CAC Screening Stratifies CVD Event Risk in Statin-Eligible Patients: Heinz Nixdorf Recall Study

Use of coronary artery calcium (CAC) testing in patients recommended to take statin therapy based on US and European guidelines improves the identification of those at high and low risk for coronary events, according to the results of a new analysis.

For both the European Society of Cardiology (ESC) and American College of Cardiology/American Heart Association (ACC/AHA) guidelines, individuals eligible for statins based on their 10-year risk of cardiovascular disease with a CAC score less than 100 had significantly fewer coronary events compared with similar statin-indicated patients with a CAC score 100 or greater.

Published online September 21, 2016, in JACC: Cardiovascular Imaging, the study led by Amir Mahabadi, MD (West German Heart and Vascular Center, Essen, Germany), showed that event rates in patients indicated for statin therapy with a low CAC score were within the range of individuals without a guideline-recommended indication for statins. These results demonstrate the “ability of CAC scoring to avoid lifelong medical lipid-lowering therapy for subjects with low observed subsequent event rates,” according to the researchers.

Khurram Nasir, MD (Baptist Health South Florida, Miami), who was not involved in the study, told TCTMD that in the United States, where the ACC/AHA indications for statin therapy are broader than the ESC guidelines, the usefulness of CAC testing lies as a decision aid, rather than as a screening tool. In this sense, the absence of atherosclerotic disease and not its presence provides greater value in guiding clinical decisions. 

This notion, he added, conflicts with the traditional approach of “testing,” where the goal is to screen or identify individuals for treatment. Using CAC to rule out treatment may appear paradoxical and be difficult to comprehend, but “if you focus on the US guidelines, which are more liberal for statin use, an absence of CAC was very reassuring,” said Nasir. On the other hand, he added, very few individuals not considered for statin therapy based on the clinical guidelines will have elevated CAC or be at high risk for clinical events, so the use of CAC scoring in these patients will not affect treatment decisions for statin use at the population level.

In an editorial, Michael Blaha, MD, and Kunihiro Matsushita, MD (Johns Hopkins Medical Institute, Baltimore, MD), make similar comments. They state that CAC should play a role as a risk stratification tool in patients at “intermediate risk,” those with a 10-year risk of atherosclerotic cardiovascular disease in the 5% to 20% range, and who might be reluctant to start therapy. The editorialists suggest that CAC might also be reasonable in patients with a 10-year risk less than 5% but who also have a nontraditional risk factor, such as a history of premature heart disease or metabolic syndrome.

Primary Prevention Cohort Study

In the new study, the German researchers looked at data from the population-based longitudinal Heinz Nixdorf Recall cohort study, which included 3,745 subjects without cardiovascular disease who were not taking lipid-lowering therapy. During a median follow-up of 10.4 years, there were 131 fatal or nonfatal MIs and 241 “hard cardiovascular events” (including MI, stroke, and cardiovascular death).   

Based on the 2012 ESC guidelines, which recommended statin therapy for those with elevated LDL cholesterol (≥ 100 mg/dL) and a 10-year risk of a fatal atherosclerotic event ranging from ≥ 5% to less than 10% (and in subjects with a 10-year risk ≥ 10% and LDL cholesterol ≥ 70/mg/dL), more than 34% of patients in the cohort were eligible for statin therapy. In contrast, more than 56% of the cohort were eligible for statin therapy based on the updated 2013 ACC/AHA guidelines, which recommends statin therapy for individuals with a 10-year risk of atherosclerotic cardiovascular disease ≥ 7.5%.

Overall, a low CAC score (< 100) was present in 59% of subjects with a statin indication using the ESC guidelines (17% had a CAC score of zero) and in 62% of subjects when using the US recommendations (19% had a CAC score of zero). Coronary heart disease and atherosclerotic cardiovascular disease event rates in all statin-eligible patients were significantly lower in those with a CAC score less than 100. 

For example, when investigators stratified the results by CAC score and statin indication using the ESC guidelines, there were 2.8 coronary events per 1,000 person-years among patients with a statin indication and a CAC less than 100 compared with 8.5 events per 1,000 person-years in statin-eligible patients with higher CAC scores. Using the ACC/AHA guidelines, there were 3.0 coronary events per 1,000 person-years among statin-eligible subjects with a CAC score less than 100 compared with an event rate of 8.0 per 1,000 person-years among those with higher scores.

The researchers point out that the majority of patients recommended statins using the ACC/AHA guidelines had a low CAC score and a low 10-year event rate, suggesting that CAC testing can help overcome the challenge of placing large segments of the population on lifelong drug therapy needlessly. Using the ESC guidelines, there were more patients not recommended statins, and higher event rates, which suggests “CAC quantification can justify statin therapy in subjects with moderate risk but without [a] statin recommendation,” according to Mahabadi and colleagues.

The Role of CAC

Last month, as reported by TCTMD, investigators published data from the BioImage study that showed the use of CAC could help reduce the number of older patients treated with statin therapy without increasing the risk of cardiovascular events among the untreated subjects. 

Similarly, researchers, including Nasir and Blaha, also published an analysis of the Multiethnic Study of Atherosclerosis (MESA) showing that the absence of coronary calcification shifts the 10-year risk of cardiovascular disease downward, which would in turn spare individuals for statin therapy.

To TCTMD, Nasir agreed that intermediate-risk patients eligible for statins are the patients most likely to benefit from CAC screening. The absence of subclinical atherosclerosis pushes their 10-year risk of cardiovascular disease below the threshold in which the current guidelines recommend statin therapy, meaning treatment could be avoided, he said. For individuals who are not candidates for statin therapy, Nasir said there are few patients who would have high CAC scores, and even if they had calcification, the presence of CAC does not increase their estimated 10-year risk to the point where statins would be considered.

“That’s why my message, along with a few others, has been really to think of calcium as a decision aid for uncertain patients, for patients who are unsure if they want to be on statins or not and are willing to avoid them if they have a calcium score of zero,” said Nasir. As for the use of CAC as a screening tool, he said “it’s time to let it go,” particularly since the majority of individuals qualify for treatment based on ESC and ACC/AHA current guidelines. In the current scenario, the value of screening is extremely limited, said Nasir.  





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Michael O’Riordan is the Managing Editor for TCTMD. He completed his undergraduate degrees at Queen’s University in Kingston, ON, and…

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  • Mahabadi AA, Möhlenkamp S, Lehmann N, et al. Coronary artery calcification improves coronary and cardiovascular risk assessment above statin indication by current ESC and AHA/ACC primary prevention guidelines. J Am Coll Cardiol Img. 2016;Epub ahead of print.

  • Blaha M, Matsushita K. Coronary artery calcium—need for more clarity in the guidelines. J Am Coll Cardiol Img. 2016;Epub ahead of print.

  • Authors and editorialist report no conflicts of interest.
  • Nasir reports serving on the advisory board of Quest Diagnostics and consulting for Regeneron.