was associated with an increased risk of future ischemic stroke in both studies (odds ratio [OR] of 4G homozygosity, 1.87; 95% CI, 1.12 to 3.15 in study A; OR of 4G homozygosity, 1.56; 95% CI, 1.12 to 2.16 in study B). Individuals with the combination of hypertriglyceridemia and 4G homozygosity were at the greatest risk of developing stroke. Multiple logistic regression analysis identified 4G homozygosity, systolic blood pressure, and diabetes as independent predictors of ischemic stroke. CONCLUSIONS: Identical findings in 2 independent studies strongly suggest a true and clinically important association between PAI-1 4G/5G genotype and risk of future ischemic stroke. The observed modification of the genotype effect by triglycerides may be interpreted as a gene-environment interaction.

Adult↗
PubMed2005

What MONICA told us about stroke.

The WHO MONICA (Multinational Monitoring of Determinants and Trends in Cardiovascular Disease) Project is the world's largest prospective study on cardiovascular disorders. In the stroke component, 34,715 individually validated stroke events were recorded; these happened during 21.7 million years of observation in 14 populations in Europe, Siberia, and China. Two important questions were addressed. What is driving stroke mortality trends-changes in stroke incidence (risk of stroke) or changes in survival? To what extent do changes in the population burden of classic cardiovascular risk factors affect stroke risk in the population? The seven lessons that I learnt from the MONICA study are described; some were about the limitations of an ecological study for testing of hypotheses and evaluation of community-based intervention programmes. Socioeconomic factors seem more important than classic risk factors for the establishment of stroke trends in the population, best shown by the development of stroke mortality in eastern Europe during the 10 years of the WHO MONICA Project. The simplest, most important, and, for clinicians, the most encouraging of the lessons is that quality of stroke care makes a profound difference, not only to the patient and his or her family but also to the burden of stroke in the population at large.

China↗
PubMed2005

Impact of age-related cerebral white matter changes on the transition to disability -- the LADIS study: rationale, design and methodology.

Age-related white matter changes (ARWMC) on brain MRI have been associated with cognitive, motor, mood and urinary disturbances. These factors are known to contribute to disability in elderly people, but the impact of ARWMC and of their progression on the transition to disability is not determined. The LADIS (Leukoaraiosis and Disability in the Elderly) study aims at assessing the role of ARWMC as an independent predictor of the transition to disability in initially nondisabled elderly (65-84 years). Subjects who are not impaired or impaired on only 1 item of the Instrumental Activity of Daily Living (IADL) scale, presenting with different grades of ARWMC severity, were enrolled. Eleven European centers are involved. All the patients were assessed at baseline using an extensive set of clinical and functional tests including global functioning, cognitive, motor, psychiatric and quality of life measures. MRI studies were performed at baseline and will be repeated at the end of the follow-up period to evaluate changes of ARWMC and other lesions. ARWMC were categorized into mild, moderate or severe using the scale of Fazekas et al. For each ARWMC severity class, the primary study outcome is the transition to disability defined as an impairment on 2 or more IADL scale items. Secondary outcomes are the occurrence of dementia, depression, vascular events or death. Six-hundred and thirty-nine subjects (mean age 74.13 +/- 5.0 years, M/F: 288/351) were enrolled in a hospital-based setting and are being followed up for up to 3 years. The large and comprehensive set of measures in LADIS enables a comprehensive description of their functional and clinical features to be examined in relation to different morphological patterns and severity of ARWMC. The longitudinal design will give insight into the possible role of ARWMC and their progression as an independent contributor to disability in the elderly, eventually helping to develop preventive strategies to reduce the burden of disability in late life. The study results may also help to standardize, on an international basis, tools and criteria to identify early stages of disability.

Activities of Daily Living↗
PubMed2004

Findings from the reanalysis of the NINDS tissue plasminogen activator for acute ischemic stroke treatment trial.

BACKGROUND AND PURPOSE: Following publication of concerns about the results of the National Institute of Neurological Disorders and Stroke (NINDS) intravenous tissue plasminogen activator (t-PA) in acute stroke treatment trial, NINDS commissioned an independent committee "to address whether there is concern that eligible stroke patients may not benefit from t-PA given according to the protocol used in the trials and, whether the subgroup imbalance (in baseline stroke severity) invalidates the entire trial." METHODS: The original NINDS trial data were reanalyzed to assess the t-PA treatment effect, the effect of the baseline imbalance in stroke severity between the treatment groups on the t-PA treatment effect, and whether subgroups of patients did not benefit from receiving t-PA. RESULTS: A clinically important and statistically significant benefit of t-PA therapy was identified despite subgroup imbalances in baseline stroke severity and an increased incidence of symptomatic intracerebral hemorrhage in t-PA treated patients. The adjusted t-PA to placebo odds ratio (OR) of a favorable outcome was 2.1 (95% CI, 1.5 to 2.9). Although these exploratory analyses found no statistical evidence that the t-PA treatment effect differed among patient subgroups, the study was not powered to detect subgroup treatment differences. CONCLUSIONS: These findings support the use of t-PA to treat patients with acute ischemic stroke within 3 hours of onset under the NINDS t-PA trial protocol. Health professionals should work collaboratively to develop guidelines to ensure appropriate use of t-PA in acute ischemic stroke patients.

Data Interpretation, Statistical↗
PubMed2004

Declining mortality from subarachnoid hemorrhage: changes in incidence and case fatality from 1985 through 2000.

BACKGROUND AND PURPOSE: Northern Sweden has one of the highest incidence rates of subarachnoid hemorrhage (SAH) among the populations covered by the WHO MONICA (Monitoring of Trends and Determinants in Cardiovascular Disease) Project, approximately twice as high as in the other populations in Europe. In this study, trends in incidence, 28-day case fatality (CF), and mortality in SAH were followed over a 16-year period. METHODS: Since 1985, all SAHs in northern Sweden among patients 25 to 74 years old have been validated using strict MONICA criteria. From 1985 through 2000, 392 men and 592 women had SAH. During 3 years, 1997 to 1999, SAH among those aged 75 and older were also included. RESULTS: The total incidence among those 25 years and older was 13.3 per 100 000 in men and 24.4 per 100 000 in women. During the 16 years of observation, age standardized incidence in the group aged 25 to 74 years decreased significantly in men (P for trend <0.0001) but remained essentially unchanged in women (P for trend=0.64). The 28-day CF for all years was 36.5% in men, with no significant trend (P=0.7). In women, average CF was 35%, with a significant decline (P=0.003). The annual mortality decreased significantly in both sexes (by 3.87 [95% CI+/-2.75 percentage points] in men and 3.97 [95% CI+/-2.29] in women). CONCLUSIONS: The decline in SAH mortality has different explanations in men (declining incidence) and in women (declining CF).

Adult↗
PubMed2004

Population effects on individual systolic blood pressure: a multilevel analysis of the World Health Organization MONICA Project.

Individuals from the same population share a number of contextual circumstances that may condition a common level of blood pressure over and above individual characteristics. Understanding this population effect is relevant for both etiologic research and prevention strategies. Using multilevel regression analyses, the authors quantified the extent to which individual differences in systolic blood pressure (SBP) could be attributed to the population level. They also investigated possible cross-level interactions between the population in which a person lived and pharmacological (antihypertensive medication) and nonpharmacological (body mass index) effects on individual SBP. They analyzed data on 23,796 men and 24,986 women aged 35-64 years from 39 worldwide Monitoring of Trends and Determinants in Cardiovascular Disease (MONICA) study populations participating in the final survey of this World Health Organization project (1989-1997). SBP was positively associated with low educational achievement, high body mass index, and use of antihypertensive medication and, for women, was negatively associated with smoking. About 7-8% of all SBP differences between subjects were attributed to the population level. However, this population effect was particularly strong (i.e., 20%) in antihypertensive medication users and overweight women. This empirical evidence of a population effect on individual SBP emphasizes the importance of developing population-wide strategies to reduce individual risk of hypertension.

Adult↗
PubMed2004

Use of oral contraceptives and hormone replacement therapy in the WHO MONICA project.

AIMS: To compare menopausal age and the use of oral contraceptives (OC) and hormonal replacement therapy (HRT) between the 32 populations of the WHO MONICA Project, representing 20 different countries. METHODS: Using a uniform protocol, age at menopause and the use of OC and HRT was recorded in a random sample of 25-64 year-old women attending the final MONICA population cardiovascular risk factor survey between 1989 and 1997. A total of 39,120 women were included. RESULTS: There were wide variations between the populations in the use of OC and HRT. The use of OC varied between 0 and 52% in pre-menopausal women aged 35-44 years, Central and East Europe and North America having the lowest and West Europe and Australasia the highest prevalence rates. Among post-menopausal women between 45 and 64 years, the prevalence of HRT use varied from 0 to 42%. In general, the use of HRT was high in Western and Northern Europe, North America and Australasia and low in Central, Eastern and Southern Europe and China. With the exception of Canada (45 years), the mean age at menopause differed only little (ranging from 48 to 50 years) between the populations. CONCLUSION: The use of OC and HRT varies markedly between populations, in general following a regional pattern. Whereas, the prevalence rates are mostly similar within a country, there are remarkable differences even between neighbouring countries, reflecting nation-specific medical practice and public attitudes that are not necessarily based on scientific evidence.

Adult↗
PubMed2004

Mishaps in the management of stroke: a review of 214 complaints to a medical responsibility board.

BACKGROUND: This is the first survey of formal complaints to a Medical Responsibility Board (MRB) in the literature concerning stroke management and the disciplinary actions to which the complaints lead. METHODS: All available complaints submitted to the Swedish MRB during a 5-year period that concerned stroke management (n = 214) were reviewed. We compiled information on the plaintiffs, the health care staff the complaints were directed against, the area of stroke management involved and the disciplinary actions taken by the MRB. RESULTS: Only 1% of all complaints to the MRB concerned stroke. Three quarters of these complaints were directed against physicians and one fifth against nurses. 23 complaints (11%) resulted in a warning or an admonition. Nearly all disciplinary actions against physicians (12 of 13) concerned misdiagnoses, of subarachnoid hemorrhage in particular. The most common reason for a nurse receiving a warning or an admonition was negligent handling of drugs. CONCLUSIONS: The survey has identified two areas in which educational programs to improve patient safety seem essential. The small number of formal complaints and disciplinary actions suggest that other, blameless procedures have a greater potential than MRB actions to reduce mishaps in routine stroke care.

Diagnostic Errors↗
PubMed2004

Self-reported depression and use of antidepressants after stroke: a national survey.

BACKGROUND AND PURPOSE: Depression after stroke is often described as underdiagnosed and undertreated. However, there are few data on self-reported depression and use of antidepressants in stroke patients at large. MATERIALS AND METHODS: In the Swedish national quality assessment register, Riks-Stroke, 15 747 stroke survivors are recorded. They were asked about depressive mood and antidepressant treatment 3 months after stroke. Age-specific prevalence of antidepressant use after stroke was calculated. RESULTS: At 3 months after stroke, 12.4% of male and 16.4% of female stroke survivors reported that they always or often felt depressed. In a multiple logistic regression model, female sex, age younger than 65 years, living alone, having had a recurrent stroke, being dependent on others, and institutional living 3 months after stroke were independent predictors of self-reported depression. Antidepressant medication was used by 22.5% of men and 28.1% of women who had had a stroke. Of patients using antidepressant drugs, 67.5% did not report depressive mood. However, 8.4% of the entire cohort reported depressive mood but no treatment with antidepressants. When compared with the general population, approximately twice as many of the stroke patients were using antidepressant treatment. CONCLUSIONS: In this national survey, 1 in 7 patients reported that they felt depressed and the use of antidepressant drugs after stroke was common. The widespread use of antidepressants challenges the contention that antidepressants are generally underused after stroke. However, the substantial proportion reporting depressive mood but not using treatment with antidepressants suggests that patient selection for treatment should be more precise.

Aged↗
PubMed2003

[Improved survival after stroke but unchanged risk of incidence].

Stroke is the third most common cause of death in Sweden. With almost one million hospital days pro year, stroke consumes more hospital days than any other somatic disease. Each year between 27,000 and 35,000 have a stroke and the mean age of stroke patients in Sweden is now 75 years (73 years for men and 77 for women). Swedish studies have shown that the stroke incidence has been unchanged or even increasing slightly over the lasts decades. However, the stroke mortality has decreased, mainly because the case fatality has improved. In patients younger than 75 years, the Northern Sweden MONICA study has shown that the case fatality has declined from almost 20% 1985 to 11% in 1998. One important reason for the declining case fatality is probably the improved care of the stroke patients. In 1994 half of the patients were treated in a stroke unit. Today 73% of all patients are treated in a stroke unit. With an ageing population and an improved survival, the prevalence of stroke will increase as long as the incidence is unchanged. This means that the number of stroke patients will increase health care facilities at all levels. Therefore, it is very important to reduce or eliminate risk factors for stroke. Preventing a stroke saves much suffering for both patients and relatives and reduces the economic burden for the society.

Adult↗
PubMed2003

[Stroke--risk factors and primary prevention].

The five major risk factors for stroke are hypertension, smoking, diabetes, atrial fibrillation and physical inactivity. All of these are amenable. In addition, although hypercholesterolemia is not strongly associated with stroke in epidemiological studies, primary prevention with statins provides a modest reduction of stroke risk. Unchanged population levels of blood pressure in Sweden over the last two decades are accompanied by constant stroke incidence rates. The single most cost-effective preventive action is detection and treatment of hypertension in the elderly. Antismoking advice and anticoagulants in patients with atrial fibrillation and other cardiac sources of embolism also have favourable effects relative to costs. There is a dearth of successful population-based programs to prevent stroke.

Cardiovascular Diseases↗
PubMed2003

Are changes in mortality from stroke caused by changes in stroke event rates or case fatality? Results from the WHO MONICA Project.

BACKGROUND AND PURPOSE: Mortality from stroke has been declining over recent decades in most countries, except in Eastern Europe. In this analysis, based on the World Health Organization Monitoring Trends and Determinants in Cardiovascular Disease (WHO MONICA) Project, we explored to what extent these trends are due to changes in stroke event rate and to changes in case fatality. METHODS: The WHO MONICA Project collected standardized data from 14 populations in 9 countries. All acute strokes occurring in men and women 35 to 64 years of age were included. Registration was carried out between 1982 and 1995, resulting in time spans from 7 to 13 years. Trends in event rates and case fatality were calculated as average annual percentage change. RESULTS: Up to 6-fold differences were observed in stroke mortality. Mortality declined in 8 of 14 populations in men and in 10 of 14 populations in women. An increase in mortality was observed in Eastern Europe. In the populations with a declining trend, about two thirds of the change could be attributed to a decline in case fatality. In populations with increasing mortality, the rise was explained by an increase in case fatality. CONCLUSIONS: In most populations, changes in stroke mortality, whether declining or increasing, were principally attributable to changes in case fatality rather than changes in event rates. Whether this was due to changes in the management of stroke or changes in disease severity cannot be established on the basis of these results.

Adult↗