Association between lipoprotein(a) (Lp(a)) levels and Lp(a) genetic variants with coronary artery calcification

Pechlivanis, Sonali GND; Mahabadi, Amir A. GND; Hoffmann, Per GND; Nöthen, Markus M.; Broecker-Preuss, Martina GND; Erbel, Raimund GND; Moebus, Susanne GND; Stang, Andreas GND; Jöckel, Karl-Heinz GND

Background: To examine the association between lipoprotein(a) (Lp(a)) levels, LPA (rs10455872 and rs3798220) and IL1F9 (rs13415097) single nucleotide polymorphisms (SNPs) with coronary artery calcification (CAC), an important predictor for coronary artery disease (CAD).

Methods: We used data from 3799 (mean age ± SD: 59.0 ± 7.7 years, 47.1% men) Heinz Nixdorf Recall study participants. We applied linear regression models to explore the relation between the log-transformed Lp(a) levels and LPA and IL1F9 SNPs with loge (CAC + 1). The association between the SNPs and log-transformed Lp(a) levels was further assessed using linear regression. The models were adjusted for age and sex (Model 1) and additionally for Lp(a) levels (Model 2).

Results: We observed a statistically significant association between log-transformed Lp(a) levels and CAC (Model 1: beta per log-unit increase in Lp(a) levels = 0.11; 95% confidence interval [95% CI] [0.04; 0.18], p = 0.002). Furthermore, the LPA SNP rs10455872 showed a statistically significant association with CAC (Model 1: beta per allele = 0.37 [0.14; 0.61], p = 0.002). The association between rs10455872 and CAC was attenuated after adjustment for Lp(a) levels (Model 2: beta per allele = 0.26 [- 0.01; 0.53], p = 0.06). Both LPA SNPs also showed a statistically significant association with Lp(a) levels (Model 1: betars10455872 per allele: 1.56 [1.46; 1.65], p < 0.0001 and betars3798220 per allele: 1.51 [1.33; 1.69], p < 0.0001)). The Mendelian randomization analysis showed that Lp(a) is a causal risk factor for CAC (estimate per log-unit increase in Lp(a) levels (95% CI), p: 0.27 [0.11; 0.44], p = 0.001). The IL1F9 SNP did not show any statistically significant association with Lp(a) levels or with CAC.

Conclusions: We provide evidence for the association of LPA rs10455872 with higher levels of Lp(a) and CAC in our study. The results of our study suggest that rs10455872, mediated by Lp(a) levels, might play a role in promoting the development of atherosclerosis leading to cardiovascular disease events.

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Pechlivanis, S., Mahabadi, A.A., Hoffmann, P., Nöthen, M.M., Broecker-Preuss, M., Erbel, R., Moebus, S., Stang, A., Jöckel, K.-H., 2020. Association between lipoprotein(a) (Lp(a)) levels and Lp(a) genetic variants with coronary artery calcification. https://doi.org/10.1186/s12881-020-01003-3
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