Effect of a Multifactorial Weight Loss Intervention on HDL Cholesterol Efflux Capacity and Immunosenescence: A Randomized Controlled Trial.

OBJECTIVE: Life expectancy and obesity prevalence are increasing worldwide, leading to an increase in the prevalence of cardiovascular disease. High-density lipoprotein (HDL) functionality and immunosenescence play key roles in cardiovascular disease, longevity, and quality of aging. Both molecular hallmarks of aging are impacted by obesity and metabolic syndrome and can be modulated by lifestyle. We aimed to evaluate the effect of a lifestyle intervention focused on an energy-reduced Mediterranean diet (erMedDiet), physical activity (PA), and behavioral support on HDL cholesterol efflux capacity (CEC) and immunosenescence. METHOD: CEC and immunosenescent T cells were determined in 60 participants from the control group (CG) and 56 from the intervention group (IG) of the PREDIMED-Plus trial at baseline and after 1 and 3 years of follow-up. PREDIMED-Plus is a randomized, controlled, parallel-group trial with an IG of erMedDiet, PA promotion, and behavioral support for weight loss and a CG of usual primary care advice. The sample included 116 volunteers from the PREDIMED-Plus-IMDEA subsample of the PREDIMED-Plus trial. Men aged 55 to 75 years and women aged 60 to 75 years with a body mass index between 27 and 40 kg/m2 and metabolic syndrome were included. RESULTS: Participants within the IG had significantly improved CEC (2.42% and 10.69% after 1 and 3 years of follow-up) and a decreased in senescent T cell profile (-3.32% ± 12.54% and -6.74% ± 11.2%, p < 0.001, after 1 and 3 years of follow-up). Baseline obesity status impacted the response to the intervention. CONCLUSIONS: A weight loss intervention program with erMedDiet and PA ameliorated senescence markers.

Dietary carbohydrate quality index and incidence of obesity-related cancers in the "Seguimiento Universidad De Navarra" (SUN) prospective cohort.

PURPOSE: The quality, rather than the quantity, of carbohydrate intake may play a major role in the etiology of obesity-related cancers (ORCs). We assessed the association between a previously defined carbohydrate quality index (CQI) and the risk of developing ORCs in the "Seguimiento Universidad de Navarra" (SUN) cohort. METHODS: A total of 18,446 Spanish university graduates [mean age 38 years (SD 12 years), 61% women, mean BMI 23.5 kg/m2 (SD 3.5 kg/m2)], with no personal history of cancer, were followed-up. Baseline CQI was assessed summing quintiles of four previously defined criteria: high dietary fiber intake, low glycemic index (GI), high whole-grain: total-grain carbohydrates ratio and high solid carbohydrates: total carbohydrates ratio. Participants were classified into tertiles of their total CQI. Incident ORCs were confirmed by an oncologist using medical records and by querying the National Death Index blindly to dietary exposures. RESULTS: During a median follow-up of 13.7 years, 269 incident cases of ORC were confirmed. A higher CQI was inversely associated with ORC incidence [multivariable-adjusted hazard ratio (HR) for the upper (T3) versus the lowest tertile (T1) of 0.68 (95% CI: 0.47-0.96), p for trend = 0.047]. Particularly, higher dietary fiber intake was inversely associated with ORC, HRT3 vs. T1=0.57 (95% CI 0.37-0.88 p for trend = 0.013). CONCLUSION: In this prospective Mediterranean cohort, an inverse association between a better global quality of carbohydrate intake and the risk of ORCs was found. Strategies for cancer prevention should promote a higher quality of carbohydrate intake.

Vitamin D and risk of developing type 2 diabetes in the SUN project: a prospective cohort study.

PURPOSE: Vitamin D deficiency has been associated with multiple chronic diseases, including metabolic disorders such as insulin resistance and type 2 diabetes (T2D). The aim of the study was to analyze the association between validated predicted serum vitamin D status and the risk of developing T2D in a large prospective cohort based on a Mediterranean population. METHODS: The SUN project is a prospective and dynamic Spanish cohort that gathers university graduates who have answered lifestyle questionnaires, including a validated Food Frequency Questionnaire. The association between predicted serum vitamin D and the risk of T2D was assessed through Cox regression models according to quartiles (Q) of predicted vitamin D at baseline. The models were adjusted for potential confounders and sensitivity analyses were performed to ensure the robustness of our findings. RESULTS: Our study included a total of 18,594 participants and after a total follow-up of 238,078 person-years (median follow-up of 13.5 years), 209 individuals were diagnosed with incident T2D. We found a significant inverse association between predicted levels of serum vitamin D and the risk of developing T2D, after adjusting for potential confounders and performing different sensitivity analyses (hazard ratio Q4 vs. Q1: 0.48, 95% CI 0.26-0.88; p for trend = 0.032). CONCLUSION: The outcomes suggest that higher levels of vitamin D at baseline may be associated with a reduced risk of developing T2D.

Intensive Weight-Loss Lifestyle Intervention Using Mediterranean Diet and COVID-19 Risk in Older Adults: Secondary Analysis of PREDIMED-Plus Trial.

OBJECTIVES: We tested the effects of a weight-loss intervention encouraging energy-reduced MedDiet and physical activity (PA) in comparison to ad libitum MedDiet on COVID-19 incidence in older adults. DESIGN: Secondary analysis of PREDIMED-Plus, a prospective, ongoing, multicentre randomized controlled trial. SETTING: Community-dwelling, free-living participants in PREDIMED-Plus trial. PARTICIPANTS: 6,874 Spanish older adults (55-75 years, 49% women) with overweight/obesity and metabolic syndrome. INTERVENTION: Participants were randomised to Intervention (IG) or Control (CG) Group. IG received intensive behavioural intervention for weight loss with an energy-reduced MedDiet intervention and PA promotion. CG was encouraged to consume ad libitum MedDiet without PA recommendations. MEASUREMENTS: COVID-19 was ascertained by an independent Event Committee until December 31, 2021. COX regression models compared the effect of PREDIMED-Plus interventions on COVID-19 risk. RESULTS: Overall, 653 COVID-19 incident cases were documented (IG:317; CG:336) over a median (IQR) follow-up of 5.8 (1.3) years (inclusive of 4.0 (1.2) years before community transmission of COVID-19) in both groups. A significantly lowered risk of COVID-19 incidence was not evident in IG, compared to CG (fully-adjusted HR (95% CI): 0.96 (0.81,1.12)). CONCLUSIONS: There was no evidence to show that an intensive weight-loss intervention encouraging energy-reduced MedDiet and PA significantly lowered COVID-19 risk in older adults with overweight/obesity and metabolic syndrome in comparison to ad libitum MedDiet. Recommendations to improve adherence to MedDiet provided with or without lifestyle modification suggestions for weight loss may have similar effects in protecting against COVID-19 risk in older adults with high cardiovascular risks.

Health-related quality of life and mortality in the 'Seguimiento Universidad de Navarra' prospective cohort study.

OBJECTIVE: To study the association between health-related quality of life (HRQoL) and all-cause mortality in a healthy middle-aged Mediterranean cohort. METHODS: We included 15,390 participants -mean age 42.8 years at first HRQoL ascertainment, all university graduates-. HRQoL was assessed with the self-administered Medical Outcomes Study Short Form-36 (SF-36) twice, with a 4-year gap. We used multivariable-adjusted Cox regression models to address the relation between self-reported health and Physical or Mental Component Summary (PCS-36 or MCS-36) and mortality, and their interaction with prior comorbidities or adherence to the Mediterranean diet (MedDiet). RESULTS: Over 8.7 years of median follow-up time, 266 deaths were identified. Hazard ratio (HR) for the excellent vs. poor/fair category in self-reported health was 0.30 (95 % confidence interval (CI), 0.16-0.57) in the model with repeated measurements of HRQoL. Both the PCS-36 (HRquartile4(Q4)vs.Q1 0.57 [95%CI, 0.36-0.90], ptrend < 0.001; HRper+10points: 0.64 [95%CI, 0.54-0.75]) and the MCS-36 (HRQ4vs.Q1 0.67 [95%CI, 0.46-0.97], ptrend = 0.025; HRper+10points: 0.86 [95%CI, 0.74-0.99]) were inversely associated with mortality in the model with repeated measurements of HRQoL. Previous comorbidities or adherence to the MedDiet did not modify these associations. CONCLUSIONS: Self-reported HRQoL -assessed as self-reported health, PCS-36 and MCS-36- obtained with the Spanish version of the SF-36 were inversely associated with mortality risk, regardless of the presence of previous comorbidities or adherence to the MedDiet.

Prevention of Alzheimer's Disease and Cognitive Decline with Diet and Lifestyle: Proceedings of the A. G. Leventis Foundation Conference.

The A. G. Leventis Foundation International Conference, "Prevention of Alzheimer's Disease and Cognitive Decline with Diet and Lifestyle", was held on May 11-12th, 2022 in Nicosia, Cyprus. This conference examined the role of diet and lifestyle for the prevention and treatment of Alzheimer's Disease and other forms of cognitive decline. Speakers from leading academic institutions presented evidence on healthy dietary patterns, with a particular focus on the traditional Mediterranean diet (MedDiet), in association with cognitive outcomes, mainly cognitive decline, dementia, and Alzheimer's disease, from both observational and interventional studies. Moreover, future directions for the potential use of olive oil, rich in polyphenols, for its therapeutic use as a nutraceutical, as well as nutritional interventions with high-quality dietary patterns (i.e. MedDiet) that support existing primarily observational evidence for the prevention of cognitive decline, as well as challenges in designing rigorous clinical trials are summarized and discussed within the conference proceedings.

Mid- and long-term changes in satiety-related hormones, lipid and glucose metabolism, and inflammation after a Mediterranean diet intervention with the goal of losing weight: A randomized, clinical trial.

Background: Obesity is produced by the enlargement of the adipose tissue. Functioning as an endocrine organ, it releases and receives information through a complex network of cytokines, hormones, and substrates contributing to a low-chronic inflammation environment. Diet and healthy habits play key roles in the prevention of obesity and its related pathologies. In this regard, there is a need to switch to healthier and more appetizing diets, such as the Mediterranean one. Objective: To compare the mid-and long-term effects of two Mediterranean diet (MedDiet) interventions, one energy-reduced plus physical activity promotion versus a non-restrictive diet, on peripheral satiety-related hormones, weight loss, glucose/lipid metabolism, and pro-inflammatory markers in subjects with obesity/overweight and metabolic syndrome. Materials and methods: A randomized, lifestyle intervention was conducted in 23 Spanish centers, with a large cohort of patients presenting metabolic syndrome. Our study is a subproject set in IMIM (Hospital del Mar Research Institute). Participants were men and women, aged 55-75 and 60-75, respectively, who at baseline met at least three metabolic syndrome components. Subjects were assigned to two intervention groups: (1) an intensive lifestyle intervention with an energy-reduced MedDiet and physical activity promotion (intervention group) with the aim of weight loss; and (2) a normocaloric MedDiet (control). We quantified in a subsample of 300 volunteers from Hospital del Mar Research Institute (Barcelona), following analytes at baseline, 6 months, and 1 year: glucose, HbA1c, triglycerides, total cholesterol, high-density lipoprotein cholesterol, LDL cholesterol, C-peptide, ghrelin, GLP-1, glucagon, insulin, leptin, PAI-1, resistin, and visfatin. Anthropometric and classical cardiovascular risk factors were also determined. A multivariate statistical model was employed to compare the two groups. Linear mixed-effect models were performed to compare changes in risk factors and biomarkers between intervention groups and over time. Results: Compared to participants in the control group, those in intervention one showed greater improvements in weight, waist circumference, insulin (P < 0.001), glucose metabolism-related compounds (P < 0.05), triglyceride-related lipid profile (P < 0.05), leptin, blood pressure, and pro-inflammatory markers such as PAI-1 (P < 0.001) at mid-and/or long-term. High-sensitivity C-reactive protein, resistin, and vifastin also decreased in both groups. Conclusion: A weight loss intervention employing a hypocaloric MedDiet and physical activity promotion has beneficial effects on adiposity, glucose metabolism, lipid profile, leptin, and pro-inflammatory markers, such as PAI-1 in both mid-and long-term.

Mediterranean diet and the risk of COVID-19 in the 'Seguimiento Universidad de Navarra' cohort.

BACKGROUND & AIMS: A potential protection against COVID-19 by a high-quality dietary pattern is to be expected given the biological plausibility supporting the beneficial effects of an adequate dietary intake on the immune system. However, knowledge on the relationship between long-term maintained healthy dietary patterns, such as the Mediterranean diet, and the risk of SARS-CoV-2 infection is still sparse. We longitudinally assessed this association in a well-known Mediterranean cohort. METHODS: We assessed 9,677 participants from the SUN Project, a prospective cohort of middle-aged university graduates in Spain. We inquired about a positive result in a COVID-19 diagnostic test during the months of February to December 2020. After excluding health professionals (HP), 5,194 participants were included in the statistical analyses (mean age: 52.6, SD: 12.4; 55.2% women). Food habits were assessed at baseline using a previously validated semiquantitative 136-item food frequency questionnaire. Adherence to the Mediterranean diet (cumulative average of 2 repeated measurements 10 years apart) was assessed using the 0-to-9 Mediterranean Diet Score (MDS). We used multivariable logistic regression models to estimate odds ratios and 95% confidence intervals for incident COVID-19 according to the MDS. RESULTS: Among 5,194 non-HP participants, 122 reported to have received a positive COVID-19 diagnostic test. Participants with intermediate adherence to the Mediterranean diet (3 < MDS ≤ 6) had a significantly lower odds of developing COVID-19 (multivariable-adjusted OR = 0.50, 95% CI: 0.34-0.73), and those with the highest adherence (MDS > 6) exhibited the lowest risk (multivariable-adjusted OR = 0.36, 95% CI: 0.16-0.84, p for trend < 0.001) as compared with participants with MDS ≤ 3. This inverse association remained robust within subgroups and in sensitivity analyses. Notwithstanding, no significant associations were observed for health professionals (p for interaction = 0.06). CONCLUSION: In conclusion, better adherence to the Mediterranean diet may be associated with a lower risk of COVID-19. Our results are applicable only to persons who are not health professionals.

Exploratory dietary patterns and cognitive function in the "Seguimiento Universidad de Navarra" (SUN) Prospective Cohort.

BACKGROUND: Dementia is projected to affect 135 million by 2050. Diet is a pertinent target for primary prevention, but firm recommendations for dementia prevention are not available yet. Our aim was to address the association between exploratory (empirically derived) dietary patterns (DP) and changes in the Spanish Telephone Interview for Cognitive Status (STICS-m, maximum score = 41 points) over 6 years. METHOD: Information on diet was collected with a validated 136-item food-frequency questionnaire from 803 participants in the Mediterranean cohort "Seguimiento Universidad de Navarra." We used principal component analysis to derive exploratory DP. The derived DP were associated with change in STICS-m scores over 6 years, through adjusted multiple linear regression models. RESULTS: Two main DP were identified. The first DP resembled a Western dietary pattern (WDP)-high in sugar, fat, processed foods, and red meat-and the second DP resembled a Mediterranean dietary pattern (MDP)-high in vegetables, fruits, nuts, fish, and olive oil. Adherence to the WDP (tertile 3 vs tertile 1) was significantly associated with negative STICS-m changes after 6 years (between-tertile difference in changes: -0.80 points; 95% confidence interval [CI] -1.51, -0.08, p value = 0.03). Meanwhile, the MDP showed a positive +0.71 point (95% CI 0.15, 1.26, p value = 0.01) between-tertile difference in changes in the STICS-m score. CONCLUSIONS: A healthy, prudent, MDP was associated with less decline in cognitive function and, thus, could help to lower dementia incidence. Western-type diets were associated with a greater decline in cognitive performance and could increase dementia incidence.

Caffeinated coffee consumption and risk of atrial fibrillation in two Spanish cohorts.

AIMS: The association between caffeinated coffee consumption and atrial fibrillation remains unclear. Recent studies suggest an inverse association only between a moderate caffeinated coffee consumption and atrial fibrillation, but others have reported no association. The aim of our study was to prospectively assess the association between caffeinated coffee consumption and atrial fibrillation in two Spanish cohorts, one of adults from a general population and another of elderly participants at high cardiovascular risk. METHODS AND RESULTS: We included 18,983 and 6479 participants from the 'Seguimiento Universidad de Navarra' (SUN) and 'Prevención con Dieta Mediterránea' (PREDIMED) cohorts, respectively. Participants were classified according to their caffeinated coffee consumption in three groups: ≤3 cups/month, 1-7 cups/week, and >1 cup/day. We identified 97 atrial fibrillation cases after a median follow-up of 10.3 years (interquartile range 6.5-13.5), in the SUN cohort and 250 cases after 4.4 years median follow-up (interquartile range 2.8-5.8) in the PREDIMED study. No significant associations were observed in the SUN cohort although a J-shaped association was suggested. A significant inverse association between the intermediate category of caffeinated coffee consumption (1-7 cups/week) and atrial fibrillation was observed in PREDIMED participants with a multivariable-adjusted hazard ratio = 0.53 (95% confidence interval 0.36-0.79) when compared with participants who did not consume caffeinated coffee or did it only occasionally. No association was found for higher levels of caffeinated coffee consumption (>1 cup per day), hazard ratio = 0.79 (95% confidence interval 0.49-1.28). In the meta-analysis of both PREDIMED and SUN studies, the hazard ratio for intermediate consumption of caffeinated coffee was 0.60 (95% confidence interval 0.44-0.82) without evidence of heterogeneity. Similar findings were found for the association between caffeine intake and atrial fibrillation risk. CONCLUSION: Intermediate levels of caffeinated coffee consumption (1-7 cups/week) were associated with a reduction in atrial fibrillation risk in two prospective Mediterranean cohorts.

Leisure-time physical activity, sedentary behavior, and risk of breast cancer: Results from the SUN ('Seguimiento Universidad De Navarra') project.

Evidence is still limited on the influence of sedentary lifestyles on breast cancer (BC) risk. Also, prospective information on the combined effects of both sedentariness and leisure-time physical activity (LTPA) is scarce. We aimed to assess the association of higher sedentary behavior and LTPA (separately and in combination) with the risk of BC in a middle-aged cohort of university graduates. The SUN Project is a follow-up study initiated in 1999 with recruitment permanently open. Baseline assessments included a validated questionnaire on LTPA and sedentary habits. Subsequently, participants completed biennial follow-up questionnaires. Multivariable adjusted Cox models were used to estimate the hazard ratios (HR) for incident BC according to LTPA, TV-watching, the joint classification of both, and a combined 8-item multidimensional active lifestyle score. We included 10,812 women, with 11.8 years of median follow-up of. Among 115,802 women-years of follow-up, we confirmed 101 incident cases of BC. Women in the highest category of LTPA (>16.5 MET-h/week) showed a significantly lower risk of BC (HR = 0.55; 95% CI: 0.34-0.90) compared to women in the lowest category (≤6 MET/h-week). Women watching >2 h/d of TV sh owed a higher risk (HR = 1.67; 95% CI:1.03-2.72) than those who watched TV <1 h/d. Women in the highest category (6-8 points) of the multidimensional combined 8-item score showed a lower BC risk (HR = 0.35; 95% CI: 0.15-0.79) than those in the lowest category (<2 points) group. There was no significant supra-multiplicative interaction between TV-watching and LTPA. Both low LTPA and TV-watching >2 h/d may substantially increase BC risk, independently of each other.

Depression and metabolic syndrome in participants of the "Seguimiento Universidad de Navarra" (SUN) cohort study.

BACKGROUND: Depression is a major public health concern worldwide and its association with metabolic syndrome (MetS) remains unclear. Thus, we prospectively examined the association between depression and the risk of MetS, according to different diagnosis criteria. METHODS: This study included 9,237 participants of a Spanish dynamic prospective cohort of adult university graduates [mean (SD) age: 36.7 year (10.7)], initially free of any specific criterion of MetS, who were followed-up for a median of 8.3 years. The exposure variables were medical diagnosis of depression at baseline or in the first 2-year follow-up questionnaire. The outcome variable was the incidence of MetS, assessed according to each of three different criteria proposed by: International Diabetes Federation (IDF); National Cholesterol Education Program's Adult Treatment Panel III (NCEP-ATP III); IDF/NCEP-ATP III (updated harmonizing definition). Multivariable-adjusted Relative Risks (RR) of new-onset MetS and their 95% Confidence Intervals (95% CI) were estimated, using Poisson regression models. RESULTS: The cumulative incidences of MetS were 475 cases (IDF definition), 288 cases (NCEP-ATP III definition) and 492 cases (update harmonized definition). No association was observed between baseline depression and incidence of MetS, but the presence of depression after 2-years of follow-up was significantly associated with a higher risk of new-onset MetS, according to NCEP-ATP III definition (multivariable-adjusted RR, 2.46; 95% CI, 1.06-5.67). LIMITATIONS: Diagnosis of depression and MetS were self-reported. CONCLUSIONS: In this large prospective cohort of Spanish middle-aged adult university graduates, a direct association between depression and the risk of MetS according to NCEP-ATP III definition was found.

Human biomonitoring of persistent organic pollutants in elderly people from the Canary Islands (Spain): A temporal trend analysis from the PREDIMED and PREDIMED-Plus cohorts.

The population of the Canary Islands has been exposed to high levels of persistent organic pollutants (POPs). Biomonitoring studies are essential to know the temporal trend in residue levels, particularly of substances banned decades ago. The purpose of this study was to analyze the distribution of plasma concentrations of 59 POPs in 175 participants from the PREDIMED-Plus trial (2014-2016), and to compare them with the distribution of these POPs in 343 participants in the PREDIMED trial (2006-2009). All participants had metabolic syndrome. No difference in the distribution of age, gender or BMI was observed between trials. POPs were determined by gas chromatography-mass spectrometry. Density plots -POP Geoffrey Rose curves- were used to represent the full population distribution of each compound. Three out of 59 POPs were detected and quantified in ≥95% of the samples (p,p'-DDE, median = 694.7 ng/g lipid; HCB, median = 57.0 ng/g lipid; and ß-HCH, median = 75.7 ng/g lipid). PCB congeners 138, 153 and 180 were detected in 64.6, 40.0 and 88.0% of the samples. Females showed highest concentrations of organochlorine pesticides and those subjects who lost ˃ 5 kg showed significant higher plasma concentrations of POPs. In a range of 6-14 years, plasma concentrations of POPs decreased 3.3-21.6 fold, being notable the decrease of 28.7-fold observed for HCB among women. Despite this sharp decline, levels of POPs are still higher than those reported in other regions, since one third of the subjects included in the present report had high concentration of more than three pollutants. Continuous biomonitoring studies are required to know the evolution of the levels of residues and to evaluate the effectiveness of environmental policies.

Health-related quality of life in individuals with metabolic syndrome: A cross-sectional study.

INTRODUCTION AND OBJECTIVES: Metabolic syndrome (MetS) is a combination of various cardiovascular risk factors with a major impact on morbidity and premature mortality. However, the impact of MetS on self-reported health-related quality of life (HRQoL) is unknown. This study evaluated the HRQoL in a Spanish adult population aged 55 years and older with MetS. METHOD: A cross-sectional analysis was performed with baseline data from the PREDIMED-Plus multicentre randomized trial. The participants were 6430 men and women aged 55-75 years with overweight/obesity (body mass index ≥27 and ≤40kg/m2) and MetS. The SF-36 questionnaire was used as a tool to measure HRQoL. Scores were calculated on each scale of the SF-36 by gender and age. RESULTS: Participants showed higher scores in the social function (mean 85.9, 95% CI; 85.4-86.4) and emotional role scales (mean 86.8, 95% CI; 86.0-87.5). By contrast, the worst scores were obtained in the aggregated physical dimensions. In addition, men obtained higher scores than women on all scales. Among men, the worst score was obtained in general health (mean 65.6, 95% CI; 65.0-66.2), and among women, in body pain (mean 54.3, 95%CI; 53.4-55.2). A significant decrease was found in the aggregated physical dimensions score among participants 70-75 years old, but an increased one in the aggregated mental dimensions, compared to younger participants. CONCLUSIONS: Our results reflect that the MetS may negatively affect HRQoL in the aggregated physical dimensions, body pain in women, and general health in men. However, this adverse association was absent for the psychological dimensions of HRQoL, which were less affected.

Mediterranean dietary pattern is associated with lower incidence of premenopausal breast cancer in the Seguimiento Universidad de Navarra (SUN) Project.

OBJECTIVE: Due to the growing interest in the role of dietary patterns (DPs) on chronic diseases, we assessed the association between a posteriori identified DPs in the Seguimiento Universidad de Navarra (SUN) Project - a prospective cohort study in a Mediterranean country - and breast cancer (BC) risk. DESIGN: DPs were ascertained through a principal component analysis based on 31 predefined food groups. BC cases were initially identified through self-report or, if deceased, from death certificates or by notification by the next kin. Women reporting BC were asked to provide a copy of their medical report and diagnoses for confirmation purposes. We fitted Cox regression models to assess the association between adherence to the identified DPs and BC risk. SETTING: Spanish university graduates. PARTICIPANTS: We included 10 713 young and middle-aged - mainly premenopausal - women. RESULTS: After a median follow-up of 10·3 years, we identified 100 confirmed and 168 probable incident BC cases. We described two major DPs: 'Western dietary pattern' (WDP) and 'Mediterranean dietary pattern' (MDP). A higher adherence to a WDP was associated with an increased risk of overall BC (multivariable-adjusted HR for confirmed BC Q4 v. Q1 1·70; 95 % CI 0·93, 3·12; P for trend = 0·045). Contrarily, adherence to a MDP was inversely associated with premenopausal BC (multivariable-adjusted HR Q4 v. Q1 0·33; 95 % CI 0·12, 0·91). No significant associations were observed for postmenopausal BC. CONCLUSIONS: Whereas a higher adherence to the WDP may increase the risk of BC, a higher adherence to the MDP may decrease the risk of premenopausal BC.

PREvention of recurrent arrhythmias with Mediterranean diet (PREDIMAR) study in patients with atrial fibrillation: Rationale, design and methods.

Background: Atrial fibrillation (AF) is the most common cardiac arrhythmia. Catheter ablation aims to restore sinus rhythm. However, relapses occur in up to 30% of patients. A Mediterranean diet (MedDiet) enriched with extra-virgin olive oil (EVOO) substantially reduced the incidence of AF in the PREDIMED trial. The PREDIMAR will test a similar intervention in secondary prevention. Methods: PREDIMAR is a multicenter, randomized, single-blind trial testing the effect of a MedDiet enriched with EVOO to reduce tachyarrhythmia relapses after AF ablation. The primary outcome is the recurrence of any sustained atrial tachyarrhythmia after ablation (excluding those occurring only during the first 3 months after ablation). The target final sample size is 720 patients (360 per group) recruited from 4 Spanish hospitals. A remote intervention, maintained for 2 years, is delivered to the active intervention group including periodic phone calls by a dietitian and free provision of EVOO. The control group will receive delayed intervention after trial completion. Routine electrocardiogram (ECG) and Holter ECG are performed, and a portable cardiac rhythm monitoring device is provided to be worn by participants during 15 months. Results: Recruitment started in March 2017. Up to July 2019, 609 patients were randomized (average inclusion rate: 5.3 patients/wk). Retention rates after 18 months are >94%. Conclusions: If our hypothesis is confirmed, the utility of the MedDiet enriched with EVOO in slowing the progression of AF will be proven, preventing recurrences and potentially reducing complications.

Longitudinal changes in Mediterranean diet and transition between different obesity phenotypes.

BACKGROUND & AIMS: Little is known about the impact of specific dietary patterns on the development of obesity phenotypes. We aimed to determine the association of longitudinal changes in adherence to the traditional Mediterranean diet (MedDiet) with the transition between different obesity phenotypes. METHODS: Data of 5801 older men and women at high cardiovascular risk from PREDIMED trial were used. Adherence to MedDiet was measured with the validated 14p-Mediterranean Diet Adherence Screener (MEDAS). Using the simultaneous combination of metabolic health- and body size-related parameters participants were categorized into one of four phenotypes: metabolically healthy and abnormal obese (MHO and MAO), metabolically healthy and abnormal non-obese (MHNO and MANO). Cox regression models with yearly repeated measures during 5-year of follow-up were built with use of Markov chain assumption. RESULTS: Each 2-point increase in MEDAS was associated with the following transitions: in MAO participants, with a 16% (95% CI 3-31%) greater likelihood of becoming MHO; in MHO participants with a 14% (3-23%) lower risk of becoming MAO; in MHNO participants with a 18% (5-30%) lower risk of becoming MHO. In MANO women, but not in men, MEDAS was associated with 20% (5-38%) greater likely of becoming MHNO (p for interaction by gender 0.014). No other significant associations were observed. CONCLUSIONS: Better adherence to the traditional MedDiet is associated with transitions to healthier phenotypes, promoting metabolic health improvement in MAO, MANO (only in women), and MHO, as well as protecting against obesity incidence in MHNO subjects.

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.