Lp(a)-Associated Oxidized Phospholipids in Healthy Black and White Participants in Relation to apo(a) Size, Age, and Family Structure.

Background Lp(a) (lipoprotein(a)) is the major lipoprotein carrier of oxidized phospholipids (OxPL) and this function mediates Lp(a) atherogenicity. However, the relationship between OxPL, Lp(a), and genetic and biological characteristics remains poorly understood. We assessed the relationship between Lp(a)-bound OxPL, apolipoprotein(a) (apo(a)) size, age, and family structure in 2 racial groups. Methods and Results Healthy Black and White families were recruited from the general population (age: 6-74 years, n=267). OxPL and Lp(a) levels were assayed enzymatically; apo(a) isoform, LPA allele sizes, and allele-specific Lp(a) levels were determined. Lp(a)-OxPL levels did not differ significantly by racial and age groups. Lp(a)-OxPL levels were associated with total plasma Lp(a) in all participants and in race-specific analyses. Further, OxPL levels were significantly associated with allele-specific Lp(a) levels carried by the smaller apo(a) size in all participants (ß=0.33, P=0.0003) as well as separately for Black (ß=0.50, P=0.0032) and White (ß=0.26, P=0.0181) participants. A significant association of OxPL with allele-specific Lp(a) levels for larger apo(a) sizes was seen only in Black participants (ß=0.53, P=0.0076). In this group, Lp(a)-OxPL levels were also heritable (h2=0.29, P=0.0235), resulting in a significant interracial difference in heritability between Black and White people (P=0.0352). Conclusions Lp(a)-OxPL levels were associated with allele-specific Lp(a) level carried on smaller apo(a) sizes and among Black participants also for larger apo(a) sizes. The heritability estimates for Lp(a)-bound OxPL differed by race.

PCSK9 in African Americans and Caucasians in Relation to Lp(a) Level, Apo(a) Size and Heritability.

CONTEXT: Inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9) reduces lipoprotein(a) [Lp(a)] levels, but the association of PCSK9 with Lp(a) level and its major determinant, apolipoprotein(a) [apo(a)] size, is not fully understood. OBJECTIVE: To assess the relationship between PCSK9, Lp(a) level, apo(a) size, age, and ethnicity/race. DESIGN: Cross-sectional. SETTING: General population. PARTICIPANTS: Healthy African Americans and Caucasians (n = 267); age range: 6 to 74 years. INTERVENTIONS: None. MAIN OUTCOME MEASURES: PCSK9 levels, apo(a) isoform and LPA allele sizes, and isoform-specific Lp(a) levels. RESULTS: Plasma PCSK9 levels were significantly higher in African Americans vs Caucasians, in females vs males, and in adults vs children. PCSK9 levels were not associated with total plasma Lp(a) levels either in all participants or in ethnicity-specific analyses. However, PCSK9 levels were significantly positively associated with isoform-specific Lp(a) levels carried by the larger apo(a) size in all participants (r = 0.139, P = 0.0361). In ethnicity/race analyses, a significant association was seen for African Americans (r = 0.268, P = 0.0199), but not for Caucasians. In contrast, there were no significant associations of PCSK9 with isoform-specific Lp(a) levels for the smaller apo(a) sizes in all participants nor in ethnic-specific analyses. Furthermore, heritability (h2) analyses revealed a significant heritability for PCSK9 level in both ethnic groups, with a higher estimate in Caucasians than in African Americans (47% vs 22%, respectively). CONCLUSIONS: Among African Americans, but not Caucasians, PCSK9 levels were associated with isoform-specific Lp(a) levels carried on larger, but not smaller, apo(a) sizes. The findings illustrate a diverging relationship of PCSK9 with isoform-specific Lp(a) levels across ethnicity.