All-cause mortality in asymptomatic persons with extensive Agatston scores above 1000

Background: Risk assessment in the extensive calcified plaque phenotype has been limited by small sample size. Objective: We studied all-cause mortality rates among asymptomatic patients with markedly elevated Agatston scores >1000. Methods: We studied a clinical cohort of 44,052 asymptomatic patients referred for coronary calcium scans. Mean follow-up was 5.6years (range, 1-13years). All-cause mortality rates were calculated after stratifying by Agatston score (0, 1-1000, 1001-1500, 1500-2000, and >2000). A multivariable Cox regression model adjusting for self-reported traditional risk factors was created to assess the relative mortality hazard of Agatston scores 1001 to 1500, 1501 to 2000, and >2000. With the use of post-estimation modeling, we assessed for the presence of an upper threshold of risk with high Agatston scores. Results: A total of 1593 patients (4% of total population) had Agatston score > 1000. There was a continuous graded decrease in estimated 10-year survival across increasing Agatston score, continuing when Agatston score > 1000 (Agatston score 1001-1500, 78%; Agatston score 1501-2000, 74%; Agatston score > 2000, 51%). After multivariable adjustment, Agatston scores 1001 to 1500, 1501 to 2000, and >2000 were associated with an 8.05-, 7.45-, and 13.26-fold greater mortality risk, respectively, than for Agatston score of 0. Compared with Agatston score 1001 to 1500, Agatston score 1501 to 2000 had a similar all-cause mortality risk, whereas Agatston score > 2000 had an increased relative risk (Agatston score 1501-2000: hazard ratio [HR], 1.01 [95% CI, 0.67-1.51]; Agatston score > 2000: HR, 1.79 [95% CI, 1.30-2.46]). Graphical assessment of the predicted survival model suggests no upper threshold for risk associated with calcified plaque in coronary arteries. Conclusion: Increasing calcified plaque in coronary arteries continues to predict a graded decrease in survival among patients with extensive Agatston score > 1000 with no apparent upper threshold.