Evaluation of the PC-1 K121Q and G2906C variants as independent risk factors for ischaemic stroke.

UNLABELLED: Overexpression of plasma cell membrane glycoprotein-1 (PC-1) inhibits insulin receptor tyrosine kinase activity and thus favours insulin resistance and atherosclerotic vascular disease. Recent findings indicate that the minor variant K121Q in the PC-1 gene confers an increased risk for early myocardial infarction independent of other established risk factors. We hypothesized that genetic variants in PC-1 may also influence the risk for cerebrovascular disease. AIM: Therefore, we assessed the association of the PC-1 K121Q variant in the coding region and a polymorphism (G2906C) in the 3' untranslated region of the PC-1 gene with the risk of stroke. PATIENTS: We analyzed 1014 patients with a history of ischaemic stroke from the Vienna stroke registry and 1001 control individuals without vascular disease. RESULTS, CONCLUSION: Genotype frequencies of both genetic variants were similar in patients and controls in the total study population. By multivariate analysis, no interactions were observed between the PC-1 genotype and established vascular risk factors. However, the PC-1 2906C allele was significantly more frequent in patients who suffered from stroke before the age of 40 years. In these patients the risk for ischaemic stroke was increased four-fold.

Polymorphisms in the coagulation factor VII gene and risk of primary intracerebral hemorrhage.

Data concerning genetic factors that may influence the risk of primary intracerebral hemorrhage (PICH) are scarce. One previous study, indicated that the carriers of the (-323)Ins allele of the coagulation factor VII (FVII) have an increased risk of PICH. Another recent study, tested the effect of apolipoprotein E. We analyzed, whether the (-401)G --> T polymorphism, which is in linkage disequilibrium (LD) with the 10-bp Ins/Del polymorphism at position (-323), or the (-402)G --> A polymorphisms of the FVII gene are associated with an increased risk for PICH. We performed a small case-control study in 85 patients with PICH and in 85 healthy control subjects. To each patient a control was individually matched for age, gender, and hypertension. We did not find any significant differences in allele frequencies for the A allele of the FVII (-402)G --> A polymorphism (0.25 vs. 0.25; P = 0.900, OR = 1, ns.) nor for the T Allele of the FVII (-401)G --> T polymorphism (0.09 vs. 0.12; P = 0.480, OR = 1.38, ns.). The analysis of haplotype distributions did not reveal significant differences. Our results do not support the hypothesis that the investigated polymorphisms in the FVII gene are significantly associated with the risk for PICH.

Prior therapy with antiplatelet agents is not associated with outcome in patients with acute ischemic stroke/TIA.

BACKGROUND AND PURPOSE: It is unclear whether prior therapy with antiplatelet agents (APA) is associated with a better outcome in patients with acute ischemic cerebrovascular events. METHODS: Within a multi-center cross-sectional study, nested in a cohort we analyzed the relation between prior therapy with APA and stroke severity in 1643 patients with acute ischemic stroke or TIA. Clinical severity of the vascular event was evaluated by the National Institutes of Health Stroke Scale on admission (NIHSS1) and after 1 week (NIHSS2). By means of analysis of variance we analyzed a possible association of APA with stroke severity and interactions regarding stroke severity between APA and other clinical measures. RESULTS: 475 patients (29 %) received aspirin prior to the cerebrovascular event, 51 patients (3 %) ticlopidine or clopidogrel and 26 patients (1.6%) aspirin combined with extended release dipyridamole. 66% (1091) of patients did not take any antiplatelet medication. Neither the NIHSS1 nor the NIHSS2 nor the change of stroke severity between these time points (NIHSS1- NIHSS2) was associated with prior APA medication. We did not find significant interactions between APA use and clinical measures regarding stroke severity. CONCLUSIONS: Our results do not indicate that prior therapy with APA is associated with a better outcome in acute ischemic cerebrovascular events. There were no interactions found with other features that were associated with stroke severity.

Structural and serum surrogate markers of cerebrovascular disease in obstructive sleep apnea (OSA): association of mild OSA with early atherosclerosis.

There is increasing evidence of a causal interaction between obstructive sleep apnea (OSA) and cerebrovascular disease. The aim of the study was to elucidate the relationship between the polysomnographically (PSG) measured severity of OSA and carotid atherosclerosis determined by ultrasonography and serum surrogate markers. 147 patients (102 males, 45 females) referred to our sleep laboratory for evaluation of snoring and sleep-disordered breathing were investigated. Carotid atherosclerosis was evaluated by serum analysis of high-sensitivity C-reactive protein (hs-CRP) and fibrinogen and four sonographic indices: intima-media thickness (IMT) of the common carotid artery (CCA), IMT from bulb to internal carotid artery (Bulb-ICA), combined IMT measurements from all segments and a plaque score (PlaS). Pearson correlation analysis, intergroup comparison (ANOVA), covariance analysis and a multiple regression were performed to assess the association between surrogate markers and respiratory variables. 44 patients had no OSA (apnea-hypopnea index AHI < 5/h), 27 mild (AHI 5-15), 25 moderate (AHI 15-30) and 51 severe OSA (AHI > 30). After adjusting for potential confounders, significant differences between the controls and all three OSA groups were observed in the CCA-IMT (p = 0.032) and in the PlaS between the controls and the severe group (p = 0.034). Multiple regression revealed the AHI as an independent predictor of CCA-IMT (p = 0.001) and combined IMT (p = 0.001), whereas the percentage of total sleep time with an oxygen saturation below 90 % was associated with Bulb-ICA IMT (p = 0.018) and hs-CRP (p = 0.015). OSA is associated with higher surrogate levels of cerebrovascular disease. Even mild OSA seems to predispose to early atherosclerosis.

Neuropsychological outcome 6 months after unilateral carotid stenting.

Percutaneous transluminal angioplasty with stenting (PTAS) has become a treatment option for severe carotid stenosis. The goal of our study was to determine prospectively neurocognitive outcome 6 months after unilateral stent-protected carotid angioplasty. Twenty consecutive patients who underwent stent-protected angioplasty for symptomatic (n=9) or asymptomatic (n=11) high-grade carotid stenosis were investigated and compared to an age and disease matched control group. Patients were administered preprocedurally and 6 months postprocedurally a battery of neuropsychological tests. We used reliable change indices methodology in order to control for practice and statistical effects unrelated to intervention. We found no cognitive change in approximately 90% of patients and cognitive improvement in approximately 10% of patients for concentration and attention variables. We further found no cognitive change in 61% of patients, cognitive improvement in 11% of patients and cognitive deterioration in 28% of patients for psychomotor speed. No cognitive change in 94% of patients and cognitive deterioration in 6% of patients was found for sustained attention; no cognitive change in 80% of patients, cognitive improvement in 15% of patients and cognitive deterioration in 5% of patients was found for verbal fluency; no cognitive change in 100% of patients was found for interference (Stroop test): no cognitive change in 95% of patients, cognitive improvement in 5% of patients was found for interference (c.I. test), respectively. Our study showed that 6 months after PTAS cognitive functioning did not change in most patients significantly. For some patients, however, significant improvement or deterioration in single neurocognitive domains can be expected. The reasons for these changes are unclear but may depend on variable type; magnitude of microemboli production; right vs. left cerebral vasculature, respectively.

Cerebral microembolism during transcatheter closure of patent foramen ovale.

BACKGROUND: Although transcatheter closure of patent foramen ovale (PFO) and atrial septal defect (ASD) has become a commonly performed intervention, the incidence of cerebral embolism with or without neurological deficits during such procedures has not been studied. METHODS: We monitored the middle cerebral artery in two different depths (48 mm and 53 mm) by continuous transcranial Doppler ultrasound during transcatheter PFO closure in 35 consecutive patients (F/M 20/15, mean age 47 +/- 11 years) and during ASD closure in 8 patients (F/M 7/1, mean age 45 +/- 5 years). All automatically detected high intensity transient signals (HITS) were manually reviewed to eliminate artifacts. RESULTS: HITS were detected in 33 of 35 patients (96%) with a median rate of 8 (interquartile range 4-19, range 2-29) HITS. The highest rates were observed when the septum was crossed with the guide wire (median 2; IQR 0-12; range 0-25) and when the left atrial disc was deployed (median 2; IQR 1-4; range 0-13). Despite this high rate of cerebral microembolism no clinically apparent neurological or neuropsychological deficit was observed. CONCLUSIONS: Silent cerebral embolism frequently occurs during transcatheter PFO and ASD closure. The peak of HITS at the time of crossing the septum with the guide wire may support the hypothesis that cerebral emboli in patients with PFO may originate from the septum itself. This may represent an alternative mechanism to the generally assumed paradoxical embolism.

Effect of pretreatment with statins on the severity of acute ischemic cerebrovascular events.

OBJECTIVE: Treatment with statins reduces the risk of ischemic stroke among patients at increased risk for vascular disease. Recent experimental data suggest neuroprotective properties of statins in acute cerebral ischemia. We investigated whether a premedication with statins is associated with a better outcome in patients with acute ischemic cerebrovascular events. METHODS: Within a cross-sectional study, nested in a cohort we identified 1691 patients with a recent ischemic stroke or transient ischemic attack. Clinical severity of the vascular event was evaluated by the modified Rankin Scale (mRS) after 1 week. By means of multivariate logistic regression modeling, we determined the influence of prior statin use on stroke severity with adjustment for potential confounding factors. RESULTS: Severe stroke, defined as a modified Rankin Scale of 5 or 6 (n=231; 14%), was less frequent in patients receiving statin treatment before the event (6% vs. 14%, OR=0.37; 95% CI 0.19 to 0.74; p=0.004). This association remained significant after adjustment for confounding factors. We found a significant interaction between the presence of diabetes and the effect of pretreatment with statins on stroke outcome. Of the patients with diabetes, none of those on statin treatment but 16% of those without a statin had a bad outcome. After exclusion of the group of diabetic patients with prior statin medication, the protective effect was reduced and not statistically significant anymore. CONCLUSIONS: Pretreatment with statins seems to be associated with reduced clinical severity in patients with acute ischemic cerebrovascular events, particularly in patients with diabetes.

Is elevated mean platelet volume associated with a worse outcome in patients with acute ischemic cerebrovascular events?

BACKGROUND AND PURPOSE: Increased mean platelet volume (MPV), indicating higher platelet reactivity, is associated with an increased risk of myocardial infarction. Higher levels of MPV have been found in patients with acute ischemic stroke than in control subjects. Data from smaller studies regarding an association between MPV and stroke severity and outcome have been controversial. If such an association exists, MPV might help to identify patients at increased risk of a severe course of acute cerebrovascular disease. METHODS: Within a multicenter, cross-sectional study nested in a cohort, we analyzed the relation between MPV and stroke severity as determined by the modified Rankin Scale after 1 week in 776 patients with acute ischemic stroke or transient ischemic attack. By multivariate logistic regression modeling, we determined the influence of MPV on stroke severity, adjusting for potential confounding factors. RESULTS: Patients within the highest quintile of MPV had a significantly higher risk of suffering a severe stroke, defined as modified Rankin Scale score of 3 to 6, compared with patients within the lowest quintile (odds ratio=2.6; 95% confidence interval, 1.6 to 4.1; P<0.001). This association remained significant after adjustment for possible confounding factors (odds ratio=2.2; 95% confidence interval, 1.2 to 4.0; P=0.013). CONCLUSIONS: Our results indicate that an elevated MPV is associated with a worse outcome for acute ischemic cerebrovascular events independent of other clinical parameters.

Association of parental history of stroke with clinical parameters in patients with ischemic stroke or transient ischemic attack.

BACKGROUND AND PURPOSE: Data regarding hereditary influences on stroke remain controversial. We investigated possible associations of a family history of stroke with clinical parameters in a large cohort of well-documented patients with ischemic cerebrovascular events, with special reference to sex-specific differences. METHODS: We analyzed the association between a maternal and/or paternal history of stroke and clinical parameters in 1564 patients with known maternal and paternal history of stroke and suffering from ischemic stroke or transient ischemic attack within the Vienna Stroke Registry. RESULTS: Patients with a maternal history of stroke were significantly more often female (54%) than those without (44%; P=0.003). Hypertension was more prevalent in female patients with than in those without a maternal history of stroke (87% versus 74%; P=0.001). These associations remained significant after multivariate adjustment (adjusted odds ratio, 1.9; 95% CI, 1.1 to 3.5; P=0.024). Of those female patients with an echocardiogram (n=225), those with a maternal history of stroke more often had left ventricular hypertrophy (48%) than those without (20%) (adjusted odds ratio, 3.6; 95% CI, 1.5 to 8.2; P=0.003). In contrast, hypertension was equally prevalent in male patients with or without a maternal history of stroke (75% versus 74%; P=0.754). We found no significant associations of clinical parameters with a paternal history of stroke. CONCLUSIONS: Our results indicate a sex-specific relationship between a maternal history of stroke and the prevalence of hypertension and left ventricular hypertrophy in female patients with ischemic cerebrovascular events.

Current strategies of secondary prevention after a cerebrovascular event: the Vienna stroke registry.

BACKGROUND AND PURPOSE: Oral anticoagulation (OAC) and antiplatelet drugs are effective in the secondary prevention of ischemic cerebrovascular events. Only few data exist about the factors influencing the choice of a specific therapy for secondary prevention in patients with a recent stroke or transient ischemic attack (TIA). METHODS: Within a cross-sectional study, nested in a cohort we identified 931 patients with a recent ischemic stroke or TIA who were discharged with OAC or with one of the antiplatelet medications aspirin, clopidogrel, or the combination of aspirin and extended-release dipyridamole. By means of multivariate logistic regression analysis, we determined the influence of several clinical variables on the decision between OAC and overall antiplatelet therapy as well as on the decision between different antiplatelet therapies. RESULTS: A cardioembolic etiology of the index event and atrial fibrillation were independently associated with the use of OAC. Age was inversely associated with the use of OAC. Different estimations of contraindications to OAC were the main reason for the considerable variability among the participating centers. The most important factor promoting the use of clopidogrel was therapy with aspirin before the index event. Patients with large- or small-vessel disease received clopidogrel more often than those with an event of undetermined etiology. We found an extremely high interhospital variability for the use of the combination of aspirin with extended-release dipyridamole. CONCLUSIONS: Current recommendations are applied in clinical practice, but great variability between different centers remains. More clearly defined guidelines for indications for, as well as contraindications against, a specific therapy are necessary.

A medial to lateral shift in pre-movement cortical activity in hemi-Parkinson's disease.

OBJECTIVE: Recent evidence suggests that cortical activity associated with voluntary movement is relatively shifted from medial to lateral premotor areas in Parkinson's disease. This shift occurs bilaterally even for unilateral responses. It is not clear whether the shift in processing reflects an overall change in movement strategy, thereby involving alternate cortical areas, or reflects a compensatory change whereby, given the appropriate conditions, less impaired cortical areas are able to provide a similar function in compensation for those areas which are more impaired. This issue was examined in patients with hemi-Parkinson's disease, in whom basal ganglia impairment is most pronounced in one hemisphere. METHODS: Fourteen patients with hemi-Parkinson's disease and 15 age-matched control subjects performed a Go/NoGo finger movement task and the contingent negative variation (CNV) was recorded from 21 scalp positions. RESULTS AND CONCLUSIONS: Maximal CNV amplitudes were found over central medial regions for control subjects, but were shifted more frontally for Parkinson's disease patients, reduced in amplitude over the midline and lateralized towards the side ipsilateral to the greatest basal ganglia impairment. This shift in cortical activity from medial to lateral areas in Parkinson's disease patients appears to reflect a compensatory mechanism operating predominantly on the side of greatest basal ganglia impairment.

Homozygosity for the C-->T polymorphism at nucleotide 46 in the 5' untranslated region of the factor XII gene protects from development of acute coronary syndrome.

Recently, a C-->T polymorphism at nucleotide 46 in the 5'-untranslated region of the factor XII (FXII) gene was shown to be associated with lower levels of FXII. To study the impact of this polymorphism on the development of an acute coronary syndrome (ACS), we compared 303 patients with ACS and 227 patients with stable coronary artery disease (CAD). In the latter group, 54.2% of individuals carried wild-type FXII:46C, 37.9% were heterozygous FXII:C46T and 7.9% were homozygous for FXII:46T. In contrast, in the ACS group (n = 303), 54.1% were wild-type FXII:46C, 42.6% were heterozygous FXII:C46T and only 3.3% carried the homozygous FXII:46T genotype. The 2.5-fold lower prevalence of the FXII:46T genotype in patients with ACS could indicate a protective effect on the development of ACS (odds ratio = 0.4, 95% CI 0.1-0.9) in patients with pre-existing CAD.

[The indications and embolism monitoring in lumen-opening therapies of the a. carotis]. / Indikationen und Embolie-Monitoring bei lumeneröffnenden Therapien der A. carotis.

Carotid endarterectomy (CEA) is proven to be beneficial in symptomatic patients with high-grade carotid stenosis (70% to 99%; residual lumen as a percentage of the normal distal internal carotid artery) on condition that the peri-operative risk for mortality and morbidity is less than 6%. A minority of the "leading experts" in North America (48%) and Western Europe (28%) recommends carotid endarterectomy in asymptomatic patients in general. Most experts suggest to perform surgery only in asymptomatic patients who are at risk for carotid occlusion in the near future or embolism. At its present state, angioplasty and stenting is an experimental although promising technique which will have to be compared to carotid endarterectomy. Criteria for duplex grading of internal carotid stenosis have been established and systematically validated to results of angiography. Pre-surgical use of angiography will more and more be restricted to selected patients in whom the results of duplex sonography remain inconclusive. The detection of microemboli with transcranial doppler sonography seems to be of particular importance before and during carotid angioplasty and stenting.

The 4G/4G genotype at nucleotide position -675 in the promotor region of the plasminogen activator inhibitor 1 (PAI-1) gene is less frequent in young patients with minor stroke than in controls.

Genetic risk factors play an important role in the aetiology of vascular diseases. The insertion/deletion polymorphism (4G/5G) in the promotor region of the plasminogen activator inhibitor 1 (PAI-1) gene has been associated with an increased risk of myocardial infarction. We investigated 136 patients with minor stroke (MS) and transient ischaemic attack (TIA) and found a prevalence of 0.32 for the 4G/4G genotype in patients compared with 0.42 in 115 age-matched healthy controls. The 4G/4G genotype was significantly less frequent among 61 patients symptomatic before the age of 60 years (prevalence 0.20) than in 75 patients symptomatic after 60 years of age (prevalence 0.42; odds ratio). Our results indicate that the 4G/4G genotype is not a risk factor for MS or TIA and may even be protective in young patients.

Reduced activation of midline frontal areas in human elderly subjects: a contingent negative variation study.

Contingent negative variation (CNV) was recorded from electrodes F7, F3, Fz, F4, F8, T7, C3, Cz, C4, T8, P7, P3, Pz, P4 and P8 in 19 young (mean age: 23 years) and 15 elderly (mean age: 66 years) healthy right-handed subjects, using a S2-choice paradigm. Young subjects showed early peak negativity shortly after the warning stimulus over mid-frontal areas, whereas for the remaining electrodes the negativity increased continuously. The amplitude of the early CNV was selectively reduced in elderly subjects over midline but not lateral frontal areas. We conclude that the activation of frontal midline areas as pre-supplementary motor area or anterior cingulate might be impaired in higher age.

The relation between erythrocyte volume and folate levels is influenced by a common mutation in the methylenetetrahydrofolate reductase (MTHFR) gene (C677T).

BACKGROUND: The enzyme 5,10 methylenetetrahydrofolate reductase (MTHFR) plays an important role in folate metabolism and folate-dependent reactions. Homozygosity for a common polymorphism in the MTHFR gene (C677T, Ala to Val) is associated with an increased risk of neural tube defects and hyperhomocysteinemia in individuals with low folate levels. Homozygous carriers of the polymorphism with adequate folate levels, on the other hand, seem to be at lower risk for colorectal cancer. Homozygous carriers of the polymorphism (5-15% of the white population) probably represent a subpopulation with increased folate needs. Hematological sequelae of folate deficiency have been recognized for a long time. However, no data exist concerning the relation between the C677T MTHFR polymorphism, folate levels, and hematological parameters. METHODS: We investigated associations between the C677T MTHFR polymorphism, folate levels, total plasma homocysteine, and hematological parameters in 94 patients with cerebrovascular disease (transient ischemic attack/minor stroke) and in 82 healthy subjects. RESULTS: Homozygous carriers (VV) of the polymorphism with low folate levels showed significantly higher homocysteine levels than mutation-negative (AA) and heterozygous (AV) subjects (P = 0.038). Furthermore, VV subjects in the lowest folate quartile exhibited significantly higher mean erythrocyte volumes (MCV) and a tendency towards higher erythrocyte hemoglobin content (MCH) than AA and AV subjects (P = 0.008 and 0.069, respectively). Although MCV was not influenced by folate levels in AA and AV subjects, in VV subjects a significant inverse correlation with folate levels could be demonstrated (P = 0.544 and 0.020, respectively). CONCLUSION: We demonstrate an association between the C677T polymorphism, folate levels, and hematological parameters. The elevation of MCV in homozygous carriers of the polymorphism with low folate levels indicates impaired DNA synthesis and/or methylation in these subjects. Considering our data and the results of previous studies, the polymorphism may have contrary effects on homocysteine metabolism and DNA synthesis/methylation dependent on a subject's folate supply. Although the polymorphism is disadvantageous in homozygous carriers with low folate levels, its presence may be beneficial in individuals with adequate folate supply.

Early occipito-parietal activity in a word recognition task: an EEG and MEG study.

OBJECTIVE: We investigated early brain activity (under 200 ms after the stimulus onset) related to the encoding and the retrieval of verbal information. METHODS: First, we compared ERPs produced by words which were encoded to ERPs produced by words from following test phases (correctly identified repetitions and correctly classified new words) in two different experiments. Experiment 1 consisted of an intentional learning paradigm and experiment 2 consisted of an incidental learning paradigm. In addition, we conducted a control experiment (experiment 3), which was a continuous recognition task with two different repetition intervals. Secondly, we conducted a magnetoencephalographic (MEG) study to further investigate early brain activity (experiment 4). The same intentional learning paradigm as in experiment 1 was used. RESULTS: We found that ERPs elicited by correctly classified test words (repeated words and new words) of both experiment 1 and experiment 2 were significantly more negative going than the ERPs elicited by the study words. This effect was apparent between 100 ms and 200 ms after the stimulus onset and was distributed over occipital and parietal scalp locations. In the control task (experiment 3), these early potential differences were missing (for both repetition intervals). Early event-related fields (ERFs) were also found to depend on the situation of the study phase and the test phase. This activity difference peaked at 120 ms after the stimulus onset. The distributions of the difference magnetic fields were occipito-parietal and thus consistent with the findings of experiment 1 (EEG-experiment). CONCLUSION: Whether the effect we defined in the present study is due to an increase of activity during the test situation or due to a decrease of activity during the study situation remains unclear. However, it might reflect attentional processes within a word recognition task depending on whether a word is encoded or an effort of word retrieval has to be made.

Genetic and nongenetic factors influencing plasma homocysteine levels in patients with ischemic cerebrovascular disease and in healthy control subjects.

Moderately elevated plasma homocysteine levels have been established as an independent risk factor for atherosclerosis and its complications, including cerebrovascular disease. A common mutation (C677T) in the gene encoding for the enzyme methylenetetrahydrofolate reductase (MTHFR) has been linked to increased plasma homocysteine levels in homozygous carriers, particularly in the presence of low folate levels. However, the results of most of the previous studies suggest that the C677T MTHFR mutation is not a significant risk factor for arterial disease. This discrepancy might, at least partly, be due to the fact that plasma homocysteine levels are influenced by several other factors, including age, gender, renal function, and vitamin status. We investigated the relation between plasma homocysteine levels, the C677T MTHFR mutation, and these other factors in a population of 96 patients with transient ischemic attacks or minor strokes and in 96 age- and sex-matched healthy control subjects. We further tested the value of a multivariate model for the prediction of plasma homocysteine levels under particular consideration of the MTHFR mutation status. In the patients, plasma homocysteine levels were significantly higher than in the healthy control subjects. With regard to the MTHFR mutation, the distribution of the C/C, C/T, and T/T genotypes was not significantly different between patients and healthy control subjects. Univariate (linear regression) analysis revealed significant (positive) correlations between plasma homocysteine levels on the one hand and age and creatinine on the other, the latter particularly in subjects with creatinine levels in the upper quartile. Significant (negative) correlations were found between plasma homocysteine levels, vitamin B12, and folate levels. However, these relations could much better be expressed by means of a multiplicative regression model. T/T subjects exhibited slightly higher homocysteine levels than C/C and C/T subjects; however, the differences between the 3 genotypes were not significant. Multivariate (stepwise regression) analysis revealed age, vitamin B12 levels, folate levels, and creatinine levels as significant independent variables influencing plasma homocysteine levels, whereas the MTHFR mutation status and gender were removed from the model. Considering all 192 subjects, only 28.8% of the variance of plasma homocysteine levels could be accounted for by the model. However, in homozygous carriers of the MTHFR mutation, the predictive power of the model is very high, explaining 76.1% of the variance of plasma homocysteine levels. According to our results, the C677T mutation does not constitute a major risk factor for transient ischemic attack or minor stroke, even under consideration of other possibly confounding factors that are known to affect plasma homocysteine levels. However, it is possible to predict plasma homocysteine levels in homozygous carriers of the mutation with high accuracy. The knowledge of the MTHFR mutation status may therefore help to identify subjects at high risk for hyperhomocysteinemia.