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A genetic risk score for hypertension is associated with risk of thoracic aortic aneurysm

Journal of Human Hypertension volume 33, pages 658–663 (2019)Cite this article

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Abstract

A genetic risk score (GRS) based on 29 single nucleotide polymorpysms (SNPs) associated with high blood pressure (BP) was prospectively associated with development of hypertension, stroke and cardiovascular events. The aim of the present study was to evaluate the impact of this GRS on the incidence of aortic disease, including aortic dissection (AD), rupture or surgery of a thoracic (TAA) or abdominal (AAA) aortic aneurysm. More than 25,000 people from the Swedish Malmo Diet and Cancer Study had information on at least 24 SNPs and were followed up for a median ≥ 18 years. The number of BP elevating alleles of each SNPs, weighted by their effect size in the discovery studies, was summed into a BP-GRS. In Cox regression models, adjusted for traditional cardiovascular risk factors including hypertension, we found significant associations of the BP-GRS, prospectively, with incident TAA (hazard ratio (HR) 1.64 (95% confidence interval (CI) 1.081–2.475 comparing the third vs. the first tertile; p = 0.020) but not with either AAA or aortic dissection. Calibration, discrimination and reclassification analyses show modest improvement in prediction using the BP-GRS in addition to the model which used only traditional risk factors. A GRS for hypertension associates with TAA suggesting a link between genetic determinants of BP and aortic disease. The effect size is small but the addition of more SNPs to the GRS might improve its discriminatory capability.

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Acknowledgements

We acknowledge the Knut and Alice Wallenberg Foundation for its economic support of the SWEGENE DNA extraction facility. Source of funding: This study was supported by grants from the European Research Council (StG-282255) Swedish Medical Research Council, the Swedish Heart and Lung Foundation, the Medical Faculty of Lund University, Malmo University Hospital, the Albert Påhlsson Research Foundation, the Crafoord Foundation, the Ernhold Lundstroms Research Foundation, the Region Skane, Hulda and Conrad Mossfelt Foundation, King Gustaf V and Queen Victoria Foundation, the Lennart Hansson Memorial Fund, the Cariverona Foundation. JGS was supported by the European Research Council, Swedish Heart-Lung Foundation, the Wallenberg Center for Molecular Medicine in Lund, the Swedish Research Council, the Crafoord Foundation, governmental funding of clinical research within the Swedish National Health Service, Skåne University Hospital in Lund, and the Scania county.

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Author notes

  1. These authors contributed equally: G. Smith, O. Melander, C. Fava

Authors and Affiliations

  1. Department of Medicine, University of Verona, Section of General Medicine and Hypertension, Verona, Italy

    A. Tagetti, S. Bonafini, P. Minuz & C. Fava

  2. Department of Clinical Sciences, Lund University, University Hospital of Malmö, Verona, Sweden

    T. Ohlsson, G. Engström, P. Almgren, O. Melander & C. Fava

  3. Department of Cardiology, Clinical Sciences, Lund University and Skåne University Hospital, Lund, Sweden

    G. Smith

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  1. A. Tagetti
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Correspondence to C. Fava.

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Tagetti, A., Bonafini, S., Ohlsson, T. et al. A genetic risk score for hypertension is associated with risk of thoracic aortic aneurysm. J Hum Hypertens 33, 658–663 (2019). https://doi.org/10.1038/s41371-018-0159-6

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