Primary aldosteronism and lower-extremity arterial disease: a two-sample Mendelian randomization study
Abstract Background and Aims Primary aldosteronism (PA) is an adrenal disorder of autonomous aldosterone secretion which promotes arterial injury. We aimed to explore whether PA is causally associated with lower-extremity arterial disease (LEAD). Methods We included 39,713 patients with diabetes and...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-12-01
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| Series: | Cardiovascular Diabetology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12933-023-02086-x |
| _version_ | 1797377213684776960 |
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| author | Jinbo Hu Qinglian Zeng Xiangjun Chen Wenjin Luo Ziwei Tang Mei Mei Wenrui Zhao Zhipeng Du Zhiping Liu Qifu Li Qingfeng Cheng Shumin Yang |
| author_facet | Jinbo Hu Qinglian Zeng Xiangjun Chen Wenjin Luo Ziwei Tang Mei Mei Wenrui Zhao Zhipeng Du Zhiping Liu Qifu Li Qingfeng Cheng Shumin Yang |
| author_sort | Jinbo Hu |
| collection | DOAJ |
| description | Abstract Background and Aims Primary aldosteronism (PA) is an adrenal disorder of autonomous aldosterone secretion which promotes arterial injury. We aimed to explore whether PA is causally associated with lower-extremity arterial disease (LEAD). Methods We included 39,713 patients with diabetes and 419,312 participants without diabetes from UK Biobank. We derived a polygenic risk score (PRS) for PA based on previous genome-wide association studies (GWAS). Outcomes included LEAD and LEAD related gangrene or amputation. We conducted a two-sample Mendelian randomization analysis for PA and outcomes to explore their potential causal relationship. Results In whole population, individuals with a higher PA PRS had an increased risk of LEAD. Among patients with diabetes, compared to the subjects in the first tertile of PA PRS, subjects in the third tertile showed a 1.24-fold higher risk of LEAD (OR 1.24, 95% CI 1.03–1.49) and a 2.09-fold higher risk of gangrene (OR 2.09, 95% CI 1.27–3.44), and 1.72-fold higher risk of amputation (OR 1.72, 95% CI 1.10–2.67). Among subjects without diabetes, there was no significant association between PA PRS and LEAD, gangrene or amputation. Two-sample Mendelian randomization analysis indicated that genetically predictors of PA was significantly associated with higher risks of LEAD and gangrene (inverse variance weighted OR 1.20 [95% CI 1.08–1.34]) for LEAD, 1.48 [95% CI 1.28–1.70] for gangrene), with no evidence of significant heterogeneity or directional pleiotropy. Conclusions Primary aldosteronism is genetically and causally associated with higher risks of LEAD and gangrene, especially among patients with diabetes. Targeting on the autonomous aldosterone secretion may prevent LEAD progression. |
| first_indexed | 2024-03-08T19:49:32Z |
| format | Article |
| id | doaj.art-a0ad75f977bf4947af6e4eb8b2df01a0 |
| institution | Directory Open Access Journal |
| issn | 1475-2840 |
| language | English |
| last_indexed | 2024-03-08T19:49:32Z |
| publishDate | 2023-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Cardiovascular Diabetology |
| spelling | doaj.art-a0ad75f977bf4947af6e4eb8b2df01a02023-12-24T12:09:15ZengBMCCardiovascular Diabetology1475-28402023-12-012211810.1186/s12933-023-02086-xPrimary aldosteronism and lower-extremity arterial disease: a two-sample Mendelian randomization studyJinbo Hu0Qinglian Zeng1Xiangjun Chen2Wenjin Luo3Ziwei Tang4Mei Mei5Wenrui Zhao6Zhipeng Du7Zhiping Liu8Qifu Li9Qingfeng Cheng10Shumin Yang11Department of Endocrinology, the First Affiliated Hospital of Chongqing Medical UniversityDepartment of Endocrinology, the First Affiliated Hospital of Chongqing Medical UniversityDepartment of Endocrinology, the First Affiliated Hospital of Chongqing Medical UniversityDepartment of Endocrinology, the First Affiliated Hospital of Chongqing Medical UniversityDepartment of Endocrinology, the First Affiliated Hospital of Chongqing Medical UniversityDepartment of Endocrinology, the First Affiliated Hospital of Chongqing Medical UniversityDepartment of Endocrinology, the First Affiliated Hospital of Chongqing Medical UniversityDepartment of Endocrinology, the First Affiliated Hospital of Chongqing Medical UniversityDepartment of Endocrinology, the First Affiliated Hospital of Chongqing Medical UniversityDepartment of Endocrinology, the First Affiliated Hospital of Chongqing Medical UniversityDepartment of Endocrinology, the First Affiliated Hospital of Chongqing Medical UniversityDepartment of Endocrinology, the First Affiliated Hospital of Chongqing Medical UniversityAbstract Background and Aims Primary aldosteronism (PA) is an adrenal disorder of autonomous aldosterone secretion which promotes arterial injury. We aimed to explore whether PA is causally associated with lower-extremity arterial disease (LEAD). Methods We included 39,713 patients with diabetes and 419,312 participants without diabetes from UK Biobank. We derived a polygenic risk score (PRS) for PA based on previous genome-wide association studies (GWAS). Outcomes included LEAD and LEAD related gangrene or amputation. We conducted a two-sample Mendelian randomization analysis for PA and outcomes to explore their potential causal relationship. Results In whole population, individuals with a higher PA PRS had an increased risk of LEAD. Among patients with diabetes, compared to the subjects in the first tertile of PA PRS, subjects in the third tertile showed a 1.24-fold higher risk of LEAD (OR 1.24, 95% CI 1.03–1.49) and a 2.09-fold higher risk of gangrene (OR 2.09, 95% CI 1.27–3.44), and 1.72-fold higher risk of amputation (OR 1.72, 95% CI 1.10–2.67). Among subjects without diabetes, there was no significant association between PA PRS and LEAD, gangrene or amputation. Two-sample Mendelian randomization analysis indicated that genetically predictors of PA was significantly associated with higher risks of LEAD and gangrene (inverse variance weighted OR 1.20 [95% CI 1.08–1.34]) for LEAD, 1.48 [95% CI 1.28–1.70] for gangrene), with no evidence of significant heterogeneity or directional pleiotropy. Conclusions Primary aldosteronism is genetically and causally associated with higher risks of LEAD and gangrene, especially among patients with diabetes. Targeting on the autonomous aldosterone secretion may prevent LEAD progression.https://doi.org/10.1186/s12933-023-02086-xPrimary aldosteronismLower-extremity arterial diseaseDiabetesMendelian randomizationCausal relationship |
| spellingShingle | Jinbo Hu Qinglian Zeng Xiangjun Chen Wenjin Luo Ziwei Tang Mei Mei Wenrui Zhao Zhipeng Du Zhiping Liu Qifu Li Qingfeng Cheng Shumin Yang Primary aldosteronism and lower-extremity arterial disease: a two-sample Mendelian randomization study Cardiovascular Diabetology Primary aldosteronism Lower-extremity arterial disease Diabetes Mendelian randomization Causal relationship |
| title | Primary aldosteronism and lower-extremity arterial disease: a two-sample Mendelian randomization study |
| title_full | Primary aldosteronism and lower-extremity arterial disease: a two-sample Mendelian randomization study |
| title_fullStr | Primary aldosteronism and lower-extremity arterial disease: a two-sample Mendelian randomization study |
| title_full_unstemmed | Primary aldosteronism and lower-extremity arterial disease: a two-sample Mendelian randomization study |
| title_short | Primary aldosteronism and lower-extremity arterial disease: a two-sample Mendelian randomization study |
| title_sort | primary aldosteronism and lower extremity arterial disease a two sample mendelian randomization study |
| topic | Primary aldosteronism Lower-extremity arterial disease Diabetes Mendelian randomization Causal relationship |
| url | https://doi.org/10.1186/s12933-023-02086-x |
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