BUSCADOR RECOLECTA

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., This project was made possible by funding from the Spanish Government-Instituto de Salud Carlos III, and the European Regional Development Fund (FEDER) (RD 06/0045, CIBER-OBN, Grants PI10/02658, PI10/02293, PI13/00615, PI14/01668, PI14/01798, PI14/01764, PI17/01795, PI18/00631, PI20/00564 and G03/140), from the Government of Navarra (27/2011, 45/2011, 122/2014), from the National Plan on Drugs (2020/021) as well as from the University of Navarra.

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., Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. The SUN project has received funding from the Spanish Government-Instituto de Salud Carlos III, the European Regional Development Fund (FEDER) (RD 06/0045, CIBER-OBN, Grants PI10/02658, PI10/02293, PI13/00615, PI14/01668, PI14/01798, PI14/01764, PI17/01795, PI20/00564, PI23/01332, and G03/140), the Navarra Regional Government (27/2011, 45/2011, 122/2014), the National Plan on Drugs (2020/021), and the University of Navarra.

Objectives: Novel findings indicate links between unhealthy lifestyles and depression based on active inflammatory processes. Thus, identifying participants with poor habits could reveal differences in trends of incident depression. This study aimed to examine the association between an objective lifestyle assessment, as measured by the Lifestyle and Well-Being Index (LWB-I), and incident depression in healthy participants of a Spanish cohort. Study design: This was a longitudinal analysis of a subsample of 10,063 participants from the Seguimiento Universidad de Navarra cohort study. Methods: Group comparisons and Cox proportional hazard models were conducted using the LWB-I, which categorizes the sample into groups with healthy and unhealthy lifestyles and well-being. The main outcome was incident depression as well as secondary outcomes. Results: Those classified to the transition category of LWB-I were associated with a hazard ratio of 0.67 (95% confidence interval: 0.52-0.87), and those in the excellent category showed a hazard ratio of 0.44 (95% confidence interval: 0.33-0.58), which in both groups reflects a significantly lower risk of incident depression compared with the group including those classified in the poor LWB-I level. Moreover, the available sensitivity analyses concerning time of depression diagnosis or antidepressant treatment further supported the role of nutrition and physical activity on incident depression. Interestingly, throughout the follow-up, incident depression was inversely related to healthier daily habits as measured by the LWB-I. Conclusions: A global assessment of lifestyles such as the LWB-I provides valuable insight into the complex relationship between lifestyle factors and their link to depression risk., Funding was received from the Spanish Government-Instituto de Salud Carlos III , the European Regional Development Fund (FEDER; RD 06/0045, CIBER-OBN, grants PI10/02658, PI10/02293, PI13/00615, PI14/01668, PI14/01798, PI14/01764, PI17/01795, PI20/00564 and G03/140), the Navarra Regional Government (27/2011, 45/2011, 122/2014), the National Plan on Drugs (2020/021), and the University of Navarra.

Current dietary patterns are negatively affecting both the environment and people’s health.
Healthy diets are generally more environmentally friendly. However, few studies have focused on
the health consequences of diets with low environmental impact. We analyzed differences in the
dietary composition (types of food, macro- and micro-nutrients) of those diets with high and low
environmental impact, according to greenhouse gas emission and resources use (water, land and
energy) using data from a Spanish cohort (17,387 participants), collected by means of a validated food
frequency questionnaire. Cox analyses were used to assess the association of dietary environmental
impact with total mortality risk. At a given level of energy intake, diets with lower environmental
impact contained higher amounts of plant-based foods and lower levels of animal-derived products.
Less polluting diets involved higher amounts of polyunsaturated fats and dietary fiber and lower
amounts of saturated fats and sodium. However, diets associated with less environmental damage
also contained more added sugars, but lower levels of vitamin B12, zinc and calcium. We did not
detect any association between dietary environmental impact and risk of mortality. Diets should
not only produce minimal environmental impact, but the maximum overall benefits for all key
dimensions encompassed in sustainable diets.

Alcohol drinking patterns may determine the risk of hypertension and may also modify the detrimental effect of high alcohol intake. We prospectively evaluated the effect of the Mediterranean alcohol-drinking pattern and its interaction with the amount of alcohol consumed on the incidence of arterial hypertension. In the Seguimiento Universidad de Navarra (SUN) cohort, we followed-up 13,805 participants, all of them initially free of hypertension, during a maximum period of 16 years. Information about diet, chronic diseases, lifestyle and newly diagnosed hypertension was collected using validated questionnaires. We used a 7-item score (0 to 9 points) that jointly considered moderate alcohol consumption, distributed over the week, with meals, and a preference for red wine and avoidance of binge-drinking. During 142,404 person-years of follow-up, 1443 incident cases of hypertension were identified. Low adherence (score < 2) to the Mediterranean alcohol-drinking pattern was significantly associated with a higher incidence of hypertension (multivariable-adjusted hazard ratio 1.81, 95% confidence interval 1.09-2.99) as compared to the high-adherence (score > 7) category. Among alcohol consumers, a high adherence to the MADP is associated with a lower incidence of hypertension. Compared with abstinence, a high adherence did not seem to differ regarding its effect on hypertension risk.

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.

The global incidence of type 2 diabetes (T2D) has been steadily increasing in recent decades. The Mediterranean dietary pattern has shown a preventive effect on the risk of T2D. Evaluating the association between bioactive compounds such as phenolic compounds (PC) in a Mediterranean cohort could help to better understand the mechanisms implicated in this protection. We evaluated the association between dietary intake of PC and the risk of T2D in a relatively young cohort of 17,821 Spanish participants initially free of T2D, through the University of Navarra Follow-up Project (Seguimiento Universidad de Navarra or SUN cohort) after 10 years of median follow-up using time-dependent Cox models. Intake of PC was estimated at baseline and repeatedly at 10-year follow-up using a 136-item validated food frequency and the Phenol-Explorer database. The incidence of T2D was identified by a biennial follow-up, and only medically confirmed cases were included. During 224,751 person-years of follow-up, 186 cases of T2D were confirmed. A suboptimal intake of stilbenes was independently associated with a higher risk of T2D in subjects over 50 years (HR: 1.75, 95% CI: 1.06-2.90, p value < 0.05) after adjusting for potential confounders. Our results suggest that a moderate-high intake of stilbenes can decrease the risk of developing T2D in subjects over 50 years in our cohort.

Background and aimsFront-of-Pack (FoP) nutrition labelling has been established as a policy, empowering consumers to choose healthy food options for preventing diet-related non-communicable diseases. This study aimed to evaluate the association between the nutrient profile underlying the Chilean warning label score and all-cause mortality and to conduct a calibration with the Nutri-Score in a large cohort of Spanish university graduates. Materials and methodsThis prospective cohort study analysed 20,666 participants (8,068 men and 12,598 women) with a mean (standard deviation) age of 38 years (+/- 12.4) from the SUN cohort. Dietary food intake was assessed by a validated semi-quantitative food-frequency questionnaire at baseline and after 10 years of follow-up. The warning label score was calculated by considering the threshold of nutrients (sugar, saturated fat, and sodium) and energy density per 100 g/ml of product, as established by Chilean Legislation. Participants were classified according to quartiles of consumption of daily label score: Q1 (<= 5.0), Q2 (>5.0-7.1), Q3 (>7.1-9.8), and Q4 (>9.8). Time-dependent, multivariable-adjusted Cox models were applied. To compare the performance of the warning label score and Nutri-Score to predict mortality, we used the Akaike information criterion (AIC) and Bayesian information criterion (BIC) methods. ResultsDuring a median of 12.2 years of follow-up, 467 deaths were identified. A higher score in the warning label values (lower nutritional quality) was associated with an increased risk of all-cause mortality [HR (95% CI) Q4 vs. Q1: 1.51 (1.07-2.13); p-trend = 0.010] and cancer mortality [HR (95% CI) Q4 vs. Q1: 1.91 (1.18-3.10); p-trend = 0.006]. However, no statistically significant association was found for cardiovascular mortality. Furthermore, the warning label score and Nutri-Score exhibited comparable AIC and BIC values, showing similar power of prediction for mortality. ConclusionA diet with a higher warning label score (>9.8 per day) was a good predictor of all cases and cancer mortality in a large Spanish cohort of university graduates. Also, the warning label score was capable to predict mortality as well as the Nutri-Score. Our findings support the validity of the warning label score as a FoP nutrition labelling policy since it can highlight less healthy food products.

(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.

Diet and physical activity (PA) have been studied extensively in epidemiology as single or combined lifestyle factors; however, their interaction has not been studied thoroughly. Studying potential synergisms between lifestyle components with a comprehensive interaction analysis, including additive measures of interaction, provides key insights into the nature of their joint effect and helps target interventions more effectively. First, a comprehensive review was conducted to assess the potential research gap regarding reported interaction analyses conducted in studies assessing the Mediterranean diet (MedDiet) in combination with PA on all-cause mortality. Thereafter, we prospectively assessed the joint association of the MedDiet with PA on all-cause mortality in the Seguimiento Universidad de Navarra (SUN) cohort, followed by both multiplicative and additive interaction analyses. The conjoint effect of low adherence to the MedDiet and low PA observed an increased risk greater than the individual risk factors, suggesting a potential additive interaction or synergism between both exposures, with relative risk due to interaction (RERI) and (95 % confidence interval (95 % CI)) = 0.46 (-0.83 to 1.75) and attributable proportion (95 % CI) due to interaction of 36 % (-0.62, 1.34). No multiplicative interaction was detected. Studying interactions between lifestyle factors, such as the MedDiet and PA, is particularly relevant given the current research gaps in studying the complexities of combined aspects of lifestyle in comparison with isolated behaviours. Our findings underline the important public health message of adhering to both the MedDiet and PA for the prevention of premature mortality.

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.

Causal reductions in cardiovascular disease (CVD) with the Mediterranean diet (MedDiet) are supported by randomized trials, but the ability of nonrandomized studies to provide causal inferences in nutritional epidemiology is questioned. The "Seguimiento Universidad de Navarra" (SUN) project, conducted during 1999-2019 with 18,419 participants, was used to try to refute non-causal explanations for the inverse association found between adherence to the MedDiet and reduced CVD risk. A framework of different analytical strategies is proposed: alternative definitions of the exposure, exploration of residual confounding, resampling methods, depiction of absolute risks across the follow-up period, trial emulation, and negative controls. Additionally, we calculated the rate advancement period (RAP). We found that one standard deviation increase in the most frequently used MedDiet score was associated with a 29% relative reduction in CVD risk (95% Confidence Interval [CI] 14-41%), which is almost identical to that found in 2 randomized trials. The RAP of CVD would be postponed by an average of 7.9 years (95% CI: 1.6 to 14.2 years) by switching from low (MDS = 0 to2) to high (MDS = 7 to 9) adherence to the MedDiet in the fully adjusted model. Sensitivity analyses, graphical representations of absolute risks, trial emulation, and negative controls also supported causality. In conclusion, a framework of analytical approaches supported the causal effect of the MedDiet on CVD prevention using observational data. Similar methodology could be applied for causal inferences regarding other hypotheses.

Background: Binge-drinking is one of the alcohol drinking patterns with the worst health consequences. Nonetheless, binge-drinking is highly prevalent. The perceived benefits that motivate it are ultimately related to subjective well-being. In this context, we analyzed the relationship between binge-drinking and quality of life.

Methods: We evaluated 8992 participants of the SUN cohort. We classified as binge-drinkers those who reported consuming six or more drinks on at least one occasion the year before recruitment (n = 3075). We fitted multivariable logistic regression models to calculate the odds ratios (ORs) of a worse physical and mental quality of life, measured with the validated SF-36 questionnaire at 8 years of follow-up (cut-off point = P75 or highest score).

Results: Binge-drinking was associated with greater odds of having a worse mental quality of life, even adjusting for quality of life at 4 years of follow-up, used as an approximation to a baseline measure (OR = 1.22 (1.07-1.38)). This value was mainly due to the effects on vitality (OR = 1.17 (1.01-1.34)) and mental health (OR = 1.22 (1.07-1.39)).

Conclusions: Binge-drinking may lead to poorer mental quality of life; therefore, binge-drinking for enhancement purposes does not seem to be justified by this effect.

Background: An inverse association between total leisure-time physical activity (LTPA) and depression has been previously documented in the scientific literature. Our objective was to prospectively assess the association of LTPA with the risk of depression, focusing on several dimensions of LTPA (intensity, duration and type).

Methods: The SUN (Seguimiento Universidad de Navarra) project is a prospective cohort study formed by Spanish university graduates. A total of 15,488 adults (40.2% men, mean age 37 ± 12 years) initially free of depression were assessed. A report of a validated medical diagnosis of depression or the habitual use of antidepressants (any of both) were considered as incident cases of depression. LTPA was estimated through previously validated self-reported questionnaires. Participants were classified following Physical Activity recommendations from the World Health Organization, and according to the intensity, duration and type of LTPA. Cox proportional hazards regression models were run, adjusted for demographic, lifestyle, and dietary factors, to estimate adjusted hazard ratios (HR) of depression and 95% confidence intervals (CI).

Results: During 163,059 person-years of follow-up we registered 870 incident cases of depression. Participants with higher total LTPA (METs-h/wk) and higher duration of LTPA (hours/wk) exhibited a lower risk of depression HR = 0.84 (95% CI: 0.72-0.99) and HR = 0.83 (0.70-0.99) respectively, whereas intensity of LTPA (MET) did not show any association with depression.

Conclusion: Participants with higher LTPA had a lower risk of depression. The inverse association was stronger for total LPTA time than for its intensity. Higher duration of LTPA should be encouraged to prevent depression.

Alcohol intake is associated with the risk of breast cancer. Different patterns of alcoholdrinking may have different effects on breast cancer even when keeping constant the total amount of
alcohol consumed. We aimed to assess the association between binge drinking and breast cancer
risk. The SUN Project is a Spanish dynamic prospective cohort of university graduates initiated in
1999. In the 556-item lifestyle baseline questionnaire a validated food-frequency questionnaire was
embedded. Participants completed biennial follow-up questionnaires. Cox regression models were
used to estimate the hazard ratio (HR) for breast cancer associated with the exposure to binge drinking.
A stratified analysis was performed according to menopausal status. We included 9577 women (mean
age = 34 years, SD = 10 years), with a median follow-up of 11.8 years. Among 104,932 women-years
of follow-up, we confirmed 88 incident cases of breast cancer. Women in the binge drinking group
showed a higher risk of breast cancer (HR = 1.76; 95% CI: 1.03–2.99) compared to women in the
non-binge drinking category. In the stratified analysis, a 2-fold higher risk for premenopausal breast
cancer was associated with binge drinking habit (HR = 2.06; 95% CI: 1.11–3.82). This study adds new
evidence on the association of binge drinking with breast cancer risk.