Prognostic Value of Cardiac Risk Factors and Coronary Artery Calcium Screening for All-Cause Mortality

PURPOSE: To develop risk-adjusted multivariable models that included risk factors and coronary calcium scores determined with electron-beam computed tomography (CT) in asymptomatic patients for the prediction of all-cause mortality.

MATERIALS AND METHODS: We followed up a cohort of 10,377 asymptomatic individuals undergoing cardiac risk factor evaluation and coronary calcium screening with electron-beam CT. Multivariable Cox proportional hazards models were developed to predict all-cause mortality. Risk-adjusted models incorporated traditional risk factors for coronary disease and coronary calcium scores.

RESULTS: Cardiac risk factors such as family history of coronary disease (69%), hypercholesterolemia (62%), hypertension (44%), smoking (40%), and diabetes (9%) were prevalent. The frequency of coronary calcium scores was 57%, 20%, 14%, 6%, and 3% for scores of 10 or less, 11–100, 101–400, 401–1,000, and greater than 1,000, respectively. 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 χ2 = 388.2, P < .001), coronary calcium was an independent predictor of mortality (P < .001). Risk-adjusted relative risk 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. Five-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 receiver operating characteristic 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.

CONCLUSION: This large observational data series shows that coronary calcium provides independent incremental information in addition to traditional risk factors in the prediction of all-cause mortality.

© RSNA, 2003

References

  • 1 O’Rourke RA, Brundage BH, Froelicher VF, et al. American College of Cardiology/American Heart Association Expert Consensus document on electron-beam computed tomography for the diagnosis of coronary artery disease. Circulation 2000; 102:126-140.
  • 2 Detrano RC, Doherty TM, Davies MJ, Stary HC. Predicting coronary events with coronary calcium: pathophysiologic and clinical problems. Curr Probl Cardiol 2000; 25:374-402.
  • 3 O’Malley PG, Taylor AJ, Jackson JL, Doherty TM, Detrano RC. Prognostic value of coronary electron-beam computed tomography for coronary heart disease events in asymptomatic populations. Am J Cardiol 2000; 85:945-948.
  • 4 Raggi P. Prognostic implications of absolute and relative calcium scores. Herz 2001; 26:252-259.
  • 5 Raggi P, Cooil B, Callister TQ. Use of electron beam tomography data to develop models for the prediction of hard coronary events. Am Heart J 2001; 141:375-382.
  • 6 Raggi P, Callister TQ, Cooil B, et al. Identification of patients at increased risk of first unheralded acute myocardial infarction by electron beam computed tomography. Circulation 2000; 101:850-855.
  • 7 Shaw LJ, O’Rourke RA. The challenge of improving risk assessment in asymptomatic individuals: the additive prognostic value of electron beam tomography? J Am Coll Cardiol 2000; 36:1261-1264.
  • 8 Detrano R, Hsiai T, Wang S, et al. Prognostic value of coronary calcification and angiographic stenoses in patients undergoing coronary angiography. J Am Coll Cardiol 1996; 27:285-290.
  • 9 Arad Y, Spadaro LA, Goodman K, et al. Predictive value of electron beam computed tomography of the coronary arteries: 19-month follow-up of 1173 asymptomatic subjects. Circulation 1996; 93:1951-1953.
  • 10 Arad Y, Spadaro LA, Goodman K, Newstein D, Guerci AD. Prediction of coronary events with electron beam computed tomography. J Am Coll Cardiol 2000; 36:1253-1260.
  • 11 National Institutes of Health, National Heart, Lung, and Blood Institute. National Cholesterol Education Panel III. Available at: www.nhlbi.nih.gov/guidelines/cholesterol. Accessed June 30 2002.
  • 12 Agatston AS, Janowitz WR, Hildner FJ, Zusmer NR, Viamonte M, Jr, Detrano R. Quantification of coronary artery calcium using ultrafast computed tomography. J Am Coll Cardiol 1990; 15:827-832.
  • 13 Marwick TH, Shaw LJ, Lauer MS, et al. The noninvasive prediction of cardiac mortality in men and women with known or suspected coronary artery disease. Am J Med 1999; 106:172-178.
  • 14 Shaw LJ, Hachamovitch R, Peterson ED, et al. Using an outcomes-based approach to identify candidates for risk stratification after exercise treadmill testing. J Gen Intern Med 1999; 14:1-9.
  • 15 Shaw LJ, Peterson ED, Kesler KL, et al. Use of a prognostic treadmill score in identifying diagnostic coronary disease subgroups and altering patient management. Circulation 1998; 98:1622-1630.
  • 16 Centers for Disease Control and Prevention. National Death Index. www.cdc.gov/nchs/r&d/ndi/. Accessed January 20 2001.
  • 17 Downs JR, Clearfield M, Weis S, et al. Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFCAPS/TexCAPS—Air Force/Texas Coronary Atherosclerosis Prevention Study. JAMA 1998; 279:1615-1622.
  • 18 West of Scotland Coronary Prevention Study: identification of high-risk groups and comparison with other cardiovascular intervention trials.Lancet1996; 348:1339-1342.
  • 19 Fuster V, Badimon L, Badimon JJ, Chesebro JH. The pathogenesis of coronary artery disease and acute coronary syndromes. N Engl J Med 1992; 362:242-250.
  • 20 Fuster V. Mechanisms leading to myocardial infarction: insights from studies of vascular biology. Circulation 1994; 90:2126-2146.
  • 21 Califf RM, Armstrong PW, Carver JR, D’Agostino RB, Strauss WE. 27th Bethesda Conference: matching the intensity of risk factor management with the hazard for coronary disease events—Task Force 5: stratification of patients into high, medium and low risk subgroups for purposes of risk factor management. J Am Coll Cardiol 1996; 27:1007-1019.
  • 22 Grundy SM, Pasternak R, Greenland P, Smith S, Jr, Fuster V. Assessment of cardiovascular risk by use of multiple-risk-factor assessment equations. Circulation 1999; 34:1348-1359.
  • 23 Greenland P, Abrams J, Aurigemma GP, et al. Prevention Conference V: beyond secondary prevention—identifying the high-risk patient for primary prevention: noninvasive tests of atherosclerotic burden—Writing Group III. Circulation 2000; 101:E16-E22.
  • 24 Greenland P, Smith SC, Jr, Grundy S. Improving coronary heart disease risk assessment in asymptomatic people: role of traditional risk factors and noninvasive cardiovascular tests. Circulation 2001; 104:1863-1867.
  • 25 Becker CR, Knez A, Ohnesorge B, et al. Visualization and quantification of coronary calcifications with electron beam and spiral computed tomography. Eur Radiol 2000; 10:629-635.
  • 26 Thom TJ, Kannel WB, Silbershatz H, D’Agostino RB. Cardiovascular disease in the United States and prevention approaches. In: Fuster V, Alexander RW, O’Rourke RA, eds. Hurst’s the heart. 10th ed. New York, NY: McGraw-Hill, 2001; 3-18.
  • 27 Lloyd-Jones DM, Larson MG, Beiser A, Levy D. Lifetime risk of developing coronary disease. Lancet 1999; 353:89-92.
  • 28 Lauer MS, Blackstone EH, Young JB, Topol EJ. Cause of death in clinical research: time for a reassessment? J Am Coll Cardiol 1999; 34:618-620.
  • 29 Farb A, Burke AP, Tang AL, et al. Coronary plaque erosion without rupture into a lipid core: a frequent cause of coronary thrombosis in sudden coronary death. Circulation 1996; 93:1354-1363.
  • 30 Burke AP, Taylor A, Farb A, Malcom GT, Virmani R. Coronary calcification: insights from sudden coronary death victims. Z Kardiol 2000; 89(suppl 2):49-53.
  • 31 Schmermund A, Schwartz RS, Adamzik M, et al. Coronary atherosclerosis in unheralded sudden coronary death under age 50: histo-pathologic comparison with ’healthy’ subjects dying out of hospital. Atherosclerosis 2001; 155:499-508.
  • 32 Wahys R, Zellinger A, Raggi P. High calcium scores pose an extremely elevated risk for hard events. J Am Coll Cardiol 2002; 39:225-230.
  • 33 Furberg CD, Hennekens CH, Hulley SB, Manolio T, Psaty BM, Whelton PK. The 27th Bethesda Conference: matching the intensity of risk factor management with the hazard for coronary disease events—Task Force 2: clinical epidemiology—the conceptual basis for interpreting risk factors. J Am Coll Cardiol 1996; 25:976-978.
  • 34 Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III).JAMA2001; 285:2486-2489.
  • 35 Kannel WB, Feinleib M. Natural history of angina pectoris in the Framingham study: prognosis and survival. Am J Cardiol 1972; 29:154-163.
  • 36 Chambless LE, Heiss G, Folsom AR, et al. Association of coronary heart disease incidence with carotid arterial wall thickness and major risk factors: the atherosclerosis risk in communities (ARIC) study, 1987–1993. Am J Epidemiol 1997; 146:483-494.
  • 37 Detrano RC, Wong ND, Doherty TM, et al. Coronary calcium does not accurately predict near-term future coronary events in high-risk adults. Circulation 1999; 99:2633-2638.
  • 38 Wilson PWF, D’Agostino RB, Levy D, Belanger AM, Silbershatz H, Kannel WB. Prediction of coronary heart disease using risk factor categories. Circulation 1998; 97:1837-1847.

Article History

Published in print: Sept 2003