Plasma lipidomic markers of diet quality are associated with incident coronary heart disease in American Indian adults: the Strong Heart Family Study

BACKGROUND:Identifying lipidomic markers of diet quality is needed to inform the development of biomarkers of diet, and to understand the mechanisms driving the diet- coronary heart disease (CHD) association. OBJECTIVE:To identify lipidomic markers of diet quality and examine whether these lipids are associated with incident CHD. METHODS:Using LC-MS, we measured 1,542 lipid species from 1,694 American Indian adults (aged 18-75, 62% female) in the Strong Heart Family Study. Participants were followed for development of CHD through 2020. Information on past year diet was collected using the Block Food Frequency Questionnaire, and diet quality was assessed using the Alternative Healthy Eating Index-2010 (AHEI). Mixed-effects linear regression was used to identify individual lipids cross-sectionally associated with AHEI. In prospective analysis, Cox frailty model was used to estimate the hazard ratio (HR) of each AHEI-related lipid for incident CHD. All models adjusted for age, sex, center, education, BMI, smoking, alcohol drinking, level of physical activity, energy intake, diabetes, hypertension, and use of lipid-lowering drugs. Multiple testing was controlled at false discovery rate <0.05. RESULTS:Among 1,542 lipid species measured, 71 lipid species (23 known) including acylcarnitine, cholesterol esters, glycerophospholipids, sphingomyelins and triacylglycerols, were associated with AHEI. Most of the identified lipids were associated with consumption of ω-3 fatty acids. In total, 147 participants developed CHD during a mean follow-up of 17.8 years. Among the diet-related lipids, 10 lipids (5 known, including CE(22:5)B, PC(p-14:0/22:1)/PC(o-14:0/22:1), PC(p-38:3)/PC(o-38:4)B, PE(p-18:0/20:4)/PE(o-18:0/20:4), and SM(d36:2)A) were associated with incident CHD. On average, each standard deviation increase in the baseline level of these 5 lipids was associated with 17%-23% increased risk of CHD [HR (95%CI) ranged from 1.17 (1, 1.36) to 1.23 (1.05, 1.43)]. CONCLUSION:We identified lipidomic markers of diet quality in American Indian adults. Some diet-related lipids are associated with risk of CHD beyond established risk factors.