Issue: February 2021
Disclosures: Blumenthal reports he was an author of the 2018 AHA/ACC Guideline on the Management of Blood Cholesterol. Gagel, Scheel and Sharma report no relevant financial disclosures.
January 26, 2021
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NLA scientific statement further cements CAC scoring in primary prevention

Issue: February 2021
Disclosures: Blumenthal reports he was an author of the 2018 AHA/ACC Guideline on the Management of Blood Cholesterol. Gagel, Scheel and Sharma report no relevant financial disclosures.
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The first technique for coronary artery calcium scoring was published in 1990. Given the lack of data at the time on CAC and coronary atherosclerosis burden, the algorithm was remarkable yet unactionable.

Roger S. Blumenthal
Paul Scheel III
Garima Sharma

Since that publication by Arthur Agatston, MD, and Warren Janowitz, MD, in 1990, a plethora of data on CAC has shown a direct, proportional relationship between CAC scores and major adverse clinical atherosclerotic CVD, and absolute CAC scores are the best predictor of near-term absolute risk of events over a 5-to-10-year period.

The 2018 American Heart Association/American College of Cardiology Guideline on the Management of Blood Cholesterol and the 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease recommended CAC scoring as reasonable to guide primary prevention risk discussions in asymptomatic adults aged 40 to 75 years with LDL 70 mg/dL to 189 mg/dL at intermediate risk (7.5% to 19.9% 10-year ASCVD risk) or in select individuals at borderline risk (5% to 7.4% 10-year risk) if risk-based decisions for statin therapy remain uncertain (class IIa; level of evidence, B-NR; see Table for 2015 ACC/AHA clinical practice guideline recommendation classification system ).

Similarly, the 2019 European Society of Cardiology/European Atherosclerosis Society Guidelines for the Management of Dyslipidaemias stated CAC scoring should be considered as a risk modifier in patients at low or moderate risk for ASCVD, defined as less than 5% 10-year risk for CV death using the Systematic Coronary Risk Evaluation (SCORE) system.

The National Lipid Association (NLA) recently released its Scientific Statement on Coronary Calcium Scoring to Guide Preventive Strategies for ASCVD Risk Reduction, further delineating and cementing the role of CAC in ASCVD primary prevention. What follows is a brief summary of the NLA guidelines (Figure).

Who is CAC not for?

CAC scoring should be done only if results will alter treatment decisions in primary prevention of ASCVD. For adults with clinical ASCVD, CAC scoring is not recommended (class III, no benefit). Furthermore, for individuals with ASCVD risk less than 5% and no family history of premature ASCVD or greater than 20%, CAC scoring is not indicated, and individuals should be treated according to the 2018 AHA/ACC lipid guidelines.

Reporting CAC

CAC scores should be reported as the absolute Agatston CAC score and the age, sex and race/ethnicity-based CAC percentiles (class I; level of evidence, B-NR). The absolute CAC score should be used to guide pharmacologic decisions, whereas the CAC score percentile (derived from MESA) should be used to estimate lifetime treatment benefit, particularly important among young and older patients.

Age-based approach

Similar to the 2018 and 2019 AHA/ACC guidelines, the NLA guidelines state in adults aged 40 to 75 years with LDL 70 mg/dL to 189 mg/dL and 5% to 19.9% 10-year ASCVD risk, CAC scoring can be useful in deciding the need for and intensity of preventive therapies (class IIa; level of evidence, B-NR). Additionally, in this demographic, if 10-year ASCVD risk is less than 5% but a strong family history of premature ASCVD is present, CAC scoring is reasonable (class IIa; level of evidence, B-NR). The guidelines further state it is reasonable to defer statin initiation if CAC equals 0 in this group, so long as diabetes, current cigarette smoking and/or a strong family history of premature ASCVD is not present (class IIa; level of evidence, B-NR).

In individuals younger than 40 years, CAC scoring is appropriate if multiple major ASCVD risk factors or a strong family history of premature ASCVD are present. In this group, CAC greater than 0 favors intensification of lifestyle therapy and, if necessary, initiation of statin therapy (class IIa; level of evidence, B-NR).

In individuals older than 75 years with LDL 70 mg/dL to 189 mg/dL in whom the decision to employ statin therapy is uncertain, CAC scoring can be useful for ASCVD risk reclassification (class IIa; level of evidence, B-R). CAC of 0 favors deferral or avoidance of statin therapy in this group (class IIb; level of evidence, B-NR).

Special populations

In individuals with diabetes, the NLA guidelines focus on the utility of CAC scoring for further risk stratification, a sentiment echoed by the Endocrine Society’s recent guidelines. In accordance with existing AHA/ACC lipid guidelines, the NLA recommends moderate- or high-intensity statin therapy regardless of CAC score in adults aged 40 to 75 years with type 2 diabetes and LDL 70 mg/dL to 189 mg/dL (class I; level of evidence, A). In this population, it is reasonable for those with a CAC score greater than 100 to be upgraded to a high-intensity statin (class IIa; level of evidence, C-LD).

In adults aged 30 to 39 years with long-standing diabetes and ASCVD risk factors and/or known microangiopathy, CAC scoring may aid in ASCVD risk stratification (class IIb; level of evidence, C-LD). In those older than 75 years with type 2 diabetes in whom the decision to employ a statin for primary prevention is uncertain, CAC scoring can aid in shared decision-making (class IIa; level of evidence, C-LD).

There are limited data on CAC scoring in individuals with LDL-C of at least 190 mg/dL; however, the guidelines state, in the absence of extreme LDL elevation, additional major ASCVD risk factors, or a family history of premature ASCVD, CAC scoring may aid in both short- and intermediate-term ASCVD risk prediction in genetic and phenotypic severe hypercholesterolemia and assist in decision-making regarding nonstatin therapies (class IIb; level of evidence, C-LD). CAC greater than 0 in this group can be an indicator for more aggressive LDL-lowering strategies. Note, CAC of 0 does not preclude the need for long-term evidence-based LDL-lowering therapy using a generic statin in this group.

General treatment strategies

The guidelines recommend initiation of statin therapy and aspirin 81 mg, if no bleeding contraindications, in adults with CAC scores of at least 100 (class IIa; level of evidence, B-NR). High-intensity statin therapy and, if necessary, guideline-based nonstatin therapies are recommended for CAC scores of at least 300.

For a given CAC score, a diffuse distribution (two or more arteries) of CAC and/or presence of left main coronary calcification (especially when > 25% of the total score) suggests higher ASCVD risk and may favor more aggressive therapy. However, in individuals with predominant left main coronary calcification, multivessel coronary involvement or a high CAC score, in the absence of clinically relevant symptoms, stress testing or invasive coronary arteriography is not recommended (class III-harm).

CAC scoring intervals

In those with a CAC of 0, CAC scoring can be done at the following intervals: low risk (< 5% 10-year risk), 5-7 years; borderline to intermediate risk (5% to 19.9% 10-year risk), 3 to 5 years; high risk or diabetes, 3 years (class IIa; level of evidence, B-NR). For CAC scores of 1 to 99, it is reasonable to repeat CAC scoring in 3 to 5 years if results may change treatment decisions (class IIb; level of evidence, B-NR); however, most clinicians would simply continue statin therapy and aim for an LDL < 70 mg/dL.

For CAC scores of at least 100 and LDL of at least 70 mg/dL, repeat CAC scoring at 3 years may be reasonable to assess for accelerated progression (> 20% to 25% per year) and/or an increase to a CAC score greater than 300, which may favor more aggressive LDL lowering (class IIb; level of evidence, C-LD). However, it is more cost-effective to simply treat the LDL to < 70 mg/dL and try to optimize other risk factors.

Incidental CAC

If incidental, mild CAC (CAC-data reporting system [DRS] visual score = 1) is found on nongated chest CT, a dedicated CAC scan to guide treatment decision-making is reasonable (class IIb; level of evidence, C-LD). If incidental, moderate or severe CAC (CAC-DRS visual score 2) is found, initiation of statin therapy without dedicated CAC imaging is suggested (class IIa; level of evidence, B-NR).

Becoming a sentinel test

Since 2018, U.S. and European guidelines have recommended selective use of CAC for guiding treatment decisions in primary prevention of ASCVD, and the NLA guidelines have further solidified and expanded this role. However, although the use of CAC scoring continues to increase, barriers to more widespread use remain.

The 2018 U.S. Preventive Services Task Force concluded the current evidence is insufficient (due to lack of sufficiently large randomized controlled trials) to recommend CAC scoring to current ASCVD risk assessment. And, as the NLA guidelines admit, clinical trials directly testing a CAC-based strategy are sparse. However, there are large-scale trials underway in Europe and the U.S.

CAC testing is a rapid, reproducible and low-cost test that does not require contrast or IV access. As further data become available, CAC scoring will likely have a larger role to play in asymptomatic primary prevention of ASCVD as well as other areas. As recent studies have opined, plaque burden and not stenosis may have greater predictive CAC scoring, which could be used in the diagnostic pathway for stable chest pain and to guide patient selection for primary prevention randomized controlled trials of novel add-on therapies. Much as the utility of Agatston’s algorithm needed time to be fully realized, it may only be a matter of time before CAC scoring becomes a sentinel test.

References:

For more information:

Andrew Gagel, MD, is a resident physician at Johns Hopkins Hospital. Twitter: @andygagel.

Paul Scheel III, MD, is a cardiovascular fellow at Johns Hopkins Hospital. Twitter: @js08paul.

Roger S. Blumenthal, MD, is director of the Johns Hopkins Ciccarone Center for the Prevention of Cardiovascular Disease and professor of medicine at Johns Hopkins University School of Medicine. He is also the editor of the Prevention section of the Cardiology Today Editorial Board. Twitter: @rblument1.

Garima Sharma, MD, is assistant professor of medicine at Johns Hopkins University School of Medicine. Twitter: @garimasharma. The authors can be reached at Johns Hopkins Ciccarone Center for the Prevention of Cardiovascular Disease, Division of Cardiology, Johns Hopkins University School of Medicine, 600 N. Wolfe St., Halsted 560, Baltimore, MD 21827.