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, while 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 two-sample Mendelian randomization (MR) using a range of pleiotropy-robust methods. RESULTS: Genetically-predicted increased systolic BP (SBP), diastolic BP (DBP), and mean arterial pressure (MAP) all significantly associate with higher AscAoD (SBP: β estimate = 0.0041 mm/mmHg, 95% confidence interval [CI] 0.0008 to 0.0074, p = 0.02, DBP: β estimate = 0.0272 mm/mmHg, 95%CI 0.0224 to 0.0320, p < 0.001, and MAP: β estimate = 0.0168 mm/mmHg, 95%CI 0.0130 to 0.0206, p < 0.001). Genetically-predicted pulse pressure (PP), meanwhile, had an inverse association with AscAoD (β estimate = -0.0155 mm/mmHg, 95%CI -0.0213 to -0.0096, p < 0.001). Multivariable MR analyses showed that genetically-predicted increased MAP and reduced PP were independently associated with AscAoD. Bidirectional MR demonstrated that genetically-predicted AscAoD was inversely associated with PP (β estimate = -2.0721 mmHg/mm, 95%CI -3.1137 to -1.0306, p < 0.001) and SBP (β estimate = -1.2878 mmHg/mm, 95%CI -2.3533 to -0.2224, p = 0.02), while directly associated with DBP (0.8203 mmHg/mm, 95%CI 0.2735 to 1.3672, p = 0.004). CONCLUSIONS: BP likely contributes causally to ascending thoracic aortic dilation. Increased AscAoD likely contributes to lower SBP and PP, but not DBP, consistent with the hemodynamic consequences of a reduced aortic diameter.