Blood Pressure and Risk of Cardiovascular Disease in UK Biobank

Author:

Wan Eric Yuk Fai12ORCID,Fung Wing Tung1,Schooling C. Mary34ORCID,Au Yeung Shiu Lun3ORCID,Kwok Man KiORCID,Yu Esther Yee Tak1ORCID,Wang Yuan1,Chan Esther Wai Yin5ORCID,Wong Ian Chi Kei26ORCID,Lam Cindy Lo Kuen1

Affiliation:

1. Department of Family Medicine and Primary Care (E.Y.F.W., W.T.F., E.Y.T.Y., Y.W., C.L.K.L.)

2. Department of Pharmacology and Pharmacy (E.Y.F.W., I.C.K.W.)

3. School of Public Health, Li Ka Shing Faculty of Medicine (C.M.S., S.L.A.Y., M.K.K.)

4. The University of Hong Kong. School of Public Health and Health Policy, City University of New York (C.M.S.).

5. Department of Pharmacology and Pharmacy, Centre for Safe Medication Practice and Research (E.W.Y.C.)

6. Research Department of Practice and Policy, School of Pharmacy, University College London, United Kingdom (I.C.K.W.).

Abstract

This study aims to evaluate the causal association of blood pressure (BP) with cardiovascular diseases (CVDs). Two-sample Mendelian randomization was performed using a large genome-wide association study (n=299 024) and the UK Biobank cohort (n=375 256). We identified 327 and 364 single-nucleotide polymorphisms strongly and independently associated with systolic BP and diastolic BP, respectively, as genetic instruments to assess the causal association of BP with total CVD, CVD mortality, and 14 cardiovascular conditions. Nonlinearity was examined with nonlinear instrumental variable assumptions. Genetically predicted BP was significantly positively associated with total CVD (systolic BP, per 10 mm Hg: odds ratio [OR], 1.32 [95% CI, 1.25–1.40]; diastolic BP, per 5 mm Hg: OR, 1.20 [95% CI, 1.15–1.26]). Similar positive causal associations were observed for 14 cardiovascular conditions including ischemic heart disease (systolic BP, per 10 mm Hg: OR, 1.33 [95% CI, 1.24–1.41]; diastolic BP, per 5 mm Hg: OR, 1.20 [95% CI, 1.14–1.27]) and stroke (systolic BP, per 10 mm Hg: OR, 1.35 [95% CI, 1.24–1.48]; diastolic BP, per 5 mm Hg: OR, 1.20 [95% CI, 1.12–1.28]). Nonlinearity Mendelian randomization test demonstrated linear causal association of BP with these outcomes. Consistent estimates were observed in sensitivity analyses, suggesting robustness of the associations and minimal horizontal pleiotropy. The linear positive causal association of BP and CVD was consistent with previous findings that lower BP is better, thus consolidating clinical knowledge on hypertension management in CVD risk reduction.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Internal Medicine

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