Impact on All-Cause and Cardiovascular Mortality Rates of Coronary Artery Calcifications Detected during Organized, Low-Dose, Computed-Tomography Screening for Lung Cancer: Systematic Literature Review and Meta-Analysis

Abstract

Although organized, low-dose, computed-tomography (CT) scan lung-cancer screening has been shown to lower all-cause and lung-cancer-specific mortality, the primary cause of death for subjects eligible for such screening remains cardiovascular (CV) mortality. This meta-analysis study was undertaken to evaluate the impact of screening-scan-detected coronary artery calcifications (CACs) on CV and all-cause mortality. We conducted a systematic review and meta-analysis of studies reporting CV mortality according to the Agatson CAC score for participants in a lung-cancer screening program of randomized clinical or cohort studies. PubMed, Embase, and Cochrane databases were screened in June 2020. Two authors independently selected articles and extracted data. Six studies, including 20,175 subjects, were retained. CV and all-cause mortality rates were higher for subjects with CAC scores >0, with respective relative risks of 2.02 [95% CI 1.23–3.32] and 2.29 [95% CI 1.00–5.21]. Both mortality rates were even higher for those with high CAC scores (>400 or >1000). CACs are more common in men than in women, with an odds ratio of 1.49 [95% CI 1.40–1.59]. The presence of CAC is associated with CV mortality with an RR of 2.05 [95% CI 1.20–3.57] in men and 2.37 [CI 95% 1.29–5.09] in women, respectively. Analysis of lung-cancer-screening scans for CACs is a tool able to predict CV mortality. Prospective studies within those programs are needed to assess the benefit of primary CV prevention based on CAC detection.

Predictive value of automated coronary calcium scoring in lung cancer screening with low dose computed tomography

“…The automated AI-driven analysis of coronary artery calcifications of MILD volunteers confirmed our previous observation that CAC is an independent predictor for all-cause mortality (3), and that CAC > 400 is associated with a significantly worse survival at 12 years. These results are in keeping with a case-cohort study from the NELSON trial demonstrating that higher strata of CAC score had a significantly higher risk of coronary events compared with negative (10), and with a meta-analysis of 6 LCS trials showing that subjects with high CAC values had more than two-fold increased relative risk of all-cause mortality (11). The extended follow-up of MILD trial revealed a 3-fold higher mortality risk for aCAC >20 and 5-fold risk for aCAC >400 (p<0.0001 and p<0.0001 respectively).…”

“…Coronary artery calcium (CAC) is an independent predictor of cardiovascular (CV) events (1). Previous studies in low dose computed tomography (LDCT) screening participants demonstrated the predictive value of CAC score for all-cause and CV mortality (2,3), with a CAC scoring accuracy of LDCT that was similar to the one achieved by electrocardiographic-gated cardiac CT (4,5).…”

“…Previous studies in low dose computed tomography (LDCT) screening participants demonstrated the predictive value of CAC score for all-cause and CV mortality (2,3), with a CAC scoring accuracy of LDCT that was similar to the one achieved by electrocardiographic-gated cardiac CT (4,5). CAC evaluation is not routinely performed in LDCT screening because manual CAC measurements is a highly time-consuming procedure, but currently available artificial intelligence (AI) software allows a fully automated quantification with high accuracy (6).…”

Automated Coronary Artery Calcium and Quantitative Emphysema in Lung Cancer Screening

“…For instance, every 1% increase in the percentage of %LAA independently predicted all-cause death in the CT arm of the National Lung Screening Trial (NLST) 26 . In a recent meta-analysis including studies from different LCS trials, subjects in high CAC categories had a relative risk of all-cause mortality of 2.47 (95% CI, 1.75-3.47) and 2.90 (95% CI, 1.57-5.36) based on a fixed-effect model and a random-effect model, respectively 31 . In keeping with these results, our findings argue in favor of %LAA and CAC to predict all-cause and noncancer mortality in LCS.…”

Fully automated calcium scoring predicts all-cause mortality at 12 years in the MILD lung cancer screening trial

“…Coronary artery calcium (CAC) is an independent predictor of cardiovascular (CV) events and mortality [ 1 ]. Previous studies in low-dose computed tomography (LDCT) lung cancer screening (LCS) participants demonstrated the predictive value of manual CAC scoring [ 2 , 3 ]. Nevertheless, the timely consuming procedure of manually computing CAC scoring currently hinders its routine evaluation in LCS.…”