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Estimating the Population Benefits of Blood Pressure Lowering: A Wide-Angled Mendelian Randomization Study in UK Biobank

By Hannah Higgins, Amy M Mason, Susanna C Larsson, Dipender Gill, Claudia Langenberg, Stephen Burgess

Posted 05 Feb 2021
medRxiv DOI: 10.1101/2021.02.02.21250515

Background The causal relevance of elevated blood pressure for several cardiovascular diseases is uncertain, as is the population impact of blood pressure lowering on risk of cardiovascular diseases more broadly. This study systematically assesses evidence of causality for various cardiovascular diseases in a two-sample Mendelian randomization framework, and estimates the potential reduction in the prevalence of these diseases attributable to long-term population shifts in the distribution of systolic blood pressure (SBP). Methods and Results We investigated associations of genetically-predicted SBP as predicted by 258 genetic variants with 21 cardiovascular diseases in UK Biobank, a population-based cohort of UK residents. The sample consisted of 376,703 participants of European ancestry aged 40-69 years at baseline. Genetically-predicted SBP was positively associated with 14 of the outcomes (p<0.001), including dilated cardiomyopathy, endocarditis, peripheral vascular disease, and rheumatic heart disease. Using genetic variation to estimate the long-term impact of blood pressure lowering on disease, population reductions in SBP were predicted to result in an overall 16.9% (95% confidence interval (CI): 12.2-21.3%) decrease in morbidity for a 5 mmHg decrease from a population mean of 137.7 mmHg, 30.8% (95% CI: 22.8-38.0%) for a 10 mmHg decrease, and 56.2% (95% CI: 43.7-65.9%) decrease for a 22.7 mmHg decrease in SBP (22.7 mmHg represents a shift from the current mean SBP to 115 mmHg). Conclusions Risk of many cardiovascular diseases is influenced by long-term differences in SBP. The burden of a broad range of CVDs could be substantially reduced by long-term population-wide reductions in the distribution of blood pressure.

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