@article{efd6824098314333a9b3a838f93dd0fc,
title = "Coronary Artery Calcium Score to Refine the Use of PCSK9i in Asymptomatic Individuals: A Multicohort Study",
abstract = "BACKGROUND: The value of coronary artery calcium (CAC) in the allocation of PCSK9i (proprotein convertase subtilisin/kexin type 9 inhibitors) among individuals without clinically evident atherosclerotic cardiovascular disease (ASCVD) is unknown for indications that do not require confirmed familial hypercholesterolemia. We aimed to assess the ability of CAC to stratify ASCVD risk under 3 non–familial hypercholesterolemia PCSK9i allocation paradigms. METHODS AND RESULTS: We included participants without clinically evident ASCVD from MESA (Multi-Ethnic Study of Atherosclerosis), CARDIA (Coronary Artery Risk Development in Young Adults) study, DHS (Dallas Heart Study), and HNR (Heinz Nixdorf Recall) study. Three PCSK9i eligibility scenarios were defined: a broad scenario informed only by high low-density lipoprotein cholesterol levels (N=567), a restrictive one combining higher low-density lipoprotein cholesterol levels and presence of ≥2 additional risk factors (N=127), and a high-risk scenario where individuals with subclinical organ damage or high estimated risk would be treated to achieve low-density lipoprotein cholesterol <55 mg/dL (N=471). The high-risk scenario had the highest ASCVD event rates (27.8% at 10 years). CAC=0 was observed in 35% participants in the broad scenario, 25% in the restrictive scenario, and 16% in the high-risk scenario. In all, CAC=0 was associated with the lowest incident ASCVD rates at 5 and 10 years, and CAC burden was independently associated with ASCVD events adjusting for traditional risk factors. CONCLUSIONS: CAC may be used to refine the allocation of PCSK9i, potentially leading to a more conservative use if CAC=0. The value of CAC testing is greater in scenarios that use low-density lipoprotein cholesterol levels and/or traditional risk factors to define PCSK9i eligibility (CAC=0 present in 1 of 3–4 patients), whereas its prevalence is lower when allocation is informed by presence of noncoronary subclinical organ damage.",
keywords = "PCSK9i, atherosclerosis, cardiovascular disease, coronary artery calcium, primary prevention, risk",
author = "Miguel Cainzos-Achirica and Renato Quispe and Reed Mszar and Ramzi Dudum and {Al Rifai}, Mahmoud and Raimund Erbel and Andreas Stang and J{\"o}ckel, {Karl Heinz} and Nils Lehmann and Sara Schramm and B{\"o}rge Schmidt and Toth, {Peter P.} and Rana, {Jamal S.} and Lima, {Joao A.C.} and {de Vasconcellos}, {Henrique Doria} and Donald Lloyd-Jones and Joshi, {Parag H.} and Colby Ayers and Amit Khera and Blaha, {Michael J.} and Philip Greenland and Khurram Nasir",
note = "Funding Information: MESA (Multi-Ethnic Study of Atherosclerosis): This research was supported by contracts HHSN268201500003I and N01-HC-95159 through N01-HC-95169 from the National Heart, Lung, and Blood Institute (NHLBI), and by grants UL1-TR-000040, UL1-TR-001079, UL1-TR-001420, and UL1-TR-001881 from the National Center for Advancing Translational Sciences. CARDIA (Coronary Artery Risk Development in Young Adults) study: This research was supported by contracts HHSN268201800003I, HHSN268201800004I, HHSN268201800005I, HHSN268201800006I, and HHSN268201800007I from the NHLBI. DHS (Dallas Heart Study): This research was supported in part by grant UL1TR001105 from the National Center for Advancing Translational Science, National Institutes of Health. HNR (Heinz Nixdorf Recall) study: This research was supported by the Heinz Nixdorf Foundation (Chairman: Martin Nixdorf; Past Chairman: Dr Jur. Gerhard Schmidt [deceased]), and parts of the study were also supported by the German Research Council (DFG) (DFG project: EI 969/2-3, ER 155/6-1;6-2, HO 3314/2-1;2-2;2-3;4-3, INST 58219/32-1, JO 170/8-1, KN 885/3-1, PE 2309/2-1, and SI 236/8-1;9-1;10-1), the German Ministry of Education and Science (BMBF project: 01EG0401, 01GI0856, 01GI0860, 01GS0820_WB2-C, 01ER1001D, and 01GI0205), the Ministry of Innovation, Science, Research and Technology, North Rhine-Westphalia, the Else Kr{\"o}ner-Fresenius-Stiftung (project: 2015_A119), and the German Social Accident Insurance (DGUV project: FF-FP295). Furthermore, the study was supported by the Competence Network for HIV/AIDS, the Deanship of the University Hospital and Interne Forschungsf{\"o}rderung Essen of the University Duisburg-Essen, the European Union, the German Competence Network Heart Failure, Kulturstiftung Essen, the Protein Research Unit within Europe, the Dr. Werner-Jackst{\"a}dt Stiftung, and the following companies: Celgene GmbH M{\"u}nchen, Imatron/GE-Imatron, Janssen Pharmaceuticals, Merck KGaA, Philips, ResMed Foundation, Roche Diagnostics, Sarstedt AG&Co, Siemens HealthCare Diagnostics, and Volkswagen Foundation. Funding Information: The authors thank the other investigators, staff, and participants of the MESA (Multi-Ethnic Study of Atherosclerosis), CARDIA (Coronary Artery Risk Development in Young Adults) study, and DHS (Dallas Heart Study) for their valuable contributions. A full list of participating MESA investigators and institutions can be found at http://www.mesa-nhlbi.org. The HNR (Heinz Nixdorf Recall) study group is indebted to all study participants and to both the dedi-cated personnel of the study center of the HNR study and to the investigative group, in particular to U. Slomiany, U. Roggenbuck, E. M. Beck, A. {\"O}ffner, S. M{\"u}nkel, R. Peter, and H. Hirche. Advisory Board: T. Meinertz, Hamburg, Germany (Chair); C. Bode, Freiburg, Germany; P. J. deFeyter, Rotterdam, the Netherlands; B. G{\"u}ntert, Halli, Austria; F. Gutzwiller, Bern, Switzerland; H. Heinen, Bonn, Germany; O. Hess, Bern, Switzerland; B. Klein, Essen, Germany; H. L{\"o}wel, Neuherberg, Germany; M. Reiser, Munich, Germany; G. Schmidt, Essen, Germany; M. Schwaiger, Munich, Germany; C. Steinm{\"u}ller, Bonn, Germany; T. Theorell, Stockholm, Sweden; S. N. Willich, Berlin, Germany. MESA (Multi-Ethnic Study of Atherosclerosis): This research was supported by contracts HHSN268201500003I and N01-HC-95159 through N01-HC-95169 from the National Heart, Lung, and Blood Institute (NHLBI), and by grants UL1-TR-000040, UL1-TR-001079, UL1-TR-001420, and UL1-TR-001881 from the National Center for Advancing Translational Sciences. CARDIA (Coronary Artery Risk Development in Young Adults) study: This research was supported by contracts HHSN268201800003I, HHSN268201800004I, HHSN268201800005I, HHSN268201800006I, and HHSN268201800007I from the NHLBI. DHS (Dallas Heart Study): This research was supported in part by grant UL1TR001105 from the National Center for Advancing Translational Science, National Institutes of Health. HNR (Heinz Nixdorf Recall) study: This research was supported by the Heinz Nixdorf Foundation (Chairman: Martin Nixdorf; Past Chairman: Dr Jur. Gerhard Schmidt [deceased]), and parts of the study were also supported by the German Research Council (DFG) (DFG project: EI 969/2-3, ER 155/6-1;6-2, HO 3314/2-1;2-2;2-3;4-3, INST 58219/32-1, JO 170/8-1, KN 885/3-1, PE 2309/2-1, and SI 236/8-1;9-1;10-1), the German Ministry of Education and Science (BMBF project: 01EG0401, 01GI0856, 01GI0860, 01GS0820_WB2-C, 01ER1001D, and 01GI0205), the Ministry of Innovation, Science, Research and Technology, North Rhine-Westphalia, the Else Kr{\"o}ner-Fresenius-Stiftung (project: 2015_A119), and the German Social Accident Insurance (DGUV project: FF-FP295). Furthermore, the study was supported by the Competence Network for HIV/AIDS, the Deanship of the University Hospital and Interne Forschungsf{\"o}rderung Essen of the University Duisburg-Essen, the European Union, the German Competence Network Heart Failure, Kulturstiftung Essen, the Protein Research Unit within Europe, the Dr. Werner-Jackst{\"a}dt Stiftung, and the following companies: Celgene GmbH M{\"u}nchen, Imatron/GE-Imatron, Janssen Pharmaceuticals, Merck KGaA, Philips, ResMed Foundation, Roche Diagnostics, Sarstedt AG&Co, Siemens HealthCare Diagnostics, and Volkswagen Foundation. Funding Information: Dr Joshi has received grants from American Heart Association (AHA), National Aeronautics and Space Administration (NASA), Novo Nordisk, AstraZeneca, GSK, Sanofi, Amgen, and Novartis; reports consulting fees from Bayer and Regeneron; and has equity in G3 Therapeutics. Dr Blaha has received research grants from National Institutes of Health, US Food and Drug Administration, AHA, Amgen Foundation, and Novo Nordisk; and is on the advisory board of Amgen, Sanofi, Regeneron, Novartis, Novo Nordisk, Bayer, Akcea, Kowa, 89Bio, Kaleido, Inozyme, and Roche. Dr Nasir is on the advisory board of Amgen, Novartis, and Novo Nordisk; and his research is partly supported by the Jerold B. Katz Academy of Translational Research. The remaining authors have no disclosures to report. Publisher Copyright: {\textcopyright} 2022 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.",
year = "2022",
month = aug,
day = "16",
doi = "10.1161/JAHA.122.025737",
language = "English (US)",
volume = "11",
journal = "Journal of the American Heart Association",
issn = "2047-9980",
publisher = "Wiley-Blackwell",
number = "16",
}