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Biomedical subjects

José Castillo

Publications and source records attributed to José Castillo.

At least 19 recordsLinked to original sources

Molecular signatures of vascular injury are associated with early growth of intracerebral hemorrhage.

BACKGROUND AND PURPOSE: To investigate whether molecular markers of inflammation and endothelial injury are associated with early growth of intracerebral hemorrhage (ICH). METHODS: In a multicenter prospective study, we determined concentrations of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), matrix metalloproteinase-9 (MMP-9), and cellular fibronectin (c-Fn) in blood samples obtained on admission from 183 patients with primary hemispheric ICH of <12 hours' duration. Patients had a neurological evaluation and a computed tomography (CT) scan performed at baseline and at 48+/-6 hours. Early growth of the ICH was defined as a volume increase >33% between the 2 CT examinations for ICH with a baseline volume <20 mL and >10% for ICH > or =20 mL. Clinical, radiological, and biochemical predictive factors of ICH enlargement were analyzed by logistic regression analysis. RESULTS: Fifty-four (29.5%) patients showed a relevant early growth of ICH. High leukocyte count and fibrinogen levels, low platelet count, and intraventricular bleeding were associated with early ICH growth in bivariate analyses. Plasma concentrations of IL-6 (median [quartiles]: 19.6 [13.6; 29.9] versus 15.9 [11.5; 19.8] pg/mL), TNF-alpha (13.5 [8.4; 30.5] versus 8.7 [4.7; 13.5] pg/mL), MMP-9 (153.3 [117.7; 204.7] versus 70.6 [47.8; 103.8] ng/mL), and c-Fn (8.8 [6.2; 12.5] versus 2.8 [1.6; 4.2] microg/mL) were significantly higher in patients with early growth of ICH (all P<0.001). C-Fn levels >6 microg/mL (OR, 92; 95%CI, 22 to 381; P<0.0001) and IL-6>24 pg/mL (OR, 16; 95%CI, 2.3 to 119; P=0.005) were independently associated with ICH enlargement in the logistic regression analysis. CONCLUSIONS: Molecular signatures of vascular injury and inflammatory markers in the early acute phase of ICH are associated with subsequent enlargement of the hematoma.

Aged↗

Plasma cellular-fibronectin concentration predicts hemorrhagic transformation after thrombolytic therapy in acute ischemic stroke.

BACKGROUND AND PURPOSE: Elevated plasma levels of cellular fibronectin (c-Fn) reflect vascular damage, so c-Fn might be a marker of secondary bleeding risk in cerebral ischemia. We investigated whether high plasma levels of c-Fn were associated with hemorrhagic transformation (HT) after treatment with tissue plasminogen activator (tPA) in patients with acute stroke. METHODS: Eighty-seven patients (mean age: 67+/-12) received tPA after the ECASS II criteria (mean time to infusion: 160+/-46 minutes; median NIHSS: 12). HT and hypodensity volume were studied on computed tomography (CT) performed 24 to 36 hours after treatment. HT was classified according to the ECASS II definitions. c-Fn and matrix metalloproteinase 9 (MMP-9) levels were determined by ELISA in blood samples obtained before treatment and in 30 healthy subjects. RESULTS: HT was found in 26 patients (30%); 15 patients had hemorrhagic infarction type 1 (HI-1), 7 had HI-2, and 4 had parenchymal hemorrhage (PH). Median c-Fn concentrations were 1.3, 1.7, 4.2, 5.4, and 7.3 microg/mL in controls, non-HT, HI-1, HI-2, and PH groups, respectively (P<0.001); median MMP-9 values were 54, 87, 154, 176, and 225 ng/mL (P<0.001). Logistic regression analysis showed that only c-Fn plasma levels remained independently associated with HT after adjusting for potential confounders (OR, 2.1; 95% CI, 1.3 to 3.4; P=0.002). Similar results were obtained in the 71 patients treated within 3 hours. CONCLUSIONS: High plasma c-Fn levels are significantly associated with subsequent HT in stroke patients treated with tPA, so plasma c-Fn determinations might be useful in clinical practice to improve the risk/benefit ratio of thrombolytic treatment.

Aged↗

Blood pressure decrease during the acute phase of ischemic stroke is associated with brain injury and poor stroke outcome.

BACKGROUND AND PURPOSE: Studies on the relation between blood pressure (BP) and stroke outcome have shown contradictory results. We explored the association of systolic (SBP) and diastolic (DBP) BP during acute stroke with early neurological deterioration, infarct volume, neurological outcome, and mortality at 3 months. METHODS: We included 304 patients with acute ischemic stroke. SBP and DBP on admission and on the first day were the average values of all readings obtained in the emergency department and during a 24-hour period after patient allocation in the stroke unit. RESULTS: A U-shaped effect was observed: for every 10 mm Hg 180 mm Hg, the risk of early neurological deterioration increased by 40% and the risk of poor outcome increased by 23%, with no effect on mortality. Mean infarct volume increased 7.3 and 5.5 cm(3) for every 10 mm Hg 180 mm Hg. A similar pattern was found in patients with DBP 100 mm Hg. These effects disappeared after adjustment for the use of antihypertensive drugs and BP drop >20 mm Hg within the first day, with the latter being the more important prognostic factor of poor outcome. CONCLUSIONS: High and low SBP and DBP, as well as a relevant drop in BP, are associated with poor prognosis in patients with ischemic stroke.

Acute Disease↗

Biochemical changes and inflammatory response as markers for brain ischaemia: molecular markers of diagnostic utility and prognosis in human clinical practice.

The study of molecular markers associated with stroke has proved to be of considerable utility. We review the main biochemical changes of neurotoxicity and of inflammation and their usefulness as markers associated with early signs of ischaemia in the neuroimage, with early neurological deterioration, with the volume of the infarct, with haemorrhagic transformation, with the efficacy of thrombolytic treatment and with malignant ischaemic syndrome. Raised plasma concentrations of interleukin-6 (IL-6) are a powerful predictor of early neurological deterioration and the more important molecular marker associated with final volume of infarct. Levels of matrix metalloproteinases-9 (MMP-9) have a significant relationship with the efficacy of thrombolytic treatment and with the incidence and seriousness of haemorrhagic complications.

Biomarkers↗

Neuroprotective effects of aspirin in patients with acute cerebral infarction.

Aspirin may reduce ischemic brain injury. The aim of this study was to explore the effect of aspirin on glutamate release after acute stroke. We studied 238 patients with a first episode of hemispheric ischemic stroke of less than 24 h duration. Early neurological deterioration was diagnosed when the Canadian Stroke Scale dropped 1 or more points between admission and 48 h. Glutamate was determined on cerebrospinal fluid (CSF) samples obtained at admission. Sixty-three patients were undergoing treatment with 75-500 mg/day of aspirin at the time of stroke onset. CSF glutamate concentrations were higher in the group of patients not taking aspirin (8.9+/-5.2 vs. 4.9+/-3.1 microM/l, P< 0.0001). Aspirin treatment at stroke onset had a 97% risk reduction of early neurological deterioration, and this effect remained unchanged after a further adjustment for glutamate concentrations. These findings suggest that low doses of aspirin may be useful in the management of patients with cerebral ischemia, not only for its antithrombotic properties, but also by direct neuroprotective effects.

Acute Disease↗

Levels of anti-inflammatory cytokines and neurological worsening in acute ischemic stroke.

BACKGROUND: Mechanisms involved in stroke progression are incompletely understood. Ischemic brain injury is characterized by acute local inflammatory response mediated by cytokines. Anti-inflammatory cytokines act in a feedback loop to inhibit continued proinflammatory cytokine production. We assessed the implication of interleukin (IL)-10 and IL-4 in deteriorating ischemic stroke. METHODS: Two hundred thirty-one patients with ischemic stroke within the first 24 hours from onset were included. Neurological worsening was defined when the Canadian Stroke Scale score fell at least 1 point during the first 48 hours after admission. Anti-inflammatory cytokines were determined in plasma obtained on admission. RESULTS: Eighty-three patients (35.9%) worsened within the first 48 hours after stroke onset. Significantly lower concentrations of IL-10 were found in patients with neurological worsening (P<0.05), but IL-4 levels were similar in patients with or without deterioration. Lower plasma concentrations of IL-10 (<6 pg/mL) were associated with clinical worsening on multivariate analysis (odds ratio=3.1, 95% CI=1.1 to 8.9) independently of hyperthermia, hyperglycemia, or neurological condition on admission. Further analysis disclosed that early worsening was independently associated with lower IL-10 plasma levels in patients with subcortical infarcts or lacunar stroke but not in patients with cortical lesions. CONCLUSIONS: Anti-inflammatory cytokine IL-10 is associated with the early clinical course of patients with acute ischemic stroke, especially in patients with small vessel disease or subcortical infarctions.

Acute Disease↗

[Intravenous tissue-type plasminogen activator for the treatment of acute cerebral ischemia].

BACKGROUND AND OBJECTIVE: Whether the risk of symptomatic hemorrhagic transformation (SHT) of cerebral infarction associated with the use of tissue plasminogen activator (t-PA) is higher in clinical practice than in clinical trials is unknown. The aim of this study was to analyze the safety profile and clinical outcome of patients with acute cerebral ischemia who received open treatment with t-PA in Spanish hospitals. PATIENTS AND METHOD: This prospective and observational study included 155 consecutive patients with an ischemic stroke treated within 3 hours from the onset of symptoms, or within 6 hours in the absence of early signs of large cerebral infarction on CT. Intravenous t-PA was administered at 0.9 mg/kg (10% as bolus) during a 60 minutes infusion. Neurological worsening within 24-36 hours was evaluated by the NIH stroke scale (NIHSS). Primary safety and outcome variables were SHT on CT performed at 24-36 hours, mortality and independence at 90 days. Patients were treated by neurologists with expertise in acute stroke, and stroke monitoring was performed in acute stroke units. RESULTS: Baseline median NIHSS was 16, and mean time from stroke onset to treatment was 163 minutes. SHT was found in 12 patients (7.7%; 95% CI, 4.0-13.1), and it was fatal in 7 (4.5%, 95% CI, 1.8-9.1). Overall mortality at 90 days was 16.8% (95% CI, 11.2-23.6). At 24 hours, 48% (95% CI, 39.7-55.9) of patients had improved >= 4 points in the NIHSS, and 29% (95 % CI, 22.0-36.8) showed a >= 10 points improvement or total recovery. At 3 months, 56% (95% CI, 47.9-64.1) of patients were independent. CONCLUSIONS: In Spanish hospitals with stroke units or stroke teams, the use in the clinical practice of intravenous t-PA by experienced neurologists is safe, and it is associated with a favourable outcome similar to that observed in clinical trials.

Acute Disease↗

The release of tumor necrosis factor-alpha is associated with ischemic tolerance in human stroke.

Tumor necrosis factor (TNF)-alpha overexpression has been related to experimental ischemic tolerance when transient ischemia precedes cerebral infarction. We investigated TNF-alpha and interleukin (IL)-6 plasma concentrations in 283 patients with an acute stroke within 24 hours after symptom onset. An ipsilateral transient ischemic attack (TIA) within 72 hours before stroke was recorded in 38 patients. The infarct volume measured on computed tomography on days 4 to 7 and the frequency of poor outcome (Barthel Index score < 85) at 3 months were significantly lower in patients with prior TIA. Plasma concentrations of TNF-alpha were higher (42.5 +/- 9.9 vs 13.1 +/- 6.4pg/ml, p < 0.0001) and IL-6 levels were lower (10.1 +/- 6.2 vs 28.3 +/- 17.3pg/ml, p < 0.0001) in patients with prior TIA. A new variable termed TNF-alpha/IL-6 index was considered positive when TNF-alpha was greater than 30pg/ml and IL-6 was less than 30pg/ml. Positive TNF-alpha/IL-6 index was found in 92% of patients with prior TIA and in 1% of those without. TNF-alpha/IL-6 index (p = 0.0003) and TIA (p = 0.0001) were associated with good outcome in logistic regression analysis after adjusting for potential confounding factors. Ischemic tolerance in acute stroke is associated with increased plasma levels of TNF-alpha in the presence of reduced concentrations of IL-6.

Aged↗

L-arginine levels in blood as a marker of nitric oxide-mediated brain damage in acute stroke: a clinical and experimental study.

There are no useful markers in blood of nitric oxide (NO)-mediated brain damage. Because l-arginine (l-arg) is the only known substrate for NO generation, the authors investigated the plasma profile of l-arg after cerebral ischemia, and the relationship of L-arg concentrations in blood with stroke outcome and infarct volume in a clinical and experimental study. l-Arg levels were determined with high-performance liquid chromatography in blood and CSF samples obtained on admission, and in blood 48 hours after inclusion, in 268 patients admitted with a hemispheric ischemic stroke lasting 8.2 +/- 5.9 hours. Infarct volume was measured by days 4 to 7 using computed tomography. Plasma l-arg profiles were analyzed in a separate group of 29 patients seen within 8 hours of onset (median, 4.5 hours) and in 24 male Fischer rats treated with subcutaneous vehicle or 20-mg/kg 1400W (a specific inducible NO synthase inhibitor) every 8 hours for 3 days after performing sham or permanent middle cerebral artery occlusion. Plasma l-arg concentrations decreased after the ischemic event, both in patients and rats, and peaked between 6 and 24 hours. In patients, there was a highly correlation between l-arg levels in CSF and plasma at 48 hours (r = 0.85, P<0.001). CSF and plasma l-arg concentrations negatively correlated with infarct volume (r = -0.40 and r = -0.35, respectively, P<0.001), and were significantly lower in patients with early neurologic deterioration and in those with poor outcome (Barthel index <85) at 90 days (P<0.001). In rats, the administration of 1400W resulted in a 55% significant reduction of infarct volume measured 72 hours after permanent middle cerebral artery occlusion, an effect that correlated with the inhibition caused by 1400W on the ischemia-induced decrease of plasma l-arg concentrations at 6 to 24 hours after the onset of the ischemia. Taken together, these data indicate that determination of l-arg levels in blood might be useful to evaluate the neurotoxic effects of NO generation. These findings might be helpful to guide future neuroprotective strategies in patients with ischemic stroke.

Acute Disease↗

Public perception of stroke in Spain.

BACKGROUND AND PURPOSE: Stroke is one of the leading causes of death and disability in western countries. Improving attention to stroke demands better public information about the illness. The aim of the present study was to determine the current knowledge of stroke among the Spanish population. METHODS: We conducted a population-based telephone interview in Spain. A total of 3,000 respondents were selected at random following a systematic procedure aimed at filling the sex/age community quotas. RESULTS: A total of 16,016 telephone calls were made. Three thousand respondents were eligible and 2,884 completed the telephone interview. Only 4.5% of respondents knew the term stroke, 1,719 (59.6%) participants were able to mention at least one stroke risk factor, and only 940 (32.6%) could mention at least one stroke sign without prompting. Most respondents considered stroke to be a severe and dangerous illness that can be treated, but less than half of the respondents went immediately to a hospital when faced with a stroke event. Suitable stroke knowledge was only achieved by 302 (10.5%) respondents. Those who had home-based occupations and no previous stroke experience were less likely to have suitable stroke knowledge. CONCLUSIONS: This study confirms that our community is still unfamiliar with stroke. Wide population-based educational programs are needed to increase public knowledge of stroke. Our results indicate that people with home-based occupations should be the main target of our education campaigns.

Adult↗

Stroke on awakening: looking for a more rational management.

BACKGROUND AND PURPOSE: Stroke on awakening (SOA) is denied the benefits of thrombolytic therapy and is typically excluded from acute clinical trials on the grounds that the time of onset is unknown. In this study we compared the clinical characteristics of SOA and of stroke while awake (SWA), particularly in the subgroup of patients seen within a time frame of 6 h after stroke awareness. MATERIAL AND METHODS: Patients were included consecutively in the Stroke Data Bank of the Spanish Neurological Society (BADISEN) that records 365 different items, including vascular risk factors, neurological findings, stroke severity, aetiopathogenic diagnosis and neuroimaging data. RESULTS: A total of 1,248 patients with acute cerebral infarction were included in the study, 301 (24.1%) with SOA and 947 (75.9%) with SWA. The peak time for stroke occurrence was between 6:01 a.m. and 12 noon, both in the whole stroke group and in each aetiopathogenic stroke subtype. Age, sex, stroke risk factors, stroke severity at admission, vital signs and stroke subtypes were not significantly different between SOA and SWA, neither in the group as a whole nor in the group of patients seen within 6 h of stroke recognition. Six hundred and fifty-four patients were seen within the potential 6-hour therapeutic window. In this group, the CT scan on admission was normal in 39.4% of SOA but the ultimate CT/MRI scan showed that 46.2% of these had a territorial infarction (in SWA these same figures were 60.8 and 67.7%, respectively). CONCLUSION: There are no relevant differences in the clinical, neuroimaging and aetiopathogenic characteristics of SOA and SWA. We should rely on new techniques such as DWI/PWI to indicate the most appropriate treatment in a more rational manner as nearly half of the patients with SOA seen early may benefit from them.

Aged↗

Matrix metalloproteinase-9 concentration after spontaneous intracerebral hemorrhage.

OBJECT: Matrix metalloproteinases (MMPs) are overexpressed in the presence of some neurological diseases in which blood-brain barrier disruption exists. The authors investigated the MMP-9 concentration in patients after acute intracerebral hemorrhage (ICH) and its relation to perihematomal edema (PHE). METHODS: Concentrations of MMP-9 and related proteins were determined in plasma by performing an enzyme-linked immunosorbent assay of samples drawn after hospital admission (< 24 hours after stroke) from 57 patients with ICH. The diagnosis of ICH was made on the basis of findings on computerized tomography (CT) scans. The volumes of ICH and PHE were measured on baseline and follow-up CT scans at the same time that the patient's neurological status was assessed using the Canadian Stroke Scale and the Glasgow Coma Scale. Increased expression of MMP-9 was found among patients with ICH. In cases of deep ICH, MMP-9 was significantly associated with PHE volume (r = 0.53; p = 0.01) and neurological worsening (237.4 compared with 111.3 ng/ml MMP-9; p = 0.04). A logistic regression model focusing on the study of absolute PHE volume showed ICH volume as an independent predictor (odds ratio [OR] 3.37; 95% confidence interval [CI] 1.1-10.3; p = 0.03). A second analysis of relative PHE volume (absolute PHE volume/ICH volume) in patients with deep ICH demonstrated that the only factor related to it was MMP-9 concentration (OR 11.6; 95% CI 1.5-89.1; p = 0.018). CONCLUSIONS: Expression of MMP-9 is raised after acute spontaneous ICH. Among patients with deep ICH this increase is associated with PHE and the development of neurological worsening within the acute stage.

Adult↗

Plasma metalloproteinase-9 concentration predicts hemorrhagic transformation in acute ischemic stroke.

BACKGROUND AND PURPOSE: Matrix metalloproteinase-9 (MMP-9) activity has been associated with hemorrhagic transformation (HT) in experimental models of cerebral ischemia. Our aim was to investigate the relationship between MMP-9 concentrations in blood within 24 hours of stroke onset and subsequent HT of cerebral infarction. METHODS: We studied 250 patients with a hemispheric ischemic stroke of 7.8+/-4.5 hours' duration. Early CT signs of cerebral infarction were evaluated on admission. The HT and infarct volume were analyzed from the CT performed on days 4 through 7. MMP-9 levels were determined by enzyme-linked immunosorbent assay in blood samples obtained on admission. RESULTS: HT was observed in 38 patients (15.2%): 24 (63.2%) had a hemorrhagic infarction, and 14 (36.8%) had a parenchymal hematoma. A total of 108 patients (43%) received anticoagulants before the second CT scan. Systolic and diastolic blood pressures, body temperature, frequency of early CT signs of ischemia (92% versus 22%), and treatment with anticoagulants (79% versus 37%) were significantly higher in the group with HT (P<0.001). Mean infarct volume was 126+/-60 cm(3) in the HT group and 90+/-68 cm3 in the group without HT (P=0.003). Median (quartiles) plasma MMP-9 concentrations were higher in the HT group (193 [163, 213] versus 62 [40, 93] ng/mL, P<0.001), even in the 24 patients seen within 3 hours of symptom onset (P=0.014). MMP-9 levels > or =140 ng/mL had a positive and negative predictive value of HT of 61% and 97%, respectively. MMP-9 > or =140 ng/mL was associated with HT (odds ratio, 12; 95% confidence interval, 3 to 51; P<0.001) after adjustment for potential confounders and final infarct volume. CONCLUSIONS: High plasma MMP-9 concentration in the acute phase of a cerebral infarct is an independent biochemical predictor of HT in all stroke subtypes.

Biomarkers↗

Iron intake increases infarct volume after permanent middle cerebral artery occlusion in rats.

Experimental and clinical data suggest an important role of iron in cerebral ischaemia. We measured infarct volume and analysed the oxidative stress, and also the excitatory and inflammatory responses to brain injury in a rat stroke model after an increased oral iron intake. Permanent middle cerebral artery occlusion (MCAO) was performed in ten male Wistar rats fed with a diet containing 2.5% carbonyl iron for 9 weeks, and in ten control animals. Glutamate, interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha) were determined in blood samples before and at 2, 4, 6, 8, 24 and 48 h after MCAO, and thiobarbituric acid reaction substances (TBARS) were analysed at 48 h. Infarct volume was measured at 48 h by image analysis on brain slices stained with 1% TTC. Tissue iron was measured by atomic absorption spectrophotometry. Infarct volume was 66% greater in the iron fed rats than in the control group (178+/-49 mm(3) versus 107+/-53 mm(3), P<0.01). Significant higher levels of glutamate, IL-6 and TNF-alpha were observed in the group with iron intake (peak values were obtained at 6, 8 and 4 h, respectively). Iron-fed animals also showed significantly higher levels of TBARS than those receiving a normal diet (6.52+/-0.59 vs. 5.62+/-0.86 micro mol/l, P=0.033) Liver iron stores (3500+/-199 vs. 352+/-28 micro g Fe/g, P<0.0001), but not brain iron stores (131 vs. 139 micro g Fe/g, P=0.617), were significantly higher in the iron fed rats group. These results suggest that iron intake is associated with larger infarct volumes after MCAO in the rat. This effect seems to be associated with higher oxidative stress, excitotoxicity and inflammatory responses.

Administration, Oral↗

Comparison of effects of strength and endurance training in patients with chronic obstructive pulmonary disease.

We determined the effect of different exercise training modalities in patients with chronic obstructive pulmonary disease, including strength training (n = 17), endurance training (n = 16), and combined strength and endurance (n = 14) (half of the endurance and half of the strengthening exercises). Data were compared at baseline, the end of the 12-week exercise-training program, and 12 weeks later. Improvement in the walking distance was only significant in the strength group. Increases in submaximal exercise capacity for the endurance group were significantly higher than those observed in the strength group but were of similar magnitude than those in the combined training modality, which in turn were significantly higher than for the strength group. Increases in the strength of the muscle groups measured in five weight lifting exercises were significantly higher in the strength group than in the endurance group but were of similar magnitude than in the combined training group, which again showed significantly higher increases than subjects in the endurance group. Any training modality showed significant improvements of the breathlessness score and the dyspnea dimension of the chronic respiratory questionnaire. In conclusion, the combination of strength and endurance training seems an adequate training strategy for chronic obstructive pulmonary disease patients.

Aged↗

Unfractionated heparin is associated with a lower rise of serum vascular cell adhesion molecule-1 in acute ischemic stroke patients.

We sought to assess the anti-inflammatory properties of unfractionated heparin (UFH) in patients with ischemic stroke treated within 24 h from the onset of symptoms. We studied prospectively 167 patients that received 1000 IU/h intravenous UFH (n=70) or 300 mg oral aspirin (n=97) at a mean treatment delay of 6.7 h. Repeated plasma levels of interleukin (IL)-6, IL-10, IL-4, tumor necrosis factor (TNF)-alpha, soluble intercellular adhesion molecule-1 (sICAM-1), and soluble vascular cell adhesion molecule-1 (sVCAM-1) were compared in both groups using multivariate analyses. Whereas TNF-alpha and sICAM-1 decreased at 48 h, IL-6, IL-4, and sVCAM-1 increased compared with baseline values (P<0.01). The rise of sVCAM-1 levels at 48 h was significantly lower in patients treated with UFH (P=0.017) and a two-fold increase of baseline sVCAM-1 was an independent predictor of poor outcome (odds ratio, 2.19, 1.1-4.39). These results suggest that adjusted high-dose UFH has anti-inflammatory effects which might improve recovery if administered early after stroke onset.

Acute Disease↗

A -174G/C polymorphism of the interleukin-6 gene in patients with lacunar infarction.

Interleukin-6 (IL-6) is a pleiotropic cytokine that plays a central role in the pathogenesis of stroke. A base pair substitution -174G/C in the promoter region of the IL-6 gene regulates IL-6 gene expression. We compared the prevalence of this polymorphism in patients with lacunar stroke and in an age- and sex-matched cohort of asymptomatic controls. Eighty-two patients with lacunar stroke and 82 asymptomatic controls were prospectively assessed and genotyped for the -174G/C polymorphism in the promoter region of the IL-6 gene. Demographics and vascular risk factors were recorded in both groups. A brain computed tomography scan/magnetic resonance imaging confirmed the clinical diagnosis of lacunar stroke in all patients. The prevalence of CC genotype (18.3 vs. 7.3%, P=0.03), and the frequency of C allele (42.7 vs. 31.1%, P=0.03) were statistically significantly higher in patients with lacunar stroke than in asymptomatic controls. Expectedly, patients with lacunar stroke had a higher prevalence of vascular risk factors than asymptomatic controls. A logistic regression model showed that independent variables associated with lacunar stroke included history of hypertension (odds ratio (OR), 7.02; 95% confidence interval (95% CI), 3.11-15.81), diabetes (OR, 5.37; 95% CI, 1.52-8.89), hyperlipidemia (OR, 3.43; 95% CI, 1.04-11.25), smoking (OR, 5.84; 95% CI, 2.15-15.84), and CC genotype of the -174G/C IL-6 gene polymorphism (OR, 4.28; 95% CI, 1.22-15.00). These findings suggest that lacunar stroke might result from genetic susceptibility to inflammation-mediated damage in concert with atherosclerotic risk factors.

Aged↗