Preventing ASCVD Events: Using Coronary Artery Calcification Scores to Personalize Risk and Guide Statin Therapy

Primary Prevention in LCS

The initial approach to primary prevention in LCS is no different from that recommended by the 2018 multisociety guidelines on the management of blood cholesterol, the 2019 American College of Cardiology/American Heart Association (ACC/AHA) guideline on primary prevention, or the 2022 USPTSF recommendations on statin use for primary prevention of CV disease in adults.^21-23 For a baseline low-density lipoprotein cholesterol (LDL-C) ≥ 190 mg/dL, high-intensity statin therapy is recommended without further risk stratification. Individuals with diabetes also are at higher-than-average risk, and moderate-intensity statin therapy is recommended.

For individuals not in either group, a validated ASCVD risk assessment tool is recommended to estimate baseline risk. The most validated tool for estimating risk in the US population is the 2013 ACC/AHA Pooled Cohort Equation (PCE) which provides an estimate of the 10-year risk for fatal and myocardial infarction and fatal and nonfatal stroke.²⁴ The PCE risk calculator uses age, presence of diabetes, sex, smoking history, total cholesterol, high-density lipoprotein cholesterol, systolic blood pressure, and treatment for hypertension to place individuals into 1 of 4 risk groups: low (< 5%), borderline (5% to < 7.5%), intermediate (≥ 7.5% to < 20%), and high (≥ 20%). Clinicians should be aware that the PCE only considers current smoking history and not prior smoking history or cumulative pack-year history. This differs from eligibility for LCS where recent smoking plays a larger role. All these risk factors are important to consider when evaluating risk and discussing risk-reducing strategies like statin therapy.

The 2018 multisociety guidelines and the 2019 primary prevention guidelines set the threshold for considering initiation of statin therapy at intermediate risk ≥ 7.5%.^21,22 The 2020 US Department of Veterans Affairs/Department of Defense guidelines set the threshold for considering statin therapy at an estimated 10-year event rate of 12%, whereas the 2022 UPSTF recommendations set the threshold at 10% with additional risk factors as the threshold for statin therapy.^23,25 The reasons for these differences are beyond the scope of this review, but all these guidelines use the PCE to estimate baseline risk as the starting point for clinical decision making.

The PCE was originally derived and validated in population studies dating to the 1960s when the importance of diet, exercise, and smoking cessation in reducing ASCVD events was not well appreciated. The application of the PCE in more contemporary populations shows that it overestimates risk, especially in older individuals and women.^26,27 Overestimation of risk has the potential to result in the initiation of statin therapy in individuals in whom the actual clinical benefit would otherwise be small.

To address this issue, current guidelines allow the use of CAC scoring to refine risk in individuals who are classified as intermediate risk and who otherwise desire to avoid lifelong statin therapy. Using current recommendations, we make suggestions on how to use CAC scores from LDCT to aid in clinical decision making for individuals in LCS (Figure).

No Coronary Artery Calcification

Between 25% and 30% of LDCT done for LCS will show no CAC.^14,16 In general population studies, a CAC score of 0 is a strong negative predictor when there are no other risk factors.^13,28 In contrast, the negative predictive ability of a CAC score of 0 in individuals with a smoking history who are eligible for LCS is unproven. In multivariate modeling, a CAC score of 0 did not reduce the significant hazard of all-cause mortality in patients with diabetes or smokers.²⁹ In an analysis of 44,042 individuals without known heart disease referred for CAC scoring, the frequency of a CAC score of 0 was only modestly lower in smokers (38%) compared with nonsmokers (42%), yet the all-cause mortality rate was significantly higher.³⁰ In addition, Multi-Ethnic Study of Atherosclerosis (MESA) participants who were current smokers or eligible for LCS and had a CAC score of 0 had an observed 11-year ASCVD event rate of 13.4% and 20.8%, respectively, leading to the conclusion that a CAC score of 0 may not be predictive of minimal risk in smokers and those eligible for LCS.³¹ Additionally, in LCS-eligible individuals, the PCE underestimated event rates and incorporation of CAC scores did not significantly improve risk estimation. Finally, data from the NLST screening trial showed that the absence of CAC on LDCT was not associated with better survival or lower CV mortality compared with individuals with low CAC scores.³²