Circulation, Vol 83, 1754-1763, Copyright © 1991 by American Heart Association
DJ Farrar, MG Bond, WA Riley and JK Sawyer
We noninvasively measured changes in average aortic stiffness in 79
cynomolgus monkeys being fed cholesterol progression, regression, and
control diets by measuring pulse wave velocity (PWV) in 260 experiments
during a 30-month period. Every 6 months, a group of monkeys was studied
with invasive aortic PWV techniques and with ultrasonically determined
pressure-strain elastic modulus (Ep) of the carotid artery, and then the
group was killed so that morphometric evaluation of atherosclerosis
severity could be made. After 6 months of a cholesterol progression diet,
PWV decreased slightly from 6.2 +/- 0.1 to 5.7 +/- 0.1 m/sec, followed by
an approximate linear increase to 8.8 +/- 1.2 m/sec after 30 months on the
diet. The corresponding ratio of intimal (plaque) area to medial area
(IA/MA) measured on perfusion-fixed cross- sections of the abdominal and
thoracic aortas increased from 0.16 +/- 0.07 at 6 months to 1.23 +/- 0.22
at 30 months. Monkeys in the regression groups were fed the cholesterol
progression diet for 18 months, followed by a chow diet for 6 or 12 months.
In the first 6 months of the cholesterol regression diet, PWV continued to
increase from 7.0 +/- 0.2 to 8.1 +/- 0.4 m/sec, and IA/MA was 1.24 +/-
0.18. However, after 12 months of the cholesterol regression diet, PWV
decreased to 6.8 +/- 0.4 m/sec, and IA/MA was 0.90 +/- 0.18. The
variability of the data demonstrates that PWV is not a simple function of
atherosclerosis severity, and the best simple correlation was r = 0.69 (r2
= 0.48) between PWV and intimal area. However, multiple regression analysis
of aortic PWV, systolic (SP) and diastolic (DP) blood pressures, and total
plasma cholesterol concentration (TPC), all of which can be measured with
minimally invasive techniques, improved the prediction of the IA/MA ratio
through the following equation: IA/MA = 0.127 PWV-0.039
DP+0.023SP+0.0003TPC-0.292 (r = 0.81, r2 = 0.66). These data suggest that
arterial stiffness in combination with minimally invasive parameters can be
used to predict the severity of diffuse asymptomatic atherosclerosis in
monkeys. However, more widespread application of these data to humans is
uncertain because of biological variability and differences between animal
models and human subjects.
ARTICLES
Anatomic correlates of aortic pulse wave velocity and carotid artery elasticity during atherosclerosis progression and regression in monkeys
Department of Physiology, Bowmann Gray School of Medicine, Wake Forest University, Winston-Salem, N.C.
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