{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T06:52:50Z","timestamp":1780469570951,"version":"3.54.1"},"reference-count":44,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"16","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2022,8,16]]},"abstract":"<jats:sec sec-type=\"background\" xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">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\u2013familial hypercholesterolemia PCSK9i allocation paradigms.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">We included participants without clinically evident ASCVD from MESA (Multi\u2010Ethnic 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\u2010density lipoprotein cholesterol levels (N=567), a restrictive one combining higher low\u2010density lipoprotein cholesterol levels and presence of \u22652 additional risk factors (N=127), and a high\u2010risk scenario where individuals with subclinical organ damage or high estimated risk would be treated to achieve low\u2010density lipoprotein cholesterol &lt;55\u2009mg\/dL (N=471). The high\u2010risk scenario had the highest ASCVD event rates (27.8% at 10\u2009years). CAC=0 was observed in 35% participants in the broad scenario, 25% in the restrictive scenario, and 16% in the high\u2010risk scenario. In all, CAC=0 was associated with the lowest incident ASCVD rates at 5 and 10\u2009years, and CAC burden was independently associated with ASCVD events adjusting for traditional risk factors.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">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\u2010density lipoprotein cholesterol levels and\/or traditional risk factors to define PCSK9i eligibility (CAC=0 present in 1 of 3\u20134 patients), whereas its prevalence is lower when allocation is informed by presence of noncoronary subclinical organ damage.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.122.025737","type":"journal-article","created":{"date-parts":[[2022,8,9]],"date-time":"2022-08-09T10:45:31Z","timestamp":1660041931000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":6,"title":["Coronary Artery Calcium Score to Refine the Use of PCSK9i in Asymptomatic Individuals: A Multicohort Study"],"prefix":"10.1161","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8073-2337","authenticated-orcid":false,"given":"Miguel","family":"Cainzos\u2010Achirica","sequence":"first","affiliation":[{"name":"Division of Cardiovascular Prevention and Wellness, Department of Cardiology Houston Methodist DeBakey Heart and Vascular Center Houston TX"},{"name":"Center for Outcomes Research Houston Methodist Houston TX"},{"name":"Johns Hopkins Ciccarone Center for the Prevention of Cardiovascular Disease Johns Hopkins Medical Institutions Baltimore MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renato","family":"Quispe","sequence":"additional","affiliation":[{"name":"Johns Hopkins Ciccarone Center for the Prevention of Cardiovascular Disease Johns Hopkins Medical Institutions Baltimore MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8152-8031","authenticated-orcid":false,"given":"Reed","family":"Mszar","sequence":"additional","affiliation":[{"name":"Center for Outcomes Research Yale School of Medicine New Haven CT"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramzi","family":"Dudum","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine Stanford University Stanford CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6933-790X","authenticated-orcid":false,"given":"Mahmoud","family":"Al Rifai","sequence":"additional","affiliation":[{"name":"Section of Cardiology Baylor College of Medicine Houston TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raimund","family":"Erbel","sequence":"additional","affiliation":[{"name":"Institute of Medical Informatics, Biometry and Epidemiology, University Hospital Essen University Duisburg\u2010Essen Essen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Stang","sequence":"additional","affiliation":[{"name":"Institute of Medical Informatics, Biometry and Epidemiology, University Hospital Essen University Duisburg\u2010Essen Essen Germany"},{"name":"Department of Epidemiology, School of Public Health Boston University Boston MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl\u2010Heinz","family":"J\u00f6ckel","sequence":"additional","affiliation":[{"name":"Institute of Medical Informatics, Biometry and Epidemiology, University Hospital Essen University Duisburg\u2010Essen Essen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2395-8708","authenticated-orcid":false,"given":"Nils","family":"Lehmann","sequence":"additional","affiliation":[{"name":"Institute of Medical Informatics, Biometry and Epidemiology, University Hospital Essen University Duisburg\u2010Essen Essen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6493-6009","authenticated-orcid":false,"given":"Sara","family":"Schramm","sequence":"additional","affiliation":[{"name":"Institute of Medical Informatics, Biometry and Epidemiology, University Hospital Essen University Duisburg\u2010Essen Essen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B\u00f6rge","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Institute of Medical Informatics, Biometry and Epidemiology, University Hospital Essen University Duisburg\u2010Essen Essen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5810-5460","authenticated-orcid":false,"given":"Peter P.","family":"Toth","sequence":"additional","affiliation":[{"name":"Johns Hopkins Ciccarone Center for the Prevention of Cardiovascular Disease Johns Hopkins Medical Institutions Baltimore MD"},{"name":"CGH Medical Center Sterling IL"},{"name":"University of Illinois College of Medicine Peoria IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamal S.","family":"Rana","sequence":"additional","affiliation":[{"name":"Divisions of Cardiology and Research Kaiser Permanente Northern California Oakland CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8756-6995","authenticated-orcid":false,"given":"Joao A. C.","family":"Lima","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Imaging Johns Hopkins Medical Institutions Baltimore MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9758-2240","authenticated-orcid":false,"given":"Henrique","family":"Doria de Vasconcellos","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Imaging Johns Hopkins Medical Institutions Baltimore MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0847-6110","authenticated-orcid":false,"given":"Donald","family":"Lloyd\u2010Jones","sequence":"additional","affiliation":[{"name":"Departments of Preventive Medicine and Medicine Northwestern University Feinberg School of Medicine Chicago IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7863-2794","authenticated-orcid":false,"given":"Parag H.","family":"Joshi","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine UT Southwestern Medical Center Dallas TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2060-2263","authenticated-orcid":false,"given":"Colby","family":"Ayers","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine UT Southwestern Medical Center Dallas TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7255-6874","authenticated-orcid":false,"given":"Amit","family":"Khera","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine UT Southwestern Medical Center Dallas TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5138-9683","authenticated-orcid":false,"given":"Michael J.","family":"Blaha","sequence":"additional","affiliation":[{"name":"Johns Hopkins Ciccarone Center for the Prevention of Cardiovascular Disease Johns Hopkins Medical Institutions Baltimore MD"},{"name":"Department of Epidemiology and Welch Center for Prevention, Epidemiology and Clinical Research Johns Hopkins University Baltimore MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6327-2439","authenticated-orcid":false,"given":"Philip","family":"Greenland","sequence":"additional","affiliation":[{"name":"Departments of Preventive Medicine and Medicine Northwestern University Feinberg School of Medicine Chicago IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5376-2269","authenticated-orcid":false,"given":"Khurram","family":"Nasir","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Prevention and Wellness, Department of Cardiology Houston Methodist DeBakey Heart and Vascular Center Houston TX"},{"name":"Center for Outcomes Research Houston Methodist Houston TX"},{"name":"Johns Hopkins Ciccarone Center for the Prevention of Cardiovascular Disease Johns Hopkins Medical Institutions Baltimore MD"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamacardio.2021.3508"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.120.045851"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehab532"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamacardio.2021.3517"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000000625"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehz455"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cjca.2021.03.016"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.116.025471"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2019.07.016"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.120.049057"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.119.045010"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.120.019331"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.118.011246"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/clc.22713"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwf113"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCIMAGING.119.009228"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2004.02.058"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2010.06.030"},{"key":"e_1_3_2_20_2","unstructured":"ACC.org Al Danaf J Martin SS Blumenthal RS. Ezetimibe: the lower the LDL\u2010C the better (even for total cardiovascular events). 2016. Available at: https:\/\/www.acc.org\/latest\u2010in\u2010cardiology\/articles\/2016\/03\/09\/06\/50\/ezetimibe\u2010the\u2010lower\u2010the\u2010ldlc\u2010the\u2010better#:~:text=Ezetimibe%20lowers%20low%2Ddensity%20lipoprotein doubling%20the%20dose%20of%20statin.&text=A%20recent%20pooled%20analysis3 were%20seen%20with%20adding%20ezetimibe. Accessed June 15 2022."},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1093\/clinchem\/18.6.499"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.2337\/dc20-S002"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-008-1173-y"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000000596"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.115.018524"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10654-006-0015-9"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2009.01.005"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/0735-1097(90)90282-t"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2016.13985"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcmg.2018.09.019"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacl.2018.04.003"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.5551\/jat.31161"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2015.09.087"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcmg.2019.11.001"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcmg.2021.06.011"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamacardio.2017.4191"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.105.580696"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2020.10.009"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2019.12.031"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcmg.2020.09.015"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehab863"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCOUTCOMES.121.008552"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMp1614154"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1615664"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.120.046501"}],"container-title":["Journal of the American Heart Association"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/JAHA.122.025737","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T11:26:08Z","timestamp":1715599568000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/JAHA.122.025737"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,16]]},"references-count":44,"journal-issue":{"issue":"16","published-print":{"date-parts":[[2022,8,16]]}},"alternative-id":["10.1161\/JAHA.122.025737"],"URL":"https:\/\/doi.org\/10.1161\/jaha.122.025737","relation":{},"ISSN":["2047-9980"],"issn-type":[{"value":"2047-9980","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,16]]},"assertion":[{"value":"2022-02-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-06-22","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-08-09","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e025737"}}