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Background/Objectives: Whether habitual dietary omega-3 fatty acid intake is reflected in circulating biomarkers of atrial fibrillation (AF)-related pathways is unclear. We assessed whether usual dietary intake of n-3 fatty acids—considered as total, marine-derived, or non-marine-derived—was associated with the trajectories of five serum markers that reflect AF-related mechanistic pathways [N-terminal pro-B-type natriuretic peptide (NT-pro-BNP), high-sensitivity troponin T (hs-TnT), high-sensitivity C-reactive protein (CRP), the C-terminal propeptide of type-I procollagen (PICP), and 3-nitrotyrosine (3-NT)] over 5 years of follow-up. Methods: In 510 participants of the PREDIMED-Plus trial (older Spanish adults with metabolic syndrome), we measured plasma NT-pro-BNP, hs-TnT, CRP, PICP, and 3-NT at baseline and after 3 and 5 years. Energy-adjusted omega-3 intake was assessed with a validated 143-item food-frequency questionnaire. Cross-sectional and 5-year longitudinal associations according to tertiles of omega-3 fatty acid intake were estimated with linear regression and mixed-effects models. Results: Median total omega-3 intake was 2.0 g/day. Total omega-3 intake was not associated with any biomarker, neither cross-sectionally nor longitudinally. Marine omega-3 was directly associated cross-sectionally with 3-NT (highest vs. lowest tertile +28.4%, 95% CI 5.5 to 56.2; p-trend = 0.014) but not longitudinally. Moderate baseline non-marine omega-3 fatty acid intake was associated with a decrease in PICP after 5 years of follow-up. Conclusions: Overall, habitual total omega-3 fatty acid intake was not associated with circulating AF-related pathways. The sporadic association between marine omega-3 fatty acid intake and 3-NT in the cross-sectional assessment and the isolated non-linear association between baseline non-marine omega-3 fatty acid intake and PICP after 5 years warrant further investigation.

Background The Mediterranean diet (MedDiet) is strongly associated with lower cardiovascular disease (CVD) risk and is particularly rich in polyphenols, bioactive compounds with potential cardioprotective effects. However, the specific phenolic compounds underlying these benefits remain unclear. The objective of this study was to develop a urinary multi-metabolite signature of phenolic compounds reflecting MedDiet adherence and to evaluate its prospective association with CVD risk. Methods In a case–cohort nested study within the PREDIMED trial, we measured 62 phenolic metabolites in spot urine by liquid chromatography–high‐resolution mass spectrometry at baseline and after 1 year in 1180 individuals: 653 incident CVD cases (stroke, myocardial infarction, CVD death, or heart failure) and a random subcohort of 603 participants (76 overlapping cases). We applied elastic net regression to derive a urinary multi-metabolite signature prospectively associated with MedDiet adherence, measured by the validated 14-item Mediterranean Diet Adherence Screener (MEDAS). Multivariable Cox models were used to estimate hazard ratios (HRs) of CVD by levels of the multi-metabolite signature. Results The urinary multi-metabolite signature, comprising eight phenolic compounds selected by elastic net regression, was inversely associated with CVD risk in a dose–response pattern (HR per SD = 0.80 (0.68–0.94); HR Q4 vs Q1 = 0.48 (0.30–0.78); p -trend = 0.002). The metabolites included in the signature were derived from foods typical of the MedDiet, particularly virgin olive oil, wine, nuts, fruits, and vegetables. After 1 year, MedDiet interventions significantly increased urolithin A metabolites (derived from walnuts) compared to the control group. Conclusions We identified a urinary multi-metabolite signature of MedDiet adherence that is prospectively associated with lower CVD incidence. These findings support that polyphenols derived from the MedDiet showed inverse associations with cardiovascular outcomes. Trial registration The study was registered with the International Standard Randomized Controlled Trial Number (ISRCTN) 35739639.

Background: Peripheral artery disease (PAD) is a major vascular condition often overlooked in prevention strategies. We aimed to evaluate the association between cardiovascular health, measured by Life’s Simple 7 (LS7), and the risk of PAD in a high-risk Mediterranean population. Methods: This prospective analysis included 7122 participants from the PREDIMED study (Prevención con Dieta Mediterránea) at high cardiovascular risk but free of cardiovascular disease at baseline. LS7 scores (0–14 points) were calculated using seven metrics: smoking status, body mass index, physical activity, blood pressure, total cholesterol, glucose metabolism, and adherence to the Mediterranean diet. Participants were categorized into inadequate (0–5), average (6–8), and optimal (9–14) cardiovascular health. Multivariable Cox regression models and Nelson–Aalen curves assessed the association between LS7 and PAD incidence over a median 4.8-year follow-up. A meta-analysis combining these results with three prior studies was also performed. Results: A total of 87 incident PAD cases were identified. Compared to participants with inadequate cardiovascular health, those with average and optimal LS7 scores exhibited significantly lower PAD risk (adjusted hazard ratio [HR] 0.37; 95% confidence interval [CI]: 0.22–0.61, and HR 0.25; 95% CI: 0.10–0.65, respectively). Each one-point increase in the LS7 score (range 0 to 14) was associated with an 22% lower PAD risk (HR 0.78; 95% CI: 0.68–0.90). The meta-analysis yielded a pooled HR of 0.81 (95% CI: 0.76–0.87), confirming consistent inverse associations across populations. Conclusions: Greater adherence to LS7 metrics is associated with a significantly reduced risk of PAD in high-risk Mediterranean individuals. Promoting LS7 adherence may represent an effective strategy for preventing both cardiovascular disease and PAD.

The metabolic syndrome (MetS) is associated with increased cardiovascular morbidity and mortality. Characterization of cardiac structural and functional abnormalities due to the MetS can help recognize individuals who would benefit the most from preventive interventions. Transthoracic echocardiography (TTE) provides an opportunity to identify those abnormalities in a reproducible and cost-efficient manner. In research settings, implementation of protocols for the acquisition and analysis of TTE images are key to ensure validity and reproducibility, thus facilitating answering relevant questions about the association of the MetS with cardiac alterations. The Palma Echo Platform (PEP) is a coordinated network that is built up to evaluate the underlying structural and functional cardiac substrate of participants with MetS. Repeated TTE will be used to evaluate 5-year changes in the cardiac structure and function in a group of 565 individuals participating in a randomized trial of a lifestyle intervention for the primary prevention of cardiovascular disease. The echocardiographic studies will be performed at three study sites, and will be centrally evaluated at the PEP core laboratory. Planned analyses will involve evaluating the effect of the lifestyle intervention on cardiac structure and function, and the association of the MetS and its components with changes in cardiac structure and function. Particular emphasis will be placed on evaluating parameters of left atrial structure and function, which have received more limited attention in past investigations. This PEP will be available for future studies addressing comparable questions. In this article we describe the protocol of a central echocardiography laboratory for the study of functional and structural alterations of the MetS.

Atrial fibrillation has been associated with cognitive impairment. Whether subclinical abnormalities in atrial function and substrate predisposing to atrial fibrillation impact cognitive function has received limited attention. We tested associations of echocardiographic markers of atrial structure and function with cognitive function and decrease in 510 participants with obesity and metabolic syndrome (mean age SD of 64.4 [5.2] years in men and 66.5 [3.9] years in women). Left atrial (LA) markers (volume index, emptying fraction, strain, function index, and stiffness index) were estimated based on transthoracic echocardiography. General cognitive functioning (Mini-mental state examination), verbal ability (verbal fluency test), memory and attention (Digit Span Tests), and processing speed and executive function (Trail-Making Tests A and B) were assessed at baseline and at 2-year follow-up. Multiple linear regression was used to test associations of atrial markers (modeled in SD units) with baseline and 2-year changes in cognitive scores adjusted for demographic and health covariates. LA structure and function were not associated with cognitive function at baseline. Larger LA volume index (standardized β [95% confidence interval] −0.13 [−0.22 to −0.03]), lower peak longitudinal strain (−0.11 [−0.20 to −0.01]), and higher stiffness index (−0.18 [−0.28 to −0.08]) were associated with 2-year worsening in Trail-Making Test A. Strain measurements were also associated with a 2-year change in the Controlled Oral Word Association Test. In conclusion, overall, adverse markers of LA structure and function were associated with 2-year detrimental executive function-related cognitive changes in a sample of participants at high risk for cardiovascular disease, highlighting LA substrate as a potential risk factor for cognitive decrease and dementia.

Men and women tend to follow different dietary patterns, but this is often disregarded when relating diet to health outcomes. Our aim was to analyze (poly)phenol intake patterns and their association with cardiovascular risk (CVR) according to sex. 6633 participants were included in this cross-sectional study. The intake of 26 (poly)phenol classes/subclasses was included in the factor analysis obtaining for the total sample, men and women. Linear regression models were performed with the estimation of absolute CVR (Framingham equation) as the dependent variable, and each (poly)phenol pattern categorized into quintiles as the independent variable. For the total sample, (poly)phenol pattern three (olives and olive oil) was positively associated with CVR (βQ5vs.Q1 = 2.71%, 95% CI = 1.45, 3.96), presenting a higher risk of diabetes prevalence, smoking more and consuming more salt. In men, pattern three (olives and olive oil) was also positively associated with CVR (βQ5vs.Q1 = 3.17%, 95% CI = 1.58, 5.64), exhibiting higher prevalence of diabetes and higher sodium intake. Also in men, pattern four (coffee) was positively associated (βQ5vs.Q1 = 1.99 %, 95% CI = 0.26, 3.73) presenting a higher diabetes and current smokers prevalence and higher sugar intake. In women, greater adherence to pattern four (coffee) was associated with higher CVR (βQ5vs.Q1 = 2.19%, 95% CI = 1.05, 3.34). We found sex differences in (poly)phenol intake patterns and in their associations with CVR. These differences may be explained by the fact that subjects at higher risk at baseline may be motivated to improve their dietary habit (reverse causality). The trial was registered at the International Standard Randomized Controlled Trial (ISRCTN89898870).

The coronavirus disease 2019 (COVID-19) has serious physiological and psychological consequences. The long-term (>12 weeks post-infection) impact of COVID-19 on mental health, specifically in older adults, is unclear. We longitudinally assessed the association of COVID-19 with depression symptomatology in community-dwelling older adults with metabolic syndrome within the framework of the PREDIMED-Plus cohort. Participants ( = 5486) aged 55-75 years were included in this longitudinal cohort. COVID-19 status (positive/negative) determined by tests (e.g. polymerase chain reaction severe acute respiratory syndrome coronavirus 2, IgG) was confirmed via event adjudication (410 cases). Pre- and post-COVID-19 depressive symptomatology was ascertained from annual assessments conducted using a validated 21-item Spanish Beck Depression Inventory-II (BDI-II). Multivariable linear and logistic regression models assessed the association between COVID-19 and depression symptomatology. COVID-19 in older adults was associated with higher post-COVID-19 BDI-II scores measured at a median (interquartile range) of 29 (15-40) weeks post-infection [fully adjusted = 0.65 points, 95% confidence interval (CI) 0.15-1.15; = 0.011]. This association was particularly prominent in women ( = 1.38 points, 95% CI 0.44-2.33, = 0.004). COVID-19 was associated with 62% increased odds of elevated depression risk (BDI-II ≥ 14) post-COVID-19 when adjusted for confounders (odds ratio; 95% CI 1.13-2.30, = 0.008). COVID-19 was associated with long-term depression risk in older adults with overweight/obesity and metabolic syndrome, particularly in women. Thus, long-term evaluations of the impact of COVID-19 on mental health and preventive public health initiatives are warranted in older adults.

The burden of depression is increasing worldwide, specifically in older adults. Unhealthy dietary patterns may partly explain this phenomenon. In the Spanish PREDIMED-Plus study, we explored (1) the cross-sectional association between the adherence to the Prime Diet Quality Score (PDQS), an a priori-defined high-quality food pattern, and the prevalence of depressive symptoms at baseline (cross-sectional analysis) and (2) the prospective association of baseline PDQS with changes in depressive symptomatology after 2 years of follow-up. After exclusions, we assessed 6612 participants in the cross-sectional analysis and 5523 participants in the prospective analysis. An energy-adjusted high-quality dietary score (PDQS) was assessed using a validated FFQ. The cross-sectional association between PDQS and the prevalence of depression or presence of depressive symptoms and the prospective changes in depressive symptoms were evaluated through multivariable regression models (logistic and linear models and mixed linear-effects models). PDQS was inversely associated with depressive status in the cross-sectional analysis. Participants in the highest quintile of PDQS (Q5) showed a significantly reduced odds of depression prevalence as compared to participants in the lowest quartile of PDQS (Q1) (OR (95 %) CI = 0·82 (0·68, 0·98))). The baseline prevalence of depression decreased across PDQS quintiles (P for trend = 0·015). A statistically significant association between PDQS and changes in depressive symptoms after 2-years follow-up was found (β (95 %) CI = −0·67 z-score (–1·17, −0·18). A higher PDQS was cross-sectionally related to a lower depressive status. Nevertheless, the null finding in our prospective analysis raises the possibility of reverse causality. Further prospective investigation is required to ascertain the association between PDQS and changes in depressive symptoms along time.

Background and aimsPrevious studies have shown beneficial associations between fruit and vegetable (FV) consumption and cardiometabolic risk factors. However, variety in FV, which may play an important role on cardiovascular health due to the different nutrient and phytochemical content among the different groups and subgroups of FV has been poorly investigated. We longitudinally investigated associations between 1-year changes in variety and quantity of FV and concurrent changes in cardiometabolic risk factors in elderly subjects with overweight/obesity and metabolic syndrome.Methodsa one-year data longitudinal analysis of 6647 PREDIMED-plus study participants (48% women) was conducted. Data were collected at baseline, six months and 1-year of follow-up. Variety and quantity of FV were estimated using a food frequency questionnaire and continuous scores for variety were created based on items/month of FV. Linear mixed-models adjusted for potential confounders were performed to estimate associations (β-coefficients and 95% confidence interval) between 1-year changes in FV variety and/or quantity and concurrent changes in cardiometabolic risk factors.ResultsTwo points increment in the FV variety score over one year was associated with a concurrent decrease in glucose (−0.33 mg/dL (0.58, −0.07)), body weight (−0.07 kg (−0.13, −0.02)) and waist circumference (WC) (−0.08 cm (−0.16, −10.01)). An increment of 100 g/d of FV over one year was associated with a concurrent decrease in triglycerides (−0.50 mg/dL (−0.93, −0.08)), glucose (−0.21 mg/dL (−0.32, −0.11)), body weight (−0.11 kg (−0.15, −0.07)) and WC (−0.10 cm (−0.14, −0.06)) over 1-year. Changes in FV consumption which led to higher quantity and variety over one year were associated with downward changes in glucose (−1.26 mg/dL (−2.09, −0.43)), body weight (−0.40 kg (−0.58, −0.23)) and WC (−0.50 cm (−0.73, −0.28)).ConclusionGreater variety, in combination with higher quantity of FV was significantly associated with a decrease in several cardiometabolic risk factors among elderly subjects at high cardiovascular risk.

It remains unclear whether caffeinated beverages could have deleterious renal effects in elderly population with underlying comorbid conditions. We investigated the associations between coffee, tea, or caffeine intake and 1-year changes in glomerular filtration rate (eGFR) in a large Spanish cohort of overweight/obese elderly with metabolic syndrome (MetS). This prospective analysis includes 5851 overweight/obese adults (55–75 years) with MetS from the PREDIMED-Plus study. We assessed coffee, tea, and caffeine consumption from a validated food-frequency questionnaire and creatinine-based eGFR using the Chronic Kidney Disease Epidemiology Collaboration equation. Multivariate-adjusted regression models were applied to test associations between baseline coffee, tea, or caffeine intake and 1-year eGFR changes. Caffeinated coffee (> 2 cups/day) and tea (at least 1 cup/day) drinkers had 0.88 and 0.93 mL/min/1.73 m 2 greater eGFR decrease respectively, compared to those with less than 1 cup/day of coffee consumption or non-tea drinkers. Furthermore, caffeinated coffee consumption of > 2 cups/day was associated with 1.19-fold increased risk of rapid eGFR decline > 3 mL/min/1.73 m 2 (95% CI 1.01–1.41). Similarly, individuals in the highest (median, 51.2 mg/day) tertile of caffeine intake had a 0.87 mL/min/1.73 m 2 greater eGFR decrease. Decaffeinated coffee was not associated with eGFR changes. In conclusion, higher consumption of caffeinated coffee, tea, and caffeine was associated with a greater 1-year eGFR decline in overweight/obese adults with MetS.