Relationship Between Ascending Thoracic Aortic Diameter and Blood Pressure: A Mendelian Randomization Study

Background:Observational studies identified elevated blood pressure (BP) as a strong risk factor for thoracic aortic dilation, and BP reduction is the primary medical intervention recommended to prevent progression of aortic aneurysms. However, although BP may impact aortic dilation, aortic size may also impact BP. The causal relationship between BP and thoracic aortic size has not been reliably established. Methods:Genome-wide association studies summary statistics were obtained for BP and ascending thoracic aortic diameter (AscAoD). Causal effects of BP on AscAoD were estimated using 2-sample Mendelian randomization using a range of pleiotropy-robust methods. Results:Genetically predicted increased systolic BP, diastolic BP, and mean arterial pressure all significantly associate with higher AscAoD (systolic BP: beta estimate, 0.0041 mm/mm Hg [95% CI, 0.0008-0.0074]; P=0.02, diastolic BP: beta estimate, 0.0272 mm/mm Hg [95% CI, 0.0224-0.0320]; P<0.001, and mean arterial pressure: beta estimate, 0.0168 mm/mm Hg [95% CI, 0.0130-0.0206]; P<0.001). Genetically predicted pulse pressure, meanwhile, had an inverse association with AscAoD (beta estimate, -0.0155 mm/mm Hg [95% CI, -0.0213 to -0.0096]; P<0.001). Multivariable Mendelian randomization analyses showed that genetically predicted increased mean arterial pressure and reduced pulse pressure were independently associated with AscAoD. Bidirectional Mendelian randomization demonstrated that genetically predicted AscAoD was inversely associated with pulse pressure (beta estimate, -2.0721 mm Hg/mm [95% CI, -3.1137 to -1.0306]; P<0.001) and systolic BP (beta estimate, -1.2878 mm Hg/mm [95% CI, -2.3533 to -0.2224]; P=0.02), while directly associated with diastolic BP (0.8203 mm Hg/mm [95% CI, 0.2735-1.3672]; P=0.004). Conclusions:BP likely contributes causally to ascending thoracic aortic dilation. Increased AscAoD likely contributes to lower systolic BP and pulse pressure, but not diastolic BP, consistent with the hemodynamic consequences of a reduced aortic diameter.