Circulation, Vol 90, 808-817, Copyright © 1994 by American Heart Association
F Dayanikli, D Grambow, O Muzik, L Mosca, M Rubenfire and M Schwaiger
BACKGROUND: The objective of this study was to compare coronary flow
reserve (CFR) as a measure of vascular integrity in asymptomatic middle-
aged men with family history of coronary artery disease (CAD) and a
high-risk lipid profile with men without risk factors for CAD using
positron emission tomography (PET). Previous studies suggested that the
assessment of CFR is a sensitive means to detect vascular abnormalities
before angiographic appearance of CAD. N-13 ammonia PET scanning allows
noninvasive evaluation of regional and global myocardial blood flow and
thereby quantification of CFR. METHODS AND RESULTS: We used dynamic N- 13
ammonia PET imaging in conjunction with intravenous adenosine to assess
regional and global CFR in asymptomatic middle-aged men with high risk
(group 1, n = 16) and men without any known risk factors (group 2, n = 11)
for CAD. Group 1 patients were selected based on positive family history of
CAD, one or more lipid abnormalities, and a normal stress test. No patient
had history of diabetes or hypertension. A three-compartment tracer kinetic
model developed and validated in our institution was used to calculate
myocardial blood flow. Absolute myocardial blood flow (mL/100 g per minute)
was calculated in five territories for each patient. CFR was defined as the
ratio of blood flow during maximum pharmacological vasodilatation to blood
flow at rest. Comparisons of CFR between the two groups of patients were
performed. The mean age was similar between groups (group 1, 49.3 +/- 0.5
years; group 2, 48.1 +/- 8.7 years; P = NS). Group 1 had higher total
cholesterol (mg/dL) (241 +/- 43 versus 173 +/- 34, P < .001), total
cholesterol to high-density lipoprotein cholesterol ratio (6.4 +/- 1.6
versus 4.1 +/- 1.4, P < .001), and low-density lipoprotein cholesterol
(mg/dL) (167 +/- 33 versus 107 +/- 32). No group 1 patient had evidence of
ischemia by exercise ECG or exercise of pharmacological radionuclide
perfusion studies. The mean global absolute myocardial blood flow at rest
was not significantly different among groups (group 1, 76 +/- 18; group 2,
66 +/- 8; P = NS; (in mL/100 g per minute). However, blood flow after
adenosine infusion was higher for group 2 (group 1, 217 +/- 56; group 2,
264 +/- 39; P < .001), which resulted in a larger CFR for group 2 (group
1, 2.93 +/- 0.86; group 2, 4.27 +/- 0.52; P < .001). Univariate linear
regression analysis revealed significant negative correlation of CFR to
total cholesterol (P < .05, r = -.41), low-density lipoprotein (P <
.05, r = -.38), and total cholesterol to high-density lipoprotein
cholesterol ratio (P < .05, r = -.47). CONCLUSIONS: Noninvasive
quantification of absolute myocardial blood flow by N-13 ammonia PET allows
the detection of abnormal vasodilatory response to intravenous adenosine in
male patients with family history of CAD and high-risk lipid profiles.
Early assessment of alterations of vascular reactivity to adenosine in
relation to high- risk lipid profiles in asymptomatic men may allow early
detection of preclinical atherosclerosis and may initiate modification
and/or elimination of risk factors that may slow, retard, or even reverse
the progression of CAD.
ARTICLES
Early detection of abnormal coronary flow reserve in asymptomatic men at high risk for coronary artery disease using positron emission tomography
Division of Nuclear Medicine, University of Michigan Hospitals, Ann Arbor.
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