Blood Pressure and Risk of Cardiovascular Disease in UK Biobank: A Mendelian Randomization Study

Eric Yuk Fai Wan, Wing Tung Fung, C. Mary Schooling, Shiu Lun Au Yeung, Man Ki Kwok, Esther Yee Tak Yu, Yuan Wang, Esther Wai Yin Chan, Ian Chi Kei Wong, Cindy Lo Kuen Lam

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47 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)367-375
Number of pages9
JournalHypertension
Volume77
Issue number2
DOIs
Publication statusPublished - 1 Feb 2021
Externally publishedYes

Keywords

  • cardiovascular diseases
  • cohort studies
  • hypertension
  • odds ratio
  • stroke

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