The National Lipid Association (NLA) published recommendations in the Journal of Clinical Lipidology regarding the use of coronary artery calcium (CAC) scoring for the purposes of preventive atherosclerotic cardiovascular disease (ASCVD) risk stratification and reduction, noting that CAC scoring is a safe, rapid, widely available test that offers improved ASCVD discrimination and risk reclassification compared with other clinical tools, when used together with global risk scoring systems such as the Pooled Cohort Equations (PCE). The guideline statement covered CAC scoring utilization in patients of different ages and races/ethnicities and with various comorbidities and PCE-assessed risk levels, as well as those taking statins. The guideline also offered guidance on repeat scoring and the use of CAC to direct anti-hypertensive and aspirin pharmacotherapy, in addition to providing a look at the future of CAC scoring.
Updated Recommendations on Appropriate CAC Scoring Utilization
As a hallmark of ASCVD, coronary arterial calcification and its assessment via CAC scoring have been revealed as important indicators of CV disease, with guidelines for lipid-lowering therapy intensity linked to CAC scores. When indications for statin treatment remain unclear despite the use of risk-enhancing factors and PCE, the 2018 Cholesterol Guideline recommends considering CAC scoring in borderline- or intermediate-risk patients aged 40 to 75 years without diabetes or existing ASCVD in whom low-density lipoprotein cholesterol (LDL-C) levels are 70 to 189 mg/dL.
Yet, even with this guidance, clinicians are often left with questions regarding CAC scoring use and optimization. The guideline authors sought to provide updated recommendations on appropriate CAC scoring utilization and offered practical advice to aid practitioners’ primary prevention therapy decision making.
The writing committee gathered with the objective of updating the NLA position on the use of CAC scoring in clinical practice, with all recommendations based on expert consensus after a review of recent literature. All guidance offered in the statement is evidence based and actionable and directed at adult patients and their providers regarding primary prevention using shared decision making.
Quantification of CAC is accomplished via the Agatston technique, which has demonstrated high reproducibility and low variability within and between scans. Scores are presented as absolute CAC scores and age-, sex- and race/ethnicity-based percentile scores. Although absolute CAC scores best predict 5- to 10-year absolute ASCVD event risk, CAC score percentiles are better predictors of lifetime risk trajectory and relative risk, it was noted.
Thus, the former is useful for number needed to treat estimations and for directing pharmacotherapy; the latter can provide lifetime treatment benefit estimates. It was recommended that clinicians should therefore report both the absolute and percentile CAC scores.
Recommendations for Scoring
Adult patients aged 40 to 75 years with a PCE-derived 10-year ASCVD risk of 5% to 19.9% and LDL-C of 70-189 mg/dL may benefit from CAC scoring for the purposes of decision making regarding preventive therapy initiation and intensity. And in those aged 40 years or older who are within the same LDL-C range with greater than 5% calculated ASCVD risk but a positive family history of premature disease, CAC scoring may also be helpful for the same reasons.
However, CAC scoring is not recommended for patients with existing clinical ASCVD or for those in the general population with less than 5% risk who lack a family history of disease.
Race, Ethnicity, Sex, Age
Whenever it is indicated as part of an ASCVD risk assessment, CAC scoring should be performed regardless of the sex or race/ethnicity of the patient. Despite demonstrated differences in CAC prevalence between races/ethnicities, there remains an independent significant association between CAC score and ASCVD events, regardless of ethnicity or race.
The increase in relative risk for ASCVD events is proportionate to CAC scoring across races and ethnicities. That said, Black and Hispanic individuals tend to show higher incidences of CVD and all-cause mortality vs their White and Asian counterparts, for a given CAC score.
Selective use of CAC scoring may also be appropriate for patients younger than 40 years old as well as those aged 76 to 80 years, for risk stratification and preventive therapy intensification in the younger group, and for risk reclassification and statin treatment optimization in the older cohort. For certain people in the younger group with a family history of premature ASCVD or multiple major risk factors, a CAC score greater than 0 may indicate a need for lifestyle modification and possibly statin therapy initiation. And within the older group, in cases of uncertainty regarding treatment with statins, CAC scoring can help reclassify ASCVD risk and guide decision making.
The Patient With CAC = 0
A score of CAC = 0 is the strongest ASCVD “negative risk marker” and is highly correlated with very favorable prognoses for both CV and non-CV disorders. For this reason, patients with CAC = 0 who are not current cigarette smokers, do not have diabetes mellitus and have no family history of premature ASCVD will derive only modest risk reduction benefit in the short- and intermediate-term from statin therapy.
Therefore, in patients aged 40 to 75 years who fulfill these criteria and in whom LDL-C is 70-189 mg/dL, CAC = 0 may be considered an acceptable rationale for deferring statin therapy. And in patients aged 76 to 80 years for whom statin initiation indications remain uncertain, CAC = 0 may be viewed as a factor arguing against initiating treatment. For those prescribed statins, there is a proportional relationship between CAC score and absolute ASCVD risk reduction.
Multivessel Involvement, Left Main Coronary Calcification
When CAC is more diffusely distributed (ie, identified in more than 1 coronary vessel) there is greater risk to the patient than when CAC is more localized (single vessel), for any given CAC score. However, left main coronary calcification is an exception to this rule and suggests higher risk, beyond the total CAC score, particularly when greater than 25% of the score is derived from the left main coronary artery.
There is no apparent clinical utility – and no evidence to suggest a potential benefit – in performing invasive coronary arteriography or stress testing in asymptomatic patients with high CAC scores, even in the presence of multivessel involvement or predominant left main coronary calcification; it is therefore not recommended in this population. When the CAC score is 100 or greater, representing a greater than 7.5% 10-year ASCVD risk, the statin benefit threshold has been met and initiation of statins is recommended.
High CAC Scores
Patients with CAC scores of 300 or greater (and especially those patients with scores of 1000 or greater) are at increasingly greater proportionate risk of ASCVD events and may benefit from more aggressive LDL-C lowering, via high intensity statin therapy and possibly add-on LDL-C lowering treatments, with the goal of achieving a 50% or greater LDL-C reduction from baseline and an LDL-C of less than 70 mg/dL.
Management of Pulmonary Nodules, Incidental CAC
If pulmonary nodules are detected during a CAC scoring exam, the size and characteristics of each nodule should be noted, and a follow-up investigation should be conducted according to the Fleischner Society recommendations. A chest computed tomography (CT) scan – performed for reasons other than CAC scoring – that detects mild incidental CAC may prompt a subsequent dedicated CAC scoring CT exam, in order to guide preventive therapy decision making. However, when a non-CAC CT scan detects incidental moderate or severe CAC, statin therapy can be reasonably initiated without relying on a separate CAC exam.
CAC Scoring in Patients With Severe Primary Hypercholesterolemia
Although data is limited, for those diagnosed with severe primary hypercholesterolemia (LDL-C of190 mg/dL or greater), CAC scoring may be helpful for short- and intermediate-term predictions of ASCVD risk, with CAC of greater than 0 indicating heightened ASCVD risk and the need for aggressive guideline-based LDL-C lowering therapy. And in select patients without premature ASCVD family history, additional major ASCVD risk factors or extreme LDL-C elevation, CAC scoring can play an important role when considering add-on therapy with maximally tolerated statins. It is also important to note that in this patient group, CAC = 0 does not obviate a requirement for evidence-based, long-term LDL-C lowering therapy.
CAC Scoring in Patients With Diabetes
Adults aged 40 to 75 years with LDL-C 70 to 189 mg/dL who have type 2 diabetes mellitus (T2DM) should be prescribed a moderate- or high-intensity statin medication, irrespective of CAC score. For those who fit these criteria to initiate statin treatment and also have a CAC score of 100 or greater, a high-intensity statin is reasonable.
In younger adults (aged 30 to 39 years) with chronic T2DM (10 years duration or longer) or type 1 diabetes (20 years duration or longer) and microangiopathic risk factors, CAC scoring may help with ASCVD risk stratification and shared decision-making regarding statin therapy. And in older adults (75 years or older) with T2DM who are at a crossroads regarding statin initiation for primary prevention, CAC scoring may aid providers and patients in making this decision.
Repeat CAC Scoring
The recommended timing for repeat CAC scoring varies from 3 to 7 years, depending on individual baseline ASCVD risk. Since CAC scores increase exponentially over time (and CAC does not regress), generally by 20% to 25% annually, lower scores of 0 to 100 offer the best risk discrimination vs higher scores. It is important that CAC scoring only be performed in patients in which the findings will alter therapeutic choices.
Clinicians must understand that CAC scoring is not useful for assessing statin therapy efficacy (and that statins actually mildly raise the CAC score). Upon repeat scoring, patients with a prior CAC of less than 0 who have CAC of 400 or greater or 20% to 25% annual progression are understood to have accelerated ASCVD progression.
The intervals for repeat scoring depend on baseline CAC score and calculated 10-year ASCVD risk levels. Patients with CAC = 0 at baseline who are at low risk (less than 5%) should repeat scoring every 5 to 7 years, and those at borderline/intermediate risk (5% to 19.9%) should do so every 3 to 5 years and those at high risk (20% or greater) or with diabetes should retest every 3 years.
In patients with CAC scores 1-99, repeat scoring in 3 to 5 years is reasonable, if the clinician believes the results might alter the treatment regimen. And for those with CAC scores of 100 or greater and LDL-C 70 mg/dL or greater, repeating the CAC scoring exam every 3 years may be useful for evaluating accelerated progression of disease or an absolute score of300 or greater, either of which may indicate the need for more aggressive therapy.
Use of CAC Scoring in Patients on Statins
For those already taking statins, it is important that the clinician understands that these medications delipidate plaque, effectively reducing noncalcified plaque volume and elevating calcified plaque volume. In these patients, CAC scoring still offers risk discrimination similar to that observed in statin naïve patients and therefore remains an ASCVD risk predictor.
Because of an increased risk for bleeding that rises together with calculated ASCVD risk, no patient group has been identified via PCE-derived risk scores to likely have a clear net benefit from aspirin treatment. That said, for those with CAC of100 or greater in whom bleeding risk is low, there appears to be greater potential benefit from aspirin therapy than there is risk for bleeding. In these patients, aspirin 81 mg once daily may be reasonably prescribed.
Patients with stage 1 hypertension may benefit from risk reclassification following CAC scoring, which in turn may help guide pharmacotherapy decisions. Thus, for hypertension, CAC scoring may have additional utility in identifying blood pressure targets for intervention.
The Future of CAC Scoring
The future of CAC scoring entails considerations regarding cost effectiveness (generally considered cost effective), support from clinical trials (currently sparse but with several studies in the pipeline), insurance coverage (not typically covered, but this is changing), its relationship to polygenic risk scores, new comprehensive scoring systems (currently being developed), and the development of new risk tools alongside the expansion of percentile scores to cover those aged 30 to 45 years.
The guideline authors noted that “[T]he evidence base supporting the clinical use of CAC scoring in primary prevention continues to grow and points to its valuable role to aid in the allocation of preventive therapies to those most likely to benefit. With the advent of future refinements in this technique and increased access based on lower cost and greater insurance coverage, more clinicians will be able to utilize this powerful tool to provide higher quality preventive care for their patients.”
Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.
Orringer CE, Blaha MJ, Blankstein R, et al. The National Lipid Association scientific statement on coronary artery calcium scoring to guide preventive strategies for ASCVD risk reduction. J Clin Lipidol. Published online December 11, 2020. doi:10.1016/j.jacl.2020.12.005