Relationship of oxidized phospholipids on apolipoprotein B-100 particles to race/ethnicity, apolipoprotein(a) isoform size, and cardiovascular risk factors: results from the Dallas Heart Study

Abstract

Background: Elevated levels of oxidized phospholipids (OxPLs) on apolipoprotein B-100 particles (OxPL/apoB) are associated with cardiovascular disease and predict new cardiovascular events. Elevated lipoprotein (a) [Lp(a)] levels are a risk factor for cardiovascular disease in whites and also in blacks if they carry small apolipoprotein(a) [apo(a)] isoforms. The relationship of OxPL/apoB levels to race/ethnicity, cardiovascular risk factors, and apo(a) isoforms is not established.

Methods and results: OxPL/apoB levels were measured in 3481 subjects (1831 black, 1047 white, and 603 Hispanic subjects) in the Dallas Heart Study and correlated with age, sex, cardiovascular risk factors, and Lp(a) and apo(a) isoforms. Significant differences in OxPL/apoB levels were noted among racial/ethnic subgroups, with blacks having the highest levels compared with whites and Hispanics (P<0.001 for each comparison). OxPL/apoB levels generally did not correlate with age, sex, or risk factors. In the overall cohort, OxPL/apoB levels strongly correlated with Lp(a) (r=0.85, P<0.001), with the shape of the relationship demonstrating a "reverse L" shape for log-transformed values. The highest correlation was present in blacks, followed by whites and Hispanics; was dependent on apo(a) isoform size; and became progressively weaker with larger isoforms. The size of the major apo(a) isoform (number of kringle type IV repeats) was negatively associated with OxPL/apoB (r=-0.49, P<0.001) and Lp(a) (r=-0.61, P<0.001) regardless of racial/ethnic group. After adjustment for apo(a) isoform size, the relationship between OxPL/apoB and Lp(a) remained significant (r=0.67, P<0.001).

Conclusions: OxPL/apoB levels vary according to race/ethnicity, are largely independent of cardiovascular risk factors, and are inversely associated with apo(a) isoform size. The association of OxPL with small apo(a) isoforms, in which a similar relationship is present among all racial/ethnic subgroups despite differences in Lp(a) levels, may be a key determinant of cardiovascular risk.

Figure 1

Levels of OxPL/apoB (A) and Lp(a) (B) categorized by racial group. Boxes indicate medians, 25^th and 75^th percentile, whiskers indicate 10^th and 90^th percentile. Differences among racial groups are all significant (p<0.001). BF=Black females, BM- Black males, WF= White females, WM= White Males, HF=Hispanic females, HM= Hispanic males.

Figure 2

Frequency distribution of OxPL/apoB (A) and Lp(a) (B) among racial groups. BF=Black females, BM- Black males, WF= White females, WM= White Males, HF=Hispanic females, HM= Hispanic males.

Figure 3

Panel A represent the frequency distribution of apo(a) isoform size according to the major apo(a) isoform. Panels B and C represent the distribution of OxPL/apoB and Lp(a) levels, respectively, according to apo(a) isoform size in all the racial groups combined.

Figure 4

This figure displays the correlation between OxPL/apoB and Lp(a). Panel A shows the relationship plotted on a geometric scale. Panel B shows the relationship plotted on a logarithmic scale. Panel C shows the relationship in the entire cohort according to apolipoprotein(a) isoform sizes.

Figure 5

The bar graph displays the OxPL/apoB (A) and Lp(a) (B) levels according to tertiles of apo(a) isoform size in Blacks, Whites and Hispanics.