Coronary artery calcium is associated with long-term mortality from lung cancer: Results from the Coronary Artery Calcium Consortium

Abstract

Background and aims: Coronary artery calcium (CAC) scores have been shown to be associated with CVD and cancer mortality. The use of CAC scores for overall and lung cancer mortality risk prediction for patients in the Coronary Artery Calcium Consortium was analyzed.

Methods: We included 55,943 patients aged 44-84 years without known heart disease from the CAC Consortium. There were 1,088 cancer deaths, among which 231 were lung cancer, identified by death certificates with a mean follow-up of 12.2 ± 3.9 years. Fine-and-Gray competing-risk regression was used for overall and lung cancer-specific mortality, accounting for the competing risk of CVD death and after adjustment for CVD risk factors. Subdistribution hazard ratios (SHR) were reported.

Results: The mean age of all patients was 57.1 ± 8.6 years, 34.9% were women, and 89.6% were white. Overall, CAC was strongly associated with cancer mortality. Lung cancer mortality increased with increasing CAC scores, with rates per 1000-person years of 0.2 (95% CI: 0.1-0.3) for CAC = 0 and 0.8 (95% CI: 0.6-1.0) for CAC ≥400. Compared with CAC = 0, hazards were increased for those with CAC ≥400 for lung cancer mortality [SHR: 1.7 (95% CI: 1.2-2.6)], which was driven by women [SHR: 2.3 (95% CI: 1.1-4.8)], but not significantly increased for men. Risks were higher in those with positive smoking history [SHR: 2.2 (95% CI: 1.2-4.2)], with associations driven by women [SHR: 4.0 (95% CI: 1.4-11.5)].

Conclusions: CAC scores were associated with increased risks for lung cancer mortality, with strongest associations for current and former smokers, especially in women. Used in conjunction with other clinical variables, our data pinpoint a potential synergistic use of CAC scanning beyond CVD risk assessment for identification of high-risk lung cancer screening candidates.

Keywords: Cancer; Cardiovascular disease; Coronary arterial calcium; Lung cancer; Prevention; Risk prediction.

Figure 1.

Mortality rates for lung cancer deaths by CAC score group and sex. Mortality rates for lung cancer as rate per 1,000 person-years in all patients, men and women are shown. CAC = coronary artery calcium score.

Figure 2.

Risks for lung cancer mortality by CAC score group and sex. Subdistribution hazard ratios (SHR) for lung cancer mortality with CVD as competing event and with CAC = 0 as a reference group are depicted. The following models are shown stratified by CAC score groups: Unadjusted model; Model 1 (*) was adjusted for age and sex (except for sex-specific SHR); Model 2 (**) was adjusted for age, sex (except for sex-specific SHR), hypertension, hyperlipidemia, smoking, family history, diabetes. CAC = coronary artery calcium score.

Figure 3.

Risks for lung cancer mortality in smokers by CAC score group and sex. Subdistribution hazard ratios (SHR) for lung cancer mortality with CVD as competing event and with CAC = 0 as a reference group are depicted. Grouped as current smokers and those with positive smoking history (current smokers + former smokers). Unadjusted data stratified by CAC score are shown.

Figure 4.

Subdistribution hazard ratios for lung cancer mortality as a function of age by CAC score group, smoking status and sex. Graphed subdistribution hazard ratios (SHR) as a function of age. SHR were adjusted for conventional risk factors for age, sex (except for sex-specific SHR), hypertension, hyperlipidemia, smoking, family history, diabetes. SHR for lung cancer mortality by CAC score groups and sex (A) and by smoking status and sex (B). All SHR are referred to the CAC = 0 group at age 60 years. Lung cancer mortality risk increased exponentially with age and showed the steepest increase for smoking men with CAC ≥ 400. Dotted grey line indicates SHR = 1. CAC = coronary artery calcium score.