CONTACTS
SUBJECTS
Default Null Subject Account for Blank Record
0403 -
0403 - ..
0404 - Summary/Objective
0405 -
040501 - Follow up ref SDS 11 0000.
040502 -
040503 -
040504 -
040505 -
040506 -
040508 - ..
0406 -
0407 -
0408 - Progress
0409 -
040901 - Received letter from Doctor Stewart saying...
040902 -
040903 - 1. Subject: RE: [EXTERNAL] CCTA Calcium Score and Labs
040904 - Date: 2015-11-19 18:44
040908 - ..
040909 - 2. Hi Mr. Welch,
040910 -
040911 - Attached are some articles on Statins and coronary artery
040912 - calcium that you may find interesting.
040914 - ..
040915 - This letter implements Doctor Stewart's work plan to submit medical
040916 - articles, as she discussed during telecon on 151104 1114, ref SDS 12
040917 - O66N, restating prior planning during a meeting on 150925 0336,
040918 - ref SDS 4 EB5F, which followed up letter to Doctor Stewart that
040919 - reviewed planning for ordering CCTA to test response to treatment for
040920 - regression of atherosclerosis, shown in the record on 151029 2257.
040921 - ref SDS 11 K17I
040922 -
040923 - [On 151120 2312 letter responds thanking Doctor Stewart for
040924 - submitting articles on statin side effects, and on CCTA to
040925 - measure response to treatment. ref SDS 13 4X5I
040927 - ..
040928 - [On 151203 0953 brief meeting with Doctor Stewart - thanked
040929 - her for articles she sent on 151124, presenting side
040930 - effects taking Atorvastatin 10 mg lowers CoQ10 required to
040931 - metabolize food into energy, ref SDS 14 4X5I; further
040932 - advised that careful review of articles submitted on
040933 - 151119, provide important guidance on CCTA protocols,
040934 - ref SDS 0 4X5I, for collaborating with Radiology to clarify
040935 - vague findings reported for CCTA test on 151019.
040936 - ref SDS 8 JW8O
040938 - ..
040939 - Letter from Doctor Stewart continues...
040940 -
040941 - 3. Lygia Stewart, MD
040942 - Chief General Surgery, SF VAMC
040943 - Professor of Clinical Surgery, UCSF
040944 - Chair VA NSO General Surgery Advisory Board
040945 -
040946 -
040948 - ..
040949 - 4. Attachments...
040950 -
040951 - 1. Coronary artery plaque composition & coronary artery stenosis severity - Results from the prospective multicenter ACCURACY trial_Min.2011.pdf
040952 -
040953 - F:\05\00003\SM\CC\AGMJ\20151119-184400\Coronary-artery-plaque-composition-coronary-artery-stenosis-severity-2011.pdf
040954 -
040955 - Reviewed below. ref SDS 0 TE4K
040957 - ..
040958 - 2. Do Statins Cause Diabetes_Goldstein.2013.pdf
040959 -
040960 - F:\05\00003\SM\CC\AGMJ\20151119-184400\Do-Statins-Cause-Diabetes_Goldstein.2013.pdf
040962 - ..
040963 - Review pending...
040965 - ..
040966 - 3. Expert Consensus Coronary Artery Calcium Scoring by CT Global Cardiovascular Risk Assessment ACCF_AHA_2007.pdf
040967 -
040968 - F:\05\00003\SM\CC\AGMJ\20151119-184400\Expert-Consensus-Coronary-Artery-Calcium-Scoring-Risk Assessment ACCF_AHA_2007.pdf
040970 - ..
040971 - Reviewed below. ref SDS 0 EJ8I
040973 - ..
040974 - 4. Long-Term Prognosis Associated With Coronary Calcification_Budoff.2007.pdf
040975 -
040976 - F:\05\00003\SM\CC\AGMJ\20151119-184400\Long-Term-Prognosis-Associated-With-Coronary-Calcification_Budoff-2007.pdf
040978 - ..
040979 - 5. Statins stimulate atherosclerosis and heart failure Pharmacological Mechanisms_Okuyama.2015.pdf
040980 -
040981 - F:\05\00003\SM\CC\AGMJ\20151119-184400\Statins-stimulate-atherosclerosis-and-heart-failure_Okuyama-2015.pdf
040983 - ..
040984 - 6. Statins use and coronary artery plaque composition - Multicenter CONFIRM Registry_Nakasato.2012.pdf
040985 -
040986 - F:\05\00003\SM\CC\AGMJ\20151119-184400\Statins-use-and-coronary-artery-plaque-composition_Nakasato-2012.pdf
040987 -
040988 -
040989 -
040990 -
040991 -
040992 -
0410 -
SUBJECTS
Default Null Subject Account for Blank Record
0503 -
050401 - ..
050402 - ACCURACY Trial CCTA Assess CVD Stenosis Severity
050403 - Coronary artery plaque composition & coronary artery stenosis severity - Results from the prospective multicenter ACCURACY trial_Min
050404 -
050405 -
050406 - F:\05\00003\SM\CC\AGMJ\20151119-184400\Coronary-artery-plaque-composition-coronary-artery-stenosis-severity-2011.pdf
050407 -
050408 - 1. Atherosclerosis 219(2011)573?578
050409 -
050410 - Contents listsavailableat ScienceDirect
050412 - ..
050413 - Atherosclerosis
050414 -
050415 - journal homepage: www.elsevier.com/locate/atherosclerosis
050417 - ..
050418 - Relationship of coronary artery plaque composition to coronary
050419 - artery stenosis severity: Results from the prospective
050420 - multicenter ACCURACY trial
050422 - ..
050423 - James K. Mina,b,*, MichaelEdwardesc, FayY.Lina, TroyLabountya,
050424 - JonathanW.Weinsafta,b,
050425 - Jin-Ho Choia,d, AugustinDelagoe, LesleeJ.Shawf,
050426 - DanielS.Bermang, MatthewJ.Budoffh
050428 - ..
050429 - a. Department of Medicine, Greenberg Division of Cardiology, Weill
050430 - Cornell Medical College and the New York Presbyterian Hospital,
050431 - 520E., 70th Street, Starr Pavilion, K-415, New York, NY 10021,
050432 - United States
050434 - ..
050435 - b. Department of Radiology, Weill Cornell Medical College and
050436 - the New York Presbyterian Hospital, New York, NY, United
050437 - States
050439 - ..
050440 - c. Everest Clinical Research Services, Ontario, Canada
050442 - ..
050443 - d. Sungkyunkwan University School of Medicine, Samsung Medical
050444 - Center, Seoul, Republic of Korea
050446 - ..
050447 - e. Capital Cardiology Associates, Albany, NY, United States
050449 - ..
050450 - f. Department of Medicine, Emory University School,United
050451 - States
050453 - ..
050454 - g. Cedars Sinai Medical Center, Los Angeles, CA, United States
050456 - ..
050457 - h. Los Angeles Biomedical Research Institute at Harbor-UCLA,
050458 - Torrance, CA, United States
050459 -
050461 - ..
050462 - 2. Article Info
050463 -
050464 - Article Histor:
050465 - Received 13 February 2011
050466 - Received in revised form 29 April 2011
050467 - Accepted 24 May 2011
050468 - Available online 31 May 2011
050470 - ..
050471 - 3. Keywords:
050472 -
050473 - Computed tomography
050474 - Coronary artery disease
050475 - Angiography
050476 - Plaque composition
050478 - ..
050479 - 4. Abstract
050480 -
050481 - Objectives: The purpose of this study was to determine the
050482 - relationship of coronary artery plaque composition as detected
050483 - by coronary computed tomographic angiography (CCTA) to luminal
050484 - diameter stenosis severity quantified by quantitative coronary
050485 - angiography (QCA) individuals without known coronary artery
050486 - disease (CAD) presenting with stable chest pain syndrome.
050488 - ..
050489 - Who performs "Quantitative coronary angiography" (QCA) that can assess
050490 - severity of stenosis identified with CCTA?
050492 - ..
050493 - Article "Coronary artery plaque composition..." continues...
050494 -
050495 - Background: While CCTA has been previously evaluated for its
050496 - ability to detect and exclude coronary artery stenosis, CCTA
050497 - also permits assessment of other important plaque
050498 - characteristics, including plaque composition. Identification
050499 - of the relationship between plaque composition by CCTA and
050500 - plaque severity by invasive angiography may provide valuable
050501 - insight into the pathophysiology of coronary artery plaque.
050503 - ..
050504 - Methods: Patients enrolled in the ACCURACY trial, a 16-site
050505 - multicenter study of patients with stable chest pain syndrome
050506 - but without known CAD undergoing both CCTA and invasive
050507 - coronary angiography(ICA), comprised the study population.
050508 - CCTAs were scored on a per-segment basis for plaque composition
050509 - and graded as non-calcified (>70% non-calcified), calcified
050510 - (>70% calcified) or?mixed? (30?70% non-calcified or calcified)
050511 - by concordance of ? 2 of 3 readers. CCTAs were also scored on
050512 - a per-patient basis, and individuals were categorized as
050513 - possessing primarily non-calcified plaques, primarily calcified
050514 - plaques or primarily mixed plaques. Quantitative coronary
050515 - angiography (QCA) was performed in all patients, used as the
050516 - reference standard for stenosis severity, and interpreted
050517 - blinded to patient characteristics and CCTA results.
050519 - ..
050520 - Results: 230 subjects comprised the study population (59.1%
050521 - male, 57 +/- 10 years). QCA was performed in all subjects
050522 - following CCTA (mean inter-testinterval 5.9 +/- 4.3 days), and
050523 - demonstrated obstructive CAD in 24.8% and 13.9% at the 50% and
050524 - 70% stenosis severity threshold, respectively. On a
050525 - per-segment based analysis, obstruction by QCA at both the 50%
050526 - and 70% stenoses thresholds was more often for mixed
050527 - composition plaques by CCTA (69.1% and 67.9%, respectively), as
050528 - compared to non-calcified plaques (24.7% and 28.6%,
050529 - respectively) and calcified plaques (6.1% and 3.6%,
050530 - respectively) [p < 0.01 for comparisons]. On a per-patient
050531 - basis, patients with mixed plaque or mixtures of plaque types
050532 - more often exhibited obstructive coronary stenosis by QCA at
050533 - the 50% level (39/96; 40.6%) compared to those with primarily
050534 - non-calcified (12/43; 27.9%) or primarily calcified (4/29;
050535 - 13.8%) plaques [p = 0.02].
050537 - ..
050538 - Conclusions: In this multicenter trial of chest pain patients
050539 - without known CAD, QCA-confirmed obstructive coronary stenosis
050540 - was associated with mixed plaque composition by CCTA at both
050541 - the per-segment and the per-patient levels. Coronary artery
050542 - segments exhibiting calcified plaque were rarely associated
050543 - with obstructive coronary stenosis.
050545 - ..
050546 - 2011 Published by Elsevier Ireland Ltd
050548 - ..
050549 - Corresponding author.Tel.:+12127462437;
050550 - fax: +12127468561.
050551 - E-mail address: jkm2001@med.cornell.edu (J.K. Min).
050552 - 0021-9150/$ ?see front matter©2011 Published by Elsevier Ireland Ltd.
050553 - doi:10.1016/j.atherosclerosis.2011.05.032
050555 - ..
050556 - 1. Introduction
050557 -
050558 - Coronary computed tomographic angiography (CCTA) has
050559 - emerged as accurate non-invasive method for the detection
050560 - and exclusion of obstructive coronary artery disease (CAD)
050561 - [1?3]. Further, CCTA permits evaluation of numerous other
050562 - coronary artery plaque characteristics, including plaque
050563 - compositions, which are generally graded as non-calcified,
050564 - calcified and mixed [4]. Classification of plaques by CCTA
050565 - based upon composition has important clinical implications,
050566 - with increasing numbers of mixed plaques possessing thin
050567 - cap fibroatheroma, associated with myocardial ischemia and
050568 - predictive of adverse CAD prognosis [5?8]. Todate,
050569 - however, the relationship of plaque composition by CCTA to
050570 - luminal diameter stenosis severity remains unknown.
050572 - ..
050573 - This section seems to indicate standard of care for radiology practice
050574 - commonly applies CCTA for both "detection" and "exclusion" of harmful
050575 - plaques that constitute obstructive coronary artery disease (CAD).
050576 -
050577 - [...below on 151119 2141 another article also reports CCTA
050578 - is appropriately applied for finding absence of
050579 - atheriosclerosis plaques. ref SDS 0 WP43
050581 - ..
050582 - [On 160104 0855 meeting disclosed that UCSF radiology
050583 - standard of care failing to expressly state in a
050584 - radiology report existence of plaque, stenosis, or
050585 - harmful blockage or condition of any kind establishes
050586 - that none were identified in the active circulatory
050587 - system visible in CCTA scan file. ref SDS 16 X64K
050589 - ..
050590 - Example using radiology to find "exclusion" occurred when Doctor Tseng
050591 - and her cardiothoracic surgery team (Neil, KC, Paula), performed CABG
050592 - x4 on 091022. ref SDS 2 LO3G After surgical opening was closed, an
050593 - inventory discovered needle count was one short. The doctor ordered
050594 - an xray study to verify harmful needle was not inside the patient. In
050595 - addition to reporting what was found, the Radiology department
050596 - affirmatively reported a finding that anything even suspicious of a
050597 - needle was not found (see report in the record, shown in the record on
050598 - 100928 0706. ref SDS 3 0W4O
050600 - ..
050601 - [On 160108 2106 letter to Doctor Jha says in part
050602 - "Authorities say CCTA is an accurate method for both
050603 - detection and exclusion of coronary plaques. This case
050604 - seems appropriate for expressly stating absence of plaques,
050605 - rather than leave to mere conjecture, surmise or conclusion
050606 - from silence alone. For example, Doctor Simpson, who
050607 - ordered the CCTA test, called me on 151021, while I was out
050608 - hiking. He advised the test report seems vague to him."
050609 - ref SDS 17 TE51
050611 - ..
050612 - Welch applies CCTA for the "exclusion" function; however, CCTA is not
050613 - commonly used for patients who have been treated with CABG, because
050614 - this treatment establishes that the patient has at one time suffered
050615 - severe build up of plaque that obstructed blood flow over 70%, the
050616 - definition of "patent." For example, this ACCURACY study excluded
050617 - patients with "known CAD and presenting with stable chest pain, per
050618 - above. ref SDS 0 VP6G
050620 - ..
050621 - Welch suffers no chest pain, but rather applies CCTA for testing
050622 - response to treatment that raised HDL 30 to HDL 70, since CABG +4 6
050623 - years ago on 091022, Has the patient "recovered" from CAD by
050624 - regressing all plaques to 0. This application conflicts with
050625 - cardiology practice, because raising HDL is difficult, and so has not
050626 - been studied because there are not enough patients to justify the cost
050627 - of doing a study, discussed with Karen in Cardiology Department at VA
050628 - Medical Center in San Francisco on 151218 0937, ref SDS 15 LU9I, and
050629 - citing meeting with Doctor Wisneski on 151005 1102. ref SDS 5 GL7G
050631 - ..
050632 - Article "Coronary artery plaque composition..." continues...
050633 -
050634 - The aim of this prospective multi-center study was to
050635 - determine the relationship of coronary artery plaque
050636 - composition by CCTA to QCA-confirmed luminal diameter
050637 - stenosis severity in chest pain subjects without known CAD.
050638 - We evaluated these relationships on a per-segment and
050639 - per-patient basis.
050641 - ..
050642 - 2. Methods
050643 -
050644 - 1. Patients
050645 -
050646 - The Assessment by coronary computed tomographic
050647 - angiography of individuals undergoing invasive coronary
050648 - angiography (ACCURACY) study was designed to
050649 - prospectively evaluate adult subjects with chest pain
050650 - who were being clinically referred for non-emergent
050651 - invasive coronary angiography (ICA) [1]. Potential
050652 - study subjects were screened and enrolled by a site
050653 - research coordinator if they met all of the inclusion
050654 - and none of the exclusion criteria. Study subjects
050655 - were asked to undergo a research CCTA, as well as data
050656 - and blood collection as specified by a pre-defined
050657 - research protocol.
050659 - ..
050660 - Individuals were eligible for participation in the
050661 - ACCURACY trial if they were - 18 years of age,
050662 - experienced typical or atypical chest pain, and were
050663 - being referred for non-emergent invasive coronary
050664 - angiography. Individuals were excluded from
050665 - participation in the ACCURACY trial for the following
050666 - reasons: known allergy to iodinated contrast; baseline
050667 - renal insufficiency [creatinine ? 1.7 mg/dl]; irregular
050668 - cardiac rhythm; resting heart rate > 100 beats per min;
050669 - resting systolic blood pressure < 100 mmHg; contra
050670 - indication to beta blocker, calcium channel blocker,or
050671 - nitro- glycerin; women of child-bearing age; known
050672 - history of CAD (prior myocardial infarction,
050673 - percutaneous transluminal coronary angio- plasty or
050674 - intracoronary stent, or coronary artery bypass
050675 - surgery). Importantly, patients were not excluded for
050676 - elevated coronary artery calcium score, body mass index
050677 - or non-tachycardic higher heart rates.
050679 - ..
050680 - See comment above on correlation of these CCTA study results with
050681 - Welch patient history of CAD based on CABG +4 on 091022, and ensuing
050682 - treatment that raised HDL 30 to 70, which regressed CAD symptoms.
050683 - ref SDS 0 TZ3M
050685 - ..
050686 - Article "Coronary artery plaque composition..." continues...
050687 -
050688 - The study was performed at 16 centers in the United
050689 - States (Appendix A). Protocols associated with patient
050690 - enrollment, safety analysis, image acquisition, image
050691 - interpretation and statistical analysis were developed
050692 - by a steering committee.
050694 - ..
050695 - 2. CCTA image acquisition
050696 -
050697 - Study subjects under went CCTA prior to conventional
050698 - catheter-based angiography. All CCTA scans were
050699 - performed with a 64-detector row computed tomography
050700 - scanner (Lightspeed VCT, GE Healthcare, Milwaukee, WI).
050701 - All patients were in normal sinus rhythm at the time of
050702 - the CCTA scan. Individuals presenting with baseline
050703 - heart rates >65 beats per minute (bpm) were
050704 - administered intravenous metoprolol at 5 mg increments
050705 - to a total possible dose of 25 mg in order to achieve a
050706 - resting heart rate <65 bpm. All patients eligible for
050707 - CCTA were scanned, irrespective of whether the goal <65
050708 - bpm heart rate was achieved.
050710 - ..
050711 - How does
050712 -
050714 - ..
050715 - Following a scout radiograph of the chest, a timing
050716 - bolus was performed to detect time to optimal contrast
050717 - opacification in the axial image at a level immediately
050718 - superior to the ostium of the left main artery. During
050719 - CCTA acquisition, 80 cm3 iodinated contrast (Visipaque,
050720 - GE Healthcare, Milwaukee, WI) was injected utilizing a
050721 - triple-phase contrast protocol at 5 ml/s: 60cm3
050722 - iodixanol, followed by 40 cm3 of a 50:50 mixture of
050723 - iodixanol and saline, followed by a 50 cm3 saline
050724 - flush. Retrospective ECG-gated helical
050725 - contrast-enhanced CCTA was performed, with scan
050726 - initiation 20 mm above the level of the left main
050727 - artery to 20 mm below the inferior myocardial apex.
050728 - The scan parameters were 64 mm x 0.625 mm collimation,
050729 - tube voltage 120 mV, effective milliampere 350?780 mA.
050730 - In all cases, automodulation of milliampere was
050731 - performed. Similarly, additional radiation reduction
050732 - algorithms using electrocardiography (ECG) modulation
050733 - were employed. After scan completion, multiphasic
050734 - reconstruction of CCTA scans was performed at 10%
050735 - intervals. Inaddition, additional phases were
050736 - reconstructed at 45%, 65%, and 75%, for a total of 13
050737 - phases. The radiation dose for CCTAs wase stimated to
050738 - be 10?20 mSv.
050740 - ..
050741 - 3. CCTA interpretation
050742 -
050743 - CCTA images were interpreted separately by three read-
050744 - ers blinded to all patient characteristics and ICA
050745 - results. All CCTA images were evaluated on a 3D image
050746 - analysis workstation (GE Advantage Workstation 4.3,GE
050747 - Healthcare, Milwaukee, WI). CCTA readers were
050748 - permitted to utilize any or all available
050749 - post-processing image reconstruction algorithms,
050750 - including two-dimensional (2D) axial,or
050751 - three-dimensional (3D) maximal intensity projection
050752 - (MIP), multiplanar reformat (MPR), cross-sectional
050753 - analysis, or volume rendered technique (VRT).
050755 - ..
050756 - How do "interpretation" protocols for this ACCURACY study of CCTA
050757 - compare with protocols for interpreting CCTA on 151019, that yielded
050758 - report findings? ref SDS 8 8Q6I
050760 - ..
050761 - CCTA interpretatio protocols may indicate reliability of findings.
050763 - ..
050764 - VA Radiology equipment for CCTA on 151119, may be newer and so yield
050765 - more accurate results with fewer readers than ACCURACY study performed
050766 - prior to publication in 2011, per above, ref SDS 0 VT5I, and
050767 - consisting of 64-detector row computed tomography scanner (Lightspeed
050768 - VCT, GE Healthcare, Milwaukee, WI), per above. ref SDS 0 Q26H
050770 - ..
050771 - Article "Coronary artery plaque composition..." continues...
050772 -
050773 - Coronary arteries were uniformly scored using a
050774 - standard 15- segment AHA coronary artery
050775 - classification. An overall assessment of image quality
050776 - and coronary supply dominance was performed on the
050777 - subject level. For each coronary segment,readers
050778 - assessed whether coronary segments were evaluable. A
050779 - semi-quantitative scale was employed by CCTA readers to
050780 - grade coronary artery plaque composition. Plaque
050781 - composition in each coronary segment was classified as
050782 - non-calcified, calcified, or mixed, as we have
050783 - previously described [6]. As the Hounsfield unit (HU)
050784 - densities of fibrous, lipoid, or thrombotic plaque are
050785 - known to overlap, these plaque types were aggregated
050786 - into a ?non-calcified? group,which comprised any plaque
050787 - greater than 70% by estimated semi-quantitative
050788 - volumetric determination which exhibited HU densities
050789 - below the observed luminal contrast density (typically
050790 - at least 130HU). Calcified plaque was defined as any
050791 - plaque greater than 70% by estimated volume which
050792 - exhibited a HU density above the observed luminal
050793 - contrast density. ?Mixed?plaque was designated as
050794 - plaque which exhibited both calcified (<70% overall
050795 - volume) and non-calcified (<70% overall volume)
050796 - plaques. The coronary artery plaque composition by
050797 - segment was based upon a consensus of ?2 of 3 blinded
050798 - CCTA readers who graded plaque within a coronary artery
050799 - segment as non-calcified, calcified or mixed. All
050800 - assessment of coronary plaque composition was based on
050801 - contrast angiography images only; non-contrast images
050802 - were not considered in the evaluation.
050804 - ..
050805 - 4. ICA image acquisition and interpretation
050806 -
050807 - Selective ICA was performed by standard transfemoral
050808 - arterial catheterization. A minimum of eight projects
050809 - were obtained (minimum of 5 views for the left coronary
050810 - artery system, and minimum of 3 views for the right
050811 - coronary artery system). All ICA images interpreted by
050812 - an independent ICA reader blinded to all patient
050813 - characteristics and CCTA results. ICAs were
050814 - quantitatively evaluated for coronary artery stenosis
050815 - with QCA software (QCA Plus, Sanders Data Systems, Palo
050816 - Alto,CA), and classified as 0%, 1-24%, 25-49%, 50-69%
050817 - and > 70% stenosis. Coronary artery segments by QCA
050818 - were also judged as having significant stenosis at two
050819 - levels, that is,if > 50% or < 70% luminal narrowing of
050820 - the coronary artery diameter was present.
050822 - ..
050823 - 5. Data analysis
050824 -
050825 - For segment-based analyses, only segments for which
050826 - CCTA agreement between at least 2 of 3 CCTA readers was
050827 - achieved were included. Segments were judged as having
050828 - no plaque, non-calcified plaque, calcified plaque or
050829 - mixed plaque. For patient-based analyses, individuals
050830 - were classified into one of three categories: (1)
050831 - individuals with primarily non-calcified plaque, (2)
050832 - individuals with primarily calcified plaque, and (3)
050833 - individuals with either solely mixed plaque or with
050834 - combinations of non-calcified, calcified and mixed
050835 - plaque. Patient plaque categories are the majority
050836 - segment-based classification of the patient?s segments
050837 - with plaque. If neither calcified nor non-calcified
050838 - segments were the most frequent by at least 50% of the
050839 - frequency of other plaque types, the patient
050840 - classification was classified as mixed. Only patients
050841 - for whom there was agreement between at least 2 of 3
050842 - CCTA readers with respect to disease evaluation
050843 - (plaque, no plaque, unevaluable) were included for
050844 - patient-based analyses.
050846 - ..
050847 - 6. Stastical analysis
050848 -
050849 - Categorical variables are presented as frequencies and
050850 - percentages, and continuous variables as mean +/-
050851 - standard deviations(SD).
050853 - ..
050854 - Patient-based CCTA variables were compared to QCA
050855 - variables with Pearson?s chi-squared tests.
050856 - Segment-based analyses corrected for within-patient
050857 - correlation through modeling logistic regression with
050858 - generalized estimating equations (GEE), and p-values
050859 - are based on contrast results with such models.
050860 - Two-tailed p < 0.05 was considered statistically
050861 - significant. All statistical analyses were performed
050862 - using SAS® Proprietary Software, Release 9.1 (SAS
050863 - Institute Inc., Cary, NC).
050865 - ..
050866 - 3. Results
050867 -
050868 - 1. Patient characteristics
050869 -
050870 - 230 subjects met study eligibility criteria, including
050871 - completion of both CCTA and ICA (mean interval 5.9 +/-
050872 - 4.3 days).The mean Agatston score was 284 +/- 538
050873 - (Table 1).
050875 - ..
050876 - Table 1
050877 - Clinical characteristics
050879 - ..
050880 - Age (years............................... 57 +/- 10
050881 - Male gender.............................. 136 (59%)
050882 - Race
050883 - Caucasian.............................. 202 (87.8%)
050884 - African American....................... 13 (5.7%)
050885 - Hispanic............................... 8 (3.5%)
050886 - Other.................................. 7 (3.1%)
050887 - Height (cm).............................. 172 +/- 11 (140-198)
050888 - Weight (kg).............................. 93 +/- 21 (49-174)
050889 - BMI (kg/m2)a............................. 31.4 +/- 6.2 (16.8-50.5)
050890 - Heart rate (meats/min)c.................. 60 +/- 12
050891 - Creatinine (gm/dl)....................... 1.0 +/- 0.2
050892 - Agatston coronary artery calcium score... 284 +/- 538
050893 - Diabetes................................. 55 (23.9%)
050894 - Hypertension............................. 154 (67.0%)
050895 - Hyperlipidemia........................... 157 (68.3%)
050896 - Family history of CADb................... 169 (73.5%)
050897 - Smoker................................... 128 (55.7%)
050898 - Obesity.................................. 90 (39.1%)
050899 -
050900 - a - body mass indes
050901 - b - Coronary artery disease
050902 - c - Maximum at the time of CCTA
050904 - ..
050905 - 2. Segment-based evaluation
050906 -
050907 - Amongst 2954 coronary segments identified, consensus
050908 - was achieved for at least 2 of 3 readers in 98.8%
050909 - (2918/2954). Amongst CCTA-identified plaques, mixed
050910 - plaques were the most com- mon (43.9%; 319/727),
050911 - followed by calcified (28.3%; 206/727) and
050912 - non-calcified (27.8%; 202/727) plaques. There was a
050913 - significant relationship between plaque composition and
050914 - stenosis severity (Table 2). At greater levels of
050915 - stenosis severity, mixed plaques were most commonand
050916 - calcified plaques were less common, while at milder
050917 - levels of stenosis severity, CCTA-identified plaques by
050918 - com- position were more evenly distributed (p < 0.001).
050919 -
050920 - ------------------------------
050921 - Table 2
050922 - Segment-based analysis of plaque composition to stenosi sseverity
050924 - ..
050925 - Plaque composition
050926 - by CCTA Stenosis severity by QCA
050927 - 0%=2021 1-24%n=308 25-49%n=211 50-69%n=55 70-100%n=30 p-Value
050928 -
050930 - ..
050931 - No Plaque 1711 (84.7% 147 (47.7%) 36 (17.1%) 2 (3.6%) 2 (6.7%)
050932 - Non-calcified 93 (4.6%) 43 (14.0%) 46 (21.8%) 12 (21.8%) 8 (26.7%)
050933 - Mixed 113 (56% 65 (21.1%) 85 (40.3%) 37 (67.3%) 19 (63.3%)
050934 - Calcified 104 (5.1%) 53 (17.2%) 44 (20.9%) 4 (7.3%) 1 (3.3%)
050935 - <verall x2,p<0.001
050936 - ------------------------------
050937 -
050939 - ..
050940 - In segments with ? 50% stenosis, calcified,
050941 - non-calcified, and mixed plaques are observed in 5
050942 - (6.1%), 10 (24.7%), and 56 (69.1%) segments
050943 - respectively (p < 0.001); while at the ? 70% stenosis
050944 - threshold, these plaques are observed in 1 (3.6%), 8
050945 - (28.6%), and 19 (67.9%) of segments, respectively (p =
050946 - 0.038). This demonstrates that within individual
050947 - plaque composition categories, plaques with mixed
050948 - plaque composition exhibited high rates of obstructive
050949 - coro- nary artery stenosis by QCA, followed by
050950 - non-calcified plaques and then calcified plaques,which
050951 - rarely demonstrated to have obstruc- tive coronary
050952 - artery stenosis (Fig. 1).
050954 - ..
050955 - ------------------------------
050956 - Figure 1
050958 - ..
050959 - There are 4 images that seem like CT scan files, as
050960 - performed on 151019. ref SDS 8 ZL5G These are identified
050961 - as "A" and "B". These 2 figure elements each have "A" and
050962 - "B" sub-image components. There is an impression these
050963 - sub-images compare CCTA scans with IVUS images, similar to
050964 - invasive catheritization angiography, performed on 091021
050965 - 0716. ref SDS 1 7L43
050967 - ..
050968 - Text explanation of Figure 1 says...
050970 - ..
050971 - (A) CCTA (a) demonstrating mixed plaque in the mid-portion
050972 - of the left anterior descending artery with a high-grade
050973 - stenosis (arrow). On invasive angiography (b), there is an
050974 - occlusion of the artery (arrowhead) just distal to origin
050975 - of the first diagonal artery (arrow). (B) CCTA (a) and
050976 - invasive angiography (b) images demon- strating mixed
050977 - plaque in the mid-portion of the left anterior descending
050978 - artery, associated with a ? 70% stenosis.
050979 -
050980 -
050982 - ..
050983 - 3. Patient-based evaluation
050984 -
050985 - In patient-based evaluation, consensus was achieved by
050986 - at least 2 of 3 readers for 98.7% subjects (227/230).
050987 - Individuals exhibiting mixed plaques or combinations of
050988 - non-calcified and calcified plaques were more common
050989 - 41.7% (96/230) than individuals exhibiting primarily
050990 - non-calcified plaques 18.7% (43/230) or primarily
050991 - calcified plaques 12.6% (29/230) (p = 0.020). When
050992 - sub-categorized as individuals possessing 1?3, 4?5 or >
050993 - 5 coronary segments exhibiting mixed plaques,
050994 - non-calcified plaques or calcified plaques,
050995 - respectively, the prevalence of obstructive coronary
050996 - stenosis as measured by QCA increased in individuals
050997 - possessing increasing numbers of coronary segments
050998 - exhibiting non-calcified and mixed plaques but not
050999 - calcified plaques (Table 3).
051001 - ..
051002 - ------------------------------
051003 - Table 3
051004 - Patient-based analysis of plaque composition to stenosi sseverity
051006 - ..
051007 - Segments plaque Calcified Non-calcified Mixed p-Value
051008 - 1-3 0% (0/15) 14.3% (4/28) 3.5% (1/29) 0.135
051009 - 4-5 80% (4/5) 16.7% (1/6) 24.0% (6/25) 0.033
051010 - >5 0% (0/9) 77.8% (7/9) 76.2% (32/42) <0.0001
051011 - Overall x2 p=0.049
051013 - ..
051014 - % =(number occluded or obstructive)/(number in the
051015 - category). Plaque categories are the most frequent
051016 - characteristic of the segments with plaque. If neither
051017 - calcified nor non-calcified segments are the most
051018 - frequent by at least 50% of the frequency of other
051019 - plaque types, the patient classification was classified
051020 - as mixed.
051021 -
051022 - ------------------------------
051024 - ..
051025 - Amongst the 55 patients with any QCA-confirmed
051026 - obstructive coronary stenosis at the ? 50% threshold,
051027 - 85 plaques were identified as obstructive by QCA.
051028 - Based on the most frequent plaque characteristic of
051029 - individuals with plaque, the 55 patients with
051030 - obstructive plaque and 113 patients with nonobstructive
051031 - plaque were observed to have majority non-calcified
051032 - plaque in 12 (27.9%) and 31 (72.1%), mixed plaque in 39
051033 - (40.6%) and 57 (59.4%), and calcified plaque in 4
051034 - (13.8%) and 25 (86.2%) of individuals, respectively
051035 - (overall chi square p = 0.019). Individuals with mixed
051036 - plaques or combinations of plaque types (57.1% of
051037 - patients with plaque) were confirmed by QCA as having ?
051038 - 50% stenosis more often than individuals possessing
051039 - primarily calcified plaques (17.3%) (p = 0.008).
051041 - ..
051042 - 4. Discussion
051043 -
051044 - These results of the ACCURACY trial represent the first
051045 - prospec- tive multicenter data relating plaque composition
051046 - by CCTA to QCA-confirmed measures of luminal diameter
051047 - stenosis severity. The current data demonstrate a strong
051048 - association between the presence of mixed plaque
051049 - composition to obstructive coronary artery stenosis at a
051050 - per-segment and per-patient level. In addition, these data
051051 - establish a negative association between calcified plaque
051052 - composition and stenosis severity, particularly on a
051053 - per-segment basis.
051055 - ..
051056 - Prior studies have examined the ability of CCTA to
051057 - discriminate presence and absence of coronary plaques, and
051058 - plaques comprised of different compositions. In a recent
051059 - study by Leber et al.,64- detector row CCTA enabled
051060 - exclusion of 94% of coronary artery segments without
051061 - plaque, as compared to intravascular ultrasound [9].
051062 - Employing IVUS as a gold standard, correct categorization
051063 - of non-calcified, mixed and calcified plaques by CCTA
051064 - occurred 83%, 94% and 95% of the time, respectively.
051065 -
051066 - [...on 151119 0941 above another article makes same
051067 - point using CCTA to evaluate the exclusion of harmful
051068 - coronary plaques, ref SDS 0 7N6J, and citing example
051069 - using radiology to exclude harmful conditions.
051070 - ref SDS 0 ZV5G
051072 - ..
051073 - [On 160104 0855 meeting disclosed that UCSF radiology
051074 - standard of care failing to expressly state in a
051075 - radiology report existence of plaque, stenosis, or
051076 - harmful blockage or condition of any kind establishes
051077 - that none were identified in the active circulatory
051078 - system visible in CCTA scan file. ref SDS 16 X64K
051080 - ..
051081 - [On 160108 2106 letter to Doctor Jha says in part
051082 - "Authorities say CCTA is an accurate method for both
051083 - detection and exclusion of coronary plaques. This case
051084 - seems appropriate for expressly stating absence of
051085 - plaques, rather than leave to mere conjecture, surmise
051086 - or conclusion from silence alone. For example, Doctor
051087 - Simpson, who ordered the CCTA test, called me on 151021,
051088 - while I was out hiking. He advised the test report
051089 - seems vague to him." ref SDS 17 TE51
051091 - ..
051092 - Recently, Motoyama and colleagues have demonstrated the
051093 - prognostic significance of plaque composition
051094 - characterization, specifically examiningn on-calcified
051095 - plaques with attenuation densities < 30 Hounsfield units.
051096 - In 1059 patients under going CCTA, these low attenuation
051097 - plaques that manifested with positive remodeling
051098 - demonstrated a significant association with the development
051099 - of incident acute coronary syndromes (ACS), while the
051100 - absence of such characteristics was associated with low
051101 - rates of ACS [10]. In a prior analysis, these same
051102 - investigators implicated these plaque types as the
051103 - ?culprit? plaques at the time of ACS presentation [11]. In
051104 - accordance with these findings, Matsumoto et al.
051105 - established the prognostic significance of non-calcified
051106 - plaques, demonstrating that plaques with Hounsfield unit
051107 - densities < 68 were associated with higher rates of major
051108 - adverse cardiac events in 810 patients at a 2.9 year
051109 - follow-up [12]. Nevertheless,a robust prognostic evidence
051110 - base exists for calcified plaque, particularly as detected
051111 - by coronary artery calcium scoring (CACS) [13]. Increasing
051112 - levels of calcified plaques are associated with greater
051113 - extent and severity of myocardial ischemia,
051114 - angiographically severe CAD and adverse prognosis [14].
051115 -
051116 - [On 151203 0953 brief meeting with Doctor Stewart -
051117 - thanked her for articles she sent on 151124, presenting
051118 - side effects taking Atorvastatin 10 mg lowers CoQ10
051119 - required to metabolize food into energy, ref SDS 14
051120 - 4X5I; further advised that careful review of articles
051121 - submitted on 151119, provide important guidance on CCTA
051122 - protocols, ref SDS 0 0R5J, for collaborating with
051123 - Radiology to clarify vague findings reported for CCTA
051124 - test on 151019. ref SDS 8 JW8O
051126 - ..
051127 - These seemingly discordant findings may be unified by
051128 - accounting for plaques of mixed compositions that contain
051129 - both calcified and non-calcified plaques. In a consecutive
051130 - cohort of 163 consecutive patients undergoing both CCTA and
051131 - myocardial perfusion single photon emission computed
051132 - tomography (MPS), we recently reported the relationship of
051133 - plaque composition to extent and severity of myocardial
051134 - ischemia [6]. While increasing numbers of coronary
051135 - segments possessing mixed plaque were associated with
051136 - myocardial ischemia, increasing numbers of coronary
051137 - segments exhibitingnon-calcified or calcified plaques were
051138 - not. In this respect,increasing levels of mixed plaque may
051139 - be associated with increasing CACS,although the
051140 - non-calcified portions of these plaques may be more
051141 - pathophysiologically and prognostically important. Our
051142 - findings are in agreement with those from a recent study by
051143 - van Werkhoven et al. of 517 individuals undergoing CCTA in
051144 - which mixed and non-calcified plaques?but not calcified
051145 - plaques?were associated with the development of MACE in a
051146 - 1.8-year follow-up [8].
051148 - ..
051149 - The reasons for differences between mixed plaques and
051150 - calcified plaques for the development of myocardial
051151 - ischemia or incident MACE are as yet unknown. Numerous
051152 - possible explanations exist, including differences in the
051153 - relative ages of plaques, the inflammatory nature of
051154 - plaques, and the shear stress associated with plaque and
051155 - their ensuant vulnerability to rupture. Some have
051156 - postulated that purely calcified plaques may represent
051157 - ?older healed? plaques, as compared to calcified components
051158 - within a mixed plaque which have been proposed as
051159 - intermediary in age between non-calcified and calcified
051160 - plaques; however,this assertion, to date, has not been
051161 - proven [15].
051163 - ..
051164 - Indeed, incontrast to this premise, if plaque progression
051165 - occurs linearly to stenosis severity, the present data
051166 - would suggest that mild luminal stenoses from purportedly
051167 - ?younger? plaques are fairly evenly distributed with
051168 - respect to plaque composition. Based upon the current
051169 - data, one feasible explanation of the importance of the
051170 - composition within plaquess imply relates to the stenosis
051171 - severity. As mixed plaque composition is associated with a
051172 - greater likelihood of obstructive stenosis severity,it is
051173 - possible that the previously noted relationship of mixed
051174 - plaque composition to myocardial ischemia and adverse CAD
051175 - prognosis simply represents identification of plaques that
051176 - are more obstructive in severity. Future studies carefully
051177 - examining the relationship of plaque composition to
051178 - stenosis severity in large well-characterized cohorts are
051179 - necessary to determine the independent role of plaque
051180 - composition and prognosis.
051182 - ..
051183 - This study is not without limitations. We elected to
051184 - examine plaque composition by CCTA but confirmed stenosis
051185 - severity by QCA. This comparison was intentionally
051186 - performed because of the well-documented reduced diagnostic
051187 - specificity of CCTA in the presence of increasing levels of
051188 - coronary artery calcium, and the need for a robust gold
051189 - standard of stenosis severity in the present study.
051190 - Interestingly, given the negative relationship between
051191 - calcified plaque and obstructive coronary artery stenosis,
051192 - the results of the present study may enhance future
051193 - diagnostic interpretation of CCTA when visualizing
051194 - calcified plaque. On a per-plaque basis, calcified plaques
051195 - rarely manifest as high-grade obstructive coronary artery
051196 - stenosis. A second limitation relates to our simple
051197 - categorization of plaques as non-calcified, calcified and
051198 - mixed. Non-calcified plaques represent a spectrum of
051199 - plaque types that include fibrous, lipoid and fibrolipoid
051200 - plaques. Nevertheless, as the Hounsfield unit densities of
051201 - these plaque subtypes demonstrate significant overlap, we
051202 - elected to combine them into a single category. Whether
051203 - subtypes of non-calcified plaque exhibit differing
051204 - relationships to stenosis severity remains unknown.
051205 - Further,it has been well documented that plaques which
051206 - appear purely calcified by CCTA may indeed possess small
051207 - amounts of non-calcified components. Future studies
051208 - examining plaque compositions employing novel CT technology
051209 - such as spectral imaging by dual energy image acquisition
051210 - may be useful to augment discrimination of these plaques
051211 - subtypes, but this technology has not yet been robustly
051212 - proven and was not available at the time of study
051213 - performance. While plaque composition in the present study
051214 - was determined by qualitative comparison to luminal
051215 - contrast attenuation as has previously been performed [9],
051216 - such future technologies may permit true quantitative
051217 - assessment of plaque composition. Also, invasive
051218 - assessment of plaque composition by IVUS or near-field
051219 - infrared spectroscopy imaging was not available in the
051220 - present study. However, the ability of CCTA to assess
051221 - plaque composition has been previously reported, with
051222 - generally favorable diagnostic performance [9]. Instead,
051223 - this study was performed to evaluate the relationship of
051224 - plaque composition by CCTA to stenosis severity by QCA as
051225 - the most relevant gold standard for assessing stenosis
051226 - severity. As such, we performed QCA on all individuals in
051227 - the present study. Further,we report the CAD risk factors
051228 - for the study cohort. These risk factors represent those
051229 - that were present at the time of study performance, and
051230 - provide little insight into the duration and/or severity of
051231 - the specific risk factors. Future studies examining the
051232 - length and severity of CAD risk factors should be performed
051233 - to provide further insight into plaque pathophysiology.
051234 - Finally,4 patients were considered by CCTA to have no
051235 - discernible plaque and yet to have moderate to high grade
051236 - stenosis by QCA. There are numerous explanations for this
051237 - discordance, including false positive QCA or false negative
051238 - CCTA. As QCA was considered the reference standard in the
051239 - present study-and thus, by definition,could not manifest
051240 - false positives-reasons for false negative CCTA include
051241 - motion artifact, coronary segment misalignment, and
051242 - inadequate discrimination of plaque from surrounding
051243 - adventitial structures. Future studies examining newer
051244 - scanners with improved temporal and/or spatial resolution
051245 - may mitigate these discordances.
051247 - ..
051248 - 5. Conclusion
051249 -
051250 - In this multicenter trial of chest pain patients without
051251 - known CAD, QCA-confirmed obstructive coronary stenosis was
051252 - associated with presence of mixed plaque composition by
051253 - CCTA at both the per-segment and the per-patient levels.
051254 - Coronary artery segments exhibiting calcified plaque were
051255 - rarely associated with obstructive coronary stenosis.
051256 -
051257 -
051258 -
051259 -
051260 -
051261 -
051262 -
0513 -
SUBJECTS
Default Null Subject Account for Blank Record
0603 -
060401 - ..
060402 - Calcium Scoring CCTA
060403 - Expert Consensus Coronary Artery Calcium Scoring by CT Global Cardiovascular Risk Assessment ACCF_AHA_2007.pdf
060404 -
060405 -
060406 - F:\05\00003\SM\CC\AGMJ\20151119-184400\Expert-Consensus-Coronary-Artery-Calcium-Scoring-Risk Assessment ACCF_AHA_2007.pdf
060408 - ..
060409 - 1. Journal of the American College of Cardiology
060410 - 2007 by the American College of Cardiology Foundation
060411 - Published by Elsevier Inc
060413 - ..
060414 - Vol 49 No 3, 2007
060415 - ISSN 0735-1097/07/$32.00
060416 - doi:10.1016/j.jacc.2006.10.001
060418 - ..
060419 - JACC Vol. 49, No. 3, 2007
060420 - January 23, 2007:378?402
060422 - ..
060423 - ACCF/AHA EXPERT CONCENSUS DOCUMENT
060425 - ..
060426 - ACCF/AHA 2007 Clinical Expert Consensus Document
060427 - on Coronary Artery Calcium Scoring By Computed
060428 - Tomography in Global Cardiovascular Risk Assessment
060429 - and in Evaluation of Patients With Chest Pain
060430 - ---------------------------------------------
060431 - A Report of the American College of Cardiology Foundation
060432 - Clinical Expert Consensus Task Force (ACCF/AHA Writing
060433 - Committee to Update the 2000 Expert Consensus Document on
060434 - Electron Beam Computed Tomography)
060436 - ..
060437 - Developed in Collaboration With the Society of Atherosclerosis
060438 - Imaging and Prevention and the Society of Cardiovascular
060439 - Computed Tomography
060441 - ..
060442 - Writing Committee Members...
060443 -
060444 - Philip Greenland, MD, FACC, FAHA, Chair
060445 - Robert O. Bonow, MD, FACC, FAHA*
060446 - Bruce H. Brundage, MD, MACC, FAHA
060447 - Matthew J. Budoff, MD, FACC, FAHA?
060448 - Mark J. Eisenberg, MD, MPH, FACC
060449 - Scott M. Grundy, MD, PHD
060450 - Michael S. Lauer, MD, FACC, FAHA
060451 - Wendy S. Post, MD, MS, FACC
060452 - Paolo Raggi, MD, FACC?
060453 - Rita F. Redberg, MD, MSC, FACC, FAHA*
060454 - George P. Rodgers, MD, FACC
060455 - Leslee J. Shaw, PHD
060456 - Allen J. Taylor, MD, FACC, FAHA
060457 - William S. Weintraub, MD, FACC
060458 -
060459 - *American Heart Association Representative;
060460 - ?Society of Cardiovascular Computed Tomography Representative;
060461 - ?Society of Atherosclerosis Imaging and Prevention Representative
060462 -
060464 - ..
060465 - Task Force Members
060466 -
060467 - Robert A. Harrington, MD, FACC, Chair
060468 - Jonathan Abrams, MD, FACC§
060469 - Jeffrey L. Anderson, MD, FACC
060470 - Eric R. Bates, MD, FACC
060471 - Mark J. Eisenberg, MD, MPH, FACC
060472 - Cindy L. Grines, MD, FACC
060473 - Mark A. Hlatky, MD, FACC
060474 - Robert C. Lichtenberg, MD, FACC
060475 - Jonathan R. Lindner, MD, FACC
060476 - Gerald M. Pohost, MD, FACC, FAHA
060477 - Richard S. Schofield, MD, FACC
060478 - Samuel J. Shubrooks, JR, MD, FACC
060479 - James H. Stein, MD, FACC
060480 - Cynthia M. Tracy, MD, FACC
060481 - Robert A. Vogel, MD, FACC¶
060482 - Deborah J. Wesley, RN, BSN
060483 -
060484 - §Former Task Force Member during the writing effort;
060485 - ¶Immediate Past Chair
060487 - ..
060488 - This document was approved by the American College of
060489 - Cardiology Board of Trustees in September 2006 and by the
060490 - American Heart Association Science Advisory and Coordinating
060491 - Committee in November 2006.
060493 - ..
060494 - When citing this document, the American College of Cardiology
060495 - and the American Heart Association would appreciate the
060496 - following citation format: Greenland P, Bonow RO, Brundage BH,
060497 - Budoff MJ, Eisenberg MJ, Grundy SM, Lauer MS, Post WS, Raggi P,
060498 - Redberg RF, Rodgers GP, Shaw LJ, Taylor AJ, Weintraub WS.
060499 - ACCF/AHA 2007 clinical expert consensus document on coronary
060500 - artery calcium scoring by computed tomography in global
060501 - cardiovascular risk assessment and in evaluation of patients
060502 - with chest pain: a report of the American College of Cardiology
060503 - Foundation Clinical Expert Consensus Task Force (ACCF/AHA
060504 - Writing Committee to Update the 2000 Expert Consensus Document
060505 - on Electron Beam Computed Tomography). J Am Coll Cardiol
060506 - 2007;49:378 ? 402.
060508 - ..
060509 - This article has been copublished in the January 23, 2007 issue
060510 - of Circulation.
060512 - ..
060513 - Copies: This document is available on the World Wide Web sites
060514 - of the American College of Cardiology (www.acc.org) and the
060515 - American Heart Association (www. americanheart.org). For
060516 - copies of this document, please contact Elsevier Inc. Reprint
060517 - Department, fax (212) 633-3820, email reprints@elsevier.com.
060519 - ..
060520 - Permissions: Multiple copies, modification, alteration,
060521 - enhancement, and/or distribution of this document are not
060522 - permitted without the express permission of the American Heart
060523 - Association. Instructions for obtaining permission are located
060524 - at
060525 -
060526 - http://www.americanheart.org/presenter.jhtml?identifier_4431
060528 - ..
060529 - A link to the ?Permission Request Form? appears on the right
060530 - side of the page.
060531 -
060533 - ..
060534 - This document has been developed as a Clinical Expert Consensus
060535 - Document (CECD), by the American College of Cardiology
060536 - Foundation (ACCF) and the American Heart Association (AHA) in
060537 - collaboration with the Society of Atherosclerosis Imaging and
060538 - Prevention (SAIP) and Society of Cardiovascular Computed
060539 - Tomography (SCCT). It is intended to provide a perspective on
060540 - the current state of the role of coronary artery calcium (CAC)
060541 - scoring by fast computed tomography in clinical practice.
060542 - Clinical Expert Consensus Documents are intended to inform
060543 - practitioners, payers, and other interested parties of the
060544 - opinion of the ACCF and AHA concerning evolving areas of
060545 - clinical practice and/or technologies that are widely available
060546 - or new to the practice community. Topics chosen for coverage
060547 - by expert consensus documents are so designed because the
060548 - evidence base, the experience with technology, and/or the
060549 - clinical practice are not considered sufficiently well
060550 - developed to be evaluated by the formal American College of
060551 - Cardiology/American Heart Association (ACC/AHA) Practice
060552 - Guidelines process. Often the topic is the subject of
060553 - considerable ongoing investigation. Thus, the reader should
060554 - view the CECD as the best attempt of the ACC and AHA to inform
060555 - and guide clinical practice in areas where rigorous evidence
060556 - may not yet be available or the evidence to date is not widely
060557 - accepted. When feasible, CECDs include indications or
060558 - contraindications. Some topics covered by CECDs will be
060559 - addressed subsequently by the ACC/AHA Practice Guidelines
060560 - Committee.
060562 - ..
060563 - The Task Force on Clinical Expert Consensus Documents makes
060564 - every effort to avoid any actual or potential conflicts of
060565 - interest that might arise as a result of an outside
060566 - relationship or personal interest of a member of the writing
060567 - panel. Specifically, all members of the writing panel are
060568 - asked to provide disclosure statements of all such
060569 - relationships that might be perceived as real or potential
060570 - conflicts of interest to inform the writing effort. These
060571 - statements are reviewed by the parent task force, reported
060572 - orally to all members of the writing panel at the first
060573 - meeting, and updated as changes occur. The relationships with
060574 - industry information for writing committee members and peer
060575 - reviewers are published in the appendices of the document.
060577 - ..
060578 - Robert A. Harrington, MD, FACC
060579 - Chair, ACCF Task Force on Clinical Expert
060580 - Consensus Documents
060582 - ..
060583 - Introduction
060585 - ..
060586 - The Writing Committee consisted of acknowledged experts in the
060587 - field of coronary artery disease. In addition to members of
060588 - ACCF and AHA, the Writing Committee included representatives
060589 - from the SAIP and SCCT. Representation by an outside
060590 - organization does not necessarily imply endorsement. The
060591 - document was reviewed by four official representatives from the
060592 - ACCF, and AHA; organizational review by the SAIP and SCCT, as
060593 - well as 14 content reviewers. This document was approved for
060594 - publication by the governing bodies of ACCF and AHA in
060595 - September 2006. In addition, the governing boards of the SAIP
060596 - and SCCT reviewed and formally endorsed this document. This
060597 - document will be considered current until the Task Force on
060598 - CECDs revises or withdraws it from publication.
060599 -
060601 - ..
060602 - Consensus Statement Method
060604 - ..
060605 - This statement builds on a previous ACC/AHA Expert Consensus
060606 - Document published in 2000 that focused on electron beam
060607 - computed tomography (CT) for diagnosis and prognosis of
060608 - coronary artery disease (1). In preparing the present
060609 - document, the Writing Committee began with the previous report
060610 - as a basis for its deliberations and subsequent literature
060611 - review. In considering the current status of research on CAC
060612 - measurement and its role in clinical practice, the Expert Panel
060613 - concluded that the majority of the research on CAC measurement
060614 - in the past 5 years has focused on 2 areas of clinical
060615 - interest: 1) Risk assessment in the asymptomatic patient, for
060616 - the primary purpose of modifying and potentially improving
060617 - selection of patients for risk reducing therapies, and 2) Use
060618 - of CAC measurement in symptomatic patients as a means of
060619 - selecting patients who might require subsequent hospitalization
060620 - or additional diagnostic or invasive procedures. The Writing
060621 - Committee also recognized that the AHA was in the process of
060622 - completing a scientific statement on assessment of coronary
060623 - artery disease by CT (2), and thus this Writing Committee?s
060624 - attention was focused on evaluating clinical aspects of CAC
060625 - measurement rather than on technical issues that are covered in
060626 - the AHA statement (2). Also, the Writing Committee is aware
060627 - that ACCF has recently published appropriateness criteria using
060628 - approaches that differ somewhat from those used in developing
060629 - this Consensus Document. Therefore, readers should be aware
060630 - that there may be slight differences in language used in this
060631 - document and the Appropriateness Criteria for Cardiac Computed
060632 - Tomography and Magnetic Resonance (3) document.
060634 - ..
060635 - At its first meeting, each member of this ACCF/AHA Writing
060636 - Committee indicated any relationship with industry. Relevant
060637 - conflicts of the Writing Committee and peer reviewers are
060638 - reported in Appendixes 1 and 2, respectively. The next step in
060639 - the development of this document was to obtain a complete
060640 - literature review from the Griffith Resource Library at the ACC
060641 - concerning CAC measurement by fast CT methods from 1998 through
060642 - early 2005 (National Library of Medicine?s Elhill System).
060643 - Additional relevant prior or subsequently published references
060644 - have also been identified by personal contacts of the Writing
060645 - Committee members, and substantial efforts were made to
060646 - identify all relevant manuscripts that were currently in press.
060647 - At the first meeting, members of the Writing Committee were
060648 - given assignments to provide descriptions and analyses of CAC
060649 - measurement for identifying and modifying coronary event risk
060650 - in the asymptomatic patient, for modifying the clinical care
060651 - and outcomes of symptomatic patients suspected of having
060652 - coronary artery disease (CAD), and for understanding the role
060653 - of CAC measurement in selected patient subgroups. Each
060654 - individual contributor to these parts of the document had his
060655 - or her initial full written presentation critiqued by all other
060656 - members of this Writing Committee. Outside peer review was
060657 - also undertaken before the document was finalized.
060659 - ..
060660 - Considerable discussion among the group focused on the best and
060661 - most proper way to assess clinical appropriateness of tests
060662 - such as CAC measurement since there have been no clinical
060663 - trials to evaluate the impact of CAC testing on clinical
060664 - outcomes in either symptomatic or asymptomatic patients. The
060665 - Writing Committee agreed uniformly that the ideal assessment of
060666 - cardiac tests would require clinical trials that utilize
060667 - important patient outcomes such as improving the quality or
060668 - quantity of a patient?s life. However, recognizing that this
060669 - standard is not available for CAC measurement, the Committee
060670 - considered other standards of evidence in reaching a consensus
060671 - opinion. A minority of the Writing Committee felt that CAC
060672 - testing could not be advised for any clinical indication until
060673 - clinical trials were available to show benefit on actual
060674 - patient outcomes. However, the majority of the Writing
060675 - Committee felt that this standard of evidence is rarely applied
060676 - in assessment of cardiac testing appropriateness. Therefore,
060677 - the majority position presented here reflects the concept that
060678 - prognostic testing such as CAC measurement can be considered
060679 - reasonable where there is evidence that the test results can
060680 - have a meaningful impact on medical decision-making.
060682 - ..
060683 - Introduction to CAC Measurement
060684 -
060685 - Coronary arterial calcification is part of the development of
060686 - atherosclerosis, occurs almost exclusively in atherosclerotic
060687 - arteries, and is absent in the normal vessel wall (4?6).
060688 - Coronary artery calcification occurs in small amounts in the
060689 - early lesions of atherosclerosis that appear in the second and
060690 - third decades of life, but it is found more frequently in
060691 - advanced lesions and in older age. Although there is a
060692 - positive correlation between the site and the amount of
060693 - coronary artery calcium and the percent of coronary luminal
060694 - narrowing at the same anatomic site, the relation is nonlinear
060695 - and has large confidence limits (7). The relation of arterial
060696 - calcification, like that of angiographic coronary artery
060697 - stenosis, to the probability of plaque rupture is unknown
060698 - (8,9). There is no known relationship between vulnerable
060699 - plaque and coronary artery calcification (10). Although
060700 - radiographically detected coronary artery calcium can provide
060701 - an estimate of total coronary plaque burden, due to arterial
060702 - remodeling, calcium does not concentrate exclusively at sites
060703 - with severe coronary artery stenoses (11).
060705 - ..
060706 - Electron-beam computed tomography (EBCT) and multi-detector
060707 - computed tomography (MDCT) are the primary fast CT methods for
060708 - CAC measurement at this time. Both technologies employ thin
060709 - slice CT imaging, using fast scan speeds to reduce motion
060710 - artifact. Thirty to 40 adjacent axial scans usually are
060711 - obtained. A calcium scoring system has been devised based on
060712 - the X-ray attenuation coefficient, or CT number measured in
060713 - Hounsfield units, and the area of calcium deposits (12). A
060714 - fast CT study for coronary artery calcium measurement is
060715 - completed within 10 to 15 min, requiring only a few seconds of
060716 - scanning time.
060718 - ..
060719 - Cardiac computed tomography has been used with increasing
060720 - frequency in the United States and other countries during the
060721 - past 15 years, initially with the goal of identifying patients
060722 - at risk of having obstructive coronary artery disease based on
060723 - the amount of coronary calcium present. However, in the past 5
060724 - to 10 years, fast CT methods have been used primarily for 2
060725 - purposes: 1) to assist in coronary heart disease (CHD) risk
060726 - assessment in asymptomatic patients, and 2) to assess the
060727 - likelihood of the presence of CHD in patients who present with
060728 - atypical symptoms which could be consistent with myocardial
060729 - ischemia.
060731 - ..
060732 - Many technical aspects are relevant to the choice of EBCT
060733 - versus MDCT, and these are beyond the scope of this document.
060734 - A related document, recently prepared by the AHA, addresses
060735 - these important technical issues (2). In contrast, this
060736 - document focuses on clinical uses of fast CT for CAC
060737 - measurement and addresses the appropriateness of CAC
060738 - measurement in defined clinical circumstances.
060739 -
060741 - ..
060742 - Role of Risk Assessment in Cardiovascular Medicine
060743 -
060744 - A major focus of this Consensus Document is the role of CAC
060745 - measurement in cardiovascular risk assessment. Thus, a brief
060746 - overview of cardiovascular risk assessment is important to
060747 - provide a frame of reference for the material that follows.
060749 - ..
060750 - Risk assessment is often regarded as a key first step in the
060751 - clinical management of cardiovascular risk factors. Risk
060752 - assessment algorithms, such as those from the Framingham Heart
060753 - Study in the United States or from the Prospective
060754 - Cardiovascular Munster (PROCAM) study in Germany, or the
060755 - European risk prediction system called SCORE (Systemic Coronary
060756 - Risk Evaluation), are among the most common and widely
060757 - available for estimating multi-factorial absolute risk in
060758 - clinical practice (13). Each of these risk assessment
060759 - algorithms, as most often used, projects 10-year, absolute
060760 - risk, which can be considered short-term or intermediate-term
060761 - (not lifetime) risk. These risk projections are often regarded
060762 - by policy makers and clinicians as useful when selecting the
060763 - most appropriate candidates for drug therapies intended to
060764 - reduce risk. Cholesterol and blood pressure guidelines in the
060765 - United States and elsewhere have followed the principle that
060766 - the intensity of treatment should be aligned with the severity
060767 - of a patient?s risk (14,15). The rationale behind this balance
060768 - between treatment intensity and patient risk is that
060769 - proportional risk reduction and cost-effectiveness analyses
060770 - indicate that there is greater benefit of drug exposure when
060771 - the patient?s risk is high. It has been considered useful to
060772 - divide patients into several categories depending on their
060773 - 10-year risk estimates. Three commonly used categories are
060774 - high risk, intermediate risk, and low risk. Beginning in 2004,
060775 - the National Cholesterol Education Program (NCEP) further
060776 - divided the intermediate-risk category into moderately high
060777 - risk and moderate risk (16). Table 1 shows the most recent
060778 - NCEP categories of 10-year absolute risk used to stratify
060779 - patients for cholesterol-lowering therapy. This classification
060780 - can be applied to other CHD risk reduction therapies as well,
060781 - such as blood pressure lowering.
060783 - ..
060784 - --------------------------------------
060785 - Table 1. Absolute Risk Categories According to National
060786 - Cholesterol Education Program Update, 2004
060787 -
060788 - 10-Year Absolute Risk Category Definition of Category
060790 - ..
060791 - High risk CHD*, CHD risk equivalents? including 2 major risk factors? plus a 10-year risk for hard CHD greater than 20%§
060792 - Moderately high risk Moderately high risk 2 major risk factors? plus a 10-year risk for hard CHD 10% to 20%
060793 - Moderate risk Moderate risk 2 major risk factors plus a 10-year risk for hard CHD less than 10%
060794 - Lower risk Lower risk 0 to 1 major risk factor (10-year risk for hard CHD usually less than 10%)§
060796 - ..
060797 - *CHD includes history of myocardial infarction, unstable
060798 - angina, stable angina, coronary artery procedures (angioplasty
060799 - or by-pass surgery), or evidence of clinically significant
060800 - myocardial ischemia.
060801 -
060802 - ?CHD risk equivalents include clinical manifestations of
060803 - non-coronary forms of atherosclerotic disease (peripheral
060804 - arterial disease, abdominal aortic aneurysm, and carotid artery
060805 - disease [transient ischemic attacks or stroke of carotid origin
060806 - or greater than 50% obstruction of a carotid artery]),
060807 - diabetes, and 2 risk factors with 10-year risk for hard CHD
060808 - less than 20%.
060809 -
060810 - ?Major risk factors include cigarette smoking, hypertension (BP
060811 - greater than or equal to 140/90 mm Hg or on antihypertensive
060812 - medication), low HDL cholesterol (less than 40 mg/dL), family
060813 - history of premature CHD (CHD in male first-degree relative
060814 - less than 55 years; CHD in female first-degree relative less
060815 - than 65 years), and age (men greater than or equal to 45 years;
060816 - women greater than or equal to 55 years).
060817 -
060818 - §Almost all people with 0 to 1 risk factor have a 10-year risk less
060819 - than 10%, and 10-year risk assessment in people with 0 to 1
060820 - risk factor is thus not necessary. Modified with permission
060821 - from Grundy SM, Cleeman JI, Merz CN, et al. Implications of
060822 - recent clinical trials for the National Cholesterol Education
060823 - Program Adult Treatment Panel III guidelines. Circulation
060824 - 2004;110:227?39 (16). BP blood pressure; CHD coronary
060825 - heart disease; HDL high-density lipoprotein.
060826 -
060827 - --------------------------------------
060829 - ..
060830 - Matching Intensity of Intervention With Severity of Risk
060831 -
060832 - As previously noted, a principle of cardiovascular disease
060833 - prevention that is generally accepted is that intensity of
060834 - intervention for an individual (or population) should be
060835 - adjusted to the level of baseline risk (17). The goals of this
060836 - principle are to optimize efficacy, safety, and costeffectiveness
060837 - of the intervention. The concept is most often
060838 - applied to higher-risk individuals who are potential candidates
060839 - for risk-reducing drugs; but it also is an important
060840 - consideration for lower risk individuals either in clinical
060841 - practice or for public health strategies. For higher risk
060842 - individuals, intensity of intervention is best adjusted to
060843 - absolute short-term risk; for lower risk individuals, relative
060844 - risk remains an important consideration because a high
060845 - relative risk generally translates into a high absolute risk in
060846 - the long term. This latter concept is most relevant to
060847 - younger men and middle-aged men and women, whereas in
060848 - older men and women, the Framingham Risk Score generally
060849 - applies.
060851 - ..
060852 - Current Approaches to Global Risk Assessment and to
060853 - Assessment of Incremental Risk Using New Tests
060854 -
060855 - In current clinical practice, in accordance with a number of
060856 - guidelines (14,15), it is common that the first step in
060857 - clinical risk assessment is to identify any high-risk
060858 - conditions that obviate the need for further risk assessment;
060859 - these mainly include established atherosclerotic cardiovascular
060860 - disease (ASCVD) and diabetes (see Table 1, High risk). If none
060861 - of these high-risk conditions is present, the second step is to
060862 - identify the presence of major risk factors (also listed in
060863 - Table 1). If 2 or more major risk factors are present, one
060864 - should then estimate the 10-year likelihood for development of
060865 - major coronary events or total cardiovascular events. In the
060866 - United States, the most-commonly used and most extensively
060867 - validated quantitative assessment is provided by the
060868 - multivariable scoring system of the Framingham Heart Study.
060869 - The Framingham algorithm for ?hard CHD? events including
060870 - myocardial infarction and cardiac death is available
060871 - available through the National Cholesterol Education Program
060872 - website (
060873 -
060874 - http://hin.nhlbi.nih.gov/atpiii/calculator.asp
060876 - ..
060877 - ). Framingham scoring includes the following major risk
060878 - factors: gender, total cholesterol, high-density lipoprotein
060879 - (HDL) cholesterol, systolic blood pressure (or on treatment for
060880 - hypertension), cigarette smoking, and age. PROCAM scoring
060881 - employs a somewhat different set of risk factors: gender, age,
060882 - low-density lipoprotein (LDL) cholesterol, HDL cholesterol,
060883 - triglycerides, systolic blood pressure, cigarette smoking,
060884 - family history, and presence or absence of diabetes (
060885 -
060886 - http://www.chd-taskforce.com/
060888 - ..
060889 - ). The European SCORE algorithm uses risk factors similar to
060890 - the Framingham Score.
060892 - ..
060893 - For each of these risk assessment tools, the most powerful risk
060894 - factors are age and gender. The other risk factors can be
060895 - examined for their additive predictive power by determining
060896 - increments in the area under the curve of the
060897 - receiver-operating characteristic (ROC). The area under the
060898 - ROC curve is also known as the C-statistic. An ROC analysis
060899 - plots sensitivity (fraction of true positives) versus 1-
060900 - specificity (fraction of false positives) of a risk factor for
060901 - predicting events. ROC curves are used to evaluate the
060902 - discrimination of a prediction, and often, the predictive power
060903 - of a set of risk factors. If a given set of risk factors
060904 - predicted the development of cardiovascular events perfectly,
060905 - the curve would reach 100% in the upper left corner (100%
060906 - sensitivity and 100% specificity), that is, all true positives
060907 - and no false positives. The area under the curve would be 100%
060908 - (C-statistic = 1.0). A random and useless predictor would give
060909 - a straight line at 45 degrees (C-statistic = 0.5) since this
060910 - would define a test where true positive rate and false positive
060911 - rate are equal to one another at every possible cutoff value.
060912 - In the evaluation of additional tests, added to the basic set
060913 - of Framingham risk factors, the area under the curve would
060914 - increase when the test provides incremental discrimination.
060915 - The Framingham algorithm applied to the Framingham population
060916 - generally gives a C-statistic of approximately 0.8, meaning
060917 - that the probability is 80% that patients who experience CHD
060918 - events will have a higher risk score than patients who did not
060919 - experience an event. An important but unresolved issue is
060920 - whether discovery and addition of new biochemical risk factors
060921 - or imaging markers to Framingham or PROCAM algorithms will
060922 - increase the C-statistic. In considering the role of CAC
060923 - measurement for risk assessment, a key issue is whether
060924 - discriminative ability is improved, often as judged by an
060925 - increase in the C-statistic compared to that derived from risk
060926 - factors alone.
060928 - ..
060929 - Risk Assessment for Coronary Heart Disease in Asymptomatic Populations
060930 - Prognosis by Coronary Artery Calcium Measurements
060931 -
060932 - In the prior ACC/AHA expert consensus document published in
060933 - 2000, only 3 reports on the prognostic capability of CAC
060934 - scoring were available to develop risk assessment indications
060935 - in asymptomatic individuals (1). At the time, the ACC/AHA
060936 - document concluded that the body of evidence using CAC
060937 - measurement to predict CHD events was insufficient. A critical
060938 - component to that recommendation was that the independent
060939 - prognostic value of CAC had not been established. In a
060940 - separate but similar evaluation using data published through
060941 - 2002, the US Preventive Services Task Force (USPSTF) concluded
060942 - that limited clinical outcomes data were available and
060943 - recommended against routine screening for the detection of
060944 - silent but severe CAD or for the prediction of CHD events in
060945 - low risk, asymptomatic adults (see
060946 -
060947 - http://www.ahrq.gov/downloads/pub/prevent/pdfser/chdser.pdf
060949 - ..
060950 - In the past several years, however, a number of publications
060951 - have reported on the incremental prognostic value of CAC in
060952 - large series of patients including asymptomatic self-referred
060953 - and population cohorts (18?22). A major rationale for the
060954 - current document is the need for an update including recent
060955 - publications regarding CAC as it relates to the estimation of
060956 - CHD death or nonfatal myocardial infarction (MI). Although
060957 - earlier evidence included the use of ?soft? endpoints including
060958 - coronary revascularization as a primary outcome, more recent
060959 - data are available on the estimation of CHD death or MI
060960 - (18?22). Models predicting ?hard? cardiac events (i.e., CHD
060961 - death or MI) are less subjective and less likely to
060962 - overestimate the predictive accuracy of CAC scoring (23).
060963 -
060965 - ..
060966 - Theoretical Relationship Between Coronary Calcification and CHD Events
060967 -
060968 - Atherosclerotic plaque proceeds through progressive stages
060969 - where instability and rupture can be followed by calcification,
060970 - perhaps to provide stability to an unstable lesion (8). As the
060971 - occurrence of calcification reflects an advanced stage of
060972 - plaque development, some researchers have proposed that the
060973 - correlation between coronary calcification and acute coronary
060974 - events may be suboptimal based largely on angiographic series
060975 - (11). In order to understand this apparent conflict between
060976 - the stability of a calcified lesion and CHD event rates, one
060977 - must recognize the association between atherosclerotic plaque
060978 - extent and more frequent calcified and non-calcified plaque
060979 - (24). That is, patients who have calcified plaque are also
060980 - more likely to have non-calcified or ?soft? plaque that is
060981 - prone to rupture and acute coronary thrombosis (24). It is the
060982 - co-occurrence of calcified and non-calcified plaque that
060983 - provides the means for estimating acute coronary events.
060984 - Furthermore, although CAC detection cannot localize a stenotic
060985 - lesion or one that is prone to rupture, CAC scoring may be able
060986 - to globally define a patient?s CHD event risk by virtue of its
060987 - strong association with total coronary atherosclerotic disease
060988 - burden, as shown by correlation with pathologic specimens
060989 - (1,24).
060991 - ..
060992 - Approaches to Technology Assessment in CHD Screening
060993 -
060994 - A major criterion utilized in many technology assessments has
060995 - been that a screening test must have a high level of evidence
060996 - on the effect of screening on actual health outcomes, such as
060997 - fewer events, extended life, or better quality of life. This
060998 - type of analysis requires research detailing an improvement in
060999 - either quantity or quality-of-life years as a result of the
061000 - screening procedure. An example of a high level of such
061001 - evidence was recently published on screening for abdominal
061002 - aortic aneurysm (AAA) (25). Using this example, a
061003 - meta-analysis reported reduced mortality in randomized trials
061004 - of AAA screening. These results allowed for favorable support
061005 - of AAA screening by the USPSTF resulting in a class B
061006 - recommendation (i.e., evidence includes consistent results from
061007 - well-designed, well-conducted studies in representative
061008 - populations that directly assess effects on health outcomes)
061009 - (26). Lack of similar controlled clinical trial evidence
061010 - played a central role in the conclusion by the USPSTF not to
061011 - support CHD screening using CAC measurement (see
061012 -
061013 - http://www.ahrq.gov/downloads/pub/prevent/pdfser/chdser.pdf
061015 - ..
061016 - Although no studies have shown a net effect on health outcomes
061017 - of CAC scoring (27), at least one randomized trial is nearing
061018 - completion (Early Identification of Subclinical Atherosclerosis
061019 - using NoninvasivE Imaging Research [EISNER]). However, the
061020 - concept of matching treatment intensity to the degree of
061021 - cardiovascular risk suggests that efforts to identify the most
061022 - accurate approach to risk stratification is an initial and
061023 - critical step that should aid in the best selection of
061024 - treatment options for patients at risk for cardiovascular
061025 - disease.
061027 - ..
061028 - Systematic Reviews and Meta-Analyses
061029 -
061030 - In the sections that follow, we review recent evidence on the
061031 - prognostic value of CAC and include data from one recent
061032 - systematic review. A comprehensive data synthesis on this
061033 - subject was published by Pletcher et al. (23) evaluating the
061034 - prognostic value of CAC from 4 studies published through 2002
061035 - meeting quality-based inclusion criteria. Articles were
061036 - considered for that meta-analysis if they evaluated the
061037 - prognostic value of CAC in asymptomatic individuals and also
061038 - presented data on CHD events. Based on a random-effects model,
061039 - the summary relative risk ratios were 2.1 (for CAC score of 1
061040 - to 100) and as high as 10 (for CAC greater than 400) as
061041 - compared to patients with a score of 0 (p less than 0.0001).
061042 - This meta-analysis (23) offers support for the concept that
061043 - there is a linear relationship between CAC and CHD events, but
061044 - the analysis did not address whether CAC measurement is
061045 - incremental to Framingham Risk Score (FRS) for CHD risk
061046 - prediction.
061047 -
061048 - --------------------------------------
061049 - Table 2. Quality Assessment Criteria for Evaluation of Reports
061050 - on the Prognostic Value of CAC
061051 -
061052 - *** data not entered in this record ***
061053 -
061054 -
061055 - ------------------------------------------
061057 - ..
061058 - Data Quality Issues
061059 -
061060 - A lack of rigor in study methodology was a focus of the 2000
061061 - ACC document (1). A detailed review of the quality of the
061062 - published data on the prognostic value of CAC was also
061063 - published by Pletcher et al. (23) noting significant
061064 - heterogeneity in study quality with often a lack of blinded
061065 - outcome adjudication, greater use of categorical or historical
061066 - risk factors, and variable tomographic slice thickness (3 vs. 6
061067 - mm) contributing to an overestimation of the relative risk of
061068 - events by CAC measurements. For example, the relative risk
061069 - ratio was significantly higher for CAC of 101 to 400 (p = 0.01)
061070 - and greater than 400 (p = 0.004) when self-reported or
061071 - historical risk factors were employed in a predictive model as
061072 - compared with measured risk factor data. The clinical
061073 - implication of this distinction is that physicians interpreting
061074 - these results may overvalue CAC scores as substantially more
061075 - predictive than traditional risk factors.
061077 - ..
061078 - Evaluation of more recent publications indicates that some of
061079 - the important methodological limitations of earlier reports
061080 - have been addressed. Notably, more recent publications report
061081 - the independent prognostic value of CAC in multivariable models
061082 - including measured risk factor data (18,19,22). Larger sample
061083 - sizes have also resulted in improved precision in risk
061084 - prediction models. However, issues of selection or referral
061085 - bias when using patient cohorts remain pertinent and are likely
061086 - to have resulted in an overestimation of risk when based on
061087 - clinical cohorts as compared with population samples (20,22).
061088 - It is important recognize that relative risk ratios from
061089 - patient cohorts have generally been higher than from studies
061090 - conducted in population samples even when the overall direction
061091 - of the prognostic findings has been concordant.
061093 - ..
061094 - Inclusion Criteria and Endpoint Definitions for the Present Analysis
061095 -
061096 - The current document focuses on the ability of CAC scoring to
061097 - estimate CHD death or MI. This approach allows for a
061098 - comparison of the expected annual event rates based on the FRS.
061099 - The FRS estimates that annual rates of CHD death or MI are less
061100 - than 1.0% for low risk, 1.0% to 2.0% for intermediate risk
061101 - (Table 1), and greater than 2.0% for high risk. When multiple
061102 - publications have been reported from the same cohort study
061103 - (1,4,5,33?36), we employ here only the most recent report in
061104 - the current analysis (19,20).
061106 - ..
061107 - The inclusion criteria for this analysis are: 1) data not
061108 - previously reported in the 2000 document (1); 2) published
061109 - series on the prognostic value of CAC in asymptomatic cohorts
061110 - reported since 2002; 3) endpoint data must be reported on the
061111 - outcome of CHD death or MI over a specified follow-up time
061112 - period (usually within 3 to 5 years); and 4) data extraction
061113 - must allow for the calculation of univariable relative risk
061114 - ratios and must also include risk-adjustment for traditional
061115 - cardiac risk factors (e.g., age, gender, cholesterol,
061116 - hypertension, etc.) or the FRS.
061118 - ..
061119 - Two committee members (AJT, LJS) evaluated the quality of each
061120 - included report with the results of this analysis being
061121 - included in Table 2. The quality assessment criteria included:
061122 - 1) documentation of prospective data collection; 2) inclusion
061123 - of self-referred patient series or from a population sample; 3)
061124 - reporting of CHD events; 4) reporting of outcome data by gender
061125 - and ethnicity; 5) sample size greater than 1000 individuals; 6)
061126 - avoiding potential for limited challenge (i.e., an inclusion of
061127 - very low to very high-risk patients resulting in a wide spread
061128 - in the outcome results) by not reporting data within strata of
061129 - clinical risk; 7) reporting measured versus historical or
061130 - self-reported risk factor data; and 8) reporting univariable
061131 - and multivariable prognostic models (i.e., ascertaining the
061132 - incremental value of CAC scores). A review of the highlighted
061133 - reports reveals that all studies identified for inclusion were
061134 - of at least moderate-high quality.
061136 - ..
061137 - Prognostic Value of CAC Scores From Published Reports From 2003?2005
061138 -
061139 - Several recent cohorts have been published including
061140 - prospective observational registries in predominantly male,
061141 - younger and middle-aged (18), unselected (19) and older-aged,
061142 - higher risk (20) asymptomatic cohorts. A self-referred patient
061143 - series of 8855 asymptomatic adults was also included in this
061144 - analysis (21). A recent population sample was also published
061145 - and included 1795 subjects greater than or equal to 55 years of
061146 - age who were prospectively enrolled in the Rotterdam coronary
061147 - calcium study (22). Finally, the prognostic value of CAC
061148 - scores was recently reported from a large series of 10 746 men
061149 - and women aged 22 to 96 years who underwent a preventive health
061150 - examination at the Cooper Clinic in Dallas, Texas (28).
061152 - ..
061153 - Using a random-effects model, an analytical approach
061154 - frequently applied to observational data such as that reported
061155 - in the CAC series, Figure 1 reports on the univariable
061156 - and summary (weighted average) relative risk ratios
061157 - from 6 recently published reports in 27 622 patients (n
061158 - 395 CHD death or MI). This figure reports the summary
061159 - relative risk ratio of 4.3 (95% confidence interval [CI] 3.5
061160 - to 5.2) for any measurable calcium as compared with a
061161 - low-risk CAC (generally using a score of 0) (p less than
061162 - 0.0001). These data imply that the 3 to 5 year risk of any
061163 - detectable calcium elevates a patient?s CHD risk of events
061164 - by nearly 4-fold (p less than 0.0001). Importantly, patients
061165 - without detectable calcium (or a CAC score 0) have a
061166 - very low rate of CHD death or MI (0.4%) over 3 to 5 years
061167 - of observation (n 49 events/11 815 individuals).
061169 - ..
061170 - As can be further seen in Figure 1, considerable variability
061171 - existed in the relative risk ratios across the 6 reports which
061172 - can, in part, be attributed to variability in the grouping of
061173 - CAC scores and in the representation of younger individuals
061174 - and women within each of the risk subsets. In the most
061175 -
061176 -
061177 - --------------------------------------
061178 - Figure 1. Meta-Analysis on the Prognostic Value of CACS
061180 - ..
061181 - Relative risk (RR) ratios (95% confidence intervals [CI]) in
061182 - six published reports (18?22,28). CACS = coronary artery
061183 - calcification score.
061185 - ..
061186 - Seems to be table comparing findings from various studies
061187 - correlating calcium score (CACS) with death or risk of death,
061188 - not sure...
061189 -
061190 - --------------------------------------------------
061191 -
061192 -
061193 -
061194 -
0612 -
SUBJECTS
Default Null Subject Account for Blank Record
0703 -
070401 - ..
070402 - Long-Term Prognosis Associated With Coronary Calcification_Budoff.2007.pdf
070403 -
070404 -
070405 - F:\05\00003\SM\CC\AGMJ\20151119-184400\Long-Term-Prognosis-Associated-With-Coronary-Calcification_Budoff-2007.pdf
070406 -
070407 - 1. Journal of the American College of Cardiology
070408 - 2007 by the American College of Cardiology Foundation
070409 - Published by Elsevier Inc
070411 - ..
070412 - Vol 49 No 18, 2007
070413 - ISSN 0735-1097/07/$32.00
070414 - doi:10.1016/j.jacc.2006.10.079
070416 - ..
070417 - JACC Vol. 49, No. 18, 2007
070418 - May 8, 2007:1860-70
070420 - ..
070421 - Cardiac Imaging
070423 - ..
070424 - Long-Term Prognosis Associated With Coronary Calcification
070425 - Observations From a Registry of 25,253 Patients
070426 -
070427 - Matthew J. Budoff, MD,* Leslee J. Shaw, PHD,? Sandy T. Liu,*
070428 - Steven R. Weinstein,*
070429 - Tristen P. Mosler, Philip H. Tseng,* Ferdinand R. Flores,*
070430 - Tracy Q. Callister, MD,?
070431 - Paolo Raggi, MD,§ Daniel S. Berman, MD?
070433 - ..
070434 - Torrance and Los Angeles, California; Nashville, Tennessee;
070435 - and Atlanta, Georgia
070437 - ..
070438 - From the *Harbor-UCLA Los Angeles Biomedical Research
070439 - Institute, Torrance, California; ?Cedars-Sinai Medical Center,
070440 - Los Angeles, California; ?EBT Research Foundation, Nashville,
070441 - Tennessee; and the §Division of Cardiology and Department of
070442 - Radiology, Emory University, Atlanta, Georgia. Dr. Budoff is
070443 - on the speakers? bureau for General Electric.
070445 - ..
070446 - Manuscript received March 6, 2006; revised manuscript received
070447 - September 18, 2006, accepted October 16, 2006.
070449 - ..
070450 - Objectives
070451 -
070452 - The purpose of this study was to develop risk-adjusted
070453 - multivariable models that include risk factors and coronary
070454 - artery calcium (CAC) scores measured with electron-beam
070455 - tomography in asymptomatic patients for the
070456 - prediction of all-cause mortality
070458 - ..
070459 - Background
070460 -
070461 - Several smaller studies have documented the efficacy of CAC
070462 - testing for assessment of cardiovascular risk. Larger
070463 - studies with longer follow-up will lend strength to the
070464 - hypothesis that CAC testing will improve outcomes,
070465 - cost-effectiveness, and safety of primary prevention
070466 - efforts.
070468 - ..
070469 - Methods
070470 -
070471 - We used an observational outcome study of a cohort of
070472 - 25,253 consecutive, asymptomatic individuals referred by
070473 - their primary physician for CAC scanning to assess
070474 - cardiovascular risk. Multivariable Cox proportional
070475 - hazards models were developed to predict all-cause
070476 - mortality. Risk-adjusted models incorporated traditional
070477 - risk factors for coronary disease and CAC scores.
070479 - ..
070480 - Results
070481 -
070482 - The frequency of CAC scores was 44%, 14%, 20%, 13%, 6%, and
070483 - 4% for scores of 0, 1 to 10, 11 to 100, 101 to 400, 401 to
070484 - 1,000, and >1,000, respectively. During a mean follow-up
070485 - of 6.8 +/- 3 years, the death rate was 2% (510 deaths).
070486 - The CAC was an independent predictor of mortality in a
070487 - multivariable model controlling for age, gender, ethnicity,
070488 - and cardiac risk factors (model chi-square = 2,017, p =
070489 - 0.0001). The addition of CAC to traditional risk factors
070490 - increased the concordance index significantly (0.61 for
070491 - risk factors vs. 0.81 for the CAC score, p < 0.0001).
070492 - Risk-adjusted relative risk ratios for CAC were 2.2-, 4.5-,
070493 - 6.4-, 9.2-, 10.4-, and 12.5-fold for scores of 11 to 100,
070494 - 101 to 299, 300 to 399, 400 to 699, 700 to 999, and 1,000,
070495 - respectively (p < 0.0001), when compared with a score of 0.
070496 - Ten-year survival (after adjustment for risk factors,
070497 - including age) was 99.4% for a CAC score of 0 and worsened
070498 - to 87.8% for a score of >1,000 (p < 0.0001).
070500 - ..
070501 - Conclusions
070502 -
070503 - This large observational data series shows that CAC
070504 - provides independent incremental information in addition to
070505 - traditional risk factors in the prediction of all-cause
070506 - mortality. (J Am Coll Cardiol 2007;49:1860?70) © 2007 by
070507 - the American College of Cardiology Foundation
070508 -
070510 - ..
070511 - Evidence-based guidelines recommend that primary care
070512 - physicians make a careful assessment of their patients?
070513 - baseline coronary heart disease (CHD) risk and focus primary
070514 - prevention interventions (such as use of cholesterol-lowering
070515 - drugs [1] and aspirin [2]) on intermediate- and high-risk
070516 - patients. Standard risk factor analyses can help stratify
070517 - patients into risk groups but are somewhat imprecise and leave
070518 - a large proportion of patients classifiable as ?intermediate?
070519 - risk, a rather undetermined state. Cholesterol therapy of
070520 - patients in this category might range from no therapy to a
070521 - low-density lipoprotein target <100 mg/dl. More effective
070522 - assessment of CHD risk might improve the outcome,
070523 - cost-effectiveness, and safety of primary prevention efforts.
070524 - We attempted to assess the prognostic power of coronary artery
070525 - calcium (CAC) assessed with electron beam tomography (EBT).
070526 - The purpose of this study was to develop long-term
070527 - risk-adjusted multivariable predictive models to estimate death
070528 - from all-causes, using cardiac risk factors and CAC scores
070529 - determined with EBT.
070531 - ..
070532 - Methods
070534 - ..
070535 - Patient entry criteria. The study sample consisted of 25,253
070536 - consecutive asymptomatic individuals referred by primary
070537 - physician for CAC measurement with EBT. Subjects were given a
070538 - risk-factor questionnaire to assess ethnicity and
070539 - cardiovascular risk factors. The presence and number of risk
070540 - factors for a subject was calculated on the basis of the
070541 - National Cholesterol Education Program guidelines (1). Risk
070542 - factors included: age (men 45 years, women 55 years), current
070543 - cigarette smoking, diabetes, history of premature coronary
070544 - disease in first-degree relative (men 55 years, women 65
070545 - years), hypertension, and hypercholesterolemia. Current
070546 - cigarette smoking was defined as any cigarette smoking in the
070547 - past month. Hypertension was defined by current use of
070548 - anti-hypertensive medication or known and untreated
070549 - hypertension. Hypercholesterolemia was defined as use of
070550 - cholesterol lowering medication or, in the absence of
070551 - cholesterol lowering medication use, as having a total serum
070552 - cholesterol 200 mg/dl. Total cholesterol measurements were
070553 - available in 11,275 subjects and were categorized as 200, 201
070554 - to 240, 241 to 260, and 260 mg/dl, respectively. Patients
070555 - also noted whether they were taking statin therapy at the time
070556 - of scanning.
070558 - ..
070559 - EBT methods.
070561 - ..
070562 - All study subjects underwent EBT with an Imatron C-150XL
070563 - Ultrafast computed tomography scanner (GE-Imatron, South San
070564 - Francisco, California). The study was approved by the
070565 - Institutional Review Board of Harbor- UCLA Medical Center.
070566 - Thirty to 40 contiguous tomographic slices were obtained at
070567 - 3-mm intervals beginning 1 cm below the carina and progressing
070568 - caudally to include the entire coronary tree. Exposure time
070569 - was 100 ms/ tomographic slice, and total irradiation dose was
070570 - 0.6 mSv/scan.
070572 - ..
070573 - An attenuation threshold of 130 HU and a minimum of 3
070574 - contiguous pixels were used for identification of a calcific
070575 - lesion. Each focus exceeding the minimum criteria was scored
070576 - with the algorithm developed by Agatston et al. (3), calculated
070577 - by multiplying the lesion area by a density factor derived from
070578 - the maximal HU within this area. The density factor was
070579 - assigned in the following manner: 1 for lesions with peak
070580 - attenuation of 130 to 199 HU, 2 for lesions with peak
070581 - attenuation of 200 to 299 HU, 3 for lesions with peak
070582 - attenuation of 300 to 399 HU, and 4 for lesions with peak
070583 - attenuation > 400 HU. The total CAC score was determined by
070584 - summing individual lesion scores from each of 4 anatomic sites
070585 - (left main, left anterior descending, circumflex, and right
070586 - coronary arteries) (3).
070588 - ..
070589 - Follow-up data collection.
070591 - ..
070592 - Epidemiologic methods for follow-up included ascertainment of
070593 - death by individuals who were blinded to historical and CAC
070594 - score results (4,5). The occurrence of all-cause death was
070595 - verified with the National Death Index (6). Individuals who
070596 - underwent cardiovascular screening were followed for a mean of
070597 - 6.8 years (SEM = 0.019) and median of 5.8 years (25th to 75th
070598 - percentile = 4.7 to 8.9 years). Follow-up was completed in
070599 - 100% of patients. In this sample, 5,218 patients had follow-up
070600 - >= 10 years and 1,404 patients had follow-up >= 12 years.
070602 - ..
070603 - Data validation in a prior 10,377 patient series. We compared
070604 - our survival analysis with a similar referral population from
070605 - patients enrolled in a prior registry (7,8) to examine
070606 - near-term (3- to 5-year) versus long-term (7- to 10-year)
070607 - survival. We pooled both datasets for validation of our
070608 - mortality model in the current 25,253 patient series and the
070609 - previously reported data in 10,377 patients.
070611 - ..
070612 - Statistical methods. We presented continuous measures as mean
070613 - SD and frequency data as proportions. Categorical variables
070614 - comparing CAC patient subsets with historical variables were
070615 - compared with a chi-square likelihood ratio test. For
070616 - comparing CAC subsets by age and other continuous measures, we
070617 - employed analysis of variance techniques. A p value 0.05 was
070618 - considered statistically significant. Time to death from all
070619 - causes was estimated with a Cox proportional hazards model.
070620 - Unadjusted survival and riskadjusted survival rates controlling
070621 - for age, gender, ethnicity, and other cardiac risk factors,
070622 - detailed in Table 1, were calculated. For all variables in a
070623 - model, univariable and risk-adjusted relative risk ratios (RRs)
070624 - with 95% confidence intervals (CIs) were calculated.
070626 - ..
070627 - Receiver-operating characteristic (ROC) curves were calculated,
070628 - including a comparative analysis of age and other cardiac risk
070629 - factors (Table 1) versus the CAC score. From the ROC curves, a
070630 - concordance (or C-) index, a measure of event and non-event
070631 - correct classification, was calculated including 95% CIs. In
070632 - our first ROC curve analysis, we evaluated the area under the
070633 - curve for age and other risk factors as compared with the
070634 - continuous CAC score. Two ROC curves are presented, including
070635 - model 1: comparing the number of cardiac risk factors with the
070636 - continuous CAC score, and model 2: comparing age with the
070637 - continuous CAC score.
070639 - ..
070640 - We then evaluated multivariable or risk-adjusted Cox models
070641 - with the CAC score in several coding schemes: 1) model 1: total
070642 - CAC score using categories of 0, 1 to 10, 11 to 100, 101 to
070643 - 400, 401 to 699, 700 to 999, and >= 1,000; and 2) model 2:
070644 - dividing the arterial segment analysis of the CAC score into 0
070645 - to 3 vessels with CAC score >= 100. In particular, for each of
070646 - these models, we calculated unadjusted analyses as well as
070647 - age-adjusted and other risk-factor-adjusted (Table 1) survival
070648 - models. From the multivariable models, we evaluated the added
070649 - value of the CAC score by calculating a C-index and 95% CIs.
070650 - As well, we calculated the Delta chi-square, a measure of the
070651 - risk predictive content of a given variable within a
070652 - multivariable model.
070653 -
070654 -
070655 -
070656 -
070657 -
070658 -
070659 -
070660 -
070661 -
070662 -
070663 -
070664 -
070665 -
070666 -
070667 -
070668 -
070669 -
070670 -
070671 -
070672 -
070673 -
070674 -
070675 -
070676 -
070677 -
070678 -
070679 -
070680 -
070681 -
070682 -
070683 -
070684 -
070685 -
070686 -
070687 -
070688 -
070689 -
0707 -