Edinburgh Research Explorer



Validation of an imaging based cardiovascular risk score in a Scottish populationRemko Kockelkoren*a, Pushpa M Jairama,d, John T. Murchisonb, Thomas P.A. Debrayd,e, Saeed Mirsadraeeb,c, Yolanda van der Graafd, Pim A. de Jonga, and Edwin J.R. van Beekb,c a University Medical Center Utrecht, Department of Radiology, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlandsb Royal Infirmary Edinburgh, Department of Radiology, 51 Little France Dr, Edinburgh EH16 4SA, Edinburgh, Scotlandc Clinical Research Imaging Centre, The Queen’s Medical Research Institute, University of Edinburgh, 47 Little France Cres, Edinburgh EH16 4TJ, Edinburgh, Scotlandd Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG, Utrecht, The Netherlandse The Dutch Cochrane Centre, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The NetherlandsEmail addresses: r.kockelkoren@umcutrecht.nl (R. Kockelkoren), pmjairam@ (P.M. Jairam), John.Murchison@nhslothian.scot.nhs.uk (J.T. Murchison), t.debray@umcutrecht.nl (T.P.A. Debray), Saeed.Mirsadraee@ed.ac.uk (S. Mirsadraee), Y.vanderGraaf@umcutrecht.nl (Y. van der Graaf), p.dejong-8@umcutrecht.nl (P.A. de Jong), edwin-vanbeek@ed.ac.uk (E.J.R. van Beek)*Corresponding Author: Remko Kockelkoren, MDUniversity Medical Center Utrecht, Department of RadiologyRoom E01.132 - PO Box 855003508 GA Utrecht, The Netherlandsr.kockelkoren@umcutrecht.nlTel +31 88 755 0846 - Fax +31 88 756 9589AbstractObjectives: A radiological risk score that determines 5-year cardiovascular disease (CVD) risk using routine care CT and patient information readily available to radiologists was previously developed. External validation in a Scottish population was performed to assess the applicability and validity of the risk score in other populations. Methods: 2915 subjects aged ≥40 years who underwent routine clinical chest CT scanning for non-cardiovascular diagnostic indications were followed up until first diagnosis of, or death from, CVD. Using a case-cohort approach, all cases and a random sample of 20% of the participant’s CT examinations were visually graded for cardiovascular calcifications and cardiac diameter was measured. The radiological risk score was determined using imaging findings, age, gender, and CT indication. Results: Performance on 5-year CVD risk prediction was assessed. 384 events occurred in 2124 subjects during a mean follow-up of 4.25 years (0-6.4 years). The risk score demonstrated reasonable performance in the studied population. Calibration showed good agreement between actual and 5-year predicted risk of CVD. The c-statistic was 0.71 (95%CI:0.67-0.75). Conclusions: The radiological CVD risk score performed adequately in the Scottish population offering a potential novel strategy for identifying patients at high risk for developing cardiovascular disease using routine care CT data.Keywords: Cardiovascular disease; Vascular calcification; Epidemiology; Risk prediction; Multidetector Computed TomographyKey pointsA model was previously developed determining CVD risk using routine-care CT dataExternal validation was performed in a Scottish population to determine applicabilityThe radiological risk score showed adequate performanceIt offers a novel strategy for identifying patients with high CVD risk AbbreviationsDSC = descending aortaICD = international classification of diseaseLAD = left anterior descending arteryMV = mitral valvePROVIDI = PROgnostic Value of unrequested Information in Diagnostic ImagingIntroductionIn Scotland, approximately 40% of all premature deaths are caused by cardiovascular disease (CVD) with coronary heart disease and stroke being the most prevalent.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "NRS Scotland", "given" : "", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "Available at: ", "title" : "Under 75s age-standardised death rates for all causes and certain selected causes , Scotland , 1994 to 2014", "type" : "article-journal" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "[1]", "plainTextFormattedCitation" : "[1]", "previouslyFormattedCitation" : "[1]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[1] Even though the cardiovascular mortality rate has dropped by more than 40% in the last 10 years it remains high compared to the rest of the UK and Western EuropeADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Information Services Division", "given" : "", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-1", "issue" : "January", "issued" : { "date-parts" : [ [ "2014" ] ] }, "title" : "Publication Report Heart Disease Statistics Update", "type" : "article-journal" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Division", "given" : "Information Services", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-2", "issue" : "January", "issued" : { "date-parts" : [ [ "2014" ] ] }, "title" : "Publication Report Stroke Statistics Update", "type" : "article-journal" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "[2,3]", "plainTextFormattedCitation" : "[2,3]", "previouslyFormattedCitation" : "[2,3]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[2,3]; the 2010 premature death rates for coronary heart disease in Scotland were 37% higher for men and 60% for women than in England.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISBN" : "9781899088126", "author" : [ { "dropping-particle" : "", "family" : "British", "given" : "Heart Foundation Health Promotion Research Group", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Department of Public Health", "given" : "University of Oxford", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2012" ] ] }, "title" : "Coronary heart disease statistics A compendium of health statistics 2012 edition", "type" : "article-journal" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "[4]", "plainTextFormattedCitation" : "[4]", "previouslyFormattedCitation" : "[4]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[4] To address the high CVD burden and identify high risk patients, several risk scores have been developed over the past few decades. Well known examples are the QRISK2ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1136/bmj.39609.449676.25", "ISBN" : "0959-8146", "ISSN" : "0959-8138", "PMID" : "18573856", "abstract" : "OBJECTIVE: To develop and validate version two of the QRISK cardiovascular disease risk algorithm (QRISK2) to provide accurate estimates of cardiovascular risk in patients from different ethnic groups in England and Wales and to compare its performance with the modified version of Framingham score recommended by the National Institute for Health and Clinical Excellence (NICE). DESIGN: Prospective open cohort study with routinely collected data from general practice, 1 January 1993 to 31 March 2008. SETTING: 531 practices in England and Wales contributing to the national QRESEARCH database. PARTICIPANTS: 2.3 million patients aged 35-74 (over 16 million person years) with 140,000 cardiovascular events. Overall population (derivation and validation cohorts) comprised 2.22 million people who were white or whose ethnic group was not recorded, 22,013 south Asian, 11,595 black African, 10,402 black Caribbean, and 19,792 from Chinese or other Asian or other ethnic groups. MAIN OUTCOME MEASURES: First (incident) diagnosis of cardiovascular disease (coronary heart disease, stroke, and transient ischaemic attack) recorded in general practice records or linked Office for National Statistics death certificates. Risk factors included self assigned ethnicity, age, sex, smoking status, systolic blood pressure, ratio of total serum cholesterol:high density lipoprotein cholesterol, body mass index, family history of coronary heart disease in first degree relative under 60 years, Townsend deprivation score, treated hypertension, type 2 diabetes, renal disease, atrial fibrillation, and rheumatoid arthritis. RESULTS: The validation statistics indicated that QRISK2 had improved discrimination and calibration compared with the modified Framingham score. The QRISK2 algorithm explained 43% of the variation in women and 38% in men compared with 39% and 35%, respectively, by the modified Framingham score. Of the 112,156 patients classified as high risk (that is, >or=20% risk over 10 years) by the modified Framingham score, 46,094 (41.1%) would be reclassified at low risk with QRISK2. The 10 year observed risk among these reclassified patients was 16.6% (95% confidence interval 16.1% to 17.0%)-that is, below the 20% treatment threshold. Of the 78 024 patients classified at high risk on QRISK2, 11,962 (15.3%) would be reclassified at low risk by the modified Framingham score. The 10 year observed risk among these patients was 23.3% (22.2% to 24.4%)-that is, above the 20% threshold.\u2026", "author" : [ { "dropping-particle" : "", "family" : "Hippisley-Cox", "given" : "Julia", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Coupland", "given" : "Carol", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vinogradova", "given" : "Yana", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Robson", "given" : "John", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Minhas", "given" : "Rubin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sheikh", "given" : "Aziz", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brindle", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "BMJ (Clinical research ed.)", "id" : "ITEM-1", "issue" : "7659", "issued" : { "date-parts" : [ [ "2008" ] ] }, "page" : "1475-1482", "title" : "Predicting cardiovascular risk in England and Wales: prospective derivation and validation of QRISK2.", "type" : "article-journal", "volume" : "336" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "[5]", "plainTextFormattedCitation" : "[5]", "previouslyFormattedCitation" : "[5]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[5] and ASSIGN score,ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1136/hrt.2006.108167", "ISBN" : "1468-201X (Electronic)\\r1355-6037 (Linking)", "ISSN" : "1355-6037", "PMID" : "17090561", "abstract" : "OBJECTIVE: To improve equity in cardiovascular disease prevention by developing a cardiovascular risk score including social deprivation and family history. DESIGN: The ASSIGN score was derived from cardiovascular outcomes in the Scottish Heart Health Extended Cohort (SHHEC). It was tested against the Framingham cardiovascular risk score in the same database. SETTING: Random-sample, risk-factor population surveys across Scotland 1984-87 and North Glasgow 1989, 1992 and 1995. PARTICIPANTS: 6540 men and 6757 women aged 30-74, initially free of cardiovascular disease, ranked for social deprivation by residence postcode using the Scottish Index of Multiple Deprivation (SIMD) and followed for cardiovascular mortality and morbidity through 2005. RESULTS: Classic risk factors, including cigarette dosage, plus deprivation and family history but not obesity, were significant factors in constructing ASSIGN scores for each sex. ASSIGN scores, lower on average, correlated closely with Framingham values for 10-year cardiovascular risk. Discrimination of risk in the SHHEC population was significantly, but marginally, improved overall by ASSIGN. However, the social gradient in cardiovascular event rates was inadequately reflected by the Framingham score, leaving a large social disparity in future victims not identified as high risk. ASSIGN classified more people with social deprivation and positive family history as high risk, anticipated more of their events, and abolished this gradient. CONCLUSION: Conventional cardiovascular scores fail to target social gradients in disease. By including unattributed risk from deprivation, ASSIGN shifts preventive treatment towards the socially deprived. Family history is valuable not least as an approach to ethnic susceptibility. ASSIGN merits further evaluation for clinical use.", "author" : [ { "dropping-particle" : "", "family" : "Woodward", "given" : "Mark", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brindle", "given" : "Peter", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tunstall-Pedoe", "given" : "Hugh", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Heart (British Cardiac Society)", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2007" ] ] }, "page" : "172-176", "title" : "Adding social deprivation and family history to cardiovascular risk assessment: the ASSIGN score from the Scottish Heart Health Extended Cohort (SHHEC).", "type" : "article-journal", "volume" : "93" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "[6]", "plainTextFormattedCitation" : "[6]", "previouslyFormattedCitation" : "[6]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[6] which were developed in the UK and Scotland, respectively. These scores provide the 10 year risk of developing CVD in the general population and are based on traditional risk factors like age, gender, high blood pressure, and also social deprivation and family history.Traditional risk scores such as QRISK2 and ASSIGN are considered moderately successful in predicting future CVD events since corresponding event rates are predominantly driven by surrogate measures of the atherosclerotic burden.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1136/bmj.e3318", "ISBN" : "1756-1833", "ISSN" : "1756-1833", "PMID" : "22628003", "abstract" : "OBJECTIVE: To evaluate the evidence on comparisons of established cardiovascular risk prediction models and to collect comparative information on their relative prognostic performance. DESIGN: Systematic review of comparative predictive model studies. DATA SOURCES: Medline and screening of citations and references. STUDY SELECTION: Studies examining the relative prognostic performance of at least two major risk models for cardiovascular disease in general populations. DATA EXTRACTION: Information on study design, assessed risk models, and outcomes. We examined the relative performance of the models (discrimination, calibration, and reclassification) and the potential for outcome selection and optimism biases favouring newly introduced models and models developed by the authors. RESULTS: 20 articles including 56 pairwise comparisons of eight models (two variants of the Framingham risk score, the assessing cardiovascular risk to Scottish Intercollegiate Guidelines Network to assign preventative treatment (ASSIGN) score, systematic coronary risk evaluation (SCORE) score, Prospective Cardiovascular Munster (PROCAM) score, QRESEARCH cardiovascular risk (QRISK1 and QRISK2) algorithms, Reynolds risk score) were eligible. Only 10 of 56 comparisons exceeded a 5% relative difference based on the area under the receiver operating characteristic curve. Use of other discrimination, calibration, and reclassification statistics was less consistent. In 32 comparisons, an outcome was used that had been used in the original development of only one of the compared models, and in 25 of these comparisons (78%) the outcome-congruent model had a better area under the receiver operating characteristic curve. Moreover, authors always reported better area under the receiver operating characteristic curves for models that they themselves developed (in five articles on newly introduced models and in three articles on subsequent evaluations). CONCLUSIONS: Several risk prediction models for cardiovascular disease are available and their head to head comparisons would benefit from standardised reporting and formal, consistent statistical comparisons. Outcome selection and optimism biases apparently affect this literature.", "author" : [ { "dropping-particle" : "", "family" : "Siontis", "given" : "G. C. M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tzoulaki", "given" : "I.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Siontis", "given" : "K. C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ioannidis", "given" : "J. P. A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "BMJ", "id" : "ITEM-1", "issue" : "may24 1", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "e3318-e3318", "title" : "Comparisons of established risk prediction models for cardiovascular disease: systematic review", "type" : "article", "volume" : "344" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "[7]", "plainTextFormattedCitation" : "[7]", "previouslyFormattedCitation" : "[7]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[7] It is for that reason that there is substantial heterogeneity between traditional risk and actual atherosclerosis burden. In this regard, vascular calcifications, as detected on computed tomography (CT), may provide a more accurate measure of atherosclerosis burden and offer an improved assessment of personalized risk.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1001/jama.2010.461", "ISBN" : "0098-7484", "ISSN" : "1538-3598", "PMID" : "20424251", "abstract" : "The coronary artery calcium score (CACS) has been shown to predict future coronary heart disease (CHD) events. However, the extent to which adding CACS to traditional CHD risk factors improves classification of risk is unclear.", "author" : [ { "dropping-particle" : "", "family" : "Polonsky", "given" : "Tamar S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McClelland", "given" : "Robyn L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jorgensen", "given" : "Neal W", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bild", "given" : "Diane E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Burke", "given" : "Gregory L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Guerci", "given" : "Alan D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Greenland", "given" : "Philip", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "JAMA : the journal of the American Medical Association", "id" : "ITEM-1", "issue" : "16", "issued" : { "date-parts" : [ [ "2010" ] ] }, "page" : "1610-1616", "title" : "Coronary artery calcium score and risk classification for coronary heart disease prediction.", "type" : "article-journal", "volume" : "303" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "[8]", "plainTextFormattedCitation" : "[8]", "previouslyFormattedCitation" : "[8]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[8] While the predictive qualities of these imaging markers are increasingly recognised in the medical literature,ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1007/s00330-011-2112-8", "ISSN" : "09387994", "PMID" : "21603881", "abstract" : "An increase in the number of CT investigations will likely result in a an increase in unrequested information. Clinical relevance of these findings is unknown. This is the first follow-up study to investigate the prognostic relevance of subclinical coronary (CAC) and aortic calcification (TAC) as contained in routine diagnostic chest CT in a clinical care population.", "author" : [ { "dropping-particle" : "", "family" : "Jacobs", "given" : "Peter C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gondrie", "given" : "Martijn J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mali", "given" : "Willem P.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Oen", "given" : "Ayke L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prokop", "given" : "Mathias", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grobbee", "given" : "Diederick E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Graaf", "given" : "Yolanda", "non-dropping-particle" : "Van Der", "parse-names" : false, "suffix" : "" } ], "container-title" : "European Radiology", "id" : "ITEM-1", "issue" : "8", "issued" : { "date-parts" : [ [ "2011" ] ] }, "page" : "1577-1585", "title" : "Unrequested information from routine diagnostic chest CT predicts future cardiovascular events", "type" : "article-journal", "volume" : "21" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "[9]", "plainTextFormattedCitation" : "[9]", "previouslyFormattedCitation" : "[9]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[9] they do not have a defining role in CVD risk prediction in contemporary guidelines because their therapeutic consequences are still unclear.The total number of chest CT examinations is steadily growing, due to technical developments, such as the implementation of ultra-low dose chest CT examinationsADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.2214/AJR.13.12312", "ISSN" : "0361-803X", "author" : [ { "dropping-particle" : "", "family" : "Padole", "given" : "Atul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Singh", "given" : "Sarabjeet", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ackman", "given" : "Jeanne B.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wu", "given" : "Carol", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Do", "given" : "Synho", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pourjabbar", "given" : "Sarvenaz", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Khawaja", "given" : "Ranish Deedar Ali", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Otrakji", "given" : "Alexi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Digumarthy", "given" : "Subba", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shepard", "given" : "Jo-Anne", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kalra", "given" : "Mannudeep", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "American Journal of Roentgenology", "id" : "ITEM-1", "issue" : "October", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "772-781", "title" : "Submillisievert Chest CT With Filtered Back Projection and Iterative Reconstruction Techniques", "type" : "article-journal", "volume" : "203" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "[10]", "plainTextFormattedCitation" : "[10]", "previouslyFormattedCitation" : "[10]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[10] and new clinical indications such as population lung cancer screening.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.7326/M13-2316", "ISSN" : "0003-4819", "PMID" : "24379002", "abstract" : "Background: The optimal screening policy for lung cancer is unknown.Objective: To identify efficient computed tomography (CT) screening scenarios in which relatively more lung cancer deaths are averted for fewer CT screening examinations.Design: Comparative modeling study using 5 independent models.Data Sources: The National Lung Screening Trial; the Prostate, Lung, Colorectal, and Ovarian trial; the Surveillance, Epidemiology, and End Results program; and the U.S. Smoking History Generator.Target Population: U.S. cohort born in 1950.Time Horizon: Cohort followed from ages 45 to 90 years.Perspective: Societal.Intervention: 576 scenarios with varying eligibility criteria (age, pack-years of smoking, years since quitting) and screening intervals.Outcome Measures: Benefits included lung cancer deaths averted or life-years gained. Harms included CT examinations, false-positive results (including those obtained from biopsy/surgery), overdiagnosed cases, and radiation-related deaths.Results of Best-Case Scenario: The most advantageous strategy was annual screening from ages 55 through 80 years for ever-smokers with a smoking history of at least 30 pack-years and ex-smokers with less than 15 years since quitting. It would lead to 50% (model ranges, 45% to 54) of cases of cancer being detected at an early stage (stage I/II), 575 screenings examinations per lung cancer death averted, a 14% (range, 8.2% to 23.5%) reduction in lung cancer mortality, 497 lung cancer deaths averted, and 5250 life-years gained per the 100 000-member cohort. Harms would include 67 550 false-positive test results, 910 biopsies or surgeries for benign lesions, and 190 overdiagnosed cases of cancer (3.7% of all cases of lung cancer [model ranges, 1.4% to 8.3%]).Results of Sensitivity Analysis: The number of cancer deaths averted for the scenario varied across models between 177 and 862; the number of overdiagnosed cases of cancer varied between 72 and 426.Limitations: Scenarios assumed 100% screening adherence. Data derived from trials with short duration were extrapolated to lifetime follow-up.Conclusion: Annual CT screening for lung cancer has a favorable benefit-to-harm ratio for individuals ages 55 through 80 years with 30 or more pack-years' exposure to smoking.Primary Funding Source: National Cancer Institute.", "author" : [ { "dropping-particle" : "", "family" : "Koning", "given" : "Harry J", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Meza", "given" : "Rafael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Plevritis", "given" : "Sylvia K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Haaf", "given" : "Kevin", "non-dropping-particle" : "ten", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Munshi", "given" : "Vidit N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jeon", "given" : "Jihyoun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Erdogan", "given" : "Saadet Ayca", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kong", "given" : "Chung Yin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Han", "given" : "Summer S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rosmalen", "given" : "Joost", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Choi", "given" : "Sung Eun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Pinsky", "given" : "Paul F", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gonzalez", "given" : "Amy Berrington", "non-dropping-particle" : "de", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Berg", "given" : "Christine D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Black", "given" : "William C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tammem\u00e4gi", "given" : "Martin C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hazelton", "given" : "William D", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Feuer", "given" : "Eric J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "McMahon", "given" : "Pamela M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Annals of Internal Medicine", "id" : "ITEM-1", "issue" : "N/A", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "N/A-N/A", "title" : "Benefits and Harms of Computed Tomography Lung Cancer Screening Strategies: A Comparative Modeling Study for the U.S. Preventive Services Task Force", "type" : "article-journal", "volume" : "N/A" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "[11]", "plainTextFormattedCitation" : "[11]", "previouslyFormattedCitation" : "[11]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[11] As a result, information on imaging markers is increasingly available in routine care for a growing number of patients. Recently, a risk score was developedADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1148/radiol.14132211", "ISSN" : "1527-1315", "PMID" : "24865309", "abstract" : "Purpose To investigate the contribution of incidental findings at chest computed tomography (CT) in the detection of subjects at high risk for cardiovascular disease (CVD) by deriving and validating a CT-based prediction rule. Materials and Methods This retrospective study was approved by the ethical review board of the primary participating facility, and informed consent was waived. The derivation cohort comprised 10 410 patients who underwent diagnostic chest CT for noncardiovascular indications. During a mean follow-up of 3.7 years (maximum, 7.0 years), 1148 CVD events (cases) were identified. By using a case-cohort approach, CT scans from the cases and from an approximately 10% random sample of the baseline cohort (n = 1366) were graded visually for several cardiovascular findings. Multivariable Cox proportional hazards analysis with backward elimination technique was used to derive the best-fitting parsimonious prediction model. External validation (discrimination, calibration, and risk stratification) was performed in a separate validation cohort (n = 1653). Results The final model included patient age and sex, CT indication, left anterior descending coronary artery calcifications, mitral valve calcifications, descending aorta calcifications, and cardiac diameter. The model demonstrated good discriminative value, with a C statistic of 0.71 (95% confidence interval: 0.68, 0.74) and a good overall calibration, as assessed in the validation cohort. This imaging-based model allows accurate stratification of individuals into clinically relevant risk categories. Conclusion Structured reporting of incidental CT findings can mediate accurate stratification of individuals into clinically relevant risk categories and subsequently allow those at higher risk of future CVD events to be distinguished. \u00a9 RSNA, 2014 Online supplemental material is available for this article.", "author" : [ { "dropping-particle" : "", "family" : "Jairam", "given" : "Pushpa M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gondrie", "given" : "Martijn J A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grobbee", "given" : "Diederick E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Th M Mali", "given" : "Willem P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jacobs", "given" : "Peter C A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Graaf", "given" : "Yolanda", "non-dropping-particle" : "van der", "parse-names" : false, "suffix" : "" } ], "container-title" : "Radiology", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "132211", "title" : "Incidental Imaging Findings from Routine Chest CT Used to Identify Subjects at High Risk of Future Cardiovascular Events.", "type" : "article-journal" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "[12]", "plainTextFormattedCitation" : "[12]", "previouslyFormattedCitation" : "[12]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[12] for detecting subjects at increased risk for CVD using incidental findings from chest CT examinations. This score includes traditional risk factors like age and gender combined with imaging results such as cardiovascular calcifications and cardiac diameter. Although initial validation of the risk score showed promising results in a Dutch population, further validation is still required to assess whether the risk score can be applied more broadly across different (but related) patient populations. The relatively high CVD burden in Scotland provides ample opportunity, not only to validate the risk score, but the potential to provide a novel radiological method of identifying (previously undiagnosed) high-risk patients. In this study we validated whether this radiological risk score is able to detect and accurately stratify individuals from a Scottish population into clinically relevant CVD risk categories.MethodsStudy PopulationThe study population (Fig. 1) consisted of 2915 subjects aged ≥ 40 years who underwent routine clinical chest CT scanning between January 2008 to July 2008 for diagnostic indications other than cardiovascular diseases in the participating hospitals (Royal Infirmary of Edinburgh, Edinburgh; Western General Hospital, Edinburgh; St John’s Hospital, Livingson) in the Lothian Region, Scotland. These hospitals serve approximately 750,000 people out of a total 5.2 million population in Scotland. This study population provided an overall comparable Caucasian population with a slightly increased cardiovascular risk profile as compared to the Dutch cohort in which the radiological cardiovascular score was developed.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISBN" : "9781899088126", "author" : [ { "dropping-particle" : "", "family" : "British", "given" : "Heart Foundation Health Promotion Research Group", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Department of Public Health", "given" : "University of Oxford", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2012" ] ] }, "title" : "Coronary heart disease statistics A compendium of health statistics 2012 edition", "type" : "article-journal" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "[4]", "plainTextFormattedCitation" : "[4]", "previouslyFormattedCitation" : "[4]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[4] Patients with a previous diagnosis of primary lung cancer (including mesothelioma or distant metastatic disease from other types of cancer (excluding hematologic malignancies) at baseline were excluded (n=740). These patients were excluded because it is highly unlikely that detection of unexpected image findings will alter clinical decision making in patients with such a poor prognosis. Also excluded were patients yielding prior history of CVD or subjects with a CT referral indication directly related to (suspected) cardiovascular pathology (n=51), to ensure that the evaluated imaging findings were truly “incidental”. After exclusion, the full baseline validation cohort consisted of 2124 subjects who were considered for analyses.The study was approved by the Research Ethics Committee of the Royal Infirmary of Edinburgh (Ref: NR/1404AB6). Written informed consent was waived for all patients because of the retrospective design and absence of intervention of the study. This study is in compliance with the declaration of Helsinki and was performed in accordance with relevant guidelines and regulations.Cardiovascular events and follow-upSubjects who developed a CVD event during follow-up were identified as cases. CVD events were defined, using the international classification of disease (ICD) 10 definitions, as all diagnosis of coronary artery disease (Angina, (sub)acute myocardial infarction, acute or chronic ischaemic heart diseases), cerebrovascular events (ischemic stroke, haemorrhagic stroke, and transient ischemic attack), peripheral artery disease (intermittent claudication), and heart failure.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "URL" : "", "author" : [ { "dropping-particle" : "", "family" : "World Health Organization", "given" : "", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2016" ] ] }, "title" : "International Statistical Classification of Diseases and Related Health Problems", "type" : "webpage" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "[13]", "plainTextFormattedCitation" : "[13]", "previouslyFormattedCitation" : "[13]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[13] Data on fatal and non-fatal CVD events were obtained from the National Health Service (NHS) registry using ICD 10 codes (Supplementary Table S1). The Information and Statistics Division (ISD) of the NHS in Scotland has linked information on all Scottish hospital inpatient discharges (1981 – 2015) and death records (1981 – 2015) using probability matching. For all patients we determined the entry date, which was the date subjects underwent chest CT examination. The censor date was determined as the date on which they developed an event as specified above, the date the study period ended (April 1st 2014) or date of death, whichever occurred first. Sample selection and study designWe used a case-cohort approach as introduced by Prentice using all cases and a subcohort resembling an approximately 20% random sample from the full validation cohort (n=2124) at the beginning of the study.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.2307/2531051", "ISSN" : "0006341X", "PMID" : "3741972", "abstract" : "A design is proposed for \"case-control within cohort\" studies. In this design, controls are sampled without replacement from failure-free members of the cohort at each distinct failure time. Upon selection, a subject ceases to be eligible for control selection at later failure times. Also, if a subject failing at time t had been selected as a control at t' less than t, then the matched controls at t are selected to have also been at risk at t'. In these circumstances correlation exists between score statistic contributions at t and t'. An estimator is developed for this correlation. A small simulation study compares the design just described to other possible synthetic case-control designs.", "author" : [ { "dropping-particle" : "", "family" : "Prentice", "given" : "R L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Biometrics", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "1986" ] ] }, "page" : "301-310", "title" : "On the design of synthetic case-control studies.", "type" : "article-journal", "volume" : "42" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "[14]", "plainTextFormattedCitation" : "[14]", "previouslyFormattedCitation" : "[14]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[14] The cases together with the subcohort define the study population. A major advantage of this design is that it enables survival analyses without the need to score the chest CT scans for the full cohort. Because this implies that cases are inherently overrepresented, we adjusted all analyses for the sampling fraction such that estimates of model performance are applicable to the full cohort. Previous studies have suggested that case-cohorts with sampling fractions above 10% yield similar to the full cohort analysis.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.jclinepi.2006.06.022", "ISSN" : "08954356", "PMID" : "17346608", "abstract" : "Objective: The case-cohort design combines the advantages of a prospective cohort study and the efficiency of a case-control design. Usually a Cox proportional-hazards model is used for the analyses. However, adaptation of the model is necessary because of the sampling. We compared three methods that were proposed in the literature, which differ in weighting of study subjects: Prentice's, Barlow's, and Self and Prentice's method. Study Design and Setting: In a cohort of 17,357 women we studied the relationship between body mass index and cardiovascular disease (n = 821) with varying subcohort sizes (sampling fraction = 0.005, 0.01, 0.05, 0.10, 0.15). Results: Even with a sampling fraction of 0.01, all three methods showed identical estimates and standard errors (SE). With sampling fractions ???0.10, results of the case-cohort analyses were similar to the full-cohort analyses. With simulations, the three methods provided different results if the full cohort is small (<1,250 subjects, subcohort = 10%, 8% failures) or if the subcohort size was smaller than 15% (full cohort of 1,000 observations, 8% failures). The difference between the methods did not change with the number of failures or with different effect sizes. Conclusion: In the above-mentioned situations, the effect estimates and SE of Prentice's method most resembled the estimates of the full-cohort estimates. ?? 2007 Elsevier Inc. All rights reserved.", "author" : [ { "dropping-particle" : "", "family" : "Onland-Moret", "given" : "N. Charlotte", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "A", "given" : "Daphne L.", "non-dropping-particle" : "van der", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Schouw", "given" : "Yvonne T.", "non-dropping-particle" : "van der", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Buschers", "given" : "Wim", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Elias", "given" : "Sjoerd G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gils", "given" : "Carla H.", "non-dropping-particle" : "van", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Koerselman", "given" : "Jeroen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Roest", "given" : "Mark", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grobbee", "given" : "Diederick E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Peeters", "given" : "Petra H M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Clinical Epidemiology", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2007" ] ] }, "page" : "350-355", "title" : "Analysis of case-cohort data: A comparison of different methods", "type" : "article-journal", "volume" : "60" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "[15]", "plainTextFormattedCitation" : "[15]", "previouslyFormattedCitation" : "[15]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[15] CT scanning and scoring of CT characteristicsAll chest CT examinations were obtained using multi-detector CT of different vendors according to the prevailing routine clinical protocols of the participating hospitals. When study subjects underwent multiple chest CT examination during follow-up, the findings from the first examination were used. All types of CT (including non-contrast) were considered eligible. Slice thicknesses had a range of 1.25 mm to 8 mm and varied according to the chest CT indication and corresponding protocol.CT examinations were graded by a qualified medical practitioner with 2 years of chest CT experience who was trained on using the radiological risk score under the supervision of an experienced chest radiologist. The training consisted of scoring 50 randomly selected patients who were not part of the study population. Weighted kappa for inter-observer reliability regarding calcifications in the training set was 0.90. CT examinations were graded for calcifications in the Left Anterior Descending (LAD) artery, descending thoracic aorta (DSC), and the mitral valve (MV) (Fig. 2) using a semi quantitative grading system (Table 1). The upper margin of the descending aorta was defined as the point where the left subclavian artery originates from the aortic arch, whereas the lower margin was defined as the level where the diaphragm becomes visible. The cardiac diameter was measured at the point where the transverse cardiac silhouette reached its maximum. The cardiac diameter was measured using a measurement tool, integral to the DICOM reviewing software (Carestream Medical and Dental Imaging Systems, Carestream Health, Inc., NY, USA). The grading and measurement techniques have been published and validated previously.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1097/RCT.0b013e3181bbcff6", "ISSN" : "0363-8715", "abstract" : "OBJECTIVE:To investigate the interobserver and intraobserver agreements for the semiquantitative assessment of markers of subclinical cardiovascular disease as identified by routine care, diagnostic computed tomography (CT) of the chest, to improve the quality of reporting of these incidental findings.\\n\\nMETHODS:Two observers independently evaluated 109 consecutive chest CT scans in routine care, clinical patients from one tertiary referral center. All nongated, contrast-enhanced scans were acquired on a 16-slice CT scanner. Images were scored for the presence of aortic wall abnormalities and calcifications of the coronary artery, the heart valves, the thoracic aorta, and the proximal supraaortic arteries. Furthermore, the presence of left ventricular scarring and elongation of the aorta were recorded. All markers were scored on a semiquantitative scale. Interobserver and intraobserver agreements are presented as weighted kappa and intraclass correlation coefficients.\\n\\nRESULTS:Interobserver and intraobserver agreements for individual markers were good to excellent, with weighted kappa coefficients of 0.54 to 0.89 for interobserver agreement and 0.55 to 0.96 for intraobserver agreement.\\n\\nCONCLUSIONS:Semiquantitative assessment of subclinical cardiovascular disease markers in routine care, diagnostic chest CT scans is possible with good to excellent interobserver and intraobserver agreements. Use of these definitions in clinical practice will enable a more standardized assessment and reporting of incidental findings in diagnostic chest CT.", "author" : [ { "dropping-particle" : "", "family" : "Jacobs", "given" : "Peter C.A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prokop", "given" : "Mathias", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Oen", "given" : "Ayke L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Graaf", "given" : "Yolanda", "non-dropping-particle" : "van der", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grobbee", "given" : "Diederick E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mali", "given" : "Willem P.Th.M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Computer Assisted Tomography", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2010" ] ] }, "page" : "279-284", "title" : "Semiquantitative Assessment of Cardiovascular Disease Markers in Multislice Computed Tomography of the Chest", "type" : "article", "volume" : "34" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "[16]", "plainTextFormattedCitation" : "[16]", "previouslyFormattedCitation" : "[16]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[16] The observer was blinded for outcome during scoring. Statistical analysisThe determinants used in the radiological risk score are: Age, gender, CT indication, cardiovascular calcifications (LAD, MW, DSC) and cardiac diameter. Development of the model was previously described.[12] The complete risk model and source code is available in the supplementary data file.All analyses are based on the entire validation cohort, and missing data arising due to the implementation of a case-cohort design were accounted for by use of multiple imputation.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1002/sim.4130", "ISBN" : "1097-0258 (Electronic)\\r0277-6715 (Linking)", "ISSN" : "02776715", "PMID" : "21351290", "abstract" : "The usual methods for analyzing case-cohort studies rely on sometimes not fully efficient weighted estimators. Multiple imputation might be a good alternative because it uses all the data available and approximates the maximum partial likelihood estimator. This method is based on the generation of several plausible complete data sets, taking into account uncertainty about missing values. When the imputation model is correctly defined, the multiple imputation estimator is asymptotically unbiased and its variance is correctly estimated. We show that a correct imputation model must be estimated from the fully observed data (cases and controls), using the case status among the explanatory variable. To validate the approach, we analyzed case-cohort studies first with completely simulated data and then with case-cohort data sampled from two real cohorts. The analyses of simulated data showed that, when the imputation model was correct, the multiple imputation estimator was unbiased and efficient. The observed gain in precision ranged from 8 to 37 per cent for phase-1 variables and from 5 to 19 per cent for the phase-2 variable. When the imputation model was misspecified, the multiple imputation estimator was still more efficient than the weighted estimators but it was also slightly biased. The analyses of case-cohort data sampled from complete cohorts showed that even when no strong predictor of the phase-2 variable was available, the multiple imputation was unbiased, as precised as the weighted estimator for the phase-2 variable and slightly more precise than the weighted estimators for the phase-1 variables. However, the multiple imputation estimator was found to be biased when, because of interaction terms, some coefficients of the imputation model had to be estimated from small samples. Multiple imputation is an efficient technique for analyzing case-cohort data. Practically, we suggest building the analysis model using only the case-cohort data and weighted estimators. Multiple imputation can eventually be used to reanalyze the data using the selected model in order to improve the precision of the results.", "author" : [ { "dropping-particle" : "", "family" : "Marti", "given" : "Helena", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Chavance", "given" : "Michel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Statistics in Medicine", "id" : "ITEM-1", "issue" : "13", "issued" : { "date-parts" : [ [ "2011" ] ] }, "page" : "1595-1607", "title" : "Multiple imputation analysis of case-cohort studies", "type" : "article-journal", "volume" : "30" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "[17]", "plainTextFormattedCitation" : "[17]", "previouslyFormattedCitation" : "[17]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[17] This strategy also allowed to account for missing values (LAD, DSC, MV, cardiac diameter) due to unavailable chest CT images in the sub-cohort (N= 5 cases and 11 non-cases). We focus on assessing the predictive accuracy of the radiological cardiovascular risk score for predicting 5 year incidence of CVD. Because the follow-up in our cohort was limited to 6.4 years, the observed cumulative baseline hazard function was extrapolated to approximate the 10 year risk using the flexible survival approach of Royston and Parmar (Supplementary Table S2). CVD event rates were calculated by dividing the total number of CVD events by the total number of person years at risk. The predictive accuracy of the score was assessed by determining its discrimination and calibration. Discrimination is the ability of the score to distinguish patients who are at high risk of developing CVD from those at low risk. The discrimination was evaluated by calculating the c-statistic in each imputed dataset, and applying Rubin's rules.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISBN" : "0-387-98784-3", "author" : [ { "dropping-particle" : "", "family" : "Therneau", "given" : "Terry M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grambsch", "given" : "Patricia M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2000" ] ] }, "publisher" : "Springer, New York", "title" : "Modeling Survival Data: Extending the Cox Model", "type" : "book" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "[18]", "plainTextFormattedCitation" : "[18]", "previouslyFormattedCitation" : "[18]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[18] We also visualized the score's discrimination in a survival plot where we stratified the predicted 5 year CVD risk by categories used in current CVD guidelines for initiating treatment: low (<10%), intermediate (10-20%), and high (>20%) risk of CVD.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.atherosclerosis.2012.05.007", "ISSN" : "00219150", "author" : [ { "dropping-particle" : "", "family" : "Perk", "given" : "Joep", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Backer", "given" : "Guy", "non-dropping-particle" : "De", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gohlke", "given" : "Helmut", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Graham", "given" : "Ian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Reiner", "given" : "\u017deljko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Verschuren", "given" : "W.M. Monique", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Albus", "given" : "Christian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Benlian", "given" : "Pascale", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Boysen", "given" : "Gudrun", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cifkova", "given" : "Renata", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Deaton", "given" : "Christi", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ebrahim", "given" : "Shah", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Fisher", "given" : "Miles", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Germano", "given" : "Giuseppe", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hobbs", "given" : "Richard", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hoes", "given" : "Arno", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Karadeniz", "given" : "Sehnaz", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mezzani", "given" : "Alessandro", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prescott", "given" : "Eva", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ryden", "given" : "Lars", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scherer", "given" : "Martin", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Syv\u00e4nne", "given" : "Mikko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Scholte Op Reimer", "given" : "Wilma J.M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vrints", "given" : "Christiaan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Wood", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zamorano", "given" : "Jose Luis", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Zannad", "given" : "Faiez", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Atherosclerosis", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "1-68", "title" : "European Guidelines on cardiovascular disease prevention in clinical practice (version 2012)", "type" : "article-journal", "volume" : "223" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "[19]", "plainTextFormattedCitation" : "[19]", "previouslyFormattedCitation" : "[19]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[19] Calibration was visually evaluated in a calibration plot comparing 5 year observed and predicted risks. Analyses were performed using R-project software package, version 3.1.1 ( HYPERLINK "" \h r-). ResultsBaseline characteristics of the validation (sub)cohort as well as the original PROVIDI (PROgnostic Value of unrequested Information in Diagnostic Imaging) subcohort can be found in Table 2. Compared to the PROVIDI subcohort, the Scottish subcohort showed a higher percentage of severe coronary artery and descending aorta calcification and were on average 5 years older. Lung disease was the most frequent CT-indication (38%) followed by suspicion of pulmonary malignancy (32%). Cases were on average 71 years old and generally showed more severe calcifications and larger cardiac diameter. A total of 384 CVD events occurred during a mean follow-up period of 4.3 years (0-6.4 years). 1183 (56%) patients were followed up for at least 5 years. The overall annualized CVD event rate (per 1000 person years) was 42.5. CVD event rates for gender and age are shown in Table 3. Event rates were higher for men (45.7) compared to women (39.4) and increased substantially with higher age. A total of 26 CVD events occurred in the 456 patients without calcifications in the LAD, descending thoracic aorta and mitral valve. The predicted and observed 5 year CVD risk in this patient group was 5.4% and 5.6% respectively.The score showed a good discriminative ability with a c-statistic of 0.71 (95% Confidence Interval: 0.67-0.74) which is comparable to the discrimination previously found in the Dutch hospital population. Discrimination is visualized with a survival plot where the cohort was stratified for <10%, 10-20%, and>20% risk of cardiovascular disease in 5 years (Fig. 3). Calibration of 5 year predicted risks also appeared adequate, although there was some evidence of overfitting. In particular, we found over-estimation between the probability range of 0.6 and 0.8 and underestimation between 0.4 and 0.6. (Fig. 4). The 5 year risks of the low (<10%), intermediate (10-20%), and high (>20%) predicted 5y CVD risk groups were 8.6%, 14.9%, and 31.7% respectively (Table 4).DiscussionIn this case-cohort study of 2124 Scottish subjects who underwent a CT examination for diagnostic indications we showed that the radiological risk score can be used to reliably predict the 5 year probability of developing cardiovascular disease in a Scottish population. Adequately identifying patients with high cardiovascular risk using readily available CT image findings in a previously undiagnosed population is of major value. Early detection of high risk individuals may facilitate targeted preventative management interventions, such as institution of statin and/or thrombocyte aggregation inhibitors therapy. With prevention and treatment plans, including the use of traditional cardiovascular risk scores like QRISK2 and ASSIGN, mortality rates for CVD have fallen steadily in Scotland over the last 10 years by more than 40%.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Information Services Division", "given" : "", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-1", "issue" : "January", "issued" : { "date-parts" : [ [ "2014" ] ] }, "title" : "Publication Report Heart Disease Statistics Update", "type" : "article-journal" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "author" : [ { "dropping-particle" : "", "family" : "Division", "given" : "Information Services", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-2", "issue" : "January", "issued" : { "date-parts" : [ [ "2014" ] ] }, "title" : "Publication Report Stroke Statistics Update", "type" : "article-journal" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "[2,3]", "plainTextFormattedCitation" : "[2,3]", "previouslyFormattedCitation" : "[2,3]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[2,3] In spite of these improvements, the cardiovascular event rates remain relatively high compared to the rest of the UK and western Europe.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISBN" : "9781899088126", "author" : [ { "dropping-particle" : "", "family" : "British", "given" : "Heart Foundation Health Promotion Research Group", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Department of Public Health", "given" : "University of Oxford", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2012" ] ] }, "title" : "Coronary heart disease statistics A compendium of health statistics 2012 edition", "type" : "article-journal" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "[4]", "plainTextFormattedCitation" : "[4]", "previouslyFormattedCitation" : "[4]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[4] This dissimilarity was also supported by our results as the annualized CVD event rate was 42.5 in Scotland compared to 29.3 in the original Dutch cohort, leaving room for further optimization of preventative and therapeutic interventions. The radiological risk score validated in this study could help drive down these rates first and foremost through the identification of patients with high cardiovascular risk. Patients with a high radiological risk score can either have a high risk based on traditional risk scores, have not been previously recognized by traditional risk scores or have a low or absent traditional risk. In patients with a high traditional as well as a high radiological risk the importance of preventive treatment or behavioural changes can be further emphasized. Confronting patients with calcification burden on their CT examinations is thought to be a strong motivator for lifestyle modification and therapy adherence.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.atherosclerosis.2005.06.018", "ISBN" : "0021-9150 (Print)\\n0021-9150 (Linking)", "ISSN" : "0021-9150", "PMID" : "16051253", "abstract" : "BACKGROUND: Many patients lack motivation to control cardiovascular risk factors and clinicians have long sought ways to activate apathetic patients. Despite significant and consistent data on the benefits of lipid-lowering agents to reduce cardiovascular events, adherence and utilization of these agents remains low. We evaluated whether visualization of coronary calcium would positively affect patients' adherence rates.\\n\\nMETHODS: We evaluated patients who underwent electron beam tomography (EBT) coronary calcium evaluation at least 1 year prior with a survey questioning them about health behaviors. Patients filled out baseline and follow-up questionnaires relating to lifestyle modifications, including statin utilization, diet, exercise, tobacco cessation and vitamin/antioxidant utilization.\\n\\nRESULTS: The study population consisted of 505 individuals on statin therapy on baseline who were followed for a mean of 3 +/- 2 years. Overall the statin compliance was lowest (44%) among those with CAC score in the first quartile (0-30), whereas 91% of individuals with baseline CAC score in the fourth quartile (>or= 526) adhered to statin therapy. In multivariable analysis, after adjusting for cardiovascular risk factors, age, and gender, higher baseline CAC scores were strongly associated with adherence to statin therapy.\\n\\nCONCLUSIONS: In addition to risk stratification for the asymptomatic person, patients visualizing coronary artery calcium may improve utilization and adherence to lipid-lowering therapy. Outcome studies and randomized trials need to be done to quantify the true value and cost-effectiveness of this approach.", "author" : [ { "dropping-particle" : "", "family" : "Kalia", "given" : "Nove K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Miller", "given" : "Loren G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nasir", "given" : "Khurram", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Blumenthal", "given" : "Roger S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Agrawal", "given" : "Nisha", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Budoff", "given" : "Matthew J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Atherosclerosis", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2006" ] ] }, "page" : "394-9", "title" : "Visualizing coronary calcium is associated with improvements in adherence to statin therapy.", "type" : "article-journal", "volume" : "185" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "[20]", "plainTextFormattedCitation" : "[20]", "previouslyFormattedCitation" : "[20]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[20] A potential second step could be preventive management in high radiological risk patients with or without high risk in traditional scores. While patients with a high traditional risk will receive treatment in current guidelines, patients with a high radiological risk and a low or absent traditional risk would not. However, while a large portion of the actual cardiovascular risk can be predicted with the use of traditional risk factors, a substantial amount of these patients will develop CVD in the absence of these risk factors.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1001/jama.290.7.898", "ISSN" : "1538-3598", "PMID" : "12928466", "abstract" : "CONTEXT: It is commonly suggested that more than 50% of patients with coronary heart disease (CHD) lack any of the conventional risk factors (cigarette smoking, diabetes, hyperlipidemia, and hypertension). This claim implies that other factors play a significant role in CHD and has led to considerable interest in nontraditional risk factors and genetic causes of CHD. OBJECTIVE: To determine the prevalence of the 4 conventional risk factors among patients with CHD. DESIGN, SETTING, AND PATIENTS: In 2002-2003, we analyzed data for 122458 patients enrolled in 14 international randomized clinical trials of CHD conducted during the prior decade. Patients included 76716 with ST-elevation myocardial infarction, 35527 with unstable angina/non-ST-elevation myocardial infarction, and 10215 undergoing percutaneous coronary intervention. MAIN OUTCOME MEASURES: Prevalence of each conventional risk factor and number of conventional risk factors present among patients with CHD, compared between men and women and by age at trial entry. RESULTS: Among patients with CHD, at least 1 of the 4 conventional risk factors was present in 84.6% of women and 80.6% of men. In younger patients (men < or =55 years and women < or =65 years) and most patients presenting either with unstable angina or for percutaneous coronary intervention, only 10% to 15% of patients lacked any of the 4 conventional risk factors. This pattern was largely independent of sex, geographic region, trial entry criteria, or prior CHD. Premature CHD was related to cigarette smoking in men and cigarette smoking and diabetes in women. Smoking decreased the age at the time of CHD event (at trial entry) by nearly 1 decade in all risk factor combinations. CONCLUSIONS: In direct contrast with conventional thinking, 80% to 90% of patients with CHD have conventional risk factors. Although research on nontraditional risk factors and genetic causes of heart disease is important, clinical medicine, public health policies, and research efforts should place significant emphasis on the 4 conventional risk factors and the lifestyle behaviors causing them to reduce the epidemic of CHD.", "author" : [ { "dropping-particle" : "", "family" : "Khot", "given" : "Umesh N", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Khot", "given" : "Monica B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Bajzer", "given" : "Christopher T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sapp", "given" : "Shelly K", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ohman", "given" : "E Magnus", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Brener", "given" : "Sorin J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ellis", "given" : "Stephen G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lincoff", "given" : "A Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Topol", "given" : "Eric J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "JAMA : the journal of the American Medical Association", "id" : "ITEM-1", "issue" : "7", "issued" : { "date-parts" : [ [ "2003" ] ] }, "page" : "898-904", "title" : "Prevalence of conventional risk factors in patients with coronary heart disease.", "type" : "article-journal", "volume" : "290" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "[21]", "plainTextFormattedCitation" : "[21]", "previouslyFormattedCitation" : "[21]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[21] Radiological findings, like cardiovascular calcifications, are a measure of subclinical target organ damage, which can provide a better estimation of CVD risk compared to traditional risk assessment in these individuals.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1161/CIRCIMAGING.111.964528", "ISBN" : "1941-9651\\n1942-0080", "ISSN" : "19419651", "PMID" : "22718782", "abstract" : "BACKGROUND: Current guidelines recommend the use of coronary artery calcium (CAC) scoring for intermediate-risk patients; however, the potential role of CAC among individuals who have no risk factors (RFs) is less established. We sought to examine the relationship between the presence and burden of traditional RFs and CAC for the prediction of all-cause mortality.\\n\\nMETHODS AND RESULTS: The study cohort consisted of 44,052 consecutive asymptomatic individuals free of known coronary heart disease referred for computed tomography for the assessment of CAC. The following RFs were considered: (1) current cigarette smoking, (2) dyslipidemia, (3) diabetes mellitus, (4) hypertension, and (5) family history of coronary heart disease. Patients were followed for a mean of 5.6 \u00b1 2.6 years for the primary end point of all-cause mortality. Among individuals who had no RF, Cox proportional model adjusted for age and sex identified that increasing CAC scores were associated with 3.00- to 13.38-fold higher mortality risk. The lowest survival rate was observed in those with no CAC and no RF, whereas those with CAC \u2265 400 and \u22653 RFs had the highest all-cause fatality rate. Notably, individuals with no RF and CAC \u2265 400 had a substantially higher mortality rate compared with individuals with \u22653 RFs in the absence of CAC (16.89 versus 2.72 per 1000 person-years).\\n\\nCONCLUSIONS: By highlighting that individuals without RFs but elevated CAC have a substantially higher event rates than those who have multiple RFs but no CAC, these findings challenge the exclusive use of traditional risk assessment algorithms for guiding the intensity of primary prevention therapies.", "author" : [ { "dropping-particle" : "", "family" : "Nasir", "given" : "Khurram", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rubin", "given" : "Jonathan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Blaha", "given" : "Michael J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shaw", "given" : "Leslee J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Blankstein", "given" : "Ron", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rivera", "given" : "Juan J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Khan", "given" : "Atif N.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Berman", "given" : "Daniel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Raggi", "given" : "Paolo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Callister", "given" : "Tracy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rumberger", "given" : "John a.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Min", "given" : "James", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jones", "given" : "Steve R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Blumenthal", "given" : "Roger S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Budoff", "given" : "Matthew J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Circulation: Cardiovascular Imaging", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "467-473", "title" : "Interplay of coronary artery calcification and traditional risk factors for the prediction of all-cause mortality in asymptomatic individuals", "type" : "article-journal", "volume" : "5" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "[22]", "plainTextFormattedCitation" : "[22]", "previouslyFormattedCitation" : "[22]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[22] Patients with subclinical target organ damage on CT without modifiable risk factors have increased hazards for CVD morbidity and mortality,ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1161/CIRCIMAGING.111.964528", "ISBN" : "1941-9651\\n1942-0080", "ISSN" : "19419651", "PMID" : "22718782", "abstract" : "BACKGROUND: Current guidelines recommend the use of coronary artery calcium (CAC) scoring for intermediate-risk patients; however, the potential role of CAC among individuals who have no risk factors (RFs) is less established. We sought to examine the relationship between the presence and burden of traditional RFs and CAC for the prediction of all-cause mortality.\\n\\nMETHODS AND RESULTS: The study cohort consisted of 44,052 consecutive asymptomatic individuals free of known coronary heart disease referred for computed tomography for the assessment of CAC. The following RFs were considered: (1) current cigarette smoking, (2) dyslipidemia, (3) diabetes mellitus, (4) hypertension, and (5) family history of coronary heart disease. Patients were followed for a mean of 5.6 \u00b1 2.6 years for the primary end point of all-cause mortality. Among individuals who had no RF, Cox proportional model adjusted for age and sex identified that increasing CAC scores were associated with 3.00- to 13.38-fold higher mortality risk. The lowest survival rate was observed in those with no CAC and no RF, whereas those with CAC \u2265 400 and \u22653 RFs had the highest all-cause fatality rate. Notably, individuals with no RF and CAC \u2265 400 had a substantially higher mortality rate compared with individuals with \u22653 RFs in the absence of CAC (16.89 versus 2.72 per 1000 person-years).\\n\\nCONCLUSIONS: By highlighting that individuals without RFs but elevated CAC have a substantially higher event rates than those who have multiple RFs but no CAC, these findings challenge the exclusive use of traditional risk assessment algorithms for guiding the intensity of primary prevention therapies.", "author" : [ { "dropping-particle" : "", "family" : "Nasir", "given" : "Khurram", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rubin", "given" : "Jonathan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Blaha", "given" : "Michael J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shaw", "given" : "Leslee J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Blankstein", "given" : "Ron", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rivera", "given" : "Juan J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Khan", "given" : "Atif N.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Berman", "given" : "Daniel", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Raggi", "given" : "Paolo", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Callister", "given" : "Tracy", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Rumberger", "given" : "John a.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Min", "given" : "James", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jones", "given" : "Steve R.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Blumenthal", "given" : "Roger S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Budoff", "given" : "Matthew J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Circulation: Cardiovascular Imaging", "id" : "ITEM-1", "issue" : "4", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "467-473", "title" : "Interplay of coronary artery calcification and traditional risk factors for the prediction of all-cause mortality in asymptomatic individuals", "type" : "article-journal", "volume" : "5" }, "uris" : [ "" ] }, { "id" : "ITEM-2", "itemData" : { "DOI" : "10.1148/radiol.13121669", "ISBN" : "1527-1315 (Electronic)\\r0033-8419 (Linking)", "ISSN" : "1527-1315", "PMID" : "23424261", "abstract" : "PURPOSE: To assess the prevalence, extent, severity, and risk of coronary artery disease (CAD) in patients suspected of having CAD but with no medically modifiable risk factors. MATERIALS AND METHODS: Institutional review board approval or waiver of consent was obtained at each center. This study was HIPAA compliant. From an international multicenter cohort study of 27 125 subjects undergoing coronary computed tomographic (CT) angiography from 12 centers, 5262 patients without known CAD and without modifiable risk factors were identified. CAD severity was defined as none (0%), mild (1%-49%), or obstructive (>/= 50%) on a per-patient, per-vessel, and per-segment basis. CAD presence, extent, and severity were related to incidence of major adverse cardiovascular event (MACE) by using Cox proportional hazards models. RESULTS: At a mean follow-up of 2.3 years +/- 1.2 (standard deviation), MACE occurred in 106 patients. CAD was common for nonobstructive (n = 1452, 27%) and obstructive (n = 629, 12%) CAD. In risk-adjusted analysis, per-patient obstructive CAD (hazard ratio [HR], 6.64; 95% confidence interval [CI]: 3.68, 12.00; P </= .001) was related to MACE. MACE was associated with a dose-response relationship to the number of vessels exhibiting obstructive CAD, increasing risk for obstructive one-vessel (HR, 6.11; 95% CI: 3.22, 11.6; P </= .001), two-vessel (HR, 5.86; 95% CI: 2.75, 12.5; P </= .0001), or three-vessel or left main (HR, 11.69; 95% CI: 5.38, 25.4; P </= .001) CAD. The increased hazard for MACE of obstructive disease holds true for symptomatic (HR, 11.9; 95% CI: 4.81, 29.6; P </= .001) and asymptomatic (HR, 6.3; 95% CI: 2.4, 16.7; P </= .001) patients. No CAD at coronary CT angiography was associated with a low annualized MACE rate: 0.31% versus 2.06% with obstructive disease. CONCLUSION: Among individuals suspected of having CAD but without modifiable risk factors, CAD is common, with significantly increased hazards for MACE and mortality.", "author" : [ { "dropping-particle" : "", "family" : "Leipsic", "given" : "J", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Taylor", "given" : "C M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grunau", "given" : "G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Heilbron", "given" : "B G", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mancini", "given" : "G B", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Achenbach", "given" : "S", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { 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"container-title" : "Radiology", "id" : "ITEM-2", "issue" : "3", "issued" : { "date-parts" : [ [ "2013" ] ] }, "page" : "718-726", "title" : "Cardiovascular risk among stable individuals suspected of having coronary artery disease with no modifiable risk factors: results from an international multicenter study of 5262 patients", "type" : "article-journal", "volume" : "267" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "[22,23]", "manualFormatting" : "[29]", "plainTextFormattedCitation" : "[22,23]", "previouslyFormattedCitation" : "[22,23]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[29] but have no indication for prevention therapies in the current guidelines.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.atherosclerosis.2012.05.007", "ISSN" : "00219150", "author" : [ { "dropping-particle" : "", "family" : "Perk", "given" : "Joep", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { 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Experts in this subject have been selected from both organizations to examine subject-specific data and write this guideline in partnership. A formal literature review, weighing the strength of evidence has been performed. When available, information from studies on cost was considered. Computed tomography (CT) acquisition, CAC scoring methodologies and clinical outcomes are the primary basis for the recommendations in this guideline. This guideline is intended to assist healthcare providers in clinical decision making. The recommendations reflect a consensus after a thorough review of the best available current scientific evidence and practice patterns of experts in the field and are intended to improve patient care while acknowledging that situations arise where additional information may be needed to better inform patient care.", "author" : [ { "dropping-particle" : "", "family" : "Hecht", "given" : "Harvey S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Cronin", "given" : "Paul", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Blaha", "given" : "Michael J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Budoff", "given" : "Matthew J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kazerooni", "given" : "Ella A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Narula", "given" : "Jagat", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Yankelevitz", "given" : "David", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Abbara", "given" : "Suhny", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Cardiovascular Computed Tomography", "id" : "ITEM-1", "issue" : "1", "issued" : { "date-parts" : [ [ "2017" ] ] }, "page" : "74-84", "title" : "2016 SCCT/STR guidelines for coronary artery calcium scoring of noncontrast noncardiac chest CT scans: A report of the Society of Cardiovascular Computed Tomography and Society of Thoracic Radiology", "type" : "article-journal", "volume" : "11" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "[24]", "plainTextFormattedCitation" : "[24]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[24] They emphasize the importance of including these imaging markers, measured volumetrically or visually, into the clinical decision making process. Still, randomized trials in which interventions can be based on the imaging biomarker are required to determine whether treatment should be given to patients based on a high radiological risk score and whether this will result in CVD risk reduction. Interestingly, in this study 46% of all patients were in the 5 year high CVD risk (>20%) group. Even though current treatment guidelines are based on 10 year CVD risk one could argue that for this specific patient group 5 year CVD risk would be a sufficient/suitable indicator for treatment. In the Multi-Ethnic Study of Atherosclerosis (MESA), absence of coronary calcifications was related to a low event rate even in patients with many cardiovascular risk factors.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1093/eurheartj/eht508", "ISSN" : "15229645", "PMID" : "24366919", "abstract" : "AIMS: We sought to evaluate the impact of coronary artery calcium (CAC) in individuals at the extremes of risk factor (RF) burden.\\n\\nMETHODS AND RESULTS: 6698 individuals from the Multi-Ethnic Study of Atherosclerosis (MESA) were followed for coronary heart disease (CHD) events over mean 7.1 \u00b1 1 years. Annualized CHD event rates were compared among each RF category (0, 1, 2, or \u22653) after stratification by CAC score (0, 1-100, 101-300, and >300). The following traditional modifiable RFs were considered: cigarette smoking, LDL cholesterol \u22653.4 mmol/L, low HDL cholesterol, hypertension, and diabetes. There were 1067 subjects (16%) with 0 RFs, whereas 1205 (18%) had \u22653 RFs. Among individuals with 0 RFs, 68% had CAC 0, whereas 12 and 5% had CAC >100 and >300, respectively. Among individuals with \u22653 RFs, 35% had CAC 0, whereas 34 and 19% had CAC >100 and >300, respectively. Overall, 339 (5.1%) CHD events occurred. Individuals with 0 RFs and CAC >300 had an event rate 3.5 times higher than individuals with \u22653 RFs and CAC 0 (10.9/1000 vs. 3.1/1000 person-years). Similar results were seen across categories of Framingham risk score.\\n\\nCONCLUSION: Among individuals at the extremes of RF burden, the distribution of CAC is heterogeneous. The presence of a high CAC burden, even among individuals without RFs, is associated with an elevated event rate, whereas the absence of CAC, even among those with many RF, is associated with a low event rate. Coronary artery calcium has the potential to further risk stratify asymptomatic individuals at the extremes of RF burden.", "author" : [ { "dropping-particle" : "", "family" : "Silverman", "given" : "Michael G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Blaha", "given" : "Michael J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Krumholz", "given" : "Harlan M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Budoff", "given" : "Matthew J.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Blankstein", "given" : "Ron", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Sibley", "given" : "Christopher T.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Agatston", "given" : "Arthur", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Blumenthal", "given" : "Roger S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Nasir", "given" : "Khurram", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "European Heart Journal", "id" : "ITEM-1", "issue" : "33", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "2232-2241", "title" : "Impact of coronary artery calcium on coronary heart disease events in individuals at the extremes of traditional risk factor burden: The Multi-Ethnic Study of Atherosclerosis", "type" : "article-journal", "volume" : "35" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "[25]", "plainTextFormattedCitation" : "[25]", "previouslyFormattedCitation" : "[24]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[25] Comparable results were found in this cohort in patients without calcifications in the LAD, descending aorta and mitral valves both in the predicted as well as the observed risk (5,4% and 5,6% respectively). Results like that of the MESA and this study can potentially play a role in reclassifying patients with a high risk based on traditional risk scores but without visible calcifications on chest CT.The number of chest CT examinations for diagnostic and screening purposes are continuing to rise with a study performed in America between 1996 and 2010 demonstrating a 30% increase.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1001/jama.2012.5960", "ISSN" : "1538-3598", "PMID" : "22692172", "abstract" : "CONTEXT: Use of diagnostic imaging has increased significantly within fee-for-service models of care. Little is known about patterns of imaging among members of integrated health care systems.\\n\\nOBJECTIVE: To estimate trends in imaging utilization and associated radiation exposure among members of integrated health care systems.\\n\\nDESIGN, SETTING, AND PARTICIPANTS: Retrospective analysis of electronic records of members of 6 large integrated health systems from different regions of the United States. Review of medical records allowed direct estimation of radiation exposure from selected tests. Between 1 million and 2 million member-patients were included each year from 1996 to 2010.\\n\\nMAIN OUTCOME MEASURE: Advanced diagnostic imaging rates and cumulative annual radiation exposure from medical imaging.\\n\\nRESULTS: During the 15-year study period, enrollees underwent a total of 30.9 million imaging examinations (25.8 million person-years), reflecting 1.18 tests (95% CI, 1.17-1.19) per person per year, of which 35% were for advanced diagnostic imaging (computed tomography [CT], magnetic resonance imaging [MRI], nuclear medicine, and ultrasound). Use of advanced diagnostic imaging increased from 1996 to 2010; CT examinations increased from 52 per 1000 enrollees in 1996 to 149 per 1000 in 2010, 7.8% annual increase (95% CI, 5.8%-9.8%); MRI use increased from 17 to 65 per 1000 enrollees, 10% annual growth (95% CI, 3.3%-16.5%); and ultrasound rates increased from 134 to 230 per 1000 enrollees, 3.9% annual growth (95% CI, 3.0%-4.9%). Although nuclear medicine use decreased from 32 to 21 per 1000 enrollees, 3% annual decline (95% CI, 7.7% decline to 1.3% increase), PET imaging rates increased after 2004 from 0.24 to 3.6 per 1000 enrollees, 57% annual growth. Although imaging use increased within all health systems, the adoption of different modalities for anatomic area assessment varied. Increased use of CT between 1996 and 2010 resulted in increased radiation exposure for enrollees, with a doubling in the mean per capita effective dose (1.2 mSv vs 2.3 mSv) and the proportion of enrollees who received high (>20-50 mSv) exposure (1.2% vs 2.5%) and very high (>50 mSv) annual radiation exposure (0.6% vs 1.4%). By 2010, 6.8% of enrollees who underwent imaging received high annual radiation exposure (>20-50 mSv) and 3.9% received very high annual exposure (>50 mSv).\\n\\nCONCLUSION: Within integrated health care systems, there was a large increase in the rate of adv\u2026", "author" : [ { "dropping-particle" : "", "family" : "Smith-Bindman", "given" : "Rebecca", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Miglioretti", "given" : "Diana L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Johnson", "given" : "Eric", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Lee", "given" : "Choonsik", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Feigelson", "given" : "Heather Spencer", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Flynn", "given" : "Michael", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Greenlee", "given" : "Robert T", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kruger", "given" : "Randell L", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Hornbrook", "given" : "Mark C", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Roblin", "given" : "Douglas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Solberg", "given" : "Leif I", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Vanneman", "given" : "Nicholas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Weinmann", "given" : "Sheila", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Williams", "given" : "Andrew E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "JAMA : the journal of the American Medical Association", "id" : "ITEM-1", "issue" : "22", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "2400-9", "title" : "Use of diagnostic imaging studies and associated radiation exposure for patients enrolled in large integrated health care systems, 1996-2010.", "type" : "article-journal", "volume" : "307" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "[26]", "plainTextFormattedCitation" : "[26]", "previouslyFormattedCitation" : "[25]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[26] In addition to the direct diagnostic impact, one needs to consider potential additional information from a CT scan that may benefit the patient. One such method is to evaluate additional findings, and the radiological risk score is one way in obtaining greater health information from a single CT investigation.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.acra.2015.03.005", "ISSN" : "10766332", "author" : [ { "dropping-particle" : "", "family" : "Dirrichs", "given" : "Timm", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Penzkofer", "given" : "Tobias", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Reinartz", "given" : "Sebastian D.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kraus", "given" : "Thomas", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mahnken", "given" : "Andreas H.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Kuhl", "given" : "Christiane K.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Academic Radiology", "id" : "ITEM-1", "issue" : "7", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "880-889", "publisher" : "Elsevier Ltd", "title" : "Extracoronary Thoracic and Coronary Artery Calcifications on Chest CT for Lung Cancer Screening", "type" : "article-journal", "volume" : "22" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "[27]", "plainTextFormattedCitation" : "[27]", "previouslyFormattedCitation" : "[26]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[27] The effectiveness of the radiological CVD risk score will, however, not be limited by the number of chest CT examinations, but will rather depend on its applicability in routine use. Thus, while the risk score is relatively easy to determine and use, applicability/impact studies are still required to evaluate whether or not it is feasible for use in daily practice. The addition of computer aided detection of cardiovascular calcifications could potentially improve applicability and facilitate future use of the risk score.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1148/radiol.12110810", "ISBN" : "1527-1315 (Electronic)\\n0033-8419 (Linking)", "ISSN" : "0033-8419", "PMID" : "22919038", "abstract" : "Arteriosclerotic cardiovascular disease is the leading cause of death in the United States, with coronary artery disease (CAD) accounting for half of all cardiovascular disease deaths. Current risk assessment approaches for coronary heart disease, such as the Framingham risk score, substantially misclassify intermediate- to long-term risk for the occurrence of CAD in asymptomatic individuals. A screening modality such as a simple non-contrast-enhanced, or noncontrast, computed tomographic (CT) detection of coronary artery calcium (CAC) improves the ability to accurately predict risk in vulnerable groups and adds information above and beyond global risk assessment as shown by the recent Multi-Ethnic Study of Atherosclerosis. In addition, absence of CAC is associated with a very low risk of future CAD and as a result can be used to identify a group among which further testing and pharmacotherapies can be avoided. The Expert Consensus Document by the American College of Cardiology Foundation and the American Heart Association now recommends screening individuals at intermediate risk but did not find enough evidence to recommend CAC testing and further stratification of those in the low- or high-risk categories for CAD. In addition, emerging guidelines have suggested that absence of CAC can act as a \"gatekeeper\" for further testing among low- and intermediate-risk patients presenting with chest pain. This review of the current literature outlines the role of CAC testing in both asymptomatic and symptomatic individuals.", "author" : [ { "dropping-particle" : "", "family" : "Nasir", "given" : "K.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Clouse", "given" : "M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Radiology", "id" : "ITEM-1", "issue" : "3", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "637-649", "title" : "Role of Nonenhanced Multidetector CT Coronary Artery Calcium Testing in Asymptomatic and Symptomatic Individuals", "type" : "article", "volume" : "264" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "[28]", "plainTextFormattedCitation" : "[28]", "previouslyFormattedCitation" : "[27]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[28]The strengths and limitations of the application of cardiovascular risk prediction based on incidental findings in Chest CT examinations as well as the development and validation of the risk score have been discussed previously.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISSN" : "0033-8419", "abstract" : "Purpose: To predict cardiovascular disease (CVD) in a clinical care population by using prevalent subclinical ancillary aortic findings detected on chest computed tomographic (CT) images. Materials and Methods: The study was approved by the medical ethics committee of the primary participating facility and the institutional review boards of all other participating centers. From a total of 6975 patients who underwent diagnostic contrast material-enhanced chest CT for noncardiovascular indications, a representative sample population of 817 patients plus 347 patients who experienced a cardiovascular event during a mean follow-up period of 17 months were assigned visual scores for ancillary aortic abnormalities - on a scale of 0-8 for calcifications, a scale of 0-4 for plaques, a scale of 0-4 for irregularities, and a scale of 0-1 for elongation. Four Cox proportional hazard models incorporating different sum scores for the aortic abnormalities plus age, sex, and chest CT indication were compared for discrimination and calibration. The prediction model that performed best was chosen and externally validated. Results: Each aortic abnormality was highly predictive, and all models performed well(c index range, 0.70-0.72; goodness-of-fit P value range, .45-.76). The prediction model incorporating the sum score for aortic calcifications was chosen owing to its good performance(c index, 0.72; goodness-of-fit P =.47) and its applicability to nonenhanced CT scanning. Validation of this model in an external data set also revealed good performance(c index, 0.71; goodness-of-fit P =.25; sensitivity, 46%; specificity, 76%). Conclusion: A derived prediction model incorporating ancillary aortic findings detected on routine diagnostic CT images complements established risk scores and may help to identify patients at high risk for CVD. Timely application of preventative measures may ultimately reduce the number or severity of CVD events. \u00a9 RSNA, 2010.", "author" : [ { "dropping-particle" : "", "family" : "M.J.A.", "given" : "Gondrie", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "W.P.T.M.", "given" : "Mali", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "P.C.", "given" : "Jacobs", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "A.L.", "given" : "Oen", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Y.", "given" : "Van Der Graaf", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Radiology", "id" : "ITEM-1", "issue" : "2", "issued" : { "date-parts" : [ [ "2010" ] ] }, "page" : "549-559", "publisher-place" : "M. J. A. Gondrie, Department of Radiology, University Medical Center Utrecht, 3508 GA Utrecht, Netherlands", "title" : "Cardiovascular disease: Prediction with ancillary aortic findings on chest CT scans in routine practice", "type" : "article-journal", "volume" : "257" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "[29]", "plainTextFormattedCitation" : "[29]", "previouslyFormattedCitation" : "[28]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[29]In this study, we found that the risk score yielded good predictive accuracy in a Scottish population with a higher CVD burden compared to the population it was developed in.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "ISBN" : "9781899088126", "author" : [ { "dropping-particle" : "", "family" : "British", "given" : "Heart Foundation Health Promotion Research Group", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Department of Public Health", "given" : "University of Oxford", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2012" ] ] }, "title" : "Coronary heart disease statistics A compendium of health statistics 2012 edition", "type" : "article-journal" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "[4]", "plainTextFormattedCitation" : "[4]", "previouslyFormattedCitation" : "[4]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[4] In particular, the score achieved a c-statistic of 0.71 and properly distinguished between low, intermediate, and high risk patients. Our findings are consistent with the previous external validation study and suggest that the radiological risk score could contribute towards cardiovascular disease prevention in Scotland by identifying high risk patients using incidental findings on chest CT. Furthermore, because performance of the score was not affected by the heterogeneity between the Dutch and Scottish population, it seems that the incorporation of CT imaging results may help to improve the generalizability of risk scores predicting the incidence CVD in individual patients. We used the recently published ‘TRIPOD method for developing and validating prognostic multivariable models’ as a guideline for writing this paper.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1136/bmj.g7594", "ISSN" : "1756-1833", "author" : [ { "dropping-particle" : "", "family" : "Collins", "given" : "G. S.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Reitsma", "given" : "J. B.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Altman", "given" : "D. G.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Moons", "given" : "K. G. M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Bmj", "id" : "ITEM-1", "issue" : "jan07 4", "issued" : { "date-parts" : [ [ "2015" ] ] }, "page" : "g7594-g7594", "title" : "Transparent reporting of a multivariable prediction model for individual prognosis or diagnosis (TRIPOD): the TRIPOD statement", "type" : "article-journal", "volume" : "350" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "[30]", "plainTextFormattedCitation" : "[30]", "previouslyFormattedCitation" : "[29]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[30] Still, some limitations of our study need to be considered.The radiological data was scored by a single researcher after extensive training on chest CT scans. While this could potentially introduce bias we feel that the previously assessed reproducibility of the scoreADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1097/RCT.0b013e3181bbcff6", "ISSN" : "0363-8715", "abstract" : "OBJECTIVE:To investigate the interobserver and intraobserver agreements for the semiquantitative assessment of markers of subclinical cardiovascular disease as identified by routine care, diagnostic computed tomography (CT) of the chest, to improve the quality of reporting of these incidental findings.\\n\\nMETHODS:Two observers independently evaluated 109 consecutive chest CT scans in routine care, clinical patients from one tertiary referral center. All nongated, contrast-enhanced scans were acquired on a 16-slice CT scanner. Images were scored for the presence of aortic wall abnormalities and calcifications of the coronary artery, the heart valves, the thoracic aorta, and the proximal supraaortic arteries. Furthermore, the presence of left ventricular scarring and elongation of the aorta were recorded. All markers were scored on a semiquantitative scale. Interobserver and intraobserver agreements are presented as weighted kappa and intraclass correlation coefficients.\\n\\nRESULTS:Interobserver and intraobserver agreements for individual markers were good to excellent, with weighted kappa coefficients of 0.54 to 0.89 for interobserver agreement and 0.55 to 0.96 for intraobserver agreement.\\n\\nCONCLUSIONS:Semiquantitative assessment of subclinical cardiovascular disease markers in routine care, diagnostic chest CT scans is possible with good to excellent interobserver and intraobserver agreements. Use of these definitions in clinical practice will enable a more standardized assessment and reporting of incidental findings in diagnostic chest CT.", "author" : [ { "dropping-particle" : "", "family" : "Jacobs", "given" : "Peter C.A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Prokop", "given" : "Mathias", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Oen", "given" : "Ayke L.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Graaf", "given" : "Yolanda", "non-dropping-particle" : "van der", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grobbee", "given" : "Diederick E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Mali", "given" : "Willem P.Th.M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Journal of Computer Assisted Tomography", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2010" ] ] }, "page" : "279-284", "title" : "Semiquantitative Assessment of Cardiovascular Disease Markers in Multislice Computed Tomography of the Chest", "type" : "article", "volume" : "34" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "[16]", "plainTextFormattedCitation" : "[16]", "previouslyFormattedCitation" : "[16]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[16] and the results of the training scans are substantial enough to allow for a single observer. The risk score was validated in a generally Caucasian population. For further implementation validation in other geographical areas and ethnicities would be desirable, as there is a significant difference in coronary artery calcification based on large population studies, such as the MESA.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1161/01.CIR.0000157730.94423.4B", "ISBN" : "1524-4539 (Electronic)\r0009-7322 (Linking)", "ISSN" : "00097322", "PMID" : "15769774", "abstract" : "BACKGROUND: There is substantial evidence that coronary calcification, a marker for the presence and quantity of coronary atherosclerosis, is higher in US whites than blacks; however, there have been no large population-based studies comparing coronary calcification among US ethnic groups. METHODS AND RESULTS: Using computed tomography, we measured coronary calcification in 6814 white, black, Hispanic, and Chinese men and women aged 45 to 84 years with no clinical cardiovascular disease who participated in the Multi-Ethnic Study of Atherosclerosis (MESA). The prevalence of coronary calcification (Agatston score >0) in these 4 ethnic groups was 70.4%, 52.1%, 56.5%, and 59.2%, respectively, in men (P<0.001) and 44.6%, 36.5%, 34.9%, and 41.9%, respectively, (P<0.001) in women. After adjustment for age, education, lipids, body mass index, smoking, diabetes, hypertension, treatment for hypercholesterolemia, gender, and scanning center, compared with whites, the relative risks for having coronary calcification were 0.78 (95% CI 0.74 to 0.82) in blacks, 0.85 (95% CI 0.79 to 0.91) in Hispanics, and 0.92 (95% CI 0.85 to 0.99) in Chinese. After similar adjustments, the amount of coronary calcification among those with an Agatston score >0 was greatest among whites, followed by Chinese (77% that of whites; 95% CI 62% to 96%), Hispanics (74%; 95% CI 61% to 90%), and blacks (69%; 95% CI 59% to 80%). CONCLUSIONS: We observed ethnic differences in the presence and quantity of coronary calcification that were not explained by coronary risk factors. Identification of the mechanism underlying these differences would further our understanding of the pathophysiology of coronary calcification and its clinical significance. Data on the predictive value of coronary calcium in different ethnic groups are needed.", "author" : [ { "dropping-particle" : "", "family" : "Bild", "given" : "Diane E.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Detrano", "given" : "Robert", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Peterson", "given" : "Do", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Guerci", "given" : "Alan", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Liu", "given" : "Kiang", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Shahar", "given" : "Eyal", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ouyang", "given" : "Pamela", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jackson", "given" : "Sharon", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Saad", "given" : "Mohammed F.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "Circulation", "id" : "ITEM-1", "issue" : "10", "issued" : { "date-parts" : [ [ "2005" ] ] }, "page" : "1313-1320", "title" : "Ethnic differences in coronary calcification: The Multi-Ethnic Study of Atherosclerosis (MESA)", "type" : "paper-conference", "volume" : "111" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "[31]", "plainTextFormattedCitation" : "[31]", "previouslyFormattedCitation" : "[30]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[31] The average age of participants in both the original Dutch and the Scottish validation study was relatively high. Because of this it could be argued that much of the cardiovascular risk is explained solely by age. To test for this possibility, the radiological risk score was compared in the derivation study to a score with only gender and age which showed that the risk score had a substantially better performance.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1148/radiol.14132211", "ISSN" : "1527-1315", "PMID" : "24865309", "abstract" : "Purpose To investigate the contribution of incidental findings at chest computed tomography (CT) in the detection of subjects at high risk for cardiovascular disease (CVD) by deriving and validating a CT-based prediction rule. Materials and Methods This retrospective study was approved by the ethical review board of the primary participating facility, and informed consent was waived. The derivation cohort comprised 10 410 patients who underwent diagnostic chest CT for noncardiovascular indications. During a mean follow-up of 3.7 years (maximum, 7.0 years), 1148 CVD events (cases) were identified. By using a case-cohort approach, CT scans from the cases and from an approximately 10% random sample of the baseline cohort (n = 1366) were graded visually for several cardiovascular findings. Multivariable Cox proportional hazards analysis with backward elimination technique was used to derive the best-fitting parsimonious prediction model. External validation (discrimination, calibration, and risk stratification) was performed in a separate validation cohort (n = 1653). Results The final model included patient age and sex, CT indication, left anterior descending coronary artery calcifications, mitral valve calcifications, descending aorta calcifications, and cardiac diameter. The model demonstrated good discriminative value, with a C statistic of 0.71 (95% confidence interval: 0.68, 0.74) and a good overall calibration, as assessed in the validation cohort. This imaging-based model allows accurate stratification of individuals into clinically relevant risk categories. Conclusion Structured reporting of incidental CT findings can mediate accurate stratification of individuals into clinically relevant risk categories and subsequently allow those at higher risk of future CVD events to be distinguished. \u00a9 RSNA, 2014 Online supplemental material is available for this article.", "author" : [ { "dropping-particle" : "", "family" : "Jairam", "given" : "Pushpa M", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gondrie", "given" : "Martijn J A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Grobbee", "given" : "Diederick E", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Th M Mali", "given" : "Willem P", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Jacobs", "given" : "Peter C A", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Graaf", "given" : "Yolanda", "non-dropping-particle" : "van der", "parse-names" : false, "suffix" : "" } ], "container-title" : "Radiology", "id" : "ITEM-1", "issued" : { "date-parts" : [ [ "2014" ] ] }, "page" : "132211", "title" : "Incidental Imaging Findings from Routine Chest CT Used to Identify Subjects at High Risk of Future Cardiovascular Events.", "type" : "article-journal" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "[12]", "plainTextFormattedCitation" : "[12]", "previouslyFormattedCitation" : "[12]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[12]No comparison with traditional risk scores was made. The radiological risk score differs from traditional cardiovascular risk score’s like the Framingham risk score in that is based solely on data readily and freely available to the radiologist (i.e. patient characteristics, indication and imaging measurements). Therefor no other patient data was obtained and no direct comparison to traditional CVD risk scores could be made. We were able to compare the discriminate ability of the risk scores and found that the c-statistic for the radiological risk score was comparable to that of the Framingham and SCORE risk scores. ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1136/bmj.e3318", "ISBN" : "1756-1833", "ISSN" : "1756-1833", "PMID" : "22628003", "abstract" : "OBJECTIVE: To evaluate the evidence on comparisons of established cardiovascular risk prediction models and to collect comparative information on their relative prognostic performance. DESIGN: Systematic review of comparative predictive model studies. DATA SOURCES: Medline and screening of citations and references. STUDY SELECTION: Studies examining the relative prognostic performance of at least two major risk models for cardiovascular disease in general populations. DATA EXTRACTION: Information on study design, assessed risk models, and outcomes. We examined the relative performance of the models (discrimination, calibration, and reclassification) and the potential for outcome selection and optimism biases favouring newly introduced models and models developed by the authors. RESULTS: 20 articles including 56 pairwise comparisons of eight models (two variants of the Framingham risk score, the assessing cardiovascular risk to Scottish Intercollegiate Guidelines Network to assign preventative treatment (ASSIGN) score, systematic coronary risk evaluation (SCORE) score, Prospective Cardiovascular Munster (PROCAM) score, QRESEARCH cardiovascular risk (QRISK1 and QRISK2) algorithms, Reynolds risk score) were eligible. Only 10 of 56 comparisons exceeded a 5% relative difference based on the area under the receiver operating characteristic curve. Use of other discrimination, calibration, and reclassification statistics was less consistent. In 32 comparisons, an outcome was used that had been used in the original development of only one of the compared models, and in 25 of these comparisons (78%) the outcome-congruent model had a better area under the receiver operating characteristic curve. Moreover, authors always reported better area under the receiver operating characteristic curves for models that they themselves developed (in five articles on newly introduced models and in three articles on subsequent evaluations). CONCLUSIONS: Several risk prediction models for cardiovascular disease are available and their head to head comparisons would benefit from standardised reporting and formal, consistent statistical comparisons. Outcome selection and optimism biases apparently affect this literature.", "author" : [ { "dropping-particle" : "", "family" : "Siontis", "given" : "G. C. M.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Tzoulaki", "given" : "I.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Siontis", "given" : "K. C.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Ioannidis", "given" : "J. P. A.", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" } ], "container-title" : "BMJ", "id" : "ITEM-1", "issue" : "may24 1", "issued" : { "date-parts" : [ [ "2012" ] ] }, "page" : "e3318-e3318", "title" : "Comparisons of established risk prediction models for cardiovascular disease: systematic review", "type" : "article", "volume" : "344" }, "uris" : [ "" ] } ], "mendeley" : { "formattedCitation" : "[7]", "plainTextFormattedCitation" : "[7]", "previouslyFormattedCitation" : "[7]" }, "properties" : { "noteIndex" : 0 }, "schema" : "" }[7] For the radiological risk score, calcifications are scored using categories of severity that are used for both thick and thin slice scans. Because of this, extent of calcification can be somewhat over or underestimated depending on the slice thickness. Furthermore, to increase applicability, calcifications are scored visually instead of volumetrically. The predictive properties of volumetric coronary calcium scoring are well known and a comparison between the radiological risk scores and volumetric coronary calcium scoring is something we want to look into in future studies. [8]Finally, the calibration plot for 5 year CVD incidence showed mild overestimation from 20 to 40% CVD risk and underestimation of patients with higher than 50% risk. Overestimation in the 20% predicted CVD range could cause some misclassification from the intermediate (10-<20%) risk group to the high risk (>20%) group. The tendency for underestimating patients with the highest risk was already visible in the original validation study. However, the relevance of underestimating patients with observed risks of 50-70% is debatable. It is unlikely this would influence clinical decision making, as these patients will be provided with maximal supportive care according to most guidelines.ADDIN CSL_CITATION { "citationItems" : [ { "id" : "ITEM-1", "itemData" : { "DOI" : "10.1016/j.atherosclerosis.2012.05.007", "ISSN" : "00219150", "author" : [ { "dropping-particle" : "", "family" : "Perk", "given" : "Joep", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Backer", "given" : "Guy", "non-dropping-particle" : "De", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Gohlke", "given" : "Helmut", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Graham", "given" : "Ian", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Reiner", "given" : "\u017deljko", "non-dropping-particle" : "", "parse-names" : false, "suffix" : "" }, { "dropping-particle" : "", "family" : "Verschuren", "given" : "W.M. 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The score adequately identified patients at low, intermediate, and high risk of cardiovascular disease in 5 year CVD incidence in individual patients. Application of the radiological risk score can help identify patients with high cardiovascular risks using readily available data from chest CT examinations. Source of fundingThis research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.Conflicts of interestThe authors have no potential conflicts of interest related with this article.ReferencesADDIN Mendeley Bibliography CSL_BIBLIOGRAPHY [1]NRS Scotland, Under 75s age-standardised death rates for all causes and certain selected causes , Scotland , 1994 to 2014, (2015) Available at: . .[2]Information Services Division, Publication Report Heart Disease Statistics Update, (2014).[3]I.S. Division, Publication Report Stroke Statistics Update, (2014).[4]H.F.H.P.R.G. British, U. of O. 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Moons, Transparent reporting of a multivariable prediction model for individual prognosis or diagnosis (TRIPOD): the TRIPOD statement, Bmj. 350 (2015) g7594–g7594. doi:10.1136/bmj.g7594.[31]D.E. Bild, R. Detrano, D. Peterson, A. Guerci, K. Liu, E. Shahar, P. Ouyang, S. Jackson, M.F. Saad, Ethnic differences in coronary calcification: The Multi-Ethnic Study of Atherosclerosis (MESA), in: Circulation, 2005: pp. 1313–1320. doi:10.1161/01.CIR.0000157730.94423.4B.TablesTable 1 Semi-quantitative grading score of the cardiovascular CT findings included in the CT based CVD risk score0 = Absent1 = Mild2 = Moderate3 =SevereLAD coronary artery calcificationNumber and size of calcificationsnone1-2 focal limited to ≤2 slices>2 focal or 1 extending >2 slicesFully calcified coronary artery extending multiple slicesDescending aorta calcificationsNumber and size of calcificationsnone≤ 3 focal4-5 focal or 1 extending ≥3 slices>5 focal or >1 extending ≥3 slicesMitral valve calcificationsNumber of affected valve leafletsnone1 leaflet2 leafletsLAD = left anterior descendingTable 2 Baseline clinical characteristics and CT characteristics for all cases and patients in the subcohort of both the Scottish cohort and the original cohortCasesSubcohort Subcohort PROVIDI Total patients3845001366Male gender, n (%)201 (52)256 (51)792 (58)Age, years 71 (41-96)67 (40-94)62 (40-96)CT-indication, n (%) Lung disease163 (42)187 (38)505 (37) Haematological malignancy25 (7)32 (6)150(11) Mediastinal abnormality18 (5)29 (6)150 (11) Suspicion pulmonary malignancy128 (33)159 (32)314 (23) Suspicion pulmonary embolism1 (0)1 (0)82 (6) Other indication49 (13)92 (18)164 (12)LAD* coronary artery calcifications, n (%) Mild72 (19)93 (19)410 (30) Moderate121 (32)93 (19)260 (19) Severe97 (25)91 (19)137 (10)Descending aorta calcifications, n (%) Mild102 (27)145 (30)382 (28) Moderate59 (15)79 (16)191 (14) Severe185 (48)151 (30)96 (7)Mitral valve calcification, n (%) 1 leaflet56 (15)36 (7)96 (7) 2 leaflets19 (5)11 (2.2)27 (2)Cardiac diameter, mm127 (71-192)124 (82-188)125 (77-185)Follow up time, years 2.1 (0-6.3)4.3 (0-6.4)3.7 (0-7)* LAD = left anterior descending, Table 3 CVD event rate (per 1000 person-years) by gender and ageWomenMenTotal person yearsNo of casesEvent rate (95% CI)Total person yearsNo of casesEvent rate (95% CI)Total464318339.4 (33.9-45.6)439520145.7 (39.6-52.5)Age, years 40-507051014.2 (6.8-26.1)612711.4 (4.6-23.6) 50-609912323.2 (14.7-34.8)10562826.4 (17.6-38.3) 60-7013193829.2 (20.4-39.5)13226649.9 (38.6-63.5) 70-8010995953.6 (40.9-69.3)10076464 (48.9-81.2) 80-9653053100 (74.9-130.8)3983690 (63.3-125.2)Table 4 Predicted vs Observed 5 year cardiovascular riskRisk Group5y Risk: Radiological risk scoreLow risk group (<10% risk) No. of patients n (%)535 (25) Observed Kaplan-Meier risk (%)8.6%Intermediate risk group (10-20% risk) No. of patients n (%)621 (29) Observed Kaplan-Meier risk (%)14.9%High risk group (>20% risk) No. of patients n (%)968 (46) Observed Kaplan-Meier risk (%)31.7%Figure LegendsFig. 1 Flowchart of study design. CVD = Cardiovascular Disease.Fig. 2 Examples of CT imaging findings included in the radiological risk score. (A) coronary calcification in left anterior descending artery, (B) cardiac diameter measurement, (C) calcification on the mitral valve, (D) calcification in the descending aorta.Fig. 3 Survival curves of the 5 year predicted cardiovascular risk categories low (<10%), intermediate (10-20%) and high (>20%) from baseline until a maximum of 6.4 years follow up.Fig. 4 Calibration plot: Predicted probability versus actual probability of surviving 5 years in deciles (dots) and overall trend (line). A reference line is added to the plot indicating perfect calibration (dashed line). ................
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