Author + information
- Received October 21, 2012
- Revision received February 5, 2013
- Accepted February 19, 2013
- Published online May 21, 2013.
- Masanao Naya, MD, PhD⁎,
- Venkatesh L. Murthy, MD, PhD⁎,†,
- Courtney R. Foster, RT‡,
- Mariya Gaber, MS‡,
- Josh Klein, BA‡,
- Jon Hainer, BS‡,
- Sharmila Dorbala, MD⁎,‡,
- Ron Blankstein, MD⁎ and
- Marcelo F. Di Carli, MD⁎,‡,⁎ ()
- ↵⁎Reprint requests and correspondence:
Dr. Marcelo F. Di Carli, Brigham and Women's Hospital, ASB L1-037C, 75 Francis Street, Boston, Massachusetts 02115
Objectives This study sought to evaluate the interrelation of atherosclerotic burden, as assessed by coronary artery calcium (CAC) score and coronary vascular function, as assessed by quantitative estimates of coronary flow reserve (CFR), with respect to prediction of clinical outcomes.
Background The contribution of coronary vascular dysfunction, atherosclerotic burden, and the 2 combined to cardiac events is unknown.
Method A total of 901 consecutive patients underwent 82Rubidium myocardial perfusion imaging (MPI) positron emission tomography (PET) and CAC scan. All patients had normal MPI. The primary endpoint was a composite of major adverse cardiac events (MACE) including cardiac death, nonfatal myocardial infarction, late revascularization, and admission for heart failure.
Results At baseline, CFR decreased (2.15 ± 0.72, 2.02 ± 0.65, and 1.88 ± 0.64, p < 0.0001) with increasing levels of CAC (0, 1 to 399, and ≥400). Over a median of 1.53 years (interquartile range: 0.77 to 2.44), there were 57 MACE. Annual risk-adjusted MACE rates were higher for patients with CFR <2.0 compared with ≥2.0 (1.9 vs. 5.5%/year, p = 0.0007) but were only borderline associated with CAC (3.1%, 3.4%, and 6.2%/year for CAC of 0, 1 to 399, and ≥400, respectively; p = 0.09). Annualized adjusted MACE was increased in the presence of impaired CFR even among patients with CAC = 0 (1.4% vs. 5.2%, p = 0.03). Cox proportional hazards analysis revealed that CFR improved model fit, risk discrimination, and risk reclassification over clinical risk, whereas CAC only modestly improved model fit without improving risk discrimination or reclassification.
Conclusions In symptomatic patients with normal MPI, global CFR but not CAC provides significant incremental risk stratification over clinical risk score for prediction of major adverse cardiac events.
The study was funded in part by grants from the U.S. National Institutes of Health (RC1 HL101060-01, T32 HL094301-01A1, and 5K23HL092299-03), and by the Society of Nuclear Medicine Wagner-Torizuka Fellowship Award (to Dr. Naya). Dr. Murthy owns equity in General Electric. Dr. Dorbala receives research grant support from Astellas Global Pharma Development and Bracco Diagnostics. Dr. Di Carli receives research grant support from Toshiba. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received October 21, 2012.
- Revision received February 5, 2013.
- Accepted February 19, 2013.
- American College of Cardiology Foundation