Dietary fatty acids, macronutrient substitutions, food sources and incidence of coronary heart disease:findings from the EPIC-CVD case-cohort study across nine European countries

Abstract2 Background: There is controversy about associations between total dietary fatty acids, their classes 3 (saturated, monounsaturated, polyunsaturated fatty acids; SFAs, MUFAs, PUFAs, respectively) and 4 risk of coronary heart disease (CHD). Specifically, the relevance of food sources of SFAs to CHD 5 associations is uncertain.6 Methods and Results: We conducted a case-cohort study involving 10,529 incident CHD cases and a 7 random subcohort of 16,730 adults selected from a cohort of 385,747 participants in nine countries of 8 the European Prospective Investigation into Cancer and Nutrition study. We estimated multivariable 9 adjusted country-specific hazard ratios (HRs) and 95% confidence intervals (CIs) per 5% of energy 10 intake from dietary fatty acids, with and without isocaloric macronutrient substitutions, using 11 Prentice-weighted Cox regression models and pooled results using random-effects meta-analysis. We 12 found no evidence for associations of the consumption of total or fatty acid classes with CHD, 13 regardless of macronutrient substitutions. In analyses considering food sources, CHD incidence was 14 lower per 1% higher energy intake of SFAs from yoghurt (HRs [95% CIs]: 0.93 [0.88-0.99]), cheese 15 (0.98 [0.96-1.00]), and fish (0.87 [0.75-1.00]), but higher for SFAs from red meat (1.07 [1.02-1.12]) 16 and butter (1.02 [1.00-1.04]).17 Conclusions: This observational study found no strong associations of total fatty acids, SFAs, 18 MUFAs, and PUFAs, with incident CHD. By contrast, we found associations of SFAs with CHD in 19 opposite directions dependent on the food source. These findings should be further confirmed, but 20 support public health recommendations to consider food sources alongside the macronutrients they 21 contain, and suggest the importance of the overall food matrix