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Tobias Kurth

Publications and source records attributed to Tobias Kurth.

At least 19 recordsLinked to original sources
PubMed2016

Gene co-expression analysis identifies brain regions and cell types involved in migraine pathophysiology: a GWAS-based study using the Allen Human Brain Atlas.

Migraine is a common disabling neurovascular brain disorder typically characterised by attacks of severe headache and associated with autonomic and neurological symptoms. Migraine is caused by an interplay of genetic and environmental factors. Genome-wide association studies (GWAS) have identified over a dozen genetic loci associated with migraine. Here, we integrated migraine GWAS data with high-resolution spatial gene expression data of normal adult brains from the Allen Human Brain Atlas to identify specific brain regions and molecular pathways that are possibly involved in migraine pathophysiology. To this end, we used two complementary methods. In GWAS data from 23,285 migraine cases and 95,425 controls, we first studied modules of co-expressed genes that were calculated based on human brain expression data for enrichment of genes that showed association with migraine. Enrichment of a migraine GWAS signal was found for five modules that suggest involvement in migraine pathophysiology of: (i) neurotransmission, protein catabolism and mitochondria in the cortex; (ii) transcription regulation in the cortex and cerebellum; and (iii) oligodendrocytes and mitochondria in subcortical areas. Second, we used the high-confidence genes from the migraine GWAS as a basis to construct local migraine-related co-expression gene networks. Signatures of all brain regions and pathways that were prominent in the first method also surfaced in the second method, thus providing support that these brain regions and pathways are indeed involved in migraine pathophysiology.

Atlases as Topic↗
PubMed2006

The relative strength of C-reactive protein and lipid levels as determinants of ischemic stroke compared with coronary heart disease in women.

OBJECTIVES: We sought to determine the relative strength of high-sensitivity C-reactive protein (hs-CRP) and lipid levels as markers for future ischemic stroke compared with coronary heart disease (CHD) in women. BACKGROUND: Although hs-CRP and lipid levels are established risk determinants for vascular disease, the relative strength of these biomarkers for ischemic stroke compared with CHD is uncertain. METHODS: Among 15,632 initially healthy women who were followed for a 10-year period, we compared hs-CRP, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), high-density lipoprotein cholesterol (HDL-C), apolipoproteins A-I and B100, and lipid ratios as determinants of ischemic stroke compared with CHD. RESULTS: After adjustment for age, smoking status, blood pressure, diabetes, and obesity, the hazard ratios (HRs) and 95% confidence intervals (CIs) for the third versus the first tertile for future ischemic stroke compared with CHD were, respectively, 1.91 (95% CI 1.13 to 3.21) and 2.26 (95% CI 1.64 to 3.12) for TC, 1.29 (95% CI 0.83 to 2.02) and 2.09 (95% CI 1.53 to 2.85) for LDL-C, 0.57 (95% CI 0.36 to 0.92) and 0.38 (95% CI 0.27 to 0.52) for HDL-C, 1.72 (95% CI 1.03 to 2.86) and 2.93 (95% CI 2.04 to 4.21) for non-HDL-C, and 2.76 (95% CI 1.51 to 5.05) and 1.66 (95% CI 1.17 to 2.34) for hs-CRP. Of the lipid ratios, that of TC to HDL-C had the largest HR for both future ischemic stroke and CHD (HR 1.95 [95% CI 1.16 to 3.26] and 4.20 [95% CI 2.79 to 6.32], respectively). CONCLUSIONS: In this large prospective cohort of initially healthy women, lipid levels are significant risk determinants for ischemic stroke, but with a magnitude of effect smaller than that observed for CHD. High-sensitivity CRP associates more closely with ischemic stroke than with CHD. Concomitant evaluation of lipid levels and hs-CRP may improve risk assessment for stroke as well as CHD. (The Women's Health Study; http://www.clinicaltrials.gov/ct/show/NCT00000479/; NCT00000479).

Aged↗
PubMed2006

Aspirin and decreased adult-onset asthma: randomized comparisons from the physicians' health study.

RATIONALE: In an observational cohort study, women who self-selected for frequent aspirin use developed less newly diagnosed asthma than women who did not take aspirin. OBJECTIVE: To explore whether low-dose aspirin decreased the risk of newly diagnosed asthma in a randomized, double-blind, placebo-controlled trial. METHODS: The Physicians' Health Study randomized 22,071 apparently healthy male physicians, aged 40-84 yr at baseline and tolerant of aspirin, over an 18-wk run-in period, to 325 mg aspirin or placebo on alternate days. The aspirin component was terminated after 4.9 yr due principally to the emergence of a statistically extreme 44% reduction in risk of first myocardial infarction among those randomly assigned to aspirin. MEASUREMENTS: Physicians could self-report an asthma diagnosis on questionnaires at baseline, 6 mo, and annually thereafter. Asthma was not an a priori endpoint of the trial. RESULTS: Among 22,040 physicians without reported asthma at randomization, there were 113 new asthma diagnoses in the aspirin group and 145 in the placebo group. The hazard ratio was 0.78 (95% confidence interval, 0.61-1.00; p = 0.045). This apparent 22% lower risk of newly diagnosed asthma among those assigned to aspirin was not modified by baseline characteristics including smoking, body mass index, or age. CONCLUSIONS: Aspirin reduced the risk of newly diagnosed adult-onset asthma in a large, randomized clinical trial of apparently healthy, aspirin-tolerant men. This result requires replication in randomized trials designed a priori to test this hypothesis; it does not imply that aspirin improves symptoms in patients with asthma.

Adult↗
PubMed2006

Migraine and risk of cardiovascular disease in women.

CONTEXT: Migraine with aura has been associated with an adverse cardiovascular risk profile and prothrombotic factors that, along with migraine-specific physiology, may increase the risk of vascular events. Although migraine with aura has been associated with increased risk of ischemic stroke, an association with cardiovascular disease (CVD) and, specifically, coronary events remains unclear. OBJECTIVE: To evaluate the association between migraine with and without aura and subsequent risk of overall and specific CVD. DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort study of 27,840 US women aged 45 years or older who were participating in the Women's Health Study, were free of CVD and angina at study entry (1992-1995), and who had information on self-reported migraine and aura status, and lipid measurements. This report is based on follow-up data through March 31, 2004. MAIN OUTCOME MEASURES: The primary outcome measure was the combined end point of major CVD (first instance of nonfatal ischemic stroke, nonfatal myocardial infarction, or death due to ischemic CVD); other measures were first ischemic stroke, myocardial infarction, coronary revascularization, angina, and death due to ischemic CVD. RESULTS: At baseline, 5125 women (18.4%) reported any history of migraine; of the 3610 with active migraine (migraine in the prior year), 1434 (39.7%) indicated aura symptoms. During a mean of 10 years of follow-up, 580 major CVD events occurred. Compared with women with no migraine history, women who reported active migraine with aura had multivariable-adjusted hazard ratios of 2.15 (95% confidence interval [CI], 1.58-2.92; P<.001) for major CVD, 1.91 (95% CI, 1.17-3.10; P = .01) for ischemic stroke, 2.08 (95% CI, 1.30-3.31; P = .002) for myocardial infarction, 1.74 (95% CI, 1.23-2.46; P = .002) for coronary revascularization, 1.71 (95% CI, 1.16-2.53; P = .007) for angina, and 2.33 (95% CI, 1.21-4.51; P = .01) for ischemic CVD death. After adjusting for age, there were 18 additional major CVD events attributable to migraine with aura per 10 000 women per year. Women who reported active migraine without aura did not have increased risk of any vascular events or angina. CONCLUSIONS: In this large, prospective cohort of women, active migraine with aura was associated with increased risk of major CVD, myocardial infarction, ischemic stroke, and death due to ischemic CVD, as well as with coronary revascularization and angina. Active migraine without aura was not associated with increased risk of any CVD event.

Cardiovascular Diseases↗
PubMed2006

Healthy lifestyle and the risk of stroke in women.

BACKGROUND: Healthy lifestyle has been associated with decreased risk of coronary heart disease. In contrast, little is known about its association with stroke risk. METHODS: This is a prospective cohort study among 37 636 women 45 years or older participating in the Women's Health Study. Stroke was self-reported and confirmed by means of medical record review. We considered the following self-reported lifestyle factors: smoking, alcohol consumption, exercise, body mass index, and diet. The health index was calculated from these variables by assigning scores from 0 to 4 to the respective variable categories, with a higher score indicating healthier behavior. Healthy behavior was defined as never smoking, alcohol consumption between 4 and 10.5 drinks per week, exercise 4 or more times per week, body mass index (calculated as weight in kilograms divided by the square of height in meters) less than 22, and a diet high in cereal fiber, folate, and omega-3 fatty acids, with a high ratio of polyunsaturated to saturated fat, and low in trans fat and glycemic load. RESULTS: During 10 years of follow-up, 450 strokes (356 ischemic, 90 hemorrhagic, and 4 undefined) were confirmed. Compared with participants with 0 to 4 health index points (4.3%), women with 17 to 20 health index points (4.7%) had multivariable-adjusted hazard ratios (95% confidence interval) of 0.45 (0.24-0.83; P<.001 for trend) for total stroke, 0.29 (0.14-0.63; P<.001 for trend) for ischemic stroke, and 1.27 (0.37-4.29; P = .62 for trend) for hemorrhagic stroke. CONCLUSIONS: In this large prospective cohort of apparently healthy women, a healthy lifestyle consisting of abstinence from smoking, low body mass index, moderate alcohol consumption, regular exercise, and healthy diet was associated with a significantly reduced risk of total and ischemic stroke but not of hemorrhagic stroke. Our findings underscore the importance of healthy behaviors in the prevention of stroke.

Aged↗
PubMed2006

Colorectal cancer after start of nonsteroidal anti-inflammatory drug use.

PURPOSE: Nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin, have been consistently shown to reduce the risk of colorectal cancer (CRC) in non-experimental studies, but little is known of the factors associated with starting and continuing regular NSAID use and their effect on the NSAID and CRC association. SUBJECTS AND METHODS: We performed a prospective cohort study of 22,071 healthy male physicians aged 40 to 84 years without indications or contraindications to regular NSAID use at baseline. Annual questionnaires assessed quantity of NSAID use, occurrence of cancer, and risk factors for CRC. Propensity for regular NSAID use (>60 days/year) was estimated using generalized estimating equations. We used a time-varying Cox proportional hazards model to estimate the association between duration since initiation of regular NSAID use and risk for CRC. RESULTS: Regular non-aspirin and any NSAID use increased from 0% to 12% and 1% to 56% over time, respectively and was predicted by age, body mass index, alcohol consumption, medication use, coronary artery disease, gastrointestinal diseases, arthritis, hypertension, and headaches. Over a median follow-up of 18 years, 495 physicians were diagnosed with CRC. There was no trend of CRC risk with increased duration of regular NSAID use. Five or more years of regular use of any NSAID were associated with a relative risk for CRC of 1.0 (95% confidence interval: 0.7-1.5), after adjustment for predictors of regular NSAID use. CONCLUSION: Regular NSAID use was not associated with a substantial risk reduction of CRC after controlling for time-varying predictors of both NSAID use and CRC.

Adult↗
PubMed2006

Cluster headache: clinical presentation, lifestyle features, and medical treatment.

BACKGROUND: Cluster headache (CH) is a rare but severe headache form with a distinct clinical presentation. Misdiagnoses and mismanagement among these patients are high. OBJECTIVE: To characterize clinical features and medical treatment in patients with CH. METHODS: We established a cohort of 246 clinic-based and non-clinic-based CH patients. The diagnosis of CH was verified according to International Headache Society (IHS) criteria. We used standardized questionnaires to assess associated factors as well as success or failure of treatments. RESULTS: The majority (75.6%) was not treated before at our clinic-77.6% were males; 74.8% had episodic CH, 16.7% had chronic CH, in the remaining patients, the periodicity was undetermined because they were newly diagnosed. Cranial autonomic features were present in 98.8%, nausea and vomiting in 27.8%, and photophobia or phonophobia in 61.2% of CH patients. Most (67.9%) reported restlessness during attacks and 23% a typical migrainous aura preceding the attacks. The rate of current smoking was high (65.9%). Half of the patients reported that alcohol (red wine in 70%) triggered CH attacks. Eighty-seven percent reported the use of drugs of first choice (triptans 77.6%, oxygen 71.1%) with sumatriptan subcutaneous injection being the most effective drug for acute therapy (81.2%). The most frequently used preventive medications were verapamil (70.3%) and glucocorticoids (57.7%) with equally high effectiveness. CONCLUSIONS: Apart from the IHS criteria additional features like nausea/vomiting and migrainous aura may guide the diagnosis of CH. A large number of CH patients do not receive adequate treatments.

Adult↗
PubMed2005

Results of multivariable logistic regression, propensity matching, propensity adjustment, and propensity-based weighting under conditions of nonuniform effect.

Observational studies often provide the only available information about treatment effects. Control of confounding, however, remains challenging. The authors compared five methods for evaluating the effect of tissue plasminogen activator on death among 6,269 ischemic stroke patients registered in a German stroke registry: multivariable logistic regression, propensity score-matched analysis, regression adjustment with the propensity score, and two propensity score-based weighted methods-one estimating the treatment effect in the entire study population (inverse-probability-of-treatment weights), another in the treated population (standardized-mortality-ratio weights). Between 2000 and 2001, 212 patients received tissue plasminogen activator. The crude odds ratio between tissue plasminogen activator and death was 3.35 (95% confidence interval: 2.28, 4.91). The adjusted odds ratio depended strongly on the adjustment method, ranging from 1.11 (95% confidence interval: 0.67, 1.84) for the standardized-mortality-ratio weighted to 10.77 (95% confidence interval: 2.47, 47.04) for the inverse-probability-of-treatment-weighted analysis. For treated patients with a low propensity score, risks of dying were high. Exclusion of patients with a propensity score of <5% yielded comparable odds ratios of approximately 1 for all methods. High levels of nonuniform treatment effect render summary estimates very sensitive to the weighting system explicit or implicit in an adjustment technique. Researchers need to be clear about the population for which an overall treatment estimate is most suitable.

Aged↗
PubMed2005

Analgesic use and risk of subsequent hypertension in apparently healthy men.

BACKGROUND: Prospective studies have suggested that women who self-select for use of analgesics have an increased risk of hypertension, but data in men are sparse. We tested whether apparently healthy male physicians who reported analgesic use had an increased risk of subsequent hypertension. METHODS: Prospective cohort study of 8229 participants in the Physicians' Health Study who were free of hypertension and completed detailed analgesic questionnaires. Hypertension was defined as self-reported blood pressure of 140/90 mm Hg or higher or use of antihypertensive medication. RESULTS: After a mean of 5.8 years' follow-up, 2234 men (27.2%) reported subsequent hypertension. We categorized the cumulative analgesic use in quintiles. After adjusting for potential confounders, men in the highest quintile had no statistically significant increased risk of hypertension (hazard ratio, 1.12; 95% confidence interval, 0.97-1.31) when compared with those in the lowest quintile. In subgroup analyses, we evaluated the cumulative use of nonsteroidal anti-inflammatory drugs, acetaminophen, and aspirin. Compared with never users, men who reported consuming at least 2500 pills had hazard ratios of 1.05 (95% confidence interval, 0.89-1.24) for nonsteroidal anti-inflammatory drugs, 1.08 (95% confidence interval, 0.87-1.34) for acetaminophen, and 1.16 (95% confidence interval, 0.92-1.48) for aspirin. The results were similar for analgesic use in the year preceding the analgesic questionnaire. CONCLUSION: In this large cohort, apparently healthy male physicians who self-selected for analgesic use had no significantly increased risk of subsequent hypertension, although a small to moderately increased risk cannot be excluded in observational studies.

Acetaminophen↗
PubMed2005

Alcohol consumption and the risk of renal dysfunction in apparently healthy men.

BACKGROUND: Moderate alcohol consumption has been consistently associated with beneficial health effects on cardiovascular disease. In contrast, the association between alcohol consumption and renal dysfunction is less clear. METHODS: We conducted a prospective cohort study of 11,023 initially healthy men who provided blood samples 14 years after a baseline assessment of alcohol consumption. We categorized alcohol consumption into 1 or fewer, 2 to 4, 5 to 6, and 7 or more drinks per week. The main outcome measures were elevated creatinine levels (defined as > or = 1.5 mg/dL [> or = 133 micromol/L]) and reduced estimated glomerular filtration rates (defined as < or = 55 mL/min). We used logistic regression to calculate multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: After 14 years, 473 men (4.3%) had elevated creatinine levels and 1296 (11.8%) had reduced glomerular filtration rates. Compared with men who consumed no more than 1 drink per week, men who consumed 2 to 4 drinks weekly had a multivariable-adjusted OR of 1.04 (95% CI, 0.81-1.32), men who consumed 5 to 6 drinks per week had an OR of 0.92 (95% CI, 0.68-1.25), and men who consumed at least 7 drinks weekly had an OR of 0.71 (95% CI, 0.55-0.92) (P = .01 for trend across categories). Similar associations were observed between alcohol consumption and decreased glomerular filtration rates. Hypertension, diabetes mellitus, and cholesterol level did not attenuate these effects. CONCLUSIONS: In this large cohort of apparently healthy men, alcohol consumption was not associated with an increased risk of renal dysfunction. Instead, these data suggest an inverse relationship between moderate alcohol consumption and the risk of renal dysfunction.

Adult↗
PubMed2005

Prospective study of body mass index and risk of stroke in apparently healthy women.

BACKGROUND: Obesity is an escalating pandemic in the United States, and its association with coronary heart disease is well understood. Several studies have found positive associations between body mass index (BMI) and stroke in men, but the association with stroke and its subtypes is less clear in women. METHODS AND RESULTS: This was a prospective cohort study among 39 053 women participating in the Women's Health Study. BMI was measured as self-reported weight (in kilograms) divided by height (in meters) squared. Incident stroke was self-reported and confirmed by medical record review. We used the Cox proportional hazards model to evaluate the association between BMI and stroke. After a mean follow-up of 10 years, a total of 432 strokes (347 ischemic, 81 hemorrhagic, and 4 undefined) occurred. We found a statistically significant trend for increased risk of total and ischemic stroke across 7 BMI categories. With World Health Organization criteria, women who were obese (BMI > or =30 kg/m2) had hazard ratios of 1.50 (95% CI 1.16 to 1.94) for total stroke, 1.72 (95% CI 1.30 to 2.28) for ischemic stroke, and 0.82 (95% CI 0.43 to 1.58) for hemorrhagic stroke compared with women with BMI <25 kg/m2. Additional control for history of hypertension, diabetes, and elevated cholesterol substantially attenuated the hazard ratios for total and ischemic stroke. There was no effect modification for age, exercise, or smoking. CONCLUSIONS: In this large prospective cohort study among women, BMI was a strong risk factor for total and ischemic stroke but not for hemorrhagic stroke. The association was highly mediated by hypertension, diabetes, and elevated cholesterol.

Body Mass Index↗
PubMed2005

Association between body mass index and CKD in apparently healthy men.

BACKGROUND: Overweight and obesity are well-established risk factors for cardiovascular disease and decline in kidney function in individuals with existing chronic kidney disease (CKD). Conversely, their association with the development of CKD is less clear. METHODS: We evaluated the association between body mass index (BMI) and risk for CKD in a cohort of 11,104 initially healthy men who participated in the Physicians' Health Study and provided a blood sample after 14 years. BMI was calculated from self-reported weight and height. We estimated glomerular filtration rate (GFR) by using the abbreviated equation from the Modification of Diet in Renal Disease Study and defined CKD as GFR less than 60 mL/min/1.73 m2 (<1 mL/s/1.73 m2). RESULTS: After an average 14-year follow-up, 1,377 participants (12.4%) had a GFR less than 60 mL/min/1.73 m2 (<1 mL/s/1.73 m2). Higher baseline BMI was associated consistently with increased risk for CKD. Compared with participants in the lowest BMI quintile (<22.7 kg/m2), those in the highest quintile (>26.6 kg/m2) had an odds ratio (OR) of 1.45 (95% confidence interval [CI], 1.19 to 1.76; P trend <0.001) after adjusting for potential confounders. We found similar associations by using different categories of BMI. Compared with men who remained within a +/-5% range of their baseline BMI, those who reported a BMI increase greater than 10% had a significant increase in risk for CKD (OR, 1.27; 95% CI, 1.06 to 1.53). CONCLUSION: In this large cohort of initially healthy men, BMI was associated significantly with increased risk for CKD after 14 years. Strategies to decrease CKD risk might include prevention of overweight and obesity.

Adult↗
PubMed2004

Aspirin, NSAIDs, and COX-2 inhibitors in cardiovascular disease: possible interactions and implications for treatment of rheumatoid arthritis.

Aspirin, nonsteroidal antiinflammatory drugs (NSAIDs), and cyclooxygenase-2 (COX-2) inhibitors are widely used in patients with rheumatoid arthritis. Aspirin has the largest and most persuasive body of randomized trial evidence to support its use in secondary prevention for cardiovascular disease (CVD) and primary prevention for myocardial infarction. There is, however, a possible deleterious interaction between aspirin and NSAIDs on CVD that requires further research. Aspirin, NSAIDs, and to a lesser extent COX-2 inhibitors are associated with increased gastrointestinal side effects and bleeding, alone and in combination. The more widespread and appropriate use of aspirin in patients with rheumatoid arthritis will avoid many premature deaths in secondary prevention for CVD and first myocardial infarctions in primary prevention.

Anti-Inflammatory Agents, Non-Steroidal↗