Gesundheitswesen 2017; 79(08/09): 656-804
DOI: 10.1055/s-0037-1605856
Vorträge
Georg Thieme Verlag KG Stuttgart · New York

Role of Polygenic Risk Score for Coronary Artery Disease and its Traditional Risk Factors with Progression of Coronary Artery Calcification

S Pechlivanis
1   University Hospital of Essen, Institute for Medical Informatics, Biometry and Epidemiology, Essen
,
N Lehmann
1   University Hospital of Essen, Institute for Medical Informatics, Biometry and Epidemiology, Essen
,
R Erbel
1   University Hospital of Essen, Institute for Medical Informatics, Biometry and Epidemiology, Essen
,
KH Jöckel
1   University Hospital of Essen, Institute for Medical Informatics, Biometry and Epidemiology, Essen
,
M Nöthen
2   University of Bonn, Department of Genomics, Life & Brain Center, Bonn
,
S Moebus
1   University Hospital of Essen, Institute for Medical Informatics, Biometry and Epidemiology, Essen
3   University Hospital Essen, Centre for Urban Epidemiology, Essen
› Author Affiliations
Further Information

Publication History

Publication Date:
01 September 2017 (online)

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Introduction:

Atherosclerosis is the primary cause of coronary artery disease (CAD). Several studies have examined the association of traditional CAD risk factors (CRF) for the progression of coronary artery calcification (CAC). Our study describes the genetic architecture of progression of CAC by assessing the combined effect of the risk alleles associated with CAD and its traditional risk factors.

Methods:

We included 2786 participants (54.4% female) of the Heinz Nixdorf Recall Study with CAC measured at baseline (BL) and 5-year follow-up. We constructed unweighted polygenic risk score (PRS) for CAD, type 2 diabetes, body mass index, low-density lipoprotein (LDL), high-density lipoprotein, total cholesterol (TC), triglycerides, pulse pressure, systolic blood pressure and diastolic blood pressure. The single nucleotide polymorphisms for each PRS were selected from the latest genome-wide association meta-analysis. Linear regression analyses applied to 5-year progression of CAC on log-scale were fitted to estimate age, sex, and BL CAC as well as CRF adjusted effects.

Results:

In our study the median 5-year progression of CAC was 44.9% (Q1, Q3: 0%,167.7%). The mean (minimum, maximum) number of the risk alleles in the CAD-PRS, TC-PRS and LDL-PRS were 58.52 (42,76), 86.39 (68,107) and 63.04 (48,80) respectively. In the age, sex and BL CAC adjusted model, the CAD-PRS was associated with an increase in 5-year progression of CAC per risk allele by 1.4% (95% confidence interval: 0.5%; 2.2%, P = 0.001). The TC-PRS 1.0% (0.3%; 1.8%, P = 0.005) and LDL-PRS 0.9% (0.02%; 1.8%, P = 0.05) were also associated with an increase in 5-year progression of CAC per risk allele. The results hardly changed after adjusting for CRF.

Conclusions:

In our study the CAD, TC and LDL polygenic risk score showed strong effect with 5-year progression of CAC. Our results indicate that genes associated with these traits might have pleiotropic effects on the progression of coronary artery calcification.