| 1. |
- Ay, Hakan, et al.
(author)
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Pathogenic Ischemic Stroke Phenotypes in the NINDS-Stroke Genetics Network
- 2014
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In: Stroke. - 0039-2499. ; 45:12, s. 3589-3596
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Journal article (peer-reviewed)abstract
- BACKGROUND AND PURPOSE: NINDS (National Institute of Neurological Disorders and Stroke)-SiGN (Stroke Genetics Network) is an international consortium of ischemic stroke studies that aims to generate high-quality phenotype data to identify the genetic basis of pathogenic stroke subtypes. This analysis characterizes the etiopathogenetic basis of ischemic stroke and reliability of stroke classification in the consortium. METHODS: Fifty-two trained and certified adjudicators determined both phenotypic (abnormal test findings categorized in major pathogenic groups without weighting toward the most likely cause) and causative ischemic stroke subtypes in 16954 subjects with imaging-confirmed ischemic stroke from 12 US studies and 11 studies from 8 European countries using the web-based Causative Classification of Stroke System. Classification reliability was assessed with blinded readjudication of 1509 randomly selected cases. RESULTS: The distribution of pathogenic categories varied by study, age, sex, and race (P<0.001 for each). Overall, only 40% to 54% of cases with a given major ischemic stroke pathogenesis (phenotypic subtype) were classified into the same final causative category with high confidence. There was good agreement for both causative (κ 0.72; 95% confidence interval, 0.69-0.75) and phenotypic classifications (κ 0.73; 95% confidence interval, 0.70-0.75). CONCLUSIONS: This study demonstrates that pathogenic subtypes can be determined with good reliability in studies that include investigators with different expertise and background, institutions with different stroke evaluation protocols and geographic location, and patient populations with different epidemiological characteristics. The discordance between phenotypic and causative stroke subtypes highlights the fact that the presence of an abnormality in a patient with stroke does not necessarily mean that it is the cause of stroke.
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| 2. |
- Hindy, George, et al.
(author)
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Role of Blood Lipids in the Development of Ischemic Stroke and its Subtypes : A Mendelian Randomization Study
- 2018
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In: Stroke. - 0039-2499 .- 1524-4628. ; 49:4, s. 820-827
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Journal article (peer-reviewed)abstract
- BACKGROUND AND PURPOSE: Statin therapy is associated with a lower risk of ischemic stroke supporting a causal role of low-density lipoprotein (LDL) cholesterol. However, more evidence is needed to answer the question whether LDL cholesterol plays a causal role in ischemic stroke subtypes. In addition, it is unknown whether high-density lipoprotein cholesterol and triglycerides have a causal relationship to ischemic stroke and its subtypes. Our aim was to investigate the causal role of LDL cholesterol, high-density lipoprotein cholesterol, and triglycerides in ischemic stroke and its subtypes through Mendelian randomization (MR).METHODS: Summary data on 185 genome-wide lipids-associated single nucleotide polymorphisms were obtained from the Global Lipids Genetics Consortium and the Stroke Genetics Network for their association with ischemic stroke (n=16 851 cases and 32 473 controls) and its subtypes, including large artery atherosclerosis (n=2410), small artery occlusion (n=3186), and cardioembolic (n=3427) stroke. Inverse-variance-weighted MR was used to obtain the causal estimates. Inverse-variance-weighted multivariable MR, MR-Egger, and sensitivity exclusion of pleiotropic single nucleotide polymorphisms after Steiger filtering and MR-Pleiotropy Residual Sum and Outlier test were used to adjust for pleiotropic bias.RESULTS: A 1-SD genetically elevated LDL cholesterol was associated with an increased risk of ischemic stroke (odds ratio: 1.12; 95% confidence interval: 1.04-1.20) and large artery atherosclerosis stroke (odds ratio: 1.28; 95% confidence interval: 1.10-1.49) but not with small artery occlusion or cardioembolic stroke in multivariable MR. A 1-SD genetically elevated high-density lipoprotein cholesterol was associated with a decreased risk of small artery occlusion stroke (odds ratio: 0.79; 95% confidence interval: 0.67-0.90) in multivariable MR. MR-Egger indicated no pleiotropic bias, and results did not markedly change after sensitivity exclusion of pleiotropic single nucleotide polymorphisms. Genetically elevated triglycerides did not associate with ischemic stroke or its subtypes.CONCLUSIONS: LDL cholesterol lowering is likely to prevent large artery atherosclerosis but may not prevent small artery occlusion nor cardioembolic strokes. High-density lipoprotein cholesterol elevation may lead to benefits in small artery disease prevention. Finally, triglyceride lowering may not yield benefits in ischemic stroke and its subtypes.
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| 3. |
- Olsson, Sandra, 1976, et al.
(author)
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Genetic Variant on Chromosome 12p13 Does Not Show Association to Ischemic Stroke in 3 Swedish Case-Control Studies
- 2011
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In: STROKE. - 0039-2499. ; 42:1, s. 214-216
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Journal article (peer-reviewed)abstract
- Background and Purpose: In a genome-wide association study and subsequent case-control studies, the single-nucleotide polymorphism rs12425791 on chromosome 12p13 was reported to be associated with ischemic stroke, but this could not be validated in a recent well-powered study. We therefore investigated whether an association between ischemic stroke and rs12425791 could be detected in 3 different case-control studies from the southwest of Sweden. Methods: We examined 3606 patients with ischemic stroke and 2528 controls from 3 independent case-controls studies. Results: No significant association between ischemic stroke and the single-nucleotide polymorphism rs12425791 was detected in any of the 3 case-control samples or in the samples combined. The odds ratio for ischemic stroke for the minor allele in the combined sample was 1.02 (95% CI, 0.93 to 1.13). Conclusions: The single-nucleotide polymorphism rs12425791 does not confer a substantial risk for ischemic stroke in our population. Our results support a recent large study including other European populations.
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| 4. |
- André-Petersson, Lena, et al.
(author)
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Adaptive behavior in stressful situations and stroke incidence in hypertensive men: results from prospective cohort study "men born in 1914" in Malmo, Sweden
- 2001
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In: Stroke: a journal of cerebral circulation. - 1524-4628. ; 32:8, s. 1712-1717
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Journal article (peer-reviewed)abstract
- BACKGROUND AND PURPOSE: Although hypertension is a major risk factor for stroke, many hypertensive persons remain healthy. The aim of the present study was to analyze whether adaptation in a stressful situation was associated with the incidence of stroke in hypertensive men. METHODS: Two hundred thirty-eight hypertensive men were followed from baseline in 1982/1983 until first stroke, death, or December 31, 1996. Adaptation to stress was studied with the serial Color-Word Test. In the Regression dimension, 4 patterns of adaptation could be distinguished according to mastering of the test. Successful mastering of the test was shown in stabilized patterns, increasing difficulty in cumulative patterns, fluctuating difficulty in dissociative patterns, and fluctuating difficulty that increased during testing in cumulative-dissociative patterns. The patterns were compared regarding stroke incidence. RESULTS: Forty-three men experienced a stroke during follow-up. Stroke rates per 1000 person-years were 12.6 for men with stabilized patterns, 14.3 for men with cumulative patterns, 16.2 for men with dissociative patterns, and 31.2 for men with cumulative-dissociative patterns. Multivariate analysis, adjusted for relevant cerebrovascular risk factors, showed that the cumulative-dissociative pattern of the Regression dimension was associated with an increased risk of stroke during follow-up (relative risk 3.00, 95% CI 1.32 to 6.81). CONCLUSIONS: The specific behavior pattern, characterized by the greatest difficulties in managing the test, was associated with incidence of stroke in hypertensive men. One interpretation is that hypertensive men who chronically fail to find successful strategies in stressful situations are vulnerable to the damaging effects of stress and thereby at an increased risk of a future stroke.
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| 5. |
- Berntsson, John, et al.
(author)
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Orosomucoid, carotid plaque, and incidence of stroke
- 2016
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In: Stroke: a journal of cerebral circulation. - 0039-2499. ; 47:7, s. 1858-1863
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Journal article (peer-reviewed)abstract
- Background and Purpose - Orosomucoid (α-1-acid glycoprotein) is an acute-phase protein that has been implicated in anti-inflammatory, immunomodulating, and angiogenic pathways. Orosomucoid has also been associated with coronary disease and stroke. The relationship between orosomucoid, carotid plaque, and stroke incidence were explored in this study. Methods - Plasma levels of orosomucoid were assessed in 4285 subjects (39.8% men; mean age 57.5±5.9 years) without cardiovascular disease, who participated in the Malmö Diet and Cancer Study, between 1991 and 1994. The right carotid artery was examined for plaque using B-mode ultrasound examination. Incidence of stroke was followed up during a median follow-up time of 17.7 years. Results - Carotid plaque was present in 43.5% at baseline. Orosomucoid was significantly higher in subjects with carotid plaque (mean±SD: 0.72±0.22 versus 0.69±0.20 g/L; P
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| 6. |
- Engström, Gunnar, et al.
(author)
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Long-term effects of inflammation-sensitive plasma proteins and systolic blood pressure on incidence of stroke.
- 2002
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In: Stroke: a journal of cerebral circulation. - 1524-4628. ; 33:12, s. 2744-2749
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Journal article (peer-reviewed)abstract
- Background and Purpose— The present study investigated the relationships between inflammation-sensitive plasma proteins (ISPs) and systolic blood pressure (SBP), as well as the joint long-term effects of ISP and SBP on incidence of stroke. Methods— BP and 5 ISPs (fibrinogen, {alpha}1-antitrypsin, haptoglobin, ceruloplasmin, orosomucoid) were assessed in 6071 healthy men 28 to 61 years of age. All-cause mortality and incidence of stroke were monitored over a mean follow-up of 18.7 years in men defined by SBP (<120, 120 to 139, >=140 mm Hg) and ISP (0 to 1 or 2 to 5 ISPs in the top quartile). Results— SBP and diastolic BP were significantly and positively associated with the number of ISPs in the top quartile. As expected, elevated SBP was associated with an increased incidence of stroke. Among men with SBP >=140 mm Hg, there were, however, significant differences between those with high and low ISP levels. After risk factor adjustment, men with SBP >=140 mm Hg and high ISP levels had a relative risk of stroke of 4.3 (95% CI, 2.3 to 7.8) compared with men with SBP <120 mm Hg and low ISP levels. In the absence of high ISP levels, the risk associated with SBP >=140 was 2.5 (95% CI,1.4 to 4.6). Men with high ISP levels had a significantly increased risk of stroke also after exclusion of the events from the first 10 years of follow-up. Conclusions— High ISP levels are associated with elevated BP. These proteins are associated with an increased risk of stroke among men with high BP and provide information on stroke risk even after many years of follow-up.
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| 7. |
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| 8. |
- Khan, Farhad, et al.
(author)
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Incidence of Stroke and Stroke Subtypes in Malmo, Sweden, 1990-2000. Marked Differences Between Groups Defined by Birth Country.
- 2004
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In: Stroke: a journal of cerebral circulation. - 1524-4628. ; 35:9, s. 2054-2058
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Journal article (peer-reviewed)abstract
- Background and Purpose-The proportion of immigrants has increased in Sweden markedly during the last decades, as in many other Western countries. Incidence of stroke has increased during this period. However, it is primarily unknown whether incidence of stroke and stroke subtypes in Sweden is related to country of birth. Methods-Incidence of first-ever stroke was followed during 10 years in a cohort consisting of all 40- to 89-year-old inhabitants in the city of Malmo, Sweden (n=118134). Immigrants from 12 different countries were compared with native-born Swedes. Results-Adjusted for age, sex, marital status, and socioeconomic indicators, the incidence of stroke ( all subtypes) was significantly higher among immigrants from former Yugoslavia (relative risk [RR], 1.31; 95% CI, 1.1 to 1.6) and Hungary (RR, 1.33; CI, 1.02 to 1.7). A significantly increased incidence of intracerebral hemorrhage was observed in immigrants from Peoples Republic of China or Vietnam (RR, 4.2; CI, 1.7 to 10.4) and the former Soviet Union ( RR, 2.7; CI, 1.01 to 7.3). Immigrants from Finland had a significantly higher incidence of subarachnoid hemorrhage (RR, 2.8; CI, 1.1 to 6.8). A significantly lower incidence of stroke was observed in the group from Romania (RR, 0.14; CI, 0.04 to 0.6). Immigrants from Denmark, Norway, Germany, Chile, Czechoslovakia, and Poland had approximately the same risk as citizens born in Sweden. Conclusions-In this urban population from Sweden, there are substantial differences in stroke incidence and stroke subtypes between immigrants from different countries. To what extent this could be accounted for by exposure to biological risk factors remains to be explored.
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| 9. |
- Li, Cairu, et al.
(author)
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Blood Pressure Control and Risk of Stroke. A Population-Based Prospective Cohort Study.
- 2005
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In: Stroke: a journal of cerebral circulation. - 1524-4628. ; 36:4, s. 725-730
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Journal article (peer-reviewed)abstract
- Background and Purpose— Adequate control of blood pressure (BP) is a cornerstone in stroke prevention. This study explored the risk of stroke in relation to the quality of BP control in a population-based cohort and whether control of hypertension was related to background characteristics of patients. Methods— A total of 27 936 subjects (10 953 men and 16 983 women), 45 to 73 years old, living in Malmö, Sweden participated in the study. Incidence of stroke was followed-up for a mean period of 6 years. Controlled BP was defined as BP <140/90 mm Hg in subjects with pharmacological treatment for hypertension. Results— In the whole cohort, 16 648 subjects (60%) had hypertension (BP ≥140/90 mm Hg) and 23% of them received treatment. Among treated hypertensives, 88.2% had BP levels ≥140/90 mm Hg and 49.5% had BP levels ≥160/100 mm Hg. During the follow-up, 137 strokes occurred among treated hypertensive subjects. The crude incidence of stroke was 289/100 000 person-year in controlled hypertensive subjects and 705/100 000 person-year in treated hypertensive subjects with BP ≥140/90 mm Hg. It was estimated that {approx}45% of all strokes among subjects with treatment for hypertension might be attributed to uncontrolled BP. In treated hypertensives, the risk of stroke increased significantly with advancing age, current smoking, high level of diastolic BP, and diabetes. In hypertensive subjects without treatment (n=12 819), incidence of stroke was 363/100 000 person-year. Conclusion— Uncontrolled BP is highly prevalent in patients with pharmacological treatment for hypertension. More than 90% of stroke in this group occurred in those with uncontrolled BP. Adequate hypertension control may prevent a substantial proportion of first-ever stroke among treated hypertensives.
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| 10. |
- Li, Cairu, et al.
(author)
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Risk Factors for Stroke in Subjects With Normal Blood Pressure. A Prospective Cohort Study.
- 2005
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In: Stroke: a journal of cerebral circulation. - 1524-4628. ; 36:2, s. 234-238
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Journal article (peer-reviewed)abstract
- Background and Purpose— Although stroke is strongly associated with hypertension, some individuals with normal blood pressure (BP) experience a stroke. This prospective study explored risk factors for stroke in subjects with normal BP. Methods— A total of 11 228 men and 17 174 women, 45 to 73 years old, were examined in a population-based cohort study. Normal BP was defined as BP <140/90 mm Hg and no treatment for hypertension. The incidence of stroke was followed over a mean period of 6 years. Results— In the cohort, 10 938 (38%) had normal BP. Of them, 56 patients experienced a first-ever stroke (12% of all stroke). Compared with subjects without stroke during follow-up, these stroke subjects were older, had lower education, were often smokers and alcohol nondrinkers, and had a history of coronary heart disease (CHD), gastric ulcer, or renal calculus. Subjects with stroke had a higher body mass index (BMI) and a high-normal BP (130 to 139/85 to 89 mm Hg) more often. In a backward stepwise Cox-regression analysis, age (per 1 year; relative risk [RR], 1.12), current smoking (RR, 3.21), BMI (per SD; RR, 1.39), high-normal diastolic BP (RR, 2.35), history of CHD (RR, 4.92), and gastric ulcer (RR, 2.21) remained significantly associated with incidence of stroke. Conclusion— In subjects with normal BP, there are a number of potentially modifiable risk factors associated with an increased incidence of stroke.
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