دورية أكاديمية
أعرض في EDS

Antihypertensive Drugs for the Prevention of Atrial Fibrillation: A Drug Target Mendelian Randomization Study.

التفاصيل البيبلوغرافية
العنوان: Antihypertensive Drugs for the Prevention of Atrial Fibrillation: A Drug Target Mendelian Randomization Study.
المؤلفون: Geurts S; Department of Epidemiology (S.G., M.J.T., Z.L., B.H.C.S., J.W.D., M.A.I., M.K.), Erasmus MC, University Medical Center Rotterdam, The Netherlands., Tilly MJ; Department of Epidemiology (S.G., M.J.T., Z.L., B.H.C.S., J.W.D., M.A.I., M.K.), Erasmus MC, University Medical Center Rotterdam, The Netherlands., Lu Z; Department of Epidemiology (S.G., M.J.T., Z.L., B.H.C.S., J.W.D., M.A.I., M.K.), Erasmus MC, University Medical Center Rotterdam, The Netherlands., Stricker BHC; Department of Epidemiology (S.G., M.J.T., Z.L., B.H.C.S., J.W.D., M.A.I., M.K.), Erasmus MC, University Medical Center Rotterdam, The Netherlands., Deckers JW; Department of Epidemiology (S.G., M.J.T., Z.L., B.H.C.S., J.W.D., M.A.I., M.K.), Erasmus MC, University Medical Center Rotterdam, The Netherlands., de Groot NMS; Department of Cardiology (N.M.S.G.), Erasmus MC, University Medical Center Rotterdam, The Netherlands., Miller CL; Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville (C.L.M.)., Ikram MA; Department of Epidemiology (S.G., M.J.T., Z.L., B.H.C.S., J.W.D., M.A.I., M.K.), Erasmus MC, University Medical Center Rotterdam, The Netherlands., Kavousi M; Department of Epidemiology (S.G., M.J.T., Z.L., B.H.C.S., J.W.D., M.A.I., M.K.), Erasmus MC, University Medical Center Rotterdam, The Netherlands.
المصدر: Hypertension (Dallas, Tex. : 1979) [Hypertension] 2024 Aug; Vol. 81 (8), pp. 1766-1775. Date of Electronic Publication: 2024 Jun 19.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Lippincott, Williams & Wilkins Country of Publication: United States NLM ID: 7906255 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1524-4563 (Electronic) Linking ISSN: 0194911X NLM ISO Abbreviation: Hypertension Subsets: MEDLINE
أسماء مطبوعة: Publication: : Hagerstown, MD : Lippincott, Williams & Wilkins
Original Publication: [Dallas, Tex.] : [American Heart Association], [©1979]-
مواضيع طبية MeSH: Mendelian Randomization Analysis* , Atrial Fibrillation*/genetics , Atrial Fibrillation*/drug therapy , Atrial Fibrillation*/prevention & control , Antihypertensive Agents*/therapeutic use , Polymorphism, Single Nucleotide* , Genome-Wide Association Study* , Hypertension*/genetics , Hypertension*/drug therapy , Blood Pressure*/drug effects , Blood Pressure*/genetics, Humans ; Male ; Female
مستخلص: Background: We investigated the potential impact of antihypertensive drugs for atrial fibrillation (AF) prevention through a drug target Mendelian randomization study to avoid the potential limitations of clinical studies.
Methods: Validated published single-nucleotide polymorphisms (SNPs) that mimic the action of 12 antihypertensive drug classes, including alpha-adrenoceptor blockers, adrenergic neuron blockers, angiotensin-converting enzyme inhibitors, angiotensin-II receptor blockers, beta-adrenoceptor blockers, centrally acting antihypertensive drugs, calcium channel blockers, loop diuretics, potassium-sparing diuretics and mineralocorticoid receptor antagonists, renin inhibitors, thiazides and related diuretic agents, and vasodilators were used. We estimated, via their corresponding gene and protein targets, the downstream effect of these drug classes to prevent AF via systolic blood pressure using 2-sample Mendelian randomization analyses. The SNPs were extracted from 2 European genome-wide association studies for the drug classes (n=317 754; n=757 601) and 1 European genome-wide association study for AF (n=1 030 836).
Results: Drug target Mendelian randomization analyses supported the significant preventive causal effects of lowering systolic blood pressure per 10 mm Hg via alpha-adrenoceptor blockers (n=11 SNPs; odds ratio [OR], 0.34 [95% CI, 0.21-0.56]; P =2.74×10 -05 ), beta-adrenoceptor blockers (n=17 SNPs; OR, 0.52 [95% CI, 0.35-0.78]; P =1.62×10 -03 ), calcium channel blockers (n=49 SNPs; OR, 0.50 [95% CI, 0.36-0.70]; P =4.51×10 -05 ), vasodilators (n=19 SNPs; OR, 0.53 [95% CI, 0.34-0.84]; P =7.03×10 -03 ), and all 12 antihypertensive drug classes combined (n=158 SNPs; OR, 0.64 [95% CI, 0.54-0.77]; P =8.50×10 -07 ) on AF risk.
Conclusions: Our results indicated that lowering systolic blood pressure via protein targets of various antihypertensive drugs seems promising for AF prevention. Our findings inform future clinical trials and have implications for repurposing antihypertensive drugs for AF prevention.
Competing Interests: M.A. Ikram reports consulting fees from BioGen Inc. The other authors report no conflicts.
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فهرسة مساهمة: Keywords: Mendelian randomization analysis; antihypertensive agents; atrial fibrillation; drug repositioning; epidemiology; genomics; polymorphism, single nucleotide
المشرفين على المادة: 0 (Antihypertensive Agents)
تواريخ الأحداث: Date Created: 20240717 Date Completed: 20240717 Latest Revision: 20240719
رمز التحديث: 20240719
مُعرف محوري في PubMed: PMC11251507
DOI: 10.1161/HYPERTENSIONAHA.123.21858
PMID: 39018378
قاعدة البيانات: MEDLINE
الوصف
تدمد:1524-4563
DOI:10.1161/HYPERTENSIONAHA.123.21858