Notes
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.
Application 53003
Understanding the role of blood pressure in vascular and non-vascular diseases
High blood pressure is a well-recognized modifiable risk factor for vascular and non-vascular diseases including cardiovascular diseases, chronic kidney diseases and dementia. International medical organizations and health authorities provide recommended blood pressure targets for hypertension management. In 2017, the American College of Cardiology and the American Heart Association (ACC/AHA) proposed to lower the diagnostic cut-off readings for hypertension from systolic and diastolic blood pressure (SBP/DBP) !140/90mmHg to !130/80mmHg, and the treatment goal for hypertension to SBP<130mmHg and DBP<80mmHg. However, the recommendation remains controversial worldwide. The aims of this study is to evaluate the role of blood pressure and its treatment in vascular and non-vascular diseases, and survival, using complimentary methods, i.e., observational and genetically, in the UK Biobank. The expected findings in this study will provide solid evidence about the role of blood pressure and its treatment in vascular and non-vascular diseases and survival to inform clinical management of diagnostic cut-off readings and treatment targets in hypertension, which is one of the commonest chronic diseases worldwide. Understanding the role of blood pressure can assist researchers and clinicians in setting evidence-based blood pressure targets and recommendations for potential interventions.
Lead investigator: | Dr Eric Yuk Fai Wan |
Lead institution: | University of Hong Kong |