Association of genetic variants related to combined lipid-lowering and antihypertensive therapies with risk of cardiovascular disease: 2 × 2 factorial Mendelian randomization analyses

Li，Ying1,2,3; Liu，Hongwei4; Shen，Chong1,5; Li，Jianxin2,3; Liu，Fangchao2,3; Huang，Keyong2,3; Gu，Dongfeng1,2,3,6,7; Li，Yun8; Lu，Xiangfeng1,2,3

2024-12-01

10.1186/s12916-024-03407-x

BMC Medicine   影响因子和分区

1741-7015

Background: Lipid-lowering drugs and antihypertensive drugs are commonly combined for cardiovascular disease (CVD). However, the relationship of combined medications with CVD remains controversial. We aimed to explore the associations of genetically proxied medications of lipid-lowering and antihypertensive drugs, either alone or both, with risk of CVD, other clinical and safety outcomes. Methods: We divided 423,821 individuals in the UK Biobank into 4 groups via median genetic scores for targets of lipid-lowering drugs and antihypertensive drugs: lower low-density lipoprotein cholesterol (LDL-C) mediated by targets of statins or proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, lower systolic blood pressure (SBP) mediated by targets of β-blockers (BBs) or calcium channel blockers (CCBs), combined genetically lower LDL-C and SBP, and reference (genetically both higher LDL-C and SBP). Associations with risk of CVD and other clinical outcomes were explored among each group in factorial Mendelian randomization. Results: Independent and additive effects were observed between genetically proxied medications of lipid-lowering and antihypertensive drugs with CVD (including coronary artery disease, stroke, and peripheral artery diseases) and other clinical outcomes (ischemic stroke, hemorrhagic stroke, heart failure, diabetes mellitus, chronic kidney disease, and dementia) (P > 0.05 for interaction in all outcomes). Take the effect of PCSK9 inhibitors and BBs on CVD for instance: compared with the reference, PCSK9 group had a 4% lower risk of CVD (odds ratio [OR], 0.96; 95%CI, 0.94–0.99), and a 3% lower risk was observed in BBs group (OR, 0.97; 95%CI, 0.94–0.99), while combined both were associated with a 6% additively lower risk (OR, 0.94; 95%CI, 0.92–0.97; P = 0.87 for interaction). Conclusions: Genetically proxied medications of combined lipid-lowering and antihypertensive drugs have an independent and additive effects on CVD, other clinical and safety outcomes, with implications for CVD clinical practice, subsequent trials as well as drug development of polypills.

Antihypertensive drugs Cardiovascular disease Factorial Mendelian randomization Lipid-lowering drugs

SCI

英语

其他

2-s2.0-85193629704

Scopus

1.Department of Epidemiology,Center for Global Health,School of Public Health,Nanjing Medical University,Nanjing,211166,China
2.Department of Epidemiology,Fuwai Hospital,National Center for Cardiovascular Diseases,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing,100037,China
3.Key Laboratory of Cardiovascular Epidemiology,Chinese Academy of Medical Sciences,Beijing,100037,China
4.Department of Cancer Epidemiology,The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital,Zhengzhou,450008,China
5.Research Units of Cohort Study On Cardiovascular Diseases and Cancers,Chinese Academy of Medical Sciences,Beijing,100730,China
6.School of Public Health and Emergency Management,Southern University of Science and Technology,Shenzhen,518055,China
7.School of Medicine,Southern University of Science and Technology,Shenzhen,518055,China
8.School of Public Health,North China University of Science and Technology,Tangshan,063210,China

Li，Ying,Liu，Hongwei,Shen，Chong,et al. Association of genetic variants related to combined lipid-lowering and antihypertensive therapies with risk of cardiovascular disease: 2 × 2 factorial Mendelian randomization analyses[J]. BMC Medicine,2024,22(1).

Li，Ying.,Liu，Hongwei.,Shen，Chong.,Li，Jianxin.,Liu，Fangchao.,...&Lu，Xiangfeng.(2024).Association of genetic variants related to combined lipid-lowering and antihypertensive therapies with risk of cardiovascular disease: 2 × 2 factorial Mendelian randomization analyses.BMC Medicine,22(1).

Li，Ying,et al."Association of genetic variants related to combined lipid-lowering and antihypertensive therapies with risk of cardiovascular disease: 2 × 2 factorial Mendelian randomization analyses".BMC Medicine 22.1(2024).