Several studies have tried to analyse the association between all-cause mortality and different risk factors, (especially those which are modifiable, such as smoking, diet or exercise), to develop public health preventive strategies. However, a specific analysis of predictors of premature and late mortality is needed to give more precise recommendations. Considering that there are risk factors which exert an influence on some diseases and not on others, we expect that, similarly, they may have a different impact depending on the timing of mortality, separating premature (<65 years) from late mortality (>65 years). Thus, we prospectively followed-up during a median of 12 years a cohort of 20,272 university graduates comprising an ample range of ages at inception. Time-dependent, covariate-adjusted Cox models were used to estimate adjusted hazard ratios (HR) and their 95 % confidence intervals (CI) for each predictor. The strongest independent predictor of mortality at any age was physical activity which was associated with reduced risk of total, premature and late mortality (range of HRs when comparing the highest vs. the lowest level: 0.24 to 0.48). Specific strong predictors for premature mortality were smoking, HR: 4.22 (95 % CI: 2.42-7.38), and the concurrence of >2 metabolic conditions at baseline, HR: 1.97 (1.10-3.51). The habit of sleeping a long nap (>30 min/d), with HR: 2.53 (1.30-4.91), and poor adherence to the Mediterranean Diet (<3 points in a 0 to 8 score vs. >6 points), with HR: 2.27 (1.08-4.76), were the strongest specific predictors for late mortality. Smoking, diet quality or lifestyles, probably should be differen-tially assessed as specific predictors for early and late mortality. In the era of precision medicine, this approach will allow tailored recommendations appropriate to each person's age and baseline condition.

The aim of this study was to assess the association between alcohol intake and premature mortality (younger than 65 years) and to explore the effect of potential alcohol underreporting by heavy drinkers. We followed-up 20 272 university graduates. Four categories of alcohol intake were considered (abstainer, light, moderate and heavy consumption). Repeated measurements of alcohol intake and updated information on confounders were used in time-dependent Cox models. Potential underreporting of alcohol intake by some heavy drinkers (likely misclassified as light or moderate drinkers) was explicitly addressed in an attempt to correct potential underreporting by using indirect information. During 12 center dot 3 years of median follow-up (interquartile range: 6 center dot 8-15 center dot 0), 226 participants died before their 65th birthday. A higher risk of early mortality was found for the highest category of alcohol intake (>= 50 g/d) in comparison with abstention (multivariable-adjusted hazard ratio (HR) = 2 center dot 82, 95 % CI 1 center dot 38, 5 center dot 79). In analyses of alcohol as a continuous variable, the multivariable-adjusted HR was 1 center dot 17 (95 % CI 1 center dot 08, 1 center dot 26), for each 10 g/d of alcohol. This harmful linear association was present both in uncorrected models and in models corrected for potential underreporting. No significant inverse association between light or moderate alcohol intake and premature mortality was observed, even after correcting for potential misclassification. Alcohol intake exhibited a harmful linear dose-response association with premature mortality (<65 years) in this young and highly educated Mediterranean cohort. Our attempts to correct for potential misclassification did not substantially change these results.

Objectives: Although low-quality diets and smoking are independently associated with higher mortality risk, a joint analysis of both risk factors in relation to mortality has not been sufficiently studied. The aim of this study was to explore the effect modification between level of adherence to a Mediterranean dietary pattern (MedDiet) and smoking status on all-cause, cancer, and cardiovascular mortality.Methods: We conducted a prospective analysis to assess the association between diet and smoking status in the SUN (Seguimiento Universidad de Navarra) cohort study. Deaths were confirmed by review of the National Death Index. Participants were classified into six categories according to the MedDiet (adherence/non-adherence) and their exposure to smoking (never/former/current smoker). Multivariate-adjusted Cox regression models were fitted to estimate hazard ratios (HR) and 95% confidence intervals (CIs) for mortality. During a mean follow-up of 11.5 y (SD 4.5), we observed 18 948 participants (mean age 38.4 y; SD 12.4) and 431 deaths (51.3% cancer deaths). Results: A higher risk for death was found among smokers with a low adherence to the MedDiet (HR, 2.20; 95% CI, 1.45-3.34) compared with never smokers with high adherence to the MedDiet. The P value for supra-multiplicative effect modification was not statistically significant, meaning that the effect of both factors is multiplicative. A higher risk for premature death from cancer was found in smokers and in those nonadherent with the MedDiet.Conclusion: Smoking and poor adherence to the MedDiet exerted a multiplicative effect in increasing allcause mortality and cancer-related mortality in a Spanish population of university graduates.(c) 2022 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Background: Most of the available epidemiological evidence on alcohol and chronic disease agrees on recommending alcohol abstention to young people, but some controversy exists about the most appropriate recommendation for alcohol abstention for people of older ages. A growing body of evidence suggests that the pattern of alcohol consumption is likely to be a strong effect modifier. The Mediterranean Alcohol Drinking Pattern (MADP) represents a score integrating several dimensions of drinking patterns (moderation, preference for red wine, drinking with meals, and avoiding binge drinking). Our aim was to clarify this issue and provide more precise recommendations on alcohol consumption. Methods: We prospectively followed-up 2226 participants (men older than 50 years and women older than 55 years at baseline) in the Seguimiento Universidad de Navarra (SUN) cohort. We classified participants into three categories of adherence to the MADP score (low, moderate, and high), and we added a fourth category for abstainers. Cox regression models estimated multivariable-adjusted hazard ratios (HR) of all-cause death and 95% confidence intervals (CI) using low MADP adherence as the reference category. Results: The strongest reduction in risk of mortality was observed for those with high adherence to the MADP, with an HR of 0.54 (95% CI: 0.37-0.80). The moderate adherence group (HR = 0.65, 95% CI: 0.44-0.96) and the abstention group (HR = 0.60, 95% CI: 0.36-0.98) also exhibited lower risks of mortality than the low MADP adherence group. Conclusions: based on the available evidence, a public health message can be provided to people older than 50 years as follows: among those who drink alcohol, high adherence to the MADP score could substantially reduce their risk of all-cause mortality.

To assess the efficacy of three lifestyle interventions on the reduction of liver fat content and metabolic syndrome (MetS), and whether such reductions would influence renal outcomes, we conducted a randomized controlled trial on 128 participants with MetS and non-alcoholic fatty liver disease (NAFLD), as well as available data on estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatine ratio (UACR). Patients were randomized in 1:1:1 ratio to either Conventional Diet, Mediterranean diet (MD)-high meal frequency, and MD-physical activity groups. Each intervention aimed at reducing caloric intake by 25%-30% of baseline intake and increase energy expenditure by 400 kcal/70 kg. Patients attended regular visits and were followed-up for 6 months. Increased albuminuria was present in 13.3% of patients, while 32.8% showed hyperfiltration. UACR reduction was associated with higher levels of UACR at baseline but not with changes in liver fat. eGFR decreased in patients presenting hyperfiltration at baseline and was associated with reduction in liver fat and insulin resistance, as well as with increase in energy expenditure (R-2 = 0.248, p = 0.006). No significant differences were observed between the three treatment groups. In patients with NAFLD and MetS, energy expenditure significantly reduced hepatic fat accumulation and insulin resistance, which reduced glomerular hyperfiltration. Increased albuminuria was reduced, but it was not associated with reduced liver fat.

Purpose The health benefits of the Mediterranean diet (MedDiet) have been widely studied. However, controversy remains for one of its components: alcohol intake. We aimed to assess the joint effect of adherence to the MedDiet and alcohol-drinking pattern on all-cause mortality. Methods We used data from 20,506 subjects from a prospective cohort of Spanish university graduates, the Seguimiento Universidad de Navarra (SUN) cohort. Adherence to the MedDiet was operationalized using four different dietary indexes and then categorized in low or high adherence, according to the median score. Alcohol-drinking pattern was evaluated with the previously defined the Mediterranean alcohol-drinking pattern (MADP), grouped into three categories of adherence (low, moderate and high adherence) and a fourth category for abstainers. The outcome was all-cause mortality. Results During a median follow-up of 12.1 years, we observed 460 deaths. No statistically significant supra-multiplicative interaction between the two exposures was found. Low adherence to both the MedDiet and MADP was associated with higher all-cause mortality compared to high adherence to both exposures [multivariable-adjusted hazard ratio (HR) = 2.02, 95% confidence interval (CI): 1.33-3.07]. Similar results were found for cancer mortality and cardiovascular mortality. Conclusions Although the combined effect of the MedDiet and MADP was not significantly higher than the product of their individual effects, a low adherence to both the MedDiet and MADP was associated with higher rates of all-cause mortality. This report also shows the usefulness of the dietary pattern approach applied to alcohol intake and of including the drinking pattern as another component of the MedDiet.

Objective: To assess the association between pregestational BMI and offspring's risk of overweight/obesity after accounting for the most important confounders, especially maternal smoking habit. Design: Prospective cohort study. Setting: The Seguimiento Universidad de Navarra (SUN) study is a prospective cohort of Spanish graduates with more than 22 000 participants nationwide. Recruitment started in 1999, and it is permanently open. Data on diet, lifestyle and clinical diagnoses are collected at baseline and every 2 years. Participants: Women from the SUN cohort who reported at least one pregnancy during follow-up (n 3496) were invited to this study. Among them, 1527 agreed to participate and completed an additional more detailed online questionnaire on their pregnancy history and their offspring's nutritional status. Results: After excluding 165 children, we analysed data of 2791 participants born to 1485 mothers and observed that each 5 kg/m(2) increase in pregestational BMI was associated with a 0 center dot 22 (95 % CI 0 center dot 15, 0 center dot 29) higher z-score in offspring's BMI and higher risk of overweight/obesity (multivariable-adjusted relative risk (RR) 1 center dot 57 (95 % CI 1 center dot 39, 1 center dot 77)) in childhood or adolescence. Furthermore, we observed stronger association in children born to smoker mothers (RR 1 center dot 91; 95 % CI 1 center dot 48, 2 center dot 46) than from non-smoker mothers (RR 1 center dot 51; 95 % CI 1 center dot 31, 1 center dot 73) (P-for interaction = 0 center dot 02). Conclusions: We found a synergistic interaction between pregestational BMI and maternal smoking habit on offspring's z-score of the BMI and in their risk of overweight/obesity. Although further research is needed to analyse dose-response relationships, these findings reinforce the importance of promoting healthy lifestyles in pregnant women in order to prevent childhood obesity.

Objective: To assess the association between pregestational BMI and offspring's risk of overweight/obesity after accounting for the most important confounders, especially maternal smoking habit. Design: Prospective cohort study. Setting: The Seguimiento Universidad de Navarra (SUN) study is a prospective cohort of Spanish graduates with more than 22 000 participants nationwide. Recruitment started in 1999, and it is permanently open. Data on diet, lifestyle and clinical diagnoses are collected at baseline and every 2 years. Participants: Women from the SUN cohort who reported at least one pregnancy during follow-up (n 3496) were invited to this study. Among them, 1527 agreed to participate and completed an additional more detailed online questionnaire on their pregnancy history and their offspring's nutritional status. Results: After excluding 165 children, we analysed data of 2791 participants born to 1485 mothers and observed that each 5 kg/m2 increase in pregestational BMI was associated with a 0·22 (95 % CI 0·15, 0·29) higher z-score in offspring's BMI and higher risk of overweight/obesity (multivariable-adjusted relative risk (RR) 1·57 (95 % CI 1·39, 1·77)) in childhood or adolescence. Furthermore, we observed stronger association in children born to smoker mothers (RR 1·91; 95 % CI 1·48, 2·46) than from non-smoker mothers (RR 1·51; 95 % CI 1·31, 1·73) (Pfor interaction = 0·02). Conclusions: We found a synergistic interaction between pregestational BMI and maternal smoking habit on offspring's z-score of the BMI and in their risk of overweight/obesity. Although further research is needed to analyse dose-response relationships, these findings reinforce the importance of promoting healthy lifestyles in pregnant women in order to prevent childhood obesity. Trial registration: ClinicalTrials.gov NCT02669602.