The United States (US) National Cholesterol Education Program (NCEP) formed the Adult Treatment Panel (ATP) in 1985 with the aim to educate clinician and provide guideline recommendations for the treatment of dyslipidemias. In its first 1998 recommendations, the approach to primary prevention of cardiovascular disease included LDL-cholesterol (LDL-C) reduction in individuals with more than two risk factors and LDL-C levels above 160mg/dL and optional treatment in those with “borderline” LDL-C levels between 130 – 159 mg/dL. In its second version, in 1994, a category of secondary prevention with a target LDL-C below 100mg/dL was introduced. In 2001 the third version of the document, ATP-III introduced the concept of “optimal” LDL-C < 100mg/dL and introduced the use of the 10-year Framingham risk score (FRS) for the estimation of risk to define the intensity of treatment and target LDL-C levels, and an update of this document introduced a more aggressive LDL-C < 70 mg/dL target for those at extremely high risk. The ATP-III also mentions coronary artery calcium (CAC) as an “emerging risk factor”, stating it could be of value for additional risk stratification, predominantly in intermediate risk groups. Interestingly, at this point the recommendations were that CAC could be of use in individuals with multiple risk factors or older individuals in whom “traditional risk factors lose some of their predictive power”. In both cases CAC was proposed as a tool to screen for individuals at an even higher than expected risk, though the ATP-III clearly advised against the widespread use of CAC as a screening tool.

After the update of ATP-III there was a considerable gap before the publication of the 2013 ACC/AHA Blood Cholesterol guidelines, and a completely new approach towards the selection of candidates for treatment of LDL-C was taken. First, this document updated the equations for calculating 10-year cardiovascular risk (the Framingham Risk Score only predicted risk of coronary heart disease). Second, it identified higher risk groups which should be treated irrespective of risk (LDL-C > 190 mg/dL, diabetics). Third, it proposed a much broader recommendation of statin use for primary prevention including all individuals with LDL-C > 70 mg/dL and a calculated atherosclerotic cardiovascular disease risk > 5% in 10 years. This broader approach has been criticized by many , as it resulted in a substantial increase in the number of individuals in whom statins would be recommended, including treatment recommendations of lower risk individuals due to overestimation of risk derived from the risk assessment tool. This document also gave CAC a class IIb indication for a selective use in individuals fitting the vague description “in whom the decision to start treatment was unclear”. In this document additional markers of risk included CAC, high sensitivity C-reactive protein, ankle braquial index, family history of premature cardiovascular disease or individuals with LDL-C > 160 mg/dL – and all were given similar IIb recommendations with little to differentiate their predictive power. As recommended in ATP-III, the use of those markers was as an additional screening tool to identify individuals with a higher risk for more aggressive treatment, though no clear recommendation on its use was provided.

[…]