Human Coronary Artery Remodeling, Beginning and End of the Atherosclerotic Process

BACKGROUND, AIMS OF THE STUDY: The objective of the study was to relate the progress of coronary artery remodeling to the earliest stages of the atherosclerotic process. For this purpose, a mathematical model for description of dimensional change of the coronary artery wall and its constituent components was developed and applied. MATERIALS AND METHODS: The study used coronary artery samples randomly taken from each of 83 consecutive, unselected postmortems. All samples were routinely fixed and processed to paraffin for the preparation of right-angled, 5-micron sections, routinely stained and mounted for subsequent analysis. Computer assisted image analysis, using 32 systematic random, radial sampling lines, was used for interactive measurements of distance from centre of lumen to points defining intima, media and adventitia thickness along the radial intercept, which were subsequently tabled for analysis of variance, calculations of (group –vessel) means, and related to stage of pathology. RESULTS: Pre-atherosclerotic changes, before any localised changes in especially intima dimensions, are found, consisting of a process of gradual vascular widening, associated with temporally at least partly dissociated increases in width, which as a fraction of total vessel radius show a phased process. In these, the intima first increases, subsequently remains stable, and finally reduces in width proportionally to the increasing diameter. The media shows a similar initial increase, on average stabilising in the third phase after reaching a plateau value in the second. The adventitia, already increasing in phase 1, continues to increase in phase 2, accelerating in phase 3. The complex process, as found, occurs systematically in all vessels, is distributed circumferentially, and precedes the development of localised lesions of the intima. CONCLUSIONS: The findings suggest the existence of a diffuse complex of changes, consisting of a gradual vascular widening followed by narrowing, with associated mural changes reflecting the atherosclerotic process

Coronary artery compliance and adaptive vessel remodelling in patients with stable and unstable coronary artery disease

OBJECTIVE—To test the hypothesis that patients with unstable coronary syndromes show accentuated compensatory vessel enlargement compared with patients with stable angina, and that this may in part be related to increased coronary artery distensibility.
DESIGN AND PATIENTS—In 23 patients with unstable coronary syndromes (10 with non-Q wave myocardial infarction and 13 with unstable angina), the culprit lesion was investigated by intravascular ultrasound before intervention. The vessel cross sectional area (VA), lumen area (LA), and plaque area (VA minus LA) were measured at end diastole and end systole at the lesion site and at the proximal and distal reference segments. Similar measurements were made in 23 patients with stable angina admitted during the same period and matched for age, sex, and target vessel. Calculations were made of remodelling index (VA at lesion site ÷ VA at reference site), distensibility index ([(ΔA/A)/ΔP] × 10(3), where ΔA is the luminal area change in systole and diastole and ΔP the difference in systolic and diastolic blood pressure measured at the tip of the guiding catheter during a cardiac cycle), and stiffness index β ([ln(P(sys)/P(dias))]/(ΔD/D), where P(sys) is systolic pressure, P(dias) is diastolic pressure, and ΔD is the difference between systolic and diastolic lumen diameters). Positive remodelling was defined as when the VA at the lesion was > 1.05 times larger than at the proximal reference site, and negative remodelling when the VA at the lesion was < 0.95 of the reference site.
RESULTS—Mean (SD) LA at the lesion site was similar in both groups (4.03 (1.8) v 4.01 (1.93) mm(2)), while plaque area was larger in the unstable group (13.29 (4.04) v 8.34 (3.6) mm(2), p < 0.001). Remodelling index was greater in the unstable group (1.14 (0.18) v 0.83 (0.15), p < 0.001). Positive remodelling was observed in 15 patients in the unstable group (65%) but in only two (9%) in the stable group (p < 0.001). Negative remodelling occurred only in two patients with unstable symptoms (9%) but in 17 (74%) with stable symptoms. At the proximal reference segment, the difference in LA between systole and diastole was 0.99 (0.66) mm(2) in the unstable group and 0.39 (0.3) mm(2) in the stable group (p < 0.001), and the calculated coronary artery distensibility was 3.09 (2.69) and 0.94 (0.83) per mm Hg in unstable and stable patients, respectively (p < 0.001). The stiffness index β was lower in patients with unstable angina (1.95( )(0.94) v 3.1 (0.96), p < 0.001).
CONCLUSIONS—Compensatory vessel enlargement occurs to a greater degree in patients with unstable than with stable coronary syndromes, and is associated with increased coronary artery distensibility.


Keywords: coronary artery disease; remodelling; compliance; angina pectori