By Annette M. Boyle
BETHESDA, MD—Primary care physicians and cardiologists increasingly rely on risk factor-based scores to determine who should start preventive therapy for atherosclerotic cardiovascular disease (ASCVD). A growing body of evidence shows that reliance may lead to large-scale overtreatment—and may miss some individuals at significant risk.
A recent review led by researchers at Walter Reed National Military Medical Center in Bethesda, MD, compared current risk factor-based scores to coronary artery calcium scoring and carotid ultrasound to determine their relative strengths and weaknesses. The review, directed by senior author Army Lt. Col. Todd C. Villines, MD, appeared in Current Cardiovascular Imaging Reports.1
While traditional risk scores are simple, inexpensive and easy to use in an office setting, they have significant limitations. The pooled cohort-based calculator included in the 2013 American College of Cardiology (ACC)/American Heart Association (AHA) Risk Assessment and Cholesterol Treatment Guidelines, for instance, has generated controversy since its release for its systematic overestimation of risk. Testing of its clinical accuracy in three cohorts separate from the four National Heart, Lung, and Blood Institute studies used in its development showed a 75% to 150% overestimation of risk.2
Overestimation “may result in treating patients who don’t need pharmacologic therapy,” said Lauren Weber, MD, a cardiology fellow at WRNMMC. “Also, they don’t include some important risk factors, like family history of heart disease or duration or extent of risk factors which may impact a patient’s overall risk.”
The Canadian Heart Association guidelines double the estimated risk for individuals who have a first-degree relative with a history of cardiovascular disease before age 60. The ACC/AHA risk calculator also does not include prior statin therapy or how long an individual smoked. The study authors noted that it also had not been prospectively validated for its ability to improve ASCVD outcomes or among many ethnicities.
Risk Factor Scores
In the same guidelines, the ACC/AHA downgraded the recommendations for coronary artery calcium (CAC) scanning to llb (scoring may be considered). CAC is a rapid, non-contrast computed tomograph (CT) of the heart used to measure calcification within the epicardial coronary arteries, with radiation exposure equivalent to a mammogram. It can produce absolute scores, where 0 indicates no calcification and very little risk of coronary events, 1-10 minimal risk, 11-100 mild risk, 101-400 moderate risk and 400 or more indicating severe risk.
“Without exception, every large-scale study performed to date has shown CAC to be superior to risk factor scores, with CAC resulting in significant reclassification of patients,” wrote the review authors.
Net reclassification index (NRI) is the degree to which a provider is able to reclassify a patient’s risk category based on a test. If a patient with a moderate risk, as measured by a risk score, is moved to higher risk based on their CAC, they would benefit from medical therapy. If reclassified to lower risk, they might be able to use diet and exercise alone, Weber explained.
“This is precision medicine: applying preventative therapies (such as statins) to those most likely to benefit and not treating those who are unlikely to benefit,” Weber said.
The downgrading of CAC in the latest ACC/AHA guidelines came as a result of the inclusion of stroke risk, rather than coronary heart disease alone, which had been the primary focus of previous guidelines, according to Weber. Concerns about radiation dose and cost effectiveness were also raised, she noted, although current scanner can consistently provide calcium scores with radiation doses of less than 1 milisievert.
In addition, some cost analyses show that CAC testing does not drive up overall costs but reduces them in patients reclassified as lower risk, according to Weber. The average cost of the test is less than $100. Downstream testing is increased in patients with elevated scores, particularly those with CAC scores above 400 and invasive coronary angiography and coronary revascularizations occur in 19% of patients with CAC scores above 1,000.
One of the significant advantages of CAC is the “impressively low 10-year cardiovascular risk (approximately 1%) observed in subjects with CAC=0, regardless of risk factor status,” wrote the authors. Calcium scoring, consequently, offers the potential to focus preventive therapy while also avoid treating patients at very low risk.
Ultrasonography for the measurement of carotid artery intima-media thickness (CIMT) and carotid plaque in asymptomatic screening populations can be performed in an office setting without radiation. Major studies that have assessed the predictive value of CIMT, however, have used a variety of measurements; some have included carotid plaque assessments, while others have not. This heterogeneity has resulted in a wide range of results, making consensus on the use of CIMT challenging, according to the study authors.
“Not included in the 2013 AHA guidelines for cardiovascular risk assessment is a relatively new technology of 3D carotid plaque measurements which has some promising initial data and may be comparable to CAC when it comes to the prediction of cardiovascular outcomes,” Weber said. The lack of radiation exposure and low rate of incidental findings also make it appealing, she noted.
So what should physicians do? “I would like to see more use of CAC scoring for moderate risk individuals as an objective answer to the question, ‘Does my patient have asymptomatic coronary disease?’ because I believe it helps get patients on the right treatment pathway, to include recommending against medical therapy,” Weber said. “I think CAC scoring can be done cost effectively with minimal radiation and can help reduce the adverse impact of heart diseases which are now the No. 1 cause of death in the world.”
- 1 1 Weber LA, Cheezum MK, Reese JM, Lane AB, Haley RD, Lutz MW, Villines TC. Cardiovascular Imaging for the Primary Prevention of Atherosclerotic Cardiovascular Disease Events. Curr Cardiovasc Imaging Rep. 2015;8(9):36. Review.
2 Martin SS, Blumenthal RS. Concepts and controversies: the 2013 American College of Cardiology/American Heart Association risk assessment and cholesterol treatment guidelines. Ann Intern Med. 2014 Mar 4;160(5):356-8.
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