Addressing Knowledge Gaps in the 2013 ACC/AHA Guideline on the Assessment of Cardiovascular Risk: a Review of Recent Coronary Artery Calcium Literature
- 512 Downloads
Purpose of Review
Coronary artery calcium (CAC) has been proposed as an integrator of information from traditionally measured, non-traditionally measured, and unmeasured risk factors for coronary atherosclerosis. The 2013 American College of Cardiology/American Heart Association Guideline on the Assessment of Cardiovascular Risk identified several knowledge gaps regarding CAC, including radiation risks, cost-effectiveness, and improving discrimination and reclassification of estimated risk over the Pooled Cohort Equations in the ACC/AHA Atherosclerotic Cardiovascular Disease Estimator. In this review, we focus on recent CAC literature addressing these knowledge gaps. We further highlight the potential for CAC to enrich future randomized controlled trials.
The use of CAC allows for personalization of cardiovascular risk despite the presence or absence of traditional risk factors across many demographics. Avenues to reduce radiation exposure associated with CAC scanning include increasing the interval between scans for those with CAC scores of zero and estimating CAC from non-cardiac gated CT scans. While limited studies have suggested cost-effectiveness in cardiac risk assessment with the incorporation of CAC in screening algorithms, several studies have demonstrated the ability of CAC to identify non-traditional risk factors that may be used to expand cardiovascular risk personalization in other high-risk populations.
Literature from the past 2 years further supports CAC as a strong marker to personalize cardiac risk assessment. While multiple potential avenues to reduce radiation are available and cost-effectiveness analyses are encouraging, further studies are necessary to clarify patient selection for CAC scanning given the interplay between CAC and other imaging modalities in risk personalization algorithms.
KeywordsCoronary artery calcium Primary prevention Cardiovascular disease Risk assessment Radiation Cost-effectiveness
Coronary artery calcium
American College of Cardiology
American Heart Association
Atherosclerotic cardiovascular disease
Coronary computed tomography angiography
Multi-ethnic Study of Atherosclerosis
Myocardial perfusion imaging
Proprotein convertase subtilisin/kexin type 9
Single photon emission computed tomography
Diagnostic likelihood ratio
Area under the curve
Receiver operating statistics
Epicardial fat volume
Chronic obstructive pulmonary disease
Non-alcoholic fatty liver disease
Systemic lupus erythematous
Compliance with Ethical Standards
Conflict of Interest
Vasanth Sathiyakumar and Roger S. Blumenthal declare that they have no conflict of interest.
Khurram Nasir declares personal fees from the Advisory Board for Quest Diagnostics and from Consultant for Regeneronon.
Seth S. Martin declares grant support from PJ Schafer Cardiovascular Research Fund, American Heart Association, Aetna Foundation, CASCADE FH, Google, Apple, and the David and June Trone Family Foundation. He also declares personal fees from Abbott Nutrition, Pressed Juicery, Quest Diagnostics, Sanofi/Regeneron, Amgen, and Pew Research Center. Dr. Martin is also listed as a co-inventor on a pending patent filed by Johns Hopkins University for the novel method of low-density lipoprotein cholesterol estimation.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
- 3.Gaziano T, Reddy KS, Paccaud F, et al. Cardiovascular disease. The international bank for reconstruction and development/The World Bank. 2006.Google Scholar
- 4.Goff DC, 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(25_PA). doi: 10.1016/j.jacc.2013.11.005.
- 8.Blaha MJ, Silverman MG, Budoff MJ. Is there a role for coronary artery calcium scoring for management of asymptomatic patients at risk for coronary artery disease?: clinical risk scores are not sufficient to define primary prevention treatment strategies among asymptomatic patients. Circ Cardiovasc Imaging. 2014;7(2):398–408. doi: 10.1161/CIRCIMAGING.113.000341. discussion 408.CrossRefPubMedGoogle Scholar
- 10.Robbins JM, Petrone AB, Carr JJ, et al. Association of ideal cardiovascular health and calcified atherosclerotic plaque in the coronary arteries: the National Heart, Lung, and Blood Institute Family Heart Study. Am Heart J. 2015;169(3):371–378.e1. doi: 10.1016/j.ahj.2014.12.017.CrossRefPubMedPubMedCentralGoogle Scholar
- 12.Bensenor IM, Goulart AC, Santos IS, et al. Association between a healthy cardiovascular risk factor profile and coronary artery calcium score: results from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). Am Heart J. 2016;174:51–9. doi: 10.1016/j.ahj.2015.12.018.CrossRefPubMedGoogle Scholar
- 13.••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. 2016;246:367–73. doi: 10.1016/j.atherosclerosis.2016.01.017. In patients with no traditional cardiovascular risk factors, CAC helps further personalize risk assessment.CrossRefPubMedGoogle Scholar
- 14.••Nasir K, Bittencourt MS, Blaha MJ, et al. Implications of coronary artery calcium testing among statin candidates according to American College of Cardiology/American Heart Association cholesterol management guidelines: MESA (Multi-Ethnic Study of Atherosclerosis). J Am Coll Cardiol. 2015;66(15):1657–68. doi: 10.1016/j.jacc.2015.07.066. CAC helps further personalize cardiovascular risk assessment across all strata of ASCVD risk estimation.CrossRefPubMedGoogle Scholar
- 16.McClelland RL, Jorgensen NW, Budoff M, et al. 10-year coronary heart disease risk prediction using coronary artery calcium and traditional risk factors: derivation in the MESA (Multi-Ethnic Study of Atherosclerosis) with validation in the HNR (Heinz Nixdorf Recall) study and the DHS (Dallas Heart Study). J Am Coll Cardiol. 2015;66(15):1643–53. doi: 10.1016/j.jacc.2015.08.035.CrossRefPubMedPubMedCentralGoogle Scholar
- 19.•Valenti V, O Hartaigh B, Heo R, et al. A 15-year warranty period for asymptomatic individuals without coronary artery calcium: a prospective follow-up of 9,715 individuals. JACC Cardiovasc Imaging. 2015;8(8):900–9. doi: 10.1016/j.jcmg.2015.01.025. Suggests that patients mwith zero CAC may have a “warranty” of 15-years before repeat CAC scan.CrossRefPubMedPubMedCentralGoogle Scholar
- 24.Takx RA, Isgum I, Willemink MJ, et al. Quantification of coronary artery calcium in nongated CT to predict cardiovascular events in male lung cancer screening participants: results of the NELSON study. J Cardiovasc Comput Tomogr. 2015;9(1):50–7. doi: 10.1016/j.jcct.2014.11.006.CrossRefPubMedGoogle Scholar
- 29.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. Eur Heart J. 2015;36(8):501–8. doi: 10.1093/eurheartj/ehu358.CrossRefPubMedGoogle Scholar
- 32.Engbers EM, Timmer JR, Ottervanger JP, et al. Prognostic value of coronary artery calcium scoring in addition to single-photon emission computed tomographic myocardial perfusion imaging in symptomatic patients. Circ Cardiovasc Imaging. 2016;9(5):pii:e003966. doi: 10.1161/CIRCIMAGING.115.003966.CrossRefGoogle Scholar
- 33.•Mahabadi AA, Lehmann N, Möhlenkamp S, et al. Noncoronary measures enhance the predictive value of cardiac CT above traditional risk factors and CAC score in the general population. JACC Cardiovasc Imaging. 2016;9(10):1177–85. doi: 10.1016/j.jcmg.2015.12.024. Non-coronary values such as EFV, LA index, and TAC may suggest underlying atherosclerosis and can personalize risk assessment by identifying which patients may benefit from CAC scans.CrossRefPubMedGoogle Scholar
- 34.Brodov Y, Gransar H, Rozanski A, et al. Extensive thoracic aortic calcification is an independent predictor of development of coronary artery calcium among individuals with coronary artery calcium score of zero. Atherosclerosis. 2015;238(1):4–8. doi: 10.1016/j.atherosclerosis.2014.10.100.CrossRefPubMedGoogle Scholar
- 36.Tanami Y, Jinzaki M, Kishi S, et al. Lack of association between epicardial fat volume and extent of coronary artery calcification, severity of coronary artery disease, or presence of myocardial perfusion abnormalities in a diverse, symptomatic patient population: results from the CORE320 multicenter study. Circ Cardiovasc Imaging. 2015;8(3), e002676. doi: 10.1161/CIRCIMAGING.114.002676.CrossRefPubMedPubMedCentralGoogle Scholar
- 37.Possner M, Liga R, Gaisl T, et al. Quantification of epicardial and intrathoracic fat volume does not provide an added prognostic value as an adjunct to coronary artery calcium score and myocardial perfusion single-photon emission computed tomography. Eur Heart J Cardiovasc Imaging. 2016;17(8):885–91. doi: 10.1093/ehjci/jev209.CrossRefPubMedGoogle Scholar
- 40.Chaikriangkrai K, Velankar P, Schutt R, et al. Additive prognostic value of coronary artery calcium score over coronary computed tomographic angiography stenosis assessment in symptomatic patients without known coronary artery disease. Am J Cardiol. 2015;115(6):738–44. doi: 10.1016/j.amjcard.2014.12.032.CrossRefPubMedGoogle Scholar
- 43.Barros MV, Nunes Mdo C, Braga G, et al. Role of coronary artery calcium score for risk stratification in patients with non significant perfusion defects by myocardial perfusion single photon emission computed tomography. Cardiol J. 2015;22(3):330–5. doi: 10.5603/CJ.a2014.0084.CrossRefPubMedGoogle Scholar
- 44.Chang SM, Nabi F, Xu J, et al. Value of CACS compared with ETT and myocardial perfusion imaging for predicting long-term cardiac outcome in asymptomatic and symptomatic patients at low risk for coronary disease: clinical implications in a multimodality imaging world. JACC Cardiovasc Imaging. 2015;8(2):134–44. doi: 10.1016/j.jcmg.2014.11.008.CrossRefPubMedGoogle Scholar
- 46.Kitagawa T, Yamamoto H, Sentani K, et al. The relationship between inflammation and neoangiogenesis of epicardial adipose tissue and coronary atherosclerosis based on computed tomography analysis. Atherosclerosis. 2015;243(1):293–9. doi: 10.1016/j.atherosclerosis.2015.09.013.CrossRefPubMedGoogle Scholar
- 48.Lu MT, Park J, Ghemigian K, et al. Epicardial and paracardial adipose tissue volume and attenuation—association with high-risk coronary plaque on computed tomographic angiography in the ROMICAT II trial. Atherosclerosis. 2016;251:47–54. doi: 10.1016/j.atherosclerosis.2016.05.033.CrossRefPubMedGoogle Scholar
- 49.••Roberts ET, Horne A, Martin SS, et al. Cost-effectiveness of coronary artery calcium testing for coronary heart and cardiovascular disease risk prediction to guide statin allocation: the Multi-Ethnic Study of Atherosclerosis (MESA). PLoS One. 2015;10(3), e0116377. doi: 10.1371/journal.pone.0116377. In a modeling study, the incorporation of CAC and selectively treating patients with positive values proved to be the most cost-effective strategy.CrossRefPubMedPubMedCentralGoogle Scholar
- 50.Demir OM, Bashir A, Marshall K, et al. Comparison of clinical efficacy and cost of a cardiac imaging strategy versus a traditional exercise test strategy for the investigation of patients with suspected stable coronary artery disease. Am J Cardiol. 2015;115(12):1631–5. doi: 10.1016/j.amjcard.2015.03.005.CrossRefPubMedGoogle Scholar
- 51.Lubbers M, Dedic A, Coenen A, et al. Calcium imaging and selective computed tomography angiography in comparison to functional testing for suspected coronary artery disease: the multicentre, randomized CRESCENT trial. Eur Heart J. 2016;37(15):1232–43. doi: 10.1093/eurheartj/ehv700.CrossRefPubMedGoogle Scholar
- 56.Kaufman JD, Adar SD, Barr RG, et al. Association between air pollution and coronary artery calcification within six metropolitan areas in the USA (the Multi-Ethnic Study of Atherosclerosis and air pollution): a longitudinal cohort study. Lancet. 2016;388(10045):696–704. doi: 10.1016/S0140-6736(16)00378-0.CrossRefPubMedGoogle Scholar
- 59.Wing JJ, August E, Adar SD, et al. Change in neighborhood characteristics and change in coronary artery calcium: a longitudinal investigation in the MESA (Multi-Ethnic Study of Atherosclerosis) cohort. Circulation. 2016;134(7):504–13. doi: 10.1161/CIRCULATIONAHA.115.020534.CrossRefPubMedGoogle Scholar
- 62.Al Rifai M, Silverman MG, Nasir K, et al. The association of nonalcoholic fatty liver disease, obesity, and metabolic syndrome, with systemic inflammation and subclinical atherosclerosis: the Multi-Ethnic Study of Atherosclerosis (MESA). Atherosclerosis. 2015;239(2):629–33. doi: 10.1016/j.atherosclerosis.2015.02.011.CrossRefPubMedPubMedCentralGoogle Scholar
- 63.Miedema MD, Petrone A, Shikany JM, et al. Association of fruit and vegetable consumption during early adulthood with the prevalence of coronary artery calcium after 20 years of follow-up: the Coronary Artery Risk Development in Young Adults (CARDIA) study. Circulation. 2015;132(21):1990–8. doi: 10.1161/CIRCULATIONAHA.114.012562.CrossRefPubMedPubMedCentralGoogle Scholar
- 66.Basaria S, Harman SM, Travison TG, et al. Effects of testosterone administration for 3 years on subclinical atherosclerosis progression in older men with low or low-normal testosterone levels: a randomized clinical trial. JAMA. 2015;314(6):570–81. doi: 10.1001/jama.2015.8881.CrossRefPubMedGoogle Scholar
- 68.Kim JJ, Hwang BH, Choi IJ, et al. A prospective two-center study on the associations between microalbuminuria, coronary atherosclerosis and long-term clinical outcome in asymptomatic patients with type 2 diabetes mellitus: evaluation by coronary CT angiography. Int J Cardiovasc Imaging. 2015;31(1):193–203. doi: 10.1007/s10554-014-0541-6.CrossRefPubMedGoogle Scholar
- 75.Chow D, Young R, Valcour N, et al. HIV and coronary artery calcium score: comparison of the Hawaii aging with HIV cardiovascular study and Multi-Ethnic Study of Atherosclerosis (MESA) cohorts. HIV Clin Trials. 2015;16(4):130–8. doi: 10.1179/1528433614Z.0000000016.CrossRefPubMedPubMedCentralGoogle Scholar
- 77.Lee MK, Park HJ, Jeon WS, et al. Higher association of coronary artery calcification with non-alcoholic fatty liver disease than with abdominal obesity in middle-aged Korean men: the Kangbuk Samsung health study. Cardiovasc Diabetol. 2015;14:88. doi: 10.1186/s12933-015-0253-9.CrossRefPubMedPubMedCentralGoogle Scholar
- 86.Newallo D, Meinel FG, Schoepf UJ, et al. Mammographic detection of breast arterial calcification as an independent predictor of coronary atherosclerotic disease in a single ethnic cohort of African American women. Atherosclerosis. 2015;242(1):218–21. doi: 10.1016/j.atherosclerosis.2015.07.004.CrossRefPubMedGoogle Scholar
- 88.Metkus TS, Brown T, Budoff M, et al. HIV infection is associated with an increased prevalence of coronary noncalcified plaque among participants with a coronary artery calcium score of zero: Multicenter AIDS Cohort Study (MACS). HIV Med. 2015;16(1):635–9. doi: 10.1111/hiv.12262.CrossRefPubMedPubMedCentralGoogle Scholar