Lipoprotein (a) cholesterol burden predicts atherosclerotic risk in patients with elevated lipoprotein a

Abstract Funding Acknowledgements Type of funding sources: Private hospital(s). Main funding source(s): Mayo Clinic Department of Laboratory Medicine and Pathology. Background Elevated lipoprotein(a) [Lp(a)] is associated with increased risk for atherosclerotic cardiovascular disease (ASCVD). Treatment of patients with elevated Lp(a) usually includes marked reduction in low density lipoprotein cholesterol (LDL-C). However, there are uncertainties about whether all increases in Lp(a) are equivalent in there risk relationship. Purpose The aim of this investigation was to risk stratify patients with elevated Lp(a) mass [Lp(a)-M] based on Lp(a) cholesterol (Lp(a)-C) measurements. We assessed coronary artery disease (CAD) by coronary angiogram and major adverse cardiac events (MACE) in a cohort of patients with elevated Lp(a) mass (≥30mg/dL) over a 15 year followup. Methods Electrophoretic and immunologic assays were used to measure Lp(a)-C and Lp(a)-M, respectively. Univariate and multivariate logistic regression analysis was employed to test for association between Lp(a) and CAD in a cohort patients with elevated Lp(a)-M (≥30mg/dL). The relationship between Lp(a) and time to major cardiac events was evaluated using cox regression analysis. Receiver operator curve (ROC) analyses were used to identify optimal cutoff values for Lp(a)-M and C for predicting CAD in our model. Results We analyzed 179 patients with elevated Lp(a)-M. Cutoff values of 3.3mg/dL for Lp(a)-C and 42.1mg/dL for Lp(a)-M optimally predicted CAD in an ROC analysis. Of these patients, 84 were found to have Lp(a)-C < 3.3mg/dL (low Lp(a)-C), while 95 patients had Lp(a)-C levels ≥ 3.3mg/dL (high Lp(a)-C). High Lp(a)-C was associated with CAD identified on coronary angiography in univariate (OR = 2.17, 95% CI = 1.18 – 4.00, p = 0.013) and multivariate (OR = 3.36, 95% CI = 1.64 – 6.89, p < 0.001) models controlling for traditional risk factors. In univariate analyses high Lp(a)-C was also associated with MACE (HR = 2.38, 95% CI = 1.19 – 4.75, p = 0.01) while Lp(a)-M ≥ 42.1mg/dL (high Lp(a)-M) was not (HR = 1.68, 95% CI = 0.82 – 3.44, p = 0.15) (Table 1, Figure 1). Lp(a)-C remained significantly correlated with MACE after adjusting for traditional risk factors. When included in a model together, Lp(a)-C maintained its significance while Lp(a)-M failed to predict MACE, indicating that Lp(a)-C is a stronger predictor of MACE than Lp(a)-M. Conclusion This study demonstrates that patients with elevated Lp(a)-M and high Lp(a)-C are approximately 2.5 times more likely to encounter MACE over time when compared to patients with elevated Lp(a)-M and low Lp(a)-C. Our investigation suggests that Lp(a)-C can be used to risk stratify patients with elevated Lp(a)-M and identify those at higher risk.