Annette Aigner

Contribution of Established Stroke Risk Factors to the Burden of Stroke in Young Adults

Background and Purpose— As stroke in young adults is assumed to have different etiologies and risk factors than in older populations, the aim of this study was to examine the contribution of established potentially modifiable cardiovascular risk factors to the burden of stroke in young adults. Methods— A German nationwide case–control study based on patients enrolled in the SIFAP1 study (Stroke In Young Fabry Patients) 2007 to 2010 and controls from the population-based GEDA study (German Health Update) 2009 to 2010 was performed. Cases were 2125 consecutive patients aged 18 to 55 years with acute first-ever stroke from 26 clinical stroke centers; controls (age- and sex-matched, n=8500, without previous stroke) were from a nationwide community sample. Adjusted population-attributable risks of 8 risk factors (hypertension, hyperlipidemia, diabetes mellitus, coronary heart disease, smoking, heavy episodic alcohol consumption, low physical activity, and obesity) and their combinations for all stroke, ischemic stroke, and primary intracerebral hemorrhage were calculated. Results— Low physical activity and hypertension were the most important risk factors, accounting for 59.7% (95% confidence interval, 56.3–63.2) and 27.1% (95% confidence interval, 23.6–30.6) of all strokes, respectively. All 8 risk factors combined explained 78.9% (95% confidence interval, 76.3–81.4) of all strokes. Population-attributable risks of all risk factors were similar for all ischemic stroke subtypes. Population-attributable risks of most risk factors were higher in older age groups and in men. Conclusions— Modifiable risk factors previously established in older populations also account for a large part of stroke in younger adults, with 4 risk factors explaining almost 80% of stroke risk. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00414583.

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.

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.

Interaction Between Awake and Sleep Bruxism Is Associated with Increased Presence of Painful Temporomandibular Disorder

AIMS To explore whether awake and sleep bruxism interact in their associations with painful temporomandibular disorders (TMD) and whether the interaction is multiplicative or additive. METHODS In this case-control study, all participants (n = 705) were part of the multicenter Validation Project and were recruited as a convenience sample of community cases and controls and clinic cases. Logistic regression analyses were applied to test for the association between self-reported bruxism (sleep and/or awake) and the presence of painful TMD, and odds ratios (ORs) with 95% confidence intervals (95% CIs) were computed. Regression models included an interaction term to test for multiplicative interaction, and additive interaction was calculated as the relative excess risk due to interaction (RERI). RESULTS Based on logistic regression analyses adjusted for age and gender, the main effects for both awake (OR = 6.7; 95% CI: 3.4 to 12.9) and sleep (OR = 5.1; 95% CI: 3.1 to 8.3) bruxism were significant. While the multiplicative interaction (OR = 0.57; 95% CI: 0.24 to 1.4) was not significant, the results indicated a significant positive additive interaction (RERI = 8.6; 95% CI: 1.0 to 19.7) on the OR scale. CONCLUSION This study has demonstrated that awake and sleep bruxism are associated with an increased presence of painful TMD, and that both types of bruxism are not independently associated, but interact additively. As such, the presence of each factor amplifies the effect of the other.

Estimating lung cancer mortality attributable to second hand smoke exposure in Germany

ObjectivesPublic health measures such as nonsmoker protection laws affect smoking prevalence and consequently the number of lung cancer deaths attributable to second hand smoke (SHS). In Germany, a risk assessment of SHS has been performed in 1994 only, and therefore, a reassessment is of interest.MethodsBased on current knowledge on the relative risk of lung cancer from SHS, SHS prevalence, lung cancer deaths in Germany, and two approaches to estimate the number of never smokers among lung cancer deaths, we estimated the current number of deaths attributable to SHS among never smokers in Germany.ResultsBased on a relative risk of 1.21 (95% CI 1.14–1.28), recent prevalence of SHS of 39.5% for men and 23.5% for women, the attributable risks are 7.66 and 4.70%, respectively. Out of about 47,000 lung cancer deaths per year, the estimated number of never smokers is about 6000, out of which we estimated 167 being attributable to SHS.ConclusionsDespite an aging population, the number of deaths from lung cancer attributable to SHS decreased considerably. This positive trend should be strengthened by further public health measures.

Association of Computed Tomography Ischemic Lesion Location With Functional Outcome in Acute Large Vessel Occlusion Ischemic Stroke

Background and Purpose— Ischemic lesion volume (ILV) assessed by follow-up noncontrast computed tomography correlates only moderately with clinical end points, such as the modified Rankin Scale (mRS). We hypothesized that the association between follow-up noncontrast computed tomography ILV and outcome as assessed with mRS 3 months after stroke is strengthened when taking the mRS relevance of the infarct location into account. Methods— An anatomic atlas with 66 areas was registered to the follow-up noncontrast computed tomographic images of 254 patients from the MR CLEAN trial (Multicenter Randomized Clinical Trial of Endovascular Treatment of Acute Ischemic Stroke in the Netherlands). The anatomic brain areas were divided into brain areas of high, moderate, and low mRS relevance as reported in the literature. Based on this distinction, the ILV in brain areas of high, moderate, and low mRS relevance was assessed for each patient. Binary and ordinal logistic regression analyses with and without adjustment for known confounders were performed to assess the association between the ILVs of different mRS relevance and outcome. Results— The odds for a worse outcome (higher mRS) were markedly higher given an increase of ILV in brain areas of high mRS relevance (odds ratio, 1.42; 95% confidence interval, 1.31–1.55 per 10 mL) compared with an increase in total ILV (odds ratios, 1.16; 95% confidence interval, 1.12–1.19 per 10 mL). Regression models using ILV in brain areas of high mRS relevance instead of total ILV showed a higher quality. Conclusions— The association between follow-up noncontrast computed tomography ILV and outcome as assessed with mRS 3 months after stroke is strengthened by accounting for the mRS relevance of the affected brain areas. Future prediction models should account for the ILV in brain areas of high mRS relevance.

Bias due to differential participation in case-control studies and review of available approaches for adjustment

Objectives Low response rates in epidemiologic research potentially lead to the recruitment of a non-representative sample of controls in case-control studies. Problems in the unbiased estimation of odds ratios arise when characteristics causing the probability of participation are associated with exposure and outcome. This is a specific setting of selection bias and a realistic hazard in many case-control studies. This paper formally describes the problem and shows its potential extent, reviews existing approaches for bias adjustment applicable under certain conditions, compares and applies them. Methods We focus on two scenarios: a characteristic C causing differential participation of controls is linked to the outcome through its association with risk factor E (scenario I), and C is additionally a genuine risk factor itself (scenario II). We further assume external data sources are available which provide an unbiased estimate of C in the underlying population. Given these scenarios, we (i) review available approaches and their performance in the setting of bias due to differential participation; (ii) describe two existing approaches to correct for the bias in both scenarios in more detail; (iii) present the magnitude of the resulting bias by simulation if the selection of a non-representative sample is ignored; and (iv) demonstrate the approaches’ application via data from a case-control study on stroke. Findings The bias of the effect measure for variable E in scenario I and C in scenario II can be large and should therefore be adjusted for in any analysis. It is positively associated with the difference in response rates between groups of the characteristic causing differential participation, and inversely associated with the total response rate in the controls. Adjustment in a standard logistic regression framework is possible in both scenarios if the population distribution of the characteristic causing differential participation is known or can be approximated well.

Association of gadolinium-enhanced magnetic resonance imaging with hepatic fibrosis and inflammation in primary sclerosing cholangitis

Objective To evaluate magnetic resonance imaging (MRI) parameters T2 signal, contrast enhancement (CE), and relative liver enhancement (RLE) of extracellular gadolinium-based contrast agent (GBCA)-enhanced MRI as a marker for hepatic fibrosis and inflammation in patients with primary sclerosing cholangitis (PSC). Methods 3.0-Tesla MRI scans and liver biopsies of 40 patients (41.2 ± 17.1 years) were retrospectively reviewed. Biopsies were obtained within a mean time of 54 ± 55 days to MRI scans and specimens were categorized according to Ishak modified hepatic activity index (mHAI) and Scheuer staging of fibrosis. T2 signal (N = 40), CE alterations (N = 29), and RLE (N = 29) were assessed by two raters. Mixed-effects regression models were applied to estimate the association between histopathology and MRI parameters. Results No significant association was observed between T2 signal or CE alterations with stages of fibrosis or mHAI grading. Regression models revealed significant positive associations of portal venous phase RLE with mHAI grade ≥ 7 points [β = 25.5; 95% CI (2.53; 48.62); p = 0.04] and delayed phase RLE with stages of fibrosis [stage 2: β = 35.13; 95% CI (11.35; 58.87); p = 0.007; stage 3/4: β = 69.24; 95% CI (45.77; 92.75); p < 0.001]. The optimal cut-off value of 66.6% delayed phase RLE distinguished fibrosis stages 0–2 from 3–4 with a sensitivity of 0.833 and specificity of 0.972. Inter-rater reliability (IRR) for quantification of RLE was ‘excellent’ (r = 0.90–0.98). IRR was ‘substantial’ for detection of T2 signal in the right liver lobe (RL) (Kappa = 0.77) and ‘almost perfect’ for T2 signal of the left liver lobe (LL) and CE of both lobes (Kappa = 0.87–1.0). Conclusion The simple and reproducible method of RLE quantification on standard extracellular GBCA-enhanced MRI may provide a correlate measure of advanced stages of hepatic fibrosis and potentially also inflammation in PSC patients, if validated in larger cohorts.

Low diet quality and the risk of stroke mortality: the multiethnic cohort study

Background/objectivesSeveral diets, e.g., those low in fruits/vegetables, high in sodium, and red/processed meat, have been related to a higher stroke risk. We investigated stroke mortality associated with a priori diet-quality indices in the Multiethnic Cohort study.Subjects/methodsBased on 172,043 observations including 3548 stroke deaths, we investigated the Healthy Eating Index-2010 (HEI-2010), the Alternative HEI-2010, the alternate Mediterranean diet score, and the Dietary Approaches to Stop Hypertension index in relation to stroke mortality. Using Cox regression, we estimated adjusted population attributable risks (PAR) and hazard ratios (HR) for tertiles of the indices while adjusting for relevant confounders.ResultsThe associations between all diet-quality indices and stroke mortality were consistent in direction; a low-quality diet was associated with a greater risk of stroke death, but the HEI-2010 was the strongest predictor. The PAR for stroke death based on HEI-2010 was 7.9% (95%-CI: 3.7–12.2%), indicating the preventable percentage of deaths if the total population had the same diet quality as those in the highest tertile for this diet-quality index. The lowest as compared to the highest tertile of the HEI-2010 was associated with a 1.23-fold (95%-CI: 1.13–1.34) risk. The PARs for low and medium adherence to the indices were similar by sex and follow-up time, but varied by ethnicity, with the highest PAR in Whites (15.4%) and no association in Latinos.ConclusionsFindings for four diet-quality indices, in particular the HEI-2010, indicated that diet quality acts as an independent risk factor for stroke mortality. Promotion of a high diet quality could have a substantial impact on the prevention of stroke deaths.

Impulsivity predicts illness severity in long-term course of bipolar disorder: A prospective approach:

Background: Bipolar disorder is a common, severe and chronic mental illness. Despite this, predictors of illness severity remain poorly understood. Impulsivity is reported to be associated with bipolar disorder and aggravating comorbidities. This study therefore sought to examine the predictive value of impulsivity for determining illness severity in euthymic bipolar disorder patients. Methods: Baseline trait impulsivity of 120 bipolar euthymic patients (81 bipolar disorder I [68%], 80 female [67%]) and 51 healthy controls was assessed using Barratt Impulsiveness Scale 11. The impact of impulsivity on illness severity (measured with morbidity index) was prospectively tested in 97 patients with sufficient follow-up data (average observation time: 54.4 weeks), using linear regression analysis. Results: Barratt Impulsiveness Scale 11 total (β = 0.01; p < 0.01) and in particular Barratt Impulsiveness Scale 11 attentional subscale scores (β = 0.04; p < 0.001) predicted illness severity in bipolar disorder, while controlling for other clinical variables. Only age at onset persisted as an additional, but less influential predictor. Barratt Impulsiveness Scale 11 total scores and Barratt Impulsiveness Scale 11 attentional subscale scores were significantly higher in euthymic patients compared to controls. This was not observed for the motor or non-planning subscale scores. Limitations: The average year-long observation time might not be long enough to account for the chronic course of bipolar disorder. Conclusion: Trait impulsivity and particularly attentional impulsivity in euthymic bipolar patients can be strong predictors of illness severity in bipolar disorder. Future studies should explore impulsivity as a risk assessment for morbidity and as a therapeutic target in bipolar disorder patients.