Lung cancer remains the most lethal cancer globally, and low-dose CT (LDCT) screening offers the promise of reduced mortality when applied to high-risk individuals. Traditional screening eligibility criteria focus on age and smoking history. However, coronary artery calcium (CAC) scores, originally intended to predict cardiovascular risk, have been proposed as a potential biomarker for lung cancer risk stratification. A large population-based cohort study evaluated the association between CAC scores and incident lung cancer and examined whether CAC measurements can enhance lung cancer screening strategies.
CAC Score and Lung Cancer Association
The Heinz Nixdorf Recall (HNR) study, a long-term, population-based cohort in Germany, provided data to assess whether CAC scores could predict lung cancer diagnoses. Participants aged 45–75 years underwent electron-beam CT (EBCT) of the heart to measure CAC at baseline. Over a median follow-up of 15.4 years, 111 participants developed lung cancer. The analysis confirmed that higher CAC scores were associated with a greater risk of lung cancer. A one-unit increase in the log-transformed CAC score correlated with a 21% higher lung cancer risk after full adjustment for confounders. Notably, those with a CAC score of 1–99 had more than twice the risk, and those with scores above 400 had over four times the risk compared to those with a score of 0.
This relationship was evident even after accounting for variables such as age, sex, smoking intensity and history, socioeconomic status and environmental exposures. These findings suggest that CAC scores reflect cumulative exposure to risk factors common to both cardiovascular disease and lung cancer, particularly smoking. Interestingly, the association persisted, albeit to a lesser extent, in never-smokers, indicating that CAC might capture other biologically relevant exposures linked to lung carcinogenesis.
Predictive Value for Lung Cancer Screening
Despite the robust association between CAC scores and lung cancer incidence, the study found that CAC alone lacks predictive power for guiding lung cancer screening (LCS) decisions. When assessed using the area under the receiver operating characteristic curve (AUC), the CAC score performed poorly as a standalone predictor. In the total sample, the AUC was 0.63, while it was even lower in subgroups: 0.56 for those eligible for LCS and 0.61 for those ineligible. Adding CAC scores to fully adjusted models offered minimal improvement in discrimination.
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These results underscore a critical limitation. Although CAC scores correlate with lung cancer risk, they do not provide sufficient discriminatory capacity to meaningfully inform LCS eligibility. Even among individuals ineligible for LCS by current U.S. Preventive Services Task Force (USPSTF) criteria, high CAC scores did not identify a subgroup with lung cancer incidence comparable to that of LCS-eligible participants. Thus, integrating CAC scores into eligibility criteria would not improve the precision of current screening guidelines.
Clinical and Research Implications
The study highlights the potential role of CAC as a biomarker of biological ageing or cumulative exposure to cardiopulmonary risk factors rather than a practical screening tool. While routine use of CAC scoring in LCS cannot be justified, it may still offer value in clinical conversations. For instance, a high CAC score identified during cardiac CT may prompt clinicians to review a patient's smoking history and consider LCS referral where appropriate. CAC scoring could also aid in motivating smoking cessation or lifestyle modifications among at-risk individuals.
Moreover, CAC scores might play a future role in individualising screening intervals after a baseline LDCT scan. For instance, people with low CAC scores could potentially undergo less frequent screening, optimising resource allocation and minimising exposure to radiation. However, the weak predictive performance observed in this study suggests that CAC-based interval adaptation strategies require further evidence before implementation.
Importantly, this investigation benefits from rigorous methodology. Its use of a directed acyclic graph to identify and control for confounders strengthens causal inference. The long follow-up period and validation of cancer diagnoses add credibility to the findings. Nonetheless, limitations exist. The relatively low number of lung cancer cases, especially among women, may reduce the statistical power to detect sex-specific differences. Furthermore, because the study cohort included a larger proportion of non-smokers, results may not generalise fully to populations with higher smoking prevalence.
Coronary artery calcium scores are independently associated with incident lung cancer in adults aged 45–75 years, reflecting shared risk factors such as tobacco exposure and biological ageing. However, their value as a predictive tool for enhancing lung cancer screening eligibility or efficiency appears limited. While CAC scoring may support broader risk awareness in clinical settings, current evidence does not support its inclusion in formal LCS protocols. Ongoing research is needed to refine risk stratification approaches and to explore how biomarkers like CAC might complement, rather than replace, established screening criteria.
Source: Radiology: Cardiothoracic Imaging
Image Credit: iStock
