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Why was the cohort set up?The Girona Heart Registry (REGICOR) population cohort was established to study cardiovascular (CV) risk factor prevalence and control, investigate novel risk factors associated with the incidence of CV diseases, and develop CV risk prediction models.Results from the Seven Countries Study showed that individuals from Southern Europe exhibited low CV mortality despite having high levels of certain CV risk factors [1, 2].Subsequent population-based registries reported that Catalonia, located in North-Eastern Spain, had a low rate of acute myocardial infarction [3] but high body mass index (BMI) and significant smoking prevalence [4].In this context, the REGICOR cohort was established in 1995 to investigate whether variations in the prevalence of classical CV risk factors could account for the observed differences in CV event rates.Additionally, the cohort aimed to identify novel biomarkers associated with first CV events in the general population.No calibrated and validated CV risk prediction models were available at the time.The first model, the 10-year Framingham coronary algorithm, was published in 1998 [5].Following this, researchers from Framingham collaborated Key Features The Girona Heart Registry (REGICOR) is a population-based study designed to analyse the magnitude of and factors related to cardiovascular (CV) diseases in Southern Europe.The REGICOR cohort integrates the participants of four population-based surveys conducted in 1995, 2000, 2005, and 2018 in the Girona province (North-Eastern Spain), with a current reference population of approximately 790 000 inhabitants. The REGICOR cohort includes 11 631 individuals (1748 in 1995, 3030 in 2000, 6308 in 2005, and 545 in 2018).At inclusion, 52% of the study population were females; their mean ages were 51, 50, 57, and 45, respectively. Two re-examinations were conducted for the participants recruited in 1995, 2000, and 2005. Follow-up data on CV events and cause-specific mortality are available for 11 518 participants since baseline, with a median follow-up time of 18.6 years.Follow-up data on non-CV events have been available since 2008. During inclusion and re-examinations, we obtained blood samples and information on CV and other risk factors using validated questionnaires, standardized tests, and imaging assessments.Genotyping was performed on the whole cohort.Circulating biomarkers, DNA methylation, microRNAs, and proteomics have been measured in a cohort subset.