Regional Deprivation, Stroke Incidence, and Stroke Care­An Analysis of Billing and Quality Assurance Data From the German State of Rhineland-Palatinate.

BACKGROUND: Regional deprivation can increase the risk of illness and adversely affect care outcomes. In this study, we investigated for the German state of Rhineland-Palatinate whether spatial-structural disadvantages are associated with an increased frequency of ischemic stroke and with less favorable care outcomes. METHODS: We compared billing data from DRG statistics (2008-2017) and quality assurance data (2017) for acute ischemic stroke with the German Index of Multiple Deprivation 2010 (GIMD 2010) for the 36 districts (Landkreise) and independent cities (i.e., cities not belonging to a district) in Rhineland-Palatinate using correlation analyses, a Poisson regression analysis, and logistic regression analyses. RESULTS: The age-standardized stroke rates (ASR) ranged from 122 to 209 per 100 000 inhabitants, while the GIMD 2010 ranged from 4.6 to 47.5; the two values were positively correlated (Spearman's ρ = 0.47; 95% confidence interval [0.16; 0.85]). In 2017, mechanical thrombectomies were performed more commonly (5.7%) in the first GIMD 2010 quartile of the regional areas (i.e., in the least deprived areas) than in the remaining quartiles (4.2-4.6%). The intravenous thrombolysis rates showed no differences from one GIMD 2010 quartile to another. Severe neurological deficits (National Institutes of Health Stroke Scale ≥ 5) on admission to the hospital were slightly more common in the fourth quartile (i.e., in the most deprived areas), while antiplatelet drugs and statins were somewhat less commonly ordered on discharge in those areas than in the first quartile. CONCLUSION: These findings document a relationship between regional deprivation and the occurrence of acute ischemic stroke. Poorer GIMD 2010 scores were associated with worse care outcomes in a number of variables, but the absolute differences were small.

Association of a Multigenetic Pro-Inflammatory Profile with Ischaemic Stroke.

OBJECTIVE: A multigenetic pro-inflammatory profile may increase stroke risk. We investigated whether a higher number of pro-inflammatory genetic variants are associated with ischaemic stroke risk and whether other risk factors further elevate this risk. METHODS: In a case-control study with 470 ischaemic stroke patients (cases) and 807 population controls, we investigated 23 haplotypes or alleles in 16 inflammatory genes (interleukin [IL]1A, IL1B, IL1 receptor antagonist, IL6, IL6 receptor, IL10, tumour necrosis factor-a; C-C motif chemokine ligand 2, C-C motif chemokine receptor 5, C-reactive protein (CRP), intercellular adhesion molecule 1, transforming growth factor ß1, E-Selectin, selenoprotein S, cluster determinant 14, histone deacetylase 9 [HDAC9]). We constructed an extended gene score (EGS) as the sum of all individual risk alleles and analysed its effect on stroke, just as its association and interaction with cardiovascular risk factors and infectious scores (IgG antibodies against 5 respectively IgA antibodies against 4 microbial antigens). RESULTS: Cases were less likely to carry the minor allele of IL10 rs1800872 and more likely to carry the HDAC9 allele rs11984041 and the pro-inflammatory haplotype of CRP, although the latter was not statistically significant in our study. Overall, cases tended to have more pro-inflammatory alleles and haplotypes than controls (mean ± SD 13.25 ± 2.25 and 13.04 ± 2.41, respectively). However, the EGS only slightly and not significantly increased the risk of stroke (OR 1.04, 95% CI 0.99-1.09). Its effect was neither associated with included risk factors nor with IgA and IgG infectious scores, and we found no significant interaction effects. CONCLUSION: A more pro-inflammatory genetic profile might increase stroke risk to some extent. This potential effect is most likely independent of established cardiovascular risk factors and the infectious burden of an individual.

Serum lipopolysaccharide neutralizing capacity in ischemic stroke.

INTRODUCTION: Periodontitis is associated with increased serum lipopolysaccharide (LPS) activity, which may be one mechanism linking periodontitis with the risk of cardiovascular diseases. As LPS-carrying proteins including lipoproteins modify LPS-activity, we investigated the determinants of serum LPS-neutralizing capacity (LPS-NC) in ischemic stroke. The association of LPS-NC and Aggregatibacter actinomycetemcomitans, a major microbial biomarker in periodontitis, was also investigated. MATERIALS AND METHODS: The assay to measure LPS-NC was set up by spiking serum samples with E. coli LPS. The LPS-NC, LPS-binding protein (LBP), soluble CD14 (sCD14), lipoprotein profiles, apo(lipoprotein) A-I, apoB, and phospholipid transfer protein (PLTP) activity, were determined in 98 ischemic stroke patients and 100 age- and sex-matched controls. Serum and saliva immune response to A. actinomycetemcomitans, its concentration in saliva, and serotype-distribution were examined. RESULTS: LPS-NC values ranged between 51-83% in the whole population. Although several of the LPS-NC determinants differed significantly between cases and controls (PLTP, sCD14, apoA-I, HDL-cholesterol), the levels did not (p = 0.056). The main determinants of LPS-NC were i) triglycerides (ß = -0.68, p<0.001), and ii) HDL cholesterol (0.260, <0.001), LDL cholesterol (-0.265, <0.001), PLTP (-0.196, 0.011), and IgG against A. actinomycetemcomitans (0.174, 0.011). Saliva A. actinomycetemcomitans concentration was higher [log mean (95% CI), 4.39 (2.35-8.19) vs. 10.7 (5.45-21) genomes/ml, p = 0.023) and serotype D more frequent (4 vs. 0%, p = 0.043) in cases than controls. Serotypeablity or serotypes did not, however, relate to the LPS-NC. CONCLUSION: Serum LPS-NC comprised low PLTP-activity, triglyceride and LDL cholesterol concentrations, as well as high HDL cholesterol and IgG against A. actinomycetemcomitans. The present findings let us to conclude that LPS-NC did not associate with stroke.

Socioeconomic decline and advancement within and between generations and the risk of stroke - a case-control study.

BACKGROUND: Disadvantageous socioeconomic conditions (SEC) in both childhood and adulthood increase the risk of stroke. We investigated whether intergenerational and lifetime social advancement decreases and/or social descent increases stroke risk. METHODS: In a case-control study with 466 patients with first-ever ischemic stroke and 807 controls randomly selected from the general population, we compared paternal profession to subjects' professional education in adolescence and their last profession in adulthood. Furthermore, we constructed a socioeconomic risk score for childhood (based on paternal and maternal profession and occupation, familial, living and material conditions), adolescence (based on highest school degree and professional education), and adulthood (based on last profession, periods of unemployment, and marital status), and compared subjects´ positions at different life stages. Odds ratios were derived based on conditional logistic regression conditioning on age and sex only, after adjustment for medical and lifestyle risk factors, and after additional adjustment for socioeconomic risk score values. RESULTS: Intergenerational upward mobility between paternal profession and subject's professional education was associated with lower ischemic stroke risk independent of medical and lifestyle risk factors (odds ratio (OR) 0.58; 95% confidence interval (CI) 0.41-0.81) and after additional adjustment for socioeconomic conditions in all three life stages (OR 0.67; 95% CI 0.45-0.99). Advancement between fathers´ profession and subject's last profession was associated with reduced odds of stroke after adjustment for risk factors (OR 0.65; 95% CI 0.47-0.89), but not significantly after additional adjustment for SEC (OR 0.77; 95% CI 0.52-1.13). Social descent between adolescence and adulthood indicated by the transition into a more disadvantageous tertile of socioeconomic risk score was associated with increased odds of stroke after adjustment for all risk factor (OR 2.93; 95% CI 1.21-7.13). Analyses by sex revealed mostly similar results in men and women with only few potential differences. CONCLUSIONS: Our study results indicate that aspects of social downward mobility during adulthood may be associated with increased risk of stroke, whereas intergenerational upward mobility may be linked to a lower stroke risk. If confirmed by future studies, such results may help to focus stroke prevention measures at high risk populations.

Low self-reported sports activity before stroke predicts poor one-year-functional outcome after first-ever ischemic stroke in a population-based stroke register.

BACKGROUND: Physical activity (PA) is associated with lower risk of stroke. We tested the hypothesis that lack of pre-stroke PA is an independent predictor of poor outcome after first-ever ischemic stroke. METHODS: We assessed recent self-reported PA and other potential predictors for loss of functional independence - modified Rankin Scale (mRS) > 2 - one year after first-ever ischemic stroke in 1370 patients registered between 2006 and 2010 in the Ludwigshafen Stroke Study, a population-based stroke registry. RESULTS: After 1 year, 717 (52.3%) of patients lost their independence including 251 patients (18.3%) who had died. In multivariate logistic regression analysis lack of regular PA prior to stroke (Odds Ratio (OR) 1.7, Confidence Interval (CI) 1.1-2.5), independently predicted poor outcome together with higher age (65-74: OR 1.7; CI 1.1-2.8, 75-84 years: OR 3.3; CI 2.1-5.3; ≥85 years OR 14.5; CI 7.4-28.5), female sex (OR 1.5; CI 1.1-2.1), diabetes mellitus (OR 1.8; CI 1.3-2.5), stroke severity (OR 1.2; CI 1.1-1.2), probable atherothrombotic stroke etiology (OR 1.8; CI 1.1-2.8) and high leukocyte count (> 9.000/mm3; OR 1.4; CI 1.0-1.9) at admission. Subclassifying unknown stroke etiology, embolic stroke of unknown source (ESUS; n = 40, OR 2.2; CI 0.9-5.5) tended to be associated with loss of independence. CONCLUSION: In addition to previously reported factors, lack of PA prior to stroke as potential indicator of worse physical condition, high leukocyte count at admission as indicator of the inflammatory response and probable atherothrombotic stroke etiology might be independent predictors for non-functional independence in first-ever ischemic stroke.

Association between infectious burden, socioeconomic status, and ischemic stroke.

BACKGROUND AND AIMS: Infectious diseases contribute to stroke risk, and are associated with socioeconomic status (SES). We tested the hypotheses that the aggregate burden of infections increases the risk of ischemic stroke (IS) and partly explains the association between low SES and ischemic stroke. METHODS: In a case-control study with 470 ischemic stroke patients and 809 age- and sex-matched controls, randomly selected from the population, antibodies against the periodontal microbial agents Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis, against Chlamydia pneumonia, Mycoplasma pneumoniae (IgA and IgG), and CagA-positive Helicobacter pylori (IgG) were assessed. RESULTS: IgA seropositivity to two microbial agents was significantly associated with IS after adjustment for SES (OR 1.45 95% CI 1.01-2.08), but not in the fully adjusted model (OR 1.32 95% CI 0.86-2.02). By trend, cumulative IgA seropositivity was associated with stroke due to large vessel disease (LVD) after full adjustment (OR 1.88, 95% CI 0.96-3.69). Disadvantageous childhood SES was associated with higher cumulative seropositivity in univariable analyses, however, its strong impact on stroke risk was not influenced by seroepidemiological data in the multivariable model. The strong association between adulthood SES and stroke was rendered nonsignificant when factors of dental care were adjusted for. CONCLUSIONS: Infectious burden assessed with five microbial agents did not independently contribute to ischemic stroke consistently, but may contribute to stroke due to LVD. High infectious burden may not explain the association between childhood SES and stroke risk. Lifestyle factors that include dental negligence may contribute to the association between disadvantageous adulthood SES and stroke.

Socioeconomic Conditions in Childhood, Adolescence, and Adulthood and the Risk of Ischemic Stroke.

BACKGROUND AND PURPOSE: The association between socioeconomic status in adulthood and the risk of stroke is well established; however, the independent effects of socioeconomic conditions in different life phases are less understood. METHODS: Within a population-based stroke registry, we performed a case-control study with 470 ischemic stroke patients (cases) aged 18 to 80 years and 809 age- and sex-matched stroke-free controls, randomly selected from the population (study period October 2007 to April 2012). We assessed socioeconomic conditions in childhood, adolescence, and adulthood, and developed a socioeconomic risk score for each life period. RESULTS: Socioeconomic conditions were less favorable in cases regarding paternal profession, living conditions and estimated family income in childhood, school degree, and vocational training in adolescence, last profession, marital status and periods of unemployment in adulthood. Using tertiles of score values, low socioeconomic conditions during childhood (odds ratio 1.77; 95% confidence interval 1.20-2.60) and adulthood (odds ratio 1.74; 95% confidence interval 1.16-2.60) but not significantly during adolescence (odds ratio 1.64; 95% confidence interval 0.97-2.78) were associated with stroke risk after adjustment for risk factors and other life stages. Medical risk factors attenuated the effect of childhood conditions, and lifestyle factors reduced the effect of socioeconomic conditions in adolescence and adulthood. Unfavorable childhood socioeconomic conditions were particularly associated with large artery atherosclerotic stroke in adulthood (odds ratio 2.13; 95% confidence interval 1.24-3.67). CONCLUSIONS: This study supports the hypothesis that unfavorable childhood socioeconomic conditions are related to ischemic stroke risk, independent of established risk factors and socioeconomic status in adulthood, and fosters the idea that stroke prevention needs to begin early in life.

Recent surgery or invasive procedures and the risk of stroke.

BACKGROUND AND PURPOSE: A recent surgery may be one of the trigger factors precipitating stroke and transient ischemic attack (TIA). While stroke in cardiac and carotid surgery has been well studied, less is known on stroke risk after surgery outside the heart and brain supplying arteries. We tested the hypothesis that preceding non-neurosurgical, non-cardiothoracic, and non-carotid surgery and other interventions temporarily increase the risk of stroke and transient ischemic attack (TIA) and investigated the risk related to different time periods between interventions and stroke/TIA. METHODS: In the Ludwigshafen Stroke Study, a population-based stroke registry, we assessed surgery and other interventions within the year preceding stroke and TIA. The risk factor profiles of patients with and without prior intervention were compared and rate ratios (RR) were calculated for different time periods with 91-365 days before stroke and TIA serving as reference period. RESULTS: In 2006 and 2007, 803 patients without and 116 patients with non-neurosurgical, non-cardiothoracic, and non-carotid intervention within the preceding year were identified. Elective (n = 21) and posttraumatic orthopedic (n = 14), eye (n = 14), and visceral surgery (n = 11) dominated. Interventions within 0-30 days (n = 34; RR 4.72; 95% confidence interval (CI) 2.70-8.26) but not within 31-60 or 61-90 days before stroke/TIA were observed more often than in the reference period. Interventions were more common within day 8-30 before stroke/TIA (RR 3.26; 95% CI 1.66-6.39), particularly common within the preceding week (RR 9.52; 95% CI 3.77-24.1) and most common in the preceding 2 days (RR 27.1; 95% CI 5.97-123) as compared to the reference period. Atrial fibrillation (AF) but not other risk factors was more common in patients with interventions within 30 days (n = 15; 44.1%) as compared to patients with more antecedent interventions (n = 19; 23.2%, p = 0.022) and those without surgery (n = 222; 27.6%, p = 0.031). Interventions within 30 days before stroke/TIA, were associated with total ischemic stroke (RR 6.11; 95% CI 3.32-11.2), first-ever in a lifetime ischemic stroke (RR 5.62; 95% CI 2.83-11.1) and recurrent ischemic stroke (RR 7.50; 95% CI 2.88-19.6). CONCLUSION: Recent non-cardiothoracic, non-carotid, and non-neurosurgical interventions are associated with an increased risk of stroke lasting for about 1 month and being particularly high within the first days. AF may be among the mechanisms linking interventions and stroke besides induction of a procoagulant state and interruption of medication.

Biomarkers of periodontitis and inflammation in ischemic stroke: A case-control study.

Periodontitis is a common infectious disease associated with increased risk for ischemic stroke though presently unclear mechanisms. In a case-control study, we investigated salivary levels of four periodontal pathogens, as well as systemic and local inflammatory markers. The population comprised 98 patients with acute ischemic stroke (mean ± SD, 68.2 ± 9.7 yrs; 45.9% women) and 100 healthy controls (69.1 ± 5.2 yrs; 47.0% women). Patients were more often edentulous and had fewer teeth than controls (13.8 ± 10.8 versus 16.6 ± 10.1). After adjusting for stroke risk factors and number of teeth, controls had higher saliva matrix metalloproteinase-8 (MMP-8), myeloperoxidase (MPO), IL-1ß, Aggregatibacter actinomycetemcomitans, and serum LPS activity levels. Patients had higher serum MMP-8 and MPO, and they were more often qPCR-positive for A. actinomycetemcomitans (37.9% versus 19.0%) and for ≥3 periodontopathic species combined (50.0% versus 33.0%). We conclude that controls more often had evidence of current periodontal infection with higher periodontal pathogen amount, endotoxemia, local inflammation and tissue destruction. Stroke patients more often had evidence of end-stage periodontitis with edentulism and missing teeth. They were more often carriers of several periodontopathic pathogens in saliva, especially A. actinomycetemcomitans. Additionally, inflammatory burden may contribute to high systemic inflammation associated with elevated stroke susceptibility.

Childhood and adult social conditions and risk of stroke.

BACKGROUND: Socioeconomic conditions may strongly influence the risk of stroke. We tested the hypotheses that indexes of social status in different life periods including childhood are inversely associated with stroke risk and that there is a cumulative effect of social conditions during lifetime on the risk of stroke. Furthermore, we investigated whether social advancement compared to the parental generation is associated with reduced stroke risk. METHODS: In a case-control study, we assessed parental professional status, highest school degree, professional education and the last professional activity in 370 consecutive patients with ischemic or hemorrhagic stroke or transient ischemic attack [TIA; age 60.7 ± 12.8 years (mean ± standard deviation); 31.1% women] and 370 age- and sex-matched control subjects randomly selected from the general population of the same area. RESULTS: Higher level of school exams [odds ratio (OR) 0.58, 95% confidence interval (CI) 0.39-0.86], university or polytechnic high school degrees (OR 0.39, 95% CI 0.24-0.63), nonmanual (last or current) professional activity (OR 0.51, 95% CI 0.37-0.71) and father's nonmanual professional activity (OR 0.64, 95% 0.43-0.97) were associated with a lower risk of stroke/TIA. Adjustment for vascular risk factors including current smoking and alcohol consumption reduced the strength of these associations and rendered them nonsignificant except for university or polytechnic high school degrees (OR 0.49, 95% CI 0.27-0.87). Additional adjustment for regular sports activity further attenuated the association between academic degrees and risk of stroke/TIA (OR 0.56, 95% CI 0.31-1.02). A score summarizing 4 lifetime social indexes was not independently associated with stroke risk (OR 0.67, 95% CI 0.39-1.16). Social advancement as assessed by changes from paternal manual work to nonmanual work in the index generation was more common among control subjects (23.5%) than patients (15.3%; p = 0.0097), but such advancement was not independently associated with stroke/TIA after adjustment for all covariables (OR 0.82, 95% CI 0.50-1.33). CONCLUSIONS: Socioeconomic conditions were inversely linked to the risk of stroke/TIA. These associations were strongly influenced by lifestyle factors such as smoking, alcohol consumption and mainly sports activity. Stroke preventive strategies may have a particularly large potential if they focus on such lifestyle habits in socially disadvantaged groups.

Stroke Incidence and Survival in Ludwigshafen am Rhein, Germany: the Ludwigshafen Stroke Study (LuSSt).

BACKGROUND AND PURPOSE: Considerable locoregional differences in stroke incidence exist even within countries. Based on data from a statewide stroke care quality monitoring project, we hypothesized a high stroke incidence mainly among younger age groups in the industrial city of Ludwigshafen am Rhein, Germany. To test this hypothesis and to provide data on stroke incidence and case-fatality rates, a population-based stroke register was initiated. METHODS: The Ludwigshafen Stroke Study is a prospective ongoing population-based stroke register among the 167 906 inhabitants of Ludwigshafen am Rhein. Starting on January 1, 2006, standard definitions and multiple overlapping methods of case ascertainment were used to identify all patients with incident stroke or transient ischemic attack. RESULTS: In 2006 and 2007, 1231 cases with stroke or transient ischemic attack including 725 patients with first-ever stroke were identified. The crude annual incidence rate per 1000 for first-ever stroke was 2.16 (95% CI 2.10 to 2.32). After age adjustment to the European population, incidence for first-ever stroke was 1.46 (95% CI 1.35 to 1.57; men: 1.63; 95% CI 1.46 to 1.81; women: 1.29; 95% CI 1.15 to 1.43). Crude annual incidence rates per 1000 were 1.86 for ischemic stroke, 0.19 for intracerebral hemorrhage, 0.05 for subarachnoid hemorrhage, and 0.05 for undetermined stroke. Case-fatality rates for first-ever stroke were 13.6%, 16.4%, and 23.2% at Days 28, 90, and 365, respectively. CONCLUSIONS: High crude incidence rates in our study reflect the rising burden of stroke in our aging population. Age-adjusted incidence rates were somewhat higher than those reported by recent studies from Western Europe, mainly due to higher incidence in subjects <65 years.

Association of symptoms of chronic bronchitis and frequent flu-like illnesses with stroke.

BACKGROUND AND PURPOSE: Acute and several chronic infectious diseases increase the risk of stroke. We tested the hypothesis that chronic bronchitis and frequent flu-like illnesses are independently associated with the risk of stroke or transient ischemic attack (TIA). METHODS: We assessed symptoms of chronic bronchitis, frequency of flu-like illnesses, and behavior during acute febrile infection in 370 consecutive patients with ischemic or hemorrhagic stroke or TIA and 370 age- and sex-matched control subjects randomly selected from the population. RESULTS: Cough with phlegm during > or = 3 months per year (grade 2 symptoms of chronic bronchitis) was associated with stroke or TIA independent from smoking history, other risk factors, and school education (odds ratio [OR] 2.63, 95% confidence interval [CI] 1.17 to 5.94; P=0.021). There was also an independent association between frequent flu-like infections (>2 per yr) and stroke/TIA (OR 3.54; 95% CI 1.52 to 8.27; P=0.003). Simultaneous assessment of chronic bronchitis and frequent flu-like infections did not attenuate the effect of either factor. Patients reported more often than control subjects to continue to work despite febrile infection (OR 3.68, 95% CI 1.80 to 7.52, multivariate analysis). CONCLUSIONS: Our results suggest that chronic bronchitis is among those chronic infections that increase the risk of stroke. Independent from chronic bronchitis, a high frequency of flu-like illnesses may also be a stroke risk factor. Infection-related behavior may differ between stroke patients and control subjects.

Association between recent sports activity, sports activity in young adulthood, and stroke.

BACKGROUND AND PURPOSE: Leisure-time physical activity protects from stroke. It is insufficiently established whether early lifetime physical activity is independently protective and whether some etiologic stroke subgroups particularly benefit from physical activity. We tested the hypothesis that both recent and early-adulthood sports activities are associated with reduced odds of stroke and analyzed their effects in stroke subtypes. METHODS: We performed a case-control study of 370 patients with acute stroke or transient ischemic attack (TIA) and 370 age- and sex-matched control subjects randomly selected from the population and assessed recent and young adulthood sports activities and their weekly duration in standardized interviews. RESULTS: Recent regular sports activities were less often reported by patients (94/370, 25.4%) than by control subjects (162/370, 43.8%; P<0.0001). After adjustment for vascular risk factors, education, and other factors, recent participation in sports was significantly associated with reduced odds of stroke/TIA (odds ratio=0.64; 95% CI, 0.43 to 0.96). Both groups did not differ with regard to sports activities in young adulthood. More control subjects (69/365, 18.9%) than patients (25/361, 6.9%) participated in sports recently after not having been active in young adulthood, and such a pattern was associated with reduced odds of stroke/TIA in multivariable analysis (odds ratio=0.37; 95% CI, 0.21 to 0.85). CONCLUSIONS: Our study supports previous results that have shown stroke protection by physical activity. Results suggest that continuous lifetime activity or starting activities during later adulthood is required to reduce stroke risk.

Inflammatory response after acute ischemic stroke.

BACKGROUND AND PURPOSE: This study aimed to characterize the time course of inflammatory parameters after acute ischemic stroke. METHODS: We serially determined high sensitivity C-reactive protein (CRP), fibrinogen, and leukocyte counts at 10 time points between days 1 and 90 after ischemic stroke and in control subjects. RESULTS: CRP did not significantly change, whereas fibrinogen increased after stroke. At all time points, CRP and fibrinogen were higher than in healthy control subjects, but not risk factor control subjects. The leukocyte count declined after stroke and was significantly elevated as compared to both control groups only on day 1 but not later. NIHSS levels were positively correlated with CRP and fibrinogen at all time points. Larger infarcts were associated with a higher CRP and leukocyte counts on day 90. Treatment with aspirin was associated with lower values for all three inflammatory parameters in the subacute phase after ischemia. CONCLUSIONS: The course after stroke was different between the parameters of inflammation. Only the leukocytes followed the paradigm of an acute phase response.

Influenza vaccination is associated with a reduced risk of stroke.

BACKGROUND AND PURPOSE: Vascular death rates and hospitalizations for stroke are increased during influenza epidemics. Influenza vaccination may prevent stroke. We investigated whether influenza vaccination is associated independently with reduced odds of stroke and whether effects are confined to stroke subgroups and winter seasons and shared by other vaccinations. METHODS: During 18 months, we performed standardized interviews assessing vaccination status, risk factors, health-related behavior, and socioeconomic factors in 370 consecutive patients with ischemic or hemorrhagic stroke or transient ischemic attack (TIA) and 370 age- and sex-matched control subjects selected randomly from the population. RESULTS: Influenza vaccination during the last vaccination campaign was less common in patients (19.2%) than control subjects (31.4%; P<0.0001). After adjustment for vascular risk factors, education, health-related behavior and other factors, influenza vaccination (odds ratio [OR], 0.46; 95% CI, 0.28 to 0.77) but not other combined recent vaccinations (OR, 0.80; 95% CI, 0.42 to 1.43) were associated with reduced odds of stroke/TIA. Significant effects were found in men, older subjects (>65 years), subjects with previous vascular diseases, and regarding ischemic stroke; nonsignificant trends existed in women, younger subjects, and regarding hemorrhagic stroke. In etiologic subgroups of cerebral ischemia, similar effects were found. No protective effects were found during summer months; however, results also varied considerably between both winter seasons examined. CONCLUSIONS: These results support the hypothesis that influenza vaccination may be associated with reduced stroke risk. However, residual confounding cannot be excluded, and interventional studies are required to evaluate the role of influenza vaccination in stroke prevention.

Association between cerebral ischemia and cytotoxin-associated gene-A-bearing strains of Helicobacter pylori.

BACKGROUND AND PURPOSE: Studies on Helicobacter pylori infection and risk of ischemic stroke yielded variable results. Infection with more virulent H. pylori strains, such as cytotoxin-associated gene-A (CagA)-bearing strains, may be of particular relevance for ischemic diseases. We investigated whether H. pylori and CagA seropositivity are independent risk factors for cerebral ischemia or its etiologic subtypes. METHODS: We determined IgG antibodies against H. pylori and CagA protein (enzyme immunoassays) in 190 patients with acute cerebral ischemia and in 229 age- and sex-matched control subjects selected randomly from the general population. RESULTS: CagA seropositivity was more common in patients (114/190; 60.0%) than in control subjects (99/229; 43.2%; odds ratio, 1.97; 95% CI, 1.33 to 2.91; P<0.001). This result remained significant after adjustment for age, sex, vascular risk factors and diseases, and childhood and adult social status (odds ratio, 1.84; 95% CI, 1.13 to 3.00; P=0.015). Subgroup analyses yielded similar results in all etiologic stroke subtypes. In contrast, H. pylori seropositivity in general was not associated with increased risk of stroke or its etiologic subtypes. CONCLUSIONS: Our results support the hypothesis of an association between infection with CagA-positive H. pylori strains and acute cerebral ischemia.

The association of gingivitis and periodontitis with ischemic stroke.

OBJECTIVES: The aim of this study was to assess the associations of different periodontal parameters with cerebral ischemia. METHODS: In a case-control study, 303 consecutive patients with ischemic stroke or transient ischemic attack, and 300 representative population controls received a complete clinical and radiographic dental examination. Patients were examined on average 3 days after ischemia. The individual mean clinical attachment loss measured at four sites per tooth was used as indicator variable for periodontitis. RESULTS: Patients had higher clinical attachment loss than population (p<0.001). After adjustment for age, gender, number of teeth, vascular risk factors and diseases, childhood and adult socioeconomic conditions and lifestyle factors, a mean clinical attachment loss >6 mm had a 7.4 times (95% confidence interval 1.55-15.3) a gingival index >1.2 a 18.3 times (5.84-57.26) and a radiographic bone loss a 3.6 times (1.58-8.28) higher risk of cerebral ischemia than subjects without periodontitis or gingivitis, respectively. CONCLUSION: Periodontitis is an independent risk factor for cerebral ischemia and acute exacerbation of inflammatory processes in the periodontium might be a trigger for the event of cerebral ischemia.

Leukocyte count as an independent predictor of recurrent ischemic events.

BACKGROUND AND PURPOSE: Inflammatory markers predict first-time ischemic events. We investigated whether leukocyte and differential counts predict recurrent events and ischemic events in high-risk populations, and whether such events are preceded by acutely exacerbated inflammation. METHODS: We studied 18 558 patients with ischemic stroke, myocardial infarction, or peripheral arterial disease who participated in the trial of Clopidogrel versus Aspirin in Patients at Risk of Ischemic Events (CAPRIE), a study that compared the occurrence of ischemic stroke, myocardial infarction, or vascular death under randomized treatment with aspirin or clopidogrel. Leukocyte counts were frequently assessed during followup. RESULTS: Compared with the quartile with lowest leukocyte counts at baseline (<5.9x10(9)/L), patients in the top quartile (>8.2x10(9)/L) had higher risks for ischemic stroke (relative risk 1.30; P=0.007), myocardial infarction (relative risk 1.56, P<0.001), and vascular death (relative risk 1.51; P<0.001) after adjustment for other risk factors. Neutrophil counts contributed most to increased risk. Assessments of regression dilution effects based on replicate measurements show that these risk associations may underestimate the real associations by 30 to 50%. Treatment with aspirin or clopidogrel did not influence predictive effects by leukocytes. In the week before a recurrent event, but not at earlier time points, the leukocyte count was significantly increased over baseline levels (n=211; mean difference +0.46x10(9)/L; P=0.005). CONCLUSIONS: Leukocyte counts and mainly neutrophil counts are independently associated with ischemic events in these high-risk populations. An increase of leukocyte counts over baseline levels heralds a period of increased risk lasting about one week.