Coronary artery calcification detected in lung cancer screening predicts cardiovascular death

Abstract

Objectives. It remains unknown whether non-electrocardiogram-gated coronary artery calcium (CAC) score in lung cancer screening provides incremental prognostic value. The aim of this study was to evaluate the prognostic value of CAC in the Danish Lung Cancer Screening Trial (DLCST), in addition to conducting a systematic review and meta-analysis including previously published studies regarding CAC in lung cancer screening. Design. In DLCST, we measured Agatston CAC scores in 1,945 current and former smokers. Causes of death were extracted from the Danish National Death Registry. We used Cox proportional hazards model to determine hazard ratios (HRs) of CAC scores. A weighted fixed-effects model was used for the meta-analysis. Results. Median follow-up in DLCST was 7.1 years, and 55% were men. Overall survival rates associated with CAC scores of 0, 1–400, and > 400 were 98%, 96%, and 92% (p < 0.001), respectively. Adjusted HR of cardiovascular death associated with CAC >400 was 3.8 (1.0–15) (p < 0.05). The meta-analysis included 28,045 asymptomatic participants. A high non-gated CAC score was associated with fatal or non-fatal cardiovascular events (p < 0.0001). Conclusion. Assessment of non-electrocardiogram-gated CAC in lung cancer screening programs is a robust prognostic measure of fatal or non-fatal cardiovascular events in current and former smokers independent of traditional cardiovascular risk factors.

Trial registration: ClinicalTrials.gov identifier: NCT00496977.

Key words::

• atherosclerosis
• coronary artery calcium score
• lung cancer screening
• smoking

Acknowledgements

Dr. TR is responsible for making the statistical work and drafting of the manuscript, while LK, JA, JHP, MMW, AD, and KFK contributed substantially in the process of critical reviewing. The authors thank the investigators, staff, and participants of the Danish Lung Cancer Screening Trial for their valuable contributions.

Financial disclosures

Dr. TR was supported by an unrestricted grant from AstraZeneca AB and the Danish Heart Foundation. The DLCST trial was funded in full by a governmental grant by the Danish Ministry of Health and Prevention from 2004 to 2011. KFK and LK were supported by the Danish Agency of Science, Technology and Innovation and by the Danish Council for Strategic Research (grant 09-066994). LK reports personal fees from Speaker for Servier and personal fees from Honorarium from Novartis, outside the submitted work.

Declaration of interests: The authors report no declarations of interest. The authors alone are responsible for the content and writing of the paper.