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1.
Environ Int ; 185: 108530, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38422877

ABSTRACT

OBJECTIVE: Factors that shape individuals' vulnerability to the effects of air pollution on COVID-19 severity remain poorly understood. We evaluated whether the association between long-term exposure to ambient NO2, PM2.5, and PM10 and COVID-19 hospitalisation differs by age, sex, individual income, area-level socioeconomic status, arterial hypertension, diabetes mellitus, and chronic obstructive pulmonary disease. METHODS: We analysed a population-based cohort of 4,639,184 adults in Catalonia, Spain, during 2020. We fitted Cox proportional hazard models adjusted for several potential confounding factors and evaluated the interaction effect between vulnerability indicators and the 2019 annual average of NO2, PM2.5, and PM10. We evaluated interaction on both additive and multiplicative scales. RESULTS: Overall, the association was additive between air pollution and the vulnerable groups. Air pollution and vulnerability indicators had a synergistic (greater than additive) effect for males and individuals with low income or living in the most deprived neighbourhoods. The Relative Excess Risk due to Interaction (RERI) was 0.21, 95 % CI, 0.15 to 0.27 for NO2 and 0.16, 95 % CI, 0.11 to 0.22 for PM2.5 for males; 0.13, 95 % CI, 0.09 to 0.18 for NO2 and 0.10, 95 % CI, 0.05 to 0.14 for PM2.5 for lower individual income and 0.17, 95 % CI, 0.12 to 0.22 for NO2 and 0.09, 95 % CI, 0.05 to 0.14 for PM2.5 for lower area-level socioeconomic status. Results for PM10 were similar to PM2.5. Results on multiplicative scale were inconsistent. CONCLUSIONS: Long-term exposure to air pollution had a larger synergistic effect on COVID-19 hospitalisation for males and those with lower individual- and area-level socioeconomic status.


Subject(s)
Air Pollutants , Air Pollution , COVID-19 , Male , Adult , Humans , Air Pollutants/adverse effects , Air Pollutants/analysis , Particulate Matter/adverse effects , Particulate Matter/analysis , Nitrogen Dioxide/analysis , Environmental Exposure/adverse effects , Environmental Exposure/analysis , COVID-19/epidemiology , Air Pollution/adverse effects , Air Pollution/analysis , Hospitalization
2.
Enferm Infecc Microbiol Clin (Engl Ed) ; 41(5): 294-297, 2023 05.
Article in English | MEDLINE | ID: mdl-37076329

ABSTRACT

INTRODUCTION: It is unclear if SARS-CoV-2 has affected people living with HIV (PLWH) more. METHODS: We compared SARS-CoV-2 testing, test positivity, hospitalisation, intensive care unit (ICU) admission, and mortality between PLWH and the general HIV-negative population of Catalonia, Spain from March 1 to December 15, 2020. RESULTS: SARS-CoV-2 testing was lower among PLWH 3556/13,142 (27.06%) compared to the general HIV-negative population 1,954,902/6,446,672 (30.32%) (p<0.001) but test positivity was higher among PLWH (21.06% vs. 15.82%, p<0.001). We observed no significant differences between PLWH and the general population in terms of hospitalisation (13.75% vs. 14.97%, p=0.174) and ICU admission (0.93% vs. 1.66%, p=0.059). Among positive cases, we found a lower mortality rate among PLWH compared to the general population (1.74% vs 3.64%, p=0.002). CONCLUSION: PLWH tested less frequently for SARS-CoV-2, had a higher test positivity, similar ICU admission and hospitalisation rates, and lower SARS-CoV-2-associated mortality compared to the general HIV-negative population.


Subject(s)
COVID-19 , HIV Infections , Humans , Spain/epidemiology , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19 Testing , SARS-CoV-2 , HIV Infections/epidemiology
3.
Enferm Infecc Microbiol Clin ; 41(5): 294-297, 2023 May.
Article in English | MEDLINE | ID: mdl-35261420

ABSTRACT

Introduction: It is unclear if SARS-CoV-2 has affected people living with HIV (PLWH) more. Methods: We compared SARS-CoV-2 testing, test positivity, hospitalisation, intensive care unit (ICU) admission, and mortality between PLWH and the general HIV-negative population of Catalonia, Spain from March 1 to December 15, 2020. Results: SARS-CoV-2 testing was lower among PLWH 3556/13,142 (27.06%) compared to the general HIV-negative population 1,954,902/6,446,672 (30.32%) (p < 0.001) but test positivity was higher among PLWH (21.06% vs. 15.82%, p < 0.001). We observed no significant differences between PLWH and the general population in terms of hospitalisation (13.75% vs. 14.97%, p = 0.174) and ICU admission (0.93% vs. 1.66%, p = 0.059). Among positive cases, we found a lower mortality rate among PLWH compared to the general population (1.74% vs 3.64%, p = 0.002). Conclusion: PLWH tested less frequently for SARS-CoV-2, had a higher test positivity, similar ICU admission and hospitalisation rates, and lower SARS-CoV-2-associated mortality compared to the general HIV-negative population.


Introducción: No está claro si el SARS-CoV-2 ha afectado más a las personas que viven con VIH (PVV). Métodos: Se compararon los test realizados de SARS-CoV-2, la positividad de la prueba, la hospitalización, los ingresos en la unidad de cuidados intensivos (UCI), las tasas de mortalidad entre PVV y la población general de Cataluña desde el 1 de marzo hasta el 15 de diciembre de 2020. Resultados: Los test realizados de SARS-CoV-2 fueron menos entre PVV 3.556/13.142 (27.06%) comparado con la población general de Cataluña 1.954.902/6.446.672 (30,32%) (p < 0,001), pero la positividad de la prueba de SARS-CoV-2 fue mayor entre las PVV (21,06 vs. 15,82%; p < 0,001). No se observaron diferencias estadísticamente significativas entre PVV y la población general en cuanto a hospitalizaciones (13,75 vs. 14,97%; p = 0,174) e ingresos en la UCI (0,93 vs. 1,66%; p = 0,059). Entre los casos positivos, se encontró una menor tasa de mortalidad entre las PVV en comparación con la población general (1,74 vs. 3,64%; p = 0,002). Conclusiones: Las PVV fueron testadas menos frecuentemente por SARS-CoV-2 que la población general, tuvieron una tasa de positividad más elevada, tasas similares de hospitalización e ingresos en la UCI, y menos mortalidad asociada al SARS-CoV-2.

4.
J Antimicrob Chemother ; 77(8): 2265-2273, 2022 07 28.
Article in English | MEDLINE | ID: mdl-35678461

ABSTRACT

BACKGROUND: Reports on the impact of some antiretrovirals against SARS-CoV-2 infection and disease severity are conflicting. OBJECTIVES: We evaluated the effect of tenofovir as either tenofovir alafenamide/emtricitabine (TAF/FTC) or tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) against SARS-CoV-2 infection and associated clinical outcomes among people living with HIV (PLWH). METHODS: We conducted a propensity score-matched analysis in the prospective PISCIS cohort of PLWH (n = 14 978) in Catalonia, Spain. We used adjusted Cox regression models to assess the association between tenofovir and SARS-CoV-2 outcomes. RESULTS: After propensity score-matching, SARS-CoV-2 diagnosis rates were similar in TAF/FTC versus ABC/3TC recipients (11.6% versus 12.5%, P = 0.256); lower among TDF/FTC versus ABC/3TC recipients (9.6% versus 12.8%, P = 0.021); and lower among TDF/FTC versus TAF/FTC recipients (9.6% versus 12.1%, P = 0.012). In well-adjusted logistic regression models, TAF/FTC was no longer associated with reduced SARS-CoV-2 diagnosis [adjusted odds ratio (aOR) 0.90; 95% confidence interval (CI), 0.78-1.04] or hospitalization (aOR 0.93; 95% CI, 0.60-1.43). When compared with ABC/3TC, TDF/FTC was not associated with reduced SARS-CoV-2 diagnosis (aOR 0.79; 95% CI, 0.60-1.04) or hospitalization (aOR 0.51; 95% CI, 0.15-1.70). TDF/FTC was not associated with reduced SARS-CoV-2 diagnosis (aOR 0.79; 95% CI, 0.60-1.04) or associated hospitalization (aOR 0.33; 95% CI, 0.10-1.07) compared with TAF/FTC. CONCLUSIONS: TAF/FTC or TDF/FTC were not associated with reduced SARS-CoV-2 diagnosis rates or associated hospitalizations among PLWH. TDF/FTC users had baseline characteristics intrinsically associated with more benign SARS-CoV-2 infection outcomes. Tenofovir exposure should not modify any preventive or therapeutic SARS-CoV-2 infection management.


Subject(s)
Anti-HIV Agents , COVID-19 , HIV Infections , Anti-HIV Agents/therapeutic use , COVID-19 Testing , Emtricitabine/therapeutic use , HIV Infections/drug therapy , Humans , Lamivudine/therapeutic use , Propensity Score , Prospective Studies , SARS-CoV-2 , Tenofovir/therapeutic use
5.
Lancet HIV ; 8(11): e701-e710, 2021 11.
Article in English | MEDLINE | ID: mdl-34655549

ABSTRACT

BACKGROUND: Factors affecting outcomes of SARS-CoV-2 infection in people living with HIV are unclear. We assessed the factors associated with SARS-CoV-2 diagnosis and severe outcomes among people living with HIV. METHODS: We did a retrospective cohort study using data from the PISCIS cohort of people with HIV in Catalonia (Spain) between March 1 and Dec 15, 2020. We linked PISCIS data with integrated health-care, clinical, and surveillance registries through the Public Data Analysis for Health Research and Innovation Program of Catalonia (PADRIS) to obtain data on SARS-CoV-2 diagnosis, chronic comorbidities, as well as clinical and mortality outcomes. Participants were aged at least 16 years in care at 16 hospitals in Catalonia. Factors associated with SARS-CoV-2 diagnoses and severe outcomes were assessed using univariable and multivariable Cox regression models. We estimated the effect of immunosuppression on severe outcomes (hospital admission for >24 h with dyspnoea, tachypnoea, hypoxaemia, asphyxia, or hyperventilation; or death) using Kaplan-Meier survival analysis. FINDINGS: We linked 20 847 (72·8%) of 28 666 participants in the PISCIS cohort with PADRIS data; 13 142 people had HIV. 749 (5·7%) people with HIV were diagnosed with SARS-CoV-2: their median age was 43·5 years (IQR 37·0-52·7), 131 (17·5%) were female, and 618 (82·5%) were male. 103 people with HIV (13·8%) were hospitalised, seven (0·9%) admitted to intensive care, and 13 (1·7%) died. SARS-CoV-2 diagnosis was more common among migrants (adjusted hazard ratio 1·55, 95% CI 1·31-1·83), men who have sex with men (1·42, 1·09-1·86), and those with four or more chronic comorbidities (1·46, 1·09-1·97). Age at least 75 years (5·2, 1·8-15·3), non-Spanish origin (2·1, 1·3-3·4), and neuropsychiatric (1·69, 1·07-2·69), autoimmune disease (1·92, 1·14-3·23), respiratory disease (1·84, 1·09-3·09), and metabolic disease (2·59, 1·59-4·23) chronic comorbidities were associated with increased risk of severe outcomes. A Kaplan-Meier estimator showed differences in the risk of severe outcomes according to CD4 cell count in patients with detectable HIV RNA (p=0·039) but no differences were observed in patients with undetectable HIV RNA (p=0·15). INTERPRETATION: People living with HIV with detectable HIV viraemia, chronic comorbidities, and some subpopulations could be at increased risk of severe outcomes from COVID-19. These groups should be prioritised in clinical management and SARS-CoV-2 vaccination programmes. FUNDING: Fundació "la Caixa". TRANSLATIONS: For the Catalan, Spanish and Russian translations of the Summary see Supplementary Materials section.


Subject(s)
COVID-19/immunology , COVID-19/mortality , HIV Infections/complications , HIV Infections/immunology , Immunoglobulin G/blood , SARS-CoV-2/immunology , Adult , Aged , Aged, 80 and over , COVID-19/complications , COVID-19/epidemiology , COVID-19 Testing , COVID-19 Vaccines , Cohort Studies , Female , HIV Infections/drug therapy , HIV Infections/epidemiology , Humans , Immunologic Factors , Male , Middle Aged , Retrospective Studies , Severity of Illness Index , Socioeconomic Factors , Spain/epidemiology
6.
N Engl J Med ; 384(5): 417-427, 2021 02 04.
Article in English | MEDLINE | ID: mdl-33289973

ABSTRACT

BACKGROUND: Current strategies for preventing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are limited to nonpharmacologic interventions. Hydroxychloroquine has been proposed as a postexposure therapy to prevent coronavirus disease 2019 (Covid-19), but definitive evidence is lacking. METHODS: We conducted an open-label, cluster-randomized trial involving asymptomatic contacts of patients with polymerase-chain-reaction (PCR)-confirmed Covid-19 in Catalonia, Spain. We randomly assigned clusters of contacts to the hydroxychloroquine group (which received the drug at a dose of 800 mg once, followed by 400 mg daily for 6 days) or to the usual-care group (which received no specific therapy). The primary outcome was PCR-confirmed, symptomatic Covid-19 within 14 days. The secondary outcome was SARS-CoV-2 infection, defined by symptoms compatible with Covid-19 or a positive PCR test regardless of symptoms. Adverse events were assessed for up to 28 days. RESULTS: The analysis included 2314 healthy contacts of 672 index case patients with Covid-19 who were identified between March 17 and April 28, 2020. A total of 1116 contacts were randomly assigned to receive hydroxychloroquine and 1198 to receive usual care. Results were similar in the hydroxychloroquine and usual-care groups with respect to the incidence of PCR-confirmed, symptomatic Covid-19 (5.7% and 6.2%, respectively; risk ratio, 0.86 [95% confidence interval, 0.52 to 1.42]). In addition, hydroxychloroquine was not associated with a lower incidence of SARS-CoV-2 transmission than usual care (18.7% and 17.8%, respectively). The incidence of adverse events was higher in the hydroxychloroquine group than in the usual-care group (56.1% vs. 5.9%), but no treatment-related serious adverse events were reported. CONCLUSIONS: Postexposure therapy with hydroxychloroquine did not prevent SARS-CoV-2 infection or symptomatic Covid-19 in healthy persons exposed to a PCR-positive case patient. (Funded by the crowdfunding campaign YoMeCorono and others; BCN-PEP-CoV2 ClinicalTrials.gov number, NCT04304053.).


Subject(s)
Anti-Infective Agents/therapeutic use , COVID-19/prevention & control , Hydroxychloroquine/therapeutic use , SARS-CoV-2 , Adult , Anti-Infective Agents/adverse effects , COVID-19/transmission , COVID-19/virology , Disease Transmission, Infectious/prevention & control , Double-Blind Method , Female , Humans , Hydroxychloroquine/adverse effects , Male , Middle Aged , Patient Compliance , Treatment Failure , Viral Load
7.
J Neurol ; 268(1): 285-292, 2021 Jan.
Article in English | MEDLINE | ID: mdl-32789606

ABSTRACT

BACKGROUND: Stroke recurrence (SR) after an ischemic stroke is an important cause of death and disability. We conducted a hospital-based study to evaluate the role of biological age (b-Age: age-related DNA-methylation changes) as a risk factor for SR. METHODS: We included 587 patients in the acute phase of stroke, assessed at one tertiary stroke center (Hospital del Mar: Barcelona, Spain). B-Age was estimated with 5 different methods based on DNA methylation, and Hannum's method was the one that better performed. We analyzed the relationships between b-Age, chronological age, sex, vascular risk factors, coronary and peripheral arterial disease, atrial fibrillation, initial neurological severity assessed by National Institutes of Health Stroke Scale (NIHSS), transient ischemic attack (TIA) in the 7 days preceding the index stroke, and symptomatic atherosclerosis. Stroke recurrence definition include: new symptoms that suggest a new ischemic event had occurred within 3 months after stroke onset and worsening by four points in the initial neurological severity (measured by National Institutes of Health Stroke Scale (NIHSS) score). RESULTS: Logistic regression analysis associated b-Age with SR [p = 0.003; OR = 1.06 (95% CI: 1.02-1.09)], independently of chronological age [p = 0.022; OR = 0.96 (95% CI 0.94-1.00)], symptomatic atherosclerosis (stenosis > 50% in the symptomatic territory), transient ischemic attack (TIA) in the 7 days preceding the index stroke, and initial NIHSS. The b-Age of patients with SR was 2.7 years older than patients without SR. CONCLUSIONS: Patients with SR were biologically older than those without SR. B-Age was independently associated with high risk of developing SR.


Subject(s)
Ischemic Attack, Transient , Stroke , Aging , Biomarkers , Child, Preschool , Humans , Ischemic Attack, Transient/diagnosis , Ischemic Attack, Transient/epidemiology , Recurrence , Risk Factors , Spain/epidemiology , Stroke/diagnosis , Stroke/epidemiology , Time Factors
8.
Neurology ; 95(13): e1819-e1829, 2020 09 29.
Article in English | MEDLINE | ID: mdl-32796129

ABSTRACT

OBJECTIVE: To describe short-term and 5-year rates of mortality and poor outcome in patients with spontaneous aneurysmal subarachnoid hemorrhage (aSAH) who received repair treatment. METHODS: In this prospective observational study, mortality and poor outcome (modified Rankin Scale score 3-6) were analyzed in 311 patients with aSAH at 3 months, 1 year, and 5 years follow-up. Sensitivity analysis was performed according to treatment modality. In-hospital and 5-year complications were analyzed. RESULTS: Of 476 consecutive patients with spontaneous subarachnoid hemorrhage, 347 patients (72.9%) had aSAH. Of these, 311 (89.6%) were treated (242 endovascular, 69 neurosurgical), with a mean follow-up of 43.4 months (range, 1 to 145). Three-month, 1-year, and 5-year mortality was 18.4%, 22.9%, and 29.0%, and poor outcome was observed in 42.3%, 36.0%, and 36.0%, respectively. Adjusted poor outcome was lower in endovascular than in neurosurgical treatment at 3 months (odds ratio [OR] 0.36 [95% confidence interval [CI] 0.18-0.74]), with an absolute difference of 15.8% (number needed to treat = 6.3), and at 1 year (OR = 0.40 [95% CI 0.20-0.81]), with an absolute difference of 15.9% (number needed to treat = 6.3). Complications did not differ between the 2 procedures. However, mechanical ventilation was less frequent with the endovascular technique (OR 0.67 [95% CI 0.54-0.84]). CONCLUSIONS: Patients with aSAH treated according to current guidelines had a short-term mortality of 18.4% and 5-year mortality of 29%. The majority (64.0%) of patients remained alive without disabilities at 5-year follow-up. Patients prioritized to endovascular treatment had better outcomes than those referred to neurosurgery because endovascular coiling was not feasible.


Subject(s)
Aneurysm, Ruptured/surgery , Intracranial Aneurysm/surgery , Subarachnoid Hemorrhage/surgery , Aneurysm, Ruptured/mortality , Female , Humans , Intracranial Aneurysm/mortality , Male , Middle Aged , Neurosurgical Procedures/statistics & numerical data , Postoperative Complications/epidemiology , Spain/epidemiology , Subarachnoid Hemorrhage/mortality , Time Factors , Treatment Outcome
9.
Circ Res ; 124(1): 114-120, 2019 01 04.
Article in English | MEDLINE | ID: mdl-30582445

ABSTRACT

RATIONALE: Ischemic stroke is among the leading causes of adult disability. Part of the variability in functional outcome after stroke has been attributed to genetic factors but no locus has been consistently associated with stroke outcome. OBJECTIVE: Our aim was to identify genetic loci influencing the recovery process using accurate phenotyping to produce the largest GWAS (genome-wide association study) in ischemic stroke recovery to date. METHODS AND RESULTS: A 12-cohort, 2-phase (discovery-replication and joint) meta-analysis of GWAS included anterior-territory and previously independent ischemic stroke cases. Functional outcome was recorded using 3-month modified Rankin Scale. Analyses were adjusted for confounders such as discharge National Institutes of Health Stroke Scale. A gene-based burden test was performed. The discovery phase (n=1225) was followed by open (n=2482) and stringent joint-analyses (n=1791). Those cohorts with modified Rankin Scale recorded at time points other than 3-month or incomplete data on previous functional status were excluded in the stringent analyses. Novel variants in PATJ (Pals1-associated tight junction) gene were associated with worse functional outcome at 3-month after stroke. The top variant was rs76221407 (G allele, ß=0.40, P=1.70×10-9). CONCLUSIONS: Our results identify a set of common variants in PATJ gene associated with 3-month functional outcome at genome-wide significance level. Future studies should examine the role of PATJ in stroke recovery and consider stringent phenotyping to enrich the information captured to unveil additional stroke outcome loci.


Subject(s)
Brain Ischemia/genetics , Polymorphism, Single Nucleotide , Stroke/genetics , Tight Junction Proteins/genetics , Brain Ischemia/diagnosis , Brain Ischemia/physiopathology , Brain Ischemia/rehabilitation , Disability Evaluation , Gene Frequency , Genetic Predisposition to Disease , Genome-Wide Association Study , Humans , Phenotype , Recovery of Function , Risk Factors , Stroke/diagnosis , Stroke/physiopathology , Stroke/therapy , Stroke Rehabilitation , Treatment Outcome
10.
Front Neurol ; 9: 427, 2018.
Article in English | MEDLINE | ID: mdl-29928257

ABSTRACT

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).

11.
Neurology ; 89(8): 830-836, 2017 Aug 22.
Article in English | MEDLINE | ID: mdl-28733340

ABSTRACT

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.


Subject(s)
Aging/metabolism , Brain Ischemia/metabolism , Brain Ischemia/therapy , DNA Methylation , Stroke/metabolism , Stroke/therapy , Aged , Aged, 80 and over , Aging/genetics , Algorithms , Brain Ischemia/diagnosis , Brain Ischemia/genetics , Cross-Sectional Studies , Female , Humans , Male , Multivariate Analysis , Prognosis , Prospective Studies , Regression Analysis , Retrospective Studies , Risk Factors , Severity of Illness Index , Stroke/diagnosis , Stroke/genetics , Treatment Outcome
12.
Aging (Albany NY) ; 8(11): 2655-2666, 2016 08 25.
Article in English | MEDLINE | ID: mdl-27922817

ABSTRACT

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 individual's 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.


Subject(s)
Aging/genetics , Brain Ischemia/genetics , CpG Islands , Epigenesis, Genetic , Stroke/genetics , Adult , Aged , Aged, 80 and over , DNA Methylation , Female , Humans , Male , Middle Aged
13.
Hum Mol Genet ; 25(3): 609-19, 2016 Feb 01.
Article in English | MEDLINE | ID: mdl-26643952

ABSTRACT

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%).


Subject(s)
Brain Ischemia/genetics , Carrier Proteins/genetics , Diabetes Mellitus, Type 2/genetics , Epigenesis, Genetic , Glycated Hemoglobin/genetics , Hyperglycemia/genetics , Stroke/genetics , Aged , Aged, 80 and over , Brain Ischemia/blood , Brain Ischemia/pathology , Carrier Proteins/blood , CpG Islands , DNA Methylation , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/pathology , Female , Genome-Wide Association Study , Glycated Hemoglobin/metabolism , Humans , Hyperglycemia/blood , Hyperglycemia/pathology , Male , Middle Aged , Retrospective Studies , Stroke/blood , Stroke/pathology
14.
Seizure ; 23(8): 670-3, 2014 Sep.
Article in English | MEDLINE | ID: mdl-24890932

ABSTRACT

PURPOSE: Ictal piloerection is an infrequent seizure semiology that is commonly overlooked as an ictal epileptic manifestation. Piloerection is considered to be principally caused by temporal lobe activity although frontal and hypothalamic seizure origins have been reported. The described etiology has shown a wide variety of structural causes such as mesial temporal sclerosis, tumors, posttraumatic, cavernomas and cryptogenic epilepsies. METHODS: We retrospectively reviewed the incidence of ictal piloerection in the clinical records of patients who underwent video-EEG monitoring (VEEGM) between 2007 and 2013 in a multicenter cooperative study. All patients presented refractory epilepsies and were evaluated with a protocol that included brain MRI, neuropsychology and VEEGM. RESULTS: A total of 766 patients were evaluated in four tertiary centers in Spain. Five patients showed piloerection as principal seizure semiology (prevalence 0.65%). The mean age at seizure onset was 39.6 years and the average epilepsy duration was 5.2 years (range 2-14) before diagnosis. Four patients were additionally examined with FDG-PET and/or SPECT-SISCOM. All presented temporal lobe epilepsy (TLE), three right-sided and two left-sided. A typical unilateral hippocampal sclerosis was described in 3 cases. The etiology detected in all cases was limbic encephalitis. Three had LGI1, one anti-Hu, and another Ma2 antibodies. CONCLUSION: Our series describes a so far not well-recognized autoimmune association of pilomotor seizures to limbic encephalitis. This etiology should be ruled out through a comprehensive diagnostic work-up even in cases of long-lasting TLE with typical hippocampal atrophy on MRI.


Subject(s)
Limbic Encephalitis/epidemiology , Limbic Encephalitis/physiopathology , Piloerection/physiology , Seizures/epidemiology , Seizures/physiopathology , Adult , Brain/pathology , Brain/physiopathology , Electroencephalography , Female , Humans , Incidence , Limbic Encephalitis/pathology , Magnetic Resonance Imaging , Male , Middle Aged , Neuropsychological Tests , Positron-Emission Tomography , Retrospective Studies , Sclerosis , Seizures/pathology , Spain/epidemiology , Tomography, Emission-Computed, Single-Photon , Video Recording
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