Evaluating the Cardiovascular Impact of Genetically Proxied PCSK9 and HMGCR Inhibition in East Asian and European Populations: A Drug-Target Mendelian Randomization Study

HomeCirculation: Genomic and Precision MedicineVol. 17, No. 1Evaluating the Cardiovascular Impact of Genetically Proxied PCSK9 and HMGCR Inhibition in East Asian and European Populations: A Drug-Target Mendelian Randomization Study No AccessResearch ArticleRequest AccessFull TextAboutView Full TextView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toNo AccessResearch ArticleRequest AccessFull TextEvaluating the Cardiovascular Impact of Genetically Proxied PCSK9 and HMGCR Inhibition in East Asian and European Populations: A Drug-Target Mendelian Randomization Study Daniel B. Rosoff, Andrew S. Bell, Lucas A. Mavromatis, Ali Hamandi, Lauren Park, Jeesun Jung, Josephin Wagner, Pal Pacher, David Ray, George Davey Smith and Falk W. Lohoff Daniel B. RosoffDaniel B. Rosoff https://orcid.org/0000-0002-5718-7668 Section on Clinical Genomics and Experimental Therapeutics (D.B.R., A.S.B., L.A.M., A.H., L.P., J.J., J.W., F.W.L.), National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health (NIH), Bethesda, MD. NIH-Oxford-Cambridge Scholars Program, University of Oxford, United Kingdom (D.B.R.). Medical Research Council Integrative Epidemiology Unit, University of Bristol, United Kingdom (D.B.R., G.D.S.). , Andrew S. BellAndrew S. Bell https://orcid.org/0000-0003-2497-9420 Section on Clinical Genomics and Experimental Therapeutics (D.B.R., A.S.B., L.A.M., A.H., L.P., J.J., J.W., F.W.L.), National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health (NIH), Bethesda, MD. , Lucas A. MavromatisLucas A. Mavromatis https://orcid.org/0000-0003-2921-4654 Section on Clinical Genomics and Experimental Therapeutics (D.B.R., A.S.B., L.A.M., A.H., L.P., J.J., J.W., F.W.L.), National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health (NIH), Bethesda, MD. , Ali HamandiAli Hamandi Section on Clinical Genomics and Experimental Therapeutics (D.B.R., A.S.B., L.A.M., A.H., L.P., J.J., J.W., F.W.L.), National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health (NIH), Bethesda, MD. , Lauren ParkLauren Park https://orcid.org/0009-0003-6958-2539 Section on Clinical Genomics and Experimental Therapeutics (D.B.R., A.S.B., L.A.M., A.H., L.P., J.J., J.W., F.W.L.), National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health (NIH), Bethesda, MD. , Jeesun JungJeesun Jung https://orcid.org/0000-0002-2668-5541 Section on Clinical Genomics and Experimental Therapeutics (D.B.R., A.S.B., L.A.M., A.H., L.P., J.J., J.W., F.W.L.), National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health (NIH), Bethesda, MD. , Josephin WagnerJosephin Wagner https://orcid.org/0000-0002-8880-5721 Section on Clinical Genomics and Experimental Therapeutics (D.B.R., A.S.B., L.A.M., A.H., L.P., J.J., J.W., F.W.L.), National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health (NIH), Bethesda, MD. , Pal PacherPal Pacher https://orcid.org/0000-0001-7036-8108 Laboratory of Cardiovascular Physiology and Tissue Injury (P.P.), National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health (NIH), Bethesda, MD. , David RayDavid Ray https://orcid.org/0000-0002-4739-6773 Radcliffe Department of Medicine, Oxford Centre for Diabetes, Endocrinology, and Metabolism, University of Oxford, United Kingdom (D.R.). National Institute for Health and Care Research Oxford Biomedical Research Centre, John Radcliffe Hospital, United Kingdom (D.R.). , George Davey SmithGeorge Davey Smith https://orcid.org/0000-0002-1407-8314 Medical Research Council Integrative Epidemiology Unit, University of Bristol, United Kingdom (D.B.R., G.D.S.). and Falk W. LohoffFalk W. Lohoff Correspondence to: Falk W. Lohoff, MD, Section on Clinical Genomics and Experimental Therapeutics, Lasker Clinical Research Scholar, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, 10 Center Dr (10CRC/2-2352), Bethesda, MD 20892. Email E-mail Address: [email protected] https://orcid.org/0000-0002-0480-7755 Section on Clinical Genomics and Experimental Therapeutics (D.B.R., A.S.B., L.A.M., A.H., L.P., J.J., J.W., F.W.L.), National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health (NIH), Bethesda, MD. Originally published23 Jan 2024https://doi.org/10.1161/CIRCGEN.122.004224Circulation: Genomic and Precision Medicine. 2024;17FootnotesFor Sources of Funding and Disclosures, see page 62.Correspondence to: Falk W. Lohoff, MD, Section on Clinical Genomics and Experimental Therapeutics, Lasker Clinical Research Scholar, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, 10 Center Dr (10CRC/2-2352), Bethesda, MD 20892. Email falk.lohoff@nih.govREFERENCES1. Meadows TA, Bhatt DL, Cannon CP, Gersh BJ, Röther J, Goto S, Liau CS, Wilson PWF, Salette G, Smith SC, et al; REACH Registry Investigators. Ethnic differences in cardiovascular risks and mortality in atherothrombotic disease: insights from the Reduction of Atherothrombosis for Continued Health (REACH) registry.Mayo Clin Proc. 2011; 86:960–967. doi: 10.4065/mcp.2011.0010CrossrefMedlineGoogle Scholar2. 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Da Dalt L, Castiglioni L, Baragetti A, Audano M, Svecla M, Bonacina F, Pedretti S, Uboldi P, Benzoni P, Giannetti F, et al. PCSK9 deficiency rewires heart metabolism and drives heart failure with preserved ejection fraction.Eur Heart J. 2021; 42:3078–3090. doi: 10.1093/eurheartj/ehab431CrossrefMedlineGoogle Scholar eLetters(0)eLetters should relate to an article recently published in the journal and are not a forum for providing unpublished data. Comments are reviewed for appropriate use of tone and language. Comments are not peer-reviewed. Acceptable comments are posted to the journal website only. Comments are not published in an issue and are not indexed in PubMed. Comments should be no longer than 500 words and will only be posted online. References are limited to 10. 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