Using a weighted genetic risk core to investigate the clinical impact of genetically determined Systolic Blood Pressure in a Large Prospective Cohort

Research output: Contribution to journalMeeting abstract

Abstract

Introduction: We investigated the clinical impact of a 162 variant weighted genetic score (wGS) for systolic blood pressure (SBP) in the type 2 diabetes (T2D) GoDARTS bioresource1, linked to long-term electronic medical records.

Methods: The wGS was constructed using published coefficients from genome-wide association studies. Each SBP value was labelled according to the number of antihypertensive therapies the patient was taking at the time of measurement. Mixed linear models for repeated measures were used to investigate the impact of the wGS on SBP, and logistic and Cox’s regression to investigate Major Adverse Cardiac Events (MACE).

Results: The study comprised 8,034 patients (97% with T2D) and 382,305 SBP recordings (median 54 [IQR 41–70]) per individual over a median of 11.6 (IQR 6.9–16.5) years. 8.9% of SBP variance was explained by wGS, age and sex. Patients were on significantly more antihypertensive therapies (p = 4.7 × 10–15) in the wGS top tertile compared with the bottom where, after adjustment for therapy, SBPs were higher by 3.1 mmHg (95%CI 2.4–3.8; p = 9.1 × 10–18). Patients in the top wGS tertile were significantly more likely to have a history of hospitalisation for MACE (OR 1.19, 95%CI 1.05–1.34; p = 0.007) and during 10 year follow-up a 25.2% (95%CI 8.6–44; p = 0.002) increased risk of cardiovascular death.

Conclusions: Patients in the top tertile of wGS have higher SBP and remain at increased risk of MACE despite increased antihypertensive therapy. With a rapidly increasing proportion of SBP variability being explained by genetic factors, such instruments may soon be used clinically to improve cardiovascular risk management.
Original languageEnglish
Pages (from-to)707-707
JournalJournal of Human Hypertension
Volume32
Issue number10
Publication statusPublished - Oct 2018
Event2018 Annual Scientific Meeting of the British and Irish Hypertension Society - Robinson College Cambridge, Cambridge, United Kingdom
Duration: 24 Sep 201826 Dec 2018
https://bihsoc.org/events/annual-scientific-meeting/previous-asms/

Cite this

@article{82d72e84b68748d3b07be8db52abb63c,
title = "Using a weighted genetic risk core to investigate the clinical impact of genetically determined Systolic Blood Pressure in a Large Prospective Cohort",
abstract = "Introduction: We investigated the clinical impact of a 162 variant weighted genetic score (wGS) for systolic blood pressure (SBP) in the type 2 diabetes (T2D) GoDARTS bioresource1, linked to long-term electronic medical records.Methods: The wGS was constructed using published coefficients from genome-wide association studies. Each SBP value was labelled according to the number of antihypertensive therapies the patient was taking at the time of measurement. Mixed linear models for repeated measures were used to investigate the impact of the wGS on SBP, and logistic and Cox’s regression to investigate Major Adverse Cardiac Events (MACE).Results: The study comprised 8,034 patients (97{\%} with T2D) and 382,305 SBP recordings (median 54 [IQR 41–70]) per individual over a median of 11.6 (IQR 6.9–16.5) years. 8.9{\%} of SBP variance was explained by wGS, age and sex. Patients were on significantly more antihypertensive therapies (p = 4.7 × 10–15) in the wGS top tertile compared with the bottom where, after adjustment for therapy, SBPs were higher by 3.1 mmHg (95{\%}CI 2.4–3.8; p = 9.1 × 10–18). Patients in the top wGS tertile were significantly more likely to have a history of hospitalisation for MACE (OR 1.19, 95{\%}CI 1.05–1.34; p = 0.007) and during 10 year follow-up a 25.2{\%} (95{\%}CI 8.6–44; p = 0.002) increased risk of cardiovascular death.Conclusions: Patients in the top tertile of wGS have higher SBP and remain at increased risk of MACE despite increased antihypertensive therapy. With a rapidly increasing proportion of SBP variability being explained by genetic factors, such instruments may soon be used clinically to improve cardiovascular risk management.",
author = "Alexander Doney and Robert Flynn and Tsz Man and Colin Palmer and Louise Donnelly and Steven Morant and Isla Mackenzie and Thomas MacDonald",
year = "2018",
month = "10",
language = "English",
volume = "32",
pages = "707--707",
journal = "Journal of Human Hypertension",
issn = "0950-9240",
publisher = "Nature Publishing Group",
number = "10",

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TY - JOUR

T1 - Using a weighted genetic risk core to investigate the clinical impact of genetically determined Systolic Blood Pressure in a Large Prospective Cohort

AU - Doney, Alexander

AU - Flynn, Robert

AU - Man, Tsz

AU - Palmer, Colin

AU - Donnelly, Louise

AU - Morant, Steven

AU - Mackenzie, Isla

AU - MacDonald, Thomas

PY - 2018/10

Y1 - 2018/10

N2 - Introduction: We investigated the clinical impact of a 162 variant weighted genetic score (wGS) for systolic blood pressure (SBP) in the type 2 diabetes (T2D) GoDARTS bioresource1, linked to long-term electronic medical records.Methods: The wGS was constructed using published coefficients from genome-wide association studies. Each SBP value was labelled according to the number of antihypertensive therapies the patient was taking at the time of measurement. Mixed linear models for repeated measures were used to investigate the impact of the wGS on SBP, and logistic and Cox’s regression to investigate Major Adverse Cardiac Events (MACE).Results: The study comprised 8,034 patients (97% with T2D) and 382,305 SBP recordings (median 54 [IQR 41–70]) per individual over a median of 11.6 (IQR 6.9–16.5) years. 8.9% of SBP variance was explained by wGS, age and sex. Patients were on significantly more antihypertensive therapies (p = 4.7 × 10–15) in the wGS top tertile compared with the bottom where, after adjustment for therapy, SBPs were higher by 3.1 mmHg (95%CI 2.4–3.8; p = 9.1 × 10–18). Patients in the top wGS tertile were significantly more likely to have a history of hospitalisation for MACE (OR 1.19, 95%CI 1.05–1.34; p = 0.007) and during 10 year follow-up a 25.2% (95%CI 8.6–44; p = 0.002) increased risk of cardiovascular death.Conclusions: Patients in the top tertile of wGS have higher SBP and remain at increased risk of MACE despite increased antihypertensive therapy. With a rapidly increasing proportion of SBP variability being explained by genetic factors, such instruments may soon be used clinically to improve cardiovascular risk management.

AB - Introduction: We investigated the clinical impact of a 162 variant weighted genetic score (wGS) for systolic blood pressure (SBP) in the type 2 diabetes (T2D) GoDARTS bioresource1, linked to long-term electronic medical records.Methods: The wGS was constructed using published coefficients from genome-wide association studies. Each SBP value was labelled according to the number of antihypertensive therapies the patient was taking at the time of measurement. Mixed linear models for repeated measures were used to investigate the impact of the wGS on SBP, and logistic and Cox’s regression to investigate Major Adverse Cardiac Events (MACE).Results: The study comprised 8,034 patients (97% with T2D) and 382,305 SBP recordings (median 54 [IQR 41–70]) per individual over a median of 11.6 (IQR 6.9–16.5) years. 8.9% of SBP variance was explained by wGS, age and sex. Patients were on significantly more antihypertensive therapies (p = 4.7 × 10–15) in the wGS top tertile compared with the bottom where, after adjustment for therapy, SBPs were higher by 3.1 mmHg (95%CI 2.4–3.8; p = 9.1 × 10–18). Patients in the top wGS tertile were significantly more likely to have a history of hospitalisation for MACE (OR 1.19, 95%CI 1.05–1.34; p = 0.007) and during 10 year follow-up a 25.2% (95%CI 8.6–44; p = 0.002) increased risk of cardiovascular death.Conclusions: Patients in the top tertile of wGS have higher SBP and remain at increased risk of MACE despite increased antihypertensive therapy. With a rapidly increasing proportion of SBP variability being explained by genetic factors, such instruments may soon be used clinically to improve cardiovascular risk management.

M3 - Meeting abstract

VL - 32

SP - 707

EP - 707

JO - Journal of Human Hypertension

JF - Journal of Human Hypertension

SN - 0950-9240

IS - 10

ER -