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January 23, 2023Research Article

Polygenic Susceptibility to Hypertension and Blood Pressure Control in Stroke Survivors

View ORCID ProfileJulián Acosta, Cameron P. Both, Zachariah S. Demarais, Carolyn J. Conlon, View ORCID ProfileAudrey C. Leasure, Victor M. Torres-Lopez, View ORCID ProfileAdam de Havenon, View ORCID ProfileNils H. Petersen, View ORCID ProfileThomas M. Gill, Lauren H. Sansing, Kevin Navin Sheth, View ORCID ProfileGuido J. Falcone
First published January 23, 2023, DOI: https://doi.org/10.1212/WNL.0000000000206763
Julián Acosta
1Division of Neurocritical Care & Emergency Neurology, Department of Neurology, Yale School of Medicine, New Haven, CT
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  • ORCID record for Julián Acosta
Cameron P. Both
1Division of Neurocritical Care & Emergency Neurology, Department of Neurology, Yale School of Medicine, New Haven, CT
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Zachariah S. Demarais
2Frank H. Netter MD School of Medicine, North Haven, CT
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Carolyn J. Conlon
2Frank H. Netter MD School of Medicine, North Haven, CT
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Audrey C. Leasure
1Division of Neurocritical Care & Emergency Neurology, Department of Neurology, Yale School of Medicine, New Haven, CT
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  • ORCID record for Audrey C. Leasure
Victor M. Torres-Lopez
1Division of Neurocritical Care & Emergency Neurology, Department of Neurology, Yale School of Medicine, New Haven, CT
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Adam de Havenon
1Division of Neurocritical Care & Emergency Neurology, Department of Neurology, Yale School of Medicine, New Haven, CT
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  • ORCID record for Adam de Havenon
Nils H. Petersen
1Division of Neurocritical Care & Emergency Neurology, Department of Neurology, Yale School of Medicine, New Haven, CT
3Division of Vascular Neurology, Department of Neurology, Yale School of Medicine, New Haven, CT
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  • ORCID record for Nils H. Petersen
Thomas M. Gill
4Department of Internal Medicine, Yale School of Medicine, New Haven, CT
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  • ORCID record for Thomas M. Gill
Lauren H. Sansing
3Division of Vascular Neurology, Department of Neurology, Yale School of Medicine, New Haven, CT
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Kevin Navin Sheth
1Division of Neurocritical Care & Emergency Neurology, Department of Neurology, Yale School of Medicine, New Haven, CT
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Guido J. Falcone
1Division of Neurocritical Care & Emergency Neurology, Department of Neurology, Yale School of Medicine, New Haven, CT
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  • ORCID record for Guido J. Falcone
  • For correspondence: guido.falcone@yale.edu
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Citation
Polygenic Susceptibility to Hypertension and Blood Pressure Control in Stroke Survivors
Julián Acosta, Cameron P. Both, Zachariah S. Demarais, Carolyn J. Conlon, Audrey C. Leasure, Victor M. Torres-Lopez, Adam de Havenon, Nils H. Petersen, Thomas M. Gill, Lauren H. Sansing, Kevin Navin Sheth, Guido J. Falcone
Neurology Jan 2023, 10.1212/WNL.0000000000206763; DOI: 10.1212/WNL.0000000000206763

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Abstract

Background and Objectives: Blood pressure (BP) is often not at goal in stroke survivors, leaving individuals vulnerable to additional vascular events. Given that BP is a highly heritable trait, we hypothesize that a higher polygenic susceptibility to hypertension (PSH) leads to worse BP control in stroke survivors.

Methods: We conducted a study within the UK Biobank evaluating persons of European ancestry who survived an ischemic or hemorrhagic stroke. To model the PSH, we created polygenic scores (PRS) for systolic and diastolic BP using 732 genetic variants. We divided the PRSs into quintiles and used linear/logistic regression to test whether higher PSH led to higher observed BP, uncontrolled BP (systolic BP >140 mmHg or diastolic BP >90 mmHg) and resistant BP (uncontrolled BP despite being on >=3 antihypertensive drugs). We conducted an independent replication using data from the Vitamin Intervention for Stroke Prevention (VISP) trial.

Results: We analyzed 5,940 stroke survivors. When comparing stroke survivors with very low versus very high PSH, the mean systolic BP was 137 (SD 18) versus 143 (SD 20, p<0.001), the mean diastolic BP was 81 (SD 10) versus 84 (SD 11, p<0001), the prevalence of uncontrolled BP was 42.8% versus 57.2% (p<0.001), and the prevalence of resistant hypertension was 3.9% versus 11% (p<0.001). Results remained significant using multivariable models (p<0.001) and were replicated in the VISP study (all tests with p<0.05).

Discussion: A higher PSH is associated with worse BP control in stroke survivors. These findings point to genetic predisposition as an important determinant of poorly controlled BP in this population.

  • Received May 8, 2022.
  • Accepted in final form November 16, 2022.
  • © 2023 American Academy of Neurology

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