Discovery and validation population
death, CVD
CVD, MYOCARDIAL INFARCTION, STROKE, CARDIOVASCULAR DISEASE
Participants involved in the discovery population analysis come from three study subsamples designed for metabolite profiling and derived from the PREDIMED study: the PREDIMED-CVD study (primary outcome of the trial) that consisted of 229 incident CVD cases (myocardial infarction, stroke, or death from cardiovascular disease) and 788 sub-cohort participants without CVD at baseline (with an overlap of 37 participants) [All participants that have baseline metabolomics data available from the aforementioned studies and have completed validated semi-quantitative 137-item food frequency questionnaires (FFQs) were included to identify the HL profile (n = 1882). Participants with data missing from their FFQs at baseline (n = 11), a daily energy intake of < 500 and > 3500 kcal/day for women or < 800 and > 4000 kcal/day for men (n = 34), or ≥ 20% missing metabolite values (n = 4) were excluded from the analysis. The final sample included a total of 1833 participants at baseline (discovery population), of whom 633 were allocated to the MedDiet group supplemented with extra virgin olive oil, 629 to the MedDiet group supplemented with the nuts, and 571 to the control diet group (Supplemental Fig. 1).To validate the results, an internal validation analysis was conducted in the same population for whom lifestyle and metabolomics data were available after 1 year of follow-up. Participants were excluded if they had missing values in FFQs (n = 269) and lifestyle habits (n = 10), a daily energy intake between < 500 and > 3500 kcal/day for women or < 800 and > 4000 kcal/day for men (n = 22) or ≥ 20% missing metabolite values (n = 57) at 1 year. The final sample at the 1-year visit (validation sample) was 1524 participants (Supplementary Fig. 