A Comparison of Models for the Forecast of Daily Concentration Thresholds of Airborne Fungal Spores

Altres ajuts: Ministerio de Ciencia y Tecnología AMB97-0457-CO7-021, REN2001-10659-CO3-01, BOS2002-03474, CGL2004-21166-E, GGL2006-12648-CO3-02Unidad de excelencia María de Maeztu CEX2019-000940-MAerobiological predictive model development is of increasing interest, despite the distribution and variability of data and the limitations of statistical methods making it highly challenging. The use of concentration thresholds and models, where a binary response allows one to establish the occurrence or non-occurrence of the threshold, have been proposed to reduce difficulties. In this paper, we use logistic regression (logit) and regression trees to predict the daily concentration thresholds (low, medium, high, and very high) of six airborne fungal spore taxa (Alternaria, Cladosporium, Agaricus, Ganoderma, Leptosphaeria, and Pleospora) in eight localities in Catalonia (NE Spain) using data from 1995 to 2014. The predictive potential of these models was analyzed through sensitivity and specificity. The models showed similar results regarding the relationship and influence of the meteorological parameters and fungal spores. Ascospores showed a strong relationship with precipitation and basidiospores with minimum temperature, while conidiospores did not indicate any preferences. Sensitivity (true-positive) and specificity (false-positive) presented highly satisfactory validation results for both models in all thresholds, with an average of 73%. However, seeing as logit offers greater precision when attempting to establish the exceedance of a concentration threshold and is easier to apply, it is proposed as the best predictive model

Mediterranean alcohol-drinking pattern, low to moderate alcohol intake and risk of atrial fibrillation in the PREDIMED study

[Background and aims] There is ongoing controversy about the effect of a low to moderate alcohol consumption on atrial fibrillation (AF). Our aim is to assess the association between adherence to a Mediterranean alcohol drinking pattern and AF incidence.[Methods and results] A total 6527 out of the 7447 participants in the PREDIMED trial met our inclusion criteria. A validated frequency food questionnaire was used to measure alcohol consumption. Participants were classified as non-drinkers, Mediterranean alcohol drinking pattern (MADP) (10–30 g/d in men and 5–15 g/day in women, preferably red wine consumption with low spirits consumption), low-moderate drinking (<30 g/day men y and < 15 g/day women), and heavy drinking. We performed multivariable Cox regression models to estimate hazard ratios (HR) with 95% confidence intervals (95% CI) of incident AF according to alcohol drinking patterns. After a mean follow up of 4.4 years, 241 new incident AF cases were confirmed. Alcohol consumption was not associated to AF incidence among low-moderate drinkers (HR: 0.96; 95%CI: 0.67–1.37), adherents to MADP (HR: 1.15 95%CI: 0.75–1.75), or heavy drinkers (HR: 0.92; 95%CI: 0.53–1.58), compared with non-drinkers.[Conclusions] In a high cardiovascular risk adult population, a Mediterranean alcohol consumption pattern (low to moderate red wine consumption) was not associated with an increased incidence of AF.[Clinical trials] URL: http://www.controlled-trials.com. Unique identifier: ISRCTN35739639.PREDIMED trial was supported by the official funding agency for biomedical research of the Spanish government (Instituto de Salud Carlos III) RTIC G03/140 (Coordinator: Dr Estruch) and RTIC RD 06/0045 (Coordinator: Dr Martínez-González). We also acknowledge grants from the National Institutes of Health, United States (1R01HL118264-01); Fondo de Investigación Sanitaria– Fondo Europeo de Desarrollo Regional (PI04/0233, PI05/0976, PI07/0240, PI10/01407, PI10/02658, PI11/00049, PI11/02505 and AGL2010-22319-C03-03); Consejería de Salud de la Junta de Andalucía (PI0105/2007), and by the Generalitat Valenciana, Spain (ACOMP/2013/165 and ACOMP/2013/159)

Complement and coagulation cascades activation is the main pathophysiological pathway in early-onset severe preeclampsia revealed by maternal proteomics

Preeclampsia is a pregnancy-specific multisystem disorder and a leading cause of maternal and perinatal morbidity and mortality. The exact pathogenesis of this multifactorial disease remains poorly defined. We applied proteomics analysis on maternal blood samples collected from 14 singleton pregnancies with early-onset severe preeclampsia and 6 uncomplicated pregnancies to investigate the pathophysiological pathways involved in this specific subgroup of preeclampsia. Maternal blood was drawn at diagnosis for cases and at matched gestational age for controls. LC-MS/MS proteomics analysis was conducted, and data were analyzed by multivariate and univariate statistical approaches with the identification of differential pathways by exploring the global human protein-protein interaction network. The unsupervised multivariate analysis (the principal component analysis) showed a clear difference between preeclamptic and uncomplicated pregnancies. The supervised multivariate analysis using orthogonal partial least square discriminant analysis resulted in a model with goodness of fit (R2X = 0.99, p < 0.001) and a strong predictive ability (Q2Y = 0.8, p < 0.001). By univariate analysis, we found 17 proteins statistically different after 5% FDR correction (q-value < 0.05). Pathway enrichment analysis revealed 5 significantly enriched pathways whereby the activation of the complement and coagulation cascades was on top (p = 3.17e-07). To validate these results, we assessed the deposits of C5b-9 complement complex and on endothelial cells that were exposed to activated plasma from an independent set of 4 cases of early-onset severe preeclampsia and 4 uncomplicated pregnancies. C5b-9 and Von Willbrand factor deposits were significantly higher in early-onset severe preeclampsia. Future studies are warranted to investigate potential therapeutic targets for early-onset severe preeclampsia within the complement and coagulation pathway

Association between serum copper levels and risk of cardiovascular disease: a nested case-control study in the PREDIMED trial

Background and aim: Certain trace elements have been associated with increased cardiovascular risk. The aim of this study was to evaluate the association between serum copper (SeCu) levels and the risk of a first event of cardiovascular disease (CVD) in a population of older adults with high cardiovascular risk. Methods and results: We conducted a case-control study nested within the PREDIMED trial. During a median follow-up of 4.8 years, a total of 207 incident cases diagnosed with CVD were matched for sex, age, and intervention group with 436 controls. Personal interviews, reviews of medical records, and validated questionnaires were used to assess known CVD risk factors. Biological serum samples were collected annually. Inductively coupled plasma mass spectrometry analysis was used to determine SeCu levels. Adjusted odds ratios were calculated using multivariate conditional logistic regression models. All participants had SeCu levels within the reference values, 750 mg/L to 1450 mg/L. Among men, but not among women, the mean SeCu concentration was higher in cases 1014.1 mg/L than in controls 959.3 mg/L; (p Z 0.004). In men, the multivariable-adjusted odds ratio for CVD was 2.36 (95% CI 1.07e5.20 for the comparison of the highest vs. the lowest quartile; p for trend Z 0.02), in women, it was 0.43 (95% CI 0.11 e1.70; p for trend Z 0.165). Conclusion: In older Spanish men with high cardiovascular risk, a significant association was observed between high SeCu levels, but still within the reference values, and an increased risk of a first event of CVD. Our findings suggest a sex difference in CVD risk and SeCu levels. To confirm this relationship and to analyze the differences observed between men and women, further studies are needed.Funding for open access charge: Universidad de Málaga / CBUA. This research was funded by the official funding agency for biomedical research of the Spanish government, Instituto de Salud Carlos III (ISCIII), through grants provided to research networks specifically developed for the trial (RTIC G03/140; RTIC RD 06/0045 “PREDIMED”), and JR14/00008, and through Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición (CIBERobn), and by grants from Centro Nacional de Investigaciones Cardiovasculares (CNIC06/2007), the Fondo de Investigación Sanitaria–Fondo Europeo de Desarrollo Regional (Proyecto de Investigación (PI04-2239, PI05/2584, CP06/00100, PI07/0240, PI07/1138, PI07/0954, PI 07/0473, PI10/01407, PI10/02658, PI11/01647, P11/02505 and PI13/00462), the Ministerio de Ciencia e Innovación (Recursos y teconologia agroalimentarias (AGL)-2009-13906-C02 and AGL2010-22319-C03 and AGL2013-49083C3-1-R), the Ministerio de Economía y Competitividad-Fondos FEDER-Instituto de Salud Carlos III (UNGR15-CE-3380), the Fundación Mapfre 2010, the Consejería de Salud de la Junta de Andalucía (PI0105/2007), the Public Health Division of the Department of Health of the Autonomous Government of Catalonia, the Generalitat Valenciana (Generalitat Valenciana Ayuda Complementatia GVACOMP) 06109, GVACOMP2010-181, GVACOMP2011-151), Conselleria de Sanitat y AP; Atención Primaria (CS) 2010-AP-111, and CS2011-AP-042), Regional Government of Navarra (P27/2011), and Centre Català de la Nutrició de l'Institut d'Estudis Catalans. Hojiblanca and Patrimonio Communal Olivarero donated extra-virgin olive oil; the California Walnut Commission donated walnuts; Borges donated almonds; La Morella Nuts donated hazelnuts

Plasma lipidome and risk of atrial fibrillation: results from the PREDIMED trial

The potential role of the lipidome in atrial fibrillation (AF) development is still widely unknown. We aimed to assess the association between lipidome profiles of the Prevención con Dieta Mediterránea (PREDIMED) trial participants and incidence of AF. We conducted a nested case-control study (512 incident centrally adjudicated AF cases and 735 controls matched by age, sex, and center). Baseline plasma lipids were profiled using a Nexera X2 U-HPLC system coupled to an Exactive Plus orbitrap mass spectrometer. We estimated the association between 216 individual lipids and AF using multivariable conditional logistic regression and adjusted the p values for multiple testing. We also examined the joint association of lipid clusters with AF incidence. Hitherto, we estimated the lipidomics network, used machine learning to select important network-clusters and AF-predictive lipid patterns, and summarized the joint association of these lipid patterns weighted scores. Finally, we addressed the possible interaction by the randomized dietary intervention.Forty-one individual lipids were associated with AF at the nominal level (p < 0.05), but no longer after adjustment for multiple-testing. However, the network-based score identified with a robust data-driven lipid network showed a multivariable-adjusted ORper+1SD of 1.32 (95% confidence interval: 1.16-1.51; p < 0.001). The score included PC plasmalogens and PE plasmalogens, palmitoyl-EA, cholesterol, CE 16:0, PC 36:4;O, and TG 53:3. No interaction with the dietary intervention was found. A multilipid score, primarily made up of plasmalogens, was associated with an increased risk of AF. Future studies are needed to get further insights into the lipidome role on AF.Current Controlled Trials number, ISRCTN35739639

American heart association's life simple 7 and the risk of atrial fibrillation in the PREDIMED study cohort

Background and aims The American Heart Association proposed 7 ideal cardiovascular health metrics (Life's Simple 7 [LS7]) namely, not smoking, body mass index <25 kg/m2, healthy diet, moderate physical activity ≥150 min/week, total blood cholesterol <200 mg/dL, blood pressure <120/80 mmHg and fasting blood glucose <100 mg/dL. Our objective was to assess the association between these LS7 metrics and the incidence of atrial fibrillation (AF). Methods and results A total of 6,479 participants of the PREDIMED study were included. We calculated the participants’ baseline LS7 index ranging 0–7 points to categorize them according to their adherence to these LS7 health metrics. Multivariable Cox regression models were used to estimate Hazard Ratios (HR) and their 95% Confidence Intervals (95% CI). After a median follow-up of 4.8 years, we identified 250 incident cases of AF. After adjusting for potential confounders, adherence to LS7 index was not associated with the incidence of AF (adjusted HR 0.90 [95% CI: 0.56–1.45] for highest vs. lowest LS7 categories). Body mass index <25 kg/m2 was the only health metric individually associated with a lower risk of AF (HR 0.36 [95% CI: 0.16–0.78]). Conclusions In a high cardiovascular risk Spanish population, adherence to American Heart Association's LS7 metrics was not associated with the risk of incident AF

Circulating Amino Acids and Risk of Peripheral Artery Disease in the PREDIMED Trial

Effective prevention and risk prediction are important for peripheral artery disease (PAD) due to its poor prognosis and the huge disease burden it produces. Circulating amino acids (AA) and their metabolites may serve as biomarkers of PAD risk, but they have been scarcely investigated. The objective was to prospectively analyze the associations of baseline levels of plasma AA (and their pathways) with subsequent risk of PAD and the potential effect modification by a nutritional intervention with the Mediterranean diet (MedDiet). A matched case-control study was nested in the PREDIMED trial, in which participants were randomized to three arms: MedDiet with tree nut supplementation group, MedDiet with extra-virgin olive oil (EVOO) supplementation group or control group (low-fat diet). One hundred and sixty-seven PAD cases were matched with 250 controls. Plasma AA was measured with liquid chromatography/mass spectrometry at the Broad Institute. Baseline tryptophan, serine and threonine were inversely associated with PAD (ORfor 1 SD increase = 0.78 (0.61–0.99); 0.67 (0.51–0.86) and 0.75 (0.59–0.95), respectively) in a multivariable-adjusted conditional logistic regression model. The kynurenine/tryptophan ratio was directly associated with PAD (ORfor 1 SD increase = 1.50 (1.14–1.98)). The nutritional intervention with the MedDiet+nuts modified the association between threonine and PAD (p-value interaction = 0.018) compared with the control group. However, subjects allocated to the MedDiet+EVOO group were protected against PAD independently of baseline threonine. Plasma tryptophan, kynurenine/tryptophan ratio, serine and threonine might serve as early biomarkers of future PAD in subjects at a high risk of cardiovascular disease. The MedDiet supplemented with EVOO exerted a protective effect, regardless of baseline levels of threonine

Plasma lipidome and risk of atrial fibrillation: results from the PREDIMED trial

The potential role of the lipidome in atrial fibrillation (AF) development is still widely unknown. We aimed to assess the association between lipidome profiles of the Prevenci\uf3n con Dieta Mediterr\ue1nea (PREDIMED) trial participants and incidence of AF. We conducted a nested case–control study (512 incident centrally adjudicated AF cases and 735 controls matched by age, sex, and center). Baseline plasma lipids were profiled using a Nexera X2 U-HPLC system coupled to an Exactive Plus orbitrap mass spectrometer. We estimated the association between 216 individual lipids and AF using multivariable conditional logistic regression and adjusted the p values for multiple testing. We also examined the joint association of lipid clusters with AF incidence. Hitherto, we estimated the lipidomics network, used machine learning to select important network-clusters and AF-predictive lipid patterns, and summarized the joint association of these lipid patterns weighted scores. Finally, we addressed the possible interaction by the randomized dietary intervention. Forty-one individual lipids were associated with AF at the nominal level (p &lt; 0.05), but no longer after adjustment for multiple-testing. However, the network-based score identified with a robust data-driven lipid network showed a multivariable-adjusted ORper+1SD of 1.32 (95% confidence interval: 1.16–1.51; p &lt; 0.001). The score included PC plasmalogens and PE plasmalogens, palmitoyl-EA, cholesterol, CE 16:0, PC 36:4;O, and TG 53:3. No interaction with the dietary intervention was found. A multilipid score, primarily made up of plasmalogens, was associated with an increased risk of AF. Future studies are needed to get further insights into the lipidome role on AF. Current Controlled Trials number, ISRCTN35739639

Arginine catabolism metabolites and atrial fibrillation or heart failure risk: 2 case-control studies within the Prevención con Dieta Mediterránea (PREDIMED) trial

Background Arginine-derived metabolites are involved in oxidative and inflammatory processes related to endothelial functions and cardiovascular risks. Objectives We prospectively examined the associations of arginine catabolism metabolites with the risks of atrial fibrillation (AF) or heart failure (HF), and evaluated the potential modifications of these associations through Mediterranean diet (MedDiet) interventions in a large, primary-prevention trial. Methods Two nested, matched, case-control studies were designed within the Prevención con Dieta Mediterránea (PREDIMED) trial. We selected 509 incident cases and 547 matched controls for the AF case-control study and 326 cases and 402 matched controls for the HF case-control study using incidence density sampling. Fasting blood samples were collected at baseline and arginine catabolism metabolites were measured using LC-tandem MS. Multivariable conditional logistic regression models were applied to test the associations between the metabolites and incident AF or HF. Interactions between metabolites and intervention groups (MedDiet groups compared with control group) were analyzed with the likelihood ratio test. Results Inverse association with incident AF was observed for arginine (OR per 1 SD, 0.83; 95% CI: 0.73–0.94), whereas a positive association was found for N1-acetylspermidine (OR for Q4 compared with Q1 1.58; 95% CI: 1.13–2.25). For HF, inverse associations were found for arginine (OR per 1 SD, 0.82; 95% CI: 0.69–0.97) and homoarginine (OR per 1 SD, 0.81; 95% CI: 0.68–0.96), and positive associations were found for the asymmetric dimethylarginine (ADMA) and symmetric dimethlyarginine (SDMA) ratio (OR per 1 SD, 1.19; 95% CI: 1.02–1.41), N1-acetylspermidine (OR per 1 SD, 1.34; 95% CI: 1.12–1.60), and diacetylspermine (OR per 1 SD, 1.20; 95% CI: 1.02–1.41). In the stratified analysis according to the dietary intervention, the lower HF risk associated with arginine was restricted to participants in the MedDiet groups (P-interaction = 0.044). Conclusions Our results suggest that arginine catabolism metabolites could be involved in AF and HF. Interventions with the MedDiet may contribute to strengthen the inverse association between arginine and the risk of HF. This trial was registered at controlled-trials.com as ISRCTN35739639

Isotemporal substitution of inactive time with physical activity and time in bed: cross-sectional associations with cardiometabolic health in the PREDIMEDPlus study

Background: This study explored the association between inactive time and measures of adiposity, clinical parameters, obesity, type 2 diabetes and metabolic syndrome components. It further examined the impact of reallocating inactive time to time in bed, light physical activity (LPA) or moderate-to-vigorous physical activity (MVPA) on cardio-metabolic risk factors, including measures of adiposity and body composition, biochemical parameters and blood pressure in older adults. Methods: This is a cross-sectional analysis of baseline data from 2189 Caucasian men and women (age 55-75 years, BMI 27-40 Kg/m2) from the PREDIMED-Plus study (http://www.predimedplus.com/). All participants had ≥3 components of the metabolic syndrome. Inactive time, physical activity and time in bed were objectively determined using triaxial accelerometers GENEActiv during 7 days (ActivInsights Ltd., Kimbolton, United Kingdom). Multiple adjusted linear and logistic regression models were used. Isotemporal substitution regression modelling was performed to assess the relationship of replacing the amount of time spent in one activity for another, on each outcome, including measures of adiposity and body composition, biochemical parameters and blood pressure in older adults. Results: Inactive time was associated with indicators of obesity and the metabolic syndrome. Reallocating 30 min per day of inactive time to 30 min per day of time in bed was associated with lower BMI, waist circumference and glycated hemoglobin (HbA1c) (all p-values < 0.05). Reallocating 30 min per day of inactive time with 30 min per day of LPA or MVPA was associated with lower BMI, waist circumference, total fat, visceral adipose tissue, HbA1c, glucose, triglycerides, and higher body muscle mass and HDL cholesterol (all p-values < 0.05). Conclusions: Inactive time was associated with a poor cardio-metabolic profile. Isotemporal substitution of inactive time with MVPA and LPA or time in bed could have beneficial impact on cardio-metabolic health