| Title: | Association of genetic variants related to combined lipid-lowering and antihypertensive therapies with risk of cardiovascular disease: 2 × 2 factorial Mendelian randomization analyses |
| Journal: | BMC Medicine |
| Published: | 20 May 2024 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/38764043/ |
| DOI: | https://doi.org/10.1186/s12916-024-03407-x |
| URL: | https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-024-03407-x |
Publication 12035
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Abstract
BackgroundLipid-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.MethodsWe 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.ResultsIndependent 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).ConclusionsGenetically 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.</p>
13 Keywords
- Aged
- Antihypertensive Agents
- Blood Pressure
- Cardiovascular Diseases
- Drug Therapy, Combination
- Female
- Genetic Variation
- Humans
- Hypolipidemic Agents
- Male
- Mendelian Randomization Analysis
- Middle Aged
- United Kingdom
9 Authors
- Ying Li
- Hongwei Liu
- Chong Shen
- Jianxin Li
- Fangchao Liu
- Keyong Huang
- Dongfeng Gu
- Yun Li
- Xiangfeng Lu
1 Application
| Application ID | Title |
|---|---|
| 69815 | Improving risk prediction of cardiometabolic diseases by integrating ethnic-specific genetic variants and environmental predictors |
Enabling scientific discoveries that improve human health