IdiSNA - Instituto de Investigación Sanitaria de Navarra (Navarra)

Permanent URI for this collectionhttps://hdl.handle.net/20.500.12105/16968

Instituto de Investigación Sanitaria de Navarra (IdiSNA) se constituye como un espacio de investigación biomédica multidisciplinar y traslacional orientado a la investigación básica, clínica, epidemiológica y en servicios de salud, fruto de la asociación entre grupos de la Clínica Universidad de Navarra (CUN), Hospital Universitario de Navarra (HUN), Universidad de Navarra (UN), Universidad Pública de Navarra (UPNA), Centro para la Investigación Médica Aplicada (CIMA), Navarrabiomed (NB), Instituto de Salud Pública y Laboral (ISPLN) y Atención Primaria del Servicio Navarro de Salud (AP-SNS).El núcleo del instituto los constituye el Hospital Universitario de Navarra (HUN). La finalidad de IdiSNA es contribuir a elevar la calidad de la investigación, y, como consecuencia de la asistencia y docencia biomédica de la Comunidad Foral de Navarra, así como optimizar los recursos humanos y materiales existentes. Para ello se fomentarán las sinergias entre grupos clínicos y básicos partiendo de los modelos de grupos traslacionales ya existentes. Acreditado por el Instituto de Salud Carlos III como Instituto de Investigación Sanitaria en 2019, y renovando esta acreditación cada 5 años, forma parte así del total de 34 Institutos de Investigación Sanitaria acreditados existentes en la actualidad.

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Mammographic density and breast cancer pathological subtypes by menopausal status and body mass index.
(BioMed Central (BMC), 2025-10-24) Fernández-Morata, Julia; Pollan-Santamaria, Marina; Fernandez de Larrea-Baz, Nerea; Pachón-Olmos, Vanessa; García-Pérez, Javier; Castelló Pastor, Adela; Sierra, Maria Angeles; de Lucas, Maria Pilar; Llobet, Rafael; Stradella, Agostina; Cantos, Blanca; Ramón Y Cajal, Teresa; Santisteban, Marta; Seguí, Miguel Ángel; Santaballa Bertrán, Ana; Granja, Mónica; Camps-Herrero, Julia; Recalde, Sabela; Núñez-García, Beatriz; Calvo Verges, Nuria; Perez-Gomez, Beatriz; Pastor-Barriuso, Roberto; Lope Carvajal, Virginia; Instituto de Salud Carlos III
Background: Mammographic density (MD) is an established biomarker of breast cancer (BC) risk. However, its relationship to BC pathological subtypes remains unclear. This study aimed to investigate this association and assess whether it differs by body mass index (BMI) and menopausal status. Methods: MD percentage was assessed in the diagnostic mammograms of the contralateral breast of 714 BC patients recruited from eight Spanish hospitals. Participants completed an epidemiological questionnaire, and hospital researchers collected clinical and pathological data. Standardized prevalences (SPs) and standardized prevalence ratios (SPRs) for each BC pathological subtype across MD categories were estimated based on multinomial logistic regression models, both overall and stratified by BMI and menopausal status. Results: Mean MD was 26.1% (SD = 17.3). Although no statistically significant differences were detected, women with MD ≥ 50% had a 13% lower SP of hormone receptor positive tumors (SPR = 0.87; 95% CI 0.67-1.13), a 36% higher SP of human epidermal growth factor receptor 2 positive (HER2+) tumors (SPR = 1.36; 95% CI 0.72-2.58), and a 23% higher SP of triple negative (TN) tumors (SPR = 1.23; 95% CI 0.47-3.22), compared to those with MD < 10%. These patterns were mainly observed in pre/perimenopausal women and in those with BMI ≥ 25 kg/m. Conclusions: High MD might be mainly associated with the development of more aggressive and non-hormone-dependent cancers, such as HER2+ and TN BC, especially among pre/perimenopausal an overweight women.
Determinants of Adherence to World Cancer Research Fund/American Institute for Cancer Research Recommendations in Women with Breast Cancer
(Multidisciplinary Digital Publishing Institute (MDPI), 2025-02-19) Pachón Olmos, Vanessa; Pollan-Santamaria, Marina; Fernandez de Larrea-Baz, Nerea; Fernández-Morata, Julia; Ruiz Moreno, Emma; García-Pérez, Javier; Castelló Pastor, Adela; Sierra, Maria Angeles; de Lucas, Maria Pilar; Alonso Ledesma, Isabel; Stradella, Agostina; Cantos, Blanca; Ramón Y Cajal, Teresa; Santisteban, Marta; Seguí, Miguel Ángel; Santaballa Bertrán, Ana; Granja, Mónica; Camps-Herrero, Julia; Recalde, Sabela; Mendez, Miriam; Calvo Verges, Nuria; Perez-Gomez, Beatriz; Pastor-Barriuso, Roberto; Lope Carvajal, Virginia; Instituto de Salud Carlos III
Background/objectives: The 2018 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) cancer prevention recommendations benefit primary prevention and survivor outcomes. This study evaluated the adherence to these recommendations during the year prior to breast cancer diagnosis and identified related clinical and sociodemographic factors. Methods: A total of 915 patients with breast cancer were recruited from eight hospitals in four regions of Spain. The participants completed an epidemiologic questionnaire and a food frequency questionnaire. The compliance with the WCRF/AICR recommendations was assessed using a standardized score based on seven recommendations. Standardized prevalences and standardized prevalence ratios (SPRs) for moderate and high adherence were calculated based on participant characteristics using binary and multinomial logistic regression models. Results: The mean adherence was 3.5 points out of 7. The recommendations with the best and worst adherence were avoiding sugar-sweetened drinks (54.4% adherence) and maintaining a fiber-rich diet (4.4% consumed ≥30 g/day). The overall adherence was better in women aged ≥60 years (SPR = 1.55; 95% CI = 1.09-2.22), and worse in those with a caloric intake ≥2000 kcal/day (SPR = 0.48; 95% CI = 0.37-0.62) or ≥2 comorbidities (SPR = 0.66; 95% CI = 0.49-0.89). The adherence to maintaining a healthy weight was worse in those with ≥2 comorbidities and stage III-IV tumors. The physical activity adherence was worse in working women and those with ≥2 comorbidities. The alcohol restriction adherence was worse in smokers. Younger women, smokers and those with a low calorie intake were less adherent to the fruit/vegetable recommendation. The consumption of fiber and limited consumption of red/processed meat adherence was poor in all the subgroups. The adherence to a limited consumption of fast food and sugary drinks was worse in younger women and high-calorie-diet consumers. Conclusions: The differences in the adherence to recommendations according to patient characteristics justify the design of personalized interventions for breast cancer patients.
Calibration of Toenail Metal Concentrations for Sample Mass Heterogeneity and Between-Batch Variability: The COMET Approach
(National Institute of Environmental Health Sciences (NIEHS), 2025-04) Pastor-Barriuso, Roberto; Gutiérrez-González, Enrique; Varea-Jiménez, Elena; Gómez-Ariza, José Luis; Castaño-Vinyals, Gemma; Aragonés, Nuria; Molina, Antonio José; Dierssen-Sotos, Trinidad; Fernández-Tardón, Guillermo; Amiano, Pilar; Ederra-Sanz, María; Moreno, Victor; Jiménez-Moleón, José Juan; Molina-Barceló, Ana; Marcos-Gragera, Rafael; Casabonne, Delphine; Alguacil, Juan; Gómez-Gómez, Jesús Humberto; García-Barrera, Tamara; Kogevinas, Manolis; Pollan-Santamaria, Marina; Perez-Gomez, Beatriz; Instituto de Salud Carlos III; Asociación Española Contra el Cáncer; Centro de Investigación Biomédica en Red - CIBERESP (Epidemiología y Salud Pública); Scientific Foundation
Background: Toenails are promising biomarkers of long-term metal exposure in epidemiological studies, but their accuracy may be compromised by systematic and random errors associated with heterogeneous toenail sample masses, as well as by substantial variability across laboratory batches. Objectives: We propose a novel modeling approach to calibrate toenail metal concentrations for the heterogeneity in sample masses and the variability between batches. Methods: We developed a heteroscedastic spline mixed model relating sample mass and laboratory batch with measured concentrations, allowing for an average bias in measurements over all batches as a smooth function of sample mass, random variation in mass-related biases across batches, and mass-related heterogeneity in within-batch error variance. The model allowed partitioning the total variance of measured concentrations into the extraneous variances (due to different sample masses and laboratory batches) and the intrinsic variance (resulting from distinct metal exposures). We derived calibrated metal concentrations from the model by removing both sources of extraneous variation and estimating the predicted concentrations had all toenail samples been analyzed in a single batch and of the same mass. We provide the R script COMET (COrrected METals) to fit the proposed model, extract variance components, and calibrate metal concentrations. Results: In a multicase-control study in Spain (MCC-Spain) with toenail determinations for 16 metals in 4,473 incident cases of five common cancers and 3,450 population controls, sample mass and batch accounted for 26%-60% of the total variance of measured concentrations for most metals. In comparison with calibrated concentrations, odds ratios for measured concentrations were biased by > 10% toward or away from the null in one-quarter of the estimated metal-cancer associations. Discussion: The proposed model allows correcting toenail metal concentrations for sample mass heterogeneity and between-batch variability and could be applied to other biological specimens of heterogeneous size, distinct laboratory techniques, and different study designs.
COVID-19 vaccine effectiveness against symptomatic infection with SARS-CoV-2 BA.1/BA.2 lineages among adults and adolescents in a multicentre primary care study, Europe, December 2021 to June 2022
(European Centre for Disease Prevention and Control (ECDC), 2024-03) Laniece Delaunay, Charlotte; Martínez-Baz, Iván; Sève, Noémie; Domegan, Lisa; Mazagatos, Clara; Buda, Silke; Meijer, Adam; Kislaya, Irina; Pascu, Catalina; Carnahan, AnnaSara; Oroszi, Beatrix; Ilić, Maja; Maurel, Marine; Melo, Aryse; Sandonis-Martin, Virginia; Trobajo-Sanmartín, Camino; Enouf, Vincent; McKenna, Adele; Pérez-Gimeno, Gloria; Goerlitz, Luise; de Lange, Marit; Rodrigues, Ana Paula; Lazar, Mihaela; Latorre-Margalef, Neus; Túri, Gergő; Castilla, Jesús; Falchi, Alessandra; Bennett, Charlene; Gallardo, Virtudes; Dürrwald, Ralf; Eggink, Dirk; Guiomar, Raquel; Popescu, Rodica; Riess, Maximilian; Horváth, Judit Krisztina; Casado, Itziar; García, Mª Del Carmen; Hooiveld, Mariëtte; Machado, Ausenda; Bacci, Sabrina; Kaczmarek, Marlena; Kissling, Esther; European Primary Care Vaccine Effectiveness Group; Unión Europea. European Centre for Disease Prevention and Control (ECDC); Unión Europea. Comisión Europea. H2020
Background: Scarce European data in early 2021 suggested lower vaccine effectiveness (VE) against SARS-CoV-2 Omicron lineages than previous variants. Aim: We aimed to estimate primary series (PS) and first booster VE against symptomatic BA.1/BA.2 infection and investigate potential biases. Methods: This European test-negative multicentre study tested primary care patients with acute respiratory symptoms for SARS-CoV-2 in the BA.1/BA.2-dominant period. We estimated PS and booster VE among adults and adolescents (PS only) for all products combined and for Comirnaty alone, by time since vaccination, age and chronic condition. We investigated potential bias due to correlation between COVID-19 and influenza vaccination and explored effect modification and confounding by prior SARS-CoV-2 infection. Results: Among adults, PS VE was 37% (95% CI: 24-47%) overall and 60% (95% CI: 44-72%), 43% (95% CI: 26-55%) and 29% (95% CI: 13-43%) < 90, 90-179 and ≥ 180 days post vaccination, respectively. Booster VE was 42% (95% CI: 32-51%) overall and 56% (95% CI: 47-64%), 22% (95% CI: 2-38%) and 3% (95% CI: -78% to 48%), respectively. Primary series VE was similar among adolescents. Restricting analyses to Comirnaty had little impact. Vaccine effectiveness was higher among older adults. There was no signal of bias due to correlation between COVID-19 and influenza vaccination. Confounding by previous infection was low, but sample size precluded definite assessment of effect modification. Conclusion: Primary series and booster VE against symptomatic infection with BA.1/BA.2 ranged from 37% to 42%, with similar waning post vaccination. Comprehensive data on previous SARS-CoV-2 infection would help disentangle vaccine- and infection-induced immunity.
Effectiveness of XBB.1.5 Vaccines Against Symptomatic SARS-CoV-2 Infection in Older Adults During the JN.1 Lineage-Predominant Period, European VEBIS Primary Care Multicentre Study, 20 November 2023-1 March 2024
(Wiley, 2024-11) Merdrignac, Lore; Laniece Delaunay, Charlotte; Verdasca, Nuno; Vega-Piris, Lorena; O'Donnell, Joan; Sève, Noémie; Trobajo-Sanmartín, Camino; Buda, Silke; Hooiveld, Mariëtte; Rodrigues, Ana Paula; Túri, Gergő; Latorre-Margalef, Neus; Mlinarić, Ivan; Lazar, Mihaela; Maurel, Marine; Castrillejo, Daniel; Bennett, Charlene; Rameix-Welti, Marie-Anne; Martínez-Baz, Iván; Dürrwald, Ralf; Meijer, Adam; Melo, Aryse; Oroszi, Beatrix; Hagey, Tove Samuelsson; Kurečić Filipović, Sanja; Dijkstra, Frederika; Gomez, Verónica; Bacci, Sabrina; Kaczmarek, Marlena; Kissling, Esther; VEBIS Primary Care Vaccine Effectiveness Group; Unión Europea. European Centre for Disease Prevention and Control (ECDC)
We estimated XBB.1.5 vaccine effectiveness (VE) against symptomatic SARS-CoV-2 infection among adults aged ≥ 65 years during the 2023/2024 JN.1 lineage-predominant period in a European multi-country test-negative case-control study at primary care level. We estimated VE adjusted by study site, age, sex, chronic conditions and onset date. We included 220 cases and 1733 controls. The VE was 48% (95% CI: 12-71), 23% (95% CI: -11-48) and 5% (95% CI: -92-56) among those with symptom onset 1-5, 6-11, and ≥ 12 weeks after vaccination, respectively. XBB.1.5 vaccine provided short and moderate protection against JN.1 symptomatic infection.
Effectiveness of catch-up and at-birth nirsevimab immunisation against RSV hospital admission in the first year of life: a population-based case-control study, Spain, 2023/24 season
(European Centre for Disease Prevention and Control (ECDC), 2025-02) Nuñez, Olivier; Olmedo, Carmen; Moreno-Perez, David; Lorusso, Nicola; Fernández Martínez, Sergio; Pastor Villalba, Pedro Eliseo; Gutierrez, Ángeles; Alonso Garcia, Marcos; Latasa, Pello; Sancho, Rosa; Mendioroz, Jacobo; Martinez-Marcos, Montserrat; Muñoz Platón, Enriqueta; García Rivera, María Victoria; Pérez-Martínez, Olaia; Álvarez-Gil, Rosa; Rivas Wagner, Eva; López González-Coviella, Nieves; Zornoza, Matilde; Barranco Boada, María Isabel; Pacheco, M Del Carmen; Álvarez Río, Virginia; Fiol Jaume, Miguel; Morey Arance, Roxana; Adiego Sancho, Begoña; Mendez Diaz, Manuel; Batalla, Noa; Andreu, Cristina; Castilla, Jesús; Garcia-Cenoz, Manuel; Fernández Ibáñez, Ana; Huerta Huerta, Marta; Ibáñez Pérez, Ana Carmen; Berradre-Sáenz, Belén; Lamas, Joaquín; Hermoso, Luisa; Casado Cobo, Susana; Galán Cuesta, Manuel; Montenegro, Sara; Domínguez, María; Jarrin Vera, Inmaculada; Limia, Aurora; Pastor-Barriuso, Roberto; Monge Corella, Susana; Nirsevimab Effectiveness Study Collaborators; Instituto de Salud Carlos III
Background: Respiratory syncytial virus (RSV) causes substantial morbidity in infants < 1 year. In October 2023, Spain recommended the monoclonal antibody nirsevimab to all children born since 1 April 2023, at birth or as catch-up if born before October 2023.AimWe estimated nirsevimab effectiveness in preventing RSV hospitalisations during the 2023/24 season. Methods: We conducted a nationwide population-based matched case-control study. Cases were children hospitalised for lower respiratory tract infection who were RSV PCR-positive. For each case, we selected four population density controls born in the same province and date (±2 days). We defined at-birth immunisation as receiving nirsevimab during the first 2 weeks of life, and catch-up immunisation within 30 days from campaign onset. Causal intention-to-treat (ITT) and per-protocol (PP) effectiveness was estimated using inverse-probability-of-immunisation weighted conditional logistic regression. Results: We included 406 cases and 1,623 controls in catch-up and 546 cases and 2,182 controls in at-birth immunisation studies. Effectiveness in preventing RSV hospitalisations for catch-up immunisation was 71% (95% confidence interval (CI): 65-76) by ITT and 80% (95% CI: 75-84) PP. Effectiveness for at-birth immunisation was 78% (95% CI: 73-82) by ITT and 83% (95% CI: 79-87) PP. Effectiveness was similar for ICU admission, need of mechanical ventilation, and RSV viral subgroups A and B. Children born pre-term or with birthweight < 2,500 g showed lower PP effectiveness of 60-70%. Conclusions: Population-level nirsevimab immunoprophylaxis in children in their first RSV season was very effective in preventing RSV hospitalisations, ICU admission and mechanical ventilation, with reduced but still high effectiveness for pre-term and low-birthweight children.
Health-Related Quality of Life in Long-Term Colorectal Cancer Survivors
(Multidisciplinary Digital Publishing Institute (MDPI), 2024-09-25) Marcos-Delgado, Alba; Martín-Sánchez, Vicente; Molina-Barceló, Ana; Alonso-Molero, Jéssica; Perez-Gomez, Beatriz; Pollán, Marina; Aragones, Nuria; Ederra-Sanz, María; Fernández-Tardón, Guillermo; Binefa, Gemma; Moreno, Victor; Barrios-Rodríguez, Rocío; Amiano, Pilar; Huerta, José María; Teso, Enrique Pastor; Alguacil, Juan; Castaño-Vinyals, Gemma; Kogevinas, Manolis; Molina de la Torre, Antonio José; Instituto de Salud Carlos III; Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF); Junta de Castilla y León (España); Regional Government of Andalusia (España)
The aim of our study is to evaluate the relationship between sociodemographic and clinical characteristics of individuals with Colorectal Cancer (CRC), tumour-intrinsic characteristics and treatment received with health-related quality of life (HRQoL). Methods: Cross-sectional analysis of data from 805 survivors from the MCC study was conducted. HRQoL was assessed through a general and specific questionnaire, SF-12 and FCSI (Colorectal Symptom Index). Statistical analyses were performed with linear regression with adjustment for sociodemographic variables, stage at diagnosis and histological grade. Results: Participants had survived a median of 7.9 years from diagnosis (IQR 7.1-8.5 years). Age at diagnosis, sex and area showed a clear association with HRQoL in both physical and mental dimensions of the SF-12 questionnaire. A direct association between CRC recurrence was also found in the PCS-12 and MCS-12 dimensions and radical surgery in the PCS-12. Regarding the scores in FCSI questionnaire, statistically significant differences were observed by sex, age and area, with older women being the most impaired (p < 0.001). Conclusions: Age, sex and area was associated with lower scores of HRQoL among CRC survivors. Knowing the determinants related to HRQoL would allow us to lay the groundwork to develop strategies that help reduce morbidity and mortality, relapses and increase HRQoL.
Monovalent XBB.1.5 COVID-19 vaccine effectiveness against hospitalisations and deaths during the Omicron BA.2.86/JN.1 period among older adults in seven European countries: A VEBIS-EHR network study
(Taylor & Francis, 2024) Nunes, Baltazar; Humphreys, James; Nicolay, Nathalie; Braeye, Toon; Van Evercooren, Izaak; Holm Hansen, Christian; Moustsen-Helms, Ida Rask; Sacco, Chiara; Fabiani, Massimo; Castilla, Jesús; Martínez-Baz, Iván; Meijerink, Hinta; Machado, Ausenda; Soares, Patricia; Ljung, Rickard; Pihlström, Nicklas; Nardone, Anthony; Bacci, Sabrina; Monge Corella, Susana; VEBIS-EHR Working Group; Unión Europea. European Centre for Disease Prevention and Control (ECDC); Fundação para a Ciência e Tecnologia (Portugal)
Background: We aimed to estimate XBB.1.5 vaccine effectiveness (VE) against COVID-19-related hospitalizations and deaths during BA.2.86/JN.1 predominance, among EU/EEA individuals with ≥65-years. Research design and methods: We linked electronic health records to create historical cohorts in Belgium, Denmark, Italy, Navarre (Spain), Norway, Portugal and Sweden. We included individuals aged ≥65-years eligible for the autumnal 2023 COVID-19 vaccine. Follow-up started when ≥80% of country-specific sequenced viruses were BA.2.86/JN.1 (4/dec/23 to 08/jan/24) and ended 25 February 2024. At study site level, we estimated the vaccine confounder-adjusted hazard ratio (aHR) of COVID-19 hospitalizations and deaths between individuals with ≥14 days after vaccination versus unvaccinated in autumn 2023, overall, by time since vaccination and age groups. VE was estimated as (1-pooled aHR)x100 with a random-effects model. Results: XBB.1.5 VE against COVID-19 hospitalizations was 50% (95%CI: 45 to 55) and 41% (95%CI: 35 to 46) in 65-79-year-olds and in ≥80-year-olds, respectively. VE against COVID19-related-death was 58% (95%CI: 42 to 69) and 48% (95%CI: 38 to 57), respectively, in both age groups. VE estimates against each outcome declined in all age groups over time. Conclusion: Monovalent XBB.1.5 vaccine had a moderate protective effect against severe and fatal COVID-19 likely caused by BA.2.86/JN.1 during the 2023/2024 winter, among persons aged ≥65.
Burden of postmenopausal breast cancer attributable to excess body weight: comparative study of body mass index and CUN-BAE in MCC-Spain study
(BMJ Publishing Group, 2024-12-10) Cubelos-Fernández, Naiara; Dávila-Batista, Verónica; Fernández-Villa, Tania; Castaño-Vinyals, Gemma; Perez-Gomez, Beatriz; Amiano, Pilar; Ardanaz, Eva; Delgado Sillero, Irene; Llorca, Javier; Tardón, Guillermo Fernández; Alguacil, Juan; Vanaclocha-Espi, Mercedes; Marcos-Gragera, Rafael; Moreno, Victor; Aragones, Nuria; Dorronsoro, Ane; Guevara, Marcela; Reguero Celada, Sofía; Pollan-Santamaria, Marina; Kogevinas, Manolis; Martín, Vicente; Instituto de Salud Carlos III; Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF); Ministerio de Ciencia e Innovación (España); Fundación Marqués de Valdecilla; International Cancer Genome Consortium; Ministerio de Economía y Competitividad (España); Red Temática de Investigación Cooperativa en Cáncer (RTICC) (España); Junta de Castilla y León (España); Regional Government of Andalusia (España); Generalitat Valenciana (España); Fundación La Caixa; Basque Government (España); Gobierno de la Región de Murcia (España); Unión Europea. Comisión Europea; Asociación Española Contra el Cáncer; Agència de Gestió d´Ajuts Universitaris i de Recerca (AGAUR); Government of Catalonia (España); Fundación Caja de Ahorros de Asturias; University of Oviedo (España); Unión Europea. Fondo Social Europeo (ESF/FSE)
Background: 10% of postmenopausal breast cancer cases are attributed to a high body mass index (BMI). BMI underestimates body fat, particularly in older women, and therefore the cancer burden attributable to obesity may be even higher. However, this is not clear. CUN-BAE (Clínica Universidad de Navarra-Body Adiposity Estimator) is an accurate validated estimator of body fat, taking into account sex and age. The objective of this study was to compare the burden of postmenopausal breast cancer attributable to excess body fat calculated using BMI and CUN-BAE. Methods: This case-control study included 1033 cases of breast cancer and 1143 postmenopausal population controls from the multicase-control MCC-Spain study. Logistic regression models were used to calculate odds ratios (ORs). The population attributable fraction (PAF) of excess weight related to breast cancer was estimated with both anthropometric measures. Stratified analyses were carried out for hormone receptor type. Results: Excess body weight attributable to the risk of breast cancer was 23.0% when assessed using a BMI value ≥30 kg/m2 and 38.0% when assessed using a CUN-BAE value of ≥40% body fat. Hormone receptor stratification showed that these differences in PAFs were only observed in hormone receptor positive cases, with an estimated burden of 19.9% for BMI and 41.9% for CUN-BAE. Conclusion: These findings suggest that the significance of excess body fat in postmenopausal hormone receptor positive breast cancer could be underestimated when assessed using only BMI. Accurate estimation of the cancer burden attributable to obesity is crucial for planning effective prevention initiatives.
Effectiveness of COVID-19 vaccines administered in the 2023 autumnal campaigns in Europe: Results from the VEBIS primary care test-negative design study, September 2023-January 2024
(Elsevier, 2024-07-25) Laniece Delaunay, Charlotte; Melo, Aryse; Maurel, Marine; Mazagatos, Clara; Goerlitz, Luise; O'Donnell, Joan; Oroszi, Beatrix; Sève, Noémie; Rodrigues, Ana Paula; Martínez-Baz, Iván; Meijer, Adam; Mlinarić, Ivan; Latorre-Margalef, Neus; Lazar, Mihaela; Pérez-Gimeno, Gloria; Dürrwald, Ralf; Bennett, Charlene; Túri, Gergő; Rameix-Welti, Marie-Anne; Guiomar, Raquel; Castilla, Jesús; Hooiveld, Mariëtte; Kurečić Filipović, Sanja; Samuelsson Hagey, Tove; Dijkstra, Frederika; Borges, Vítor; Ramos Marín, Violeta; Bacci, Sabrina; Kaczmarek, Marlena; Kissling, Esther; European Primary Care Vaccine Effectiveness Group; Unión Europea. European Centre for Disease Prevention and Control (ECDC)
In autumn 2023, European vaccination campaigns predominantly administered XBB.1.5 vaccine. In a European multicentre study, we estimated 2023 COVID-19 vaccine effectiveness (VE) against laboratory-confirmed symptomatic infection at primary care level between September 2023 and January 2024. Using a test-negative case-control design, we estimated VE in the target group for COVID-19 vaccination overall and by time since vaccination. We included 1057 cases and 4397 controls. Vaccine effectiveness was 40 % (95 % CI: 26-53 %) overall, 48 % (95 % CI: 31-61 %) among those vaccinated < 6 weeks of onset and 29 % (95 % CI: 3-49 %) at 6-14 weeks. Our results suggest that COVID-19 vaccines administered to target groups during the autumn 2023 campaigns showed clinically significant effectiveness against laboratory-confirmed, medically attended symptomatic SARS-CoV-2 infection in the 3 months following vaccination. A longer study period will allow for further variant-specific COVID-19 VE estimates, better understanding decline in VE and informing booster administration policies.
Targeted Next-Generation Sequencing in a Large Cohort of Genetically Undiagnosed Patients with Neuromuscular Disorders in Spain.
(2020-05-11) Gonzalez-Quereda, Lidia; Rodriguez, Maria Jose; Diaz-Manera, Jordi; Alonso-Perez, Jorge; Gallardo, Eduard; Nascimento, Andres; Ortez, Carlos; Natera-de Benito, Daniel; Olive, Montse; Gonzalez-Mera, Laura; Munain, Adolfo Lopez de; Zulaica, Miren; Poza, Juan Jose; Jerico, Ivonne; Torne, Laura; Riera, Pau; Milisenda, Jose; Sanchez, Aurora; Garrabou, Gloria; Llano, Isabel; Madruga-Garrido, Marcos; Gallano, Pia
The term neuromuscular disorder (NMD) includes many genetic and acquired diseases and differential diagnosis can be challenging. Next-generation sequencing (NGS) is especially useful in this setting given the large number of possible candidate genes, the clinical, pathological, and genetic heterogeneity, the absence of an established genotype-phenotype correlation, and the exceptionally large size of some causative genes such as TTN, NEB and RYR1. We evaluated the diagnostic value of a custom targeted next-generation sequencing gene panel to study the mutational spectrum of a subset of NMD patients in Spain. In an NMD cohort of 207 patients with congenital myopathies, distal myopathies, congenital and adult-onset muscular dystrophies, and congenital myasthenic syndromes, we detected causative mutations in 102 patients (49.3%), involving 42 NMD-related genes. The most common causative genes, TTN and RYR1, accounted for almost 30% of cases. Thirty-two of the 207 patients (15.4%) carried variants of uncertain significance or had an unidentified second mutation to explain the genetic cause of the disease. In the remaining 73 patients (35.3%), no candidate variant was identified. In combination with patients' clinical and myopathological data, the custom gene panel designed in our lab proved to be a powerful tool to diagnose patients with myopathies, muscular dystrophies and congenital myasthenic syndromes. Targeted NGS approaches enable a rapid and cost-effective analysis of NMD- related genes, offering reliable results in a short time and relegating invasive techniques to a second tier.
Marked increase in cryptosporidiosis cases, Spain, 2023
(European Centre for Disease Prevention and Control (ECDC), 2024-07) Peñuelas, Marina; Carmena, David; Guzmán Herrador, Bernardo R; Palau Miguel, Margarita; Saravia Campelli, Gabriela; García Álvarez, Rosa María; Guerrero-Vadillo, María; Dashti, Alejandro; Köster, Pamela Carolina; Guevara Alemany, Esperanza; Simón Soria, Fernando; Fuentes Corripio, Isabel; Varela Martinez, Maria del Carmen; Sierra Moros, María José; Working group for the National Surveillance Network
Background: By mid-September 2023, several event notifications related to cryptosporidiosis had been identified from different regions in Spain. Therefore, a request for urgent notification of cryptosporidiosis cases to the National Surveillance Network was launched. Aim: We aimed at assessing the extent of the increase in cases, the epidemiological characteristics and the transmission modes and compared to previous years. Methods: We analysed data on case notifications, outbreak reports and genotypes focusing on June-October 2023 and compared the results to 2016-2022. Results: In 2023, 4,061 cryptosporidiosis cases were notified in Spain, which is an increase compared to 2016-2022. The cumulative incidence was 8.3 cases per 100,000 inhabitants in 2023, sixfold higher than the median of 1.4 cases per 100,000 inhabitants 2016-2022. Almost 80% of the cases were notified between June and October. The largest outbreaks were related to contaminated drinking water or swimming pools. was the most common species in the characterised samples (115/122), and the IfA12G1R5 subtype, previously unusual in Spain, was detected from 76 (62.3%) of the 122 characterised samples. Conclusions: A substantial increase in cryptosporidiosis cases was observed in 2023. Strengthening surveillance of is essential for prevention of cases, to better understand trends and subtypes circulating and the impact of adverse meteorological events.
Microbial Phenolic Metabolites Are Associated with Improved Cognitive Health
(Wiley, 2024-01) Domínguez-López, Inés; Galkina, Polina; Parilli-Moser, Isabella; Arancibia-Riveros, Camila; Martínez-González, Miguel Ángel; Salas-Salvado, Jordi; Corella, Dolores; Malcampo, Mireia; Martínez, J Alfredo; Tojal-Sierra, Lucas; Wärnberg, Julia; Vioque, Jesus; Romaguera, Dora; López-Miranda, José; Estruch, Ramon; Tinahones, Francisco J; Santos-Lozano, José Manuel; Serra-Majem, Lluis; Bueno-Cavanillas, Aurora; Tur, Josep A; Rubín-García, María; Pintó, Xavier; Fernández-Aranda, Fernando; Delgado-Rodríguez, Miguel; Barabash-Bustelo, Ana; Vidal, Josep; Vazquez, Clotilde; Daimiel, Lidia; Ros, Emilio; Toledo, Estefanía; Atzeni, Alessandro; Asensio, Eva M; Vera, Natàlia; Garcia-Rios, Antonio; Torres-Collado, Laura; Pérez-Farinós, Napoleón; Zulet, Marian; Chaplin, Alice; Casas, Rosa; Martín-Peláez, Sandra; Vaquero-Luna, Jessica; Gómez-Pérez, Ana Maria; Vazquez-Ruiz, Zenaida; Shyam, Sangeetha; Ortega-Azorín, Carolina; Talens, Natàlia; Peña-Orihuela, Patricia J; Oncina-Canovas, Alejandro; Diez-Espino, Javier; Babio, Nancy; Fitó, Montserrat; Lamuela-Raventós, Rosa M
Scope: Diets rich in polyphenols has been associated with better cognitive performance. The aim of this study is to assess the relationship between microbial phenolic metabolites (MPM) in urine and cognition in the context of an older population at high cardiovascular risk. Methods and results: A cross-sectional analysis is conducted in 400 individuals of the PREDIMED-Plus study. Liquid chromatography coupled to mass spectrometry is used to identify urinary MPM. Mediterranean diet (MedDiet) adherence is estimated with a 17-item questionnaire and cognitive function is evaluated with a battery of neuropsychological tests. Multivariable-adjusted linear regression models are fitted to assess the relationship of urinary MPM with the MedDiet and cognitive tests. Protocatechuic acid and enterolactone glucuronide are associated with higher adherence to the MedDiet. Regarding cognitive function, protocatechuic acid, vanillic acid glucuronide, 3-hydroxybenzoic acid, enterodiol glucuronide, and enterolactone glucuronide are directly associated with a global composite score of all the cognitive tests. Furthermore, protocatechuic acid and enterolactone glucuronide are associated with higher scores in the Mini-Mental State Examination, whereas enterodiol glucuronide is associated with improved Clock Drawing Test scores. Conclusions: These results suggest that the MedDiet is linked to MPM associated with better cognitive performance in an older population.
Association between type 2 diabetes and depressive symptoms after a 1-year follow-up in an older adult Mediterranean population
(Springer, 2024-01-13) Baenas, I; Camacho-Barcia, L; Granero, R; Razquin, C; Corella, D; Gómez-Martínez, Carlos; Castañer-Niño, O; Martínez, JA; Alonso-Gómez, ÁM; Wärnberg, Julia; Vioque, Jesus; Romaguera, Dora; López-Miranda, J; Estruch, R; Tinahones, Francisco J; Lapetra, J; Serra-Majem, Lluis; Cano-Ibáñez, N; Tur, Josep A; Martín-Sánchez, V; Pintó, X; Gaforio, J J; Matía-Martín, P; Vidal, Josep; Vazquez, Clotilde; Daimiel, L; Ros, Emilio; Jiménez-Murcia, S; Dalsgaard, S; Garcia-Arellano, A; Babio, N; Sorli, Jose V; Lassale, C; García-de-la-Hera, M; Gómez-García, E; Zulet, MA; Konieczna, Jadwiga; Martín-Peláez, S; Tojal-Sierra, Lucas; Basterra-Gortari, FJ; de Las Heras-Delgado, S; Portoles, O; Muñoz-Pérez, MÁ; Arenas-Larriva, AP; Compañ-Gabucio, L; Eguaras, S; Shyam, Sangeetha; Fitó, M; Baños, RM; Salas-Salvado, Jordi; Fernández-Aranda, F
Objectives: To examine the cross-sectional association between baseline depressive symptoms and the presence of type 2 diabetes (T2D), and its association with glycated hemoglobin (HbA1c) and other metabolic variables, and the prospective association of depressive symptoms and HbA1c after 1 year of follow-up. Methods: n = 6224 Mediterranean older adults with overweight/obesity and metabolic syndrome (48% females, mean age 64.9 ± 4.9 years) were evaluated in the framework of the PREDIMED-Plus study cohort. Depressive symptoms were assessed using the Beck Depression Inventory-II and HbA1c was used to measure metabolic control. Results: The presence of T2D increased the likelihood of higher levels of depressive symptoms (χ2 = 15.84, p = 0.001). Polynomial contrast revealed a positive linear relationship (χ2 = 13.49, p = 0.001), the higher the depressive symptoms levels, the higher the prevalence of T2D. Longitudinal analyses showed that the higher baseline depressive symptoms levels, the higher the likelihood of being within the HbA1c ≥ 7% at 1-year level (Wald-χ2 = 24.06, df = 3, p < .001, for the full adjusted model). Additionally, depressive levels at baseline and duration of T2D predicted higher HbA1c and body mass index, and lower physical activity and adherence to Mediterranean Diet at 1 year of follow-up. Conclusions: This study supports an association between T2D and the severity of depressive symptoms, suggesting a worse metabolic control from mild severity levels in the short-medium term, influenced by lifestyle habits related to diabetes care. Screening for depressive symptoms and a multidisciplinary integrative therapeutic approach should be ensured in patients with T2D.
Yearly attained adherence to Mediterranean diet and incidence of diabetes in a large randomized trial
(BioMed Central (BMC), 2023-09-29) Martínez-González, Miguel A; Montero, Pedro; Ruiz-Canela, Miguel; Toledo, Estefanía; Estruch, Ramón; Gómez-Gracia, Enrique; Li, Jun; Ros, Emilio; Arós, Fernando; Hernáez, Alvaro; Corella, Dolores; Fiol Sala, Miquel; Lapetra, José; Serra-Majem, Lluis; Pintó, Xavier; Cofán, Montse; Sorli, Jose V; Babio, Nancy; Márquez-Sandoval, Yolanda F; Castañer, Olga; Salas-Salvado, Jordi
Background: Several large observational prospective studies have reported a protection by the traditional Mediterranean diet against type 2 diabetes, but none of them used yearly repeated measures of dietary intake. Repeated measurements of dietary intake are able to improve subject classification and to increase the quality of the assessed relationships in nutritional epidemiology. Beyond observational studies, randomized trials provide stronger causal evidence. In the context of a randomized trial of primary cardiovascular prevention, we assessed type 2 diabetes incidence according to yearly repeated measures of compliance with a nutritional intervention based on the traditional Mediterranean diet. Methods: PREDIMED (''PREvención con DIeta MEDiterránea'') was a Spanish trial including 7447 men and women at high cardiovascular risk. We assessed 3541 participants initially free of diabetes and originally randomized to 1 of 3 diets: low-fat diet (n = 1147, control group), Mediterranean diet supplemented with extra virgin olive (n = 1154) or Mediterranean diet supplemented with mixed nuts (n = 1240). As exposure we used actual adherence to Mediterranean diet (cumulative average), yearly assessed with the Mediterranean Diet Adherence Screener (scoring 0 to 14 points), and repeated up to 8 times (baseline and 7 consecutive follow-up years). This score was categorized into four groups: < 8, 8-< 10, 10- < 12, and 12-14 points. The outcome was new-onset type 2 diabetes. Results: Multivariable-adjusted hazard ratios from time-varying Cox models were 0.80 (95% confidence interval, 0.70-0.92) per + 2 points in Mediterranean Diet Adherence Screener (linear trend p = .001), and 0.46 (0.25-0.83) for the highest (12-14 points) versus the lowest (< 8) adherence. This inverse association was maintained after additionally adjusting for the randomized arm. Age- and sex-adjusted analysis of a validated plasma metabolomic signature of the Mediterranean Diet Adherence Screener (constituted of 67 metabolites) in a subset of 889 participants also supported these results. Conclusions: Dietary intervention trials should quantify actual dietary adherence throughout the trial period to enhance the benefits and to assist results interpretation. A rapid dietary assessment tool, yearly repeated as a screener, was able to capture a strong inverse linear relationship between Mediterranean diet and type 2 diabetes. Trial registration ISRCTN35739639.
Ultra-processed foods consumption as a promoting factor of greenhouse gas emissions, water, energy, and land use: A longitudinal assessment
(Elsevier, 2023-05-24) Garcia, Silvia; Pastor, Rosario; Monserrat-Mesquida, Margalida; Álvarez-Álvarez, Laura; Rubín-García, María; Martínez-González, Miguel Ángel; Salas-Salvado, Jordi; Corella, Dolores; Fito, Montserrat; Martínez, J Alfredo; Tojal-Sierra, Lucas; Wärnberg, Julia; Vioque, Jesus; Romaguera, Dora; López-Miranda, José; Estruch, Ramon; Tinahones, Francisco J; Santos-Lozano, José Manuel; Serra-Majem, Lluis; Cano-Ibañez, Naomi; Pintó, Xavier; Delgado-Rodriguez, Miguel; Matía-Martín, Pilar; Vidal, Josep; Vazquez, Clotilde; Daimiel, Lidia; Ros, Emilio; Buil-Cosiales, Pilar; Martínez-Rodríguez, María Ángeles; Coltell, Oscar; Castañer, Olga; Garcia-Rios, Antonio; Barceló Cañellas, María de la Concepión; Gómez-Gracia, Enrique; Zulet, Maria Ángeles; Konieczna, Jadwiga; Casas, Rosa; Massó-Guijarro, Paloma; Goicolea-Güemez, Leire; Rosa Bernal-Lopez, Maria; Bes-Rastrollo, Maira; Shyam, Sangeetha; González, José I; Zomeño-Fajardo, María Dolores; Peña-Orihuela, Patricia J; González-Palacios, Sandra; Toledo, Estefanía; Khoury, Nadine; Perez, Karla Alejandra; Martín-Sánchez, Vicente; Tur, Josep A; Bouzas, Cristina
Background: Dietary patterns can produce an environmental impact. Changes in people's diet, such as the increased consumption of ultra-processed food (UPF) can not only influence human health but also environment sustainability. Objectives: Assessment of the impact of 2-year changes in UPF consumption on greenhouse gas emissions and water, energy and land use. Design: A 2-year longitudinal study after a dietary intervention including 5879 participants from a Southern European population between the ages of 55-75 years with metabolic syndrome. Methods: Food intake was assessed using a validated 143-item food frequency questionnaire, which allowed classifying foods according to the NOVA system. In addition, sociodemographic data, Mediterranean diet adherence, and physical activity were obtained from validated questionnaires. Greenhouse gas emissions, water, energy and land use were calculated by means of the Agribalyse® 3.0.1 database of environmental impact indicators for food items. Changes in UPF consumption during a 2-year period were analyzed. Statistical analyses were conducted using computed General Linear Models. Results: Participants with major reductions in their UPF consumption reduced their impact by -0.6 kg of CO2eq and -5.3 MJ of energy. Water use was the only factor that increased as the percentage of UPF was reduced. Conclusions: Low consumption of ultra-processed foods may contribute to environmental sustainability. The processing level of the consumed food should be considered not only for nutritional advice on health but also for environmental protection. Trial registration: ISRCTN, ISRCTN89898870. Registered 05 September 2013, http://www.isrctn.com/ISRCTN89898870.
Trends in Adherence to the Mediterranean Diet in Spanish Children and Adolescents across Two Decades
(Multidisciplinary Digital Publishing Institute (MDPI), 2023-05-17) Herrera-Ramos, Estefania; Tomaino, Laura; Sanchez-Villegas, Almudena; Ribas-Barba, Lourdes; Gómez, Santiago F; Wärnberg, Julia; Osés, Maddi; González-Gross, Marcela; Gusi, Narcis; Aznar, Susana; Marín-Cascales, Elena; González-Valeiro, Miguel Ángel; Terrados, Nicolás; Tur, Josep A; Segu, Marta; Fito, Montserrat; Homs, Clara; Benavente-Marín, Juan Carlos; Labayen, Idoia; Zapico, Augusto Garcia; Sánchez-Gómez, Jesús; Jiménez-Zazo, Fabio; Alcaraz-Ramón, Pedro Emilio; Sevilla-Sanchez, Marta; Pulgar-Muñoz, Susana; Bouzas, Cristina; Sistac-Sorigué, Clara; Schröder, Helmut; Serra-Majem, Lluis
Unhealthy dietary habits determined during childhood may represent a risk factor to many of the chronic non-communicable diseases (NCDs) in adulthood. Mediterranean Diet (MD) adherence in children and adolescents (8-16 years) living in Spain was investigated using the KIDMED questionnaire in a comparative analysis of two cross-sectional nationwide representative studies: enKid (1998-2000, n = 1001) and PASOS (2019-2020, n = 3540). Taking into account the educational level of pupils, as well as the characteristics of the place of living, a significant association was found between a KIDMED score ≥ 8 (optimal MD adherence) and primary education as well as residency in an area of <50,000 inhabitants, while living in the southern regions was associated with non-optimal MD adherence (p < 0.001). Participants of the 2019-2020 study showed an increase in the consumption of dairy products (31.1% increase), pasta/rice (15.4% increase), olive oil (16.9% increase), and nuts (9.7% increase), as well as a decreased sweets and candies intake (12.6% reduction). In contrast, a significantly lower MD adherence was found when comparing the 2019-2020 (mean ± SE: 6.9 ± 0.04) and the 1998-2000 study (7.37 ± 0.08); p < 0.001), due to less consumption of fish (20.3% reduction), pulse (19.4% reduction), and fruits (14.9% reduction), and an increased intake of commercial goods/pastries or fast-food intake (both 19.4% increase). The lowest adherence was recorded for adolescents also in the most recent study, where 10.9% of them presented a KIDMED score ≤ 3. This study shows that eating habits are deteriorating among Spanish children and adolescents. Such findings point out the urgency of undertaking strong measures to promote the consumption of healthy, sustainable, and non-ultra-processed food, such as those available in an MD, not only at a scientific and academic level, but also at a governmental one.
The CARBA-MAP study: national mapping of carbapenemases in Spain (2014-2018)
(Frontiers Media, 2023) Gracia-Ahufinger, Irene; López-González, Laura; Vasallo, Francisco José; Galar, Alicia; Siller, María; Pitart, Cristina; Bloise, Iván; Torrecillas, Miriam; Gijón-Cordero, Desirée; Viñado, Belén; Castillo-García, Javier; Campo, Rainer; Mulet, Xavier; Madueño-Alonso, Ana; Chamizo-López, Francisco Javier; Arrastia-Erviti, Maitane; Galán-Sánchez, Fátima; Fernández-Quejo, Melisa; Rodríguez-Díaz, Juan Carlos; Gutiérrez-Zufiaurre, María Nieves; Rodríguez-Maresca, Manuel Angel; Ortega-Lafont, María Del Pilar; Yague-Guirao, Genoveva; Chaves-Blanco, Lucía; Colomina-Rodríguez, Javier; Vidal-Acuña, María Reyes; Portillo, María Eugenia; Franco-Álvarez de Luna, Francisco; Centelles-Serrano, María José; Azcona-Gutiérrez, José Manuel; Delgado-Iribarren García Campero, Alberto; Rey-Cao, Sonia; Muñoz, Patricia; Calvo-Montes, Jorge; Zboromyrska, Yuliya; Grandioso, David; Càmara, Jordi; Cantón, Rafael; Larrosa-Escartín, Nieves; Díaz-Regañón, Jazmín; Martínez-Martínez, Luis
Introduction: Infections caused by carbapenem-resistant Enterobacterales (CRE) and carbapenem-resistant Pseudomonas aeruginosa, including isolates producing acquired carbapenemases, constitute a prevalent health problem worldwide. The primary objective of this study was to determine the distribution of the different carbapenemases among carbapenemase-producing Enterobacterales (CPE, specifically Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae complex, and Klebsiella aerogenes) and carbapenemase-producing P. aeruginosa (CPPA) in Spain from January 2014 to December 2018. Methods: A national, retrospective, cross-sectional multicenter study was performed. The study included the first isolate per patient and year obtained from clinical samples and obtained for diagnosis of infection in hospitalized patients. A structured questionnaire was completed by the participating centers using the REDCap platform, and results were analyzed using IBM SPSS Statistics 29.0.0. Results: A total of 2,704 carbapenemase-producing microorganisms were included, for which the type of carbapenemase was determined in 2692 cases: 2280 CPE (84.7%) and 412 CPPA (15.3%), most often using molecular methods and immunochromatographic assays. Globally, the most frequent types of carbapenemase in Enterobacterales and P. aeruginosa were OXA-48-like, alone or in combination with other enzymes (1,523 cases, 66.8%) and VIM (365 cases, 88.6%), respectively. Among Enterobacterales, carbapenemase-producing K. pneumoniae was reported in 1821 cases (79.9%), followed by E. cloacae complex in 334 cases (14.6%). In Enterobacterales, KPC is mainly present in the South and South-East regions of Spain and OXA-48-like in the rest of the country. Regarding P. aeruginosa, VIM is widely distributed all over the country. Globally, an increasing percentage of OXA-48-like enzymes was observed from 2014 to 2017. KPC enzymes were more frequent in 2017-2018 compared to 2014-2016. Discussion: Data from this study help to understand the situation and evolution of the main species of CPE and CPPA in Spain, with practical implications for control and optimal treatment of infections caused by these multi-drug resistant organisms.
Plasma metabolite profiles associated with the World Cancer Research Fund/American Institute for Cancer Research lifestyle score and future risk of cardiovascular disease and type 2 diabetes
(BioMed Central (BMC), 2023-09-16) Rios, Santiago; García-Gavilán, Jesús F; Babio, Nancy; Paz-Graniel, Indira; Ruiz-Canela, Miguel; Liang, Liming; Clish, Clary B; Toledo, Estefanía; Corella, Dolores; Estruch, Ramón; Ros, Emilio; Fitó, Montserrat; Arós, Fernando; Fiol Sala, Miquel; Guasch-Ferré, Marta; Santos-Lozano, José Manuel; Li, Jun; Razquin, Cristina; Martínez-González, Miguel Ángel; Hu, Frank B; Salas-Salvado, Jordi
Background: A healthy lifestyle (HL) has been inversely related to type 2 diabetes (T2D) and cardiovascular disease (CVD). However, few studies have identified a metabolite profile associated with HL. The present study aims to identify a metabolite profile of a HL score and assess its association with the incidence of T2D and CVD in individuals at high cardiovascular risk. Methods: In a subset of 1833 participants (age 55-80y) of the PREDIMED study, we estimated adherence to a HL using a composite score based on the 2018 Word Cancer Research Fund/American Institute for Cancer Research recommendations. Plasma metabolites were analyzed using LC-MS/MS methods at baseline (discovery sample) and 1-year of follow-up (validation sample). Cross-sectional associations between 385 known metabolites and the HL score were assessed using elastic net regression. A 10-cross-validation procedure was used, and correlation coefficients or AUC were assessed between the identified metabolite profiles and the self-reported HL score. We estimated the associations between the identified metabolite profiles and T2D and CVD using multivariable Cox regression models. Results: The metabolite profiles that identified HL as a dichotomous or continuous variable included 24 and 58 metabolites, respectively. These are amino acids or derivatives, lipids, and energy intermediates or xenobiotic compounds. After adjustment for potential confounders, baseline metabolite profiles were associated with a lower risk of T2D (hazard ratio [HR] and 95% confidence interval (CI): 0.54, 0.38-0.77 for dichotomous HL, and 0.22, 0.11-0.43 for continuous HL). Similar results were observed with CVD (HR, 95% CI: 0.59, 0.42-0.83 for dichotomous HF and HR, 95%CI: 0.58, 0.31-1.07 for continuous HL). The reduction in the risk of T2D and CVD was maintained or attenuated, respectively, for the 1-year metabolomic profile. Conclusions: In an elderly population at high risk of CVD, a set of metabolites was selected as potential metabolites associated with the HL pattern predicting the risk of T2D and, to a lesser extent, CVD. These results support previous findings that some of these metabolites are inversely associated with the risk of T2D and CVD. Trial registration: The PREDIMED trial was registered at ISRCTN (http://www.isrctn.com/ , ISRCTN35739639).
Olive oil consumption, plasma metabolites, and risk of type 2 diabetes and cardiovascular disease
(BioMed Central (BMC), 2023-12-13) García-Gavilán, Jesús F; Babio, Nancy; Toledo, Estefanía; Semnani-Azad, Zhila; Razquin, Cristina; Dennis, Courtney; Deik, Amy; Corella, Dolores; Estruch, Ramón; Ros, Emilio; Fitó, Montserrat; Arós, Fernando; Fiol Sala, Miquel; Lapetra, José; Lamuela-Raventos, Rosa; Clish, Clary; Ruiz-Canela, Miguel; Martínez-González, Miguel Ángel; Hu, Frank; Salas-Salvado, Jordi; Guasch-Ferré, Marta
Background: Olive oil consumption has been inversely associated with the risk of type 2 diabetes (T2D) and cardiovascular disease (CVD). However, the impact of olive oil consumption on plasma metabolites remains poorly understood. This study aims to identify plasma metabolites related to total and specific types of olive oil consumption, and to assess the prospective associations of the identified multi-metabolite profiles with the risk of T2D and CVD. Methods: The discovery population included 1837 participants at high cardiovascular risk from the PREvención con DIeta MEDiterránea (PREDIMED) trial with available metabolomics data at baseline. Olive oil consumption was determined through food-frequency questionnaires (FFQ) and adjusted for total energy. A total of 1522 participants also had available metabolomics data at year 1 and were used as the internal validation sample. Plasma metabolomics analyses were performed using LC-MS. Cross-sectional associations between 385 known candidate metabolites and olive oil consumption were assessed using elastic net regression analysis. A 10-cross-validation (CV) procedure was used, and Pearson correlation coefficients were assessed between metabolite-weighted models and FFQ-derived olive oil consumption in each pair of training-validation data sets within the discovery sample. We further estimated the prospective associations of the identified plasma multi-metabolite profile with incident T2D and CVD using multivariable Cox regression models. Results: We identified a metabolomic signature for the consumption of total olive oil (with 74 metabolites), VOO (with 78 metabolites), and COO (with 17 metabolites), including several lipids, acylcarnitines, and amino acids. 10-CV Pearson correlation coefficients between total olive oil consumption derived from FFQs and the multi-metabolite profile were 0.40 (95% CI 0.37, 0.44) and 0.27 (95% CI 0.22, 0.31) for the discovery and validation sample, respectively. We identified several overlapping and distinct metabolites according to the type of olive oil consumed. The baseline metabolite profiles of total and extra virgin olive oil were inversely associated with CVD incidence (HR per 1SD: 0.79; 95% CI 0.67, 0.92 for total olive oil and 0.70; 0.59, 0.83 for extra virgin olive oil) after adjustment for confounders. However, no significant associations were observed between these metabolite profiles and T2D incidence. Conclusions: This study reveals a panel of plasma metabolites linked to the consumption of total and specific types of olive oil. The metabolite profiles of total olive oil consumption and extra virgin olive oil were associated with a decreased risk of incident CVD in a high cardiovascular-risk Mediterranean population, though no associations were observed with T2D incidence. Trial registration: The PREDIMED trial was registered at ISRCTN (http://www.isrctn.com/ , ISRCTN35739639).

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