The 2018 and 2019 American Heart Association and American College of Cardiology (AHA/ACC) guidelines for primary prevention of atherosclerotic cardiovascular disease (ASCVD) recommend consideration of so-called “risk-enhancing factors” in borderline to intermediate risk individuals. These include high-risk race/ethnicity (e.g. South Asian origin), chronic kidney disease, a family history of premature ASCVD, the metabolic syndrome, chronic inflammatory disorders (e.g. rheumatoid arthritis [RA], psoriasis, or chronic human immunodeficiency virus [HIV]), and conditions specific to women, among others. Studies suggest, however, that risk may be highly heterogeneous within these subgroups. The AHA/ACC guidelines also recommend consideration of coronary artery calcium (CAC) scoring for further risk assessment in borderline to intermediate risk individuals in whom management is uncertain. Although the combination of risk enhancing factors and CAC burden (together with Pooled Cohort estimates) may lead to more accurate ASCVD risk assessment, few publications have closely examined the interplay between risk enhancing factors and CAC scoring for personalized risk estimation. Our aim is to review the relevant literature in this area. Although further research is clearly needed, CAC assessment seems a highly valuable option to inform individualized ASCVD risk management in these important, often highly heterogeneous patient subgroups.Copyright © 2019 Elsevier Inc. All rights reserved.