Coronary Artery Calcium and Atherosclerotic Cardiovascular Disease: Bridging the Gap to Optimize Primary Prevention of Cardiovascular Disease

Risk assessment to inform management decisions is an integral component of cardiovascular (CV) prevention, with recent guidelines emphasizing the use of the pooled cohort equation (PCE) to estimate 10-year atherosclerotic cardiovascular disease (ASCVD) risk to guide treatment with anti-hypertensive, statin, and aspirin therapies.1-3 Currently utilized risk assessment tools based on traditional risk factors such as the PCE and Framingham Risk Score are useful but do not directly assess the burden of atherosclerosis and have known challenges in accurately assessing risk, particularly in modern, ethnically diverse cohorts.4-7

Of interest is the role of coronary artery calcium (CAC) scoring as an assessment of coronary disease burden and cardiovascular risk. Tools such as the Multi-Ethnic Study of Atherosclerosis 10-year coronary heart disease risk score (MESA CHD Risk Score) incorporate traditional risk factors with CAC score to improve upon risk assessment.8 However, it does not predict stroke risk, which is typically about half as common as the risk of myocardial infarction (MI) in persons less than age 70.

The CAC scan is a noninvasive 10-minute chest computerized tomography study that assesses concentration of calcium in artery walls. The scan identifies hardened plaques, which are correlated with later stage atherosclerosis.9 According to the 2016 Society of Cardiovascular Computed Tomography Annual Scientific Sessions, the average cost of a CAC scan is below $100, although Medicare and some private insurance companies do not cover the cost, forcing patients to pay out of pocket. Radiation exposure is limited--less than a bilateral mammogram, the average background radiation experienced in one year, or that encountered during a round-trip transatlantic travel by air. The amount of calcium in the walls of the coronary arteries is assessed by the Agatston score, which is provided as an absolute number or as a percentile for age, sex and race/ethnicity.

A variety of studies have demonstrated that CAC is especially useful as a decision tool for primary prevention. Analysis of the MESA and Evaluation of Coronary Calcium and Lifestyle Factors studies showed a robust association between CAC and rate of hard cardiac events (MI, cardiac death, resuscitated cardiac arrest), which held true when factoring in rate of revascularization and stroke at 5-year follow-up.10 A large observational data series showed that CAC was correlated with all-cause mortality with an incremental relationship.11

CAC has also been shown to be particularly instructive with a score of zero, such that when added to standard PCE, a pre-test risk estimate of up to 15% was shown to confer post-test risk estimate of <7.5% after a CAC score of zero.12-13 The 2013 ACC/AHA and 2016 Canadian Cardiovascular Society (CCS) guidelines support its use in patients with intermediate risk in whom preventive treatment strategy is uncertain.2,14 Current international guidelines, however, have variably incorporated CAC score (Table 1), with one major concern that effect seen on CHD over shorter term follow-up may not fully translate to 10-year risk of hard ASCVD events, which additionally include peripheral arterial disease and stroke.15

Table 1: International Guideline Recommendations for Use of CAC Score for Primary Prevention2,14,19-20

Guideline

Recommendation

Notes

2013 American College of Cardiology/American Heart Association

Class IIB recommendation when “a risk-based treatment decision is uncertain”

Guideline authors pointed to the lack of studies where ASCVD was the outcome instead of CHD as a reason for uncertainty

2016 European Society Cardiology/ European Atherosclerosis Society

No recommendation is provided for use of CAC scoring for risk estimation

State that CAC scans have the best reclassification ability of current validated secondary markers

2014 Canadian Cardiovascular Society

Most clinical utility for middle-aged, intermediate risk subjects (Framingham Risk Score between 10 and 20%)

Repeat screenings not recommended

2014 Veterans Affairs/Department of Defense

Suggest against the routine use of CAC scans

Not recommended because CAC scans were incorrectly thought to have had a relatively small effect on risk prediction accuracy; theoretical utility in intermediate-risk situations with uncertainty about treatment benefits

Much of the CAC literature has focused on coronary heart disease risk whereas guideline-based practice has moved on from a coronary heart disease focus to ASCVD. In this context, a recent study by Budoff et al. is particularly notable.16 This study utilizes the diverse MESA cohort to demonstrate that CAC scoring is strongly associated in a graded fashion with 10-year risk of incident ASCVD in patients both on and off of lipid therapy. They demonstrated that CAC is strongly associated with major adverse ASCVD events regardless of sex, race/ethnicity or age, so that CAC score of zero lead to ASCVD risk of 1-6% whereas those with CAC score >300 had rates of 13-26%. Although CAC scores independently predicted risk in all ethnic groups, relationship between CAC scores and ASCVD risk occurred at different rates of increase across subgroups. For patients on lipid-lowering medications, CAC was associated with ASCVD risk but at a lower rate of increase, which was previously unclear given that statins have been associated with microcalcification development.17

With the increasing body of evidence showing that CAC scoring strongly predicts cardiovascular risk across all races, age, groups and sexes, its use in preventive cardiology has the potential to expand. Rather than being a broad-based screening tool, we view CAC as a valuable test to be considered selectively to help make better decisions about preventive treatments. In the context of clinician-patient risk discussion, CAC can empower the shared decision-making process with information about atherosclerosis burden and ASCVD risk.18 Given the high negative predictive value of a CAC score, in patients already on statin treatment but with possible side effects, CAC scores may also be used to push re-consideration of the necessity of primary prevention drug treatment. Conversely, elevated CAC may allow preventative health specialists to identify and treat patients who may derive great benefit from primary prevention medical intervention who have falsely reassuring low ASCVD risk as calculated via PCE. The paper by Budoff and colleagues provides further impetus to explore the integration of selective use of a CAC in guidelines and practice when the patient or the clinician is not certain what the patient's true risk really is.

References

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  12. McClelland RL, Jorgensen NW, Budoff M, et al. 10-year coronary heart disease risk prediction using coronary artery calcium and traditional risk factors: derivation in the MESA (Multi-Ethnic Study of Atherosclerosis) with validation in the HNR (Heinz Nixdorf Recall) study and the DHS (Dallas Heart Study). J Am Coll Cardiol 2015;66:1643-53.
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  16. Budoff MJ, Young R, Burke G, et al. Ten-year association of coronary artery calcium with atherosclerotic cardiovascular disease (ASCVD) events: the Multi-Ethnic Study of Atherosclerosis (MESA). Eur Heart J 2018;39:2401-8.
  17. Dykun I, Lehmann K, Kalsch H, et al. Statin medication enhances progression of coronary artery calcification: the Heinz Nixdorf Recall study. J Am Coll Cardiol 2016;68:2123-5.
  18. Martin SS, Sperling LS, Blaha MJ, et al. Clinician-patient risk discussion for atherosclerotic cardiovascular disease prevention: importance to implementation of the 2013 ACC/AHA guidelines. J Am Coll Cardiol 2015;65:1361-8.
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Clinical Topics: Arrhythmias and Clinical EP, Diabetes and Cardiometabolic Disease, Dyslipidemia, Noninvasive Imaging, Prevention, Vascular Medicine, Atherosclerotic Disease (CAD/PAD), Implantable Devices, SCD/Ventricular Arrhythmias, Lipid Metabolism, Nonstatins, Novel Agents, Statins

Keywords: Dyslipidemias, Risk Factors, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Antihypertensive Agents, Coronary Vessels, Peripheral Arterial Disease, Calcium, Ethnic Groups, Background Radiation, Atherosclerosis, Risk Assessment, Myocardial Infarction, Stroke, Primary Prevention, Coronary Disease, Heart Arrest, Tomography, Lipids, Aspirin


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