Response to Letter Regarding Article, “Coronary Artery Calcium: Should We Rely on This Surrogate Marker?”
Drs Schmermund and Erbel take issue with my assertion1 that coronary artery calcium (CAC) scores, as of now, are not reliable predictors of cardiac events. However, they offer no data to refute this statement. First, they correctly note that CAC is related to coronary atherosclerosis. This relation, however, does not mean CAC is a predictor of cardiac events. Indeed, as coronary atherosclerosis is so prevalent, “only a small proportion of persons with atherosclerosis and detectable coronary calcium will eventually develop clinical coronary events.”2 Therefore, although levels of coronary calcium and atherosclerosis are associated with increased cardiac events on a population level, the relationship in any individual person is weak. Indeed, calcification may stabilize atherosclerotic lesions and make them less likely to rupture and cause an acute cardiac event.
Secondly, Schmermund and Erbel argue that CAC scores add prognostic information “over and above” cardiovascular risk factors. I respectfully disagree. The great majority of cardiac events that CAC predicts3–5 are soft events—revascularizations and unstable angina. Use of such soft events as end points may be misleading. As stated in the 2000 American College of Cardiology/American Heart Association Expert Consensus document, the test result itself often determines who undergoes these procedures, and it is improper to include them as events predicted by the test.6 In addition, the high rate of revascularization after CAC testing is of concern, because no data show any benefit of revascularization in asymptomatic patients.7
Thirdly, the studies cited include no data regarding the best proof of incremental predictive value, an increase in area under the receiver operator characteristic curve for risk prediction from CAC testing that is incremental to Framingham Risk Scoring (FRS).
Finally, they seem to suggest that calcification does not correlate with cardiac events in people taking statins, but that calcification does correlate in others. Although this hypothesis is interesting, it remains untested.
We are fairly skilled at cardiac risk prediction. FRS remains the reference standard, and no test, CAC included, has been shown to significantly increase the accuracy of FRS. More importantly, additional tests such as evaluation of CAC levels have not been shown to lead to better patient outcomes. Risk factors in FRS, including high blood pressure and cholesterol levels, indisputably may be lowered to reduce cardiovascular risk. CAC cannot be treated, even if lowering CAC were shown to reduce cardiovascular risk. On one point, we are in agreement: We clearly need more epidemiological and clinical trial data on the use of CAC.
Dr Redberg has received honoraria from Medtronic and serves on the advisory board for CVTherapeutics.
Redberg RF. Coronary artery calcium: should we rely on this surrogate marker? Circulation. 2006; 113: 427–437.
Wexler L, Brundage B, Crouse J, Detrano R, Fuster V, Maddahi J, Rumberger J, Stanford W, White R, Taubert K. Coronary artery calcification: pathophysiology, epidemiology, imaging methods, and clinical implications. A statement for health professionals from the American Heart Association. Writing Group. Circulation. 1996; 94: 1175–1192.
Kondos GT, Hoff JA, Sevrukov A, Daviglus ML, Garside DB, Devries SS, Chomka EV, Liu K. 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: 2571–2576.
LaMonte MJ, FitzGerald SJ, Church TS, Barlow CE, Radford NB, Levine BD, Pippin JJ, Gibbons LW, Blair SN, Nichaman MZ. Coronary artery calcium score and coronary heart disease events in a large cohort of asymptomatic men and women. Am J Epidemiol. 2005; 162: 421–429.
O’Rourke RA, Brundage BH, Froelicher VF, Greenland P, Grundy SM, Hachamovitch R, Pohost GM, Shaw LJ, Weintraub WS, Winters WL, Jr., Forrester JS, Douglas PS, Faxon DP, Fisher JD, Gregoratos G, Hochman JS, Hutter AM Jr, Kaul S, Wolk MJ. American College of Cardiology/American Heart Association Expert Consensus document on electron-beam computed tomography for the diagnosis and prognosis of coronary artery disease. Circulation. 2000; 102: 126–140.
Curtis JP, Krumholz HM. Keeping the patient in view: defining the appropriateness of percutaneous coronary interventions. Circulation. 2004; 110: 3746–3748.