Natural history of coronary atherosclerosis using quantitative angiography in men, and implications for clinical trials of coronary regression

Abstract

Previous studies of the natural history of coronary disease generally relied on estimates of percent stenosis derived from visual assessment of the coronary angiogram. In a study of 26 patients, serial quantitative angiography was performed 3 years apart to determine changes in both absolute measurements of the luminal diameter and relative percent stenosis. Initially, the mean minimal diameter of 74 coronary obstructions was 1.94 ± 0.09 mm, the mean “normal” reference diameter was 3.06 ± 0.11 mm, and the mean percent stenosis was 37%. At follow-up, there was a mild reduction of 0.12 ± 0.04 mm (6%) in the minimal diameter (p < 0.005), and an increase in percent stenosis to 39% (p = 0.03). The average diameter of 85 arterial segments without a focal obstruction either initially or at follow-up showed mild but significant progression (−0.11 ± 0.04 mm; p = 0.02). Using a minimal change of 0.27 mm in arterial diameter as a categoric variable, progression occurred in 26% of 74 arterial segments, no significant change in 65%, and regression in 9%. The only significant determinant of disease progression was the initial severity of disease. Obstructed arteries with a larger initial minimal diameter and presumably milder disease progressed more rapidly than did those with a smaller diameter (r = −0.42; p = 0.0002). There was no effect of age on the rate of progression (r = 0.02; p = NS). Although overall there was a correlation between the direction and magnitude of change in minimal diameter and those in percent stenosis (r = 0.56; p < 0.0001), changes in percent stenosis can be misleading, because the minimal and adjacent normal diameters may progress independently at different rates. The outcome variable of an atherosclerosis regression trial should be the absolute minimal diameter, as well as percent stenosis.