Entzündliche, genetische und sozioökonomische Determinanten des ischämischen Schlaganfalls und ihre Interdependenz
Final Report Abstract
In this case-control study we investigated the separate and joint effects of inflammatory variables, genetic and socio-economic determinants on ischemic stroke. Known risk factors, such as previous diseases, health conditions, and lifestyle factors were considered for a best possible adjustment for their confounding effects. Overall, 470 cases and 809 controls were included in the analysis. The study area, the city of Ludwigshafen, was particularly useful for this investigation since it was possible to take advantage of an existing stroke registry. The study confirmed the effect of major known risk factors for stroke including hypertension, diabetes mellitus, atrial fibrillation and current smoking. We had hypothesized that evidence of chronic/ persistent infection is particularly detected in subjects with lower socioeconomic status and that high infectious burden is a sroke risk factor particularly in this group. In accordance with previous studies, we found strong association between the prevalence of positive serology of CagA-positive Hp and low socioeconomic conditions in all life stages. When all microbial agents assessed were analysed together, there was a clear association between the infectious burden and socioeconomic conditions in childhood but no significant association with the other life stages. The association in cases was stronger than in controls. For cases, a trend was detected for an association between socioeconomic conditions in adolescence and during the total life span and infectious burden; this was not observed in controls. We found a significant interaction between infectious burden and socioeconomic status in the adulthood era but not in other life stages. However, since this is based on relatively few numbers and since we did not make a formal α-adjustment for the p-values, we take this result as an indication which needs to be explored further in future research. In our study, we had hypothesized that a stronger proinflammatory genetic profile may be a risk factor for stroke particularly in those subjects that have evidence of a higher number of of chronic or persistent infections, e.g. a higher infectious burden as shown by serological results. Most interestingly, analyses including both genetic and seroepidemiological results suggest that there is in fact a positive interaction between a high proinflammatory genetic score and a high infectious burden in serological analyses. This means that those subjects do have a particularly high risk of stroke who possess both a higher number of proinflammatory alleles and a high number of chronic/ persistent infectious diseases. The results of our study thus indicate that our initial hypothesis is not rejected by our data. Of note, the positive interaction between genetic and infectious results only became significant in models that adjusted for traditional stroke risk factors and was particularly evident when adjustment was also performed for dental parameters. This finding may be due to chance, however, it could also be biologically meaningful as it is well known that stroke risk factors such as smoking, diabetes mellitus and also hypertension can be associated with a stronger proinflammatory response. Our study results support the need of further research on the interaction between genetic and acquired proinflammatory mechanisms and the risk of stroke.
Publications
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Stroke Incidence and Survival in Ludwigshafen am Rhein, Germany: the Ludwigshafen Stroke Study (LuSSt). Stroke. 2010 Sep;41(9):1865-70. Epub 2010 Aug 5
Palm F, Urbanek C, Rose S, Buggle F, Bode B, Hennerici MG, Schmieder K, Inselmann G, Reiter R, Fleischer R, Piplack KO, Safer A, Becher H, Grau AJ
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2011: 6. DGEpi-Jahrestagung und 56. GMDS-Jahrestagung und in Mainz 26.-29.9.2011. Stroke Incidence by Age, Gender and Stroke Type in the Industrial City Ludwigshafen from a Population-based Stroke Registry
Safer A, Palm F , Buggle F, Urbanek C, Grau A , Becher H
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Etiology, risk factors and sex differences in ischemic stroke in the Ludwigshafen Stroke Study, a population-based stroke registry. Cerebrovasc Dis. 2012;33(1):69-75. Epub 2011 Dec 1
Palm F, Urbanek C, Wolf J, Buggle F, Kleemann T, Hennerici MG, Inselmann G, Hagar M, Safer A, Becher H, Grau AJ
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Stroke due to atrial fibrillation in a population-based stroke registry (Ludwigshafen Stroke Study) CHADS(2) , CHA(2) DS(2)-VASc score, underuse of oral anticoagulation, and implications for preventive measures. Eur J Neurol. 2013 Jan;20(1):117-23. Epub 2012 Jul 12
Palm F, Kleemann T, Dos Santos M, Urbanek C, Buggle F, Safer A, Hennerici MG, Becher H, Zahn R, Grau AJ
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2013: 8. DGEpi-Jahrestagung in Leipzig; 26.9.3013. Socioeconomic factors from childhood to adulthood as risk factors for stroke
Henschke N, Palm F, Safer A, Buggle F, Grond-Ginsbach C, Grau A, Becher H
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Biomarkers of periodontitis and inflammation in ischemic stroke: A case-control study. Innate Immun. 2013 Sep 17;20(5):511-518. [Epub ahead of print]
Palm F, Lahdentausta L, Sorsa T, Tervahartiala T, Gokel P, Buggle F, Safer A, Becher H, Grau AJ, Pussinen P
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Intracerebral haemorrhage in a population-based stroke registry (LuSSt): incidence, aetiology, functional outcome and mortality. J Neurol. 2013 Oct;260(10):2541-50. Epub 2013 Jun 28
Palm F, Henschke N, Wolf J, Zimmer K, Safer A, Schröder RJ, Inselmann G, Brenke C, Becher H, Grau AJ
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Stroke seasonality associations with subtype, etiology and laboratory results in the Ludwigshafen Stroke Study (LuSSt). Eur J Epidemiol. 2013 May;28(5):373-81. Epub 2013 Feb 6
Palm F, Dos Santos M, Urbanek C, Greulich M, Zimmer K, Safer A, Grau AJ, Becher H
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Validity of self-reported BMI in older adults and an adjustment model, 2014 J Public Health, published online 29-April-2014
Vuksanović M, Safer A, Palm F. Stieglbauer G, Grau AJ, Becher H
