Fluoroscopic coronary artery calcification and associated coronary disease in asymptomatic young men.

Little is known about the diagnostic significance of coronary artery calcification detected fluoroscopically in apparently healthy young men. This study compared the presence of fluoroscopically detected coronary artery calcification with angiographic coronary artery disease in asymptomatic male military aircrew undergoing noninvasive cardiac screening tests and coronary arteriography for occupational indications. Of 1,466 men screened with coronary fluoroscopy, 613 underwent coronary arteriography because of one or more abnormal noninvasive test results. The mean age (+/- SD) of all subjects screened was 40.2 +/- 5 years (range 26 to 65). Significant coronary artery disease (greater than or equal to 50% diameter stenosis) was found in 104 of the 613 subjects with arteriograms (16.9% disease prevalence). Overall sensitivity and specificity for coronary artery calcification detection of significant disease, based only on those subjects undergoing arteriography, were 66.3% and 77.6%, respectively. For measurable disease (mild plus significant), sensitivity was 60.6% and specificity 85.9%. Positive and negative predictive values were 37.7% and 91.9%, respectively, for significant disease. For measurable disease, positive and negative predictive values were 68.9% and 80.9%, respectively. In these asymptomatic young men, a fluoroscopic examination negative for coronary artery calcification indicated a low risk of significant coronary artery disease, whereas a positive test result (calcification present) substantially increased the likelihood of angiographically significant coronary artery disease.

Angiographic diagnosis of posterior mitral valve leaflet prolapse.

The left ventricular cineangiograms of 22 asymptomatic, apparently healthy male aviators without noninvasive (echocardiographic or auscultatory) evidence of mitral valve prolapse were reviewed and compared with those of 12 men with noninvasive evidence of mild mitral valve prolapse. The maximal protrusion of the posterior mitral valve leaflet superior and posterior to a line perpendicular to the long axis of the left ventricle at end-systole was measured from the right anterior oblique left ventricular cineangiogram by repeated observation of left ventricular inflow. The values were 7.5 +/- 1.6 mm in patients without mitral valve prolapse and 11.2 +/- 3.4 mm in patients with mitral valve prolapse (mean +/- 1 standard deviation). This measurement did not exceed 11 mm in any patient without prolapse. It is concluded that: 1) with meticulous attention to angiographic landmarks of the left ventricular inflow area, the limits of normal systolic posterior mitral leaflet motion can be defined; and 2) systolic motion outside these limits constitutes a quantitative criterion for the angiographic diagnosis of mitral valve prolapse.

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.

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.

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.

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.

Hostility in asymptomatic men with angiographically confirmed coronary artery disease.

The association of hostility and coronary artery disease was evaluated in a case-control study of aircrew members who had been referred for coronary angiography on the basis of noninvasive tests or risk factor status. The asymptomatic status of the sample and the structured nature of the referral process minimize the methodologic problems normally associated with studies of patients undergoing angiography. Cases (n = 24) had some angiographic evidence of coronary artery disease, whereas controls (n = 25) were found to have no evidence of occlusion. An interaction was observed between smoking history and a measurement of hostility based on observations of the respondent's behavior during a standard interview. Among nonsmokers, cases had higher hostility scores than did controls (p = 0.004). This association was not present among smokers. Self-reported hostility did not discriminate cases from controls. These findings support the notion that hostility plays a role in the pathogenesis of coronary atherosclerosis and point to the potential importance of interactions between hostility and other risk factors.

Rapid removal of platelets from plasma utilizing the Hepcheck heparin removal filter.

We investigated whether Hepcheck heparin removal filters could remove residual platelets from platelet-poor plasma (PPP) without compromising samples for lupus anticoagulant (LA) testing. Furthermore we assessed what effect, if any, plasma filtration has on various clotting tests that form the foundation for LA testing. Citrated blood was obtained from 35 normal donors. Two sets of citrated tubes were processed in order to obtain PPP. Citrated blood was also obtained from a single donor to check the actual amounts of platelets removed by the Hepcheck filtration device. One set of PPP samples was filtered using the Hepchek filter device and the other was not processed, i.e. unfiltered. Prothrombin time (PT), activated partial thromboplastin time (APTT), and kaolin clotting time (KCT) were performed on both unfiltered and filtered samples that were tested immediately and after freezing at -70 degrees C for 24 h. Platelet counts on the single donor's citrated plasma were dramatically reduced after filtration. PT and APTT values showed small but statistically significant differences between unfiltered and filtered plasmas whether these were fresh or frozen samples. However, these differences were not clinically significant. KCT data showed statistical and clinical differences between unfiltered and filtered plasmas whether fresh or frozen plasmas were used. In contrast, KCT values were similar if unfiltered, fresh plasmas or filtered, frozen plasmas were used. Coagulation factor assays for factors VIII, IX and X were performed on both sets of PPP samples after freezing to determine if the filtration device affected these levels and would as a result, compromise APTT based lupus testing. Factor IX levels demonstrated a loss of activity following use of the device but no change was observed in factor VIII or factor X. Von Willebrand factor antigen and function as well as multimer structure were not affected by the filtration device in 10 normal donors. Filtering plasmas of two donors with a history of an LA dramatically prolonged clotting times for APTT, Dilute Viper Venom Time, mixing studies, and STACLOT LA tests in comparison with unfiltered plasmas. The data indicate that plasma filtration using the Hepchek device does not adversely affect coagulation testing. Furthermore samples requiring testing for the lupus anticoagulant can be filtered and subsequently frozen and compare favorably with freshly processed samples.

Peripheral blood lymphocyte apoptosis: a clue to the diagnosis of acute infectious mononucleosis.

OBJECTIVE: To describe the morphology and significance of apoptotic lymphocytes in peripheral blood smears of patients with acute infectious mononucleosis. To our knowledge this has not been previously reported. DESIGN: Peripheral blood smears from 27 patients with a positive heterophile antibody test were collected and reviewed for the presence of apoptotic lymphocytes. Flow cytometry was performed on three cases to document the previously described low expression of bcl-2 in lymphocytes in infectious mononucleosis. Four control patient populations comprising 80 cases were similarly screened for the presence of apoptotic lymphocytes. SETTING: The specimens were collected over a 3-month period in two laboratories at our tertiary care hospital; all specimens were processed according to a standard protocol. PATIENTS: Young adult military recruits and their spouses, military dependent adolescents, and retired military personnel. RESULTS: Twenty-four (88.9%) of 27 peripheral blood smears of patients with acute infectious mononucleosis contained readily identifiable apoptotic lymphocytes. Three (3.75%) of 80 control peripheral blood smears were identified with rare apoptotic lymphocytes, all occurring in patients with viral upper respiratory infections. CONCLUSIONS: The finding of apoptotic lymphocytes in a peripheral blood smear is useful in the differential diagnosis of infectious mononucleosis and neoplastic hematolymphoid processes.

Panel summary: from Zen riddle to the razor's edge.

A summary of the Panel on Deliberate G-induced Loss of Consciousness reviews the global issue of rendering human subjects unconscious in the centrifuge as a research procedure. Major issues summarized are informed consent, a common taxonomy for G-LOC events, and medical surveillance of subjects made deliberately unconscious.

Acceleration tolerance of asymptomatic aircrew with mitral valve prolapse and significant +Gz-induced ventricular dysrhythmias.

The +Gz tolerance of asymptomatic aircrew with mitral valve prolapse (MVP) who had advanced Lown grade ventricular ectopy (multiformed or paired premature ventricular contractions and ventricular tachycardia) during +Gz-stress testing was investigated. The +Gz tolerance to an aeromedical centrifuge stress testing protocol revealed that these individuals had slightly lower +Gz tolerance for each of the different types of +Gz profiles, with the gradual onset of +Gz while using an anti-G straining maneuver (GOR-S) tolerance being significantly lower (p less than 0.05). As a subgroup of a larger group of individuals with MVP, these MVP individuals with advanced ventricular ectopy had an increased incidence of +Gz-induced loss of consciousness and motion sickness. The advanced ventricular ectopy occurred before, during, and after +Gz stress; however, there was a tendency for the ectopy to occur in the post +Gz stress period. The post +Gz stress period is a period of high parasympathetic (vagal) tone, and these findings may indicate that these individuals are in some way sensitive to high vagal tone. Acceleration stress testing is a valuable tool in the aeromedical evaluation of asymptomatic individuals desiring to fly fighter aircraft. Advanced ventricular ectopy not seen in other clinical testing (treadmill and ambulatory monitoring) occurred in these individuals. The current results suggest that these individuals with MVP and advanced ventricular ectopy are not currently prime candidates for flying fighter aircraft, not only because of the ventricular ectopy, but because of decreased +Gz tolerance and susceptibility to +Gz-induced loss of consciousness.

Mitral valve prolapse--a review.

The past decade has seen a notable resurgence of interest in the systolic click-murmur syndrome. Previously regarded as extracardiac and benign, it is now clear that these auscultatory findings are central to a disorder characterized by abnormal systolic herniation (prolapse) of the mitral leaflets into the left atrium. Although it may be the result of diverse etiologies, the usual case represents an idiopathic, hereditary disorder of the valve leaflets with pathologic findings similar to those in Marfan's syndrome. The condition is very common and generally benign, and asymptomatic; however, a wide variety of clinical manifestations has been described, with a clinical picture at times indistinguishable from that of coronary artery disease. The small subset of patients at risk for malignant arrhythmias and sudden death has yet to be fully characterized. Although noninvasive techniques generally suffice for the diagnosis of MVP, left ventricular cineangiography is the definitive procedure. It remains for future studies in symptomatic and asymptomatic patients to define the relation between severity of MVP, its clinical manifestations, and its prognosis.

Physical standards for high-performance fighter aircraft pilots.

The new generation of high-performance aircraft has clearly emphasized man's physiological limitations to withstand sustained high G loading. The selection and retention standards required to function in this environment have not been completely defined. The authors will offer a format of standards and screening tests, placing special emphasis on the detection of subclinical disease, particularly coronary artery disease. Cases which illustrate the spectrum of asymptomatic coronary disease will be presented. Other entities discussed will include conduction defects, mild valvular lesions, arrhythmias, and degenerative joint disease of the spine. An overall approach based on age, screening milestones, and specialized tests will be presented. Finally, a data repository on all pilots with chronic high G exposure will be discussed.

Concurrent loss of consciousness and sino-atrial block during +Gz stress.

Current USAF fighter aircraft easily exceed human physiologic limits with their rapid onset of head-to-foot acceleration forces (+Gz). Sudden in-flight incapacitation caused by these increased +Gz forces could be disastrous with loss of materiel and human life. The physiologic mechanisms responsible for loss of consciousness (LOC) secondary to high +Gz must be fully understood so that maximum protection against it can be provided. An interesting case of an episode of LOC with concurrent sino-atrial block occurring during a relaxed rapid onset (1 G/s) centrifuge run is presented. The patient was undergoing flight medical evaluation for an episode of syncope, etiology unknown. An unusual characteristic of the patient was his high level of endurance training. The possibility of an excessive increase in vagal tone, developed by endurance training, is discussed as a probable etiology for this patient's prolonged time of incapacitation evidenced after +Gz-induced loss of consciousness.

High +Gz centrifuge training: the electrocardiographic response to +Gz-induced loss of consciousness.

Neural control of the heart involves complex interconnections within the central nervous system (CNS). Although various CNS abnormalities and processes (acute cerebrovascular accidents, cerebral ischemia, subarachnoid hemorrhages, and seizures) have been associated with alteration of cardiac electrophysiology, the effect of +Gz-induced loss of consciousness (G-LOC) on autonomic control of the heart is unknown. From a group of 59 healthy subjects undergoing centrifuge high +Gz training, 15 suffered G-LOC episodes. The +Gz training profiles included gradual (0.1 G/s) and rapid (approximately 6 G/s) exposures to levels as high as +9 Gz. Electrocardiographic rate and rhythm disturbances were evaluated during each of the +Gz training profiles. Rate and rhythm disturbances associated with the +Gz stress exposures were observed in 73% of the subjects. When considering only the period when the subjects were exposed to +Gz (During-G), 67% of the individuals had atrial or ventricular ectopy. When considering the period of unconsciousness (During-LOC), which lasted an average of 12.6 s, 33% of the individuals had atrial or ventricular ectopy. Electrocardiographic changes were related to +Gz stress and unrelated to the period of occurrence of G-LOC. Significant ectopy (ventricular tachycardia and supraventricular tachycardia) was observed only during +Gz stress and not related to the G-LOC period. The results of the study do not indicate that G-LOC alters the electrocardiographic response to +Gz stress.

The West Point Study: occurrence of coronary artery disease after 34 years.

This report reviews the current status of the West Point Study and addresses the prediction of risk of coronary artery disease (CAD) based on cholesterol levels measured at various times during the study. Subjects were grouped into quintiles by their risk index score calculated from the Framingham risk equation. The number of cases of CAD among the subjects in each of the quintiles was tabulated. The cases of CAD in these quintiles increased from the lowest to the highest quintiles and produced a significant correlation between the risk score and the percent of subjects in the quintiles having CAD, even when the data used for calculating the risk scores had been collected up to 26 years earlier. The numbers of CAD cases are small; they are only approximately 50% of the expected numbers computed for U.S. males of comparable ages, despite the increases in serum cholesterol and low density lipoprotein levels recorded during the first 6 years of the study. The authors speculate about possible explanations of these findings.

Limitations of the exercise stress test in the detection of coronary artery disease in apparently healthy men.

During a 1-year period, the United States Air Force School of Aerospace Medicine reviewed routine exercise tests by 771 completely asymptomatic male flying personnel aged 35-54 years, who underwent the stress test as the sole screening procedure to detect latent coronary artery disease. All of the aviators had a normal baseline 12-lead electrocardiogram, which would not have required a stress test in accordance with current policies of the USAF Central Electrocardiographic Library. Of these 771 exercise tests, 153 were maximal treadmill tests without a previous Double Master's Step test, and 618 were Double Master's tests. Borderline abnormal or abnormal Double Master's tests were followed by treadmill testing. Airmen with abnormal treadmill tests were offered coronary angiography for clarification of the aeromedical significance of the test result. The predictive value of a routine abnormal treadmill test in a population of aircrew members with a borderline abnormal or abnormal Double Master's test ranged from 17-55%. Thus, mass screening for coronary artery disease with exercise stress tests in apparently asymptomatic individuals is hampered by a low yield of true positive test in an unacceptably high proportion of false positive results.

Detection of coronary artery disease in asymptomatic aircrew members with thallium-201 scintigraphy.

Thallium-201 exercise myocardial perfusion scintigraphy was accomplished in 130 aircrew members prior to their undergoing coronary angiography. Most were undergoing cardiac catheterization for an abnormal exercise response to treadmill testing. Of these, 22 men had arteriographic evidence of obstructive coronary disease of at least 50% narrowing in a single vessel. All had abnormal myocardial scintigrams. There were 12 other aviators who had minimal degrees of coronary artery disease with lesions less than 50% as the maximum degree of obstruction. Of these, 8 had abnormal thallium scans showing a perfusion defect in the area of the myocardium, presumably supplied by the diseased coronary artery. Of the 96 men with normal angiograms, only 4 had abnormal myocardial scintigraphy. An abnormal myocardial scintigram was often associated with significant obstructive disease. A normal scan accurately ruled out the presence of high-grade obstructive lesions and missed only four cases of minimal coronary disease. The application of gated thallium myocardial perfusion scans in the practice of aerospace cardiology has important significant applications for followup of therapeutic modalities as well as screening for evidence of myocardial ischemia in apparently healthy aircrew members.

The West Point Study: 40 years of follow-up.

Completion of cardiovascular evaluations of 387 members marked the end of 40 years of follow-up in the West Point Study. Coronary artery disease (CAD) caused 4 cases of sudden death, 14 cases of myocardial infarction (MI), 13 cases of angina, and 17 cases of silent CAD. Using risk factors (serum cholesterol, estimated HDL-cholesterol, systolic blood pressure, and smoking status) measured before age 28, we derived a multivariate regression formula for predicting which members of the study, had they been pilots, would have been grounded for CAD before age 55. This derivation used data from only those subjects with CAD or with no evidence of CAD. We then used the formula to compute a risk-related score for each member of the study. In the tertile group with the highest risk-related scores, 17% manifested CAD by age 55 and the first event occurred at age 39. In the tertile group of lowest scores, 2% experienced CAD by age 55 and the first event occurred at age 51. We conclude that it is possible to select pilot candidates with the lowest risk for CAD.

Primary idiopathic optic neuritis in U.S. Air Force Aviators.

The records of 31 male aviators seen at the Ophthalmology Branch of the USAF Aeromedical Consultation Service (formerly the USAF School of Aerospace Medicine) for a diagnosis of primary idiopathic optic neuritis (PION) were reviewed. Each subject received comprehensive ophthalmologic and neurologic examinations. The long-term follow-up data were collected through repeat examinations and by survey. Despite 39% of aviators being grounded due to complications of their PION or multiple sclerosis (MS), many aviators diagnosed with PION may be safely returned to flying duties. However, any aviator diagnosed with PION has a risk of recurrence or a potential to develop systemic MS and must be carefully reevaluated and followed to ensure they remain a viable asset and do not compromise flight safety or mission completion.