Risk prediction for coronary heart disease by a genetic risk score: results from the Heinz Nixdorf Recall study

Pechlivanis, Sonali; Lehmann, Nils; Hoffmann, Per; Nöthen, Markus, M.; Jöckel, Karl-Heinz; Erbel, Raimund; Moebus, Susanne

doi:10.1186/s12881-020-01113-y

Artikel / Aufsatz Do., 10. Sept.. 2020 CC BY 4.0

Veröffentlicht

Risk prediction for coronary heart disease by a genetic risk score : results from the Heinz Nixdorf Recall study

Pechlivanis, Sonali ; Lehmann, Nils ; Hoffmann, Per ; Nöthen, Markus M.; Jöckel, Karl-Heinz ; Erbel, Raimund ; Moebus, Susanne

Background: A Genetic risk score for coronary artery disease (CAD) improves the ability of predicting coronary heart disease (CHD). It is unclear whether i) the use of a CAD genetic risk score is superior to the measurement of coronary artery calcification (CAC) for CHD risk assessment and ii) the CHD risk assessment using a CAD genetic risk score differs between men and women.

Methods: We included 4041 participants (age-range: 45–76 years, 1919 men) of the Heinz Nixdorf Recall study without CHD or stroke at baseline. A standardized weighted CAD genetic risk score was constructed using 70 known genetic variants. The risk score was divided into quintiles (Q1-Q5). We specified low (Q1), intermediate (Q2- Q4) and high (Q5) genetic risk groups. Incident CHD was defined as fatal and non-fatal myocardial infarction, stroke and coronary death. The association between the genetic risk score and genetic risk groups with incident CHD was assessed using Cox models to estimate hazard ratios (HR) and 95%-confidence intervals (CI). The models were adjusted by age and sex (Model1), as well as by established CHD risk factors (RF) and CAC (Model2). The analyses were further stratified by sex and controlled for multiple testing.

Results: During a median follow-up time of 11.6 ± 3.7 years, 343 participants experienced CHD events (219 men). Per-standard deviation (SD) increase in the genetic risk score was associated with 18% increased risk for incident CHD (Model1: p = 0.002) which did not change after full adjustment (Model2: HR = 1.18 per-SD (p = 0.003)). In Model2 we observed a 60% increased CHD risk in the high (p = 0.009) compared to the low genetic risk group. Stratifying by sex, only men showed statistically significantly higher risk for CHD (Model2: HR = 1.23 per-SD (p = 0.004); intermediate: HR = 1.52 (p = 0.04) and high: HR = 1.88 (p = 0.008)) with no statistically significant risk observed in women.

Conclusion: Our results suggest that the CAD genetic risk score could be useful for CHD risk prediction, at least in men belonging to the higher genetic risk group, but it does not outbalance the value of CT-based quantification of CAC which works independently on both men and women and allows better risk stratification in both the genders.

Vorschau

Einordnung

Datum der Veröffentlichung:

10.09.2020

URN:

urn:nbn:de:hbz:465-20240812-143345-8

DOI:

10.1186/s12881-020-01113-y

Sprache:

Englisch

Ressourcentyp:

Text

Schlagwörter:

Coronary heart disease; Coronary artery disease; Coronary artery calcification; Genetic risk score; Cohort study

Kollektion:

E-Publikationen

Sachgruppen der Deutschen Nationalbibliographie:

610 Medizin, Gesundheit

Einrichtung:

Medizinische Fakultät, Universitätsklinikum Essen, Institut für Medizinische Informatik, Biometrie und Epidemiologie

Förderung:

The publication of this article was supported by the Publication Fund of the University of Duisburg-Essen.

We thank the Heinz Nixdorf Foundation [Chairman: M. Nixdorf; Past Chairman: G. Schmidt^‡], the “Deutsche Forschungsgemeinschaft” (Project numbers: PE 2309/2–1, ER 155/6–1 and ER 155/6–2) and the “Bundesministerium für Bildung und Forschung” for the generous support of this study. We thank the Ministry of Innovation, Science and Research, Nordrhine-Westfalia for the generous support for the genotyping of the Heinz Nixdorf Recall study participants. An additional research grant was received from Imatron Inc., South San Francisco, CA, which produced the EBCT scanners, and GE-Imatron, South San Francisco, CA, after the acquisition of Imatron Inc. We acknowledge the support of the Sarstedt AG & Co. (Nümbrecht, Germany) concerning laboratory equipment. There is no role of any funding body in the design of the study and collection, analysis, and interpretation of data and writing of manuscript.

Open Access funding provided by Projekt DEAL.

Informationen zur Erstveröffentlichung:

Pechlivanis, S., Lehmann, N., Hoffmann, P. et al. Risk prediction for coronary heart disease by a genetic risk score - results from the Heinz Nixdorf Recall study. BMC Med Genet 21, 178 (2020). https://doi.org/10.1186/s12881-020-01113-y

Published 10 September 2020

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