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.
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 language | English |
|---|---|
| Pages (from-to) | 707-707 |
| Journal | Journal of Human Hypertension |
| Volume | 32 |
| Issue number | 10 |
| Publication status | Published - Oct 2018 |
| Event | 2018 Annual Scientific Meeting of the British and Irish Hypertension Society - Robinson College Cambridge, Cambridge, United Kingdom Duration: 24 Sept 2018 → 26 Dec 2018 https://bihsoc.org/events/annual-scientific-meeting/previous-asms/ |
