Rosa Maria Vivanco-Hidalgo

Epigenome-wide association study identifies TXNIP gene associated with type 2 diabetes mellitus and sustained hyperglycemia

Type 2 diabetes mellitus (DM) is an established risk factor for a wide range of vascular diseases, including ischemic stroke (IS). Glycated hemoglobin A1c (HbA1c), a marker for average blood glucose levels over the previous 12 weeks, is used as a measure of glycemic control and also as a diagnostic criterion for diabetes (HbA1c levels ≥ 6.5%). Epigenetic mechanisms, such as DNA methylation, may be associated with aging processes and with modulation of the risk of various pathologies, such as DM. Specifically, DNA methylation could be one of the mechanisms mediating the relation between DM and environmental exposures. Our goal was to identify new CpG methylation sites associated with DM. We performed a genome-wide methylation study in whole-blood DNA from an IS patient cohorts. Illumina HumanMethylation450 BeadChip array was used to measure DNA methylation in CpG sites. All statistical analyses were adjusted for sex, age, hyperlipidemia, body mass index (BMI), smoking habit and cell count. Findings were replicated in two independent cohorts, an IS cohort and a population-based cohort, using the same array. In the discovery phase (N = 355), we identified a CpG site, cg19693031 (located in the TXNIP gene) that was associated with DM (P = 1.17 × 10(-12)); this CpG was replicated in two independent cohorts (N = 167 and N = 645). Methylation of TXNIP was inversely and intensely associated with HbA1c levels (P = 7.3 × 10(-16)), specifically related to diabetic patients with poor control of glucose levels. We identified an association between the TXNIP gene and DM through epigenetic mechanisms, related to sustained hyperglycemia levels (HbA1c ≥ 7%).

Glycated Hemoglobin Value Combined with Initial Glucose Levels for Evaluating Mortality Risk in Patients with Ischemic Stroke

Background: Hyperglycemia is a marker of poor outcome in acute ischemic stroke (IS) patients. We aimed at evaluating the effect of combined HbA1c and first glucose measurement values on 3-month mortality prediction. Methods: In a prospective analysis, 1,317 first-ever IS patients with HbA1c values were classified by first glycemia value (<155, 155-199, ≥200 mg/dl). Three-month mortality was analyzed by glycemia category in nondiabetics, diabetics with good previous glucose control (PGC) (HbA1c <7%), and diabetics with poor PGC (HbA1c ≥7.0%). Results: Mortality at 3 months was 13.1%, with no differences (p = 0.339) between non-diabetes mellitus (DM) (12.3%), good PGC-DM (12.4%), and poor PGC-DM (15.6%) patients. The unadjusted relative risk of 3-month mortality for patients with glucose ≥200 mg/dl was 3.76 (95% CI 1.48-9.56) in non-DM, 6.10 (95% CI 1.76-21.09) in good PGC-DM, and 1.44 (95% CI 0.77-2.69) in poor PGC-DM. Glycemia cutoffs most highly correlated with mortality increased as PGC declined: 107 mg/dl in non-DM, 152 mg/dl in good PGC-DM, and 229 mg/dl in poor PGC-DM patients. Glycemia correlated with stroke severity in nondiabetics and diabetic patients with good PGC, but not in those with poor PGC. Conclusions: HbA1c determination combined with first measured glucose value is useful to stratify mortality risk in IS patients: hyperglycemia is a poor prognostic marker in non-DM and DM patients with good PGC; results are inconsistent in poor PGC-DM patients. Our data suggest the relationship between hyperglycemia and poor outcome reflects stress response rather than a deleterious effect of glucose.

Biological age is better than chronological as predictor of 3-month outcome in ischemic stroke

Objective: To analyze the effect of age-related DNA methylation changes in multiple cytosine-phosphate-guanine (CpG) sites (biological age [b-age]) on patient outcomes at 3 months after an ischemic stroke. Methods: We included 511 patients with first-ever acute ischemic stroke assessed at Hospital del Mar (Barcelona, Spain) as the discovery cohort. Demographic and clinical data, including chronological age (c-age), vascular risk factors, initial stroke severity, recanalization treatment, and previous and 3-month modified Rankin Scale (p-mRS and 3-mRS, respectively) were registered. B-age was estimated with an algorithm, based on DNA methylation in 71 CpGs. Bivariate analysis determined variables associated with 3-mRS for inclusion in ordinal multivariate analysis. Results: After ordinal regressions for 3-month ischemic stroke outcome (3-mRS), b-age was associated with outcome (odds ratio 1.04 [95% confidence interval 1.01–1.07]), nullifying c-age. Stepwise regression kept b-age, basal NIH Stroke Scale, sex, p-mRS, and recanalization treatment as better explanatory variables, instead of c-age. These results were successfully replicated in an independent cohort. Conclusions: B-age, estimated by DNA methylation, is an independent predictor of ischemic stroke outcome regardless of chronological years.

Ischemic stroke patients are biologically older than their chronological age

Ischemic stroke is associated with aging. It is possible to predict chronological age by measuring age-related changes in DNA methylation from multiple CpG sites across the genome, known as biological age. The difference between biological age and actual chronological age would indicate an individuals level of aging. Our aim was to determine the biological age of ischemic stroke patients and compare their aging with controls of the same chronological age. A total of 123 individuals, 41 controls and 82 patients with ischemic stroke were paired by chronological age, ranging from 39 to 82 years. Illumina HumanMethylation450 BeadChip array was used to measure DNA methylation in CpG sites in both groups, and biological age was estimated using methylation values of specific CpGs. Ischemic stroke patients were biologically an average 2.5 years older than healthy controls (p-value=0.010). Stratified by age tertiles, younger stroke patients (≤57 years old) were biologically older than controls (OR=1.19; 95%CI 1.00-1.41, p-value=0.046). The older groups showed no biological age differences between cases and controls, but were close to reaching the significance level. Ischemic stroke patients are biologically older than controls. Biological age should be considered as a potential new biomarker of stroke risk.

People with epilepsy receive more statins than the general population but have no higher cardiovascular risk: results from a cross‐sectional study

Epilepsy has been associated with cardiovascular comorbidity. Risk prediction equations are the standard tools in primary prevention of cardiovascular disease. Our aim was to compare the prevalence of cardiovascular risk factors (CVRFs), cardiovascular risk and statin use in people with epilepsy (PWE) and the general population.

Short-term exposure to traffic-related air pollution and ischemic stroke onset in Barcelona, Spain

Objective To assess the relationship between short‐term exposure to outdoor ambient air pollutants (fine particulate matter [PM2.5] and black carbon [BC]), ischemic stroke (IS) and its different subtypes, and the potential modifying effect of neighborhood greenspace and noise. Methods This time‐stratified case‐crossover study was based on IS and transient ischemic attacks (TIA) recorded in a hospital‐based prospective stroke register (BASICMAR 2005–2014) in Barcelona (Catalonia, Spain). Daily and hourly pollutant concentrations and meteorological data were obtained from monitoring stations in the city. Time‐lags (from previous 72 h to acute stroke onset) were analyzed. Greenness and noise were determined from the Normalized Difference Vegetation Index (NDVI) and daily average noise level at the street nearest to residential address, respectively. Results The 2742 cases with known onset date and time, living in the study area, were analyzed. After adjusting for temperature, no statistically significant association between pollutants exposure and overall stroke risk was found. In subtype analysis, an association was detected between BC exposure at 24–47 h (odds ratio, 1.251; 95% confidence interval [CI], 1.001–1.552; P = 0.042) and 48–72 h (1.211; 95% CI, 0.988–1.484; P = 0.065) time‐lag prior to stroke onset and large‐artery atherosclerosis subtype. No clear modifying effect of greenness or noise was observed. Conclusions Overall, no association was found between PM2.5 and BC exposure and acute IS risk. By stroke subtype, large‐artery atherosclerotic stroke could be triggered by daily increases in BC, a diesel fuel‐related pollutant in the study area. HighlightsBC levels are associated with higher risk of large‐artery atherosclerosis stroke.This association did not vary by levels of green space and traffic noise.Setting BC air quality standards could have valuable health benefits.

Prevalence of cardiovascular risk factors in people with epilepsy

Epilepsy has been associated with cardiovascular comorbidity. This study aimed to assess the potential association between cardiovascular risk factors (CRFs), antiepileptic drugs (AEDs), and etiology.

Innovation in Systems of Care in Acute Phase of Ischemic Stroke. The Experience of the Catalan Stroke Programme

Stroke, and mainly ischemic stroke, is the second cause of death and disability. To confront the huge burden of this disease, innovative stroke systems of care are mandatory. This requires the development of national stroke plans to offer the best treatment to all patients eligible for reperfusion therapies. Key elements for success include a high level of organization, close cooperation with emergency medical services for prehospital assessment, an understanding of stroke singularity, the development of preassessment tools, a high level of commitment of all stroke teams at Stroke Centres, the availability of a disease-specific registry, and local government involvement to establish stroke care as a priority. In this mini review, we discuss recent evidence concerning different aspects of stroke systems of care and describe the success of the Catalan Stroke Programme as an example of innovation. In Catalonia, reperfusion treatment rates have increased in recent years and currently are among the highest in Europe (17.3% overall, 14.3% for IVT, and 6% for EVT in 2016).

Interaction of Sex and Diabetes on Outcome After Ischemic Stroke

Background The relationship between ischemic stroke (IS), diabetes mellitus (DM), and sex is intriguing. The aim of this study was to assess the effect modification of sex in the association between DM and short- and long-term disability and mortality in first-ever IS patients. Methods In a retrospective, observational, hospital-based study of a prospective series including first-ever IS patients from January 2006 until July 2011, differences in 3-month and 5-year mortality, and disability between diabetic and non-diabetic patients [modified Rankin Scale (mRS) from 3 to 5] were analyzed by sex. Results In total, 933 patients (36.3% with DM, 50.5% women) were included. Overall 3-month and 5-year mortality were 150 (16.1%) and 407 (44.1%), respectively. Adjusted for age, previous mRS, and stroke severity, patients with DM had significantly higher 3-month disability [hazard ratio (HR): 1.49 (95% confidence interval (CI): 1.39–1.70), p < 0.0001], 5-year disability [HR: 1.41 (95% CI: 1.07–1.86), p = 0.015], and 5-year mortality [HR: 1.48 (95% CI: 1.20–1.81), p < 0.0001], compared with the non-DM group. Compared with non-DM women, women with diabetes had worse 3-month disability [HR: 1.81 (95% CI: 1.33–2.46), p < 0.0001] and 5-year mortality [HR: 1.72 (95% CI: 1.30–2.20), p < 0.0001], and a trend for 5-year disability [HR: 1.40 (95% CI: 0.99–2.09), p = 0.057]. In men, DM had an effect on 3-month disability [HR: 1.45 (95% CI: 1.07–1.96), p = 0.018], a trend for 5-year disability [HR: 1.43 (95% CI: 0.94–2.19), p = 0.096], but no clear effect on 5-year mortality [HR: 1.22 (95% CI: 0.91–1.65), p = 0.186]. Conclusion Sex has a modifier effect on mortality in first-ever IS diabetic patients. Long-term mortality is increased in diabetic women compared with non-diabetic women, a difference not observed in men.

Ultra-early hematoma growth in antithrombotic pretreated patients with intracerebral hemorrhage.

Patients with acute intracerebral hemorrhage (ICH) pretreated with antithrombotic drugs may have increased early hematoma growth, which would increase mortality risk. The effect of antiplatelet (AP) and vitamin K antagonist (VKA) pretreatment on ultra‐early hematoma growth (uHG) and its relationship with mortality in patients with acute supratentorial ICH was analyzed.