BackgroundThe 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 ResultsWe 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 or 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).ConclusionsNoninvasive 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.