Cohort Of Spanish University Graduates Research Articles

Daytime napping and the risk of atrial fibrillation in the SUN cohort

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): European Regional Development Fund (FEDER) and Spanish Ministry of Health. Introduction Previous research has identified a potential relationship between sleep patterns and atrial fibrillation (AF). Short daytime napping is a widespread healthy habit particularly in Mediterranean countries. However, as far as we know, daytime napping and the risk of developing AF has not been analysed before. Purpose Our objective was to assess the association between daytime napping and the incidence of AF in a Mediterranean cohort. Methods The SUN project is a dynamic, prospective cohort of Spanish university graduates. A total of 20,348 participants, free of AF at baseline, were followed-up for a median time of 13.8 years, with a retention proportion of 91%. Daytime napping was assessed at baseline and participants were categorised according to their average daily napping time. Incident cases of AF were confirmed by a cardiologist according to a prespecified protocol. Multivariable Cox regression models were used to estimate hazard ratios (HR) of AF according to daytime napping time. Results During follow-up, we identified 131 incident cases of AF. In comparison to participants with short daytime napping (<30 minutes/day), those who slept ≥30 minutes/day exhibited a significant 90% higher relative risk of incident AF (adjusted HR= 1.90; 95% CI: 1.26, 2.86), whereas no significant risk was observed for participants who did not have nap (adjusted HR = 1.26; 95% CI: 0.82, 1.93). After excluding participants that reported not having nap, those with shorter daytime napping had a lower risk of developing AF, with the greatest risk reduction between 15-30 minutes/day (adjusted HR = 0.44; 95% CI: 0.27, 0.72), in comparison to sleeping >30 minutes/day. Conclusions Daytime napping was significantly associated with the risk of developing AF. Sleeping a longer nap (≥30 minutes/day) was associated with an increased risk, while a shorter nap between 15-30 minutes/day was associated with a lower risk of incident AF. These findings suggest a potential novel healthy lifestyle habit in the primary prevention of AF.

Mortality prediction of the nutrient profile of the Chilean front-of-pack warning labels: Results from the Seguimiento Universidad de Navarra prospective cohort study.

Front-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. This 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. During 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. A 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.

Body adiposity estimated with CUN-BAE predicts atrial fibrillation: the SUN cohort

Abstract Background Obesity is widely recognised as a strong risk factor for atrial fibrillation and recent interest has focused on epicardial fat. Although body mass index is commonly used in the clinical practice, it doesn't precisely estimate adiposity. The Clínica Universidad de Navarra-Body Adiposity Estimator (CUN-BAE) is an equation developed for body fat calculation, that has been previously associated with cardiometabolic disease. Our objective was to assess the association between body fat, as captured by the CUN-BAE index, and the incidence of atrial fibrillation in a prospective cohort. Methods The SUN project is a dynamic, prospective cohort of Spanish university graduates. A total of 20.136 participants, free of atrial fibrillation at baseline, were followed-up for a median time of 12 years, with a retention proportion of 91%. CUN-BAE was calculated for each participant taking into account only sex, age and body mass index. Incident cases of atrial fibrillation were confirmed by a cardiologist according to a prespecified protocol. Multivariable Cox regression models were used to estimate hazard ratios (HR) of atrial fibrillation according to calculated body fat. Results During follow-up, we identified 128 incident cases of atrial fibrillation. There was a strong direct association between a higher CUN-BAE index at baseline and incident atrial fibrillation during follow-up. In comparison to participants with a lower body fat category (median 21.3%), those with a higher category of body fat (median 34.8%) exhibited a significant 118% higher relative risk of incident atrial fibrillation (adjusted HR=2.18; 95% CI: 1.22, 3.90). For each 2-unit increase in the CUN-BAE index, atrial fibrillation risk significantly increased by 10%. The risk of incident atrial fibrillation remained significantly associated with adiposity even after further adjustment for obesity (body mass index ≥30 kg/m2) and in repeated measures analysis of the CUN-BAE index every other year. Conclusions Increased body adiposity, as captured by CUN-BAE index, was strongly and independently associated with a higher risk of atrial fibrillation in a Spanish cohort. These findings support the hypothesis that adiposity is closely related with arrhythmogenic mechanisms that could lead to atrial fibrillation and may be predicted using an equation to estimate body fat. Funding Acknowledgement Type of funding sources: Public grant(s) – EU funding. Main funding source(s): Spanish Ministry of Health and European Regional Development Fund (FEDER)

Vitamin D and Risk of Obesity-Related Cancers: Results from the SUN ('Seguimiento Universidad de Navarra') Project.

Obesity is associated with a higher risk of several types of cancer, grouped as obesity-related cancers (ORC). Vitamin D deficiency is more prevalent in obese subjects, and it has been suggested to play a role in the association between obesity and cancer risk. The aim of the study was to analyze the association between vitamin D intake and the subsequent risk of ORC in a prospective Spanish cohort of university graduates. The SUN Project, initiated in 1999, is a prospective dynamic multipurpose cohort. Participants answered a 556-item lifestyle baseline questionnaire that included a validated food-frequency questionnaire. We performed Cox regression models to estimate the hazard ratios (HRs) of ORC according to quartiles of energy-adjusted vitamin D intake (diet and supplements). We included 18,017 participants (mean age = 38 years, SD = 12 years), with a median follow-up of 12 years. Among 206,783 person-years of follow-up, we identified 225 cases of ORC. We found no significant associations between vitamin D intake and ORC risk after adjusting for potential confounders: HRQ2vsQ1 = 1.19 (95% CI 0.81–1.75), HRQ3vsQ1 = 1.20 (95% CI 0.81–1.78), and HRQ4vsQ1 = 1.02 (95% CI 0.69–1.51). Dietary and supplemented vitamin D do not seem to be associated with ORC prevention in the middle-aged Spanish population.

The Mediterranean Lifestyle and the Risk of Depression in Middle-Aged Adults

BackgroundRecent evidence has indicated a greater number of protective factors are associated with a greater decreased risk for depression and depressive symptoms compared with individual factors alone. Moreover, adherence to healthy modifiable lifestyle behaviors may lower the risk of depression regardless of underlying genetic risk. ObjectivesWe longitudinally evaluated the association of the Mediterranean lifestyle (MEDLIFE) with the risk of depression. MethodsWe prospectively analyzed data from 15,279 participants (6089 men and 9190 women, mean age 37 y) in the Seguimiento Universidad de Navarra cohort. The MEDLIFE index is composed of 28 items on food consumption, dietary habits, physical activity, rest, social habits, and conviviality, each of which was assigned 0 or 1 point. Final scores ranged from 0 to 28 points and were categorized into quartiles of MEDLIFE adherence. Cox proportional regression models determined the association of total MEDLIFE adherence, each item, and block with incident depression. ResultsAfter a mean follow-up of 11.7 y, 912 (6%) incident cases of depression were reported. The mean ± SD final score for MEDLIFE adherence was 11.9 ± 2.7 points. The multivariable model showed that compared with the first quartile, the second and third quartiles of MEDLIFE adherence were significantly associated with a decreased relative risk for incident depression (HR: 0.82; 95% CI: 0.69, 0.96 and HR: 0.74; 95% CI: 0.61, 0.89, respectively). The fourth quartile did not show a statistically significant association with incident depression (HR: 0.89; 95% CI: 0.73, 1.09). ConclusionsMEDLIFE adherence may decrease the risk of depression in a Spanish cohort of university graduates. Given no clear association was observed among the highest MEDLIFE adherence, future studies are warranted to better understand the nature of this association. Evidence on MEDLIFE, beyond the Mediterranean diet, may contribute toward more effective prevention strategies for depression.

Dietary calcium, vitamin D, and breast cancer risk in women: findings from the SUN cohort.

Epidemiological evidence concerning the relationship between calcium and vitamin D intake and breast cancer (BC) is inconclusive. Moreover, the association according to menopausal status remains unclear. We aimed to assess whether total intakes from dietary and supplemental sources of calcium and vitamin D were associated with the incidence of BC in a Mediterranean cohort. We prospectively evaluated the association between intakes of calcium and vitamin D and BC risk among 10,812 women in the Seguimiento Universidad de Navarra (SUN) Project, a Spanish cohort of university graduates. During a mean follow-up of 10.7years, 101 incident BC cases were confirmed. Evidence of a non-linear association between total calcium intake and BC risk was found (Pnon-linearity = 0.011) with risk reductions associated with higher intake up to approximately 1400mg/day. Moderate intake [Tertile 2 (T2)] of total calcium was associated with lower overall BC risk [HR for T2 vs. Tertile 1 (T1): 0.55; 95% CI 0.33-0.91] and also among postmenopausal women (HRT2 vs. T1 = 0.38; 95% CI 0.16-0.92). Intake of vitamin D was not associated with BC risk. Our findings suggest an L-shaped association between total calcium intake and BC incidence. Moderate calcium intake may be associated with lower BC risk among overall and postmenopausal women, but not among premenopausal women. No evidence for any association between vitamin D intake and BC was found. Adherence to current guidelines recommendations for calcium intake may help to reduce BC risk.

A Mediterranean lifestyle reduces the risk of cardiovascular disease in the “Seguimiento Universidad de Navarra” (SUN) cohort

Background and aimsA healthy lifestyle is essential to prevent cardiovascular disease (CVD). However, beyond dietary habits, there is a scarcity of studies comprehensively assessing the typical traditional Mediterranean lifestyle with a multi-dimensional index. We assessed the association between the Mediterranean lifestyle (measured with the MEDLIFE index including diet, physical activity, and other lifestyle factors) and the incidence of CVD. Methods and resultsThe “Seguimiento Universidad de Navarra” (SUN) project is a prospective, dynamic and multipurpose cohort of Spanish university graduates. We calculated a MEDLIFE score, composed of 28 items on food consumption, dietary habits, physical activity, rest, social habits, and conviviality, for 18,631 participants by assigning 1 point for each typical Mediterranean lifestyle factor achieved, for a theoretically possible final score ranging from 0 to 28 points. During an average follow-up of 11.5 years, 172 CVD cases (myocardial infarction, stroke or cardiovascular death) were observed. An inverse association between the MEDLIFE score and the risk of primary cardiovascular events was observed, with multivariable-adjusted hazard ratio (HR) = 0.50; (95% confidence interval, 0.31–0.81) for the highest MEDLIFE scores (14–23 points) compared to the lowest scores (0–9 points), p (trend) = 0.004. ConclusionA higher level of adherence to the Mediterranean lifestyle was significantly associated with a lower risk of CVD in a Spanish cohort. Public health strategies should promote the Mediterranean lifestyle to preserve cardiovascular health.

The Association Between the Mediterranean Lifestyle Index and All-Cause Mortality in the Seguimiento Universidad de Navarra Cohort

Overall lifestyle patterns rather than individual factors may exert greater reductions on chronic disease risk and mortality. The objective is to study the association between a Mediterranean lifestyle index and all-cause and cause-specific mortality. Investigators analyzed data from 20,494 participants in the Seguimiento Universidad de Navarra cohort in 2019. The Mediterranean lifestyle index is composed of 28 items on food consumption, dietary habits, physical activity, rest, and social interactions that score 0 or 1 point; scores theoretically could range from 0 to 28 points. After a median follow-up of 12.1 years, 407 deaths were observed. In the multivariable-adjusted model, high adherence (>14 points) to the Mediterranean lifestyle was associated with a 41% relative reduction in all-cause mortality (hazard ratio=0.59, 95% CI=0.42, 0.83) compared with low adherence (3-10 points, p<0.001 for trend). For each additional point, the multivariable hazard ratios for all-cause mortality were 0.95 (95% CI=0.89, 1.02) for food consumption; 1.00 (95% CI=0.92, 1.08) for dietary habits; and 0.73 (95% CI=0.66, 0.80) for physical activity, rest, social habits, and conviviality. Significant interaction with age at last contact (p<0.001) suggested a lower risk for each additional point among participants aged ≥50 years (hazard ratio=0.50, 95% CI=0.34, 0.74), whereas no association was found for participants aged <50 years (hazard ratio=1.15, 95% CI=0.54, 2.44). Adherence to a Mediterranean lifestyle may reduce the risk of mortality in a Spanish cohort of university graduates. Inverse associations were found for the overall Mediterranean lifestyle score and lifestyle block, whereas no associations were observed for the dietary blocks. Future research should consider the Mediterranean lifestyle beyond the Mediterranean diet in different populations for the promotion of healthy longevity. This study is registered at www.clinicaltrials.gov NCT02669602.

Mediterranean diet, alcohol-drinking pattern and their combined effect on all-cause mortality: the Seguimiento Universidad de Navarra (SUN) cohort.

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. 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. During a median follow-up of 12.1years, 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. 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.

Association between the nutrient profile system underpinning the Nutri-Score front-of-pack nutrition label and mortality in the SUN project: A prospective cohort study

Front-of-pack nutrition labelling is a key public health policy that can be adopted as part of a comprehensive set of measures to promote healthy diets. The Nutri-Score, a five-colour summary label based on a modified version of the British Food Standards Agency Nutrient Profiling System (FSAm-NPS), is being considered for implementation in several European countries including Spain. This study aimed to prospectively assess the association between the FSAm-NPS and mortality rate in a Spanish cohort of university graduates. Analyses included 20503 participants (mean [SD] age: 38 [12] years) from the SUN cohort. Dietary intake was assessed at baseline and after 10-years of follow-up with a validated semi-quantitative food-frequency questionnaire. The FSAm-NPS was calculated for each food/beverage based on their amount of energy, saturated fat, sugar, sodium, fibre, protein, fruits, vegetables, legumes, nuts, rapeseed, walnut and olive oils per 100g of product. The FSAm-NPS Dietary Index (DI) was computed as an energy-weighted mean of the FSAm-NPS scores of all foods and beverages consumed by each participant. Multivariable-adjusted Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause and cause-specific mortality according to baseline and updated FSAm-NPS DI scores. Over a median follow-up of 10.9 years, 407 participants died. A higher baseline FSAm-NPS DI score, reflecting consumption of foods with lower nutritional quality and hence less favourable Nutri-Score rating, was directly associated with all-cause mortality (HR Q4 versus Q1=1.82; 95% CI: 1.34 to 2.47; p-trend<0.001) and cancer mortality (HR: 2.44; 95% CI: 1.54 to 3.85; p-trend<0.001). No association was found for cardiovascular mortality. The consumption of food products with a higher FSAm-NPS score (lower nutritional quality) was associated with a higher rate of all-cause and cancer mortality in a large prospective cohort of Spanish, middle-aged university graduates. These findings further support the implementation of Nutri-Score in Euro-Mediterranean countries.

Association of the Dietary-Based Diabetes-Risk Score (DDS) with the risk of gestational diabetes mellitus in the Seguimiento Universidad de Navarra (SUN) project

It is crucial to identify people at risk for type 2 diabetes mellitus (T2DM) and gestational diabetes mellitus (GDM) to implement preventive interventions in order to address these pandemics. A simple score exclusively based on dietary components, the Dietary-Based Diabetes-Risk Score (DDS) showed a strong inverse association with incident T2DM. The objective was to assess the association between DDS and the risk of GDM in a cohort of Spanish university graduates. The 'Seguimiento Universidad de Navarra' project is a prospective and dynamic cohort which included data of 3455 women who notified pregnancies between 1999 and 2012. The diagnosis of GDM is self-reported and further confirmed by physicians. A validated 136-item semi-quantitative FFQ was used to assess pre-gestational dietary habits. The development of the DDS was aimed to quantify the association between the adherence to this a priori dietary score and T2DM incidence. The score exclusively included dietary components (nine food groups with reported inverse associations with T2DM incidence and three food groups which reported direct associations with T2DM). Three categories of adherence to the DDS were assessed: low (11-24), intermediate (25-39) and high (40-60). The upper category showed an independent inverse association with the risk of incident GDM compared with the lowest category (multivariate-adjusted OR 0·48; 95 % CI 0·24, 0·99; P for linear trend: 0·01). Several sensitivity analyses supported the robustness of these results. These results reinforce the importance of pre-gestational dietary habits for reducing GDM and provide a brief tool to practically assess the relevant dietary habits in clinical practice.

Ultra-processed food consumption and the incidence of depression in a Mediterranean cohort: the SUN Project.

A growing body of evidence shows that consumption of ultra-processed foods (UPF) is associated with a higher risk of cardiometabolic diseases, which, in turn, have been linked to depression. This suggests that UPF might also be associated with depression, which is among the global leading causes of disability and disease. We prospectively evaluated the relationship between UPF consumption and the risk of depression in a Mediterranean cohort. We included 14,907 Spanish university graduates [mean (SD) age: 36.7year (11.7)] initially free of depression who were followed up for a median of 10.3years. Consumption of UPF (industrial formulations made mostly or entirely from substances derived from foods and additives, with little, if any, intact food), as defined by the NOVA food classification system, was assessed at baseline through a validated semi-quantitative 136-item food-frequency questionnaire. Participants were classified as incident cases of depression if they reported a medical diagnosis of depression or the habitual use of antidepressant medication in at least one of the follow-up assessments conducted after the first 2years of follow-up. Cox regression models were used to assess the relationship between UPF consumption and depression incidence. A total of 774 incident cases of depression were identified during follow-up. Participants in the highest quartile of UPF consumption had a higher risk of developing depression [HR (95% CI) 1.33 (1.07-1.64); p trend = 0.004] than those in the lowest quartile after adjusting for potential confounders. In a prospective cohort of Spanish university graduates, we found a positive association between UPF consumption and the risk of depression that was strongest among participants with low levels of physical activity.

The role of lifestyle behaviour on the risk of hypertension in the SUN cohort: The hypertension preventive score

Lifestyles may influence the risk of hypertension. Our objective was to assess the association between a healthy-lifestyle score and the incidence of hypertension. The SUN Project is a dynamic, prospective cohort of Spanish university graduates (1999–2014). Among 14,057 participants initially free of hypertension, we assessed the influence of lifestyle-related factors based on a 10-item score that we previously reported to be associated with lower risk of major cardiovascular events. However, we focused on factors related to hypertension risk according to previous scientific evidence and international clinical guidelines and constructed a 6-item score including: no smoking, moderate-to-high physical activity, Mediterranean diet adherence, healthy body mass index, moderate alcohol intake and no binge drinking. We fitted Cox regression models to adjust for potential confounders. During a median follow-up of 10.2 years, we identified 1406 incident cases of medically diagnosed hypertension. The risk of developing hypertension was linearly reduced as participants better adhered to a healthy lifestyle pattern built by summing up these 6 factors (p for trend<0.001). The highest category (5–6 factors) exhibited a significant 46% relative reduction in the risk of developing hypertension compared to the lowest category (0–1 factors) (multivariable-adjusted hazard ratio = 0.54; 95% CI: 0.42–0.68). Among the components of the score, BMI was apparently the main factor driving the association between the HLS and lower risk of hypertension. A healthy-lifestyle score including six simple healthy habits was longitudinally and linearly associated with a substantially reduced risk of hypertension. This index may be a useful tool for hypertension prevention.

Sugar-sweetened beverage consumption and incidence of breast cancer: the Seguimiento Universidad de Navarra (SUN) Project.

Breast cancer (BC) incidence is increasing worldwide. Higher insulin resistance may potentially lead to an increased risk of BC. Sugar-sweetened beverages (SSB) are an acknowledged dietary factor that increases insulin resistance. However, the association between SSB and BC has not been widely explored. We evaluated the association between baseline consumption of SSB and the incidence of BC among relatively young women in a cohort of Spanish university graduates. We evaluated 10,713 middle-aged, Spanish female university graduates (median age 33) from the Seguimiento Universidad de Navarra (SUN) cohort, initially free of BC. SSB consumption was collected at baseline using a validated136-item semi-quantitative food-frequency questionnaire. Incidence of BC was confirmed by a trained oncologist using medical records. We fitted Cox regression models to assess the relationship between baseline categories of SSB consumption and the incidence of BC during follow-up. We stratified the analyses by menopausal status. During 106,189 person-years follow-up, 100 incident cases of BC were confirmed. Among postmenopausal women, regular consumption of SSB was associated with a significantly higher incidence of BC (HR 2.12; 95% CI 1.02, 4.41) in the fully adjusted model, compared to women who never or seldom consumed SSB. No association was found among premenopausal women (HR 1.16; 95% CI 0.66, 2.07). Even though the number of cases was small, in this Mediterranean cohort, we observed a direct association between SSB consumption and BC risk among postmenopausal women. Nonetheless further larger longitudinal studies are needed to support this association.

Ultra-Processed Food Consumption and All-Cause Mortality: The University of Navarra Follow-Up (SUN) Cohort

Background: Ultra-processed foods (UPFs) consumption has increased in the past decade. Because of its nutritional composition, evidence suggests a potential association between UPFs consumption and higher risk of all-cause mortality. No prospective study has investigated this relationship. Methods: We evaluated the association between UPFs consumption and the risk of mortality in a dynamic, prospective Spanish cohort of university graduates, the Seguimiento Universidad de (SUN) study. We used data from 19,897 participants followed-up between December 1999 and February 2014 for a median of 10·4 years with a retention rate of 90·9%. UPFs consumption (defined as food and drink products ready to eat, drink, or heat and made predominantly or entirely from processed items extracted or refined from whole foods or synthesized in the laboratory) was assessed with the use of a validated semi-quantitative 136-item foodfrequency questionnaire (FFQ). We adjusted UPFs consumption for energy intake using the residuals method. Participants were classified according to their energy-adjusted UPFs consumption into quartiles. Cox proportional hazards models were used to estimate adjusted Hazards Ratio (HR) and 95% confidence intervals (CI) for all-cause mortality. Findings: We registered 335 deaths in 198,556 persons-years of follow-up. Participants in the highest quartile of UPFs consumption had a higher risk for all-cause mortality compared to those in the first quartile (multivariable-adjusted HR=1·62; 95% CI: 1·13-2·32) with a significant dose-response trend (p for linear trend=0·005). For each additional serving of UPFs consumption, mortality relatively increased by 9% (HR=1·09; 95% CI: 1·02-1·17). Interpretation: UPFs consumption was associated with an increased risk for all-cause mortality in a prospective cohort of Spanish middle-aged adult university graduates. Further longitudinal studies are needed to confirm our results. Funding Statement: The SUN Project has been supported by the Spanish Government-Instituto de Salud Carlos III, and the European Regional Development Fund (FEDER) (RD 06/0045, PI14/01798, PI14/01764, PI17/01795), the Navarra Regional Government, and the University of Navarra. Declaration of Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and publication of this article. Ethics Approval Statement: The Institutional Review Board (IRB) of the University of Navarra approved the protocol and the methods used to obtain consent of participants, conforming to the principles embodied in the Declaration of Helsinki. The SUN project was registered at clinicaltrials.gov as NCT02669602.

Strong inverse associations of Mediterranean diet, physical activity and their combination with cardiovascular disease: The Seguimiento Universidad de Navarra (SUN) cohort.

Background Inverse associations of the Mediterranean diet (MedDiet) and physical activity with cardiovascular disease have been previously reported. We investigated the individual and combined contributions of both to this inverse association in a Mediterranean cohort. Design We used data from 19,536 participants from a prospective cohort of Spanish university graduates, the 'Seguimiento Universidad de Navarra' (SUN) cohort, followed up between December 1999 and December 2016. Methods Adherence to the MedDiet was obtained from a 136-item validated food-frequency questionnaire and categorized in tertiles using four previously reported dietary scores. A validated questionnaire assessed the physical activity levels according to volume, intensity and frequency. Results Participants were followed up during a median time of 10.4 years. Compared with the lowest category of adherence to the MedDiet (≤3 in the Mediterranean Diet Score), higher adherence (6-9 points) was strongly inversely associated with cardiovascular disease (multivariable adjusted hazard ratio = 0.33; 95% confidence interval (CI) 0.20-0.55). Also, engaging in an active lifestyle (6-8 points in an eight-item score) compared with low activity (<2 points) was associated with a reduced risk of incident cardiovascular disease (hazard ratio = 0.43; 95% CI 0.20-0.90). Greater adherence to the MedDiet and engaging in high levels of active lifestyle showed a 75% relatively reduced risk of cardiovascular disease (hazard ratio = 0.25; 95% CI 0.13-0.48). Conclusions The combined effect of adherence to the MedDiet and adopting an active lifestyle showed a synergistic inverse association with cardiovascular disease risk.

Association Between a Healthy Lifestyle Score and the Risk of Cardiovascular Disease in the SUN Cohort

Introduction and objectivesA healthy lifestyle (HLS) is essential to attaining optimal cardiovascular health. Our objective was to assess the association between a HLS score and the incidence of hard cardiovascular disease (CVD) events. MethodsThe SUN project is a dynamic, prospective, multipurpose cohort of Spanish university graduates with a retention proportion of 92%. In 19 336 participants, we calculated a HLS score ranging from 0 to 10 points: never smoking, physical activity (> 20 METs-h/wk), Mediterranean diet adherence (≥ 4/8 points), low body mass index (≤ 22), moderate alcohol intake (women, 0.1-5g/d; men, 0.1-10g/d), low television exposure (≤ 2h/d), no binge drinking (≤ 5 alcoholic drinks anytime), taking a short afternoon nap (< 30min/d), meeting up with friends> 1h/d and working> 40h/wk. ResultsAfter a median follow-up of 10.4 years, we identified 140 incident cases of CVD. After adjustment for potential confounders, the highest category of HLS score adherence (7-10 points) showed a significant 78% relative reduction in the risk of primary CVD compared with the lowest category (0-3 points) (adjusted HR, 0.22; 95%CI, 0.11-0.46). Each healthy habit was individually associated with a lower risk of CVD. ConclusionsA HLS score including several simple healthy habits was associated with a lower risk of developing primary CVD. This index may be useful to reinforce CVD prevention without the need to include traditional risk factors.

Relación entre un índice de estilo de vida saludable y el riesgo de enfermedad cardiovascular en la cohorte SUN

Introduction and objectivesA healthy lifestyle (HLS) is essential to attaining optimal cardiovascular health. Our objective was to assess the association between a HLS score and the incidence of hard cardiovascular disease (CVD) events. MethodsThe SUN project is a dynamic, prospective, multipurpose cohort of Spanish university graduates with a retention proportion of 92%. In 19 336 participants, we calculated a HLS score ranging from 0 to 10 points: never smoking, physical activity (> 20 METs-h/wk), Mediterranean diet adherence (≥ 4/8 points), low body mass index (≤ 22), moderate alcohol intake (women, 0.1-5g/d; men, 0.1-10g/d), low television exposure (≤ 2h/d), no binge drinking (≤ 5 alcoholic drinks anytime), taking a short afternoon nap (< 30min/d), meeting up with friends> 1h/d and working> 40h/wk. ResultsAfter a median follow-up of 10.4 years, we identified 140 incident cases of CVD. After adjustment for potential confounders, the highest category of HLS score adherence (7-10 points) showed a significant 78% relative reduction in the risk of primary CVD compared with the lowest category (0-3 points) (adjusted HR, 0.22; 95%CI, 0.11-0.46). Each healthy habit was individually associated with a lower risk of CVD. ConclusionsA HLS score including several simple healthy habits was associated with a lower risk of developing primary CVD. This index may be useful to reinforce CVD prevention without the need to include traditional risk factors.Full English text available from:www.revespcardiol.org/enFull English text available from:www.revespcardiol.org/en

Mediterranean diet, physical activity and their combined effect on all-cause mortality: The Seguimiento Universidad de Navarra (SUN) cohort

The health benefits of the Mediterranean diet (MedDiet) and of physical activity (PA) have been widely documented. However, no longitudinal studies have investigated their combined effect on mortality. We assessed the individual and combined effects of adherence to the MedDiet and PA on all-cause mortality.We used data from 19,467 participants from a prospective cohort of Spanish university graduates, the SUN cohort, followed-up between December 1999 and February 2016. Adherence to the MedDiet was assessed using four different dietary scores, categorizing the quantitative scores into tertiles of adherence. To assess multiple dimensions of PA, an 8-item score was built. Multivariable Cox regression models were used to study the individual and combined relationship of adherence to the MedDiet and PA with all-cause mortality.During a median follow-up of 10.3years, we registered 305 deaths. Compared with the lowest adherence to the MedDiet (<20 in the modified Mediterranean diet score), better adherence (23–30 points) was associated with lower mortality (multivariable-adjusted hazard ratio [HR]=0.66, 95% confidence interval [CI]: 0.46–0.96). Engaging in moderate or high levels of PA (versus lower levels) was associated with 44% and 52% relative reductions in mortality, respectively. High adherence to the MedDiet combined with engaging in higher amounts of PA showed a HR=0.36 (95% CI: 0.19–0.67).We documented that the combined effect of better adherence to the MedDiet and increased PA had multiplicative effects on mortality risk reduction.

Living at Higher Altitude and Incidence of Overweight/Obesity: Prospective Analysis of the SUN Cohort.

BackgroundResidence at high altitude has been associated with lower obesity rates probably due to hypoxia conditions. However, there is no evidence of this association in a free-living population.ObjectivesWe assessed the association between the altitude where each participant of a Spanish cohort (the SUN Project) was living and the incidence of overweight/obesity.MethodsThe SUN Project is a dynamic, prospective, multipurpose cohort of Spanish university graduates with a retention rate of 89%. We included in the analysis 9 365 participants free of overweight/obesity at baseline. At the baseline questionnaire, participants reported their postal code and the time they had been living in their city/village. We imputed the altitude of each postal code according to the data of the Spanish National Cartographic Institute and categorized participants in tertiles. We used Cox regression models to adjust for potential confounding variables.ResultsDuring a median follow-up of 10 years, we identified 2 156 incident cases of overweight/obesity. After adjusting for sex, age, time of residence at current city, baseline body mass index, physical activity, sedentarism and years of education (≤ 3 years, ≥ 4 years, Master/PhD), those participants in the third tertile (>456 m) exhibited a statistically significant 14% reduction in the risk of developing overweight/obesity in comparison to those in the first tertile (<124 m) (adjusted HR = 0.86; 95% CI: 0.77, 0.96).ConclusionsLiving in cities of higher altitude was inversely associated with the risk of developing overweight/obesity in a cohort of Spanish university graduates.