Lipoprotein(a) Response to Dietary Saturated Fat Reduction: Relationship to Apolipoprotein(a) Size Polymorphism in...

An elevated lipoprotein(a) [Lp(a)] level, which is a prevalent cardiovascular risk factor, is genetically determined by a size polymorphism of its apolipoprotein(a) [apo(a)] component. Despite its genetic control, Lp(a) level increases in response to dietary saturated fat (SFA) reduction. We tested the roles of apo(a) size and characteristics in modulating Lp(a) response to SFA reduction.

We assessed apo(a) characteristics in 165 African Americans experiencing a 24% Lp(a) increase resulting from SFA reduction [16% at an average American Diet diet (AAD) to 6% at a DASH-type diet]. Apo(a) effects were tested based on the following factors: (1) the presence of a small atherogenic size (≤22 kringles), (2) phenotype (single or two isoforms), (3) isoform dominance, and (4) tertiles of combined kringle sizes.

There were no significant differences in Lp(a) increases between carriers vs. non-carriers of a small apo(a), between those with a single vs. two expressed isoforms, or in those with differing isoform dominance patterns (p > 0.05 for all). The extent of Lp(a) increase differed across increasing tertiles of combined kringle sizes (p = 0.006 for trend). In a multivariate model, the AAD Lp(a) level was a significant predictor of Lp(a) changes (p < 0.05). Relative increases in the allele-specific apo(a) level-an Lp(a) level associated with a defined apo(a) size-were similar across the apo(a) size spectrum.

Reducing dietary SFA intake results in a 24% increase in Lp(a) level in African Americans across apo(a) sizes. Individuals with smaller apo(a) sizes reached an elevated Lp(a) level post-intervention compared to those with larger sizes, in some cases resulting in cardiovascular risk reclassification.