Abstract 14134: Relationship Between Blood Pressure and Thoracic Aortic Diameter

Abstract

Introduction: The impact of blood pressure (BP) traits, including systolic/diastolic blood pressure (SBP/DBP), pulse pressure (PP) and mean arterial pressure (MAP), on thoracic aorta (TA) diameter remains poorly understood. Hypothesis: We hypothesize that genetic predisposition to elevated SBP, DBP, MAP and PP is related to risk of TA dilation suggesting enhanced primary and secondary prevention strategies for thoracic aortic aneurysm (TAA). Methods: We performed two-sample Mendelian randomization to investigate the effect of BP traits on TA diameter. We considered SBP, DBP, MAP, and PP in 479,103 participants of diverse ancestry from UK Biobank. We considered 32,215 participants from UK Biobank who underwent cardiac MRI for TA diameter. Genetic instruments were constructed from uncorrelated (r 2 < 0.001) genetic variants associated with each BP trait at genome-wide significance (p < 5 x 10 -8 ) in a pan-UK Biobank GWAS of BP traits. Results: Each of genetically-predicted MAP (beta = 0.017, 95% CI 0.013 to 0.021, p = 2 x 10 18 ), SBP (beta = 4.1 x 10 -3 , 95% CI 8.4 x 10 -4 to 7.4 x 10 -3 , p = 0.01) and DBP (beta = 0.27, 95% CI 0.022 to 0.032, p = 9 x 10 -29 ) were positively associated with increased TA diameter. PP was inversely associated with TA dimension (beta = -0.015, 95% CI -0.021 to -0.010, p = 2.4 x 10 -7 ). When considered jointly in multivariable Mendelian randomization, both genetically-predicted PP (beta = -0.037 mm/mmHg increase, 95% CI -0.045 to -0.029, p = 2 x 10 -20 ) and MAP (beta = 0.038mm/mmHg increase, 95% CI 0.031 to 0.046, p = 3 x 10 -23 ) were independently associated with TA diameter. In bi-directional analyses, increased TA diameter was associated with decreased PP and SBP, and increased DBP. Results were robust to MR methods that make different assumptions about the presence of pleiotropic variants, and using alternative genetic variants to proxy BP traits. Conclusions: These data suggest elevated BP contributes to TA diameter. Multivariable analysis suggests both steady pressure (proxied by MAP) and pulsatility (proxied by PP) directly contribute to aortic size. These findings suggest societal-level intervention to lower blood pressure to prevent TAA development and related morbidity and mortality.