Introduction: The 2013 AHA/ACC Guideline recommended limiting saturated fatty acids (SFA) and substituting SFA with monounsaturated fatty acids (MUFA) or polyunsaturated fatty acids (PUFA) in diet. Dietary intake data derived from self-reports is prone to measurement error and studies have been criticized for this reason. An objective alternative approach to examining the role of different dietary fatty acids on coronary heart disease (CHD) risk is to measure plasma phospholipid fatty acid (PL-FA) profiles, which reflect both dietary intake and endogenous metabolism, hence are proximal to the pathophysiologic processes of CHD. Our aim was to evaluate the role of plasma PL-FA profiles on CHD risk both directly and by estimating the theoretical effects of plasma “substitution” of various fatty acids for each other on CHD risk, and evaluate the consistence with the AHA/ACC Guideline.
Hypothesis: Plasma SFA is associated with increased CHD risk, and “substituting” plasma SFA with MUFA, PUFA n-6 or n-3 is associated with lower CHD risk.
Methods: We performed a nested case-control study with 2428 postmenopausal women in Women’s Health Initiative Observational Study (1214 CHD cases-controls pairs matched for baseline age, enrollment date, ethnicity and hysterectomy). Plasma PL-FA profiles were measured using gas chromatography methodology and expressed as molar percentage (mol%). Multivariate conditional logistic regression was used to calculate ORs for CHD risk associated with 1 mol% PL-FA increase, and “substitutions” of various fatty acids for each other, adjusting for matching factors, physical activity, body mass index (BMI), smoking, family history of diabetes, anticoagulant medication, hormone therapy, hypertension, diabetes mellitus, dyslipidemia and alternative healthy eating index. In addition, we tested the interactions of BMI and hormone therapy with PL-FAs.
Results: In multivariate conditional logistic regression analysis, plasma PL SFA was associated with increased CHD risk (OR=1.16, 95% CI 1.09 to 1.24) and PUFA n-3 was associated with decreased CHD risk (OR=0.92, 95% CI 0.86 to 0.97). No significant associations were observed for MUFA, PUFA n-6 and trans-fatty acids. “Substituting” 1 mol% SFA with an equivalent proportion of MUFA, PUFA n-6, or n-3 were associated with lower CHD risk (OR=0.81, 95% CI 0.74 to 0.88; OR=0.77, 95% CI 0.70 to 0.84;and OR=0.85, 95%CI 0.80 to 0.92, respectively). “Substituting” PUFA n-6 with n-3 was associated with lower CHD risk (OR=0.92, 95% CI 0.86 to 0.98) while no significant effect was found for “substituting” PUFA n-6 with MUFA. No significant interactions were obtained of BMI and hormone therapy with PL-FAs.
Conclusion: This plasma PL-FA “substitution” analysis is consistent with the AHA/ACC Guideline and suggests that “substituting” PL SFA with MUFA, PUFA n-6 or n-3, and “substituting” PUFA n-6 with n-3 is associated with lower CHD risk.