Dariusz Kotlęga

Potential role of statins in the intracerebral hemorrhage and subarachnoid hemorrhage

Statins are used in primary and secondary prevention of cardiovascular episodes. Most of recent studies regard ischemic stroke. There are more emerging results of studies suggesting usefulness of these drugs in the other types of stroke e.g. intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH). Searching for new methods of treatment is important, because both ICH and SAH lead to poor prognosis and severe psychomotor disability. The unquestionable role of inflammatory factors in the pathogenesis of these disorders justifies considering statin treatment. Previous results are contradictory, thus in present study we review results of studies and try to explain the potential pathomechanism of statin use in hemorrhagic strokes.

Anti-oxLDL antibodies are clinically insignificant for stroke patients.

Abstract Objectives: The question about anti-oxidized low-density lipoprotein antibodies (anti-oxLDL Abs) involvement in the pathogenesis of atherosclerosis-related ischemic stroke is still open. The aim of this study was to determine how anti-oxLDL Abs are involved in the pathogenesis of atherosclerosis-related ischemic stroke and identify the main risk factors for stroke, such as arterial hypertension, diabetes mellitus type 2, dyslipidemia, and atherosclerotic changes in the common and internal carotid arteries. Material and Methods: A total of 40 stroke patients and 25 age- and sex-matched healthy individuals were included in the study. For each subject, IgG anti-oxLDL Abs expression in peripheral blood was assessed and analyzed in relation to clinical data, carotid Doppler ultrasonography results, and results of peripheral blood laboratory tests, including inflammatory parameters and lipid profile. Results: The blood level of assessed antibodies was significantly higher in stroke patients than in control group. It did not relate to stroke severity and stroke outcome. The relationship between anti-oxLDL Abs and carotid plaques hyperechogenicity was observed. The antibodies concentration was significantly higher in patients with diabetes mellitus type 2 and also positively correlated with C-reactive protein blood level. However, multiple regression method did not confirm their independent influence. Discussion: Patients with atherogenic ischemic stroke may have significantly higher anti-oxLDL Abs concentrations. This should be interpreted as an attempt to limit the consequences of oxLDL production; however, this phenomenon does not seem to protect patients against cerebrovascular events.

Risk factors of stroke and -717A>G (rs2794521) CRP gene polymorphism among stroke patients in West Pomerania province of Poland.

BACKGROUND AND PURPOSE Some of the risk factors of ischaemic stroke influence the development of atherosclerosis, which is a significant cause of vascular incidents. An inflammatory component plays a role in pathogenesis of both atherosclerosis and atrial fibrillation, the most important risk factor of embolic strokes. C-reactive protein (CRP) concentration in blood reflects the inflammatory process. Concentration of this protein depends on the CRP gene polymorphism. The aim of the study was to assess the relationship between selected risk factors of stroke and variant of -717A>G (rs2794521) CRP gene polymorphism in population of West Pomerania Province of Poland. MATERIALS AND METHODS There were 125 consecutive patients with ischaemic stroke analysed, who met the inclusion and exclusion criteria. In all patients, -717A>G CRP gene polymorphism was genotyped and analysed in relation to selected stroke risk factors. RESULTS Prevalence of type 2 diabetes was lower in patients with AA genotype of -717A>G CRP gene polymorphism than in patients with other alleles (p=0.017). Subjects with GG genotype had significantly higher concentration of CRP comparing to AG genotype (p=0.023). No correlation was found between -717A>G CRP gene polymorphism and the lipid profile and other selected risk factors of stroke. CONCLUSIONS In patients with ischaemic stroke in West Pomerania Province, the GG genotype of -717A>G CRP gene polymorphism is associated with significantly higher CRP concentration in relation to AG genotype. Patients with AA genotype may be characterised by lower prevalence of type 2 diabetes.

Association between selected gene polymorphisms and statin metabolism, risk of ischemic stroke and cardiovascular disorders.

Statins are increasingly widely used in primary and secondary prevention of cardiovascular disorders, including ischemic stroke. The initial studies regarded mainly coronary heart disease, but recently more attention has been paid to statin use in ischemic stroke, including primary and secondary prevention as well as the acute phase treatment. Besides their main hypolipemic activity, statins have been proved to have immunomodulating properties that are called a pleiotropic effect. Drug metabolism is under genetic influence, exemplified by the single nucleotide polymorphisms (SNPs). This also applies to statins. Pharmacogenetic studies are conducted in many disorders including stroke. The aim of this study was to review selected common genetic variants in lipid or statin metabolism-related genes and indicate associations with cardiovascular disorders, especially with ischemic stroke. We present available data of SNPs in regard to the most significant and promising proteins such as cytochrome P450, ATPase superfamily, organic anion transporter family, apolipoprotein E, lipoprotein-associated phospholipase A2, lipoprotein(a), LDLR, proprotein convertase subtilisin/kexin type 9, HMGCR, and CETP. A presentation of particular SNPs may help in future studies to aim for individual and thus more effective statin therapy in stroke patients.

Association between CRP gene polymorphism 717A/G, C-reactive protein and neurological deficit in ischemic stroke.

Inflammatory components play an important role in the pathogenesis of arteriosclerosis, one of the main causes of stroke. Blood C-reactive protein (CRP) level is connected with the severity of neurological deficit and disability after stroke. Production of CRP depends on CRP gene polymorphism. This study enrolled 125 patients with ischemic stroke. CRP 717A/G polymorphism was tested in all patients along with an assay of CRP levels measured on the first and tenth day after stroke onset. Neurological deficit on admission and before discharge from hospital was evaluated according to National Institutes of Health Stroke Scale (NIHSS), and then associated with CRP levels and the CRP polymorphism. The CRP 717AA genotype was the most frequent, observed in 53.6% of patients; AG genotype in 40%, and GG genotype in 6.4%. Carriers of the 717GG genotype had a significantly higher CRP level on the first day after stroke versus heterozygotes (p=0.023). The improvement in neurological state evaluated with the NIHSS was significantly better in CRP 717AA patients in comparison with other CRP 717 genotypes (p=0.035). A higher level of CRP on the first day after ischemic stroke was slightly associated with the CRP 717AG genotype. The CRP 717AA genotype promotes improvement of neurological state in patients with ischemic stroke.

Risk Factors of Fatigue in Idiopathic Parkinson's Disease in a Polish Population

Introduction. Fatigue syndrome is one of the nonmotor symptoms in Parkinsons disease (PD). The aim of the study was assessment of prevalence of fatigue syndrome in PD and answering the question what are the independent risk factors connected with intensity of fatigue in PD. Methods. 114 patients with idiopathic PD (mean age 62.2 + 10.8 years) were enrolled. The fatigue was assessed according to the Fatigue Severity Scale (FSS). We analyzed associations between fatigue and sex, age, education, duration and severity of the disease, everyday activity, intensity of the main symptoms, treatment, presence of dyskinesias and fluctuations, depression and excessive sleep during the day, and presence of pain and nycturia. Results. The fatigue syndrome was detected in 57.9% of patients. The score in the FSS was 1 to 7 points, 4.3 average. Greater fatigue intensity correlated with higher total daily levodopa equivalent dose. Patients with moderate depression had significantly greater fatigue. Conclusions. Fatigue syndrome affects 57.9% of patients with PD. Use of higher LED and presence of moderate depression are independent risk factors of greater intensity of fatigue.

The emotional stress and risk of ischemic stroke

Stroke is the second leading cause of death worldwide, and the leading cause of acquired disability in adults in most regions. There have been distinguished modifiable and non-modifiable risk factors of stroke. Among them the emotional stress was presented as a risk factor. The aim of this review was to present available data regarding the influence of acute and chronic mental stress on the risk of ischemic stroke as well as discussing the potential pathomechanisms of such relationship. There is an evident association between both acute and chronic emotional stress and risk of stroke. Several potential mechanisms are discussed to be the cause. Stress can increase the cerebrovascular disease risk by modulating symphaticomimetic activity, affecting the blood pressure reactivity, cerebral endothelium, coagulation or heart rhythm. The emotional stress seems to be still underestimated risk factor in neurological practice and research. Further studies and analyses should be provided for better understanding of this complex, not fully known epidemiological problem.

Early Emergency Medical Service Calls for Stroke: Was the Long-Term Education Program Based on the Experience of West Pomerania Successful?

BACKGROUND Our objectives are to investigate whether the percentage of early emergency calls for stroke had increased and to assess current factors determining the time of deciding to seek medical help in the event of early stroke symptoms. MATERIALS AND METHODS We analyzed data concerning the decision to call for medical help in relation to observed stroke symptoms. Group I comprised 287 people who made the decision to call emergency medical service (EMS) in the first 10 minutes after observing stroke symptoms. Group II included 275 people who called EMS after that time. Data from the current database (2013-2014) were compared with relevant data from the period 2003-2005. RESULTS In 2013-2014, awareness of stroke signs was 2.5 times greater than in 2003-2005. Among the groups of early and delayed EMS calls during 2003-2005 and 2013-2014, there were no significant differences in the number of people who suspected stroke. Advanced patient age, young caller age, hemiparesis, facial weakness, and the severity of neurological deficit were independent factors that correlated strongly with an early EMS call, whereas feelings of numbness and dizziness correlated significantly with delayed EMS calls. CONCLUSIONS In the West Pomeranian community, general knowledge of stroke is not a significant factor when making appropriate decisions at the onset of stroke symptoms. The education campaign regarding the initial symptoms of stroke and the possible fatal consequences appears to have been ineffective.

Effects of Angiotensin-Converting Enzyme Inhibition on Circulating Endothelial Progenitor Cells in Patients with Acute Ischemic Stroke

Background Therapeutic neovascularization might represent an important strategy to salvage tissue after ischemia. Circulating bone marrow-derived endothelial progenitor cells (EPCs) were previously shown to augment the neovascularization of ischemic tissue. Angiotensin-converting enzyme inhibitors (ACEIs) might modulate EPC mobilization. We evaluated populations of circulating stem cells and early EPCs in acute ischemic stroke (AIS) patients and the effect of ACEI on circulating EPCs in these patients with respect to aspects of stroke pathogenesis. Methods We studied 43 AIS patients (group I), comprising 33 treated with ACEI (group Ia) and 10 untreated (group Ib). Risk factor controls (group II) included 22 subjects. EPCs were measured by flow cytometry. Results In AIS patients, the number of circulating stem cells and early EPCs upon admission was similar to that in control group individuals. There were no significant differences in the numbers of stem cells and early EPCs over subsequent days after AIS. There were also no significant differences in stem cell and early EPC numbers over the first 3 days between group Ia and group Ib. However, on day 7, these numbers were significantly higher in group Ib than in group Ia (p < 0.05). In AIS patients chronically treated with ACEI, there was a negative correlation between CD133+ cell number and neurological deficit on the first, third, and seventh days (p < 0.005). Conclusions An increased number of circulating stem cells and early EPCs were not observed in stroke patients chronically treated with ACEI. In patients chronically treated with ACEI, a significant correlation was observed between decreased neurological deficit and higher levels of CD133+ cells; this could be due to the positive influence of these cells on the regeneration of the endothelium and improved circulation in the ischemic penumbra.

Wpływ simwastatyny na stężenie białka C-reaktywnego i profil lipidowy u chorych w ostrej fazie niedokrwiennego udaru mózgu w zależności od polimorfizmu -717A>G genu CRP

Introduction: The pathogenesis and risk of ischaemic stroke are associated with the inflammatory process that is involved in the development of atherosclerosis. The blood level of C‐reac‐ tive protein (CRP) is a widely used predictor of inflammation. The level of this protein is used for the assessment of risk and prognosis in cardiovascular disorders and stroke. C‐reactive protein level depends on genetic and environmental factors such as genetic polymorphism and statin use. The aim of the study was to assess the potential effects of sim‐ vastatin on the CRP level and lipid profile in stroke in regard to the variant of ‐717A>G CRP gene polymorphism. Materials and methods: There were 125 subjects enrolled in the study, hospitalized with a diagnosis of ischaemic stroke (95 patients in group 1 and 30 patients in group 2). Patients in group 1 were treated with a 40 mg dose of simvastatin from the 1st day; in group 2 simvastatin was not used. Blood CRP level and lipid profile were measured in all patients on day 1 and 10 after admission. The ‐717A>G CRP gene polymorphism status was genotyped in all patients. Results: In both groups there was a significant increase in CRP level, despite simvastatin treatment. No association was found between genotype and levels of both CRP and lipids change from the 1st to the 10th day. Conclusions: Simvastatin does not affect the CRP level in rela‐ tion to any of the ‐717A>G CRP gene polymorphism variants in the acute phase of stroke. Simvastatin significantly changes lipid levels, but it does not depend on ‐717A>G CRP gene polymorphism.