Regional coronary endothelial function is closely related to local early coronary atherosclerosis in patients with mild coronary artery disease: pilot study

Abstract

Background: Coronary endothelial function is abnormal in patients with established coronary artery disease and was recently shown by MRI to relate to the severity of luminal stenosis. Recent advances in MRI now allow the noninvasive assessment of both anatomic and functional (endothelial function) changes that previously required invasive studies. We tested the hypothesis that abnormal coronary endothelial function is related to measures of early atherosclerosis such as increased coronary wall thickness.

Methods and results: Seventeen arteries in 14 healthy adults and 17 arteries in 14 patients with nonobstructive coronary artery disease were studied. To measure endothelial function, coronary MRI was performed before and during isometric handgrip exercise, an endothelial-dependent stressor, and changes in coronary cross-sectional area and flow were measured. Black blood imaging was performed to quantify coronary wall thickness and indices of arterial remodeling. The mean stress-induced change in cross-sectional area was significantly higher in healthy adults (13.5%±12.8%, mean±SD, n=17) than in those with mildly diseased arteries (-2.2%±6.8%, P<0.0001, n=17). Mean coronary wall thickness was lower in healthy subjects (0.9±0.2 mm) than in patients with coronary artery disease (1.4±0.3 mm, P<0.0001). In contrast to healthy subjects, stress-induced changes in cross-sectional area, a measure of coronary endothelial function, correlated inversely with coronary wall thickness in patients with coronary artery disease (r=-0.73, P=0.0008).

Conclusions: There is an inverse relationship between coronary endothelial function and local coronary wall thickness in patients with coronary artery disease but not in healthy adults. These findings demonstrate that local endothelial-dependent functional changes are related to the extent of early anatomic atherosclerosis in mildly diseased arteries. This combined MRI approach enables the anatomic and functional investigation of early coronary disease.

Figures

Figure 1. Typical anatomical and functional coronary images using magnetic resonance imaging at rest and with isometric handgrip stress

In a healthy subject, in image A, a scout scan obtained along the RCA (right coronary artery) in a healthy adult subject is shown together with the location for cross-sectional imaging (red line). In B, a view perpendicular to the RCA in a healthy adult subject is shown, illustrating a black blood vessel wall cross section. In C, a view perpendicular to the RCA in a healthy subject is shown at rest (C) and during stress (D). In a patient with CAD, shown in images E-H, a scout scan obtained parallel to the RCA is shown (E) together with the location for cross-sectional imaging (red line). F: RCA black blood vessel wall cross-sectional image in the same CAD patient. In G, a view perpendicular to the RCA in a CAD patient is shown at rest (G) and during stress (H).

Figure 2. Relative changes in coronary artery area, peak diastolic coronary flow velocity and blood-flow during isometric handgrip stress and mean coronary wall thickness

(A) Relative changes in coronary vasoreactive parameters with stress for healthy subjects (blue bars, n=17 arteries studied in 14 subjects) and patients with CAD (red bars, n=17 arteries in 14 subjects). Bars indicate standard deviations. (B) Average coronary wall thickness (mm) for healthy individuals and CAD patients (* p

Figure 3. MRI measures of coronary wall thickness (mm) versus % coronary cross sectional area changes with isometric handgrip stress in healthy subjects and patients with coronary artery disease (combined)

Individual data points shown for healthy subjects (blue diamonds) and patients with coronary artery disease (red diamonds). The standard error of the estimate (SEE)=0.27.

Figure 4. MRI measures of coronary wall thickness (CWT) versus % coronary cross sectional area changes and % velocity changes with isometric handgrip stress

Individual data points shown for healthy subjects (blue diamonds) and for patients with coronary artery disease (red diamonds). CWT (mm) versus % coronary area change with stress is shown for (A) healthy subjects (standard error of the estimate, SEE=0.18), and (B) patients with CAD (SEE=0.22). Coronary wall thickness versus % coronary velocity change with stress is shown in (C) for healthy subjects (SEE=0.18) and (D) for CAD patients (SEE=0.31).

Figure 5

MRI measure of normalized wall index (NWI) versus % coronary cross sectional area change with isometric handgrip stress in (A) healthy subjects (standard error of the estimate, SEE=0.08) and (B) patients with coronary artery disease (SEE=0.06).