Only the type of virgin olive oil reduces the risk of mortality. Results of a cohort based on the Mediterranean population
Study design and population
Data were taken from the Nutrition and Cardiovascular Risk Study in Spain (ENRICA), the methods of which have been reported elsewhere . Briefly, 12,948 people aged ≥ 18 years were selected between June 2008 and October 2010 by stratified random cluster sampling to ensure a representative sample of the non-institutionalized Spanish population. First, the sample was stratified by province and municipality size. Second, the clusters were randomly selected in two stages: municipalities and census sections. Finally, households in each section were selected by random telephone dialing using the telephone directory as the sampling frame. Participants in households were selected in proportion to the gender and age distribution of the Spanish population. During the first phone call, the general objectives and procedures of the study were explained, and those selected gave their initial consent to participate; an official letter of invitation and detailed written information about the characteristics of the study were sent to the participant’s home. Collection of blood and urine samples were included for participant acceptance, and the overall response rate was 51.5%. Among those who did not participate, the most common reasons were refusal to accept a blood test (51.7%), lack of interest in the study (37.8%) and lack of time to participate (10.7%). .
The study was approved by the clinical research ethics committees of the University Hospital La Paz in Madrid and the Hospital Clinic of Barcelona (Spain). Written consent was obtained from all participants.
Basic data collection
Baseline (over the years 2008-2010), socio-demographics, lifestyle such as hours spent watching television and physical activity , as well as morbidities were collected. Self-reported information was obtained on gender, age, education level (no formal education, primary and secondary or higher) and tobacco use (current, former and never smoker). Weight and height were measured at home under standardized conditions, and body mass index (BMI) was calculated. The number of drugs was checked against the drug packages. Hypertriglyceridemia was defined as fasting plasma triglycerides ≥ 150 mg/dL; hypercholesterolaemia with total fasting plasma cholesterol level ≥ 200 mg/dL or taking lipid-lowering drugs; high blood pressure was defined as ≥140/90 mmHg or taking antihypertensive drugs; and self-reported diabetes or taking diabetes medications. Finally, self-reported and physician-diagnosed chronic diseases (chronic obstructive respiratory disease, coronary heart disease, stroke, heart failure, osteoarthritis, cancer, and depression requiring treatment) were also collected.
Trained and certified personnel collected information in three sequential steps: (1) a telephone interview to obtain data on sociodemographic factors, health behaviors, self-rated health status, and morbidity; (2) an initial home visit to collect blood samples, and (3) a second home visit to perform a physical examination and obtain a usual diet using a computerized food history .
To determine the participant’s usual food consumption, we used a validated computerized food history (DH-ENRICA), developed from that used in the Spanish EPIC cohort. . It is a structured questionnaire administered by a trained interviewer after each eating occasion, from breakfast until bedtime. During the interview, respondents were asked about their food consumption during the week and weekends, as well as seasonal variations. The DH-ENRICA collects standardized information on 880 foods and 184 recipes for dishes commonly consumed in Spain. Tables of composition of standard Spanish foods allowed for the calculation of the amount of energy and nutrients consumed [30, 31]. Study participants reported how often they consumed different types of oils and fats, and they specified the type of oil used for cooking and salad dressings, as well as the oil that was part of the recipes and sauces. In particular, detailed data was obtained on the consumption of common and virgin olive oil, taking into account in a comprehensive way the methods of dressing and cooking and frying.
We also calculated the Mediterranean diet score, based on the definition proposed by Trichopoulou et al. [32, 33] where the consumption of vegetables, legumes, fruits and nuts, cereals and fish was considered beneficial. A value of 1 was assigned to subjects with consumption above the gender-specific median in the study sample. In contrast, consumption of red meat, processed meat and poultry, and dairy products was considered detrimental, and a value of 0 was assigned to consumption above the median. Two items, alcohol consumption (to be able to fit the models independently of alcohol consumption without over-fitting) and the monounsaturated/saturated fatty acid ratio (because OO consumption is the main source of monounsaturated fatty acids (MUFA ) in the Spanish population ) were not included in the index. The range of this modified index was from 0 (lowest adherence) to 7 (highest adherence).
For all-cause mortality, we used the Spanish National Death Index which contains information on the vital status of all residents in Spain. Data on the specific cause of death were obtained from the National Institute of Statistics of Spain (https://www.ine.es/en/index.htm). All-cause deaths were obtained from baseline in 2008–2010 through the end of follow-up on January 31, 2020, while those from cardiovascular disease or cancer were obtained from baseline through January 31, 2017. Follow-up was censored at the date of death or at the end of follow-up, whichever comes first.
Of 13,105 participants, after excluding those who reported extreme total energy intake (800 or 5,000 kcal/day for men and 500 or 4,000 kcal/day for women ) (not = 884) and those with incomplete basic dietary data (not= 60), a total of 12,161 participants were included in the present analysis (5708 men and 6346 women, mean age: 47 ± 17 years).
Total OO consumption (in g per day) was estimated by adding common and virgin varieties. OO consumption was adjusted to total energy intake by the residual method  and participants were categorized according to gender-specific tertiles of total, common, and virgin OO consumption.
To assess associations between OO consumption and all-cause, cardiovascular, and cancer mortality, Cox proportional hazard models were fitted, with attained age as the underlying time scale (date of birth as origin). Hazard ratios (HR) and their 95% confidence intervals (CI) were calculated using the lowest tertile of OO consumption as a reference or considering OO consumption as a continuous variable (for each 10g/day, ~1 tbsp). To study linear trends across the OO consumption tertiles, we assigned the median value to each category and considered the variable to be continuous.
We fitted Cox regression models for several potential confounders defined “a priori” and selected based on prior causal knowledge. . Thus, three models were constructed with progressive levels of adjustment for confounding factors based on information collected at registration. Model 1 included sex and age (continuous) and total energy intake (kcal/day). Model 2 was then adjusted for education level, smoking status, BMI (2), total physical activity (household and leisure activities in METs-hour/week), watching television (hours/day), alcohol consumption (g/day), fiber intake (g/day), diet score Mediterranean (continuous from 0 to 7), number of drugs (0, 1–3 and >3). Finally, model 3 was also adjusted for the possible mediators of the association of interest, namely hypertriglyceridemia (yes/no), hypercholesterolemia (yes/no), hypertension (yes/no), diabetes (yes/no), number of chronic conditions reported (0, 1 and ≥ 2). When evaluating common and virgin OO consumption separately, the models were mutually adjusted. When missing values were less than 1% for individual covariates, we used stochastic regression (which adds a random error term that appropriately replicates the correlation between X and Y) to impute the data. All results were compared to models with complete information for all variables.
Restricted cubic spline analyzes with 3 nodes (at the 10th, 50th, and 90th percentiles) adjusted for the same potential confounders were plotted to visually display the dose-response relationship between total, common, and virgin OO consumption and the mortality risk.
We rerun the total and cardiovascular mortality models by including or excluding participants already diagnosed with cardiovascular disease or diabetes at baseline. In addition, subgroup analyzes were performed for all-cause mortality, stratifying the sample (above or below the median) by possible effect modifiers, such as age ( ≤ or > 60 years), gender, BMI (≤ or > 26.3 kg/m2), physical activity (≤ or >61.5 METs-h/week), as well as adherence to the MedDiet (≤ or >score 3). P for the interaction was obtained using the likelihood ratio test of the models with and without the interaction term. Finally, sensitivity analyzes were performed after excluding the first 2 years of follow-up.
Analyzes were performed using STATA/SE version 16.0 (StataCorp, College Station, TX, USA). Analyzes were weighted using the svy Stata command to account for the complex sampling design. Pvalues were two-sided and p