Our study confirms that Lp-PLA2 mass and activity levels vary significantly between White and non-White races in healthy older adults without clinically diagnosed CHD and not taking dyslipidemia medications. Whites have the highest Lp-PLA2 mass and activity levels, Hispanics have intermediate levels, and African-Americans and Asians have the lowest Lp-PLA2 mass and activity levels. These relationships were not affected by statistical adjustment for lifestyle and demographic factors, standard biological risk factors, and three SNPs known to be associated with Lp-PLA2 activity levels. These findings suggest that differences in Lp -PLA2 mass and activity levels between Whites and non-Whites may be due to other genetic factors or perhaps to unmeasured lifestyle factors.
The differences between White, Hispanic, and African-American race and Lp-PLA2 mass and activity levels in our study were similar to the results from the Dallas Heart Study, the largest community-based study of Lp-PLA2
]. One key difference was that our study also included Asians, who were found to have Lp-PLA2
mass and activity levels that were similar to African-Americans, but lower than Whites. Our study also demonstrated that racial differences in Lp-PLA2
mass and activity levels apply to older adults, given the fact that individuals in our study (mean age of 66 years) were substantially older than those in the Dallas Heart Study (mean age of 45 years). The Dallas Heart Study cohort included individuals taking statin medication, whereas our study excluded individuals taking any dyslipidemia medication, because such medications may reduce Lp-PLA2
mass and activity levels[25
]. Other studies that were in a small cohort[26
] and in a selected population with vascular disease[27
] also showed that Whites have higher Lp-PLA2
mass and activity levels as compared with other races.
circulates bound to LDL particles, Lp-PLA2
mass and activity levels depend greatly upon lipid metabolism and are strongly association with LDL and HDL levels[16
]. Although we also found this association, adjustment for LDL and HDL levels did not alter the relation between race and Lp-PLA2
mass and activity levels, suggesting that variations in LDL and HDL levels do not explain these racial differences. Diet and physical activity also affect lipid metabolism,[28
] but adjustment for these lifestyle factors did not attenuate the association between race and Lp-PLA2
mass and activity levels.
Various studies have shown associations between Lp-PLA2
mass and activity levels and different genotypes of Lp-PLA2
, bolstering the hypothesis that there is a substantial genetic influence on Lp-PLA2
levels. A study of the Framingham cohort, using 1943 SNPs, suggested that Lp-PLA2
mass had a multivariable adjusted heritability of 25% and Lp-PLA2
activity had 41% heritability[29
]. Among Whites, the Ala379Val coding variant in the PLA2G7 locus was associated with increased Lp-PLA2
activity, while the Arg92His coding variant was associated with decreased activity[22
]. Among Japanese individuals, the Val279Phe SNP also in the PLA2G7 locus, which is much more prevalent in Japanese than in Whites, is associated with greatly decreased Lp-PLA2
]. In fact, people who are homozygous for the Val279Phe polymorphism have almost no detectable Lp-PLA2
]. Because of the probable strong genetic influence on Lp-PLA2
mass and activity levels, one could hypothesize that the racial variations are due to genetic differences between races. Our study included only three SNPs, while the Framingham study revealed 12 SNPs linked with Lp-PLA2
]. Therefore, adjusting for only three SNPs in our study was a limited test of genetic influence on the racial differences in Lp-PLA2
and did not attenuate the strong association between race and Lp-PLA2
mass and activity levels.
In addition to the limited number of Lp-PLA2-related SNPs, another limitation of this analysis is that it is cross-sectional as we were unable to study whether Lp-PLA2 level predicts subsequent risk of CHD events differentially by race. Before Lp-PLA2 results can be added to existing CHD risk prediction equations, further evidence is needed to validate its incremental prognostic value in an ethnically-diverse cohort. Another limitation is the ability of questionnaires to accurately and fully characterize all the lifestyle variations that could explain the racial differences of Lp-PLA2 mass and activity levels. For example, there could be other lifestyle factors, such as diet choices unrelated to fat and carbohydrate intake, which influence Lp-PLA2 mass and activity levels but are not captured by the survey. The relatively modest number of non-White participants may also limit our ability to detect the effects of lifestyle factors.
is viewed as a novel CHD risk marker that could be used to risk stratify individuals when considering primary prevention strategies, such as initiating statin therapy or setting lipid treatment goals. Various authors have suggested using a uniform threshold for Lp-PLA2
mass, regardless of sex and race, for categorizing risk[1
]. However, the results from this study confirm that Lp-PLA2
mass and activity levels vary significantly between Whites and non-Whites, independent of known biological and lifestyle factors. These racial variations could affect the performance of Lp-PLA2
as a prognostic risk marker. For example, African-Americans may have lower Lp-PLA2
mass and activity levels than Whites despite having similar degrees of atherosclerosis and vascular inflammation or they may simply have less underlying atherosclerotic disease. In light of the high cardiovascular event rates in African-Americans, the former possibility seems more likely. As a result, using the same Lp-PLA2
threshold in Whites and African-Americans may underestimate risk in African-Americans compared with Whites.