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April 11, 2023; 100 (15) Research Article

Polygenic Susceptibility to Hypertension and Blood Pressure Control in Stroke Survivors

View ORCID ProfileJulián N. 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 N. Sheth, View ORCID ProfileGuido J. Falcone
First published January 23, 2023, DOI: https://doi.org/10.1212/WNL.0000000000206763
Julián N. Acosta
From the Division of Neurocritical Care & Emergency Neurology (J.N.A., C.P.B., A.C.L., V.M.T.-L., A.H., N.H.P., K.N.S., G.J.F.), Department of Neurology, Yale School of Medicine; Frank H. Netter MD School of Medicine (Z.S.D., C.J.C.); Division of Vascular Neurology (N.H.P., L.H.S.), Department of Neurology, Yale School of Medicine; and Department of Internal Medicine (T.M.G.), Yale School of Medicine, New Haven, CT.
MD
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  • ORCID record for Julián N. Acosta
Cameron P. Both
From the Division of Neurocritical Care & Emergency Neurology (J.N.A., C.P.B., A.C.L., V.M.T.-L., A.H., N.H.P., K.N.S., G.J.F.), Department of Neurology, Yale School of Medicine; Frank H. Netter MD School of Medicine (Z.S.D., C.J.C.); Division of Vascular Neurology (N.H.P., L.H.S.), Department of Neurology, Yale School of Medicine; and Department of Internal Medicine (T.M.G.), Yale School of Medicine, New Haven, CT.
BS
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Zachariah S. Demarais
From the Division of Neurocritical Care & Emergency Neurology (J.N.A., C.P.B., A.C.L., V.M.T.-L., A.H., N.H.P., K.N.S., G.J.F.), Department of Neurology, Yale School of Medicine; Frank H. Netter MD School of Medicine (Z.S.D., C.J.C.); Division of Vascular Neurology (N.H.P., L.H.S.), Department of Neurology, Yale School of Medicine; and Department of Internal Medicine (T.M.G.), Yale School of Medicine, New Haven, CT.
BS
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Carolyn J. Conlon
From the Division of Neurocritical Care & Emergency Neurology (J.N.A., C.P.B., A.C.L., V.M.T.-L., A.H., N.H.P., K.N.S., G.J.F.), Department of Neurology, Yale School of Medicine; Frank H. Netter MD School of Medicine (Z.S.D., C.J.C.); Division of Vascular Neurology (N.H.P., L.H.S.), Department of Neurology, Yale School of Medicine; and Department of Internal Medicine (T.M.G.), Yale School of Medicine, New Haven, CT.
BS
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Audrey C. Leasure
From the Division of Neurocritical Care & Emergency Neurology (J.N.A., C.P.B., A.C.L., V.M.T.-L., A.H., N.H.P., K.N.S., G.J.F.), Department of Neurology, Yale School of Medicine; Frank H. Netter MD School of Medicine (Z.S.D., C.J.C.); Division of Vascular Neurology (N.H.P., L.H.S.), Department of Neurology, Yale School of Medicine; and Department of Internal Medicine (T.M.G.), Yale School of Medicine, New Haven, CT.
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Victor M. Torres-Lopez
From the Division of Neurocritical Care & Emergency Neurology (J.N.A., C.P.B., A.C.L., V.M.T.-L., A.H., N.H.P., K.N.S., G.J.F.), Department of Neurology, Yale School of Medicine; Frank H. Netter MD School of Medicine (Z.S.D., C.J.C.); Division of Vascular Neurology (N.H.P., L.H.S.), Department of Neurology, Yale School of Medicine; and Department of Internal Medicine (T.M.G.), Yale School of Medicine, New Haven, CT.
MA
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Adam de Havenon
From the Division of Neurocritical Care & Emergency Neurology (J.N.A., C.P.B., A.C.L., V.M.T.-L., A.H., N.H.P., K.N.S., G.J.F.), Department of Neurology, Yale School of Medicine; Frank H. Netter MD School of Medicine (Z.S.D., C.J.C.); Division of Vascular Neurology (N.H.P., L.H.S.), Department of Neurology, Yale School of Medicine; and Department of Internal Medicine (T.M.G.), Yale School of Medicine, New Haven, CT.
MD
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Nils H. Petersen
From the Division of Neurocritical Care & Emergency Neurology (J.N.A., C.P.B., A.C.L., V.M.T.-L., A.H., N.H.P., K.N.S., G.J.F.), Department of Neurology, Yale School of Medicine; Frank H. Netter MD School of Medicine (Z.S.D., C.J.C.); Division of Vascular Neurology (N.H.P., L.H.S.), Department of Neurology, Yale School of Medicine; and Department of Internal Medicine (T.M.G.), Yale School of Medicine, New Haven, CT.
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Thomas M. Gill
From the Division of Neurocritical Care & Emergency Neurology (J.N.A., C.P.B., A.C.L., V.M.T.-L., A.H., N.H.P., K.N.S., G.J.F.), Department of Neurology, Yale School of Medicine; Frank H. Netter MD School of Medicine (Z.S.D., C.J.C.); Division of Vascular Neurology (N.H.P., L.H.S.), Department of Neurology, Yale School of Medicine; and Department of Internal Medicine (T.M.G.), Yale School of Medicine, New Haven, CT.
MD
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Lauren H. Sansing
From the Division of Neurocritical Care & Emergency Neurology (J.N.A., C.P.B., A.C.L., V.M.T.-L., A.H., N.H.P., K.N.S., G.J.F.), Department of Neurology, Yale School of Medicine; Frank H. Netter MD School of Medicine (Z.S.D., C.J.C.); Division of Vascular Neurology (N.H.P., L.H.S.), Department of Neurology, Yale School of Medicine; and Department of Internal Medicine (T.M.G.), Yale School of Medicine, New Haven, CT.
MD, MS
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Kevin N. Sheth
From the Division of Neurocritical Care & Emergency Neurology (J.N.A., C.P.B., A.C.L., V.M.T.-L., A.H., N.H.P., K.N.S., G.J.F.), Department of Neurology, Yale School of Medicine; Frank H. Netter MD School of Medicine (Z.S.D., C.J.C.); Division of Vascular Neurology (N.H.P., L.H.S.), Department of Neurology, Yale School of Medicine; and Department of Internal Medicine (T.M.G.), Yale School of Medicine, New Haven, CT.
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Guido J. Falcone
From the Division of Neurocritical Care & Emergency Neurology (J.N.A., C.P.B., A.C.L., V.M.T.-L., A.H., N.H.P., K.N.S., G.J.F.), Department of Neurology, Yale School of Medicine; Frank H. Netter MD School of Medicine (Z.S.D., C.J.C.); Division of Vascular Neurology (N.H.P., L.H.S.), Department of Neurology, Yale School of Medicine; and Department of Internal Medicine (T.M.G.), Yale School of Medicine, New Haven, CT.
MD, ScD, MPH
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Citation
Polygenic Susceptibility to Hypertension and Blood Pressure Control in Stroke Survivors
Julián N. 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 N. Sheth, Guido J. Falcone
Neurology Apr 2023, 100 (15) e1587-e1597; 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 risk scores (PRSs) 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 mm Hg or diastolic BP > 90 mm Hg), 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 vs very high PSH, the mean systolic BP was 137 (SD 18) vs 143 (SD 20, p < 0.001), the mean diastolic BP was 81 (SD 10) vs 84 (SD 11, p < 0.001), the prevalence of uncontrolled BP was 42.8% vs 57.2% (p < 0.001), and the prevalence of resistant hypertension was 3.9% vs 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.

Glossary

BP=
blood pressure;
ICD=
International Classification of Diseases;
PRS=
polygenic risk score;
PSH=
polygenic susceptibility to hypertension;
SNVs=
single nucleotide variations;
VISP=
Vitamin Intervention for Stroke Prevention

Footnotes

  • Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Submitted and externally peer reviewed. The handling editor was Editor-in-Chief José Merino, MD, MPhil, FAAN.

  • Editorial, page 693

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