(P23-068-23) Lp(a) Changes Are Positively Correlated With Thrombogenic Factor Changes When SFA Is Replaced With MUFA or CHO: A Secondary Data Analysis of the DELTA Study

Objectives: Elevated lipoprotein(a) [Lp(a)] and thrombogenic factors (e.g., fibrinogen, factor VIIc and plasminogen activator inhibitor-1, PAI-1) increase risk for atherosclerotic cardiovascular disease (ASCVD). Studies show increases in Lp(a) and thrombogenic factors when saturated fat (SFA) is replaced with monounsaturated fat (MUFA) and carbohydrates (CHO). The aim was to assess the relationship between changes in Lp(a) and thrombogenic factors when SFA is replaced with MUFA or CHO in controlled feeding studies.

Methods: Data are from two randomized, crossover trials [Dietary Effects on Lipoproteins and Thrombogenic Activity (DELTA) 1 (normolipidemic) and DELTA 2 (high metabolic risk)]. Both trials (sites.cscc.unc.edu/cscc/projects/DELTA) examined the effect of replacing SFA with MUFA or CHO on lipids/lipoproteins and thrombogenic markers (fibrinogen, factor VIIc, and PAI-1). In both studies, the average American diet [AAD; designed to provide 37% of energy (%E) as fat, 16% SFA] was the reference diet. DELTA 1 included a Step 1 (30%E fat, 9% SFA) and low SFA, higher CHO (Low-Sat; 26%E fat, 5% SFA) diet. DELTA 2 included a Step 1 and a high-MUFA (37%E fat, 8% SFA, 22% MUFA) diet. Pearson’s or Spearman’s correlations were used to assess the association between changes in Lp(a), other lipids/lipoproteins, and thrombogenic factors in response to the AAD vs. the lower SFA diets.

Results: Analyses included 188 adults (52% male; 37±12 y; and 25.9±4.1 kg/m²). In DELTA 1, the change in Lp(a) in response to the Step 1 (r = 0.20; P = 0.04) and Low-Sat (r = 0.22; P = 0.03) diets compared to the AAD was positively correlated with the change in fibrinogen. In DELTA 2, a positive correlation was observed between the difference in Lp(a) and fibrinogen with the AAD vs. the MUFA (rho = 0.27; P = 0.01) but not the Step 1 diet. No correlations between changes in lipids/lipoproteins and Lp(a) were observed.

Conclusions: These results show a positive relationship between changes in fibrinogen and Lp(a) following replacement of SFA. Interestingly, Lp(a) changes were not associated with lipid/lipoprotein changes. Mechanistic studies to clarify the relationship between Lp(a) and thrombogenic factors are needed to better understand Lp(a) mediated ASCVD risk.

Funding Sources: NHLBI: 5-U01-HL49644, 49648, 49649, 49651, and 49659 and National Center for Research Resources: MO1-RR00400 and MO1-RR00645