Coronary artery calcium in primary prevention: "the one with a zero wins".

Identifying high-risk asymptomatic individuals remains the cornerstone of cardiovascular disease prevention. Coronary artery calcium is a highly specific marker of atherosclerosis that can be quantified using non-contrast computed tomography. The resulting calcium score has the capacity to improve current methods of risk stratification especially for individuals in intermediate risk category.

While chronic angina is a common presentation of coronary artery disease (CAD), up to half of individuals will initially present with myocardial infarction or sudden cardiac death. For the purposes of prevention, it is necessary to identify asymptomatic at-risk individuals likely to benefit from the early detection and treatment of CAD.

Cardiovascular risk assessment for the purpose of initiating primary prevention is usually based on pooled equations like ASCVD risk score, Framingham equation etc. While these tools offer a quick and cost-effective method of risk assessment, it is recognised that many patients are not identified as high risk prior to their first coronary event.

To fill this lacunae, the quantification of coronary calcium by non-contrast computed tomography (CT) has emerged as an attractive tool to improve risk stratification and risk reclassification in asymptomatic individuals.

History: the journey of more than 4 decades

The link between coronary calcium and atherosclerosis has been known since the 1970s, when fluoroscopically detected calcium was associated with adverse cardiovascular events. With the development of CT imaging, coronary calcium was found to correlate with atherosclerotic plaque volumes. As a surrogate measure of atherosclerotic burden, calcium score can be considered a reflection of an individual's cumulative risk factor exposure across their lifetime.

Interpretation of calcium scores

Calcium quantified by Agatston method is represented by an absolute numerical value and a percentile based on sex, age and ethnicity. Most classifications systems divides calcium scores into the following groups on the basis of absolute values: CAC = 0, CAC = 1–100, CAC = 101–400, and CAC >400, with each group corresponding to a particular level of cardiovascular risk (Figure).

Benefits of scoring:

1. Large prospective studies of asymptomatic individuals have shown that calcium score predicts important cardiovascular outcomes, including coronary events, myocardial infarction and all-cause mortality.

2. A key advantage of calcium scoring is that while high scores are associated with elevated cardiovascular risk, the absence of coronary calcium is a negative risk marker that confers a favourable prognosis.

3. The negative predictive value of zero coronary calcium appears to be greatest in individuals at intermediate risk by traditional risk calculators; 45% of these patients will have CAC = 0, placing them at a low cardiovascular risk and removing the need for preventive therapy such as statins.

4. Studies have shown that the addition of calcium scoring to traditional risk calculators improves the accuracy of risk prediction.

5. In particular, the use of calcium scoring results in a significant net reclassification improvement (NRI), defined as the proportion of a population correctly reassigned to a higher or lower risk class following calcium scoring. Data from MESA determined that calcium scoring produced an NRI of 25% when added to the Framingham Risk Equation, and that this improvement was greatest in the intermediate-risk population, for whom the NRI was 55%.

Limitations:

1. Studies have generally reported smaller reclassification benefits among low- and high-risk individuals, therefore its use in these categories of patients is not warranted.

2. Calcium scoring is not currently recommended for symptomatic patients. Instead, guidelines recommend the upfront use of stress testing or cardiac CT angiography, which provide assessment of ischaemia and luminal stenosis, respectively.

3. Calcium scoring does not provide information on the presence or burden of non-calcified plaque, which has low radiological attenuation and requires contrast administration to be assessed.

The prognostic value of CAC in primary prevention has resulted in a prominent role in current clinical practice guidelines around the world. Current United States (US) and European guidelines all recommend selective use of CAC for guiding treatment decisions for primary prevention of ASCVD in individuals at borderline or intermediate risk. US guidelines have seen a growing role for CAC, upgrading the most recent CAC related recommendations to IIa.

On the basis of the available evidence, the guidelines recommend that preventive therapy with aspirin and a statin is appropriate for individuals with CAC >100 and recommends no therapy for individuals with CAC = 0.

Although statins may themselves increase the CAC score due to plaque stabilisation but their overall benefit is undebated. There is no role for serial CAC measurement in assessing response to primary prevention strategies.

To summarise, Coronary calcium score is a surrogate marker of calcified atherosclerotic burden that independently predicts cardiovascular risk and mortality. It is a widely available test typically performed in intermediate-risk asymptomatic patients. Risk estimates provided by calcium scoring improves the accuracy of traditional risk calculators and can be used for the risk-based selection of patients for preventive pharmacotherapy.

Source: 1. https://www.acc.org/latest-in-cardiology/articles/2021/06/21/13/05/the-ever-growing-role-of-cac-in-primary-prevention

2. Chua A, Blankstein R, Ko B. Coronary artery calcium in primary prevention. Aust J Gen Pract. 2020 Aug;49(8):464-469. doi: 10.31128/AJGP-03-20-5277.