Which patients may benefit from coronary artery calcification scoring?

Improving the accuracy of risk prediction

If a patient’s 10-year coronary risk is intermediate (10% to 20%), calcification scoring can reclassify the risk as low or high in about 50% of cases and can improve the accuracy of risk prediction.^6–8

For example, Elias-Smale et al⁶ evaluated the effect of calcification scoring in 2,028 asymptomatic patients, with median follow-up of 9.2 years and 135 coronary events observed. Adding the calcification score to the Framingham model significantly improved risk classification, with a net reclassification improvement (NRI) of 0.14 (P < .01). (NRI is a measure of discriminatory performance for a diagnostic test; higher is better.⁹) Reclassification was most robust in those at intermediate risk, 52% of whom were reclassified, with 30% reclassified to low risk and 22% reclassified to high risk.

Erbel et al⁷ reported data from the Heinz Nixdorf Recall study, which used calcification scoring to estimate the NRI in 4,129 patients followed for 5 years. During this time there were 93 coronary deaths and non-fatal myocardial infarctions. The addition of the calcification score to the Framingham risk model resulted in an NRI of 0.21 (P = .0002) for patients with a risk of 6% to 20% and 0.31 (P < .0001) for those with a risk of 10% to 20%. Erbel et al also estimated the C statistic (area under the receiver operating characteristic curve; the maximum value is 1.0 and the higher the value the better) for the addition of the calcification score to the Framingham risk model and to the Adult Treatment Panel (ATP) III algorithm. They reported a significant increase of 0.681 to 0.749 with the Framingham model and 0.653 to 0.755 with the ATP III algorithm.

Polonsky et al⁸ studied a cohort of 5,878 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) and estimated the event risk using a model based on Framingham risk characteristics. When the calcification score was added to the prediction model, 26% of the sample was reclassified to a new risk category. In intermediate-risk patients, 292 (16%) were reclassified as high risk, and 712 (39%) were reclassified as low risk, achieving an NRI of 0.55 (95% confidence interval 0.41 to 0.69; P < .001). In addition, the C statistic for the prediction of cardiovascular events was 0.76 for the model based on Framingham risk characteristics and increased to 0.81 (P < .001) with the addition of calcification scoring.

Improving adherence and care

Knowing that a patient has a higher calcification score, physicians are more likely to prescribe lipid-lowering and antihypertensive drugs (Table 1),^10–12 and patients with a higher score are also more often adherent to recommendations regarding diet and exercise.¹³

Rozanski et al,¹⁴ in a randomized controlled trial, showed that measuring coronary artery calcification did not increase downstream medical spending. A modest improvement in systolic blood pressure (P = .02), serum low-density lipoprotein level (P = .04), and waist circumference (P = .01) was observed in patients who had their calcification measured. Patients with the highest scores had the greatest improvement in coronary risk factors, including blood pressure, cholesterol, weight, and regular exercise.

On the other hand, other analyses have suggested that imaging tests are not effective for motivating behavioral changes. This topic deserves more research.¹⁵

Less utility in symptomatic disease

Coronary artery calcification scoring has less clinical utility in patients who already have coronary symptoms. Villines et al¹⁶ described a cohort of 10,037 patients with coronary symptoms who underwent calcification scoring and computed tomographic coronary angiography and found that stenosis of greater than 50% was present in 3.5% of those who had a score of 0 and in 29% of those with a score higher than 0. Therefore, a score of 0 does not rule out obstructive coronary heart disease if the patient has symptoms. Conversely, these patients may still have coronary artery calcification even if perfusion stress imaging is normal,^17,18 and calcification scoring may have a role in the evaluation of equivocal stress tests.¹⁹

CALCIFICATION SCORING GUIDELINES

In their most recent (2010) joint guidelines for assessing risk of coronary heart disease in asymptomatic patients,²⁰ the American College of Cardiology and the American Heart Association say coronary artery calcification scoring:

• Is recommended for asymptomatic patients at intermediate 10-year risk (10% to 20%) of coronary heart disease (class IIa recommendation, level of evidence B)
• May be acceptable for asymptomatic patients at low to intermediate risk (6% to 10%) (class IIb recommendation)
• Is discouraged for those at low risk (< 6%) (class III recommendation).

The most recent (2010) criteria for the appropriate use of cardiac computed tomography²¹ provide similar recommendations. Specifically, coronary artery calcification scoring with noncontrast computed tomography was rated as appropriate for patients at intermediate risk (10% to 20%) of coronary heart disease and for the specific subset of patients who are at low risk (6% to 10%) but who have a family history of premature coronary heart disease.

These recommendations are based on multiple lines of evidence that calcification scoring is a robust risk-predictor, can enhance risk estimates beyond traditional scoring strategies, and may—in theory—improve outcomes.

CALCIFICATION SCORING’S LIMITATIONS

The images used for measuring coronary calcification do predict risk of cardiovascular events, but they are not adequate to assess the severity of coronary stenosis. Further, calcification scoring often leads to incidental findings, which can cause anxiety and possibly lead to more imaging, entailing more radiation exposure and expense. And as noted, there are no randomized trial data demonstrating a reduction in cardiovascular events with the use of calcification scoring.