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This investigation determined the prevalence of low-density lipoprotein (LDL) subclass distribution abnormalities, elevated lipoprotein(a) (Lp(a)), and elevated total plasma homocysteine in asymptomatic subjects with subclinical coronary artery disease determined by electron beam tomography (EBT). Fifty-five percent of subjects were classified as higher risk patients and 45% as lower risk patients, employing the National Cholesterol Education Program (NCEP) lipid criteria. EBT was performed in 296 consecutive asymptomatic subjects, and blood was analyzed for total, LDL, and high-density lipoprotein (HDL) cholesterol, triglycerides, LDL subclass distribution by S(3) gradient gel electrophoresis, Lp(a), and total homocysteine. Disorders of LDL subclass distribution were the most common disorder with 60.6% of the population expressing a distribution in the small regions IIIa + IIIb of >20%; and this was more common in the NCEP higher risk group (LDL cholesterol > or =130 and/or HDL cholesterol <35 mg/dl) (p <0.0004). A Lp(a) value >25 mg/dl was found significantly more often in the NCEP higher (36.9%) compared with lower (14.3%) risk group (p <0.001). None of the laboratory measurements correlated with the calcium score or calcium score percentile rank, with the exception of a weak correlation of mean LDL peak particle diameter and calcium percentile (r = 0.14, p = 0.02). Determination of metabolic disorders in addition to LDL cholesterol and HDL cholesterol increased the diagnostic yield from 55.1%, based on NCEP lipid criteria, to 84.1% with the addition of LDL subclass distribution, Lp(a), and total homocysteine. We conclude that: (1) disorders of LDL subclass distribution and elevated Lp(a) occur frequently in NCEP higher risk patients with subclinical coronary artery disease and are the only identifiable disorders in lower NCEP risk patients; and (2) electron beam tomographic evaluation and determination of LDL subclass distribution and Lp(a) should be considered for incorporation into primary prevention guidelines.

Electron-beam tomography (EBT) plaque imaging has the potential to fundamentally change the practice of prevention, through application of the following principles: (1) Asymptomatic patients with significant calcified plaque should be considered to have a clinical coronary artery disease risk equivalent. (2) Measurement of nontraditional parameters should be incorporated into the evaluation of patients with calcified plaque. (3) Drug treatment should focus on the asymptomatic patient with subclinical atherosclerosis. (4) Change in plaque rather than change in lipid values should guide treatment.

This study was designed to determine whether the National Cholesterol Education Program (NCEP) lipid guidelines accurately identify subclinical atherosclerosis and whether low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) levels are related to the extent and prematurity of coronary artery disease (CAD) as determined by electron beam tomography (EBT). Out of personal concern for CAD risk, 930 consecutive asymptomatic subjects, without clinical CAD and on no lipid-lowering agents, underwent EBT. Calcium score and percentile were correlated with total cholesterol (TC), LDL-C, HDL-C, triglycerides, and demographic parameters. A calcium score of > 0 (EBT+) was found in 55% of patients; 45% of patients had a 0 score (EBT-). Mean age (58.0 +/- 10.5 vs 49.3 +/- 9.7 years, p = 0.0001), TC (218 +/- 39 vs 211 +/- 41 mg/dl, p = 0.006), LDL-C (136 +/- 36 vs 127 +/- 27 mg/dl, p = 0.005), and TC/HDL-C (4.6 +/- 1.4 vs 4.2 +/- 1.5, p = 0.0001) were significantly higher and HDL-C (52.2 +/- 17.6 vs 55.4 +/- 19.3 mg/dl, p = 0.008) lower in the EBT+ compared with EBT- group. In the EBT+ group, 75.1% of subjects had LDL-C < 160 mg/dl and would not be advised to use lipid-lowering medications according to NCEP guidelines. In subjects with LDL-C < 160 mg/dl, 51.8% of subjects were EBT+, as were 46.1% of those with LDL-C < 100 mg/dl. There were no significant differences in the calcium scores throughout the entire range of all lipid parameters; calcium percentiles were virtually identical within lipid value subgroups. We conclude that asymptomatic patients with EBT-defined subclinical atherosclerosis are not reliably identified by NCEP guidelines, and TC, LDL-C, HDL-C, TC/HDL-C, and triglyceride levels do not correlate with either the extent or prematurity of calcified plaque burden.

Practice guidelines for the use of electron beam tomography to detect and quantitate coronary atherosclerotic plaque burden have been formulated by the Society of Atherosclerosis Imaging using American College of Cardiology/American Heart Association classifications of indications.

The role of supine bicycle stress echocardiography (SBSE) for detecting restenosis after percutaneous transluminal coronary angioplasty (PTCA) was evaluated in 80 patients: 41 (51%) with single and 39 (49%) with multivessel PTCA (total 129 dilated vessels). Total revascularization was performed in 54 (68%) and partial revascularization in 26 (32%) patients. Restenosis was angiographically demonstrated in 60 patients (75%) and in 72 vessels (56%) 6.1 +/- 2.9 months after PTCA. The results for detecting restenosis were: (1) SBSE versus exercise electrocardiographic sensitivity, 87 versus 55% (p < 0.001); (2) specificity, 95 versus 79%; and (3) accuracy, 89 versus 61% (p < 0.001). SBSE was 83% sensitive, 95% specific and 88% accurate for restenosis detection in specific vessels with comparable results for single versus multivessel PTCA and total versus partial revascularization. Sensitivity, specificity and accuracy were: 91, 93 and 91% for the left anterior descending coronary artery; 77, 94 and 85% for the right coronary artery; and 76, 96 and 88% for the left circumflex coronary artery. Ninety-four percent of the nondilated diseased vessels were correctly identified. It is concluded that SBSE is an excellent tool for identifying restenosis after PTCA.

The role of tomographic thallium-201 exercise and redistribution imaging in the detection of restenosis after percutaneous transluminal coronary angioplasty (PTCA) was evaluated in 116 patients: 61 (53%) with 1- and 55 (47%) with multivessel PTCA, with a total of 185 dilated vessels. Complete revascularization was performed in 89 (77%) and partial revascularization in 27 (23%) of the patients. Restenosis was angiographically demonstrated in 69 (60%) of the patients and 85 (46%) of the vessels 6.4 +/- 3.1 months after PTCA. Disease progression in previously normal vessels was noted in 11 patients. The results were: (1) for detection of restenosis in the group of patients, single-photon emission computed tomographic (SPECT) versus exercise electrocardiographic sensitivity was 93 vs 52% (p less than 0.001), specificity 77 vs 64%, and accuracy 86 vs 57% (p less than 0.001). The results were similar in the complete and partial revascularization groups. (2) SPECT was 86% sensitive, specific and accurate for restenosis detection in specific vessels with comparable results for 1-versus multivessel PTCA and complete versus partial revascularization. Sensitivity, specificity and accuracy were: 89, 95 and 92% for the left anterior descending coronary artery; 88, 79 and 82% for the right coronary artery; and 76, 83 and 85% for the left circumflex coronary artery. Eighty-one percent of the diseased nondilated vessels were correctly identified. (3) Disease progression to greater than 50% stenosis was detected with 91% sensitivity, 84% specificity and 85% accuracy. SPECT thallium-201 imaging is an excellent tool for the detection of restenosis and disease progression after PTCA in the settings of 1- and multivessel angioplasty and complete and partial revascularization.

Exercise-induced regional wall motion abnormalities on radionuclide angiography have been thought to be a reliable indicator of coronary artery disease. To evaluate their reliability, particularly in patients with valvular heart disease, exercise radionuclide angiography was performed in 12 normal subjects, 35 patients with coronary artery disease and 19 patients with valvular heart disease and normal coronary arteries. Exercise-induced regional wall motion abnormalities were found in none of the normal subjects, 63 percent of the patients with coronary artery disease and 42 percent of those with valvular heart disease and were predominantly inferoapical in location in the group with valvular heart disease. We conclude that exercise-induced regional wall motion abnormalities are not reliable for the detection of coronary artery disease in patients with valvular heart disease.

Twenty-four patients with coronary artery disease were studied during cardiac catheterization to determine the effects of sustained isometric handgrip exercise and intravenous dipyridamole and their combination on coronary and systemic hemodynamics and measured coronary luminal caliber. During 4 to 5 minutes of 25 percent maximal handgrip, blood pressure and heart rate increased 24 and 19 percent, respectively, coronary sinus flow increased to 1.7 x baseline value, and epicardial coronary arteries constricted to increase predicted flow resistance by 40 percent in 36 diseased arterial segments. After a 4 minute intravenous infusion of dipyridamole (0.56 mg/kg body weight), systemic pressure decreased 8 percent, heart rate increased 23 percent, coronary sinus flow increased to 2.4 x baseline value and coronary luminal caliber was unchanged. During isometric handgrip initiated 6 minutes after the infusion of dipyridamole, systemic pressure and heart rate increased to 14 and 31 percent, respectively, above control values, coronary sinus flow increased to 3.3 x baseline value (3.8 x baseline value in patients with normal anterior perfusion) and stenotic flow resistance increased by 36 percent. The response of coronary flow to the combined stresses was 68 percent greater than the response to dipyridamole alone (p less than 0.02); these flow levels exceed values previously reported for the human coronary circulation. Aminophylline plus nitroglycerin appears to assure patient safety.