Author + information
- Received November 21, 2016
- Revision received March 30, 2017
- Accepted April 6, 2017
- Published online August 7, 2017.
- Michael H. Criqui, MD, MPHa,∗ (, )
- Jessica B. Knox, MD, MBA, MPHa,
- Julie O. Denenberg, MAa,
- Nketi I. Forbang, MD, MPHa,
- Robyn L. McClelland, PhDb,
- Thomas E. Novotny, MD, MPHc,
- Veit Sandfort, MDd,
- Jill Waalen, MD, MPHa,
- Michael J. Blaha, MD, MPHe and
- Matthew A. Allison, MD, MPHa
- aDepartment of Family Medicine and Public Health, University of California, San Diego, La Jolla, California
- bDepartment of Biostatistics, University of Washington, Seattle, Washington
- cDivision of Epidemiology and Biostatistics, San Diego State University, San Diego, California
- dNational Institutes of Health Clinical Center, Department of Radiology and Imaging Sciences, Bethesda, Maryland
- eJohns Hopkins Ciccarone Center for the Prevention of Heart Disease, Baltimore, Maryland
- ↵∗Address for correspondence:
Dr. Michael H. Criqui, Department of Family Medicine and Public Health, University of California San Diego, 9500 Gilman Drive #0607, La Jolla, California 92093-0607.
Objectives This study sought to determine the possibility of interactions between coronary artery calcium (CAC) volume or CAC density with each other, and with age, sex, ethnicity, the new atherosclerotic cardiovascular disease (ASCVD) risk score, diabetes status, and renal function by estimated glomerular filtration rate, and, using differing CAC scores, to determine the improvement over the ASCVD risk score in risk prediction and reclassification.
Background In MESA (Multi-Ethnic Study of Atherosclerosis), CAC volume was positively and CAC density inversely associated with cardiovascular disease (CVD) events.
Methods A total of 3,398 MESA participants free of clinical CVD but with prevalent CAC at baseline were followed for incident CVD events.
Results During a median 11.0 years of follow-up, there were 390 CVD events, 264 of which were coronary heart disease (CHD). With each SD increase of ln CAC volume (1.62), risk of CHD increased 73% (p < 0.001) and risk of CVD increased 61% (p < 0.001). Conversely, each SD increase of CAC density (0.69) was associated with 28% lower risk of CHD (p < 0.001) and 25% lower risk of CVD (p < 0.001). CAC density was inversely associated with risk at all levels of CAC volume (i.e., no interaction was present). In multivariable Cox models, significant interactions were present for CAC volume with age and ASCVD risk score for both CHD and CVD, and CAC density with ASCVD risk score for CVD. Hazard ratios were generally stronger in the lower risk groups. Receiver-operating characteristic area under the curve and Net Reclassification Index analyses showed better prediction by CAC volume than by Agatston, and the addition of CAC density to CAC volume further significantly improved prediction.
Conclusions The inverse association between CAC density and incident CHD and CVD events is robust across strata of other CVD risk factors. Added to the ASCVD risk score, CAC volume and density provided the strongest prediction for CHD and CVD events, and the highest correct reclassification.
Funding for this project comes from National Institutes of Health, National Heart, Lung, and Blood Institute (NHLBI) R01HL116395. The MESA study was supported by contracts N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, and N01-HC-95169 from the NHLBI. All authors have reported that they have no relationships relevant to the contents of this paper to disclose. Dr. Novotny is now Deputy Assistant Secretary for Health in the U.S. Department of Health and Human Services. This work was completed during his previous position as a University of California San Diego/San Diego State University Faculty member. Drs. Criqui and Knox contributed equally to this work.
- Received November 21, 2016.
- Revision received March 30, 2017.
- Accepted April 6, 2017.
- 2017 American College of Cardiology Foundation