The early-life exposome and epigenetic age acceleration in children.

The early-life exposome influences future health and accelerated biological aging has been proposed as one of the underlying biological mechanisms. We investigated the association between more than 100 exposures assessed during pregnancy and in childhood (including indoor and outdoor air pollutants, built environment, green environments, tobacco smoking, lifestyle exposures, and biomarkers of chemical pollutants), and epigenetic age acceleration in 1,173 children aged 7 years old from the Human Early-Life Exposome project. Age acceleration was calculated based on Horvath's Skin and Blood clock using child blood DNA methylation measured by Infinium HumanMethylation450 BeadChips. We performed an exposure-wide association study between prenatal and childhood exposome and age acceleration. Maternal tobacco smoking during pregnancy was nominally associated with increased age acceleration. For childhood exposures, indoor particulate matter absorbance (PMabs) and parental smoking were nominally associated with an increase in age acceleration. Exposure to the organic pesticide dimethyl dithiophosphate and the persistent pollutant polychlorinated biphenyl-138 (inversely associated with child body mass index) were protective for age acceleration. None of the associations remained significant after multiple-testing correction. Pregnancy and childhood exposure to tobacco smoke and childhood exposure to indoor PMabs may accelerate epigenetic aging from an early age.

Role of lipoprotein-associated phospholipase A2 activity for the prediction of silent brain infarcts in women.

OBJECTIVES: Lipoprotein-associated phospholipase A2 (Lp-PLA2), predicts risk of coronary events and stroke and might be associated with cerebral small vessel disease. We aimed to determine whether silent brain infarcts relate to Lp-PLA2 activity and also, whether the addition of Lp-PLA2 activity to prognostic clinical models improves silent brain infarcts' discrimination. METHODS: Cross-sectional study in 921 stroke-free individuals. On baseline, demographic and vascular risk factors were collected and a brain magnetic resonance was performed to assess for the presence of silent brain infarcts. Serum Lp-PLA2 activity was tested by an enzymatic assay (PLAC Test for activity) for all study participants and 49 healthy individuals free of vascular risk factors. Multivariate analysis and Integrated Discrimination Improvement were performed to assess whether Lp-PLA2 activity was independently associated with silent brain infarcts and improved their discrimination added to clinical variables. RESULTS: Lp-PLA2 activity was independently associated with silent brain infarcts in women (OR per one standard deviation increase: 2.14, from 1.31 to 3.50) but not in men (OR = 1.09, from 0.81 to 1.48) after adjustment by age, diastolic blood pressure, total cholesterol, statin treatment and other potential confounders. Adding Lp-PLA2 to clinical information for SBIs diagnosis resulted in a non-significant and mild improvement in discrimination (IDI = 3.1%) in women. CONCLUSIONS: Although Lp-PLA2 is independently associated with silent brain infarcts in women, its addition to clinical variables does not lead to any improvement in their prediction.

Diabetes is the main factor accounting for hypomagnesemia in obese subjects.

OBJECTIVE: Type 2 diabetes (T2DM) and obesity are associated with magnesium deficiency. We aimed to determine whether the presence of type 2 diabetes and the degree of metabolic control are related to low serum magnesium levels in obese individuals. METHODS: A) Case-control study: 200 obese subjects [50 with T2DM (cases) and 150 without diabetes (controls)] prospectively recruited. B) Interventional study: the effect of bariatric surgery on serum magnesium levels was examined in a subset of 120 obese subjects (40 with type 2 diabetes and 80 without diabetes). RESULTS: Type 2 diabetic patients showed lower serum magnesium levels [0.75±0.07 vs. 0.81±0.06 mmol/L; mean difference -0.06 (95% CI -0.09 to -0.04); p<0.001] than non-diabetic patients. Forty-eight percent of diabetic subjects, but only 15% of non-diabetic subjects showed a serum magnesium concentration lower than 0.75 mmol/L. Significant negative correlations between magnesium and fasting plasma glucose, HbA1c, HOMA-IR, and BMI were detected. Multiple linear regression analysis showed that fasting plasma glucose and HbA1c independently predicted serum magnesium. After bariatric surgery serum magnesium increased only in those patients in whom diabetes was resolved, but remain unchanged in those who not, without difference in loss weight between groups. Changes in serum magnesium negatively correlated with changes in fasting plasma glucose and HbA1c. Absolute changes in HbA1c independently predicted magnesium changes in the multiple linear regression analysis. CONCLUSIONS: Our results provide evidence that the presence of diabetes and the degree of metabolic control are essential in accounting for the lower levels of magnesium that exist in obese subjects.

Lipoprotein-associated phospholipase A(2) activity is associated with large-artery atherosclerotic etiology and recurrent stroke in TIA patients.

BACKGROUND: Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) has emerged as a novel biomarker in cardiovascular diseases due to its ability to predict stroke in population-based studies. We aimed to investigate Lp-PLA(2) levels in transient ischemic attack (TIA) patients and to study their relationship with stroke recurrence. METHODS: Lp-PLA(2) mass and activity were measured by means of the PLAC test with an automated Olympus analyzer and by a colorimetric activity method (diaDexus) in 166 TIA patients and 144 healthy controls. Vascular risk factors and stroke etiology were assessed. Outcome was defined as the presence of recurrent stroke/TIA within 7 and 30 days after the index TIA. Multivariate analyses were performed to identify potential predictors of recurrence. RESULTS: Both Lp-PLA(2) mass and activity (p < 0.05) were higher in TIA than in controls. Several risk factors or previous treatments were associated with Lp-PLA(2) mass and activity level. During follow-up, 20 strokes/TIA (12%) occurred within the first 30 days and the presence of a large-artery atherosclerosis etiology of stroke (HR 3.28, p = 0.011), together with the past medical history of hyperlipidemia (HR 3.68, p = 0.008) and Lp-PLA(2) activity of >207 nmol/ml/min (HR 2.7, p = 0.042) were all significant predictors for recurrent stroke/TIA. CONCLUSIONS: Lp-PLA(2) activity might add significant prognostic information in the early evaluation of TIA patients.

Temporal profile and prognostic value of Lp-PLA2 mass and activity in the acute stroke setting.

BACKGROUND: Lp-PLA2 is a novel biomarker in cardiovascular diseases due to its ability to predict first-ever and recurrent stroke. Little information is known regarding its influence on early outcome after stroke. OBJECTIVES: We aimed to investigate Lp-PLA2 in t-PA-treated stroke patients and to study its relationship with early outcome. METHODS: Lp-PLA2 mass and activity were measured in 135 healthy controls and also in stroke patients treated with t-PA at baseline (n=99) and serially thereafter (n=34) by means of the PLAC test at an automated Olympus analyzer and by a colorimetric activity method (diaDexus). NIHSS scores and TCD recordings were also obtained serially. Outcome was defined according to early neurological status, the presence of arterial recanalization and functional outcome at third month. RESULTS: Lp-PLA2 mass was increased as compared to controls, whereas Lp-PLA2 activity was significantly decreased at baseline as compared with controls and with 1 and 24 h determinations. Lp-PLA2 mass and activity were not related with early (48 h) neurological status. Regarding recanalization, higher mass and activity were found among patients who did not achieve complete recanalization by the end of t-PA treatment (p=0.029 for mass, p=0.044 for activity). Lp-PLA2 mass and the existence of a proximal occlusion at baseline were the most powerful predictors for persistent occlusions (OR for proximal occlusion 6.8. p=0.036, OR for Lp-PLA2 mass 7.2 per standard deviation increase, p=0.008). CONCLUSIONS: Significant changes in Lp-PLA2 concentrations occur early after stroke onset. Lp-PLA2 mass may add relevant information regarding early arterial recanalization in intravenous t-PA-treated stroke patients.

Lipoprotein-associated phospholipase A2 testing usefulness among patients with symptomatic intracranial atherosclerotic disease.

BACKGROUND AND PURPOSE: Circulating lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) has emerged as a novel biomarker for cardiovascular diseases. Our aim was to determine Lp-PLA(2) mass and activity in a selected cohort of first-ever transient ischemic attack (TIA) or ischemic stroke patients with intracranial atherosclerotic disease (ICAD) and to investigate its relationship with the presence of classical vascular risk factors, response to secondary prevention treatments and risk of recurrent vascular events. METHODS: Lp-PLA(2) mass and activity were measured 3 months after TIA or stroke by means of the PLAC test and CAM-assay (diaDexus, Inc.) respectively in 75 patients. Classic vascular risk factors, preventive treatments and clinical characteristics at the time of the index event were recorded. Follow-up transcranial Doppler ultrasonography (TCD) was performed and the presence of a new vascular event was assessed every 6 months. RESULTS: Several preventive treatments (statins and clopidogrel) were significantly associated with lower Lp-PLA(2) mass and activity. During follow-up (median time 23 months), eighteen patients (24%) suffered a new vascular event. Baseline factors associated with new vascular events were: history of coronary artery disease, number of intracranial stenoses detected by TCD and also Lp-PLA(2) activity, which was the only independent predictor for new vascular events (hazard ratio 2.89; 95% CI 1.029 to 8.096; p=0.044) after multivariate analysis (Cox regression). CONCLUSIONS: Lp-PLA(2) activity might be a useful tool to identify intracranial large-artery occlusive disease patients at higher risk of suffering new vascular events.

[Ambulatory anesthesia in Catalonia, Spain]. / Anestesia ambulatoria en Cataluña.

BACKGROUND AND OBJECTIVE: The aim of this arm of the ANESCAT study was to describe the characteristics of ambulatory anesthesia in Catalonia, Spain. PATIENTS AND METHOD: Relevant data was extracted from a survey of anesthetic procedures in 131 public, publicly contracted, and private hospitals on 14 representative days in 2003. RESULTS: Of the estimated 603,189 anesthesias performed, 206,992 (34.32%; 95% confidence interval, 33.3%-35.4%) were on outpatients. The median (10th to 90th percentile) age of patients was 59 (22-80) years and 56.6% were women. The physical status of patients according to the American Society of Anesthesiologists (ASA) classification was ASA I or II for 75.1% of the patient sample. The most common approach to anesthesia was sedation/monitoring (47.7%), followed by regional anesthesia (28.9%). The types of regional anesthesia reported most often were peri- or retrobulbar blocks (50.8% of the regional blocks), followed by spinal anesthesia (22.2%). Anesthesia was required for surgery in 76.5% of the cases and for diagnostic or other nonsurgical procedures in 22%. The individual surgical specialties creating the greatest demand for anesthetic procedures were ophthalmology (39%) and orthopedic and trauma surgery (10.9%). The specific interventions accounting for the largest percentages of anesthetic procedures were cataract extraction (32.3%) and digestive tract endoscopy (16.7%). In 8.2% of the cases, patients did not require a stay in the postanesthetic recovery unit. Private hospitals, facilities with fewer than 250 beds, and those not accredited to provide medical resident training had higher rates of ambulatory anesthesia. CONCLUSIONS: Ambulatory procedures account for approximately a third of the anesthesia workload in Catalonia. Sedation/monitoring and regional anesthesia are the approaches that predominate in this category. Ambulatory anesthesia is applied mainly in ophthalmology and the rate of endoscopic procedures requiring outpatient anesthesia is also high.

Anestesia ambulatoria en Cataluña / Ambulatory anesthesia in Catalonia, Spain

Fundamento y objetivo: Describir las características de la anestesia ambulatoria en Cataluña (España) en 2003. Pacientes y método: Datos referentes a anestesia de la encuesta epidemiológica ANESCAT 2003, basada en los actos anestésicos realizados en 131 hospitales públicos, concertados y privados de Cataluña durante 14 días representativos del año 2003. Resultados: De la estimación de 603.189 anestesias realizadas, 206.992 (34,32%; intervalo de confianza del 95%, 33,3-35,4%) fueron ambulatorias. La edad mediana (percentiles 10-90) de los pacientes fue de 59 (22-80) años y el 56,6% eran mujeres. El 75,1% correspondió a pacientes con clase 1 o 2 de la clasificación de la American Society of Anesthesiologists (ASA). La sedación/vigilancia fue la forma de anestesia más frecuente (47,7%), seguida de la anestesia regional (28,9%); de esta última, las técnicas más utilizadas fueron los bloqueos peri/retrobulbares (un 50,8% de las anestesias regionales), seguidos de la anestesia subaracnoidea (22,2%). El 76,5% de las anestesias se aplicaron para intervenciones quirúrgicas y el 22% para exploraciones o procedimientos no quirúrgicos. Las especialidades quirúrgicas más implicadas fueron la oftalmología (39%) y la cirugía ortopédica y traumatología (10,9%). Los procedimientos más frecuentes fueron la cirugía de cataratas (32,3%) y las endoscopias digestivas (16,7%). El 8,2% de los pacientes no requirió recuperación postanestésica. El índice de anestesias ambulatorias fue superior en hospitales privados, de tamaño inferior a 250 camas y sin docencia de programa de residencia. Conclusiones: La anestesia ambulatoria en Cataluña supone aproximadamente la tercera parte de todas las anestesias, con predominio de la sedación/vigilancia y anestesia regional. Se aplica principalmente a cirugía oftalmológica y tiene una importante tasa de procedimientos endoscópicos

Background and objective: The aim of this arm of the ANESCAT study was to describe the characteristics of ambulatory anesthesia in Catalonia, Spain. Patients and method: Relevant was extracted from a survey of anesthetic procedures in 131 public, publicly contracted, and private hospitals on 14 representative days in 2003. Results: Of the estimated 603,189 anesthesias performed, 206,992 (34.32%; 95% confidence interval, 33.3%-35.4%) were on outpatients. The median (10th to 90th percentile) age of patients was 59 (22-80) years and 56.6% were women. The physical status of patients according to the American Society of Anesthesiologists (ASA) classification was ASA I or II for 75.1% of the patient sample. The most common approach to anesthesia was sedation/monitoring (47.7%), followed by regional anesthesia (28.9%). The types of regional anesthesia reported most often were peri- or retrobulbar blocks (50.8% of the regional blocks), followed by spinal anesthesia (22.2%). Anesthesia was required for surgery in 76.5% of the cases and for diagnostic or other nonsurgical procedures in 22%. The individual surgical specialties creating the greatest demand for anesthetic procedures were ophthalmology (39%) and orthopedic and trauma surgery (10.9%). The specific interventions accounting for the largest percentages of anesthetic procedures were cataract extraction (32.3%) and digestive tract endoscopy (16.7%). In 8.2% of the cases, patients did not require a stay in the postanesthetic recovery unit. Private hospitals, facilities with fewer than 250 beds, and those not accredited to provide medical resident training had higher rates of ambulatory anesthesia. Conclusions: Ambulatory procedures account for approximately a third of the anesthesia workload in Catalonia. Sedation/monitoring and regional anesthesia are the approaches that predominate in this category. Ambulatory anesthesia is applied mainly in ophthalmology and the rate of endoscopic procedures requiring outpatient anesthesia is also high