Gregory S. Uhl

Screening for asymptomatic coronary artery disease

Because it will be some time before the primary prevention of cardiovascular disease is a reality, it is advisable to evaluate screening methods for detecting latent cardiovascular disease. Because risk factor screening and techniques with the patient at rest have limited sensitivity, exercise testing that brings out abnormalities not present at rest deserves consideration. Numerous studies have shown the exercise electrocardiogram to have a sensitivity of approximately 50% and a specificity of 90%. The different reported predictive values are related to its use in populations with different prevalences of disease. Various techniques have been recommended to improve the sensitivity and specificity of exercise testing, including other exercise measurements, computerized probability estimates, nuclear cardiology, cardiokymography, cardiac fluoroscopy and risk factor analysis. There is promise that these techniques will improve attempts to screen asymptomatic subjects for coronary disease.

Computer-enhanced thallium scintigrams in asymptomatic men with abnormal exercise tests

The use of treadmill testing in asymptomatic patients and those with an atypical chest pain syndrome is increasing, yet the proportion of false positive stress electrocardiograms increases as the prevalence of disease decreases. To determine the diagnostic accuracy of computer-enhanced thallium perfusion scintigraphy in this subgroup of patients, multigated thallium scans were obtained after peak exercise and 3 or 4 hours after exercise and the raw images enhanced by a computer before interpretations were made. The patient group consisted of 191 asymptomatic U.S. Air force aircrewmen who had an abnormal exercise electrocardiogram. Of these, 135 had normal coronary angiographic findings, 15 had subcritical coronary stenosis (less than 50 percent diameter narrowing) and 41 had significant coronary artery disease. Use of computer enhancement resulted in only four false positive and two false negative scintigrams. The small subgroup with subcritical coronary disease had equivocal results on thallium scintigraphy, 10 men having abnormal scans and 5 showing no defects. The clinical significance of such subcritical disease in unclear, but it can be detected with thallium scintigraphy. Thallium scintigrams that have been enhanced by readily available computer techniques are an accurate diagnostic tool even in asymptomatic patients with an easily interpretable abnormal maximal stress electrocardiogram. Thallium scans can be effectively used in counseling asymptomatic patients on the likelihood of their having coronary artery disease.

Limitation of exercise-induced R wave amplitude changes in detecting coronary artery disease in asymptomatic men.

The exercise electrocardiograms of 255 asymptomatic men were analyzed for changes in R wave amplitude and ST segments. The results were correlated with findings at cardiac catheterization. There were 65 men with coronary artery disease and 190 normal subjects. R wave amplitude changes were evaluated in bipolar leads X, Y and Z. The predictive value of an abnormal ST segment response for detecting disease was only 29%. This value was improved to 42% using R wave amplitude changes with a sensitivity of 28% and specificity of 87%. Exercise-induced R wave amplitude changes enhance the specificity of detecting coronary disease in asymptomatic men over ST segment criteria alone but the sensitivity is poor and the predictive value is not enhanced. Thus, these criteria are limited in adding to the diagnostic accuracy of stress testing.

Relationship between cortisol and cholesterol in men with coronary artery disease and type A behavior.

To further understand the hormonal mechanisms linking behavior pattern and coronary artery disease (CAD), we Investigated the relationship between 0930-hour plasma cortisol and cholesterol In relatively young males who had undergone coronary anglography and In a subgroup of Individuals who had undergone the structured interview for classification of behavior pattern. A statistically significant association (p < 0.05) was found between cortisol and cholesterol for Individuals who had either minimal CAD (20% to 49% narrowing) or significant CAD (⩾50% narrowing), but not for subjects without CAD. An association between cortisol and cholesterol was also found to be significant for the subgroup of individuals with Type A-1 behavior pattern, but not for those with Type A-2, X, or B behavior patterns. The findings suggest that hormonal mechanisms involving cortisol and cholesterol metabolism may be operative In Individuals with CAD as well as In Individuals with Type A-1 behavior.

Relation between high density lipoprotein cholesterol and coronary artery disease in asymptomatic men

The well established inverse relation of high density lipoprotein cholesterol (HDL) and the risk of coronary artery disease was tested in a cross-sectional group of 572 asymptomatic aircrew members who were being screened for risk of coronary artery disease. A battery of tests was performed, including determinations of fasting serum cholesterol, HDL cholesterol and triglycerides and performance of a maximal symptom-limited exercise tolerance test. Of the 572 patients, 132 also had an abnormal S-T segment response to exercise testing or were otherwise believed to have an increased risk of organic heart disease and subsequently underwent coronary angiography. Significant coronary artery disease was found in 16 men and minimal or subcritical coronary disease in 14; coronary angiograms were normal in the remaining 102 men. The remaining 440 men, who were believed to have a 1 percent chance of having coronary artery disease by sequential testing of risk factors and treadmill testing, had a mean cholesterol level of 213 mg/100 ml, a mean HDL cholesterol of 51 mg/100 ml and a mean cholesterol/HDL ratio of 4.4. The mean values of cholesterol, HDL cholesterol and cholesterol/HDL cholesterol did not differ significantly in men with normal angiographic finding and those with subcritical coronary disease. However, 14 of 16 men with coronary artery disease had a cholesterol/HDL ratio of 6.0 or more whereas only 4 men with normal coronary arteries had a ratio of 6.0 or more. Of the classical coronary risk factors evaluated, the cholesterol/HDL ratio of 6.0 or more had the highest odds ratio (172:1). It appears that determination of HDL cholesterol level helps to identify asymptomatic persons with a greater risk of having coronary artery disease.

Analysis of exercise-induced R wave amplitude changes in detection of coronary artery disease in asymptomatic men with left bundle branch block.

The exercise electrocardiograms of 44 asymptomatic men with acquired left bundle branch block were analyzed for changes in R wave amplitude. Results were correlated with findings on selective coronary angiography. There were two subgroups: 7 men with significant angiographic coronary artery disease (Group I) and 37 with normal coronary angiograms (Group II). Exercise induced an increase in R wave amplitude in all seven men with coronary artery disease but in only 10 of the 37 men without significant coronary artery disease. This criterion thus had a sensitivity of 100 percent but a poor specificity of 73 percent, a predictive value of 41 percent and an accuracy rate of 77 percent for the diagnosis of coronary artery disease. The greater the increase in R wave amplitude the greater was the likelihood of some degree of left ventricular dysfunction as measured by wall motion abnormalities and elevated left ventricular end-diastolic pressure. The increase in R wave amplitude with exercise appears to be a sensitive test in identifying coronary artery disease in asymptomatic men with acquired left bundle branch block.

Discriminant value of clinical and exercise variables in detecting significant coronary artery disease in asymptomatic men

To determine whether clinical or exercise test variables could reliably detect coronary disease in asymptomatic men, several variables were compared with angiographic findings in 225 asymptomatic men. None of the individual clinical or rest electrocardiographic variables were able to detect coronary artery disease. The three individual exercise variables with a high likelihood ratio were: 1) at least 0.3 mV ST depression, 2) persistence of ST depression 6 minutes after exercise, and 3) total duration of exercise of less than 10 minutes. However, because of low sensitivity and predictive value, these single variables were not helpful in identifying individual patients with coronary disease. The combination of any single clinical risk factor and any two of these exercise risk predictors was highly predictive (89%) but relatively insensitive (37%) for detecting any coronary disease. These criteria have a sensitivity of 55% and a predictive value of 84% for the detection of two and three vessel coronary disease. The effectiveness of exercise testing for detecting asymptomatic coronary disease is improved when the group is first screened for the presence of risk factors and additional exercise variables other than ST segment criteria are evaluated.

Variations in normal electrocardiographic response to treadmill testing

Forty healthy young men at low risk for coronary artery disease underwent progressive maximal treadmill testing. Four bipolar electrocardiographic leads including CM5, CC5, inferior-superior Y, anterior-posterior Z, and a standard V5 were recorded and later computer-processed. Measurements included amplitudes of the Q, R, S, J junction and T wave, R-T and Q-S intervals and S-T segment slope. These variables are presented as the 10th, 50th (median) and 90th percentiles throughout the testing procedure to define reference values for the electrocardiographic response to maximal treadmill testing. The medians are presented graphically so that the exercise-induced changes can be visualized. In addition, the percent change of R wave amplitude in V5 compared with the supine pretest value is displayed for each subject during and after testing.

New criteria for computer interpretation of exercise electrocardiograms in a largely asymptomatic population

We developed new discriminant functions for analyzing treadmill ECGs from a largely asymptomatic population. Treadmill ECG data were gathered from two patient groups: 70 patients with coronary artery disease with occlusions greater than or equal to 30% by angiography, and 138 patients without coronary artery disease. The group without coronary artery disease consisted of 76 false positive responders to treadmill testing using standard ST segment criteria, 22 supraventricular tachycardia patients (both groups free of coronary artery disease by angiography), and 40 patients at very low risk for having coronary artery disease. ECG leads CC5, CM5, V5, Yh and Z were recorded before, during and after exercise protocol conditions. Computer-averaged ECGs were processed to provide Q, R, S and T-wave amplitudes, ST amplitudes and slope, and QS and RT intervals. Each patient provided over 100 variables per lead for analysis. Stepwise statistical procedures yielded lead-specific linear discriminant functions containing four to six variables/lead. Application of these functions provided sensitivity and specificity in the range 70-84%. When compared with other standard interpretive criteria, these results provided improved diagnostic accuracy for the largely asymptomatic population.