Angiographic findings in asymptomatic aircrewmen with electrocardiographic abnormalities

Angiographic Findings in Asymptomatic Aircrewmen With Electrocardiographic Abnormalities

VICTOR F. FROELICHER, Jr., LT COL, USAF, MC, FACC* A. J. THOMPSON, MD ROGER WOLTHUIS, PhD ROBERT FUCHS, MS ROBERT BALUSEK, MS MICHAEL R. LONGO, Jr., MD JOHN H. TRIEBWASSER, COL, USAF MC MALCOLM C. LANCASTER, COL, USAF MC, FACC

Brooks Air Force Base, Texas

The research reported in this paper was conducted by personnel of the Clinical Sciences and Biometrics Division, U. S. Air Force School of Aerospace Medicine, Aerospace Medical Division, U. S. Air Force, Brooks Air Force Base, Texas. Manuscript received April 5, 1976; revised manuscript received June 10, 1976, accepted June 30, 1976. *Now with Wilford Hall USAF Medical Center, Texas. Address for reprints: Victor F. Froelicher, Jr., 8314 Little Port, San Antonio, Texas 78239.

32

Cardiac catheterization was used to evaluate 298 asymptomatic, apparently healthy aircrewmen with electrocardiographic abnormalities. These men were identified from annual electrocardiograms and exercise tests used to screen for latent heart disease. Data from 27 additional symptomatic aircrewmen who underwent cardiac catheterization because of mild probable angina pectoris are also included. The men were grouped according to major reason for cardiac catheterization. The order of groups by increasing prevalence of coronary artery disease was as follows: abnormal treadmill test (labile lead only), supraventricular tachycardia, right bundle branch block, left bundle branch block, abnormal treadmill test, ventricular irritability, probable infarct and angina. Approximately 60 percent of the men were completely free of angiographic coronary artery disease. Risk factors and other possible causes for the electrocardiographic abnormalities are discussed. The electrocardiographic abnormaliUes studied have a poorer predictive value for coronary artery disease in asymptomatic apparently healthy men than in a hospital or clinic population.

The mission of the Aeromedical Consultation Service at the United States Air Force School of Aerospace Medicine is to detect and diagnose disease processes that could compromise flying safety. Two methods used to screen aircrewmen for health problems are (1) interpretation of annual electrocardiograms at the USAF Central Electrocardiographic Repository, 1 and (2) medical evaluations including annual physical examinations performed at local USAF bases. In addition, all men referred to the Consultation Service receive complete medical screening including maximal treadmill testing. 2-4 The first two screening techniques account for most referrals and all three procedures can indicate abnormalities suggestive of heart disease in apparently healthy aircrewmen. In evaluating men with various abnormal electrocardiographic findings, the Consultation Service has utilized cardiac catheterization studies to confirm or disprove the diagnosis of heart disease. Such studies enable reasonable judgments to be made regarding the flying and health status of aircrewmen with abnormalities of questionable origin. Because of their previous medical examinations, Air Force crewmen manifest few of the typical and obvious cardiovascular diseases. Coronary artery disease is the most commonly suspected disease and our cardiac catheterization laboratory has been designed to perform safely coronary angiograms of superior quality.. In clinical practice, coronary angiography is most often performed in patients with symptomatic coronary artery disease in order to evaluate the severity of disease and to delineate the coronary anatomy in consideration of coronary bypass surgery. In contrast, the diagnosis is relatively uncertain in aircrewmen referred to us for evaluation, and coronary angiography most often performs the important function of removing the diagnosis of coronary artery disease. In this paper we report the prevalence of angiographic coronary artery disease in asymptomatic men with electrocardiographic abnormalities suggestive of heart disease.

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Methods Subjects: The subjects were 325 aircrewmen studied with coronary angiography between February 1971 and December 1974. All diagnostic procedures performed were reviewed and coded by two of us (A. J. T. and V. F. F.). Our methods of coding cardiac catheterization and electrocardiographic data have previously been described. 5 All patients included had technically adequate diagnostic procedures. Except for 27 men with possible mild angina pectoris, the subjects were asymptomatic apparently healthy aircrewmen on flying status until referred for evaluation of recently detected flying, visual or medical problems or electrocardiographic abnormalities. After undergoing a thorough noninvasive evaluation (Table I), candidates for invasive study were given a careful explanation of the risks and possible complications of cardiac catheterization. Almost all candidates agreed to this procedure; although motivated because they wanted to continue their flying career, many were primarily interested in clarifying their cardiovascular health status. The Cardiac Catheterization Laboratory used a General Electric Fluricon 300 system with a 35 mm cine camera. Ventricular pressures were measured before and after left ventriculography. The Sones technique was used almost exclusively. 7,s The coronary arteries were injected and viewed in multiple projections, but axial views were not possible. Nitroglycerin was given before the injections, and coronary spasm was not encountered. The procedure usually was accomplished within 30 to 45 minutes, and patients were monitored until their release the following morning. No deaths or significant morbidity occurred secondary to cardiac catheterization.

Significant coronary artery disease was defined, for purposes of analysis, as angiographic evidence of a lesion compromising 50 percent or more of the luminal diameter in any major branch of the three main coronary arteries. The cutoff point of 50 percent or more was chosen on the basis of mortality data from follow-up studies, 9,1othe probability that such lesions have a hemodynamic effect during exercise 11 and the recognition, that coronary angiography underestimates pathologic findings of coronary artery disease. 12 Because of

TABLE I Noninvasive Testing Performed As Part of the Cardiovascular Evaluation of Aircrewmen Referred to the Aeromedical Consultation Service Routine Biochemical risk factor screen Risk factor questionnaire Chest roentgenogram Electrocardiogram Vectorcardiogram 5 hour Holter monitor Maximal treadmill test (Balke-Ware or USAFSAM protocol 6) Special Echocardiogram Phonocardiogram Personality assessment interview and questionnaire 24 hour Holter monitor Human centrifuge test Tilt table test Radioisotope myocardial scan

TABLE II Angiographic Findings and Risk Factor Data in 325 Aircrewmen Grouped by Major Reason for Cardiac Catheterization*

Groups RBBB (no. = 41 ) LBBB (no. = 34) Labile lead abnormal treadmill test (no. = 27) Abnormal treadmill test (no. = 111) Supraventricular tachycardia (no. = 36) Ventricular irritability (no. = 24) Probable infarction (no. = 25) Angina (no. = 27) All (no. = 325)

Blood P re ssu re (mm Hg)t

Positive Family

Positive Smoking History (% of group)

for CAD (% of group)

54

27

65

29

44

42

History

Age (yr)t

no. (% of group) With Significant CAD

no. (% of group) With No CAD

Serum Cholesterol (mg/100 m l ) t

Serum Triglycerides (mg/100 m l ) t

41 +7 42 -+5 38 -+7

8 (20%) 8 (24%) 1 (4%)

29 (7%) 23 (68%) 22 (82%)

224 +-40 223 -+29 233 -+38

140. -+45 124 -+39 150 -+72

125 81 129 82 131 86

43 -+7

34 (31%)

60 (54%)

245 +-47

157 -+85

133 +- 15 85 -+ 10

52

38

38 -+7

5 (14%)

29 (81%)

217 -+29

116 -+41

127 -+ 11 83 + 8

44

36

45 -+6

9 (38%)

12 (50%)

230 -+28

153 +-58

132 -+ 12 85 -+ 10

54

21

41 -+8

14 (56%)

8 (32%)

269 -+61

152 _+55

132 -+ 15 86 + 9

80

64

44 -+8 42 -+7

19 (70%) 98 (30%)

7 (26%) 190 (58%)

245 -+34 237 +43

182 -+118 148 +-73

130 84 130 84

67

74

56

39

+ 11 -+ 7 -+ 13 -+ 10 + 11 -+ 8

-+ 10 +8 -+ 13 -+ 9

* Minimal angiographic coronary artery disease was found in the men not included in the column for either significant or no coronary artery disease. The percent of men with significant coronary artery disease in each group is the predictive value of that group classification. t Values expressed as mean + standard deviation. CAD = coronary artery disease (significant CAD = 50 percent or more luminal occlusion); LBBB = left bundle branch block; RBBB = right bundle branch block.

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our responsibility for public safety it would have been inappropriate to consider only higher grade lesions significant. Risk factors were graded as follows5: The men were considered to have a positive smoking history if they had 8 or more pack-years of cigarette smoking and a positive family history if a blood-related primary family member had had a coronary event before age 66. The casual blood pressure measurement obtained by the patient's physician was used unless the patient had a history of hypertension and the measurement obtained at his referring facility was consistently higher. In that case the latter measurement was used. Results The patients, grouped according to major reason for cardiac catheterization, are presented in Table II together with angiographic and risk factor data. There were no significant differences in height and weight among groups; the overall mean value (± standard deviation) was 178 + 7 cm for height and 79 ± 8 kg for weight. Because the results of statistical testing of other findings could be misleading, they are not presented; results of multivariate analysis techniques should prove to be more meaningful. The groups were kept mutually exclusive; thus, in Table II, some men with an abnormal treadmill test are only included in groups listed below the group with an abnormal treadmill test. B u n d l e branch block: None of the asymptomatic men studied because of the development of acquired bundle branch block had a clinical history to explain its occurrence. There were 41 men with right bundle branch block and 34 with left bundle branch block. The frequency of left dominant, right dominant and balanced circulatory patterns in these men did not differ from the frequency in other groups. Comparison of the length of the left main coronary artery and the number of septal perforators in the men with left bundle branch block and in 55 patients without bundle branch block

TABLE

revealed no significant differences. This finding was in disagreement with data from other investigators. 13 Five of the men with left bundle branch block and normal coronary angiograms had generalized left ventricular dyskinesia and left ventricular end-diastolic pressure greater than 12 mm Hg. In one of the men with left bundle branch block an apical bulge and an $3 gallop were detected on a follow-up examination even though his functional capacity had not changed. A second catheterization, performed because of these findings, revealed marked left ventricular dilatation and generalized dyskinesia that had not been present previously. Two months later this patient died suddenly although he had normal coronary arteries. Abnormal maximal treadmill test: In 138 men cardiac catheterization was performed only because of 0.1 mv or more of horizontal or downward sloping S-T segment depression induced by maximal treadmill testing. Twenty-seven of these men were considered separately because the abnormality was evident only in a labile vertical lead prone to excessive false positive results. Use of this labile lead (negative electrode near the top of the manubrium, positive electrode at the sixth interspace left anterior axillary line) was discontinued after its poor specificity became apparent. The remaining 111 men, where abnormal S-T depression occurred in bipolar lead CC5 or Vs, constituted the largest group of asymptomatic men undergoing coronary angiography. This group was further classified into four subgroups on the basis of the resting electrocardiogram (Table III). The greater prevalence of coronary artery disease in the subgroup with persistent resting S-T straightening or mild depression was not due to differences in risk factors. Supraventrieular tachycardia: Cardiac catheterization was performed in 36 men because of a documented single transient episode of supraventricular

III

A n g i o g r a p h i c F i n d i n g s a n d R i s k F a c t o r D a t a in 111 A i r c r e w m e n W i t h an A b n o r m a l T r e a d m i l l T e s t G r o u p e d According

to Annual Resting Electrocardiographic D a t a

Annual Resting Electrocardiograms Normal (no. = 34) Previous tracings with repolarization changes but current tracing normal (no. = 21) Repola rization changes with persistent low amplitude T waves (no. = 24) Persistent S-T segment depression or straightening (no. = 32)

Serum Serum Cholesterol Triglycerides (mg/100 (mg/100 ml)* ml)*

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Positive Family History for CAD (% of group)

Age* (yr)

no. (% of group) With Significant CAD

no. (% of group) With No CAD

44 +-8 43 +-6

8 (23.5%) 5 (23.8%)

20 (58.8%) 10 (47.6%)

241 +-48 226 +-46

145 +-73 162 +-86

130 84 130 82

15 9 15 10

32

32

71

50

42 +8

6 (25.0%)

15 (62.5%)

259 +45

164 +-85

137 + 18 87 + 11

67

39

44 +-6

15 (46.9%)

15 (46.9%)

250 -+47

160 +98

136 + 10 86 -+ 10

50

34

* Values expressed as mean -+ standard deviation. CAD = coronary artery disease.

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Blood Pressure (mm Hg)*

Positive Smoking History (% of group)

+ + + +

ANGIOGRAPHIC-ELECTROCARDIOGRAPHIC FINDINGS IN ASYMPTOMATIC MEN--FROELICHER El" AL.

tachycardia (Table II). Of these, 21 had atrial fibrillation and 10 a regular rate supraventricular tachycardia; these 31 patients had normal sinus rhythm without medication and had a normal treadmill test. The remaining five patients with a single documented episode of supraventricular tachycardia also had abnormal S-T segment depression in response to maximal treadmill testing. No angiographic abnormalities were noted in the appearance, location, or distribution of the atrial arteries; particularly in those supplying the sinoatrial and atrioventricular nodes. Two of the men had mitral valve prolapse detected only with left ventriculography. Ventricular arrhythmia: There were 24 men who underwent cardiac catheterization mainly because of significant ventricular irritability. This was defined as one or more of the following: (1) A documented history of frequent premature ventricular contractions; (2) treadmill test-induced frequent premature ventricular contractions occurring at near maximal or maximal exercise; (3) a documented history of three or more consecutive ectopic ventricular complexes; and (4) three or more consecutive ectopic ventricular complexes occurring with maximal treadmill testing. Frequent premature ventricular contractions were defined as 20 or more ectopic beats occurring in any series of 50 beats. Of these 24 men, 38 percent also had treadmill testinduced abnormal S-T segment depression in nonpremature beats. Probable myocardial infarction or angina pectoris: Twenty-five currently asymptomatic patients had a probable myocardial infarction on the basis of one or more of the following criteria: typical electrocardiographic changes, a past history of pain or clinical studies consistent with myocardial infarction. A definite diagnosis of infarction had not been made or the patient would not have been referred for evaluation. The last subgroup in Table II, the 27 men with angina, comprised the only men who were symptomatic at the time of evaluation. These men related a history of mild but definite chest pain or tightness related to emotions or exertion, but most were moderately active and their

normal activities were only mildly limited. All but two had a completely normal resting electrocardiogram. Because of these characteristics, they were distinctly different from most patients with angina pectoris. Table IV describes the maximal treadmill test results in the combined group of patients with angina or probable infarction. Correlation of risk factors and coronary angiographic findings: Table V presents an analysis of the risk factor data grouped by the angiographic findings in the 325 men. Angiographic studies found nearly 60 percent of the men to be completely free of angiographic coronary artery disease. Thus, these men were "delabeled" of the diagnosis of coronary artery disease. In general, there was an increasing frequency of risk factors from no disease to significant disease, but the group with minimal coronary artery disease appeared more similar to the group with significant disease than to the group with no disease. Table VI presents an analysis of the risk factor data in the 98 men with significant angiographic disease grouped by the number of coronary vessels involved. There was a minimal increase in the percent of men with risk factors as the amount of disease increased. Also, in men able to perform a maximal treadmill effort, there

TABLE IV Maximal Treadmill Testing: Results of Use As Screening Factor in 52 Men With Angina or Probable Myocardial Infarction Men With Abnormal Test Who Had Significant CAD (Predictive Value)

Men With Abnormal Treadmill Test no.

%

no.

%

34 52

65

25 34

74

Men With Relative Risk Significant of Having CAD Who Had CAD if Test Abnormal Test Response is (Sensitivity) Abnormal Versus no. % Normal 25 33

76

1.9x

CAD = angiographic coronary artery disease.

TABLE V

Risk Factors and Maximal Treadmill Functional Data in 325 Aircrewmen Grouped by Angiographic Findings

Smoking History (% of group)

Positive Family History for CAD (% of group)

46

34

76

41

67

50

Positive Angiographic CAD No Minimal Significant

Age

no. (%) of Men

(yr) *

190 (58.5) 37 ( 11.4) 98 (30.2)

40 +7 42 +6 45 -+6

Serum Serum TriCholesterol glycerides (mg/100 (mg/100 ml)* ml)* 224 -+35 249 -+40 256 +50

130 +53 168 -+67 172 -+97

Blood Pressure (mm Hg)* 129 83 129 82 134 86

+ 12 -+ 9 -+ 11 -+ 9 -+ 15 -+ 10

VO 2 (cc O2/ kg-min)*

Maximal Double Heart Rate Product*t (beats/min)*

37.0 -+5.7 35.4 +4.5 34.8 -+5.6

36.7 +4.7 36.4 +4.8 34.4 -+5.3

184 -+11 183 +11 175 +13

* Values expressed as mean + standard deviation. t (Maximal systolic blood pressure X maximal heart rate)/103. CAD = coronary artery disease; VO 2 = oxygen consumption.

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ANGIOGRAPHIC-ELECTROCARDIOGRAPHIC FINDINGS IN ASYMPTOMATIC MEN--FROELICHER ET AL.

TABLE VI Risk Factors and Maximal Treadmill Functional Data in 98 Aircrewmen With Significant Coronary Artery Disease Grouped by Number of Vessels Involved Positive Positive Serum

Vessels With Significant

no. of

Age

CAD

Men (%) 45 (45.9) 40 (40.8) 13 (13.3)

One Two

Three

History

Blood

History

Pressure (mm Hg)*

(% of group)

f o r CAD (% of group)

VO 2 (cc 02/ kg-min)*

Double Product*

(beats/min)*

64

44

70

53

69

62

35.7 ±5.4 33.7 +5.4 34.1 +-6.7

33.7 ±4.8 36.3 ±5.6 30.6 +-3.7

175 ± 13 178 ±13 164 +10

Cholesterol glycerices (yr)*

(rag/100 ml)*

(rag/100 ml)*

44 +6 46 +6 46 ±7

243 +35 266 ±62 273 +43

157 ±72 194 ±128 154 +-37

Family

Smoking

Serum Tri-

132 85 137 88 135 85

-+ 12 ±9 ± 18 + 11 ± 16 +9

Maximal Heart Rate

* Values expressed as mean + standard deviation. CAD = coronary artery disease; VO 2 = oxygen consumption.

TABLE VII

TABLE VIII

Serum Cholesterol Value in 90th Percentile for Age: Results of Use As Screening Factor in 325 Aircrewmen

Estimate of Prevalence or Occurrence Rate of Electrocardiographic Abnormalities in Asymptomatic Apparently Healthy Men of the Same Age Range as the Aircrewmen Studied

Men < 4 0 Years (no. = 125) Serum cholesterol screening value (90th percentile for age) (rag/100 ml) Men with significant CAD if cholesterol lower than screening value (%) Men with significant CAD if cholesterol equal to or greater than screening value (%) Predictive value (%) Sensitivity (%) Relative risk

250

Men >/40 Years (no. = 200)

8.3

34.6

34.1

52.3

34.1 66.7 4.1

52.3 29.9 1.5

CAD = angiographic coronary artery disease.

was very little difference in maximal oxygen consumption. In these 98 men with 164 arteries containing significant lesions, the left anterior descending coronary artery was most frequently involved (41 percent), with involvement of the right coronary artery (33 percent) and then the left circumflex system (26 percent) following in decreasing frequency. Age and coronary artery disease: The prevalence rate of significant coronary artery disease was 16.8 percent in the 125 men less than 40 years old and 38.5 percent in the 200 men 40 years or older. A serum cholesterol value exceeding the 90th percentile for age had a greater sensitivity and risk for coronary artery disease in men less than 40 years old than in the older men (Table VII). Discussion

The future delivery of health care should emphasize the early detection and prevention of coronary artery disease. 14 Analysis of the data obtained in the USAF experience in the early detection of coronary artery disease, particularly in using electrocardiographic

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Estimated Prevalence Groups as Defined in This Study

or Occurrence Rate (as percent o f men screened)

Right bundle branch block Left bundle branch block Abnormal maximal exercise test Supraventricular tachycardia Ventricular irritability Probable infarction

0.2 0.08 5.0 0.1 2.0 0.16

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screening and exercise testing for this purpose, should be of considerable benefit to the medical community. Our study gives an angiographic description of a population not previously evaluated in such detail or numbers. From our study, it is apparent that electrocardiographic abnormalities are poorer predictors of heart disease in asymptomatic apparently healthy men than in hospital or clinic populations. This finding can be explained in terms of Bayes' theorem of statistics and the predictive model; that is, the predictive value of a test (the percent of those with an abnormal test who have disease) is directly related to the prevalence of disease in the population tested. 15 This is demonstrated by the high predictive value for an abnormal treadmill test in the two groups in Table IV compared with results in apparently healthy populations. 2,3,16 When apparently healthy populations are screened with routine electrocardiograms and exercise testing, persons will be identified with abnormalities such as those seen in our subgroups. The prevalence of electrocardiographic abnormalities in the USAF aircrew population has previously been demonstrated, t,17 and reasonable estimates of the occurrence rates of the abnormalities evaluated in our study are presented in Table VIII. However, the specificity, sensitivity, pre-

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ANGIOGRAPHIC-ELECTROCARDIOC~APHIC FINDINGS IN ASYMPTOMATIC MENmFROELICHER ET AL.

dictive value and risk ls,19 of electrocardiographic abnormalities in asymptomatic populations have not been established. Prevalence of Angiographic Coronary Artery Disease

Nearly 60 percent of the aircrewmen who underwent cardiac catheterization were found to be completely free of angiographic coronary artery disease and were "delabeled" of the diagnosis of coronary artery disease. There may be other causes of their electrocardiographic abnormalities, b u t these men should have a better prognosis than those with coronary artery disease. Our study did not establish the relative risk of having coronary artery disease by classification in any of our subgroups. Autopsy studies of military men after accidental or violent deaths have demonstrat~ed the prevalence of coronary artery disease in a similar population20; however, because of differences in technique, angiographic and autopsy findings cannot be equatedJ 2 Thus, one can only speculate on the prevalence of angiographic coronary artery disease in asymptomatic populations without electrocardiographic abnormalities but otherwise comparable with the men in our study. The order of the groups by increasing prevalence of coronary artery disease was as follows: abnormal treadmill test (labile vertical lead only), supraventricular tachycardia, right bundle branch block, left bundle branch block, abnormal treadmill test, ventricular irritability, probable infarct and angina. The low prevalence rate (3.7 percent) of angiographic coronary artery disease in the men with an abnormal treadmill test result only in the labile vertical lead illustrates the danger of using other than standard leads (that is, V5 or a comparable bipolar lead) for exercise testing. 21 This prevalence rate of angiographic coronary artery disease may be comparable with that found in an age-matched segment of the general population. A high risk for coronary artery disease in the groups with angina and probable infarction is implied by their relatively high prevalence rate (63.5 percent) of significant disease, particularly since their mean age was similar to that of the other groups. The predictive value (30.6 percent) of an abnormal treadmill test for significant angiographic coronary artery disease in our study was somewhat higher than the predictive value (20.0 percent) demonstrated in an earlier 6.3 year follow-up study using angina, sudden death and myocardial infarction as end points. 3 That earlier study also demonstrated an increased relative risk for coronary artery disease in men similar to that in our group with an abnormal treadmill test and in the group with ventricular irritability. 3,14 Unlike the earlier study, this study revealed a greater prevalence of coronary artery disease in the group with ventricular irritability than in the group with an abnormal treadmill test. This occurred because the group with ventricular irritability was highly selected for cardiac catheterization; their mean age was older than that of the other groups, and nearly half of them also had abnormal S-T segment depression in response to treadmill testing.

EUology of Electrocardiographic AbnormaliUes

Because it has been demonstrated that the electrocardiographic abnormalities in asymptomatic men are not always due to coronary artery disease, other causes must be considered. Although their electrocardiographic findings may represent normal variations, our men with normal coronary angiograms could have noncoronary heart disease or have changes secondary to a subclinical viral myocarditis. Other investigators have reported normal coronary angiograms in patients with angina 22 and in those who have had a myocardial infarction. 23 Approximately 7 percent of persons studied at autopsy after death from a definite myocardial infarction have patent nondiseased coronary arteries. 24 Therefore, other causes of myocardial ischemia are possible, including coronary arterial spasm and small vessel disease. 25~27 Although follow-up studies of asymptomatic men with bundle branch block have demonstrated that such men have a good prognosis, 28 left bundle branch block can be due to a progressive cardiomyopathy or Lenegre's disease leading to complete heart block. 29 Follow-up of the men in our study will be helpful in defining their prognosis according to the specific origin of their electrocardiographic abnormalities. Maximal Oxygen Consumption

Analysis of the maximal oxygen consumption, maximal heart rate and maximal blood pressure data on exercise showed little or no difference between the groups listed in Table II and the groups with coronary artery disease listed in Tables V and VI. There is much overlap between these data and published findings in normal men. 5,3° Maximal oxygen consumption has not been helpful in screening for latent heart disease; many patients with heart disease have had normal maximal oxygen consumption. Indeed, we have reported the case of an asymptomatic pilot with severe triple vessel disease and exceptional maximal oxygen consumptionY Risk Factor Data

Statistical comparison of risk factors among groups is of questionable value because of interaction, sample size and the need for tenuous age adjustments. Multivariate equations using the risk factors and other data might permit prediction of the probabiliW that a person will have coronary artery disease and improve the predictive value and sensitivity of screening techniques for latent coronary artery disease. As shown in Table V, the frequency of risk factors increased from men with no coronary artery disease to men with significant angiographic disease, but the group with minimal coronary artery disease was more similar to the group with significant disease than the group with no disease. In preliminary work using multivariate analysis, classification in a particular group, with the exception of having a probable infarction or angina, has been a poorer predictor of angiographic coronary artery disease than has age, cholesterol, blood pressure or smoking history. Surprisingly, in the 98 men (Table VI) with significant angiographic coronary artery disease, there was a

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minimal difference in risk factors as the amount of coronary artery disease increased. Thus, in regard to risk factors, there appeared to be a noticeable separation between those with angiographically normal coronary arteries and those with any disease. It could be hypothesized that men with minimal coronary artery disease are likely to have severe disease in time unless 'risk factors are altered. Knowledge of one's disease can be a powerful influence changing one's life style. This is a secondary but yet an important reason for angiographically delineating the amount of coronary artery disease present in asymptomatic men. The influences of age and serum cholesterol as risk factors are demonstrated in Table VII. The prevalence of angiographic coronary artery disease was two times greater in men aged 40 years or older than in the younger men. Of men whose serum cholesterol value exceeded the 90th percentile for their age group, 44 percent had significant disease. The risk of a serum cholesterol value exceeding the 90th percentile was almost three times greater for the men less than 40, than for men 40 years or older. This age-dependent risk is con-

sistent with the results from the Framingham study. 32

Conclusions Our experience indicates that electrocardiographic abnormalities are poorer predictors of coronary artery disease in asymptomatic apparently healthy men than in populations with a greater prevalence of coronary artery disease. Most often, performance of coronary angiography in aircrewmen has served to remove the diagnosis of coronary .artery disease. False positive findings represent a considerable problem in.the electrocardiographic screening of apparently healthy men. Follow-up studies of such populations are necessary to determine the specificity, sensitivity, predictive value and risk of electrocardiographic abnormalities for heart disease. The value to health care and cost effectiveness of such screening efforts need to be established.

Acknowledgment We express our appreciation to Mrs. Julie Froelicher for editing and Mrs. Theresa Diaz and Mrs. Jean Hubbert for typing the many drafts of this paper.

References 1. Averlll KH, Lamb LE: Electrocardiographic findings in 67,375 asymptomatic subjects. I. Incidence of abnormalities. Am J Cardiol 6:76-95, 1960 2. Froellcher VF: The application of electrocardiographic screening and exercise testing to preventive cardiology. Preventive Med 2: 592-607, 1973 3. Froelicher VF, Thomas M, Pillow C, et ah An epidemiologic study of asymptomatic men screened by maximal treadmill testing for latent coronary artery disease. Am J Cardiol 34:770-776, 1974 4. Froelicher VF, Yanowitz F, Thompson AJ, et al: The correlation of coronary angiography and the electrocardiographic response to maximal treadmill testing in 76 asymptomatic men. Circulation 48:597-604, 1973 5. Froelicher VF, Thompson AJ, Yanowitz F, et ah Treadmill Exercise Testing at the USAFSAM: Physiological Responses in Aircrewmen and the Detection of Latent Coronary Artery Disease. AGARDOGRAPH No. 210, 1975, NASA, Langley Field, Virginia 23365, p 37-45 6. Froelicher VF, Thompson AJ, Noguera I, et ah Prediction of maximal oxygen consumption: comparison of the Bruce and Balke protocols. Chest 68:325-336, 1975 7. Thompson AJ: Description of a technique for performing Sones coronary arteriography. In, Cardiac Catheterization, third edition (Zimmerman H, ed). Springfield, Ill, Charles C Thomas, 1976, p 105-136 8. Sones FM, Shirey EK: Cine-coronary arteriography. Mod Concepts Cardiovasc Dis 31:735-741, 1962 9. Oberman A, Jones WB, Riley CP, et al: Natural history of coronary artery disease. Bull NY Acad Med 48:1109-1120, 1972 10. Bruschke AV, Proudfit WL, Sones FM: Progress study of 590 consecutive nonsurgical cases of coronary disease followed 5-9 years. Circulation 47:1147-1153, 1973 11. Gould KL, Lipscomb K: Effects of coronary stenoses on coronary flow reserve and resistance. Am J Cardiol 34:48-54, 1974 12. Schwartz JN, Kong Y, Hackel DB, et al: Comparison of anglographic and postmortem findings in patients with coronary artery disease. Am J Cardiol 36:174-180, 1975 13. Herbert WH: Left bundle branch block and coronary artery disease. J Electroc 8:317-324, 1975 14. Abelmann WH: Cardiologic manpower resources and their distribution: a challenge for the future. Am J Cardiol 36:550-555, 1975 15. Froellcher VF: The detection of asymptomatic coronary artery disease, chap 15. In, Annual Review of Medicine, vol 28 (Creger

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January 1977

The American Journal of CARDIOLOGY

WP, ed). Palo Alto, Calif, Annual Reviews, 1976, p 115-134 16. Froellcher VF, Thompson AJ, Lon9o MR, et ah The value of exercise testing for screening asymptomatic men for latent coronary artery disease. Prog Cardiovasc Dis 18:265-276, 1976 17. Hiss RG, Lamb LE: Electrocardiographic findings in 122,043 individuals. Circulation 25:947-956, 1962 18. Vecchio TJ: Predictive value of a single diagnostic test in unselected populations. N Engl J Med 274:1171-1174, 1966 19. Galen RS, Gambino SR: Beyond Normality. New York, Wiley, 1975, p 27 20. Pettyjohn FS, McMeekln RR: Coronary artery disease and preventive cardiology in aviation medicine. Aviat Space Environ Med 46:1299-1305, 1975 21. Froelicher VF, Wolthuis R, Keiser N, et ah A comparison of two bipolar exercise leads to Vs. Chest 70:611-616, 1976 22. Richardson PJ, Livesley B, Oram S, et ah Angina pectoris with normal coronary arteries: transvenous myocardial biopsy in diagnosis. Lancet 2:677-681, 1974 23. Khan AH, Haywood LJ: Myocardial infarction in nine patients with radiologically patent coronary arteries. N Engl J Med 291:427-432, 1974 24. Eliot RS, Baroldi G, Leone A: Necropsy studies in myocardial infarction with minimal or no coronary luminal reduction due to atherosclerosis. Circulation 49:1127-1136, 1974 25. Cheitlin MD, McAIIister HA, de Castro CM: Myocardial infarction without atherosclerosis. JAMA 231:951-955, 1975 26. Maseri A, Mimmo R, Chierchla S, et al: Coronary artery spasm as a cause of acute myocardial ischemia in man. Chest 88: 625-632, 1975 27. Gensini GG: Coronary artery spasm and angina pectoris. Chest 68:709-715, 1975 28. Rotman M, Trlebwasser JH: A clinical and follow-up study of right and left bundle branch block. Circulation 51:477-482, 1975 29. Dhingra RC, Ashfaque K, Pouget JM, et al: Lenegre's disease in a young adult. Am Heart J 88:487-492, 1974 30. Wollhuis R, Froelicher VF, Fischer J, et ah The response of healthy men to treadmill exercise. Circulation 55:25-37, 1977 31. Thompson AJ, Froelicher VF" Kugel's artery as a major collateral channel in severe coronary disease. Aerospace Med 45:12761280, 1974 32. Kannel WB, Castelll WP, Gordon T, et al: Serum cholesterol, lipoproteins, and the risk of coronary heart disease. Ann Intern Med 74:1-9, 1972

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