• Marta Guasch-Ferré, Nancy Babio, Miguel A Martínez-González, Dolores Corella, Emilio Ros, Sandra Martín-Peláez, Ramon Estruch, Fernando Arós, Enrique Gómez-Gracia, Miquel Fiol, José M Santos-Lozano, Lluís Serra-Majem, Mònica Bulló, Estefanía Toledo, Rocío Barragán, Montserrat Fitó, Alfredo Gea, Jordi Salas-Salvadó, and PREDIMED Study Investigators.
• Human Nutrition Unit, University Hospital of Sant Joan de Reus, Department of Biochemistry and Biotechnology, Faculty of Medicine and Health Sciences, IISPV, Rovira i Virgili University, Reus, Spain; Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Institute of Health Carlos III, Madrid, Spain;
• Am. J. Clin. Nutr. 2015 Dec 1; 102 (6): 1563-73.

BackgroundDietary fat quality and fat replacement are more important for cardiovascular disease (CVD) prevention than is total dietary fat intake.ObjectiveThe aim was to evaluate the association between total fat intake and fat subtypes with the risk of CVD (myocardial infarction, stroke, or death from cardiovascular causes) and cardiovascular and all-cause death. We also examined the hypothetical effect of the isocaloric substitution of one macronutrient for another.DesignWe prospectively studied 7038 participants at high CVD risk from the PREvención con DIeta MEDiterránea (PREDIMED) study. The trial was conducted from 2003 to 2010, but the present analysis was based on an expanded follow-up until 2012. At baseline and yearly thereafter, total and specific fat subtypes were repeatedly measured by using validated food-frequency questionnaires. Time-dependent Cox proportional hazards models were used.ResultsAfter 6 y of follow-up, we documented 336 CVD cases and 414 total deaths. HRs (95% CIs) for CVD for those in the highest quintile of total fat, monounsaturated fatty acid (MUFA), and polyunsaturated fatty acid (PUFA) intake compared with those in the lowest quintile were 0.58 (0.39, 0.86), 0.50 (0.31, 0.81), and 0.68 (0.48, 0.96), respectively. In the comparison between extreme quintiles, higher saturated fatty acid (SFA) and trans-fat intakes were associated with 81% (HR: 1.81; 95% CI: 1.05, 3.13) and 67% (HR: 1.67; 95% CI: 1.09, 2.57) higher risk of CVD. Inverse associations with all-cause death were also observed for PUFA and MUFA intakes. Isocaloric replacements of SFAs with MUFAs and PUFAs or trans fat with MUFAs were associated with a lower risk of CVD. SFAs from pastries and processed foods were associated with a higher risk of CVD.ConclusionsIntakes of MUFAs and PUFAs were associated with a lower risk of CVD and death, whereas SFA and trans-fat intakes were associated with a higher risk of CVD. The replacement of SFAs with MUFAs and PUFAs or of trans fat with MUFAs was inversely associated with CVD. This trial was registered at www.controlled-trials.com as ISRCTN 35739639.© 2015 American Society for Nutrition.

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