Personal Reflections on Coronary Artery Calcium Quantitation by CT: John A. Rumberger, PhD, MD, FACC

by John A. Rumberger, PhD, MD, FACC Director of Cardiovascular Imaging, the Princeton Longevity Center

Despite a number of controversies in the past 30 years regarding clinical cardiac [i.e. heart] imaging using x-ray computed tomography [CT], we have now settled an unbelievably simple matter – CAC [coronary artery calcification] quantified by CT is a validated means to estimate global coronary artery plaque burden; furthermore, the greater the burden or the more premature its development (for gender/age) the greater the personal cardiovascular risk. But this conclusion has not been easy for many in the Cardiovascular Disease community to accept and, as I reflect on personal issues and battles, I am reminded that we go through three stages of acceptance: First, “it is not true”; Second, “it is not important”; Third, “it is not new!”

My journey with CAC began in the early 1990’s. I had been using the exciting “new” technology of Electron Beam CT (EBT) for nearly a decade. We had successfully validated during 1985-87 the ability to quantify cardiac muscle mass and ventricular volumes and my Mayo Clinic laboratory had embarked upon studies of changes in heart size and shape after a first heart attack – called ventricular remodeling.
At that time I was approached by Mr. David King, the visionary and “father” of the CAC method, regarding whether I was interested in this ‘other’ application of the EBT technology. As a traditional cardiologist, I immediately launched a diatribe about how we already knew CAC did not tell us percent stenosis [i.e. percent narrowing of the heart artery as could be done using invasive angiography] and I could not possibly see how this would be of clinical benefit. I asked him to talk to a colleague, but I was simply “not interested”. I was moving through the first phase of acceptance (or maybe rejection): “it is not true” that CAC has any clinical value.

A year later I ran across one of the Mayo Internal Medicine residents who had measured CAC using EBT in autopsy hearts. He had raw data on a computer diskette and wondered if I could help him organize the information and point towards some analytical methods. Using a spreadsheet program we looked at the paired CT calcium areas and microscopic atherosclerotic plaque areas. In a perfunctory manner, I told him that we were going to graph these data and look at the potential for some sort of correlation. I recall this moment well; frankly it was an epiphany. I displayed the graph and saw what I did not think possible; these data, of course with scatter, showed a direct and linear correlation between coronary atherosclerotic plaque and the amount of coronary artery calcification [as measured by CT] in the same heart segments. I turned to him and said “Where the hell did you get this?” Three publications later I was still amazed at what had been “discovered”.(1-3) By that time, it had been nearly 5 years since Dr. Warren Janowitz and Dr. Arthur Agatston had published their paper demonstrating the prevalence of CAC by EBT paralleled the epidemiology of adult coronary disease across age and gender.(4) After re-reviewing their data in a new light I was hooked, and did not looked back.

David King had organized a fledgling group of researchers dubbed the “calcium club” (which formed the foundation for the future development of the Society of Atherosclerotic Imaging and for the Society of Cardiovascular Computed Tomography). We had early morning meetings before each major cardiology convention [twice per year]. During these one hour meetings we presented new research, shared concerns, formed bonds, and had arguments. Our little band grew in size at each meeting. More and more data had come forth, including early data on prognostication. We realized that guidelines on CAC use and interpretation in clinical practice should be devised. It was apparent to all that the greatest use was in the asymptomatic, intermediate risk subjects, in which traditional Framingham risk remains least predictive. By Fall 1996, we had CAC scoring categories and percentile rankings for age and gender. It was my job to put this together as a manuscript. The paper was ready for journal submission by Spring 1997. Each major cardiology and internal medicine journal we contacted was not interested or had other “opinions”. It took literally three years to get the “guidelines” paper published and it appeared in the Mayo Clinic Proceedings in 1999.(5) As an interesting aside, in 2003 the then Editor of the Mayo Clinic Proceedings told me that this paper was amongst their most requested reprints.

The general interest was clearly there, but the adult cardiology community remained skeptical. For instance, there was a review by the American College of Cardiology(6) on CAC that somewhat reversed a prior publication by the American Heart Association. These controversies and concerns focused on the second phase of acceptance: “it is not important” and most certainly the prevailing opinion was that CAC was not as “good” as established Framingham risk calculations.

In 2004 and 2005 there was literally a rapid fire of publications presenting new scientific data and consensus opinions regarding CAC, each now confirming older data and guidelines while expanding the database across populations. The research confirmed CAC as THE most powerful “risk factor” in asymptomatic patients as an individual providing data actually incremental to conventional risk assessments(7-9)– especially in those 40-50% of the population seen by the Internist or Family Practitioner who fall into the “intermediate” risk group. We had come full circle; in short, “it is not new!”

As cardiac CT has now come of age and EBT has been replaced with 64+-slice MDCT (multi-detector CT) devices, the issue of CAC is now center stage, along with the ability to visualize non-calcified (“soft”) plaque and segmental coronary stenoses using intravenous contrast enhancement.

Another milestone was reached just recently with the February 2015 release of a documentary film called ‘The Widowmaker’ [Oxford, Films, London, UK] detailing the difficulties of the ‘calcium club’ to get a foot hold in preventive cardiology and early diagnosis of coronary atherosclerotic plaque versus the much more profitable world of advanced coronary disease and use of stents. The film will soon undergo global release and can be found on iTunes and Amazon. The story is worth seeing!

Cited References:
1. Simons DB, Schwartz RS, Edwards WD, Sheedy PF, Breen JF, Rumberger JA: Non Invasive Definition of Anatomic Coronary Artery Disease by Ultrafast CT: A Quantitative Pathologic Study. J Am Coll Cardiol 1992; 20: 1118 26
2. Rumberger JA, Schwartz RS, Simons DB, Sheedy PF, Edwards WD, Fitzpatrick LA: Relations of Coronary Calcium Determined by Electron Beam Computed Tomography and Lumen Narrowing Determined at Autopsy. Am J Cardiol 1994;73:1169 1173
3. Rumberger JA, Simons DB, Fitzpatrick LA, Sheedy PF, Schwartz RS: Coronary Artery Calcium Areas by Electron Beam Computed Tomography and Coronary Atherosclerotic Plaque Area: A Histopathologic Correlative Study. Circulation 1995;92:2157-2162
4. Agatston AS, Janowitz WR, Hildner FJ, Zusmer NR, Viamonte M, Detrano R: Quantification of coronary artery calcium suing Ultrafast computed tomography. J Am Coll Cardiol 1990:15:827-32
5. Rumberger JA, Brundage BH, Rader JD, Kondos G. Electron beam computed tomographic coronary calcium scanning: a review and guidelines for use in asymptomatic persons. Mayo Clin Proc 1999;74:243-252
6. O’Rourke RA, Brundage BH, Froelicker VF et at. 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
7. Arad Y, Goodman KJ, Roth M, Newstein D, Guerci AD: Coronary Calcification, Coronary Disease Risk Factors, C-Reactive Protein, and Atherosclerotic Cardiovascular Disease Events: The St. Francis Heart Study. J Am Coll Cardiol 2005; 46:173-9
8. LaMonte MJ, FitzGerald SJ, Church TS, Barlow CD, 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;162:1-9
9. Taylor AJ, Bindeman J, Feuerstein I, Cao F, Brazaitis M, O’Malley PG. Coronary Calcium Independently Predicts Incident Premature Coronary Disease Over Measured Cardiovascular Risk Factors: Mean Three-Year Outcomes in the Prospective Army Coronary Calcium (PACC) Project. J Am Coll Cardiol 2005;46:807-14