{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T16:48:17Z","timestamp":1791996497540,"version":"4.4.0"},"reference-count":55,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2023,7,27]],"date-time":"2023-07-27T00:00:00Z","timestamp":1690416000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"name":"VA VHA BLR&D","award":["IK2BX002527"],"award-info":[{"award-number":["IK2BX002527"]}]},{"name":"VA VHA CSR&D","award":["I01CX002231"],"award-info":[{"award-number":["I01CX002231"]}]},{"name":"VA VHA CSR&D","award":["I01CX001892"],"award-info":[{"award-number":["I01CX001892"]}]},{"name":"National Heart, Lung, and Blood Institute of the National Institutes of Health","award":["HL139795"],"award-info":[{"award-number":["HL139795"]}]},{"name":"National Heart, Lung, and Blood Institute of the National Institutes of Health","award":["HL163005"],"award-info":[{"award-number":["HL163005"]}]},{"name":"National Institute of General Medical Sciences of the National Institutes of Health","award":["P20GM103652"],"award-info":[{"award-number":["P20GM103652"]}]},{"name":"National Heart, Lung, and Blood Institute of the National Institutes of Health","award":["R01HL148727"],"award-info":[{"award-number":["R01HL148727"]}]},{"name":"National Institute of General Medical Sciences of the National Institutes of Health","award":["P20GM103652"],"award-info":[{"award-number":["P20GM103652"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Atherosclerosis and consequent risk of cardiovascular events or mortality can be accurately assessed by quantifying coronary artery calcium score (CACS) derived from computed tomography. HMG-CoA-reductase inhibitors (statins) are the primary pharmacotherapy used to reduce cardiovascular events, yet there is growing data that support statin use may increase coronary calcification. We set out to determine the likelihood of severe CACS in the context of chronic statin therapy.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>We established a retrospective, case-control study of 1,181 U.S. veterans without coronary artery disease (CAD) from a single site, the Providence VA Medical Center. Duration of statin therapy for primary prevention was divided into 5-year categorical increments. The primary outcome was CACS derived from low-dose lung cancer screening computed tomography (LCSCT), stratified by CACs severity (none = 0; mild = 1\u201399; moderate = 100\u2013399; and severe \u2265400 AU). Statin duration of zero served as the referent control. Ordinal logistic regression analysis determined the association between duration of statin use and CACS categories. Proportional odds assumption was tested using likelihood ratio test. Atherosclerotic cardiovascular disease (ASCVD) risk score, body mass index, and CKD (glomerular filtration rate of &lt;60 ml\/min\/1.73 m<jats:sup>2<\/jats:sup>) were included in the adjustment models.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>The mean age of the study population was 64.7\u00b17.2 years, and 706 (60%) patients were prescribed a statin at baseline. Duration of statin therapy was associated with greater odds of having increased CACS (&gt;0\u20135 years, OR: 1.71 [CI: 1.34\u20132.18], <jats:italic>p<\/jats:italic>&lt;0.001; &gt;5\u201310 years, OR: 2.80 [CI: 2.01\u20133.90], <jats:italic>p<\/jats:italic>&lt;0.001; &gt;10 years, OR: 5.30 [CI: 3.23\u20138.70], <jats:italic>p<\/jats:italic>&lt;0.001), and the relationship between statin duration and CACS remained significant after multivariate adjustment (&gt;0\u20135 years, OR: 1.49 [CI: 1.16\u20131.92], <jats:italic>p<\/jats:italic> = 0.002; &gt;5\u201310 years, OR: 2.38 [CI: 1.7\u20133.35], <jats:italic>p<\/jats:italic>&lt;0.001; &gt;10 years, OR: 4.48 [CI: 2.7\u20137.43], <jats:italic>p<\/jats:italic>&lt;0.001).<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>Long-term use of statins is associated with increased likelihood of severe CACS in patients with significant smoking history. The use of CACS to interpret cardiovascular event risk may require adjustment in the context of chronic statin therapy.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0289111","type":"journal-article","created":{"date-parts":[[2023,7,27]],"date-time":"2023-07-27T17:43:55Z","timestamp":1690479835000},"page":"e0289111","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":28,"title":["Long-term statin therapy is associated with severe coronary artery calcification"],"prefix":"10.1371","volume":"18","author":[{"given":"Kyari Sumayin","family":"Ngamdu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dhairyasheel S.","family":"Ghosalkar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hojune E.","family":"Chung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7366-8357","authenticated-orcid":true,"given":"Jared L.","family":"Christensen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5437-4273","authenticated-orcid":true,"given":"Cadence","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celia A.","family":"Butler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiffany","family":"Ho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice","family":"Chu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob R.","family":"Heath","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7825-062X","authenticated-orcid":true,"given":"Muhammad","family":"Baig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Chih","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaurav","family":"Choudhary","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2412-7669","authenticated-orcid":true,"given":"Alan R.","family":"Morrison","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,7,27]]},"reference":[{"issue":"8","key":"pone.0289111.ref001","doi-asserted-by":"crossref","first-page":"e254","DOI":"10.1161\/CIR.0000000000000950","article-title":"Heart Disease and Stroke Statistics-2021 Update: A Report From the American Heart Association","volume":"143","author":"SS Virani","year":"2021","journal-title":"Circulation"},{"issue":"13","key":"pone.0289111.ref002","doi-asserted-by":"crossref","first-page":"1336","DOI":"10.1056\/NEJMoa072100","article-title":"Coronary calcium as a predictor of coronary events in four racial or ethnic groups","volume":"358","author":"R Detrano","year":"2008","journal-title":"The New England journal of medicine"},{"issue":"16","key":"pone.0289111.ref003","doi-asserted-by":"crossref","first-page":"1610","DOI":"10.1001\/jama.2010.461","article-title":"Coronary artery calcium score and risk classification for coronary heart disease prediction","volume":"303","author":"TS Polonsky","year":"2010","journal-title":"JAMA: the journal of the American Medical Association"},{"issue":"1","key":"pone.0289111.ref004","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.jacc.2008.04.004","article-title":"Coronary artery calcium to predict all-cause mortality in elderly men and women","volume":"52","author":"P Raggi","year":"2008","journal-title":"Journal of the American College of Cardiology"},{"issue":"7","key":"pone.0289111.ref005","doi-asserted-by":"crossref","first-page":"1272","DOI":"10.1161\/01.ATV.0000127024.40516.ef","article-title":"Progression of coronary artery calcium and risk of first myocardial infarction in patients receiving cholesterol-lowering therapy","volume":"24","author":"P Raggi","year":"2004","journal-title":"Arteriosclerosis, thrombosis, and vascular biology"},{"issue":"1","key":"pone.0289111.ref006","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1161\/01.HYP.0000164575.16609.02","article-title":"Progression of coronary artery calcium and occurrence of myocardial infarction in patients with and without diabetes mellitus","volume":"46","author":"P Raggi","year":"2005","journal-title":"Hypertension"},{"issue":"7","key":"pone.0289111.ref007","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1016\/S0002-9149(03)00892-0","article-title":"Progression of coronary calcium on serial electron beam tomographic scanning is greater in patients with future myocardial infarction","volume":"92","author":"P Raggi","year":"2003","journal-title":"The American journal of cardiology"},{"issue":"1","key":"pone.0289111.ref008","doi-asserted-by":"crossref","first-page":"185","DOI":"10.2147\/VHRM.S4822","article-title":"Vascular calcifications as a marker of increased cardiovascular risk: a meta-analysis","volume":"5","author":"RJ Rennenberg","year":"2009","journal-title":"Vascular health and risk management"},{"issue":"3","key":"pone.0289111.ref009","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1001\/jama.2013.282535","article-title":"Calcium density of coronary artery plaque and risk of incident cardiovascular events.","volume":"311","author":"MH Criqui","year":"2014","journal-title":"JAMA: the journal of the American Medical Association"},{"issue":"1","key":"pone.0289111.ref010","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.jacc.2009.02.068","article-title":"Computed tomographic angiography characteristics of atherosclerotic plaques subsequently resulting in acute coronary syndrome","volume":"54","author":"S Motoyama","year":"2009","journal-title":"Journal of the American College of Cardiology"},{"issue":"7","key":"pone.0289111.ref011","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1016\/j.jacc.2014.05.039","article-title":"High-Risk Plaque Detected on Coronary CT Angiography Predicts Acute Coronary Syndromes Independent of Significant Stenosis in Acute Chest Pain: Results From the ROMICAT-II Trial","volume":"64","author":"SB Puchner","year":"2014","journal-title":"Journal of the American College of Cardiology"},{"issue":"13","key":"pone.0289111.ref012","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1016\/j.jacc.2015.01.036","article-title":"Impact of statins on serial coronary calcification during atheroma progression and regression","volume":"65","author":"R Puri","year":"2015","journal-title":"Journal of the American College of Cardiology"},{"key":"pone.0289111.ref013","doi-asserted-by":"crossref","first-page":"7495","DOI":"10.1038\/ncomms8495","article-title":"Identifying active vascular microcalcification by (18)F-sodium fluoride positron emission tomography","volume":"6","author":"A Irkle","year":"2015","journal-title":"Nat Commun"},{"key":"pone.0289111.ref014","article-title":"2019 ACC\/AHA Guideline on the Primary Prevention of Cardiovascular Disease","author":"DK Arnett","year":"2019","journal-title":"Circulation"},{"issue":"21","key":"pone.0289111.ref015","doi-asserted-by":"crossref","first-page":"2195","DOI":"10.1056\/NEJMoa0807646","article-title":"Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein","volume":"359","author":"PM Ridker","year":"2008","journal-title":"The New England journal of medicine"},{"key":"pone.0289111.ref016","first-page":"CD004816","article-title":"Statins for the primary prevention of cardiovascular disease","volume":"1","author":"F Taylor","year":"2013","journal-title":"The Cochrane database of systematic reviews"},{"issue":"20","key":"pone.0289111.ref017","doi-asserted-by":"crossref","first-page":"1615","DOI":"10.1001\/jama.279.20.1615","article-title":"Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFCAPS\/TexCAPS. Air Force\/Texas Coronary Atherosclerosis Prevention Study","volume":"279","author":"JR Downs","year":"1998","journal-title":"JAMA: the journal of the American Medical Association"},{"issue":"9326","key":"pone.0289111.ref018","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/S0140-6736(02)09327-3","article-title":"MRC\/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial","volume":"360","author":"Heart Protection Study Collaborative G","year":"2002","journal-title":"Lancet"},{"issue":"13","key":"pone.0289111.ref019","doi-asserted-by":"crossref","first-page":"1711","DOI":"10.1001\/jama.285.13.1711","article-title":"Effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes: the MIRACL study: a randomized controlled trial","volume":"285","author":"GG Schwartz","year":"2001","journal-title":"JAMA: the journal of the American Medical Association"},{"issue":"22","key":"pone.0289111.ref020","doi-asserted-by":"crossref","first-page":"2583","DOI":"10.1161\/01.CIR.0000017822.82512.62","article-title":"Inflammatory biomarkers, statins, and the risk of stroke: cracking a clinical conundrum","volume":"105","author":"PM Ridker","year":"2002","journal-title":"Circulation"},{"issue":"5","key":"pone.0289111.ref021","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1056\/NEJM200008033430502","article-title":"Pravastatin therapy and the risk of stroke","volume":"343","author":"HD White","year":"2000","journal-title":"The New England journal of medicine"},{"issue":"25","key":"pone.0289111.ref022","first-page":"e1082","article-title":"2018 AHA\/ACC\/AACVPR\/AAPA\/ABC\/ACPM\/ADA\/AGS\/APhA\/ASPC\/NLA\/PCNA Guideline on the Management of Blood Cholesterol: A Report of the American College of Cardiology\/American Heart Association Task Force on Clinical Practice Guidelines","volume":"139","author":"SM Grundy","year":"2019","journal-title":"Circulation"},{"issue":"1","key":"pone.0289111.ref023","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1161\/CIRCRESAHA.116.308537","article-title":"Pleiotropic Effects of Statins on the Cardiovascular System","volume":"120","author":"A Oesterle","year":"2017","journal-title":"Circulation research"},{"issue":"23 Suppl 1","key":"pone.0289111.ref024","first-page":"III39","article-title":"Beneficial cardiovascular pleiotropic effects of statins","volume":"109","author":"J. Davignon","year":"2004","journal-title":"Circulation"},{"issue":"9","key":"pone.0289111.ref025","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1161\/01.CIR.0000027567.49283.FF","article-title":"Influence of lipid-lowering therapy on the progression of coronary artery calcification: a prospective evaluation","volume":"106","author":"S Achenbach","year":"2002","journal-title":"Circulation"},{"issue":"1","key":"pone.0289111.ref026","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/j.jacc.2005.02.089","article-title":"Treatment of asymptomatic adults with elevated coronary calcium scores with atorvastatin, vitamin C, and vitamin E: the St. Francis Heart Study randomized clinical trial","volume":"46","author":"Y Arad","year":"2005","journal-title":"Journal of the American College of Cardiology"},{"issue":"27","key":"pone.0289111.ref027","doi-asserted-by":"crossref","first-page":"1972","DOI":"10.1056\/NEJM199812313392703","article-title":"Effect of HMG-CoA reductase inhibitors on coronary artery disease as assessed by electron-beam computed tomography","volume":"339","author":"TQ Callister","year":"1998","journal-title":"The New England journal of medicine"},{"issue":"11","key":"pone.0289111.ref028","doi-asserted-by":"crossref","first-page":"1307","DOI":"10.1093\/ehjci\/jez022","article-title":"Differential association between the progression of coronary artery calcium score and coronary plaque volume progression according to statins: the Progression of AtheRosclerotic PlAque DetermIned by Computed TomoGraphic Angiography Imaging (PARADIGM) study","volume":"20","author":"SE Lee","year":"2019","journal-title":"Eur Heart J Cardiovasc Imaging"},{"issue":"1","key":"pone.0289111.ref029","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/S0002-9149(00)00820-1","article-title":"Rates of progression of coronary calcium by electron beam tomography","volume":"86","author":"MJ Budoff","year":"2000","journal-title":"The American journal of cardiology"},{"issue":"3","key":"pone.0289111.ref030","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1016\/S0002-9149(03)00642-8","article-title":"Relation of aggressiveness of lipid-lowering treatment to changes in calcified plaque burden by electron beam tomography","volume":"92","author":"HS Hecht","year":"2003","journal-title":"The American journal of cardiology"},{"issue":"2","key":"pone.0289111.ref031","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1016\/j.ijcard.2013.03.024","article-title":"Exploring coronary atherosclerosis with intravascular imaging","volume":"168","author":"R Puri","year":"2013","journal-title":"International journal of cardiology"},{"key":"pone.0289111.ref032","article-title":"Statins Disrupt Macrophage Rac1 Regulation Leading to Increased Atherosclerotic Plaque Calcification","author":"A Healy","year":"2020","journal-title":"Arteriosclerosis, thrombosis, and vascular biology"},{"key":"pone.0289111.ref033","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1016\/j.ijcard.2015.02.072","article-title":"High dose and long-term statin therapy accelerate coronary artery calcification","volume":"184","author":"M Henein","year":"2015","journal-title":"International journal of cardiology"},{"issue":"11","key":"pone.0289111.ref034","doi-asserted-by":"crossref","first-page":"2390","DOI":"10.2337\/dc12-0464","article-title":"Progression of vascular calcification is increased with statin use in the Veterans Affairs Diabetes Trial (VADT)","volume":"35","author":"A Saremi","year":"2012","journal-title":"Diabetes care"},{"issue":"23","key":"pone.0289111.ref035","doi-asserted-by":"crossref","first-page":"2218","DOI":"10.1016\/j.jacc.2007.08.032","article-title":"Determinants of progression of coronary artery calcification in type 2 diabetes role of glycemic control and inflammatory\/vascular calcification markers","volume":"50","author":"DV Anand","year":"2007","journal-title":"Journal of the American College of Cardiology"},{"issue":"21","key":"pone.0289111.ref036","doi-asserted-by":"crossref","first-page":"2722","DOI":"10.1161\/CIRCULATIONAHA.106.674143","article-title":"Risk factors for the progression of coronary artery calcification in asymptomatic subjects: results from the Multi-Ethnic Study of Atherosclerosis (MESA)","volume":"115","author":"RA Kronmal","year":"2007","journal-title":"Circulation"},{"key":"pone.0289111.ref037","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.atherosclerosis.2020.06.019","article-title":"Aortic valve calcification predicts all-cause mortality independent of coronary calcification and severe stenosis","volume":"307","author":"JL Christensen","year":"2020","journal-title":"Atherosclerosis"},{"issue":"1","key":"pone.0289111.ref038","doi-asserted-by":"crossref","first-page":"337","DOI":"10.3233\/ADR-200253","article-title":"Aortic Valve Calcification Is Associated with Future Cognitive Impairment","volume":"5","author":"HE Chung","year":"2021","journal-title":"J Alzheimers Dis Rep"},{"issue":"4","key":"pone.0289111.ref039","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1016\/0735-1097(90)90282-T","article-title":"Quantification of coronary artery calcium using ultrafast computed tomography","volume":"15","author":"AS Agatston","year":"1990","journal-title":"Journal of the American College of Cardiology"},{"issue":"2 Suppl 1","key":"pone.0289111.ref040","first-page":"S1","article-title":"K\/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification","volume":"39","author":"National Kidney F","year":"2002","journal-title":"Am J Kidney Dis"},{"issue":"25 Suppl 2","key":"pone.0289111.ref041","first-page":"S49","article-title":"2013 ACC\/AHA guideline on the assessment of cardiovascular risk: a report of the American College of Cardiology\/American Heart Association Task Force on Practice Guidelines","volume":"129","author":"DC Goff","year":"2014","journal-title":"Circulation"},{"issue":"14","key":"pone.0289111.ref042","doi-asserted-by":"crossref","first-page":"1406","DOI":"10.1001\/jama.2014.2630","article-title":"Validation of the atherosclerotic cardiovascular disease Pooled Cohort risk equations","volume":"311","author":"P Muntner","year":"2014","journal-title":"JAMA: the journal of the American Medical Association"},{"issue":"9","key":"pone.0289111.ref043","doi-asserted-by":"crossref","first-page":"1322","DOI":"10.1016\/j.cjca.2020.11.010","article-title":"Missing Data in Clinical Research: A Tutorial on Multiple Imputation","volume":"37","author":"PC Austin","year":"2021","journal-title":"The Canadian journal of cardiology"},{"issue":"3","key":"pone.0289111.ref044","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1016\/j.jacc.2006.10.001","article-title":"ACCF\/AHA 2007 clinical expert consensus document on coronary artery calcium scoring by computed tomography in global cardiovascular risk assessment and in evaluation of patients with chest pain: a report of the American College of Cardiology Foundation Clinical Expert Consensus Task Force (ACCF\/AHA Writing Committee to Update the 2000 Expert Consensus Document on Electron Beam Computed Tomography) developed in collaboration with the Society of Atherosclerosis Imaging and Prevention and the Society of Cardiovascular Computed Tomography","volume":"49","author":"P Greenland","year":"2007","journal-title":"Journal of the American College of Cardiology"},{"issue":"2","key":"pone.0289111.ref045","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.jcct.2017.02.010","article-title":"Clinical indications for coronary artery calcium scoring in asymptomatic patients: Expert consensus statement from the Society of Cardiovascular Computed Tomography","volume":"11","author":"H Hecht","year":"2017","journal-title":"J Cardiovasc Comput Tomogr"},{"issue":"20","key":"pone.0289111.ref046","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1056\/NEJM199511163332001","article-title":"Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. West of Scotland Coronary Prevention Study Group","volume":"333","author":"J Shepherd","year":"1995","journal-title":"The New England journal of medicine"},{"issue":"6","key":"pone.0289111.ref047","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1016\/j.amjcard.2019.12.031","article-title":"Coronary Artery Calcification, Statin Use and Long-Term Risk of Atherosclerotic Cardiovascular Disease Events (from the Multi-Ethnic Study of Atherosclerosis)","volume":"125","author":"MA Rifai","year":"2020","journal-title":"The American journal of cardiology"},{"issue":"18","key":"pone.0289111.ref048","doi-asserted-by":"crossref","first-page":"1860","DOI":"10.1016\/j.jacc.2006.10.079","article-title":"Long-term prognosis associated with coronary calcification: observations from a registry of 25,253 patients","volume":"49","author":"MJ Budoff","year":"2007","journal-title":"Journal of the American College of Cardiology"},{"issue":"15","key":"pone.0289111.ref049","doi-asserted-by":"crossref","first-page":"1643","DOI":"10.1016\/j.jacc.2015.08.035","article-title":"10-Year Coronary Heart Disease Risk Prediction Using Coronary Artery Calcium and Traditional Risk Factors: Derivation in the MESA (Multi-Ethnic Study of Atherosclerosis) With Validation in the HNR (Heinz Nixdorf Recall) Study and the DHS (Dallas Heart Study)","volume":"66","author":"RL McClelland","year":"2015","journal-title":"Journal of the American College of Cardiology"},{"key":"pone.0289111.ref050","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.atherosclerosis.2020.10.009","article-title":"Prognostic value of coronary artery calcium score, area, and density among individuals on statin therapy vs. non-users: The coronary artery calcium consortium","volume":"316","author":"AD Osei","year":"2021","journal-title":"Atherosclerosis"},{"issue":"2","key":"pone.0289111.ref051","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1161\/ATVBAHA.116.308507","article-title":"Rac2 Modulates Atherosclerotic Calcification by Regulating Macrophage Interleukin-1beta Production","volume":"37","author":"N Ceneri","year":"2017","journal-title":"Arteriosclerosis, thrombosis, and vascular biology"},{"issue":"4","key":"pone.0289111.ref052","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1161\/01.RES.0000204727.46710.5e","article-title":"Regulation of NADPH oxidases: the role of Rac proteins","volume":"98","author":"PL Hordijk","year":"2006","journal-title":"Circulation research"},{"issue":"2","key":"pone.0289111.ref053","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1172\/JCI43758","article-title":"Geranylgeranyltransferase type I (GGTase-I) deficiency hyperactivates macrophages and induces erosive arthritis in mice","volume":"121","author":"OM Khan","year":"2011","journal-title":"The Journal of clinical investigation"},{"key":"pone.0289111.ref054","article-title":"Effect of interleukin-1beta inhibition with canakinumab on incident lung cancer in patients with atherosclerosis: exploratory results from a randomised, double-blind, placebo-controlled trial","author":"PM Ridker","year":"2017","journal-title":"Lancet"},{"issue":"10118","key":"pone.0289111.ref055","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/S0140-6736(17)32814-3","article-title":"Relationship of C-reactive protein reduction to cardiovascular event reduction following treatment with canakinumab: a secondary analysis from the CANTOS randomised controlled trial","volume":"391","author":"PM Ridker","year":"2018","journal-title":"Lancet"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0289111","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,27]],"date-time":"2023-07-27T17:45:45Z","timestamp":1690479945000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0289111"}},"subtitle":[],"editor":[{"given":"Xinlin","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2023,7,27]]},"references-count":55,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2023,7,27]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0289111","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,27]]}}}