A Comparison of Mortality Rates in a Large Population of Smokers and Non-smokers: based on the Presence or Absence of Coronary Artery Calcification

Objectives— To further study the interplay between smoking status, Coronary Artery Calcium (CAC) and all-cause mortality. Background— Prior studies have not directly compared the relative prognostic impact of CAC in smokers versus non-smokers. In particular, while zero CAC is a known favorable prognostic-marker, whether smokers without CAC have as good a prognosis as non-smokers without CAC is unknown. Given computed tomography (CT) screening for lung cancer appears effective in smokers, the relative prognostic implications of visualizing any CAC versus no CAC on such screening also deserve study. Methods— Our study cohort consisted of 44,042 asymptomatic individuals referred for non-contrast cardiac CT (age 54±11 years, 54% males). Subjects were followed for a mean of 5.6 years. The primary endpoint was all-cause mortality. Results— Approximately 14% (n=6020) of subjects were active smokers at enrollment. There were 901 deaths (2.05%) overall, with increased mortality in smokers vs. non-smokers (4.3% vs. 1.7%, p<0.0001). Smoking remained a risk factor for mortality across increasing strata of CAC scores (1-100, 101-400, and >400). In multivariable analysis within these strata, we found mortality hazard ratios (HRs) of 3.8 (95% CI, 2.8-5.2), 3.5 (2.6-4.9), and 2.7 (2.1-3.5), respectively, in smokers compared to nonsmokers. At each stratum of elevated CAC score, mortality in smokers was consistently higher than mortality in non-smokers from the CAC stratum above. However, among the 19,898 individuals with CAC=0, the mortality HR for smokers without CAC was 3.6 (95% CI, 2.3-5.7), compared to non-smokers without CAC. Conclusion— Smoking is a risk factor for death across the entire spectrum of subclinical coronary atherosclerosis. Smokers with any coronary calcification are at significantly increased future mortality risk than smokers without CAC. However, the absence of CAC may not be as useful a “negative risk factor” in active smokers; as this group has mortality rates similar to nonsmokers with mild to moderate atherosclerosis.