Abstract Body: Background and Objectives: An elevated level of plasma lipoprotein(a) [Lp(a)] is a prevalent, causal, and genetically regulated risk factor for cardiovascular disease (CVD). A size polymorphism of its apolipoprotein(a) [apo(a)] component determined with a number of Kringle (K) repeats is the major genetic regulator of Lp(a) level. Beyond genetics, non-genetic factors, including dietary saturated fats (SFA), modulate Lp(a) level. This study aimed to investigate the potential relationship between Lp(a) response to SFA modulation and apo(a) characteristics.
Methods and Results: The effect of apo(a) size and expression was tested among 166 African Americans, who previously reported to experience a 24% increase in Lp(a) level following dietary SFA reduction from 16% to 6%. The participants’ mean age was 35 years, 70% were women, the mean BMI was 28 kg/m², and the mean LDL-C concentration was 116 mg/dL. Apo(a) analyses were conducted by: (1) presence of an atherogenic small size apo(a) (<22 K repeats), (2) apo(a) phenotype (single or two isoforms), and in the case of two expressed apo(a) isoforms: (3) isoform dominance, and (4) tertiles of combined K repeats. There were no significant differences in Lp(a) increases following dietary SFA reduction between carriers vs non-carriers of a small size apo(a), between those with a single vs two expressed apo(a) isoforms, or in those with differing apo(a) isoform dominance patterns. However, among participants with two similarly expressed apo(a) isoforms, a greater increase in Lp(a) level was found for those with an average size of less than or equal to the median size (<28 K repeats) (p=0.034). Additionally, a gradual decrease in the extent of Lp(a) increase was observed across increasing tertiles of combined K repeats (mean ± SD): 15 ± 14, 14 ± 10, and 8 ± 9 mg/dL, respectively (p=0.024).
Conclusions: While carrying an atherogenic small size apo(a) was not a significant predictor of Lp(a) response to dietary SFA reduction among African Americans, other apo(a) characteristics, particularly those associated with two expressed apo(a) isoforms, modulated the response. The generalization of these findings to other ethnic/racial groups as well as relevance to CVD risk require further investigations.