The relative agreement between changes in Lp(a) in response to replacement of saturated fat with walnuts or avocados measured by the VAP and ELISA methods



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Lipoprotein(a) [Lp(a)] is independently and positively associated with risk of atherosclerotic cardiovascular disease (ASCVD), which is the leading cause of death worldwide. Lp(a) consists of an apolipoprotein (a) that is connected to an apolipoprotein B-100 through a disulfide bridge; its lipid core contains free and esterified cholesterol in similar amounts to low density lipoprotein (LDL) particles. Apo(a) inhibits fibrinolysis and promotes thrombosis while the LDL component of Lp(a) promotes cholesterol deposition in the arterial intima causing ASCVD. Dietary guidelines for ASCVD risk reduction emphasize a healthy dietary pattern; however, limited evidence is available for the effect of dietary modification on Lp(a). A barrier to assessment of the effect of dietary modification on Lp(a) is difficulty in measuring Lp(a) due to the variable size of the apo(a) component. The vertical auto profile (VAP) method is widely used to measure Lp(a); however, the enzyme-linked immunoassay (ELISA) method is considered the gold standard for Lp(a) measurement. The overarching aim of this study is to compare Lp(a) measured by the VAP method, to the ELISA method, when dietary saturated fats are replaced with sources of unsaturated fats (i.e., walnuts and avocados) in individuals at risk for ASCVD. Research Design and Methods Serum samples from two previously conducted studies were analyzed for Lp(a) using the ELISA method and the VAP method. The two randomized crossover-controlled feeding trials included a total of 90 (n=45 from each study) participants at risk for ASCVD. For my master’s Project, I conducted analyses to assess the relative and absolute agreement between the VAP and ELISA methods for assessment of Lp(a). The correlation between Lp(a) measured through ELISA and VAP was determined using Pearson’s or Spearman’s correlation depending on the data distribution. Bland-Altman plots were constructed to assess the absolute agreement between the two methods. Paired samples t-tests were conducted to assess the mean difference between the two methods. Results Statistically significant differences were observed between Lp(a) assessed by the VAP method compared to the ELISA method in both studies. In both the studies overall, Lp(a) assessed by VAP was weak to moderately correlated with Lp(a) measured by ELISA (p>0.05). Bland-Altman plots showed poor agreement between the two methods and proportional bias was evident. Conclusion The analyses show weak to moderate relative agreement and poor absolute agreement between VAP assessed Lp(a) and the ELISA method. Thus, use of the VAP method to assess the effect of dietary interventions on Lp(a) will provide erroneous results, and the gold standard ELISA method should be used.

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enzyme-linked immunoassay (ELISA), Lipoprotein(a) [Lp(a)], vertical auto profile (VAP)