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Reference Study Type Patients/Events Study Objective(Purpose of Study) Study Results Study Quality
1. Cooper R, Cutler J, Desvigne-Nickens P, et al. Trends and disparities in coronary heart disease, stroke, and other cardiovascular diseases in the United States: findings of the national conference on cardiovascular disease prevention. Circulation. 2000;102(25):3137-3147. Review/Other-Dx N/A To assess the magnitude and causes of trends in CHD, stroke, and other CVDs; to examine various explanations for increasing health disparities across socioeconomic status, race/ethnicity, and region; and to explore opportunities to rectify these disparities. No results stated in abstract. 4
2. Greenland P, Alpert JS, Beller GA, et al. 2010 ACCF/AHA guideline for assessment of cardiovascular risk in asymptomatic adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2010;56(25):e50-103. Review/Other-Dx N/A To provide clinical practice guidelines to assess the magnitude and causes of trends in CHD, stroke, and other CVDs; to examine various explanations for increasing health disparities across socioeconomic status, race/ethnicity, and region; and to explore opportunities to rectify these disparities. N/A 4
3. Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 73(24):e285-e350, 2019 Jun 25. Review/Other-Dx N/A The purpose of the evidence-based guideline is to address the practical management of patients with high blood cholesterol and related disorders. N/A 4
4. Greenland P, Knoll MD, Stamler J, et al. Major risk factors as antecedents of fatal and nonfatal coronary heart disease events. JAMA. 2003;290(7):891-897. Observational-Dx 3 prospective cohort studies To determine the frequency of exposure to major coronary heart disease (CHD) risk factors. For fatal CHD (n=20,995), exposure to at least 1 clinically elevated major risk factor ranged from 87% to 100%. Among those aged 40 to 59 years at baseline with fatal CHD (n=19,263), exposure to at least 1 major risk factor ranged from 87% to 94%. For nonfatal MI, prior exposure was documented in 92% (95% CI, 87%-96%) (n=167) of men aged 40 to 59 years at baseline and in 87% (95% CI, 80%-94%) (n=94) of women in this age group. 3
5. Goff DC, Jr., Lloyd-Jones DM, Bennett G, et al. 2013 ACC/AHA guideline on the assessment of cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2014;63:2935-59. Review/Other-Dx N/A To provide clinical practice guidelines to assess the magnitude and causes of trends in CHD, stroke, and other CVDs; to examine various explanations for increasing health disparities across socioeconomic status, race/ethnicity, and region; and to explore opportunities to rectify these disparities. No results stated in abstract. 4
6. Wilson SR, Lin FY, Min JK. Role of coronary artery calcium score and coronary CT angiography in the diagnosis and risk stratification of individuals with suspected coronary artery disease. Curr Cardiol Rep. 2011;13(4):271-279. Review/Other-Dx N/A To review the role of coronary artery calcium scoring (CACS) and coronary computed tomography angiography (CCTA) in the diagnosis and risk stratification of individuals with suspected coronary artery disease (CAD). No results stated in abstract. 4
7. Perez de Isla L, Alonso R, Muniz-Grijalvo O, et al. Coronary computed tomographic angiography findings and their therapeutic implications in asymptomatic patients with familial hypercholesterolemia. Lessons from the SAFEHEART study. J. clin. lipidol.. 12(4):948-957, 2018 Jul - Aug. Review/Other-Dx 440 patients To describe coronary computed tomographic angiography (CTA) findings in asymptomatic molecularly defined familial hypercholesterolemia (FH) individuals, to identify those factors related to its presence and extension, and to assess the impact of these results in patients' care and estimated risk. Mean age was 46.4 years (231 women, 52%). Coronary calcium was present in 55%, mean CCS was 130.9, 46% had a plaque with lumen involvement, and mean PCS was 1.1. During follow-up, there were 17 (4%) nonfatal events and 2 (1%) fatal events. CCS was independently associated to the estimated risk and low-density lipoprotein-cholesterol life-years, sum of stenosis severity to the estimated risk, and PCS to the estimated risk and low-density lipoprotein-cholesterol life-years. CTA findings induced a positive change in patients' care and in their estimated risk. 4
8. Detrano R, Guerci AD, Carr JJ, et al. Coronary calcium as a predictor of coronary events in four racial or ethnic groups. N Engl J Med 2008;358:1336-45. Observational-Dx 6,722 patients To determine whether coronary-artery calcium predicts coronary heart disease in other racial or ethnic groups. There were 162 coronary events, of which 89 were major events (myocardial infarction or death from coronary heart disease). In comparison with participants with no coronary calcium, the adjusted risk of a coronary event was increased by a factor of 7.73 among participants with coronary calcium scores between 101 and 300 and by a factor of 9.67 among participants with scores above 300 (P<0.001 for both comparisons). Among the four racial and ethnic groups, a doubling of the calcium score increased the risk of a major coronary event by 15 to 35% and the risk of any coronary event by 18 to 39%. The areas under the receiver-operating-characteristic curves for the prediction of both major coronary events and any coronary event were higher when the calcium score was added to the standard risk factors. 3
9. American College of Radiology. ACR Appropriateness Criteria®: Acute Nonspecific Chest Pain—Low Probability of Coronary Artery Disease. Available at: https://acsearch.acr.org/docs/69401/Narrative/. Review/Other-Dx N/A Evidence-based guidelines to assist referring physicians and other providers in making the most appropriate imaging or treatment decision for a specific clinical condition. No abstract available. 4
10. Expert Panel on Cardiac Imaging:, Shah AB, Kirsch J, et al. ACR Appropriateness Criteria Chronic Chest Pain-Noncardiac Etiology Unlikely-Low to Intermediate Probability of Coronary Artery Disease. J. Am. Coll. Radiol.. 15(11S):S283-S290, 2018 Nov. Review/Other-Dx N/A Evidence-based guidelines to assist referring physicians and other providers in making the most appropriate imaging or treatment decision for chronic chest pain, noncardiac etiology unlikely, low to intermediate probability of coronary artery disease. No results stated in abstract. 4
11. Expert Panel on Cardiac Imaging:, Akers SR, Panchal V, et al. ACR Appropriateness Criteria Chronic Chest Pain-High Probability of Coronary Artery Disease. [Review]. J. Am. Coll. Radiol.. 14(5S):S71-S80, 2017 May. Review/Other-Dx N/A Evidence-based guidelines to assist referring physicians and other providers in making the most appropriate imaging or treatment decision for chronic chest pain, high probability of coronary artery disease/ No results stated in abstract. 4
12. Nesto RW, Kowalchuk GJ. The ischemic cascade: temporal sequence of hemodynamic, electrocardiographic and symptomatic expressions of ischemia. Am J Cardiol. 59(7):23C-30C, 1987 Mar 09. Review/Other-Dx N/A To review the pathophysiologic chain of events that occur before angina and place them in perspective. No results stated in abstract. 4
13. American College of Radiology. ACR–NASCI–SIR–SPR Practice Parameter for the Performance and Interpretation of Body Computed Tomography Angiography (CTA). Available at: https://www.acr.org/-/media/ACR/Files/Practice-Parameters/body-cta.pdf. Review/Other-Dx N/A Guidance document to promote the safe and effective use of diagnostic and therapeutic radiology by describing specific training, skills and techniques. No abstract available. 4
14. Joshi PH, Patel B, Blaha MJ, et al. Coronary artery Calcium predicts Cardiovascular events in participants with a low lifetime risk of Cardiovascular disease: The Multi-Ethnic Study of Atherosclerosis (MESA). Atherosclerosis. 246:367-73, 2016 Mar. Observational-Dx 6,814 patients To evaluate predictors for coronary heart disease (CHD) among "low lifetime risk" participants in the population-based Multi-Ethnic Study of Atherosclerosis (MESA). Over 10.4 years median follow-up, there were 33 events (2.4%) in participants with low lifetime risk. There were 479 participants (34%) with CAC>0 including 183 (13%) with CAC>100. CAC was present in 25 (76%) participants who experienced an event. In multivariable analyses, only CAC>100 remained predictive of CHD (HR 4.6; 95% CI: 1.6-13.6; p = 0.005). The event rates for CAC = 0, CAC>0 and CAC>100 were 0.9/1,000, 5.7/1,000, and 11.0/1000 person-years, respectively. The NNS to identify one participant with CAC>0 and > 100 were 3 and 7.6, respectively. 3
15. Hecht H, Blaha MJ, Berman DS, et al. Clinical indications for coronary artery calcium scoring in asymptomatic patients: Expert consensus statement from the Society of Cardiovascular Computed Tomography. [Review]. J Cardiovasc Comput Tomogr. 11(2):157-168, 2017 Mar - Apr. Review/Other-Dx N/A To summarize the available data regarding the prognostic value of  coronary artery calcium (CAC) scoring in the asymptomatic population and its ability to refine individual risk prediction, addresses the limitations identified in the current traditional risk factor-based treatment strategies recommended by the 2013 ACC/AHA Prevention guidelines including use of the Pooled Cohort Equations (PCE), and the US Preventive Services Task Force (USPSTF) Recommendation Statement for Statin Use for the Primary Prevention of Cardiovascular Disease in Adults. No results stated in abstract. 4
16. Dudum R, Dzaye O, Mirbolouk M, et al. Coronary artery calcium scoring in low risk patients with family history of coronary heart disease: Validation of the SCCT guideline approach in the coronary artery calcium consortium. J Cardiovasc Comput Tomogr. 2019 Mar 27. Observational-Dx 14,169 Patients To critically assess the unique 2017 Society of Cardiovascular Computed Tomography (SCCT) recommendation of considering Coronary Artery Calcium (CAC) scoring in low-risk individuals (< 5%) with a family history (FH) of CHD using the largest multicenter observational cohort study of CAC scoring yet assembled, the CAC Consortium. This cohort had a mean age of 48.1 (SD 7.4), was 91.3% white, 47.4% female, had an average ASCVD score of 2.3% (SD 1.3), and 59.4% had a CAC = 0. The event rate for all-cause mortality was 1.2 per 1000 person-years, 0.3 per 1000 person-years for CVD-specific mortality, and 0.2 per 1000 person-years for CHD-specific mortality. In multivariable Cox proportional hazard models, those with CAC>100 had a 2.2 (95% CI 1.5-3.3) higher risk of all-cause mortality, 4.3 (95% CI 1.9-9.5) times higher risk of CVD-specific mortality, and a 10.4 (95% CI 3.2-33.7) times higher risk of CHD-specific mortality compared to individuals with CAC = 0. The NNS to detect CAC >100 in this sample was 9. 4
17. Mitchell JD, Paisley R, Moon P, Novak E, Villines TC. Coronary Artery Calcium and Long-Term Risk of Death, Myocardial Infarction, and Stroke: The Walter Reed Cohort Study. JACC Cardiovasc Imaging. 11(12):1799-1806, 2018 12. Observational-Dx 23,637 patients To assess the long-term risk of death and atherosclerotic cardiovascular disease (ASCVD) outcomes, including stroke, in a real-world cohort that underwent coronary artery calcium (CAC) scoring. Patients (mean age 50.0 ± 8.5 years) were followed over a median of 11.4 years. The relative adjusted subhazard ratio (aSHR) for CAC 1 to 100, 101 to 400, and >400 was 2.2, 3.8, and 5.9 for MI; 1.2, 1.4, and 1.9 for stroke; 1.4, 2.0, and 2.8 for MACE; and 1.2, 1.5 and 2.1 for death (p < 0.0001). The addition of CAC score to risk factors significantly improved the prognostic accuracy for all outcomes by the likelihood ratio test. Area under the curve increased from 0.658 to 0.738 for MI, 0.703 to 0.704 for stroke, 0.685 to 0.705 for MACE, and 0.759 to 0.767 for mortality. Among subjects without traditional risk factors (n = 6,208; mean age 43.8 ± 4.4 years), the presence of any CAC (>0; n = 848) was associated with an increased risk of MACE (aSHR: 1.67; 95% confidence interval: 1.16 to 2.39). 3
18. Carr JJ, Jacobs DR Jr, Terry JG, et al. Association of Coronary Artery Calcium in Adults Aged 32 to 46 Years With Incident Coronary Heart Disease and Death. JAMA Cardiol. 2(4):391-399, 2017 04 01. Observational-Dx 5,115 patients To determine if coronary artery calcium (CAC) in adults aged 32 to 46 years is associated with incident clinical coronary heart disease (CHD), and cardiovascular disease (CVD), and all-cause mortality during 12.5 years of follow-up. At year 15 of the study among 3043 participants (mean [SD] age, 40.3 [3.6] years; 1383 men and 1660 women), 309 individuals (10.2%) had CAC, with a geometric mean Agatston score of 21.6 (interquartile range, 17.3-26.8). Participants were followed up for 12.5 years, with 57 incident CHD events and 108 incident CVD events observed. After adjusting for demographics, risk factors, and treatments, those with any CAC experienced a 5-fold increase in CHD events (hazard ratio [HR], 5.0; 95% CI, 2.8-8.7) and 3-fold increase in CVD events (HR, 3.0; 95% CI, 1.9-4.7). Within CAC score strata of 1-19, 20-99, and 100 or more, the HRs for CHD were 2.6 (95% CI, 1.0-5.7), 5.8 (95% CI, 2.6-12.1), and 9.8 (95% CI, 4.5-20.5), respectively. A CAC score of 100 or more had an incidence of 22.4 deaths per 100 participants (HR, 3.7; 95% CI, 1.5-10.0); of the 13 deaths in participants with a CAC score of 100 or more, 10 were adjudicated as CHD events. Risk factors for CVD in early adult life identified those above the median risk for developing CAC and, if applied, in a selective CAC screening strategy could reduce the number of people screened for CAC by 50% and the number imaged needed to find 1 person with CAC from 3.5 to 2.2. 3
19. Choi EK, Choi SI, Rivera JJ, et al. Coronary computed tomography angiography as a screening tool for the detection of occult coronary artery disease in asymptomatic individuals. J Am Coll Cardiol. 2008;52(5):357-365. Review/Other-Dx 1,000 consecutive subjects To evaluate the prevalence of occult CAD with CCTA to characterize plaque composition and to evaluate the potential of this new technology to impact risk stratification in asymptomatic middle-aged subjects. 52 (5%) subjects had significant =50%) diameter stenosis and 21 (2%) had severe (=75%) stenosis. 13 (25%) and 30 (58%) subjects with significant stenosis were classified into National Cholesterol Education Program low-risk and mild coronary calcification (CACSs <100), respectively. Midterm follow-up (17 +/- 2 months) revealed 15 cardiac events only in those with CAD on CCTA: 1 unstable angina requiring hospital stay and 14 revascularization procedures. Most (87%) events occurred within 90 days of index CCTA. 4
20. Heijenbrok-Kal MH, Fleischmann KE, Hunink MG. Stress echocardiography, stress single-photon-emission computed tomography and electron beam computed tomography for the assessment of coronary artery disease: a meta-analysis of diagnostic performance. Am Heart J 2007;154:415-23. Meta-analysis 351 patients, 11 meta-analyses To review the literature on noninvasive imaging tests (stress echocardiography, stress single-photon-emission computed tomography (SPECT), and electron beam computed tomography (EBCT)) for the diagnosis of coronary artery disease, to compare the diagnostic performance of the tests, and to identify study characteristics that may influence the diagnostic performance. We analyzed the data of 351 patient series, which were reported in 11 meta-analyses. The sensitivity of EBCT was significantly higher than that of stress SPECT, which had a significantly higher sensitivity than stress echocardiography (respectively, 93.1% [95% confidence interval, 90.7-95.6], 88.1 [95% confidence interval, 86.6-89.6], and 79.1% [95% confidence interval, 77.6-80.5]). The specificity of stress echocardiography was significantly higher than that of stress SPECT, which had a significantly higher specificity than EBCT (respectively, 87.1% [95% confidence interval, 85.7-88.5], 73.0% [95% confidence interval, 69.1-76.9], and 54.5% [95% confidence interval, 45.3-63.8]). The diagnostic odds ratios did not differ significantly between the 3 modalities, which resulted in one underlying summary receiver operating characteristic curve. Good
21. Song KD, Kim SM, Choe YH, et al. Integrated cardiac magnetic resonance imaging with coronary magnetic resonance angiography, stress-perfusion, and delayed-enhancement imaging for the detection of occult coronary artery disease in asymptomatic individuals. Int J Cardiovasc Imaging. 31 Suppl 1:77-89, 2015 Jun. Observational-Dx 341 patients To evaluate the feasibility of using coronary magnetic resonance angiography (CMRA) with stress-perfusion and delayed-enhancement MRI as a screening tool for the detection of coronary artery disease (CAD) in asymptomatic subjects. The occurrence of new chest pain and cardiac events was assessed in 332 subjects (97.3 %) over an average 29 ± 6 months (range, 18–39 months) follow-up period. A total of 3296 (82.4 %) of 4000 coronary artery segments examined exhibited diagnostic image quality on combined whole-heart and volume-targeted CMRA. Combined MRI detected significant CADs in 13 (3.8 %) of 341 subjects. Among these, 11 subjects (84.6 %) had both coronary artery stenosis (=50 % by diameter) on CMRA and stress-perfusion defects in corresponding areas. Five of the 13 subjects showed evidence of old myocardial infarctions on delayed-enhancement MRI. Three subjects (0.9 %) underwent percutaneous coronary intervention after CAD was detected on cardiac MRI. There were no cardiac events during the follow-up period in subjects who complied with follow-up. Normal stress-perfusion and delayed-enhancement MRI lead to excellent outcomes when used to predict future cardiac events in asymptomatic subjects. 4
22. Weir-McCall JR, Fitzgerald K, Papagiorcopulo CJ, et al. Prevalence of unrecognized myocardial infarction in a low-intermediate risk asymptomatic cohort and its relation to systemic atherosclerosis. Eur Heart J Cardiovasc Imaging 2017;18:657-62. Review/Other-Dx 1,529 patients (931 females, 577 males) To ascertain the prevalence of unrecognized myocardial infarctions (UMIs) in a non-high-risk population using magnetic resonance imaging (MRI). A total of 5000 volunteers aged >40 years with no history of CVD and a 10-year risk of CVD of <20%, as assessed by the ATP-III risk score, were recruited to the Tayside Screening for Cardiac Events study. Those with a B-type natriuretic peptide (BNP) level greater than their gender-specific median were invited for a whole-body MR angiogram and cardiac MR including LGE assessment. LGE was classed as absent, UMI, or non-specific. A total of 1529 volunteers completed the imaging study; of these, 53 (3.6%) were excluded because of either missing data or inadequate LGE image quality. Ten of the remaining 1476 (0.67%) displayed LGE. Of these, three (0.2%) were consistent with UMI, whereas seven were non-specific occurring in the mid-myocardium (n = 4), epicardium (n = 1), or right ventricular insertion points (n = 2). Those with UMI had a significantly higher BNP [median 116 (range 31–133) vs. 22.6 (5–175) pg/mL, P = 0.015], lower ejection fraction [54.6 (36–62) vs. 68.9 (38–89)%, P = 0.007], and larger end-systolic volume [36.3 (27–61) vs. 21.7 (5–65) mL/m2, P = 0.014]. Those with non-specific LGE had lower diastolic blood pressure [68 (54–70) vs. 72 (46–98) mmHg, P = 0.013] but no differences in their cardiac function. 4
23. Mordi IR, Badar AA, Irving RJ, Weir-McCall JR, Houston JG, Lang CC. Efficacy of noninvasive cardiac imaging tests in diagnosis and management of stable coronary artery disease. Vasc Health Risk Manag 2017;13:427-37. Review/Other-Dx N/A To discuss the current literature regarding the utility of noninvasive imaging in diagnosis and management of stable coronary artery disease (CAD) including recent data from large randomized trials assessing diagnosis and prognosis. Current guidelines recommend revascularization in patients with refractory angina and in those with potential prognostic benefit. Appropriate risk stratification through noninvasive assessment is important in ensuring patients are not exposed to unnecessary invasive coronary angiograms. The past 20 years have seen an unprecedented expansion in noninvasive imaging modalities for the assessment of stable CAD, with cardiovascular magnetic resonance and computed tomography complementing established techniques such as myocardial perfusion imaging, echocardiography and exercise electrocardiogram. 4
24. Kondos GT, Hoff JA, Sevrukov A, et al. Electron-beam tomography coronary artery calcium and cardiac events: a 37-month follow-up of 5635 initially asymptomatic low- to intermediate-risk adults. Circulation. 2003;107(20):2571-2576. Observational-Dx 8,855 patients To examine the association between electron beam tomography (EBT) coronary artery calcium (CAC) and cardiac events in initially asymptomatic low- to intermediate-risk individuals, with adjustment for the presence of hypercholesterolemia, hypertension, diabetes, and a history of cigarette smoking. Conventional CAD risk factors were elicited by use of a questionnaire. After 37 +/- 12 months, information on the occurrence of cardiac events was collected and confirmed by use of medical records and death certificates. In men, events (n=192) were associated with the presence of CAC (RR=10.5, P<0.001), diabetes (RR=1.98, P=0.008), and smoking (RR=1.4, P=0.025), whereas in women, events (n=32) were linked to the presence of CAC (RR=2.6, P=0.037) and not risk factors. The presence of CAC provided incremental prognostic information in addition to age and other risk factors. 4
25. Shaw LJ, Raggi P, Schisterman E, Berman DS, Callister TQ. Prognostic value of cardiac risk factors and coronary artery calcium screening for all-cause mortality. Radiology. 2003;228(3):826-833. Observational-Dx 10,377 asymptomatic patients To develop risk-adjusted multivariable models that included risk factors and coronary calcium scores determined with electronic beam computed tomography (EBCT) in asymptomatic patients for the prediction of all-cause mortality. During a mean follow-up of 5.0 years +/- 0.0086 (standard error of the mean), the death rate was 2.4%. In a risk-adjusted model (model chi2 = 388.2, P<.001), coronary calcium was an independent predictor of mortality (P<.001). Risk-adjusted RR values for coronary calcium were 1.64, 1.74, 2.54, and 4.03 for scores of 11-100, 101-400, 401-1,000, and greater than 1,000, respectively (P<.001 for all values), as compared with that for a score of 10 or less. 5-year risk-adjusted survival was 99.0% for a calcium score of 10 or less and 95.0% for a score of greater than 1,000 (P<.001). With a ROC curve, the concordance index increased from 0.72 for cardiac risk factors alone to 0.78 (P<.001) when the calcium score was added to a multivariable model for prediction of death. 3
26. Budoff MJ, Shaw LJ, Liu ST, et al. Long-term prognosis associated with coronary calcification: observations from a registry of 25,253 patients. J Am Coll Cardiol. 2007;49(18):1860-1870. Observational-Dx 25,253 consecutive asymptomatic individuals To develop risk-adjusted multivariable models that include risk factors and CACSs measured with EBCT in asymptomatic patients for the prediction of all-cause mortality. The frequency of CACSs was 44%, 14%, 20%, 13%, 6%, and 4% for scores of 0, 1 to 10, 11 to 100, 101 to 400, 401 to 1,000, and >1,000, respectively. During a mean follow-up of 6.8 +/- 3 years, the death rate was 2% (510 deaths). The CAC was an independent predictor of mortality in a multivariable model controlling for age, gender, ethnicity, and cardiac risk factors (model chi-square = 2,017, P<0.0001). The addition of CAC to traditional risk factors increased the concordance index significantly (0.61 for risk factors vs 0.81 for the CACS, P<0.0001). Risk-adjusted RR ratios for CAC were 2.2-, 4.5-, 6.4-, 9.2-, 10.4-, and 12.5-fold for scores of 11 to 100, 101 to 299, 300 to 399, 400 to 699, 700 to 999, and >1,000, respectively (P<0.0001), when compared with a score of 0. 10-year survival (after adjustment for risk factors, including age) was 99.4% for a CACS of 0 and worsened to 87.8% for a score of >1,000 (P<0.0001). 3
27. Okwuosa TM, Greenland P, Ning H, Liu K, Lloyd-Jones DM. Yield of screening for coronary artery calcium in early middle-age adults based on the 10-year Framingham Risk Score: the CARDIA study. JACC Cardiovasc Imaging. 5(9):923-30, 2012 Sep. Review/Other-Dx 2,832 patients To assess the prevalence and distribution of coronary artery calcium (CAC) across Framingham Risk Score (FRS) strata and therefore determine FRS levels at which asymptomatic, young to early middle-age individuals could potentially benefit from CAC screening. CAC scores >0 and =100 were present in 9.9% and 1.8% of participants, respectively. CAC prevalence and amount increased across higher FRS strata. A CAC score >0 was observed in 7.3%, 20.2%, 19.1%, and 44.8% of individuals with FRSs of 0 to 2.5%, 2.6% to 5%, 5.1% to 10%, and >10%, respectively (NNS = 14, 5, 5, and 2, respectively). A CAC score of =100 was observed in 1.3%, 2.4%, and 3.5% of those with FRSs of 0 to 2.5%, 2.6% to 5%, and 5.1% to 10%, respectively (NNS = 79, 41, and 29, respectively), but in 17.2% of those with an FRS >10% (NNS = 6). Similar trends were observed when findings were stratified by sex and race. 4
28. Gibson AO, Blaha MJ, Arnan MK, et al. Coronary artery calcium and incident cerebrovascular events in an asymptomatic cohort. The MESA Study. JACC Cardiovasc Imaging. 7(11):1108-15, 2014 Nov. Observational-Dx 6,779 patients To examine the relationship of coronary artery calcium (CAC) measured during the baseline examination to adjudicated cerebrovascular events (CVE) in participants of the MESA (Multi-Ethnic Study of Atherosclerosis) over a 10-year follow-up. During the follow-up, 234 (3.5%) adjudicated CVE occurred. In Kaplan-Meier analysis, the presence of CAC was associated with a lower CVE event-free survival versus the absence of CAC (log-rank chi-square: 59.8, p < 0.0001). Log-transformed CAC was associated with increased risk for CVE after adjusting for age, sex, race/ethnicity, body mass index, systolic and diastolic blood pressure, total cholesterol, high-density lipoprotein cholesterol, cigarette smoking status, blood pressure medication use, statin use, and interim atrial fibrillation (hazard ratio [HR]: 1.13 [95% confidence interval (CI): 1.07 to 1.20], p < 0.0001). The American College of Cardiology/American Heart Association–recommended CAC cutoff was also an independent predictor of CVE and strokes (HR: 1.70 [95% CI: 1.24 to 2.35], p = 0.001, and HR: 1.59 [95% CI: 1.11 to 2.27], p = 0.01, respectively). CAC was an independent predictor of CVE when analysis was stratified by sex or race/ethnicity and improved discrimination for CVE when added to the full model (c-statistic: 0.744 vs. 0.755). CAC also improved the discriminative ability of the Framingham stroke risk score for CVE. 3
29. Polonsky TS, McClelland RL, Jorgensen NW, et al. Coronary artery calcium score and risk classification for coronary heart disease prediction. JAMA. 2010;303(16):1610-1616. Observational-Dx 6,814 patients To determine whether adding coronary artery calcium score (CACS) to a prediction model based on traditional risk factors improves classification of risk. During a medium of 5.8 years of follow-up among a final cohort of 5,878, 209 CHD events occurred, of which 122 were MI, death from CHD, or resuscitated cardiac arrest. Model 2 resulted in significant improvements in risk prediction compared with model 1 (net reclassification improvement = 0.25; 95% CI, 0.16-0.34; P<.001). In model 1, 69% of the cohort was classified in the highest or lowest risk categories compared with 77% in model 2. An additional 23% of those who experienced events were reclassified as high risk, and an additional 13% without events were reclassified as low risk using model 2. 3
30. Erbel R, Mohlenkamp S, Moebus S, et al. Coronary risk stratification, discrimination, and reclassification improvement based on quantification of subclinical coronary atherosclerosis: the Heinz Nixdorf Recall study. J Am Coll Cardiol. 2010;56(17):1397-1406. Observational-Dx 4,129 patients To determine net reclassification improvement and improved risk prediction based on CAC scoring in comparison with traditional risk factors. After 5 years of follow-up, 93 coronary deaths and nonfatal MIs occurred (cumulative risk 2.3%; 95% CI: 1.8% to 2.8%). Reclassifying intermediate (defined as 10% to 20% and 6% to 20%) risk subjects with CAC <100 to the low-risk category and with CAC =400 to the high-risk category yielded a net reclassification improvement of 21.7% (P=0.0002) and 30.6% (P<0.0001) for the Framingham Risk Score, respectively. Integrated discrimination improvement using Framingham Risk Score variables and CAC was 1.52% (P<0.0001). Adding CACSs to the Framingham Risk Score and National Cholesterol Education Panel ATP III categories improved the area under the curve from 0.681 to 0.749 (P<0.003) and from 0.653 to 0.755 (P=0.0001), respectively. 3
31. Mulders TA, Taraboanta C, Franken LC, et al. Coronary artery calcification score as tool for risk assessment among families with premature coronary artery disease. Atherosclerosis. 245:155-60, 2016 Feb. Observational-Dx 704 patients To use coronary artery calcification score as a tool for risk assessment among families with premature coronary artery disease. Individuals with a family history (FamHis) for CAD had an increased risk for elevated CACS (adjusted odds ratio (OR) 2.23 (95% CI 1.48–3.36); p < 0.05), compared to those without a FamHis. In the prospective study (3.5 years follow-up), the event rate equally low in those with a positive FamHis and a negative FamHis (0% vs. 1%), if they had a CAC of 0. However, in those with CACS >80th percentile, a FamHis of CAD doubled the CAD event rate (positive FamHis 12.5% vs. negative FamHis 6.8%; adjusted HR 2.08 (95% CI 1.09–3.87; p < 0.05). 3
32. Nasir K, Rubin J, Blaha MJ, et al. Interplay of coronary artery calcification and traditional risk factors for the prediction of all-cause mortality in asymptomatic individuals. Circ Cardiovasc Imaging. 5(4):467-73, 2012 Jul. Observational-Dx 44,052 patients To examine the relationship between the presence and burden of traditional risk factors (RFs) and coronary artery calcium (CAC) for the prediction of all-cause mortality. The following RFs were considered: (1) current cigarette smoking, (2) dyslipidemia, (3) diabetes mellitus, (4) hypertension, and (5) family history of coronary heart disease. Patients were followed for a mean of 5.6±2.6 years for the primary end point of all-cause mortality. Among individuals who had no RF, Cox proportional model adjusted for age and sex identified that increasing CAC scores were associated with 3.00- to 13.38-fold higher mortality risk. The lowest survival rate was observed in those with no CAC and no RF, whereas those with CAC=400 and =3 RFs had the highest all-cause fatality rate. Notably, individuals with no RF and CAC=400 had a substantially higher mortality rate compared with individuals with =3 RFs in the absence of CAC (16.89 versus 2.72 per 1000 person-years). 3
33. Di Cesare E, Patriarca L, Panebianco L, et al. Coronary computed tomography angiography in the evaluation of intermediate risk asymptomatic individuals. Radiol Med (Torino). 123(9):686-694, 2018 Sep. Review/Other-Dx 185 Patients To assess the prevalence of coronary artery disease (CAD) detected by coronary computed tomography angiography (CCTA) in asymptomatic patients with an intermediate risk of CAD. Atherosclerotic plaques were present in 112 out of 185 patients (60.5%); 56 subjects (30.2%) had mild stenosis, 49 (26.5%) moderate stenosis, only 3 patients (1.6%) had severe stenosis and in 4 cases (2.2%) the "blooming effect" did not allow for evaluation of the degree of stenosis. Among the positive cases, a high number of patients (44.6%) [50] showed coronary artery disease in one vessel, 33 patients (29.4%) in two vessels, 22 patients (19.6%) in three vessels and 5 patients in four vessels or more (4.5%). Patients with moderate stenosis were older, had hypertension in most cases, higher total cholesterol levels and more often were smokers. The radiation dose (mSv) dispensed to the patients was 3.7?±?1.6 mSv. 4
34. Picano E, Molinaro S, Pasanisi E. The diagnostic accuracy of pharmacological stress echocardiography for the assessment of coronary artery disease: a meta-analysis. Cardiovasc Ultrasound 2008;6:30. Meta-analysis 5 studies; 435 patients To evaluate the diagnostic accuracy of dobutamine versus dipyridamole stress echocardiography through an evidence-based approach. The 5 analyzed papers recruited 435 patients, 299 with and 136 without angiographically assessed coronary artery disease (quantitatively assessed stenosis > 50%). Dipyridamole and dobutamine showed similar accuracy (87%, 95% confidence intervals, CI, 83-90, vs. 84%, CI, 80-88, p = 0.48), sensitivity (85%, CI 80-89, vs. 86%, CI 78-91, p = 0.81) and specificity (89%, CI 82-94 vs. 86%, CI 75-89, p = 0.15). M
35. Cruz G, Atkinson D, Henningsson M, Botnar RM, Prieto C. Highly efficient nonrigid motion-corrected 3D whole-heart coronary vessel wall imaging. Magn Reson Med 2017;77:1894-908. Observational-Dx N/A To develop a respiratory motion correction framework to accelerate free-breathing three-dimensional (3D) whole-heart coronary lumen and coronary vessel wall magnetic resonance imaging (MRI). No significant differences (P>0.01) were found between the proposed method and the gated and tracked scan for coronary lumen, despite an average improvement in scan efficiency to 96% from 59%. Significant differences (P<0.01) were found in right coronary artery vessel wall thickness, right coronary artery vessel wall sharpness, and vessel wall visual score between the proposed method and translational correction (TC). 3
36. Moghari MH, Roujol S, Henningsson M, et al. Three-dimensional heart locator for whole-heart coronary magnetic resonance angiography. Magn Reson Med 2014;71:2118-26. Observational-Dx 9 patients To implement and validate a motion compensation technique based on three-dimensional (3D) spatial registration in which data are accepted throughout the respiratory cycle. There was no significant difference between the subjective image score of diaphragmatic navigator (NAV) and low-resolution 3D-image of the heart (3D-LOC) in three main coronary branches. The vessel sharpness of 3D-LOC was higher than NAV in the right (0.44 ± 0.08 vs. 0.49 ±.08; P=0.055) and left circumflex arteries (0.49 ± 0.05 vs. 0.52 ± 0.04; P=0.039). Scan time for 3D-LOC was significantly shorter than NAV (4.3 ± 0.6 vs. 8.3 ± 2.3 min; P=0.004). 3
37. Schwitter J, Wacker CM, Wilke N, et al. MR-IMPACT II: Magnetic Resonance Imaging for Myocardial Perfusion Assessment in Coronary artery disease Trial: perfusion-cardiac magnetic resonance vs. single-photon emission computed tomography for the detection of coronary artery disease: a comparative multicentre, multivendor trial. Eur Heart J. 2013;34(10):775-781. Observational-Tx 533 patients To compare the diagnostic performance of perfusion-CMR and SPECT for the detection of coronary artery disease (CAD) using conventional X-ray coronary angiography (CXA) as the reference standard. The prevalence of CAD in the sample was 49%. Drop-out rates for CMR and SPECT were 5.6 and 3.7%, respectively (P = 0.21). The primary endpoint was non-inferiority of CMR vs. SPECT for both sensitivity and specificity for the detection of CAD. Readers were blinded vs. clinical data, CXA, and imaging results. As a secondary endpoint, the safety profile of the CMR examination was evaluated. For CMR and SPECT, the sensitivity scores were 0.67 and 0.59, respectively, with the lower confidence level for the difference of +0.02, indicating superiority of CMR over SPECT. The specificity scores for CMR and SPECT were 0.61 and 0.72, respectively (lower confidence level for the difference: -0.17), indicating inferiority of CMR vs. SPECT. No severe adverse events occurred in the 515 patients. 2
38. Hendel RC, Abbott BG, Bateman TM, et al. The role of radionuclide myocardial perfusion imaging for asymptomatic individuals. J Nucl Cardiol 2011;18:3-15. Review/Other-Dx N/A To review evidence for the use of radionuclide myocardial perfusion imaging (RMPI) specifically for asymptomatic individuals in an attempt to provide guidance for clinicians. No results stated in abstract. 4
39. Multimodality Writing Group for Stable Ischemic Heart Disease, Wolk MJ, Bailey SR, et al. ACCF/AHA/ASE/ASNC/HFSA/HRS/SCAI/SCCT/SCMR/STS 2013 multimodality appropriate use criteria for the detection and risk assessment of stable ischemic heart disease: a report of the American College of Cardiology Foundation Appropriate Use Criteria Task Force, American Heart Association, American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Failure Society of America, Heart Rhythm Society, Society for Cardiovascular Angiography and Interventions, Society of Cardiovascular Computed Tomography, Society for Cardiovascular Magnetic Resonance, and Society of Thoracic Surgeons. [Review]. J Card Fail. 20(2):65-90, 2014 Feb. Review/Other-Dx N/A To provide an update of the prior appropriate use criteria published for radionuclide imaging (RNI), stress echocardiography (Echo), calcium scoring, coronary computed tomography angiography (CCTA), stress cardiac magnetic resonance (CMR), and invasive coronary angiography for stable ischemic heart disease (SIHD). No results stated in abstract. 4
40. Sarwar A, Shaw LJ, Shapiro MD, et al. Diagnostic and prognostic value of absence of coronary artery calcification. JACC Cardiovasc Imaging. 2009;2(6):675-688. Review/Other-Dx 49 studies To systematically assessed the diagnostic and prognostic value of absence of coronary artery calcification (CAC) in asymptomatic and symptomatic individuals. A systematic review of published articles revealed 49 studies that fulfilled our criteria for inclusion. These included 13 studies assessing the relationship of CAC with adverse cardiovascular outcomes in 64,873 asymptomatic patients. In this cohort, 146 of 25,903 patients without CAC (0.56%) had a cardiovascular event during a mean follow-up period of 51 months. In the 7 studies assessing the prognostic value of CAC in a symptomatic population, 1.80% of patients without CAC had a cardiovascular event. Overall, 18 studies demonstrated that the presence of any CAC had a pooled sensitivity and negative predictive value of 98% and 93%, respectively, for detection of significant coronary artery disease on invasive coronary angiography. In 4,870 individuals undergoing myocardial perfusion and CAC testing, in the absence of CAC, only 6% demonstrated any sign of ischemia. Finally, 3 studies demonstrated that absence of CAC had a negative predictive value of 99% for ruling out acute coronary syndrome. 4
41. Blaha MJ, Budoff MJ, DeFilippis AP, et al. Associations between C-reactive protein, coronary artery calcium, and cardiovascular events: implications for the JUPITER population from MESA, a population-based cohort study. Lancet. 378(9792):684-92, 2011 Aug 20. Observational-Dx 2,083 participants To determine whether coronary artery calcification (CAC) testing might identify a subgroup of JUPITER-eligible patients expected to derive the most, and the least, benefit from statin treatment.to directly compare CAC versus hsCRP as additional markers for discriminating risk in otherwise JUPITER-eligible individual independent of hsCRP inclusion criteria. Median follow-up was 5·8 years (IQR 5·7-5·9). 444 (47%) patients in the MESA JUPITER population had CAC scores of 0 and, in this group, rates of coronary heart disease events were 0·8 per 1000 person-years. 74% of all coronary events were in the 239 (25%) of participants with CAC scores of more than 100 (20·2 per 1000 person-years). For coronary heart disease, the predicted 5-year NNT was 549 for CAC score 0, 94 for scores 1-100, and 24 for scores greater than 100. For cardiovascular disease, the NNT was 124, 54, and 19. In the total study population, presence of CAC was associated with a hazard ratio of 4·29 (95% CI 1·99-9·25) for coronary heart disease, and of 2·57 (1·48-4·48) for cardiovascular disease. hsCRP was not associated with either disease after multivariable adjustment. 4
42. Cho I, Chang HJ, O Hartaigh B, et al. Incremental prognostic utility of coronary CT angiography for asymptomatic patients based upon extent and severity of coronary artery calcium: results from the COronary CT Angiography EvaluatioN For Clinical Outcomes InteRnational Multicenter (CONFIRM) study.[Erratum appears in Eur Heart J. 2015 Dec 7;36(46):3287; PMID: 26063448]. Eur Heart J. 36(8):501-8, 2015 Feb 21. Observational-Dx 3,217 patients To determine the prognostic value of coronary CT angiography (CCTA) according to varying coronary artery calcium score (CACS) categories in a population of asymptomatic patients. From a 12-centre, 6-country observational registry, 3217 asymptomatic individuals without known coronary artery disease (CAD) underwent CACS and CCTA. Individuals were categorized by CACS as: 0–10, 11–100, 101–400, 401–1000, >1000. For CCTA analysis, the number of obstructive vessels—as defined by the per-patient presence of a =50% luminal stenosis—was used to grade the extent and severity of CAD. The incremental prognostic value of CCTA over and above FRS was measured by the likelihood ratio (LR) ?2, C-statistic, and continuous net reclassification improvement (NRI) for prediction, discrimination, and reclassification of all-cause mortality and non-fatal myocardial infarction. During a median follow-up of 24 months (25th–75th percentile, 17–30 months), there were 58 composite end-points. The incremental value of CCTA over FRS was demonstrated in individuals with CACS >100 (LR?2, 25.34; increment in C-statistic, 0.24; NRI, 0.62, all P < 0.001), but not among those with CACS =100 (all P > 0.05). For subgroups with CACS >100, the utility of CCTA for predicting the study end-point was evident among individuals whose CACS ranged from 101 to 400; the observed predictive benefit attenuated with increasing CACS. 2
43. Dedic A, Ten Kate GJ, Roos CJ, et al. Prognostic Value of Coronary Computed Tomography Imaging in Patients at High Risk Without Symptoms of Coronary Artery Disease. Am J Cardiol. 117(5):768-74, 2016 Mar 01. Observational-Dx 665 patients (417 men, 248 women) To determine the prognostic value of coronary computed tomography (CT) angiography (CCTA) next to the coronary artery calcium score (CACS) in patients at high cardiovascular disease (CVD) risk without symptoms suspect for coronary artery disease (CAD). A total of 665 patients at high risk (mean age 56 ± 9 years, 417 men), having at least one important CVD risk factor (diabetes mellitus, familial hypercholesterolemia, peripheral artery disease, or severe hypertension) or a calculated European systematic coronary risk evaluation of >10% were included from outpatient clinics at 2 academic centers. Follow-up was performed for the occurrence of adverse events including all-cause mortality, nonfatal myocardial infarction, unstable angina, or coronary revascularization. During a median follow-up of 3.0 (interquartile range 1.3 to 4.1) years, adverse events occurred in 40 subjects (6.0%). By multivariate analysis, adjusted for age, gender, and CACS, obstructive CAD on CCTA (=50% luminal stenosis) was a significant predictor of adverse events (hazard ratio 5.9 [CI 1.3 to 26.1]). Addition of CCTA to age, gender, plus CACS, increased the C statistic from 0.81 to 0.84 and resulted in a total net reclassification index of 0.19 (p <0.01). 2
44. Plank F, Friedrich G, Dichtl W, et al. The diagnostic and prognostic value of coronary CT angiography in asymptomatic high-risk patients: a cohort study. Open Heart. 1(1):e000096, 2014. Observational-Dx 711 patients To prospectively assess the value of coronary CT angiography (CTA) in asymptomatic patients with high 'a priori' risk of coronary artery disease (CAD). Of 711 patients, 28.3% were negative for CAD and 71.7% positive (CAD+) by CTA (15.6% had plaques without stenosis, 23.9% mild, 10.7% intermediate and 21.5% high-grade stenosis). CCS zero prevalence was 306 (43%), out of those 100 (32.7%) had non-calcified plaque only. Mean follow-up period was 2.65 years. MACE rate was 0% in CAD negative and higher (1.2%) in CAD positive by CTA. Coronary revascularisation rate was 5.5%. Patients with SIS =5 had an HR of 6.5 (95% CI 1.6 to 25.8, p<0.013) for MACE, patients with ncSIS =1 had an HR of 2.4 (95% CI 1.2 to 4.6, p<0.01) for secondary end point. The sensitivity of CTA for stenosis >50% compared with invasive angiography was 92.9% (95% CI 83.0% to 98.1%). Negative predictive value of CTA was 99.4% (95% CI 98.3% to 99.8%) for combined end points. 2
45. Min JK, Labounty TM, Gomez MJ, et al. Incremental prognostic value of coronary computed tomographic angiography over coronary artery calcium score for risk prediction of major adverse cardiac events in asymptomatic diabetic individuals. Atherosclerosis. 232(2):298-304, 2014 Feb. Observational-Dx 400 patients To determine whether coronary CT angiography (CTA)-detected coronary artery disease (CAD) enables improved risk assessment of asymptomatic diabetic individuals beyond clinical risk factors and coronary artery calcium scoring (CACS) remains unexplored. Mean age was 60.4 ± 9.9 years; 65.0% were male. At a mean follow-up 2.4 ± 1.1 years, 33 MACE occurred (13 deaths, 8 MI, 12 REV) [8.25%; annualized rate 3.4%]. By univariate analysis, per-patient maximal stenosis [hazards ratio (HR) 2.24 per stenosis grade, 95% confidence interval (CI) 1.61–3.10, p < 0.001], increasing numbers of obstructive vessels (HR 2.30 per vessel, 95% CI 1.75–3.03, p < 0.001) and segment stenosis score (HR 1.14 per segment, 95% CI 1.09–1.19, p < 0.001) were associated with increased MACE. After adjustment for CAD risk factors and CACS, maximal stenosis (HR 1.80 per grade, 95% CI 1.18–2.75, p = 0.006), number of obstructive vessels (HR 1.85 per vessel, 95% CI 1.29–2.65, p < 0.001) and segment stenosis score (HR 1.11 per segment, 95% CI 1.05–1.18, p < 0.001) were associated with increased risk of MACE. Beyond age, gender and CACS (C-index 0.64), CCTA improved discrimination by maximal stenosis, number of obstructive vessels and segment stenosis score (C-index 0.77, 0.77 and 0.78, respectively). Similarly, CCTA findings improved risk reclassification by per-patient maximal stenosis [integrated discrimination improvement (IDI) index 0.03, p = 0.03] and number of obstructive vessels (IDI index 0.06, p = 0.002), and by trend for segment stenosis score (IDI 0.03, p = 0.06). 2
46. Muhlestein JB, Lappe DL, Lima JA, et al. Effect of screening for coronary artery disease using CT angiography on mortality and cardiac events in high-risk patients with diabetes: the FACTOR-64 randomized clinical trial. JAMA. 312(21):2234-43, 2014 Dec 03. Observational-Dx 900 patients To assess whether routine screening for CAD by coronary computed tomography angiography (CCTA) in patients with type 1 or type 2 diabetes deemed to be at high cardiac risk followed by CCTA-directed therapy would reduce the risk of death and nonfatal coronary outcomes. At a mean follow-up time of 4.0 (SD, 1.7) years, the primary outcome event rates were not significantly different between the CCTA and the control groups (6.2% [28 events] vs 7.6% [34 events]; hazard ratio, 0.80 [95% CI, 0.49-1.32]; P?=?.38). The incidence of the composite secondary end point of ischemic major adverse cardiovascular events also did not differ between groups (4.4% [20 events] vs 3.8% [17 events]; hazard ratio, 1.15 [95% CI, 0.60-2.19]; P?=?.68). 3
47. Guaricci AI, Lorenzoni V, Guglielmo M, et al. Prognostic relevance of subclinical coronary and carotid atherosclerosis in a diabetic and nondiabetic asymptomatic population. Clin Cardiol. 41(6):769-777, 2018 Jun. Observational-Dx 517 patients To evaluate the incremental prognostic benefit of carotid artery disease and subclinical coronary artery disease (CAD) features in addition to clinical evaluation in an asymptomatic population. We enrolled 517 consecutive asymptomatic patients (63% male, mean age 64?±10?years; 17.6% with diabetes). Median (interquartile range) coronary artery calcium score (CACS) was 34 (0–100). Over a median follow-up of 4.4 (3.4–5.1) years, there were 53 MACE (10%). Patients experiencing MACE had higher CACS, incidence of carotid disease, presence of CAD =50%, and remodeled plaque as compared with patients without MACE. At multivariable analyses, presence of CAD =50% (HR: 5.14, 95% CI: 2.1–12.4) and percentage of segments with remodeled plaque (HR: 1.04, 95% CI: 1.03–1.06) independently predicted MACE (P?<?0.001). Models adding CAD =50% or percentage of segments with remodeled plaque resulted in higher discrimination and reclassification ability compared with a model based on 10-year FRS, carotid disease, and CACS. Specifically, the C-statistic improved to 0.75 with addition of CAD and 0.84 when adding percentage of segments with remodeled plaque, whereas net reclassification improvement indices were 0.86 and 0.92, respectively. 2
48. Halon DA, Lavi I, Barnett-Griness O, et al. Plaque Morphology as Predictor of Late Plaque Events in Patients With Asymptomatic Type 2 Diabetes: A Long-Term Observational Study. JACC Cardiovasc Imaging. 2018 May 11. Observational-Dx 630 Patients To use coronary computed tomography angiography (CTA) to determine plaque characteristics predicting individual late plaque events precipitating acute coronary syndromes (ACS) in a cohort of asymptomatic type 2 diabetic patients. Among 2,242 plaques in 499 subjects, 24 ACS culprit plaques were identified in 24 subjects during median follow-up of 9.2 years (interquartile range: 8.4 to 9.8 years). Plaque volume (upper vs. lower quartile hazard ratio [HR]: 6.9; 95% confidence interval [CI]: 1.6 to 30.8; p = 0.011), percentage of low-density plaque content <50 Hounsfield units (HR: 14.2; 95% CI: 1.9 to 108; p = 0.010), and mild plaque calcification (HR vs. all other plaques 3.3 [95% CI: 1.5 to 7.3]; p = 0.004) predicted plaque events univariately and after adjustment by clinical risk score. A culprit plaque event occurred in 13 of 376 (3.5%) high-risk plaques (HRP) (plaques with =2 risk predictors) versus 11 of 1,866 (0.6%) in non-HRPs (p < 0.0001), at 12 of 343 (3.5%) stenotic sites (=50%) versus 12 of 1,899 (0.6%) nonstenotic sites (p < 0.0001) and in 7 of 131 (5.3%) HRP with stenosis (p < 0.0001 vs. all others). In 130 (20.6%) subjects, no coronary plaque was present on baseline CTA. 3
49. Beller E, Meinel FG, Schoeppe F, et al. Predictive value of coronary computed tomography angiography in asymptomatic individuals with diabetes mellitus: Systematic review and meta-analysis. [Review]. J Cardiovasc Comput Tomogr. 12(4):320-328, 2018 Jul - Aug. Meta-analysis 10 studies (5,012 individuals) To determine if the controversial Coronary CT angiography (CTA) test which is generally not established as a screening tool for asymptomatic individuals may have a role for screening asymptomatic individuals with diabetes mellitus (DM) due to the high prevalence of asymptomatic coronary artery disease (CAD) in this subgroup. A total of 10 studies reporting on 5012 individuals with DM (median age: 62.3 years, median proportion of women: 40.5%) were included in the analysis. The presence of obstructive CAD on coronary CTA (vs. nonobstructive or no CAD) was associated with a significantly elevated risk for adverse events (summary HR: 4.07, 95% CI: 2.30 to 7.21). The estimated summary HR for non-obstructive plaque (vs. no CAD) was 2.17 (95% CI: 1.11 to 4.25). The pooled HRs per unit for segment stenosis score and segment involvement score were 1.44 (95% CI: 0.98 to 2.12), and 1.73 (95% CI: 1.07 to 2.80) respectively. On meta-regression analysis, we observed a trend towards a higher risk estimate in studies with a higher proportion of females (p=0.1063). Good
50. Takx RA, Blomberg BA, El Aidi H, et al. Diagnostic accuracy of stress myocardial perfusion imaging compared to invasive coronary angiography with fractional flow reserve meta-analysis. Circ Cardiovasc Imaging 2015;8. Meta-analysis 37 studies; 2048 patients To determine the diagnostic accuracy of myocardial perfusion imaging by single-photon emission computed tomography, echocardiography, MRI, positron emission tomography, and computed tomography compared with invasive coronary angiography with fractional flow reserve for the diagnosis of hemodynamically significant coronary artery disease. Thirty-seven studies, reporting on 4721 vessels and 2048 patients, were included. Meta-analysis yielded pooled sensitivity, pooled specificity, pooled likelihood ratios (LR), pooled diagnostic odds ratio, and summary area under the receiver operating characteristic curve. The negative LR (NLR) was chosen as the primary outcome. At the vessel level, MRI (pooled NLR, 0.16; 95% confidence interval [CI], 0.13–0.21) was performed similar to computed tomography (pooled NLR, 0.22; 95% CI, 0.12–0.39) and positron emission tomography (pooled NLR, 0.15; 95% CI, 0.05–0.44), and better than single-photon emission computed tomography (pooled NLR, 0.47; 95% CI, 0.37–0.59). At the patient level, MRI (pooled NLR, 0.14; 95% CI, 0.10–0.18) performed similar to computed tomography (pooled NLR, 0.12; 95% CI, 0.04–0.33) and positron emission tomography (pooled NLR, 0.14; 95% CI, 0.02–0.87), and better than single-photon emission computed tomography (pooled NLR, 0.39; 95% CI, 0.27–0.55) and echocardiography (pooled NLR, 0.42; 95% CI, 0.30–0.59). Good
51. Young LH, Wackers FJ, Chyun DA, et al. Cardiac outcomes after screening for asymptomatic coronary artery disease in patients with type 2 diabetes: the DIAD study: a randomized controlled trial. JAMA. 2009;301(15):1547-1555. Experimental-Dx 1.123 patients To assess whether routine screening for CAD identifies patients with type 2 diabetes as being at high cardiac risk and whether it affects their cardiac outcomes. The cumulative cardiac event rate was 2.9% over a mean (SD) follow-up of 4.8 (0.9) years for an average of 0.6% per year. 7 nonfatal MIs and 8 cardiac deaths (2.7%) occurred among the screened group and 10 nonfatal MIs and 7 cardiac deaths (3.0%) among the not-screened group (HR, 0.88; 95% CI, 0.44-1.88; P=.73). Of those in the screened group, 409 participants with normal results and 50 with small MPI defects had lower event rates than the 33 with moderate or large MPI defects; 0.4% per year vs 2.4% per year (HR, 6.3; 95% CI, 1.9-20.1; P=.001). Nevertheless, the PPV of having moderate or large MPI defects was only 12%. The overall rate of coronary revascularization was low in both groups: 31 (5.5%) in the screened group and 44 (7.8%) in the unscreened group (HR, 0.71; 95% CI, 0.45-1.1; P=.14). During the course of study there was a significant and equivalent increase in primary medical prevention in both groups. 2
52. Zellweger MJ, Maraun M, Osterhues HH, et al. Progression to overt or silent CAD in asymptomatic patients with diabetes mellitus at high coronary risk: main findings of the prospective multicenter BARDOT trial with a pilot randomized treatment substudy. JACC Cardiovasc Imaging. 7(10):1001-10, 2014 Oct. Observational-Tx 400 patients To evaluate prevalence, progression, treatment, and outcome of silent coronary artery disease (CAD) in asymptomatic patients with diabetes (DM) at high coronary risk. An abnormal myocardial perfusion single-photon emission computed tomography (MPS) was found in 87 of 400 patients (22%). In patients with normal MPS, major adverse cardiac events (MACE) occurred in 2.9% and ischemia or new scar in 3.2%. Patients with abnormal MPS had more MACE (9.8%; hazard ratio: 3.44; 95% confidence interval [CI]: 1.32 to 8.95; p ¼ 0.011) and ischemia or new scar (34.2%; odds ratio: 15.91; 95% CI: 7.24 to 38.03; p < 0.001) despite therapy, resulting in “overt or silent CAD  progression” of 35.6% versus 4.6% (odds ratio: 11.53; 95% CI: 5.63 to 24.70; p < 0.001). Patients with abnormal MPS randomized to medical versus invasive medical strategies had similar event rates (p ¼ 0.215), but more ischemic or new scar findings (54.3% vs. 15.8%; p < 0.001). 1
53. Budoff MJ, Raggi P, Beller GA, et al. Noninvasive Cardiovascular Risk Assessment of the Asymptomatic Diabetic Patient: The Imaging Council of the American College of Cardiology. [Review]. JACC Cardiovasc Imaging. 9(2):176-92, 2016 Feb. Review/Other-Dx N/A To review the evidence regarding the use of noninvasive testing to stratify asymptomatic patients with diabetes with regard to coronary heart disease(CHD) risk. No results stated in abstract. 4
54. American College of Radiology. ACR Appropriateness Criteria® Radiation Dose Assessment Introduction. Available at: https://www.acr.org/-/media/ACR/Files/Appropriateness-Criteria/RadiationDoseAssessmentIntro.pdf. Review/Other-Dx N/A To provide evidence-based guidelines on exposure of patients to ionizing radiation. No abstract available. 4
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