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

Abstract

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: β estimate, 0.0041 mm/mm Hg [95% CI, 0.0008–0.0074]; P =0.02, diastolic BP: β estimate, 0.0272 mm/mm Hg [95% CI, 0.0224–0.0320]; P <0.001, and mean arterial pressure: β 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 (β 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 (β estimate, −2.0721 mm Hg/mm [95% CI, −3.1137 to −1.0306]; P <0.001) and systolic BP (β 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.

Determinants of ascending aortic morphology: Cross-sectional deep learning-based analysis on 25,073 non-contrast-enhanced MRI of NAKO

“…Although males showed significantly larger mid-AAoD than females, no causal relationship between sex and mid-AAoD was found, suggesting that the difference is likely confounded by height and BSA. As shown in other studies 35,13,36 , we observed a larger mid-AAoD in hypertensive subjects independent of age and BSA. Causal analysis confirmed direct causal relations between hypertension and mid-AAoD.…”

“…Previous studies performed automated analysis of the thoracic aorta either on CT data 25,26,11,27 or only analyzed single points instead of describing the whole thoracic aorta 14,15,13 . To overcome these limitations, we improved our previous DL-based framework 20 for three-dimensional segmentation of the thoracic aorta in NE-MRA by simultaneously predicting landmark points on the thoracic aorta.…”

“…higher age groups as UK Biobank study). [13][14][15][16] Most of these studies primarily conducted conventional statistical analyses that examined correlations between individual risk factors and morphological changes in the thoracic aorta. Such analyses, however, fail to capture causal determinants of aortic morphology.…”

2024 Heart Disease and Stroke Statistics: A Report of US and Global Data From the American Heart Association

“…In a mendelian randomization analysis from the UK Biobank and MVP, genetically predicted SBP, DBP, and mean arterial pressure were all associated with increased ascending thoracic aortic diameter (all P <0.05). 102…”