Background
The long‐term course of coronary atherosclerosis has not been studied in large nationwide cohorts. Understanding the natural history of coronary atherosclerosis could help identify patients at risk for future coronary events.

Methods and Results
All coronary artery segments with <50% luminal stenosis in patients with a first‐time coronary angiogram between 1989 and 2017 were identified (n=2 661 245 coronary artery segments in 248 736 patients) and followed until a clinically indicated angiography within 15 years was performed or until death or end of follow‐up (April 2018) using SCAAR (Swedish Coronary Angiography and Angioplasty Registry). The stenosis progression and incidence rates were 2.6% and 1.45 (95% CI, 1.43–1.46) per 1000 segment‐years, respectively. The greatest progression rate occurred in the proximal and middle segments of the left anterior descending artery. Male sex and diabetes were associated with a 2‐fold increase in risk, and nearly 70% of new stenoses occurred in patients with baseline single‐vessel disease (hazard ratio, 3.86 [95% CI, 3.69–4.04]). Coronary artery segments in patients with no baseline risk factors had a progression rate of 0.6% and incidence rate of 0.36 (95% CI, 0.34–0.39), increasing to 8.1% and 4.01 (95% CI, 3.89–4.14) per 1000 segment‐years, respectively, in patients with ≥4 risk factors. The prognostic impact of risk factors on stenosis progression was greatest in younger patients and women.

Conclusions
Coronary atherosclerosis progressed slowly but more frequently in the left coronary artery in men and in the presence of traditional risk factors. Coronary artery segments in patients without risk factors had little or no risk of stenosis progression, and the relative impact of risk factors appears to be of greater importance in younger patients and women. These findings help in the understanding the long‐term course of coronary atherosclerosis.