Endogenous tissue-type plasminogen activator and cardioembolic brain infarct subtype.
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Atrial Fibrillation↗
Biomedical subjects
GENIC Investigators
Publications and source records attributed to GENIC Investigators.
Basilar artery diameter and 5-year mortality in patients with stroke.
BACKGROUND AND PURPOSE: Few and conflicting data exist on the case fatality rate in stroke patients with basilar artery dolichoectasia. We analyzed basilar artery characteristics (diameter, height of bifurcation, transverse position) and 5-year mortality (all-cause, nonstroke vascular, and stroke) in patients with brain infarction. METHODS: The basilar artery diameter was measured with a 16-diopter lens in 466 consecutively recruited patients with brain infarction confirmed by magnetic resonance imaging. The height of the bifurcation and the transverse position of the basilar artery were assessed on semiquantitative scales. Patients were followed up for a median of 5.3 years (range, 1.5 to 6.6) and were classified as having had stroke, nonstroke vascular, and nonvascular death according to the French national registry of death certificates. RESULTS: Of the 157 deaths, 88 were vascular (including 54 stroke deaths). Basilar artery diameter was associated with an increased 5-year stroke mortality rate but not with all-cause or nonstroke vascular mortality. The adjusted hazard ratio (HR) of stroke mortality per 1-mm increase in basilar artery diameter was 1.23 (95% confidence interval [CI], 1.07 to 1.41). A higher risk of stroke death was associated with basilar artery diameter at the 95th percentile (diameter >4.3 mm; adjusted HR 3.69; 95% CI, 1.63 to 8.38) and the height of bifurcation (adjusted HR for score >1, 2.08; 95% CI, 0.93 to 4.68) but not with transverse position. CONCLUSIONS: Basilar artery diameter was independently associated with cerebrovascular mortality. A diameter >4.3 mm may be a marker for a high risk of fatal stroke.
Aged↗
Cytokine polymorphisms associated with carotid intima-media thickness in stroke patients.
BACKGROUND AND PURPOSE: Carotid intima-media thickness (IMT) reflects generalized atherosclerosis and is predictive of future vascular events. Evidence exists that carotid IMT is heritable, and genetic studies can provide clues in the pathogenesis of atherosclerosis. METHODS: We recruited 470 white ischemic stroke patients, measured common carotid artery (CCA) IMT, and analyzed 54 polymorphisms with suspected roles in atherosclerosis. RESULTS: Among the polymorphisms tested, the angiotensin-converting enzyme insertion/deletion, osteopontin (OPN) T-443C, monocyte chemoattractant protein-1 (MCP-1) G-927C, and MCP-1 A-2578G polymorphisms were associated with CCA-IMT in age-gender-adjusted analysis. In multivariate analysis, the association between the OPN and MCP-1 polymorphisms remained significant. The OPN-443C allele was associated with increased IMT in the dominant model (0.053 mm for the TC and CC genotypes; P=0.001). The MCP-1-927C allele was associated with increased IMT in the additive model (0.040 mm for each C allele; P=0.001), and the MCP-1-2578 G allele was associated with decreased IMT in the recessive model (0.088 mm for the GG genotype; P=0.002). CONCLUSIONS: The OPN and MCP-1 genes, coding for 2 cytokines with known roles in atherosclerosis, may contribute to increased carotid IMT and warrant further study.
Adolescent↗
Blood lipids in brain infarction subtypes.
BACKGROUND: Little is known about the relationship between hypercholesterolaemia and specific aetiological subtypes of brain infarction (BI). METHODS: In a cross-sectional study of 492 pairs of patients with a BI proven by MRI and matched hospital controls, we determined the blood levels of triglycerides, total, HDL and LDL cholesterol, and apolipoprotein A(1) and B, in the same centralized laboratory. We performed aetiological BI subtype classification. RESULTS: Except for triglycerides, the risk of BI increased continuously with the lipid levels, without any heterogeneity between the main BI subtypes or the group on lipid-lowering therapy. The adjusted odds ratio per standard deviation in LDL cholesterol (0.93 mmol/l) was 1.74 (95% confidence interval, 1.02-2.98) in atherothrombotic strokes (n = 109) and 2.71 (95% confidence interval, 1.60-4.55) in lacunar strokes (n = 105). Eighty percent of patients were above the ATP-III guideline threshold LDL cholesterol of 2.59 mmol/l (100 mg/dl), with a major contribution of both atherothrombotic and lacunar stroke subtypes to this group. CONCLUSIONS: These findings suggest that blood lipids, particularly total and LDL cholesterol levels, are associated with all subtypes of BI, and that LDL above 2.59 mmol/l is highly prevalent.
Aged↗
Insular involvement in brain infarction increases risk for cardiac arrhythmia and death.
OBJECTIVE: Brain injuries may induce cardiac dysrhythmias and sudden cardiac death. METHODS: We analyzed 12-lead electrocardiograms of 493 consecutive patients with brain infarction (BI) proved by an magnetic resonance imaging and 493 control subjects matched for age, sex, and center. Insular involvement (insula (+/-)) was assessed by two independent readings of the magnetic resonance imaging scans. Cases were followed for 5 years. RESULTS: Acute BI was independently associated with heart rate (< or = 64 beats/min), abnormal repolarization, atrial fibrillation, and ventricular and supraventricular ectopic beats. Lower heart rate in BI patients was due to an interaction with smoking (p for interaction = 0.004). Insula(+) group was significantly associated with abnormal repolarization with no interaction with infarct side. Atrial fibrillation by history was also more frequent in the insula(+) than in the insula(-) group (p = 0.07). After adjustment for age, sex, cardiovascular history, and handicap at admission, right insula(+) BI was significantly associated with 2-year all-cause death (hazard ratio, 2.11; 95% confidence interval, 1.27-3.52) and with vascular death (hazard ratio, 2.00; 95% confidence interval, 1.00-3.93). In multivariate analysis including age, sex, cardiovascular history, handicap at admission, and lesion side, increased QTc interval and left bundle branch block were independent predictors of all-cause and vascular mortality at 2 years in right insula(+) patients. INTERPRETATION: These findings support the notion that right insular involvement may lead to electrocardiographic abnormalities with potential prognostic implications. This could be important for optimal care in patients with right insular infarct.
Adult↗
High blood pressure in early acute stroke: a sign of a poor outcome?
OBJECTIVE: To evaluate the prognostic value of admission blood pressure in patients with acute ischemic stroke by determining whether it contributes to clinical outcome and vascular death. METHODS: We studied 230 consecutive patients admitted within the first 24 h after the onset of ischemic stroke. We used the first systolic and diastolic blood pressure measurements recorded on admission. The functional outcome was assessed on the basis of mortality or dependency (Rankin Scale > 3) at the 10-day and 6-month visits. RESULTS: High systolic blood pressure on admission was associated with poor outcome at the 10-day and 6-month visits, independent of the baseline risk factors but not of the severity of the initial stroke (odds ratio, 1.39; 95% confidence interval, 0.50-3.87). The spontaneous decrease in systolic blood pressure within the first 10 days was higher in patients with functional improvement. The admission blood pressure was not significantly associated with total and vascular deaths, except for a threshold effect of diastolic blood pressure. CONCLUSIONS: After an acute stroke, the relationship between blood pressure and clinical outcome depended on the severity of the stroke on presentation, and on the level and trend of the systolic blood pressure during the first 24 h.
Acute Disease↗
Carotid intima-media thickness, plaques, and Framingham risk score as independent determinants of stroke risk.
BACKGROUND AND PURPOSE: The Framingham stroke risk score (FSRS) and Framingham cardiovascular risk score (FCRS) estimate the individual absolute cardiovascular and stroke risks. Common carotid artery intima-media thickness (CCA-IMT) and carotid plaques (CPs) are markers of subclinical atherosclerosis and help in the early identification of presymptomatic individuals. The purpose of this study was to correlate Framingham risk score (FRS) with CCA-IMT and CPs and evaluate their respective contribution to stroke risk. METHODS: In 510 consecutive patients with brain infarction and 510 matched controls, we calculated the FSRS and FCRS for each individual and performed carotid ultrasonography. Mean CCA-IMT was measured off-line at a central core laboratory, and presence of CPs was assessed. RESULTS: FRS progressively increased according to tertiles of CCA-IMT (P for trend <0.0001). The part of the variances of FSRS and FCRS explained by CCA-IMT was respectively 11% and 20%. The relationships between CCA-IMT and FRS were significantly different between patients with or without CPs (P for interaction <0.005). With increasing CCA-IMT, the 10-year FRS gradually increased between 10% and 20% in the presence of CPs and between 5% and 20% in the absence of CPs. Multiple conditional logistic regression for matched sets showed that CCA-IMT, FCRS, and CPs were independently associated with stroke risk, with an odds ratio of 1.68 (1.25 to 2.26; P=0.0006), 2.16 (1.57 to 2.98; P<0.0001), and 2.73 (1.68 to 4.44; P<0.0001), respectively, meaning that each of them may be important for evaluation of the individual cardiovascular risk. CONCLUSIONS: CCA-IMT, CPs, and FRSs correlated well. The CCA-IMT value may help discriminate between subjects at low or high 10-year risk.
Adult↗
Adverse associations between CX3CR1 polymorphisms and risk of cardiovascular or cerebrovascular disease.
OBJECTIVE: We investigated the role of monocyte-recruiting chemokines in cerebrovascular diseases among the subjects of the GENIC case-control study of brain infarction (BI). METHODS AND RESULTS: Of the genotypes tested, only homozygosity for the rare CX3CR1 alleles was more frequent in cases than in controls: the I249 and M280 alleles were associated with an increased risk of BI (OR, 1.66 and OR, 2.62 with P<0.05, respectively). This effect was independent of other established risk factors and uncorrelated with disease severity. The study confirmed previous reports of a dominant protective association between CX3CR1-I249 allele and the risk of cardiovascular history. The risk of BI associated with homozygosity for the rare CX3CR1 alleles was enhanced in patients with no previous cardiovascular events. Ex vivo studies showed that the number of monocytes adhering to immobilized CX3CL1, the CX3CR1 ligand, increased proportionally to the number of CX3CR1 mutated alleles carried by the individual. CONCLUSIONS: The rare CX3CR1 alleles were associated with an increased risk of BI and with reduced frequency of cardiovascular history. We propose that the extra adhesion of monocytes observed in individuals carrying rare alleles of CX3CR1 may favor mechanisms leading to stroke.
Adult↗
Renin-angiotensin-aldosterone system in brain infarction and vascular death.
The renin-angiotensin-aldosterone system has functions that may contribute to brain infarction (BI). In 459 matched pairs of white patients and control subjects, we measured plasma angiotensin-converting enzyme (ACE) levels, seven polymorphisms (angiotensinogen T174M and M235T, ACE I/D and 4656 2/3CT repeat [rpt], angiotensin II type 1 receptor A1166C and A153G, and aldosterone synthase CYP11B2), and evaluated 5-year poststroke mortality. Mean plasma ACE levels (+/-standard error) were significantly greater in patients than control subjects (37.5 +/- 0.9 vs 33.9 +/- 0.9), in patients with lacunar stroke, and in patients with no previous vascular (cerebrovascular or cardiovascular) history. The risk for BI increased with tertiles of plasma ACE, without an interaction with hypertension. After adjustments, the association disappeared except among patients with cardioembolic BI and those without previous vascular events. Among the polymorphisms, there was a weak association of BI with angiotensin II type 1 receptor 1166C, a weak protective effect with angiotensinogen 174M, and a strong association of angiotensinogen 235T with 5-year vascular mortality. These results suggest that renin-angiotensin-aldosterone system activity and genes contribute to cerebrovascular disease and poststroke vascular death in white patients.
Adolescent↗
Soluble thrombomodulin and brain infarction: case-control and prospective study.
BACKGROUND AND PURPOSE: Increased soluble thrombomodulin (sTM) concentration has been associated with recurrent coronary events, whereas in one prospective study it predicted fewer first-ever coronary events. One study found no relationship between brain infarction (BI) and sTM levels. Among all subjects of the Etude du Profil Génétique de l'Infarctus Cérébral (GENIC) cohort and those free of previous vascular history, we investigated the relationship between sTM level and BI risk, and among cases, its relationship with BI prognosis. METHODS: Patients with BI (n=492) were consecutively recruited from 12 centers. Hospital controls without a history of stroke (n=492) were individually matched for age, sex, and center. Blood samples were collected after hospitalization. Determination of sTM levels was centralized in a single laboratory. RESULTS: Soluble TM concentration significantly increased with age and hypertensive status, but was similar in cases and controls. With analyses restricted to 278 pairs of subjects with no previous vascular history, sTM concentration >59.6 microg/L (second and third tertiles compared with the first) was associated with fewer first-ever BI (adjusted odds ratio of 0.56 (95% CI, 0.35 to 0.89; P=0.014). Among the cases, increased sTM concentration was associated with a higher death rate after a median follow-up of 5.2 (1.4 to 6.4) years. The adjusted hazard ratio per 1 SD of sTM concentration increase (34.2 microg/L) was 1.19 (95% CI, 1.02 to 1.39; P=0.028). CONCLUSIONS: Increased sTM concentration may be protective against BI in subjects with no previous vascular disease, whereas it may predict a fatal outcome in patients who have already had a BI. Consequently, sTM levels should be interpreted according to vascular history.
Adult↗
Predictive values of lacunar transient ischemic attacks.
BACKGROUND AND PURPOSE: We postulated that a lacunar syndrome occurring with transient ischemic attacks (TIAs) or progressive nonsudden onset predicts a brain infarction (BI), presumably caused by a small artery disease (ie, lacunar BI) better than a lacunar syndrome with sudden onset. METHODS: We included 510 patients with BI. BI was classified into etiologic groups including lacunar BI group. We identified the patients with lacunar or nonlacunar syndrome, and those with TIAs preceding the BI or with symptoms of nonsudden onset. RESULTS: Nonlacunar syndrome had a negative predictive value for a lacunar BI of 95%. A lacunar syndrome had a positive predictive value (PPV) of 57% for lacunar infarction (n=109), and the PPV increased to 79% in the case of recent TIAs preceding the lacunar syndrome. Hypertension was present in 95% of cases with lacunar TIAs (odds ratio: 10.69; 95% confidence interval: 1.34 to 84.82; P=0.02). CONCLUSIONS: Lacunar TIAs are almost always associated with history of arterial hypertension and have a high PPV for lacunar BI. This subgroup of patients may reflect different underlying mechanisms than the group of patient with lacunar syndrome of sudden onset.
Adolescent↗
Intracranial arterial dolichoectasia and its relation with atherosclerosis and stroke subtype.
OBJECTIVE: To investigate the relationship between intracranial arterial dolichoectasia (IADE) and vascular risk factors, atherosclerosis of the carotid arteries as measured by ultrasound scan, and stroke subtypes. METHODS: The sample consists of 510 consecutively recruited patients with brain infarction confirmed by MRI. The diagnosis of IADE was made by consensus between two neurologists based on MRI results. An independent reading of the 510 scans was made, with measurement of the diameter of the seven main intracranial arteries with a 16-diopter lens to validate the consensus and to better characterize patients with IADE. RESULTS: Sixty-three IADE(+) patients were identified by consensus (12%), of whom 59 (94%) had at least one intracranial artery in the fourth quartile of the distribution of diameters of intracranial arteries. Multivariate analyses found an association between IADE(+) and age (OR [95% CI] 1.04 [1.01-1.08]), male sex (3.31 [1.67-6.55]), hypertension (1.94 [1.01-3.72]), and previous myocardial infarction (2.68 [1.33-5.38]). There was no association between IADE and carotid atherosclerosis markers such as plaque or intima-media thickening. Lacunar infarct was more frequent in patients with IADE (36% versus 19%), with an adjusted OR of 2.89 (95% CI 1.29-6.46) compared with atherothrombotic infarct. CONCLUSIONS: IADE was associated with vascular risk factors such as age, male sex, hypertension, previous history of myocardial infarction, and lacunar infarct, but not with carotid atherosclerosis.
Adolescent↗