PuSH - Publication Server of Helmholtz Zentrum München: Pharmacogenetic association of diabetes-associated genetic risk score with rapid progression of coronary artery calcification following treatment with HMG-CoA-reductase inhibitors -results of the Heinz Nixdorf Recall Study.

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Pechlivanis, S. ; Jung, J.* ; Moebus, S.* ; Lehmann, N.* ; Mahabadi, A.A.* ; Hoffmann, P.* ; Erbel, R.* ; Nöthen, M.M.* ; Bachmann, H.S.*

Pharmacogenetic association of diabetes-associated genetic risk score with rapid progression of coronary artery calcification following treatment with HMG-CoA-reductase inhibitors -results of the Heinz Nixdorf Recall Study.

Naunyn-Schmiedebergs Arch. Pharmakol. 394, 1713-1725 (2021)

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HMG-CoA-Reductase inhibitors (HMGRIs) are currently the most widely used group of drugs in patients with coronary artery disease (CAD) and are given preemptively to patients with high levels of cholesterol, including those with diabetes mellitus (DM). However, intake of HMGRIs also increases the progression of coronary artery calcification (CAC) and the risk of developing DM. This study aimed to investigate whether HMGRI intake interacts with the diabetes-associated genetic risk score (GRS) to affect CAC progression using data from the population-based Heinz Nixdorf Recall (HNR) study. CAC was measured in 3157 participants using electron-beam computed tomography twice, at baseline (CAC_b) and 5 years later (CAC_5y). CAC progression was classified as slow, expected, or rapid based on predicted values. Weighted DM GRS was constructed using 100 diabetes mellitus-associated single nucleotide polymorphisms (SNPs). We used log-linear regression to evaluate the interaction of HMGRI intake with diabetes-associated GRS and individual SNPs on CAC progression (rapid vs. expected/slow), adjusting for age, sex, and log(CAC_b + 1). The prevalence of rapid CAC progression in the HNR study was 19.6%. We did not observe any association of the weighted diabetes mellitus GRS with the rapid progression of CAC (relative risk (RR) [95% confidence interval (95% CI)]: 1.01 [0.94; 1.10]). Furthermore, no indication of an interaction between GRS and HMGRI intake was observed (1.08 [0.83; 1.41]). Our analyses showed no indication that the impact of HMGRIs on CAC progression is significantly more severe in patients with a high genetic risk of developing DM than in those with a low GRS.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Cohort Study ; Diabetes Mellitus ; Genetic Risk Score ; Hmg-coa-reductase Inhibitors ; Pleiotropic Effects ; Progression Of Coronary Artery Calcification; Subclinical Atherosclerosis; Calcium; Statins; Loci; Prediction; Disease; Events; Quantification; Prevention; Guidelines

ISSN (print) / ISBN 0028-1298

e-ISSN 1432-1912

Journal Naunyn-Schmiedeberg's Archives of Pharmacology

Quellenangaben Volume: 394, Issue: 4, Pages: 1713-1725

Publisher Springer

Publishing Place One New York Plaza, Suite 4600, New York, Ny, United States

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Asthma and Allergy Prevention (IAP)

Grants Deutsche Stiftung für Herzforschung