By Michael Crawford, MD
Professor of Medicine, Chief of Clinical Cardiology, University of California, San Francisco
Dr. Crawford reports no financial relationships relevant to this field of study.
SYNOPSIS: Researchers determined recently that if serial scans are performed, the most recent scan should be used for risk assessment, and the degree of CT calcium score progression adds no further prognostic information.
SOURCES: Radford NB, DeFina LF, Barlow CE, et al. Progression of CAC score and risk of incident CVD. JACC Cardiovasc Imaging 2016;9:1420-1429.
Shah PK. Temporal change in CAC score and prognosis: Follow-up score is simpler and as good as a change in score. JACC Cardiovasc Imaging 2016;9:1430-1431.
Hecht H, Chandrashekhar Y, Narula J. Coronary artery calcium progression and residual risk. JACC Cardiovasc Imaging 2016;9:1477-1479.
The clinical utility of repeat coronary CT calcium scores (CAC) in patients at risk of coronary heart disease (CHD) is unclear. Thus, investigators from the Cooper Clinic in Dallas evaluated the prospective Cooper Center Longitudinal Study database to answer this question. Since 1998, CAC was included in the clinical evaluation of patients enrolled in this study. Because the CT equipment changed significantly in 2007, only CAC data to that time are included in this analysis. Among these patients, more than 8,000 underwent at least two visits with CAC; follow-up information was available on 80% of them. Patients were excluded if they experienced revascularization within 90 days of their CT scan or between CT scans, if they suffered a cardiovascular event before their scan, or if CAC regressed by > 50 Agatston units. The final population studied was 5,933 prevention patients who were largely white and well-educated. In addition to clinical data and basic blood tests, each patient was subjected to a maximum Balke-type treadmill exercise test. Deaths were determined by the National Death Index Service and Medicare data. Other cardiovascular (CV) events were ascertained by a mailed survey, and nonresponders were contacted by phone. Hospital records were then obtained and the events adjudicated by two independent cardiologists. A CAC score > 0 was found in 48% of the subjects. The average time to the second scan was 3.5 years. Those with a CAC score were older, had a higher blood pressure and lower cardiorespiratory fitness, and were more often on a statin. After a mean follow-up of seven years after their second scan, 161 of those with CAC experienced a cardiovascular event. This rate was higher than observed in those without baseline CAC (7.7 vs. 1.4 events/1,000 patient years; P < 0.001). In those without CAC at baseline who developed CAC at the second scan, CV event rates were no different than those who maintained a 0 score. Progression of CAC was associated with CV events (hazard ratio [HR], 1.14; 95% confidence interval [CI], 1.01-1.3; P = NS) in the model that included baseline CAC, but the incremental contribution of CAC progression was small relative to the baseline CAC (chi-square 4.2 vs. 66.0). Also, CAC progression was not associated with CV events in the model using the second CAC score (HR, 1.05; 95% CI, 0.92-1.21; P = NS). The model using follow-up CAC alone predicted CV events as well as the model using baseline and progression. Adjustment for other clinical variables did not change these results. The authors concluded that if serial scans are performed, the most recent scan should be used for risk assessment, and the degree of CAC progression adds no further prognostic information.
COMMENTARY
Frequently, I see patients who have undergone a CAC in the past and now want to know if they should undergo another one to assess their progress. Since we know atherosclerosis is dynamic and often progressive, this would seem to make sense. However, current guidelines do not recommend serial CAC studies. In fact, performing CAC is a IIb recommendation in those whom the new pooled risk equation shows borderline risk. CAC clearly predicts CV events as well or better than any other approach, but unless it will change management, there is little reason to conduct a relatively expensive test with some radiation exposure, when there are other less expensive and less invasive ways to accomplish the same thing. The value of repeat or serial testing also has been explored in other studies, with mixed results. It has been concluded that atherosclerotic disease progression is inevitable, genetic, and related to the initial CAC. Several studies have shown an increase in CAC, but a paradoxical decrease in CV events. Other studies have shown that high-dose statins can reduce CAC and presumably events. These interstudy differences may relate to the stage of the disease process. It could be that in some situations, increasing CAC actually represents plaque healing and stabilization, which could be a good thing. Thus, the interpretation of changes over time in the CAC is unclear.
This study further reduces enthusiasm for serial studies. It shows that an increase in CAC over time increases risk compared to the first CAC, but not enough to overcome the predictive accuracy of the second scan alone. This result stood up no matter which of the several methods of measuring a change in CAC was used. Also, the authors considered all CV events, not just coronary events. The robust conclusion was that if your patient receives a second scan, you need only consider those results, and you don’t need to consider changes from the first scan.
There are weaknesses in this study. It involved a homogeneous population that was not randomly selected. There was a relatively short interval between the two scans (mean 3.5 years). There was no information on the details of risk factor reduction therapy. Electron beam CT was used, not the current multidetector CT. There was no follow-up in 20% of subjects. The authors excluded patients with large reductions in CAC between scans. There were a few hard endpoints observed (coronary death, myocardial infarction, and stroke; n = 55), and although the same trends were seen, CAC prediction of hard events was not statistically significant. Finally, there are no details on plaque morphology, which may be an important determinant of outcomes.
This leaves us with the question of how to measure the results of the risk-reduction therapy besides waiting for events since CAC does not seem to be the answer, and the jury is still out on low-density lipoprotein cholesterol levels.
Researchers determined recently that if serial scans are performed, the most recent scan should be used for risk assessment, and the degree of CT calcium score progression adds no further prognostic information.
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