CAC score helps calculate more accurate atherosclerotic CVD risk

PHILADELPHIA — Coronary artery calcium scoring leads to an improved determination of CHD and atherosclerotic CVD risk, according to a presentation at the National Lipid Association Scientific Sessions.

The evidence, presented by Michael J. Blaha, MD, MPH, director of clinical research at Johns Hopkins Ciccarone Center for the Prevention of Heart Disease and Cardiology Today Next Gen Innovator, was illustrated by a profile of an asymptomatic patient that reflects one that Blaha treated. The patient was aged 55 years, did not smoke or have diabetes, had good diet and exercised, had a family history of premature CAD, and had BP 139 mm Hg systolic/85 mm Hg diastolic, HDL 60 mg/dL and LDL 145 mg/dL.

Pooled cohort equation

With the specific patient profile and the 2013 American College of Cardiology/American Heart Association guidelines, the clinician would have to calculate the pooled cohort equations to determine a patient’s 10-year atherosclerotic CVD risk.

“[The pooled cohort equations] look almost exactly the same as the Framingham risk score published 25 years ago,” Blaha, a Cardiology Today Next Gen Innovator, said. “Age, sex, race, total cholesterol, HDL, systolic [BP], treatment for high [BP], diabetes and smoking are considered as the … variables. These are the same variables — except for race — in the Framingham risk score. Unfortunately, the guidelines haven’t moved much beyond where we were 25 years ago in risk prediction, but we’ve collectively done a lot of work in this area.”

The patient’s 10-year atherosclerotic CVD risk would be 6.4%, but Blaha questioned whether this information would be helpful for the patient to understand their risk or for the clinician to dictate their decision, even though the ACC/AHA guidelines would suggest moderate evidence for “considering” a moderate-intensity statin.

Part of the 2013 guidelines focus on the clinician-patient risk reduction discussion for patients before they start statin therapy. Clinicians are recommended to speak with their patients not only about the risk reduction, but also about healthy lifestyle, drug-drug interactions and patient preferences, but if the decision is unclear, factors such as family history, primary LDL above 160 mg/dL and an abnormal coronary artery calcium (CAC) score may be considered.

CAC score

The CAC score is determined by a non-contrast CT scan, which takes about 10 to 15 minutes and exposes the patient to a minimum amount of radiation.

“What we now know is that there are excellent data that suggests [that of] alternative approaches for risk prediction, coronary calcium score is by far the best tool of the ones listed in the guidelines. And actually, we knew this before the guidelines were published,” Blaha said.

Researchers in a study from 2012 in JAMA analyzed nontraditional risk markers in the Framingham Risk Score such as CAC, C-reactive protein, family history and ankle-brachial index. Compared with other risk markers, coronary artery calcium had the highest sensitivity.

In a study that Blaha and colleagues published in Circulation, researchers observed that a coronary artery calcium score of zero was a positive sign.

“The calcium score by far is the most reassuring in those patients in whom it’s negative for reducing the risk of an event,” Blaha said. “This is consistent with what we call the imaging hypothesis, which is due to imaging superior sensitivity, imaging tests for subclinical atherosclerosis are excellent at ruling out or downgrading risk estimates when they’re negative. That also explains why [CTA], for example, is so great in the [ED] to rule out patients who are unlikely to have a significant coronary syndrome.”

CAC and risk

In an analysis from the MESA study, researchers used CAC scores to analyze patients who were recommended statin therapy according to the atherosclerotic CVD pooled cohort equation guidelines. Of patients who were recommended statin therapy, 41% had a calcium score of 0, 30% of patients had a score between 1 and 100 and 29% were above 100.

Patients with a 10-year atherosclerotic CVD risk score between 5% and 7.5% who were considered for statins had a 2% event rate for the next 10 years, or 1.5 per 1,000 patient years. Those with atherosclerotic CVD risk of 20% or greater regardless of their calcium score were at high risk.

“This led to the Society of Cardiovascular Computed Tomography to publish guidelines on calcium scores for use in treatment in 2017,” Blaha said.

Blaha explained the guidelines, which suggest that CAC testing is appropriate for shared decision making, targets patients who are asymptomatic without clinical atherosclerotic CVD aged 40 to 75 years with an atherosclerotic CVD risk between 5% and 20% or those with a risk score lower than 5% with a family history of CAD.

“These guidelines, I hope most people find them very flexible,” Blaha said. “Five to 20% is a large intermediate-risk group, bringing back this concept of intermediate risk, these patients who are ‘in between’ clearly low-risk patients and high-risk patients. In those patients who are < 5% by the pooled cohort equations, what we know is the potential increased risk of metabolic syndrome, triglyceride disorders and family history makes consideration of calcium scoring potentially attractive for risk stratification.”

Personalizing risk

Blaha said the above patient, whose 10-year atherosclerotic CVD risk was 6.4%, had a calcium score of 378, which put them at the 94th percentile for age/sex/race, a clearly high-risk situation.

“If you told this person they were at 6.4% risk over the next 10 years, what would they think?” Blaha said. “Some patients would say, ‘Sweet, 94% chance I’m not going to have a coronary event. Fantastic.’ Some people would say 6.4%? What does that mean? It’s very difficult for patients to understand what that means. Calcium scoring can materialize or personalize their risk and say, what do your arteries look like? Do your arteries afflicted by this disease for which we think that risk reduction therapy is beneficial?”

With the MESA 10-year CHD risk calculator, clinicians can enter risk factors either before or after the CAC score is determined.

 “Once you include the calcium score in the model, the risk factors are far less important because the calcium scores help integrate the effect of those risk factors on your patient’s arteries,” Blaha said.

The patient Blaha discussed would have a risk well above 15% using the MESA Risk Score. Blaha added that he and his colleagues are working on a CVD risk score tool for clinicians who want to factor in stroke.

The SCCT guidelines reference the recommendation of statin therapy and its intensity based on calcium score. Patients with higher calcium scores may be recommended high-intensity statin therapy, while those with lower scores may be considered for or recommended moderate-intensity statin therapy.

Future guidelines

“I envision the next set of guidelines being much more comprehensive. This is more like the way I practice,” Blaha said. “This will maybe be the future SCCT guidelines, and not just look at statins, but look at multiple therapies.”

Blaha added his interest is in patients with high calcium scores who are in the 90th percentile or have a score greater than 300. For high-risk patients, he said he recommends more aggressive lifestyle therapy and high-intensity statin therapy, along with nonstatin therapy to attain LDL less than 70 mg/dL. Aspirin and BP goals may also be considered.

“We know that aspirin has a very narrow margin of benefit and can cause harm,” Blaha said. “When we model this out, patients with a calcium score of zero tend to project down as a net harm from aspirin therapy. Now patients with a score above 100, we project would get a net benefit. This is consistent with the [U.S. Preventive Services Task Force] guidelines that say that … high-risk patients can benefit from aspirin. Patients between 1 and 100, it depends on how many risk factors that are present.”

Regarding BP targets, Blaha referred to a study in Circulation in 2016, where researchers found that CAC scores and global atherosclerotic CVD risk can potentially guide systolic BP goals, especially in patients with an estimated risk between 5% and 15% and pre-hypertension or mild hypertension.

Lipid-lowering therapy

Patients with advanced subclinical atherosclerosis fall in between primary and secondary prevention. Blaha said that he would treat this patient population very aggressively, but clinicians should consider a patient’s condition before determining how to progress with statin therapy.

“I treat my patients with advanced subclinical atherosclerosis more like patients with existing CVD,” Blaha said.

The new SCCT guidelines as well as the MESA CHD Risk Score both consider CAC a significant tool in determining CHD and atherosclerotic CVD risk.

 “If we didn’t have this risk information, you wouldn’t know how to personalize this patient’s therapy,” Blaha said. – by Darlene Dobkowski

References:

Blaha MJ. Coronary Artery Calcium – Refining Risk Estimates and Defining Treatment. Presented at: National Lipid Association Scientific Sessions; May 18-21, 2017; Philadelphia.

Blaha MJ, et al. Circulation. 2016;doi:10.1161/CIRCULATIONAHA.115.018524.

McEvoy JW, et al. Circulation. 2016;doi:10.1161/CIRCULATIONAHA.116.025471.

Nasir K, et al. J Am Coll Cardiol. 2016;doi:10.1016/j.jacc.2015.07.066.

Yeboah J, et al. JAMA. 2012;doi:10.1001/jama.2012.9624.

Disclosure: Blaha reports receiving grants from Aetna Foundation and Amgen; serving on advisory boards for Akcea, Amgen, MedImmune, Novartis and Sanofi/Regeneron, and serving on the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee.