Wojciech Turaj

Hypercortisolemia in acute stroke is related to the inflammatory response

Hypercortisolemia is thought to be a marker of the stress response following stroke. The aim of this study was to investigate the prevalence and prognostic significance of hypercortisolemia. The circadian variation of cortisol level and the relationship between serum cortisol levels and other stress, inflammatory, and haemostatic markers were also investigated. Seventy consecutive patients with their first ischemic stroke and 24 age- and sex-matched controls were included in the study. Serum cortisol levels (at 6:00 AM, 10:00 AM, 6:00 PM, and 10:00 PM), 24-h urine catecholamine excretion, beta-thromboglobulin levels, and other standard biochemical and haematological parameters were measured on the first day of hospitalisation and in control subjects. Outcome measures used the Barthel Index at Day 30, as well as 30- and 90-day mortality rates. Hypercortisolemia, defined as at least two of the four measurements above the normal range of serum cortisol levels (i.e. >618 nmol/l from the morning samples and >460 nmol/l from the evening samples) was found in 25 (35.7%) of the acute stroke patients and in 3 (12.5%) of the controls (p<0.05). Hypercortisolemia was associated with older age, greater severity of neurological deficit, larger ischemic lesions on CT, and worse prognoses (p<0.05). The study did not find a correlation between serum cortisol levels and other markers of the stress response such as catecholamines excretion and glucose levels. A significant correlation between serum cortisol levels and some markers of the inflammatory response, such as fever, fibrinogen level, white blood cell (WBC) count, and beta-thromboglobulin level, was established in stroke patients. Prognostic significance of hypercortisolemia in acute stroke patients seems to be related to the inflammatory response rather than to the stress response.

Microalbuminuria in nondiabetic patients with acute ischemic stroke: prevalence, clinical correlates, and prognostic significance.

Microalbuminuria is a frequent finding in several acute clinical conditions and predicts poor outcome; its role in acute ischemic stroke, however, is unknown. This study was designed to investigate the prevalence and predictive power of microalbuminuria in acute stroke patients and to establish the relationship between microalbuminuria and the patients’ clinical status. We studied 60 patients admitted within 24 h of their first ischemic stroke, 50 patients with a history of ischemic stroke, and 30 control subjects without known cerebrovascular diseases. Neurological deficit was assessed by the Scandinavian Stroke Scale (SSS) on admission and on days 1, 7, 14, and 30. Urinary albumin excretion was measured using immunonephelometric method, with 24-hour collections performed on day 2. Outcome was assessed by 30-day, 90-day and 1-year mortality. Microalbuminuria was found in 46.7% of patients with acute stroke, 16% of subjects with a history of stroke, and 16.7% of controls. On admission, acute stroke patients with microalbuminuria had more severe neurological deficit (median of SSS score on admission was 28 vs. 40, and on day 1, 22 vs. 39, both p < 0.05; Mann-Whitney U test) and more often had a decreased level of consciousness (32 vs. 10%, p < 0.05; Fisher exact test). Mortality was higher in the group of patients with microalbuminuria in acute stroke (21 vs. 3% after 30 days, 39 vs. 6% after 90 days and 50 vs. 9% after 1 year, p < 0.05 for all differences; Fisher exact test). In logistic regression analysis, microalbuminuria was found to be an independent predictor of 1-year mortality after ischemic stroke (OR = 6.0; p = 0.022; 95% CI = 1.3–27.7).

Transient hyperglycemia in ischemic stroke patients

The aim of the study was to investigate glucose derangement and its short- and long-term prognostic significance in nondiabetic ischemic stroke patients. The study involved 262 consecutive patients, mean age: 70.1+/-12.4 years, with a supratentorial ischemic stroke. The following data were collected: patients characteristics, risk factors, comorbidities, and stroke severity assessed by the Scandinavian Stroke Scale (SSS). Serum glucose levels were measured on admission, on the next, 2nd, 3rd, 5th, 7th and 14th day after stroke onset. The outcome measures on day 30 were mortality and capacity to perform daily activities: the Barthel Index and Rankin Scale. The 1-year survival was estimated by the Kaplan-Meier method. Cox proportional hazards regression was used to assess predictors of 1-year mortality in nondiabetics. Diabetes mellitus was found in 24.8% of patients and transient hyperglycemia in 36.3% of patients. Patients with transient hyperglycemia scored lower on SSS in the subsequent days of assessment than patients with either diabetes mellitus or normoglycemia. They had larger ischemic lesions on computer tomography (CT) than diabetics and had higher 30-day mortality than normoglycemics (p<0.05). One-year mortality was similar in transient hyperglycemics and diabetics, and both were significantly higher than in normoglycemics (p<0.05). A proportional hazards model analysis showed that transient hyperglycemia is not an independent predictor of death within a year after stroke.

A2 Alelle of GpIIIa Gene Is a Risk Factor for Stroke Caused by Large-Vessel Disease in Males

Background and Purpose— Glycoprotein IIIa (GpIIIa) is a platelet membrane receptor for fibrinogen and von Willebrand factor. It plays a key role in platelet aggregation. Previous studies in stroke patients, without analysis based on specific subtypes of stroke cause, have not shown any link between GpIIIa A1/A2 polymorphism and stroke risk. We studied the significance of the GpIIIa gene A1/A2 polymorphism in stroke patients with different stroke causes. Methods— We genotyped 92 patients with stroke caused by large-vessel disease (LVD stroke) and 184 matched controls; 103 patients with stroke caused by small-vessel disease (SVD stroke) and 206 controls; and 182 patients with cardioembolic stroke (CE stroke) and 182 controls (TOAST criteria). The GpIIIa A1/A2 polymorphism was analyzed by polymerase chain reaction followed by restriction enzyme digestion and electrophoresis. Results— The genotype distribution of the GpIIIa gene in patients with LVD stroke (A1/A1, 63%; A1/A2, 34.8%; A2/A2, 2.2%) differed significantly from their controls (A1A1, 79.3%; A1/A2, 20.1%; A2/A2, 0.6%). The distribution of the GpIIIa A1/A2 polymorphism in patients with SVD stroke and CE stroke was similar to that of their controls. In contrast to females with LVD stroke, we found that males with LVD stroke presented with an overrepresentation of at least 1 A2 allele of the GpIIIa gene when compared with their controls (39.7% versus 23.0%; P =0.003). Conditional logistic regression analysis showed that possession of at least 1 A2 allele of the GpIIIa gene was an independent risk factor for LVD stroke in males (OR, 2.51; 95% CI, 1.21 to 5.20). Conclusion— A2 allele of the GpIIIa gene is an independent risk factor for LVD stroke in males.

Increased plasma fibrinogen predicts one-year mortality in patients with acute ischemic stroke

BACKGROUND AND PURPOSE Increased plasma fibrinogen is a risk factor for vascular diseases related to atherosclerosis. Its long-term predictive value in stroke survivors is not established. We conducted this study to establish the significance of hyperfibrinogenemia as the possible predictor of 30-day and one-year mortality in patients with acute ischemic stroke. METHODS We studied 900 unselected patients with ischemic stroke admitted to the hospital within 24 h after onset of symptoms. We noted demographic data, risk factors for stroke, neurological deficit and disturbances of consciousness on admission. We measured plasma concentration of fibrinogen and the body temperature on day 1 and registered vital status at 1, 3, 6 and 12 months after stroke. RESULTS Mean concentration of plasma fibrinogen was 2.9 g/L and 25.2% of patients had increased plasma concentration of fibrinogen (i.e. > or = 3.5 g/L) on day 1. Patients with hyperfibrinogenemia were more likely to die after 1, 3, 6 and 12 months than those with normal plasma fibrinogen (21.1% vs. 15.6%, 36.4% vs. 24.6%, 42.6% vs. 27.3%, 45.7% vs. 31.2%, respectively; P < 0.001 for the last three differences). Hyperfibrinogenemia did not predict short-term case-fatality, but increased concentration of plasma fibrinogen was an independent predictor of one-year case-fatality (P = 0.013; OR: 1.69 (95% CI 1.12-2.55)). Other independent predictors of one-year case-fatality were: neurological deficit on admission, age, white blood cell count, and body temperature on day 1. CONCLUSIONS Increased concentration of plasma fibrinogen shortly after ischemic stroke independently increases risk of death within one year after stroke.

Paraoxonase 2 Gene C311S Polymorphism Is Associated with a Risk of Large Vessel Disease Stroke in a Polish Population

Background: Oxidative stress plays a role in atherosclerosis. Human paraoxonase (PON) gene products exhibit antioxidant properties. We studied the significance of the Q192R and M55L polymorphisms of the PON1 gene and the C311S polymorphism of the PON2 gene in different etiologies of ischemic stroke. Methods: One hundred and thirty-six patients with large vessel disease (LVD) stroke, 140 with small vessel disease stroke, 272 with cardioembolic stroke, and their age- and sex-matched controls were included. PON genotypes were evaluated by PCR-RFLP analyses. Results: The distribution of PON1 polymorphisms was similar in each stroke group and in the respective controls. Genotypes with the C allele of the PON2 gene C311S polymorphism were overrepresented in LVD stroke patients as compared with their controls, both in univariate and multivariate (dominant model: OR = 1.58, 95% CI: 1.006–2.48) analyses. Conclusion: The genotype with the C allele of the PON2 gene is a risk factor for LVD stroke in a Polish population.

Interleukin 1β –511 C/T polymorphism and risk of aneurysmal subarachnoid haemorrhage

Production of the proinflammatory cytokine interleukin 1β (IL1β) increases in several acute or chronic diseases.1 The IL1β gene is a member of the IL1 gene family clustered on chromosome 2.1 A C/T polymorphism in the promoter region of the IL1β gene at position −511 influences the protein production, with the highest levels in T allele carriers.2 Data suggest that inflammation plays a role in the pathogenesis of subarachnoid haemorrhage (SAH) from ruptured aneurysm.3 We hypothesise that individuals genetically predisposed to an exaggerated cytokine production may be at risk of aneurysmal SAH. We studied the significance of IL1β –511 C/T polymorphism in patients with aneurysmal SAH and in healthy controls. We included 231 unrelated patients with aneurysmal SAH, of a total of 401 patients with SAH admitted to the Institute of Neurology, Krakow, Poland between 2003 and 2005. Patients with dissecting and fusiform aneurysms (n = 10), arteriovenous malformations (n = 30), SAH of unknown origin (n = 39), those who were comatose …

A-G-4G haplotype of PAI-1 gene polymorphisms −844 G/A, HindIII G/C, and −675 4G/5G is associated with increased risk of ischemic stroke caused by small vessel disease

Background –  Plasminogen activator inhibitor type 1 (PAI‐1) is the major inhibitor of fibrinolysis. It was reported that PAI‐1 gene polymorphisms affected PAI‐1 level and might therefore influence the risk of vascular diseases, including stroke. We studied the association of three common polymorphisms in PAI‐1 gene (−844 G/A, −675 4G/5G, and HindIII G/C) with the odds of different causes of ischemic stroke.

α1-Antichymotrypsin Gene (SERPINA3) A/T Polymorphism as a Risk Factor for Aneurysmal Subarachnoid Hemorrhage

Background and Purpose— The member 3 of clade A of serine proteinase inhibitors (SERPINA3), known previously as the &agr;1-antichymotrypsin, is an acute phase protein, the levels of which increase in acute and chronic inflammation. The A/T polymorphism of the SERPINA3 gene influences expression of SERPINA3 protein. SERPINA3 can be related to aneurysmal subarachnoid hemorrhage (SAH) by influencing inflammation or by regulating cathepsin G activity. We studied the significance of SERPINA3 A/T polymorphism in patients with aneurysmal SAH compared with healthy controls. Methods— A total of 180 patients with aneurysmal SAH and 263 healthy controls were genotyped for the SERPINA3 A/T polymorphism. Aneurysmal SAH was diagnosed by cranial computed tomography or lumbar puncture and digital subtraction angiography. SERPINA3 polymorphism was detected by polymerase chain reaction amplification and restriction enzyme digestion. Results— The SERPINA3 genotype distribution in patients with aneurysmal SAH (AA-29 16.1%; AT-108 60.0%; TT-43 23.9%) differed significantly from controls (AA-70 26.6%; AT-123 46.8%; TT-70 26.6%; P=0.009). A logistic regression model showed that the presence of genotype with T allele (AT+TT; odds ratio [OR], 2.01; 95% CI, 1.19 to 3.38; P=0.009) or AA genotype (OR, 0.49; 95% CI, 0.30 to 0.84; P=0.009) of the SERPINA3 influences the risk for aneurysmal SAH independently from smoking, excessive alcohol consumption, and hypertension. Conclusion— The A/T polymorphism of SERPINA3 gene is associated with the risk factor for aneurysmal SAH.

LDL phenotype B and other lipid abnormalities in patients with large vessel disease and small vessel disease.

BACKGROUND AND PURPOSE Controversies concerning the significance of lipid abnormalities in stroke come mostly from the researches that studied lipid profile without considering stroke aetiologies. We investigated the prevalence of LDL phenotype B and other lipid abnormalities in stroke survivors with large vessel disease (LVD) or small vessel disease (SVD) (TOAST criteria) and in control subjects (CS). METHODS We studied 30 patients with LVD and 41 patients with SVD screened out of 585 stroke patients and 30 CS who fulfilled the following exclusion criteria: cardiac disorders, renal or hepatic failure, diabetes mellitus, or treatment with lipid-lowering agents. At least 3 months after stroke, the concentrations of total cholesterol (TC), HDL cholesterol (HDL-C), LDL cholesterol (LDL-C), triglycerides (TGs), apolipoprotein E (apoE), and lipoprotein (a) [lp(a)] were measured and LDL phenotypes and apoE isoforms were identified. RESULTS Patients with LVD had significantly higher concentrations of LDL-C than CS (p<0.05). They had higher concentrations of TGs and lower concentrations of HDL-C than patients with SVD and CS (p<0.05). LDL phenotype B was more frequent in patients with LVD (63.3%) than in patients with SVD (39.0%) or in CS (16.7%) (p<0.05). The concentration of apoE was higher in patients with LVD than in patients with SVD or in CS (p<0.05). The percentage of patients with increased level of lp(a) (i.e., >30 mg/ml) was greater in patients with LVD (36.7%) than in CS (10%) (p<0.05). CONCLUSIONS Patients with stroke due to LVD, but not SVD, have high prevalence of atherogenic lipid abnormalities, including increased frequency of LDL phenotype B and higher percentage of increased lp(a) level, like patients with other atherogenic diseases.