Associations of Alcohol Consumption With Left Atrial Morphology and Function in a Population at High Cardiovascular Risk.

BACKGROUND: Excessive alcohol consumption has been associated with increased risk of atrial fibrillation, although the underlying mechanisms remain unclear. An enlarged left atrium and impaired left atrial function may lead to atrial fibrillation. The association of alcohol consumption with structural and functional left atrial measures, however, has received limited attention. METHODS AND RESULTS: We studied 503 participants from the PREDIMED-Plus (Prevención con Dieta Mediterránea) trial, a randomized trial testing intensive weight loss intervention with an energy-reduced Mediterranean diet and physical activity promotion in preventing cardiovascular disease in adults with metabolic syndrome. Participants underwent transthoracic echocardiography at baseline, year 3, and year 5 of the study. Outcomes of interest included volume index and reservoir, conduit, and contractile strains of the left atrium. Alcohol consumption was calculated through food frequency questionnaires and presented as drinks consumed per day. Multiple linear regression and mixed models estimated the association of alcohol consumption with left atrial measurements at baseline and through follow-up. Cross-sectionally, higher alcohol consumption (per 1 drink/day increases) was associated with larger left atrial volume (0.65 mL/m2 [95% CI, 0.18-1.11]) and lower left atrial reservoir and contractile strain (-0.44% [95% CI, -0.87 to -0.01]; and -0.44% [95% CI, -0.75 to -0.14]). Baseline alcohol consumption was not associated with changes in left atrial measurements, but increases in alcohol consumption (per 1 drink/day increase) during follow-up were associated with left atrial enlargement (0.71 mL/m2 [95% CI, 0.17-1.26]). CONCLUSIONS: In a population at high cardiovascular risk, increased alcohol consumption was associated with left atrial enlargement and worsening atrial function. REGISTRATION: URL: http://www.controlled-trials.com; Unique identifier: ISRCTN89898870.

Daily time spent on screens and psychological well-being: Cross-sectional association within the SUN cohort.

BACKGROUND: The impact of various lifestyles on psychological well-being (PWB) remains under-studied. We aimed to explore the cross-sectional association between daily screen use (television, tablet and mobile phone) and PWB within the SUN cohort. METHODS: PWB was assessed using the 29-item Ryff scale (ranging from 29 to 174), and participants with scores >75th percentile were considered as having optimal PWB. Participants were categorized based on their self-reported weekly screen usage hours. Postestimation logistic regression models assessing the prevalence likelihood of not achieving optimal PWB were adjusted for sociodemographic, psychological, personality and lifestyles factors. Isotemporal substitution models explored the potential impact on PWB resulting from replacing 1 h/day of screen time with 1 h/day of exercise. RESULTS: The study included 3051 participants (55.8% women, mean age 57.3 ± 11.1 years, mean Ryff's score: 139.1 ± 17.4 points). Daily screen use for ≥2 h was associated with a higher prevalence likelihood of not achieving an optimal PWB (Prevalence Ratio [PR]:1.09; 95% CI:1.01-1.18). Among PWB dimensions, screen use ≥2 h/day was linked to an increased likelihood of not achieving optimal scores in environmental mastery (PR:1.11; 95% CI:1.02-1.20), life purpose (PR:1.10; 95% CI:1.02-1.18), and personal growth (PR:1.09; 95% CI:1.01-1.18). Replacing 1 h of daily screens time with 1 h of exercise may lead to potential improvements in environmental mastery (Odds Ratio [OR]:0.87; 95% CI:0.76-0.99), purpose in life (OR:0.86; 95% CI: 0.76-0.98), personal growth (OR:0.84; 95% CI:0.73-0.96) and positive interpersonal relationships (OR:0.86; 95% CI:0.75-0.99). CONCLUSIONS: These findings highlight the importance of reducing screen use activities and increasing physical exercise for achieving optimal PWB.

Plasma metabolites of a healthy lifestyle in relation to mortality and longevity: Four prospective US cohort studies.

BACKGROUND: A healthy lifestyle is associated with a lower premature mortality risk and with longer life expectancy. However, the metabolic pathways of a healthy lifestyle and how they relate to mortality and longevity are unclear. We aimed to identify and replicate a healthy lifestyle metabolomic signature and examine how it is related to total and cause-specific mortality risk and longevity. METHODS: In four large cohorts with 13,056 individuals and 28-year follow-up, we assessed five healthy lifestyle factors, used liquid chromatography mass spectrometry to profile plasma metabolites, and ascertained deaths with death certificates. The unique healthy lifestyle metabolomic signature was identified using an elastic regression. Multivariable Cox regressions were used to assess associations of the signature with mortality and longevity. FINDINGS: The identified healthy lifestyle metabolomic signature was reflective of lipid metabolism pathways. Shorter and more saturated triacylglycerol and diacylglycerol metabolite sets were inversely associated with the healthy lifestyle score, whereas cholesteryl ester and phosphatidylcholine plasmalogen sets were positively associated. Participants with a higher healthy lifestyle metabolomic signature had a 17% lower risk of all-cause mortality, 19% for cardiovascular disease mortality, and 17% for cancer mortality and were 25% more likely to reach longevity. The healthy lifestyle metabolomic signature explained 38% of the association between the self-reported healthy lifestyle score and total mortality risk and 49% of the association with longevity. CONCLUSIONS: This study identifies a metabolomic signature that measures adherence to a healthy lifestyle and shows prediction of total and cause-specific mortality and longevity. FUNDING: This work was funded by the NIH, CIHR, AHA, Novo Nordisk Foundation, and SciLifeLab.

Effect of the Mediterranean diet in cardiovascular prevention.

The Mediterranean diet is the best evidence-based model for cardiovascular prevention. In addition to 2 major randomized secondary prevention trials (Lyon Heart and CORDIOPREV) and 1 primary prevention trial (PREDIMED) that have demonstrated these benefits, there is an unprecedented body of high-quality prospective epidemiological evidence supporting these beneficial effects. The key elements of this traditional pattern are the abundant use of extra-virgin olive oil and high consumption of foods of natural plant-based origin (fruits, vegetables, nuts, and legumes) and fish, along with a reduction in processed meats, red meats, and ultraprocessed products. Moderate consumption of wine, preferably red wine, with meals is an essential element of this traditional pattern. Although removing wine consumption from the Mediterranean diet has been associated with a reduction in its preventive efficacy, doubts have recently arisen about the possible adverse effect of even low or moderate intake of any alcoholic beverages. A new large Spanish trial, UNATI, which will begin in June 2024, will randomize 10 000 drinkers aged 50 to 75 years to abstention or moderate consumption. UNATI aims to answer these doubts with the best possible evidence.

Plasma metabolite profile of legume consumption and future risk of type 2 diabetes and cardiovascular disease.

BACKGROUND: Legume consumption has been linked to a reduced risk of type 2 diabetes (T2D) and cardiovascular disease (CVD), while the potential association between plasma metabolites associated with legume consumption and the risk of cardiometabolic diseases has never been explored. Therefore, we aimed to identify a metabolite signature of legume consumption, and subsequently investigate its potential association with the incidence of T2D and CVD. METHODS: The current cross-sectional and longitudinal analysis was conducted in 1833 PREDIMED study participants (mean age 67 years, 57.6% women) with available baseline metabolomic data. A subset of these participants with 1-year follow-up metabolomics data (n = 1522) was used for internal validation. Plasma metabolites were assessed through liquid chromatography-tandem mass spectrometry. Cross-sectional associations between 382 different known metabolites and legume consumption were performed using elastic net regression. Associations between the identified metabolite profile and incident T2D and CVD were estimated using multivariable Cox regression models. RESULTS: Specific metabolic signatures of legume consumption were identified, these included amino acids, cortisol, and various classes of lipid metabolites including diacylglycerols, triacylglycerols, plasmalogens, sphingomyelins and other metabolites. Among these identified metabolites, 22 were negatively and 18 were positively associated with legume consumption. After adjustment for recognized risk factors and legume consumption, the identified legume metabolite profile was inversely associated with T2D incidence (hazard ratio (HR) per 1 SD: 0.75, 95% CI 0.61-0.94; p = 0.017), but not with CVD incidence risk (1.01, 95% CI 0.86-1.19; p = 0.817) over the follow-up period. CONCLUSIONS: This study identified a set of 40 metabolites associated with legume consumption and with a reduced risk of T2D development in a Mediterranean population at high risk of cardiovascular disease. TRIAL REGISTRATION: ISRCTN35739639.

Plasma metabolite predictors of metabolic syndrome incidence and reversion.

BACKGROUND: Metabolic Syndrome (MetS) is a progressive pathophysiological state defined by a cluster of cardiometabolic traits. However, little is known about metabolites that may be predictors of MetS incidence or reversion. Our objective was to identify plasma metabolites associated with MetS incidence or MetS reversion. METHODS: The study included 1468 participants without cardiovascular disease (CVD) but at high CVD risk at enrollment from two case-cohort studies nested within the PREvención con DIeta MEDiterránea (PREDIMED) study with baseline metabolomics data. MetS was defined in accordance with the harmonized International Diabetes Federation and the American Heart Association/National Heart, Lung, and Blood Institute criteria, which include meeting 3 or more thresholds for waist circumference, triglyceride, HDL cholesterol, blood pressure, and fasting blood glucose. MetS incidence was defined by not having MetS at baseline but meeting the MetS criteria at a follow-up visit. MetS reversion was defined by MetS at baseline but not meeting MetS criteria at a follow-up visit. Plasma metabolome was profiled by LC-MS. Multivariable-adjusted Cox regression models and elastic net regularized regressions were used to assess the association of 385 annotated metabolites with MetS incidence and MetS reversion after adjusting for potential risk factors. RESULTS: Of the 603 participants without baseline MetS, 298 developed MetS over the median 4.8-year follow-up. Of the 865 participants with baseline MetS, 285 experienced MetS reversion. A total of 103 and 88 individual metabolites were associated with MetS incidence and MetS reversion, respectively, after adjusting for confounders and false discovery rate correction. A metabolomic signature comprised of 77 metabolites was robustly associated with MetS incidence (HR: 1.56 (95 % CI: 1.33-1.83)), and a metabolomic signature of 83 metabolites associated with MetS reversion (HR: 1.44 (95 % CI: 1.25-1.67)), both p < 0.001. The MetS incidence and reversion signatures included several lipids (mainly glycerolipids and glycerophospholipids) and branched-chain amino acids. CONCLUSION: We identified unique metabolomic signatures, primarily comprised of lipids (including glycolipids and glycerophospholipids) and branched-chain amino acids robustly associated with MetS incidence; and several amino acids and glycerophospholipids associated with MetS reversion. These signatures provide novel insights on potential distinct mechanisms underlying the conditions leading to the incidence or reversion of MetS.

Should we remove wine from the Mediterranean diet?: a narrative review.

Moderate alcohol intake (or, more specifically, red wine) represents one of the postulated beneficial components of the traditional Mediterranean diet. Many well-conducted nonrandomized studies have reported that light-to-moderate alcohol intake is not only associated with reduced risk of cardiovascular disease, but also of all-cause mortality. Nonetheless, alcohol is an addictive substance imposing huge threats for public health. Alcohol consumption is associated with increased risks of cancer, neurological harms, injuries, and other adverse outcomes. Both the Global Burden of Disease (2016) and Mendelian randomization studies recently supported that the healthiest level of alcohol intake should be 0. Therefore, despite findings of conventional observational epidemiologic studies supporting a potential beneficial role of wine in the context of a healthy Mediterranean dietary pattern, a strong controversy remains on this issue. Age, sex, and drinking patterns are likely to be strong effect modifiers. In this context, a new 4-y noninferiority pragmatic trial in Spain (University of Navarra Alumni Trialist Initiative or "UNATI"), publicly funded by the European Research Council, will randomly assign >10,000 current drinkers (males, 50-70 y; females, 55-75 y) to repeatedly receive advice on either abstention or moderation in alcohol consumption. The recruitment will begin in mid-2024. The primary endpoint is a composite of the main clinical outcomes potentially related to alcohol intake including all-cause mortality. Clinical trial registry number: PREDIMED, ISRCTN35739639, www.predimed.es; SUN, clinicaltrials.gov identifier: NCT02669602, https://medpreventiva.es/i2CmeL.

Association between COVID-19 and outstanding academic performance at a Spanish university.

BACKGROUND: SARS-CoV-2 is the causative agent of COVID-19 identified in December 2019, an acute infectious respiratory disease that can cause persistent neurological and musculoskeletal symptoms such as headache, fatigue, myalgias difficulty concentrating, among others including acute cerebrovascular disease with a prevalence of 1-35%. The aim of this study is to evaluate the impact of COVID-19 in undergraduate students on their academic performance as an indicator of their intellectual ability and performance in a university that maintained 100% face-to-face teaching during the 2020-2021 academic year. METHODS: A total of 7,039 undergraduate students were analyzed in a prospective cohort study at the University of Navarra. A questionnaire including sociodemographic and behavioral questions was sent. PCRs were performed throughout the academic year for the diagnosis of SARS-CoV-2 infection and students' academic results were provided by the academic center, adjusted descriptive and multivariate models were performed to assess the association. RESULTS: A total of 658 (9.3%) participants were diagnosed with COVID-19, almost 4.0% of them achieved outstanding academic results, while uninfected students did so in 7.3%. SARS-CoV-2 infection was associated with a significant decrease in having outstanding academic results (OR = 0.57; 95% CI: 0.38-0.86). CONCLUSION: Having COVID-19 disease, decreased academic performance in undergraduate students. Therefore, it is necessary to prevent infection even in the youngest sections of the population.

Association of alcohol consumption with circulating biomarkers of atrial fibrillation-related pathways in a population at high cardiometabolic risk.

Background: The effect of alcohol consumption on cardiovascular health, including atrial fibrillation risk, remains controversial. Evaluating the association of alcohol consumption with circulating atrial fibrillation-related biomarkers may help better understand the relevant mechanistic underpinnings. Methods: We studied 523 participants from 3 sites for the PREDIMED-Plus study, a weight-loss randomized intervention trial in metabolically unhealthy adults. N-terminal pro-B-type natriuretic protein (NTproBNP), high sensitivity troponin-T (hsTnT), high-sensitivity C-reactive protein (hsCRP), 3-nitrotyrosine (3-NT), and procollagen type 1 carboxy-terminal propeptide (PICP) were measured in fasting serum samples at baseline and years 3 and 5 of follow-up. We calculated alcohol consumption in drinks/day (1 drink = 14 grams alcohol) with validated food frequency questionnaires at each visit. Using multiple linear regression and mixed models we estimated the association of alcohol consumption with log-transformed biomarkers at baseline and longitudinally adjusting for potential confounders. Results: Among 523 participants (mean age: 65 years, 40% female), mean alcohol consumption was 1 drink/day. Cross-sectionally, alcohol consumption was not associated with cardiac biomarker concentrations. Longitudinally, compared to non-consumers, heavy drinkers (≥4 drinks/day) had smaller increases in hsTnT (ß: -0.11, 95%CI: -0.20, -0.01)and PICP (ß: -0.15, 95%CI: -0.30, 0.01) over the 5-year follow-up. In contrast, those who increased alcohol consumption over the 5-year period experienced greater increases in hsCRP (ß: 0.42, 95%CI: 0.11, 0.73) compared to those whose drinking behavior stayed the same. Conclusion: Alcohol consumption was associated with complex changes in circulating biomarkers, including comparatively lower fibrotic and myocardial damage, but higher levels of overall inflammation over time. These results underscore the need for further research to better understand the effects of alcohol on cardiovascular health.

Changes in Coffee Intake, Added Sugar and Long-Term Weight Gain - Results from Three Large Prospective US Cohort Studies.

BACKGROUND: Consumption of both caffeinated and decaffeinated coffee has been reported to attenuate long-term weight gain. Whether the association between coffee consumption and weight gain depends on the addition of sugar, cream, or coffee whitener remains unclear. OBJECTIVE: We aimed to study the associations between changes in coffee consumption, caffeine intake, and weight changes by considering the addition of sugar, cream, or a nondairy coffee whitener. METHODS: We used 3 large prospective cohorts - the Nurses' Health Study (1986 - 2010), Nurses' Health Study II (1991 - 2015) and Health Professional Follow-up Study (1991 - 2014). We applied multivariable linear regression models with robust variance estimators to assess the association of changes in coffee habits within each 4-y interval with concurrent weight changes. Results across the 3 cohorts were pooled using inverse-variance weights. RESULTS: After multivariable adjustment, each 1 cup per day increment in unsweetened caffeinated coffee was associated with a reduction in 4-y weight gain of -0.12 kg (95 % CI: -0.18, -0.05 kg) and of -0.12 kg (95 % CI: -0.16, -0.08 kg) for unsweetened decaffeinated coffee. The habits of adding cream or nondairy coffee whitener were not significantly linked to weight changes. Adding a teaspoon of sugar was associated with a 4-y weight gain of +0.09 kg (0.07, 0.12 kg). Stratified analyses suggested stronger magnitude of the observed associations with younger age and higher baseline BMI. Neither caffeine nor coffee modified the association of adding sugar to any food or beverage with weight changes. CONCLUSIONS: An increase in intake of unsweetened caffeinated and decaffeinated coffee was inversely associated with weight gain. The addition of sugar to coffee counteracted coffee's benefit for possible weight management. To the contrary, adding cream or coffee whitener was not associated with greater weight gain.

Plasma metabolomic profiles associated with mortality and longevity in a prospective analysis of 13,512 individuals.

Experimental studies reported biochemical actions underpinning aging processes and mortality, but the relevant metabolic alterations in humans are not well understood. Here we examine the associations of 243 plasma metabolites with mortality and longevity (attaining age 85 years) in 11,634 US (median follow-up of 22.6 years, with 4288 deaths) and 1878 Spanish participants (median follow-up of 14.5 years, with 525 deaths). We find that, higher levels of N2,N2-dimethylguanosine, pseudouridine, N4-acetylcytidine, 4-acetamidobutanoic acid, N1-acetylspermidine, and lipids with fewer double bonds are associated with increased risk of all-cause mortality and reduced odds of longevity; whereas L-serine and lipids with more double bonds are associated with lower mortality risk and a higher likelihood of longevity. We further develop a multi-metabolite profile score that is associated with higher mortality risk. Our findings suggest that differences in levels of nucleosides, amino acids, and several lipid subclasses can predict mortality. The underlying mechanisms remain to be determined.

Yearly attained adherence to Mediterranean diet and incidence of diabetes in a large randomized trial.

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.

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 (S-Cu) 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 S-Cu levels. Adjusted odds ratios were calculated using multivariate conditional logistic regression models. All participants had S-Cu levels within the reference values, 750 µg/L to 1450 µg/L. Among men, but not among women, the mean S-Cu concentration was higher in cases 1014.1 µg/L than in controls 959.3 µg/L; (p = 0.004). In men, the multivariable-adjusted odds ratio for CVD was 2.36 (95% CI 1.07-5.20 for the comparison of the highest vs. the lowest quartile; p for trend = 0.02), in women, it was 0.43 (95% CI 0.11-1.70; p for trend = 0.165). CONCLUSION: In older Spanish men with high cardiovascular risk, a significant association was observed between high S-Cu 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 S-Cu levels. To confirm this relationship and to analyze the differences observed between men and women, further studies are needed.

Consumption of olive oil and risk of breast cancer in U.S. women: results from the Nurses' Health Studies.

BACKGROUND: Olive oil consumption may reduce breast cancer risk, but it is unclear whether olive oil is beneficial for breast cancer prevention in populations outside of Mediterranean regions, namely in the U.S., where the average consumption of olive oil is low compared with Mediterranean populations. We examined whether olive oil intake was associated with breast cancer risk in two prospective cohorts of U.S. women. METHODS: We used multivariable-adjusted time-varying Cox proportional hazards models to estimate hazard ratios (HR) and 95% confidence interval (CI) for breast cancer among 71,330 (Nurses' Health Study, 1990-2016) and 93,295 women (Nurses' Health Study II, 1991-2017) who were free of cancer at baseline. Diet was assessed by a validated semi-quantitative food frequency questionnaire every 4 years. RESULTS: During 3,744,068 person-years of follow-up, 9,638 women developed invasive breast cancer. The multivariable-adjusted HR (95% CI) for breast cancer among women who had the highest consumption of olive oil (>1/2 tablespoon/d or >7 g/d) compared with those who never or rarely consumed olive oil, was 1.01 (0.93, 1.09). Higher olive oil consumption was not associated with any subtype of breast cancer. CONCLUSION: We did not observe an association between higher olive oil intake and breast cancer risk in two large prospective cohorts of U.S. women, whose average olive oil consumption was low. Prospective studies are needed to confirm these findings and to further investigate whether different varieties of olive oil (e.g., virgin and extra virgin olive oil) may play a role in breast cancer risk.

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.

Behavioral and Personal Characteristics Associated With Risk of SARS-CoV-2 Infection in a Spanish University Cohort.

The aim of this study was to analyze the life habits and personal factors associated with increased severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) risk in a university environment with in-person lectures during the coronavirus disease 2019 (COVID-19) pandemic. To our knowledge, there are no previous longitudinal studies that have analyzed associations of behavioral and personal factors with the risk of SARS-CoV-2 infection on an entire university population. A cohort study was conducted in the 3 campuses of the University of Navarra between August 24, 2020, and May 30, 2021, including 14,496 students and employees; the final sample included 10,959. Descriptive and multivariate-adjusted models were fitted using Cox regression. A total of 1,032 (9.4%) participants were diagnosed with COVID-19 (879 students and 153 employees), almost 50% living with their families. COVID-19 was associated with living in college or residence (hazard ratio (HR) = 1.96, 95% CI: 1.45, 2.64), motor transportation (HR = 1.35, 95% CI: 1.14, 1.61), South American origin (HR = 1.43, 95% CI: 1.20, 1.72), and belonging to Madrid's campus (HR = 3.11, 95% CI: 2.47, 3.92). International students, especially from Latin America, mostly lived in university apartments or shared flats and cohabited with 4-11 people. Living in a big city (Madrid), was a significant risk factor.

Coffee Consumption and the Risk of Metabolic Syndrome in the 'Seguimiento Universidad de Navarra' Project.

(1) Background: Metabolic Syndrome (MetS) affects over a third of the United States population, and has similar prevalence in Europe. Dietary approaches to prevention are important. Coffee consumption has been inversely associated with mortality and chronic disease; however, its relation to the risk of MetS is unclear. We aimed to investigate the association between coffee consumption and incident MetS in the 'Seguimiento Universidad de Navarra' cohort. (2) Methods: From the SUN project, we included 10,253 participants initially free of MetS. Coffee consumption was assessed at baseline, and the development of MetS was assessed after 6 years of follow-up. All data were self-reported by participants. MetS was defined according to the Harmonizing Definition. We used multivariable logistic regression models to estimate odds ratios and 95% confidence intervals for incident MetS according to four categories of coffee consumption: <1 cup/month; ≥1 cup/month to <1 cup/day; ≥1 cup/day to <4 cups/day; ≥4 cups/day. (3) Results: 398 participants developed MetS. Coffee consumption of ≥1 to <4 cups/day was associated with significantly lower odds of developing MetS (multivariable adjusted OR = 0.71, 95% CI (0.50-0.99)) as compared to consumption of <1 cup/month. (4) Conclusions: In a Mediterranean cohort, moderate coffee consumption may be associated with a lower risk of MetS.

Increase from low to moderate, but not high, caffeinated coffee consumption is associated with favorable changes in body fat.

BACKGROUND & AIMS: Higher consumption of coffee and caffeine has been linked to less weight gain and lower body mass index in prospective cohort studies. The aim of the study was to longitudinally assess the association of changes in coffee and caffeine intake with changes in fat tissue, in particular, visceral adipose tissue (VAT) using dual x-ray absorptiometry (DXA). METHODS: In the setting of a large, randomized trial of Mediterranean diet and physical activity intervention, we evaluated 1483 participants with metabolic syndrome (MetS). Repeated measurements of coffee consumption from validated food frequency questionnaires (FFQ) and DXA measurements of adipose tissue were collected at baseline, 6 months, 12 months and 3 years of follow-up. DXA-derived measurements of total and regional adipose tissue expressed as % of total body weight were transformed into sex-specific z-scores. Linear multilevel mixed-effect models were used to investigate the relationship between changes in coffee consumption and corresponding concurrent changes in fat tissue during a 3-year follow-up. RESULTS: After adjustment for intervention group, and other potential confounders, an increase in caffeinated coffee consumption from no or infrequent consumption (≤3 cups/month) to moderate consumption (1-7 cups/week) was associated with reductions in total body fat (Δ z-score: -0.06; 95% CI: -0.11 to -0.02), trunk fat (Δ z-score: -0.07; 95% CI: -0.12 to -0.02), and VAT (Δ z-score: -0.07; 95% CI: -0.13 to -0.01). Neither changes from no or infrequent consumption to high levels of caffeinated coffee consumption (>1 cup/day) nor any changes in decaffeinated coffee consumption showed significant associations with changes in DXA measures. CONCLUSIONS: Moderate changes in the consumption of caffeinated coffee, but not changes to high consumption, were associated with reductions in total body fat, trunk fat and VAT in a Mediterranean cohort with MetS. Decaffeinated coffee was not linked to adiposity indicators. Moderate consumption of caffeinated coffee may be part of a weight management strategy. TRIAL REGISTRATION: The trial was registered at the International Standard Randomized Controlled Trial (ISRCTN: http://www.isrctn.com/ISRCTN89898870) with number 89898870 and registration date of 24 July 2014, retrospectively registered.

Circulating citric acid cycle metabolites and risk of cardiovascular disease in the PREDIMED study.

BACKGROUND AND AIM: Plasma citric acid cycle (CAC) metabolites might be likely related to cardiovascular disease (CVD). However, studies assessing the longitudinal associations between circulating CAC-related metabolites and CVD risk are lacking. The aim of this study was to evaluate the association of baseline and 1-year levels of plasma CAC-related metabolites with CVD incidence (a composite of myocardial infarction, stroke or cardiovascular death), and their interaction with Mediterranean diet interventions. METHODS AND RESULTS: Case-cohort study from the PREDIMED trial involving participants aged 55-80 years at high cardiovascular risk, allocated to MedDiets or control diet. A subcohort of 791 participants was selected at baseline, and a total of 231 cases were identified after a median follow-up of 4.8 years. Nine plasma CAC-related metabolites (pyruvate, lactate, citrate, aconitate, isocitrate, 2-hydroxyglutarate, fumarate, malate and succinate) were measured using liquid chromatography-tandem mass spectrometry. Weighted Cox multiple regression was used to calculate hazard ratios (HRs). Baseline fasting plasma levels of 3 metabolites were associated with higher CVD risk, with HRs (for each standard deviation, 1-SD) of 1.46 (95%CI:1.20-1.78) for 2-hydroxyglutarate, 1.33 (95%CI:1.12-1.58) for fumarate and 1.47 (95%CI:1.21-1.78) for malate (p of linear trend <0.001 for all). A higher risk of CVD was also found for a 1-SD increment of a combined score of these 3 metabolites (HR = 1.60; 95%CI: 1.32-1.94, p trend <0.001). This result was replicated using plasma measurements after one-year. No interactions were detected with the nutritional intervention. CONCLUSION: Plasma 2-hydroxyglutarate, fumarate and malate levels were prospectively associated with increased cardiovascular risk. CLINICAL TRIAL NUMBER: ISRCTN35739639.

Effects of Supplemented Mediterranean Diets on Plasma-Phospholipid Fatty Acid Profiles and Risk of Cardiovascular Disease after 1 Year of Intervention in the PREDIMED Trial.

BACKGROUND: Plasma fatty acids (FAs) have been associated with cardiovascular disease (CVD) risk. Diet and endogenous metabolism influence the FA profile of the plasma phospholipid (PL) fraction. In the PREDIMED trial, we examined 1-year changes in the FA profile of plasma PL according to a nutritional intervention with Mediterranean diets, either supplemented with extra-virgin olive oil (MedDiet + EVOO) or mixed nuts (MedDiet + nuts), in a high cardiovascular risk population. We also analyzed if 1-year changes in PL FAs were associated with subsequent cardiovascular risk. METHODS: We included 779 participants in our case-cohort study: 185 incident cases and 594 participants in the subcohort (including 31 overlapping cases). The end point was the incidence of CVD. We measured the FAs of plasma PL at baseline and after 1 year of intervention. RESULTS: MedDiet + EVOO increased C17:0 and C20:3n9 in linear regression models [ß coefficientperSD : 0.215 (95% CI, 0.032-0.399) and 0.271 (0.107-0.434), respectively] and decreased 16:1n7 and C22:4n6 [ßperSD: -0.239 (95% CI, -0.416 to -0.061) and -0.287 (95% CI, -0.460 to -0.113), respectively] vs the control group. MedDiet + nuts increased C18:3n3 [ßperSD: 0.382 (95% CI, 0.225 - 0.539)], C18:2n6 [ßper SD: 0.250 (95% CI, 0.073 - 0.428)], C18:0 [ßperSD: 0.268 (95% CI, 0.085-0.452)], and C22:0 [ßper SD: 0.216 (95% CI, 0.031-0.402)]; and decreased the sum of six n6 FAs [ßper SD: -0.147 (95% CI, -0.268 to -0.027)] vs the control group. The 1-year increase in C18:2n6 was inversely associated with the subsequent CVD risk (HRperSD: 0.64 (95% CI, 0.44-0.92)). CONCLUSIONS: MedDiet interventions changed n6 FAs and C16:1n7c; other changes were specific for each group: MedDiet + EVOO increased C17:0 and C20:3n9, and MedDiet + Nuts C18:3n3, C18:2n6, C18:0, and C22:0 FAs.