OBJECTIVE:Τo evaluate the combined modifying effect of dietary habits and/or features of healthy aging, on the lipoprotein-alpha [Lp(a)] and CVD risk association. DESIGN AND METHODS:Τhe ATTICA is a prospective, population-based study conducted in the greater metropolitan area of Athens (Attica, Greece). During 2001-2002, 3042 CVD-free adults (men/women: 1514/1528, 18-89 years) agreed to participate. In 2011-2012, the 10-year study follow-up was performed, recording the fatal/non-fatal CVD incidence in 2020 participants (mean follow-up: 8.41 years). Various bio-clinical characteristics [including low-density lipoprotein-cholesterol (LDL-C), Lp(a)] were derived through standard procedures. Dietary habits were assessed through the MedDietScore (an index assessing adherence to the Mediterranean diet with theoretical range 0-55). A validated successful aging index (SAI), ranging from 0 to 10, was used to assess healthy aging. RESULTS:Lp(a) levels were positively associated with 10-year CVD incidence (Hazard Ratio: 1.02, 95%CI 1.01-1.04); when MedDietScore was included in the model the observed association between Lp(a) levels and CVD risk disappeared (1.00, 95%CI 0.98-1.01), and a mediating effect of Mediterranean diet was revealed (Sobel's test p < 0.001). In the model that included both MedDietScore and SAI, the interaction effect of these two features on 10-year CVD risk was highly protective (p < 0.001), whereas the association between Lp(a) levels and CVD risk was further mediated (Sobel's test p < 0.001). CONCLUSIONS:Adherence to a healthy dietary pattern, like the Mediterranean diet seems to mediate the association between Lp(a) with CVD risk whereas a successful aging together with a healthy diet seems to further explain the previously mentioned association.