Lancet: CAC bests C-reactive protein for predicting CV events
Coronary artery calcium (CAC) may further stratify risk in patients eligible for the JUPITER trial and could be used to identify who will benefit the most, or least, from statin therapy, according to a study published in the Aug. 18 issue of The Lancet.

“Findings from landmark clinical trials have led to progressive liberalization of statin use for primary prevention of cardiovascular disease,” Michael J. Blaha, MD, of Johns Hopkins School of Medicine in Baltimore, and colleagues wrote. Findings from the previously published JUPITER trial outlined that patients with normal concentrations of LDL cholesterol (3.37 mmol/L) and a high-sensitivity C-reactive protein concentration of 2 mg/L benefit from treatment with rosuvastatin (Crestor, AstraZeneca).

Because CAC detected by cardiac CT can provide further risk stratification of asymptomatic patients, Blaha and colleagues set out to evaluate whether or not testing for CAC could identify patients eligible for the JUPITER trial and those who may fare better and worse on rosuvastatin.

After JUPITER, it has been estimated that 6.5 million people in the U.S. may not be eligible for statin treatment; however, this would have huge implications for guidelines and for cost-effectiveness.

Blaha et al used the MESA study to identify 950 patients who met criteria for JUPITER and then compared coronary heart disease and cardiovascular event rates and hazard ratios after stratifying by burden of CAC (scores of 0, 1 through 100, or more than 100). The authors calculated a five-year number needed to treat (NNT) by applying the benefit recorded in JUPITER to the event rates within each CAC tier.

Fifty-four percent of study participants had a high-sensitivity C-reactive protein (hsCRP) less than 2 mg/L and 46 percent had hsCRP 2 mg/L or more. The researchers reported that patients in the MESA JUPITER population had CAC scores of 0 and the group had rates of coronary heart disease events that equated to 0.8 per 1,000 person-years. Additionally, the authors found that 74 percent of coronary events took place in 239 patients with CAC scores of more than 100. The rates of these events were 20.2 per 1,000 person-years.

The predicted five-year NNT for coronary heart disease for a CAC score of 0 was 549, 94 for scores 1 through 100 and 24 for scores greater than 100. These numbers for cardiovascular disease were 124, 54 and 19, respectively.

“Future guidelines might incorporate the recommendation for statin treatment in patients with normal cholesterol who are at increased risk because of another risk factor or biomarker (such as hsCRP),” the authors wrote. “In view of our results, CAC should be strongly considered in these patients; this supports the IIA recommendation for CAC screening in the updated American Heart Association guidelines for testing in adults who are asymptomatic.”

The authors noted that while CAC predicts cardiovascular disease “less strongly” than coronary heart disease, it is still a better predictor when compared to hsCRP. However, CAC also has disadvantages, which include radiation exposure and costs.

“We think that it is time to move past traditional risk factors and blood tests and toward incorporation of direct measures of subclinical atherosclerosis in risk prediction,” Blaha said in a statement. “This makes sense because CAC uses modern technology to directly measure the disease we propose to treat with statins.

“While not everyone needs a calcium scoring test,” Blaha concluded, “we believe looking for calcification in coronary vessels in certain patients makes sense in order to predict who may benefit from statin therapy because the test gets right to the heart of the disease we want to treat.”

A clinical trial and cost-effectiveness analyses will be necessary before CAC is endorsed to stratify risk in adults with unclear treatment decisions.

In an accompanying editorial, Axel Schmermund and Thomas Voigtländer, of Cardioangiologisches Centrum Bethanien in Frankfurt am Main, Germany, wrote, “We cannot be content with statistical significance, and a practical approach towards expanded risk stratification should be established. Although definitive proof of treatment effects is scarce, CAC identifies high cardiovascular risk, and statin therapy is most effective in high-risk patients.”