Causal effect of hypertension and blood pressure on aortic diseases: evidence from Mendelian randomization

Tao Yang; Xin Yuan; Wei Gao; Min-Jie Lu; Meng-Jin Hu; Han-Song Sun

doi:10.1038/s41440-023-01351-6

Causal effect of hypertension and blood pressure on aortic diseases: evidence from Mendelian randomization

Hypertens Res. 2023 Sep;46(9):2203-2212. doi: 10.1038/s41440-023-01351-6. Epub 2023 Jul 13.

Authors

Tao Yang¹, Xin Yuan¹, Wei Gao¹, Min-Jie Lu², Meng-Jin Hu³, Han-Song Sun⁴

Affiliations

¹ Department of Cardiovascular Surgery, Cardiovascular Institute and Fu Wai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, National Center for Cardiovascular Diseases, No.167 North Lishi Road, Xicheng District, Beijing, 100037, China.
² Department of Magnetic Resonance Imaging, Cardiovascular Institute and Fu Wai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, National Center for Cardiovascular Diseases, No.167 North Lishi Road, Xicheng District, Beijing, 100037, China. coolkan@163.com.
³ Department of Cardiology, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China.
⁴ Department of Cardiovascular Surgery, Cardiovascular Institute and Fu Wai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, National Center for Cardiovascular Diseases, No.167 North Lishi Road, Xicheng District, Beijing, 100037, China. drsunhs@sina.com.

PMID: 37443259
DOI: 10.1038/s41440-023-01351-6

Abstract

Hypertension or elevated blood pressure was documented to be an important risk factor for aortic diseases in observational studies, yet the causality remains to be determined. By applying a two-sample Mendelian randomization (MR) approach, we aim to determine whether hypertension or elevated blood pressure (systolic blood pressure [SBP] or diastolic blood pressure [DBP]) is linked causally to aortic aneurysm or aortic dissection. Genetic instruments and summary statistics for hypertension and aortic diseases were obtained from large genome-wide association studies. The traditional inverse variance weighted (IVW) method was used to obtain the causal estimates. Sensitivity analyses including MR-Egger, weighted median and multivariable MR were also performed. Our results suggested that genetic liability to hypertension was associated with aortic dissection (odds ratio [OR]: 1.81; 95% confidence interval [CI]: 1.27-2.58; P = 1.13 × 10^-3) and aortic aneurysm (OR: 1.43; 95% CI: 1.22-1.66; P = 7.79 × 10^-6). Per standard deviation increase in genetically-determined DBP was significantly associated with increased aortic dissection (OR: 1.14; 95% CI: 1.09-1.19; P = 1.58 × 10^-9) and aortic aneurysm (OR: 1.07; 95% CI: 1.05-1.09; P = 8.37 × 10^-14). There was a null association between SBP and aortic dissection (OR: 1.01; 95% CI: 0.99-1.94; P = 0.38) or aortic aneurysm (OR: 1.00; 95% CI: 0.99-1.01; P = 0.92). Sensitivity analyses documented similar results. Therefore, hypertension and elevated DBP are causally associated with higher risks of aortic aneurysm and aortic dissection. Preventive interventions for aortic diseases may consider individuals with hypertension, especially those with higher DBP. Meanwhile, further research is required to determine the mechanisms underlying the significantly greater correlation between DBP and aortic diseases than SBP.

Keywords: Aortic aneurysm; Aortic dissection; Diastolic blood pressure; Hypertension; Systolic blood pressure.

MeSH terms

Aortic Dissection* / genetics
Blood Pressure / genetics
Genome-Wide Association Study
Humans
Hypertension* / etiology
Mendelian Randomization Analysis
Polymorphism, Single Nucleotide