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| 2. |
- Rolfs, Arndt, et al.
(författare)
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Acute Cerebrovascular Disease in the Young The Stroke in Young Fabry Patients Study
- 2013
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Ingår i: Stroke: a journal of cerebral circulation. - 1524-4628. ; 44:2, s. 340-349
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Tidskriftsartikel (refereegranskat)abstract
- Background and Purpose-Strokes have especially devastating implications if they occur early in life; however, only limited information exists on the characteristics of acute cerebrovascular disease in young adults. Although risk factors and manifestation of atherosclerosis are commonly associated with stroke in the elderly, recent data suggests different causes for stroke in the young. We initiated the prospective, multinational European study Stroke in Young Fabry Patients (sifap) to characterize a cohort of young stroke patients. Methods-Overall, 5023 patients aged 18 to 55 years with the diagnosis of ischemic stroke (3396), hemorrhagic stroke (271), transient ischemic attack (1071) were enrolled in 15 European countries and 47 centers between April 2007 and January 2010 undergoing a detailed, standardized, clinical, laboratory, and radiological protocol. Results-Median age in the overall cohort was 46 years. Definite Fabry disease was diagnosed in 0.5% (95% confidence interval, 0.4%-0.8%; n=27) of all patients; and probable Fabry disease in additional 18 patients. Males dominated the study population (2962/59%) whereas females outnumbered men (65.3%) among the youngest patients (18-24 years). About 80.5% of the patients had a first stroke. Silent infarcts on magnetic resonance imaging were seen in 20% of patients with a first-ever stroke, and in 11.4% of patients with transient ischemic attack and no history of a previous cerebrovascular event. The most common causes of ischemic stroke were large artery atherosclerosis (18.6%) and dissection (9.9%). Conclusions-Definite Fabry disease occurs in 0.5% and probable Fabry disease in further 0.4% of young stroke patients. Silent infarcts, white matter intensities, and classical risk factors were highly prevalent, emphasizing the need for new early preventive strategies.
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| 3. |
- Steinicke, Robert, et al.
(författare)
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Kidney Function and White Matter Disease in Young Stroke Patients Analysis of the Stroke in Young Fabry Patients Study Population
- 2012
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Ingår i: Stroke: a journal of cerebral circulation. - 1524-4628. ; 43:9, s. 2382-2388
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Tidskriftsartikel (refereegranskat)abstract
- Background and Purpose-Impaired kidney function is thought to be associated with small vessel disease, outcome, and mortality in the general stroke population. Data are limited regarding young patients. The aim of this study was to investigate the association of kidney function and white matter hyperintensities (WMHs) in young patients with first ischemic stroke. Methods-We analyzed 2500 young (18-55 years) patients with first-ever ischemic stroke from the prospective observational Stroke in Young Fabry Patients (SIFAP1) study with available MRI data on WMH. Of these, 2009 had available data concerning estimated glomerular filtration rate (eGFR). Kidney function was expressed as eGFR by the Modification of Diet in Renal Disease method. Deep WMHs on MRI were classified by the Fazekas score. Multivariate analysis was performed using a regression model with random effects. Results-Mean eGFR was 96.7 mL/min in those with WMH Grade 0 to 1 (none to mild), 90.7 mL/min in WMH Grade 2 (moderate), and 89 mL/min in WMH Grade 3 (severe). Univariate analysis revealed WMH to be associated with age (P<0.001), hypertension (P<0.001), cardiovascular disease (P=0.015), overweight (body mass index >25 kg/m(2); P=0.013), current smoking (P=0.044), and eGFR (P=0.009). In multivariate analysis, age, hypertension, and eGFR remained associated with WMH severity. Conclusions-In young patients with acute ischemic stroke, lower eGFR values in the normal range are associated with the presence of moderate to severe WMH.
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| 4. |
- von Sarnowski, Bettina, et al.
(författare)
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Lifestyle Risk Factors for Ischemic Stroke and Transient Ischemic Attack in Young Adults in the Stroke in Young Fabry Patients Study
- 2013
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Ingår i: Stroke: a journal of cerebral circulation. - 1524-4628. ; 44:1, s. 119-125
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Tidskriftsartikel (refereegranskat)abstract
- Background and Purpose-Although many stroke patients are young or middle-aged, risk factor profiles in these age groups are poorly understood. Methods-The Stroke in Young Fabry Patients (sifap1) study prospectively recruited a large multinational European cohort of patients with cerebrovascular events aged 18 to 55 years to establish their prevalence of Fabry disease. In a secondary analysis of patients with ischemic stroke or transient ischemic attack, we studied age-and sex-specific prevalences of various risk factors. Results-Among 4467 patients (median age, 47 years; interquartile range, 40-51), the most frequent well-documented and modifiable risk factors were smoking (55.5%), physical inactivity (48.2%), arterial hypertension (46.6%), dyslipidemia (34.9%), and obesity (22.3%). Modifiable less well-documented or potentially modifiable risk factors like high-risk alcohol consumption (33.0%) and short sleep duration (20.6%) were more frequent in men, and migraine (26.5%) was more frequent in women. Women were more often physically inactive, most pronouncedly at ages <35 years (18-24: 38.2%; 25-34: 51.7%), and had high proportions of abdominal obesity at age 25 years or older (74%). Physical inactivity, arterial hypertension, dyslipidemia, obesity, and diabetes mellitus increased with age. Conclusions-In this large European cohort of young patients with acute ischemic cerebrovascular events, modifiable risk factors were highly prevalent, particularly in men and older patients. These data emphasize the need for vigorous primary and secondary prevention measures already in young populations targeting modifiable lifestyle vascular risk factors. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique Identifier: NCT00414583. (Stroke. 2013; 44: 119-125.)
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| 5. |
- Biffi, Alessandro, et al.
(författare)
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APOE genotype and extent of bleeding and outcome in lobar intracerebral haemorrhage: a genetic association study
- 2011
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Ingår i: Lancet Neurology. - 1474-4465. ; 10:8, s. 702-709
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Tidskriftsartikel (refereegranskat)abstract
- Background Carriers of APOE epsilon 2 and epsilon 4 have an increased risk of intracerebral haemorrhage (ICH) in lobar regions, presumably because of the effects of these gene variants on risk of cerebral amyloid angiopathy. We aimed to assess whether these variants also associate with severity of ICH, in terms of haematoma volume at presentation and subsequent outcome. Methods We investigated the association of APOE epsilon 2 and epsilon 4 with ICH volume and outcomes in patients with primary ICH in three phases: a discovery phase of 865 individuals of European ancestry from the Genetics of Cerebral Hemorrhage on Anticoagulation study, and replication phases of 946 Europeans (replication 1) and 214 African-Americans (replication 2) from an additional six studies. We also assessed the association of APOE variants with ICH volume and outcomes in meta-analyses of results from all three phases, and the association of APOE epsilon 4 with mortality in a further meta-analysis including data from previous reports. Admission ICH volume was quantified on CT scan. We assessed functional outcome (modified Rankin scale score 3-6) and mortality at 90 days. We used linear regression to establish the effect of genotype on haematoma volume and logistic regression to assess the effect on outcome from ICH. Findings For patients with lobar ICH, carriers of the APOE epsilon 2 allele had larger ICH volumes than did non-carriers in the discovery phase (p=2. 5x10(-5)), in both replication phases (p=0.008 in Europeans and p=0.016 in African-Americans), and in the meta-analysis (p=3.2x10(-8)). In the meta-analysis, each copy of APOE epsilon 2 increased haematoma size by a mean of 5.3 mL (95% CI 4.7-5.9; p=0.004). Carriers of APOE epsilon 2 had increased mortality (odds ratio [OR] 1.50, 95% CI 1.23-1.82; p=2.45x10(-5)) and poorer functional outcomes (modified Rankin scale score 3-6; 1-52, 1.25-1.85; p=1.74x10(-5)) compared with non-carriers after lobar ICH. APOE epsilon 4 was not associated with lobar ICH volume, functional outcome, or mortality in the discovery phase, replication phases, or meta-analysis of these three phases; in our further meta-analysis of 2194 patients, this variant did not increase risk of mortality (1.08,0.86-1.36; p=0.52). APOE allele variants were not associated with deep ICH volume, functional outcome, or mortality. Interpretation Vasculopathic changes associated with the APOE epsilon 2 allele might have a role in the severity and clinical course of lobar ICH. Screening of patients who have ICH to identify the epsilon 2 variant might allow identification of those at increased risk of mortality and poor functional outcomes.
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| 6. |
- Falcone, Guido J., et al.
(författare)
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Burden of Risk Alleles for Hypertension Increases Risk of Intracerebral Hemorrhage
- 2012
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Ingår i: Stroke: a journal of cerebral circulation. - 1524-4628. ; 43:11, s. 2877-2883
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Tidskriftsartikel (refereegranskat)abstract
- Background and Purpose-Genetic variation influences risk of intracerebral hemorrhage (ICH). Hypertension (HTN) is a potent risk factor for ICH and several common genetic variants (single nucleotide polymorphisms [SNPs]) associated with blood pressure levels have been identified. We sought to determine whether the cumulative burden of blood pressure-related SNPs is associated with risk of ICH and pre-ICH diagnosis of HTN. Methods-We conducted a prospective multicenter case-control study in 2272 subjects of European ancestry (1025 cases and 1247 control subjects). Thirty-nine SNPs reported to be associated with blood pressure levels were identified from the National Human Genome Research Institute genomewide association study catalog. Single-SNP association analyses were performed for the outcomes ICH and pre-ICH HTN. Subsequently, weighted and unweighted genetic risk scores were constructed using these SNPs and entered as the independent variable in logistic regression models with ICH and pre-ICH HTN as the dependent variables. Results-No single SNP was associated with either ICH or pre-ICH HTN. The blood pressure-based unweighted genetic risk score was associated with risk of ICH (OR, 1.11; 95% CI, 1.02-1.21; P=0.01) and the subset of ICH in deep regions (OR, 1.18; 95% CI, 1.07-1.30; P=0.001), but not with the subset of lobar ICH. The score was associated with a history of HTN among control subjects (OR, 1.17; 95% CI, 1.04-1.31; P=0.009) and ICH cases (OR, 1.15; 95% CI, 1.01-1.31; P=0.04). Similar results were obtained when using a weighted score. Conclusion-Increasing numbers of high blood pressure-related alleles are associated with increased risk of deep ICH as well as with clinically identified HTN. (Stroke. 2012; 43: 2877-2883.)
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| 7. |
- Rolfs, Arndt, et al.
(författare)
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Protocol and Methodology of the Stroke in Young Fabry Patients (sifap1) Study: A Prospective Multicenter European Study of 5,024 Young Stroke Patients Aged 18-55 Years
- 2011
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Ingår i: Cerebrovascular Diseases. - : S. Karger AG. - 1421-9786 .- 1015-9770. ; 31:3, s. 253-262
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Tidskriftsartikel (refereegranskat)abstract
- Background: Stroke in the young has not been thoroughly investigated with most previous studies based on a small number of patients from single centers. Furthermore, recent reports indicate that Fabry disease may be a significant cause for young stroke. The primary aim of our study was to determine the prevalence of Fabry disease in young stroke patients, while the secondary aim was to describe patterns of stroke in young patients. Methods: We initiated the Stroke in Young Fabry Patients (sifap1) study as a multinational prospective European study of stroke patients aged 18-55 years and collected a broad range of clinical, laboratory, and radiological data using stringent standardized methods. All patients were tested for Fabry disease and blood was stored for future genetic testing. Results: We managed to enroll 5,024 eligible young stroke patients in 15 countries and 47 centers across Europe between April 2007 and January 2010. The median number of patients included per center was 98 with a range between 8 and 315. The average duration of patient recruitment per center was 22 months, ranging between 5 and 33 months. The database was closed in July 2010. This paper describes protocol and methodology of the sifap1 study. Conclusion: The sifap1 study included the largest series of young stroke patients so far and will allow for analyses on a large number of aspects of stroke in the young. Copyright (C) 2010 S. Karger AG, Basel
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| 8. |
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| 9. |
- Woo, Daniel, et al.
(författare)
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Meta-Analysis of Genome-Wide Association Studies Identifies 1q22 as a Susceptibility Locus for Intracerebral Hemorrhage.
- 2014
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297. ; 94:4, s. 511-521
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Tidskriftsartikel (refereegranskat)abstract
- Intracerebral hemorrhage (ICH) is the stroke subtype with the worst prognosis and has no established acute treatment. ICH is classified as lobar or nonlobar based on the location of ruptured blood vessels within the brain. These different locations also signal different underlying vascular pathologies. Heritability estimates indicate a substantial genetic contribution to risk of ICH in both locations. We report a genome-wide association study of this condition that meta-analyzed data from six studies that enrolled individuals of European ancestry. Case subjects were ascertained by neurologists blinded to genotype data and classified as lobar or nonlobar based on brain computed tomography. ICH-free control subjects were sampled from ambulatory clinics or random digit dialing. Replication of signals identified in the discovery cohort with p < 1 × 10(-6) was pursued in an independent multiethnic sample utilizing both direct and genome-wide genotyping. The discovery phase included a case cohort of 1,545 individuals (664 lobar and 881 nonlobar cases) and a control cohort of 1,481 individuals and identified two susceptibility loci: for lobar ICH, chromosomal region 12q21.1 (rs11179580, odds ratio [OR] = 1.56, p = 7.0 × 10(-8)); and for nonlobar ICH, chromosomal region 1q22 (rs2984613, OR = 1.44, p = 1.6 × 10(-8)). The replication included a case cohort of 1,681 individuals (484 lobar and 1,194 nonlobar cases) and a control cohort of 2,261 individuals and corroborated the association for 1q22 (p = 6.5 × 10(-4); meta-analysis p = 2.2 × 10(-10)) but not for 12q21.1 (p = 0.55; meta-analysis p = 2.6 × 10(-5)). These results demonstrate biological heterogeneity across ICH subtypes and highlight the importance of ascertaining ICH cases accordingly.
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