Circulation, Vol 89, 1530-1538, Copyright © 1994 by American Heart Association
KL Gould, JP Martucci, DI Goldberg, MJ Hess, RP Edens, R Latifi and SJ Dudrick
BACKGROUND: Cholesterol lowering over 1- to 3-year trials is associated
with modest regression or no progression of focal coronary artery stenoses
compared with progression in controls, a decrease in cardiac events
proportionately more than the modest improvement in percent stenosis, and
in experimental animals improved endothelial-mediated coronary
vasodilation. METHODS AND RESULTS: Accordingly, we hypothesized that there
would be improvement in size and severity of perfusion abnormalities by
rest-dipyridamole positron emission tomography (PET) imaging in a
randomized intensive cholesterol-lowering trial with each patient studied
after a baseline control period, a 90- day intensive cholesterol-lowering
treatment, and a final control period off cholesterol-lowering regimens.
Completely automated, objective measures of size and severity of perfusion
abnormalities on rest-dipyridamole PET images were made by computer
algorithm in 12 patients with coronary artery disease. There were
statistically significant decreases (improvement) in size and severity of
perfusion abnormalities by rest-dipyridamole PET on comparison of baseline
control with perfusion abnormalities after intensive 90-day cholesterol
lowering and significant increases (worsening) in size and severity after
the final control period, respectively, as follows. (1) The percent of left
ventricle outside 2.5 SD of normal values on the dipyridamole-to-rest ratio
image of normalized counts was 22 +/- 20% after the initial control period,
13 +/- 14% after the treatment period, and 26 +/- 22% after the final
control period with a significant decrease (improvement) occurring between
the initial control and treatment periods (P = .02) and an increase
(worsening) occurring between the treatment and final control periods (P =
.009). (2) The percent of left ventricle with a ratio of < or = 0.66 in
the dipyridamole-to-rest ratio image of normalized counts was 11 +/- 13%
after the initial control period, 5.8 +/- 10% after the treatment period,
and 14 +/- 19% after the final control period with a significant decrease
(improvement) occurring between the initial control and treatment periods
(P = .04) and an increase (worsening) occurring between the treatment and
final control periods (P = .02). (3) The myocardial quadrant on the polar
display with the lowest average activity expressed as a percent of maximal
activity was 0.81 +/- 0.18 after the initial control period, 0.87 +/- 0.014
after the treatment period, and 0.77 +/- 0.23 after the final control
period with significant improvement occurring between the initial control
and treatment periods (P = .05) and worsening occurring between the
treatment and final control periods (P = .05). CONCLUSIONS: These results
suggest that relatively short-term, intensive cholesterol lowering over 90
days improves myocardial perfusion capacity before anatomic regression of
stenoses occurs and that such improvement, or deterioration after
withdrawal of lipid-lowering treatment, can be followed noninvasively by
dipyridamole PET, reflecting the integrated flow capacity of the entire
coronary arterial/arteriolar vascular system affected by diffuse
atherosclerosis.
ARTICLES
Short-term cholesterol lowering decreases size and severity of perfusion abnormalities by positron emission tomography after dipyridamole in patients with coronary artery disease. A potential noninvasive marker of healing coronary endothelium
Department of Medicine and Positron Diagnostic, University of Texas Medical School, Houston 77030.
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