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Biomedical subjects

Virgilio Gallai

Publications and source records attributed to Virgilio Gallai.

At least 19 recordsLinked to original sources

Influence of dementia on antithrombotic therapy prescribed before stroke in patients with atrial fibrillation.

BACKGROUND AND PURPOSE: Oral anticoagulation (OAC) decreases the risk of stroke in patients with nonvalvular atrial fibrillation (NVAF), but remains underused in practice. The aim of this study was to test the hypothesis that prestroke dementia influenced the nonprescription of OAC before stroke. METHODS: This is an ancillary study of Stroke in Atrial Fibrillation Ensemble II, an observational study conducted in patients with a previously known NVAF, consecutively admitted for an acute stroke to French and Italian centers. Prestroke dementia was evaluated by the clinical physician and validated by an Informant Questionnaire for Cognitive Decline in the Elderly score of >or=104 in patients with a reliable informant. RESULTS: Of 204 patients, 24 patients met criteria for prestroke dementia according to GP's opinion. The only variables independently associated with OAC before stroke were follow-up by a cardiologist (adjusted OR: 3.33; 95% CI: 1.47-7.53) and a younger age of patients (adjusted OR: 0.94; 95% CI: 0.89-0.99). Variables independently associated with any antithrombotic drug therapy before stroke were follow-up by a general practitioner (adjusted OR: 2.78; 95% CI: 1.09-7.11), and by a cardiologist (adjusted OR: 3.15; 95% CI: 1.48-6.69). CONCLUSION: In daily practice, the under-prescription of OAC in patients with NVAF mainly depends on co-morbidity and on characteristics of the physician, not on prestroke dementia.

Administration, Oral↗

Secondary prevention of stroke in patients with atrial fibrillation: factors influencing the prescription of oral anticoagulation at discharge.

BACKGROUND: Oral anticoagulation (OAC) is the only treatment that has shown a significant benefit to reduce the risk of recurrence in patients with ischemic stroke and nonvalvular atrial fibrillation (NVAF). However, OAC is still underused, even at discharge from neurological centers. The objective of this study was to identify the reasons underlying the prescription of OAC at discharge after an ischemic stroke in patients with NVAF. METHODS: We investigated the reasons why ischemic stroke patients with NVAF were not treated with OAC at discharge from 40 centers located in 5 European countries (Austria, Belgium, France, Italy, and Portugal). RESULTS: Of 320 ischemic stroke survivors at discharge, 186 (58.1%) received OAC, while 260 (81.3%) patients were theoretically eligible according to guidelines and the absence of contraindications. There were significant differences between countries and the logistic regression analysis found being already under OAC before stroke, having no leukoaraiosis, having no potential contraindication, being younger than 75 years, being married and suffering from angina pectoris as independent predictors of being discharged under OAC. CONCLUSION: This study suggests that besides patient-related factors, the prescription of OAC is also significantly influenced by the social environment and national practices.

Administration, Oral↗

Novel parkin mutations detected in patients with early-onset Parkinson's disease.

A multiethnic series of patients with early-onset Parkinson's disease (EOP) was studied to assess the frequency and nature of parkin/PARK2 gene mutations and to investigate phenotype-genotype relationships. Forty-six EOP probands with an onset age of < 45 years, and 14 affected relatives were ascertained from Italy, Brazil, Cuba, and Turkey. The genetic screening included direct sequencing and exon dosage using a new, cost-effective, real-time polymerase chain reaction method. Mutations were found in 33% of the indexes overall, and in 53% of those with family history compatible with autosomal recessive inheritance. Fifteen parkin alterations (10 exon deletions and five point mutations) were identified, including four novel mutations: Arg402Cys, Cys418Arg, IVS11-3C > G, and exon 8-9-10 deletion. Homozygous mutations, two heterozygous mutations, and a single heterozygous mutation were found in 8, 6, and 1 patient, respectively. Heterozygous exon deletions represented 28% of the mutant alleles. The patients with parkin mutations showed significantly earlier onset, longer disease duration, more frequently symmetric onset, and slower disease progression than the patients without mutations, in agreement with previous studies. This study confirms the frequent involvement of parkin and the importance of genetic testing in the diagnostic work-up of EOP.

Adolescent↗

Dysphagia following Stroke.

BACKGROUND: Dysphagia is common after stroke. We aimed to study the prognosis of dysphagia (assessed clinically) over the first 3 months after acute stroke and to determine whether specific neurovascular-anatomical sites were associated with swallowing dysfunction. METHODS: We prospectively examined consecutive patients with acute first-ever stroke. The assessment of dysphagia was made using standardized clinical methods. The arterial territories involved were determined on CT/MRI. All patients were followed up for 3 months. RESULTS: 34.7% of 406 patients had dysphagia. Dysphagia was more frequent in patients with hemorrhagic stroke (31/63 vs. 110/343; p = 0.01). In patients with ischemic stroke, the involvement of the arterial territory of the total middle cerebral artery was more frequently associated with dysphagia (28.2 vs. 2.2%; p < 0.0001). Multivariate analysis revealed that stroke mortality and disability were independently associated with dysphagia (p < 0.0001). CONCLUSIONS: The frequency of dysphagia was relatively high. Regarding anatomical-clinical correlation, the most important factor was the size rather than the location of the lesion. Dysphagia assessed clinically was a significant variable predicting death and disability at 90 days.

Aged↗

Stroke prevention and atrial fibrillation: reasons leading to an inappropriate management. Main results of the SAFE II study.

AIMS: The aim of the Stroke and Atrial Fibrillation Ensemble (SAFE) II study was to identify the reasons underlying the under-utilization of oral anticoagulation (OAC) in patients with nonvalvular atrial fibrillation (NVAF). METHODS: We investigated from all available sources the reasons why patients hospitalized for a stroke, who had a previously known NVAF, were not receiving OAC beforehand. We interviewed general practitioners (GPs) and cardiologists with a structured questionnaire, to identify the reasons for their therapeutic choice. RESULTS: Of 370 patients, 257 were theoretically eligible for OAC according to guidelines and the presence of contra-indications, but only 82 (22.2%) of them had actually received OAC before. We found that factors independently associated with the prescription of OAC were being followed-up by a cardiologist and having a younger GP. The leading reason evoked by GPs or cardiologists to explain why patients were not treated with OAC was the presence of a 'potential contra-indication', which was often inappropriate, followed by 'there was no indication', 'low compliance' and 'fear of bleeding'. CONCLUSIONS: An important reason for not prescribing OAC was the lack of knowledge about trials and guidelines. Medical education about OAC in NVAF should therefore be improved.

Aged↗

Nerve growth factor and chronic daily headache: a potential implication for therapy.

The pivotal role of nerve growth factor in inducing hyperalgesia and central sensitization has been emphasized in experimental pain models. Higher nerve growth factor levels have recently been found in the cerebrospinal fluid of patients with chronic daily headache. These levels were significantly correlated with the cerebrospinal fluid levels of substance P and calcitonin gene-related peptide, supporting the involvement of this neurotrophin in enhancing the production of the two sensory neuropeptides of the trigemino-vascular system in chronic daily headache. This may, in part, account for the long-lasting sensitization and activation of this system, which could contribute to headache chronicity. More recent research has shown a significant correlation between the higher cerebrospinal fluid levels of nerve growth factor and those of another neurotrophin, the brain-derived neurotrophic factor, as well as glutamate in chronic daily headache patients. These findings suggest the potential involvement of nerve growth factor-mediated upregulation of brain-derived neurotrophic factor in persistent head pain. Therefore, nerve growth factor appears to indirectly exert its effect through enhancing glutamatergic transmission involved in the processing of head pain via brain-derived neurotrophic factor. Based on these data, a potential application can be hypothesized for novel strategies targeting neurotrophins (nerve growth factor and brain-derived neurotrophic factor) and their receptors to chronic daily headache. To date, the majority of the molecules discovered in this regard have been scarcely or never proved in animal pain models and are far from clinical use in chronic pain, including chronic daily headache. If this approach is to be developed in the near future, research should be focused on identifying strategies with few central side effects and specific selective action on central sites involved in chronic head pain and more generally in chronic pain conditions. This will represent a very difficult challenge, taking into account the pleiotropic effect of nerve growth factor and the wide range of intracellular signalling pathways activated by this neurotrophin which are not limited to the nociceptive system.

Brain↗

Recanalization of cervical artery dissection: influencing factors and role in neurological outcome.

BACKGROUND AND PURPOSE: Generally, the prognosis for cervical artery dissection (CAD) is uncertain. The recanalization rate of CAD can be up to 85% within 3 months. This study evaluates the variables that might affect recanalization and the role of recanalization as a predictor for neurological outcome. PATIENTS AND RESULTS: This study prospectively included 38 patients with acute stroke following occlusion due to CAD (18 males, 20 females, median age 50.5 years, range 16-82). Vertebral and carotid dissections were equally distributed (19 carotid dissections). The recanalization rate was influenced by the presence of hypertension (p = 0.001). Outcomes were dependent on infarct location. Patients with lateral medullary infarction returned to functional independence (p = 0.026), while patients with deep hemispheric infarction tended to have a disabling stroke (p = 0.068). The presence of good collaterals seemed to influence functional independence (p = 0.03). CONCLUSION: There seemed to be no relationship between outcome and the rate of recanalization following CAD. Recanalization appeared to be a spontaneous mechanism, which could have depended on the intrinsic condition of the vessels. Finally, neurological outcome was dependent on lesion localization and the presence of good collaterals.

Acute Disease↗

Excitatory amino acids and multiple sclerosis: evidence from cerebrospinal fluid.

BACKGROUND: Recent evidence suggests an altered glutamate homeostasis in the brain of patients with multiple sclerosis (MS), as seen in experimental models of MS. OBJECTIVE: To test whether the excitotoxic insult contributes to the pathological process in MS by measuring glutamate and aspartate levels in the cerebrospinal fluid of MS patients and control individuals. PARTICIPANTS: Twenty-five patients with the relapsing-remitting form of MS during a stable clinical phase, 30 patients with relapsing-remitting MS during relapse, and 25 patients with the secondary progressive form of MS were included in the study. Data were compared with those of 20 age-matched control subjects without diseases of the central and peripheral nervous systems. METHODS: Glutamate and aspartate levels in the cerebrospinal fluid were measured by high-performance liquid chromatography. RESULTS: Cerebrospinal fluid glutamate levels were significantly higher in patients assessed during relapse compared with those of the patients with relapsing-remitting MS examined during the stable clinical phase and the controls (P<.001). The levels of glutamate detected in patients with relapsing-remitting MS during the stable phase who had active lesions were significantly higher than in those without neuroradiological evidence of disease activity (P<.001). Significantly higher levels of glutamate were found in patients with secondary progressive MS with an increase of 1 or more points on the Expanded Disability Status Scale score compared with stable patients with secondary progressive MS and control subjects (P<.001). CONCLUSIONS: Neurotoxic events occur in MS patients, and they can be responsible for oligodendrocyte and neuronal cell death in patients with this demyelinating disease. The manipulation of glutamate-altered homeostasis or antagonizing glutamate receptor-mediated excitotoxicity may have therapeutic implications in MS patients.

Adult↗

Selection of thrombogenetic antiphospholipid antibodies in cerebrovascular disease patients.

BACKGROUND AND PURPOSE: The association between anticardiolipin antibodies (aCL) and thrombosis is well recognized, but its role as an independent risk factor for stroke is not. The study's aim was to investigate the presence of antiphospholipid antibodies (aPL) and ischemic vascular events by using both traditional means the estimation of aCL and glycoprotein (beta(2)GP1) antibodies. Additionally both aCL/beta(2)GP1 and aPLmix/beta(2)GP1 antibodies were measured. The measurement of these two antibodies was determined by using as target antigens, either cardiolipin alone or a mixture of different phospholipids coated with human beta(2)GP1 in order to select only the autoimmune antibodies. One hundred and twenty-two consecutive patients with first-ever acute ischemic cerebrovascular event were included and compared with controls. The presence of aCl in patients (20.5 %) and controls (14.7 %) was not significantly different (p = 0.1). The presence of abeta(2)GP1 (6.5 % versus 4.9 %, p = 0.7) was also not significant, while there were associations for aCL/b2GP1 13.9 % versus 4.9 % (p = 0.02) and aPLmix/beta(2)GP1 15.6 % versus 4.9 % (p = 0.01). These latter tests seem to be useful in assessing the autoimmune and therefore the thrombogenetic antibodies.

Adult↗

Plasma cytokine levels in patients with obstructive sleep apnea syndrome: a preliminary study.

The levels of some pro- and anti-inflammatory cytokines [interleukin (IL)-1beta, tumor necrosis factor (TNF)-alpha, IL-6, IL-10, and transforming growth factor (TGF)-beta], were measured by enzyme-linked immunosorbent assay (ELISA) method in the plasma of patients affected by obstructive sleep apnea syndrome (OSAS) at 22:00 hours before polysomnographic recording and immediately after the first obstructive apnea causing an SaO2 below 85%. Significantly higher levels of TNF-alpha were found in OSAS patients assessed before polysomnography compared with the control group (P < 0.01). A slight but significant increase in the plasma levels of IL-6 was also present (P < 0.05). Conversely, a significant decrease in the plasma levels of IL-10 was evident at baseline in OSAS patients (P < 0.04). No significant difference emerged between the mean values of IL-1alpha and TGF-beta between OSAS patients and controls. The present data support a prevailing activation of the Th1-type cytokine pattern in OSAS patients, which is not associated with the severity and duration of OSAS. This can have important consequences for the outcome of OSAS patients, especially with regard to the increased risk for developing atherosclerosis and cardiovascular and cerebrovascular diseases. Immediately after the first obstructive apnea causing an SaO2 <85%, a significant variation was observed in the plasma levels of TNF-alpha in OSAS patients compared with those measured before the beginning of polysomnographic recording (P < 0.001). The role played by this further increase in TNF-alpha levels after the obstructive apnea in OSAS patients remains to be established in the light of the pathogenic mechanisms of this sleep disorder.

Analysis of Variance↗

Is ultrasound examination sufficient in the evaluation of patients with internal carotid artery severe stenosis or occlusion?

BACKGROUND AND PURPOSE: Carotid endarterectomy (CE) has been shown to be beneficial in patients with symptomatic high-grade internal carotid artery (ICA) stenosis. Some authors have suggested that when ultrasound shows a stenosis 70-99%, CE can be performed without further imaging study. However, ultrasound findings that suggest an ICA occlusion, not confirmed by angiography but which instead show a near-occlusion usually benefit from CE. The objectives of this study are: (1). to evaluate how angiography-obtained information on intracranial arteries affects the treatment decision in patients with 70-99% ICA stenosis, and (2). to evaluate when a symptomatic ICA occlusion shown by ultrasound could actually be a patent artery and therefore benefit from CE. MATERIALS AND METHODS: We prospectively collected the cerebral angiograms of 133 consecutive patients with TIA or non-disabling stroke due to large artery disease where ultrasound suggested a stenosis >or=70% or occlusion of symptomatic ICA; we calculated the frequency of intracranial vascular malformations and intracranial artery disease (IAD) located in the infraclinoid or supraclinoid portion of the ICA, and in the anterior or middle cerebral artery. RESULTS: Ultrasound showed 31 ICA occlusions and 102 ICA with 70-99% stenosis. All the patients with an ICA stenosis 70-99% on ultrasound examination had the degree of stenosis confirmed by angiography. Two out of 31 patients did not have a complete occlusion but angiography showed a near-occlusion and consequently they underwent CE. Sixty-five (62.5%) out of 104 patients with patent ICA had IAD (mild 26.9%, moderate 21.2%, and severe 14.4%). Five patients (4.8%) had intracranial vascular malformations (4 aneurysms and 1 arteriovenous malformation). One patient had disabling stroke during angiography. Seven patients (6.7%) did not undergo CE after angiography (1 patient had an aneurysm >10 mm, 1 patient had a very tight stenosis of the basilar artery, 5 patients had intracranial stenosis more severe than the extracranial stenosis). CONCLUSIONS: In patients that on the basis of ultrasound examination can benefit from CE, information on intracranial arteries is necessary. Moreover, complete occlusion cannot be detected with certainty only by ultrasound examination.

Aged↗

L-Arginine/nitric oxide pathway in chronic tension-type headache: relation with serotonin content and secretion and glutamate content.

Previous research of our group demonstrated an increase in L-arginine/nitric oxide (NO) pathway activity in patients with chronic daily headache (CDH) with a previous history of migraine, which was associated with a reduced platelet serotonin content and increased Ca(2+) levels. In the present work, we assessed the variations in L-arginine/NO pathway activity and platelet cyclic guanosine 3',5'-monophosphate (cGMP) levels in 25 patients affected by chronic tension-type headache (CTTH) (8 M, 17 F; age range: 34-54 years). The NO production, shown spectrophotometrically by stoichiometric transformation of oxyhemoglobin to methemoglobin due to NO synthase (NOS) activity, and inter platelet cGMP concentration, assessed with a RIA method, were determined in parallel to variations of aggregation response to 0.3 microg/ml collagen. The intracellular platelet calcium concentrations were also determined using fluorescence polarisation spectrometry. Platelet serotonin content and collagen-induced secretion as well as glutamate content were also determined with high-performance liquid chromatography (HPLC). The above parameters were compared with those of an age-matched control group. A reduction in aggregation platelet response was found. The reduction in platelet aggregation was coupled with an increased NO and cGMP production (p<0.0002 and p<0.001, respectively). A significant increase in cytosolic Ca(2+) concentration was also detected compared to control individuals (p<0.001). This was accompanied by a reduced platelet content and collagen-induced secretion of serotonin and increased content of glutamate (p<0.0001, p<0.0001 and p<0.001, respectively). The above findings were more evident in patients with analgesic abuse. It can be hypothesized that the increased NOS activity shown in platelets of CTTH patients reflects an analogous central up-regulation of NOS activity in the spinal horn/trigeminal nucleus and supraspinal structures involved in the modulation of nociceptive input from myofascial cranial structures contributing to central sensitization. The increase in NOS activity seems to be associated with a hyposerotonergic status, particularly in patients with analgesic abuse, and this can contribute to central sensitization in CTTH patients. The increase in platelet glutamate content in the same patients suggests the implication of the above excitatory amino acid in spinal and supraspinal structures involved in head pain induction and maintenance.

Adult↗

Brain-derived neurotrophic factor in patients with multiple sclerosis.

UNLABELLED: The aim of the present research was to verify the production of BDNF by peripheral blood mononuclear cells (PBMCs), unstimulated and stimulated with phytohemagglutinin (PHA), anti-OKT3 Ab and myelin basic protein (MBP), in 35 patients affected by multiple sclerosis (MS), 20 with relapsing-remitting (R-R) MS and 15 with secondary progressive (SP) MS. Seven R-R MS patients were assessed during the attack, in the subsequent recovery phase and also 3 months after relapse. The production of BDNF by PBMCs was also evaluated in 20 age- and sex-matched control subjects. Levels of BDNF were also determined in CSF of both patient groups and 20 control subjects. RESULTS: Levels of BDNF (pg/ml) in the supernatants of unstimulated and PHA-, anti-OKT3 Ab- and MBP-stimulated PBMCs in patients with R-R MS were significantly higher during relapse and in the recovery phase compared with values detected in the stable phase of the disease. Significantly lower BDNF values were found in unstimulated and stimulated PBMC supernatants of patients with SP MS compared to control subjects. This reduction was greater in patients with a 1-point increase in the EDSS score in the last 6 months compared with that in patients without a progression of the disability score. Reduction in the levels of BDNF was also confirmed in the CSF of SP MS patients compared with R-R MS patients assessed during a stable phase of the disease and control subjects. DISCUSSION: On the basis of recent experimental findings, a neuroprotective effect of BDNF produced by inflammatory cells can be hypothesized during relapses in MS. This can favor remyelination. The reduced production of BDNF by PBMCs of patients with SP MS can contribute to the progression of demyelinating disease and axonal loss in this form.

Adult↗

Modulation of trigeminal reflex excitability in migraine: effects of attention and habituation on the blink reflex.

The modulation of trigeminal reflex excitability in migraine patients was evaluated during the asymptomatic phase by studying the effects of attention, habituation and preconditioning stimulus on the R2 and R3 components of the blink reflex (BR). Fifty patients suffering from migraine without aura, 20 affected by migraine with aura and 35 sex- and age-matched controls were selected. In subgroups of migraine with-aura and without-aura patients, and normal controls, the blink reflex was elicited during different cognitive situations: (a) spontaneous mental activity; (b) stimulus anticipation; (c) recognition of target numbers. In the remaining subjects, R2 and R3 habituation was evaluated by repetitive stimulation at 1, 5, 10, 15, 20, 25 and 30 s intervals. The R2 and R3 recovery curves were also computed. A reduced R3 threshold with a normal pain threshold was found in migraine with-aura and without-aura patients; the R3 component was not significantly correlated with the pain thresholds in patients and controls. The R2 and R3 components were less influenced by the warning of the stimulus in migraine without-aura and migraine with-aura patients, in comparison with the control group. A slight increase of both R2 and R3 recovery after preconditioning stimulus was also observed in migraine patients, probably caused by a phenomenon of trigeminal hyperexcitability persisting after the last attack. The abnormal BR modulation by alerting expresses in migraine a dysfunction of adaptation capacity to environmental conditions, probably predisposing to migraine.

Adult↗

Application of the 1988 International Headache Society diagnostic criteria in nine Italian headache centers using a computerized structured record.

BACKGROUND: The actual application of the current International Headache Society (IHS) diagnostic criteria in clinical practice has not been investigated thoroughly. OBJECTIVES: To develop a computerized, structured, medical record based exclusively on the IHS classification system. DESIGN AND METHOD: We tested the computerized structured record by entering and analyzing data reported on the case sheets of 500 consecutive patients attending nine headache centers in Italy. All clinical diagnoses in the study were made according to current IHS criteria. The rate of concordance between the diagnosis provided by the computerized structured record and that reported by clinicians on the case sheets was calculated, and reasons for any discrepancies between the two diagnoses were analyzed. RESULTS: Concordance between the two diagnoses was found in 345 of 500 cases examined (69%). In the remaining 155 cases, diagnoses reached with the computerized structured record and case sheets were impossible or discordant with respect to the diagnoses made by the clinician. In 144 of these cases (28.8%), this was due to missing information or errors in the diagnosis recorded by the clinicians on the patient case sheet. In particular, the diagnosis could not be reached using the computerized structured record in 105 cases (20.6%) because of a lack of one or more data needed in formulating a correct diagnosis according to the IHS operational criteria for one of the primary headache disorders. In the remaining 41 cases some data were missing, but the data available were sufficient to reach a diagnosis according to the IHS criteria. Moreover, the diagnoses reached using the computerized structured record were not in agreement with those made by the clinicians in another 39 cases (7.9%) due to an incorrect interpretation by the clinicians of the data reported on the patients' case sheets. In only 2.2% of the cases (n = 11) misdiagnoses were due to errors of the program that were promptly corrected. CONCLUSIONS: The present study suggests that incorrect application of IHS criteria for the diagnosis of primary headache may occur in as many as one third of patients attending headache centers and that use of a computerized structured record based exclusively on current IHS criteria may overcome this deficiency.

Ambulatory Care Facilities↗

The Perugia hospital-based Stroke Registry: report of the 2nd year.

This study reports the characteristics of stroke patients admitted to our hospital in the period Jan 1st, 1998-Dec 31st 1999. Seven hundred and ninety seven consecutive subjects (412 males; mean age 71 +/- 13 years) with a first-ever stroke were registered. Two-thirds of patients (65%) were admitted to the Stroke Unit (SU). The remaining part was managed in six general medicine wards (GM) or other services [neurosurgery and intensive care units (ICU+ NS)]. Ischemic stroke occurred in 534 subjects (67%). The high prevalence (30.1%) of haemorrhages can be partly explained by the presence of specialized neurosurgical services. Athero-thrombotic infarctions occurred in 21.7% of patients, lacunar in 24.7%, cardioembolic in 18.1%, other determined in 6.1%, and other undetermined in 27.5%. Overall hospital mortality was 10%. In cerebral hemorrhage mortality was 18% (44/240) vs. 6.3% (32/534) in ischemic stroke (p < 0.05). The distribution of stroke types and mortality was similar to other previous reports.

Adult↗

Hyperhomocyst(e)inemia: a risk factor for cerebrovascular disease.

Many case-control and cohort studies have identified a strong, independent and dose-related association between moderate hyperhomocyst(e)inemia and atherosclerotic vascular disease, with respect to the pathogenetic link between hyperhomocyst(e)inemia and stroke, the possible role in inducing an endothelial wall damage deserves special attention. Some prospective cohort studies have failed to demonstrate a positive association between elevated homocyst(e)ine (Hcy) levels and stroke. Further studies are needed, in order to better characterize the association between Hcy concentrations and risk of stroke.

Biomarkers↗