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April 10, 1987, Vol 257, No. 14 >
ARTICLE | April 10, 1987

Asymptomatic Ischemia in Patients With Coronary Artery Disease FREE

Elizabeth G. Nabel, MD; Michael B. Rocco, MD; Joan Barry; Stephen Campbell, BSc, MRCP; Andrew P. Selwyn, MD
[+] Author Affiliations

This article is one of a series sponsored by the American Heart Association.

Reprint requests to Cardiovascular Division, Brigham and Women's Hospital, 75 Francis St, Boston, MA 02115 (Dr Nabel).


JAMA. 1987;257(14):1923-1928. doi:10.1001/jama.1987.03390140093034
Text Size: A A A
Published online
Article
References

ANGINA pectoris is the hallmark symptom of coronary artery disease and its frequency and severity has traditionally provided the basis for evaluation and treatment.

Assessment of patients with coronary artery disease and decisions regarding their treatment are usually based on the patient's subjective account of symptoms. Studies (exercise tolerance tests, radionuclide angiography, and coronary arteriography) performed during brief visits to the clinic or hospital can only provide an indirect estimate of the patient's ischemic activity out of the hospital. Recent studies suggest that a large population of adults with coronary artery disease experience many episodes of asymptomatic or silent transient myocardial ischemia on a daily basis, apart from the events that occur with pain.1,2 Ambulatory electrocardiographic (ECG) monitoring of ST segments provides an objective measurement of transient ischemia during everyday life, and, as a result, a more extensive and detailed understanding of the pathophysiology of coronary artery disease has

REFERENCES

1 +
Stern S, Tzivoni D:  Early detection of silent ischaemic heart disease by 24-hour electrocardiographic monitoring of active subjects . Br Heart J 1974;;36:481-486.
2 +
Selwyn AP, Fox K, Eves M, et al:  Myocardial ischaemia in patients with frequent angina pectoris . Br Med J 1978;;2:1594-1596.
3 +
Cecci AC, Dovellini EV, Marchi F, et al:  Silent myocardial ischemia during ambulatory electrocardiographic monitoring in patients with effort angina . J Am Coll Cardiol 1983;;1:934-939.
4 +
Deanfield JE, Shea M, Ribeiro P, et al:  Transient ST-segment depression as a marker of myocardial ischemia during daily life . Am J Cardiol 1984;;54:1195-1200.
5 +
Theroux P, Waters DD, Halphen C, et al:  Prognostic value of exercise testing soon after myocardial infarction . N Engl J Med 1979;;301:341-345.
6 +
Langou RA, Huang EK, Kelley MJ, et al:  Predictive accuracy of coronary artery calcification and abnormal exercise test for coronary artery disease in asymptomatic men . Circulation 1980;; 62:1196-1203.
7 +
Erikssen J, Thoulaw E:  Follow-up of patients with asymptomatic myocardial ischemia , in Rutishauser W, Roskamm H (eds): Silent Myocardial Ischemia . Berlin, Springer-Verlag, 1984;, pp 154-164.
8 +
Kannel WB, Abbott RD:  Incidence and prognosis of unrecognized myocardial infarction . N Engl J Med 1984;;311:1144-1147.
9 +
Kent KM, Rosing DR, Ewels CJ, et al:  Prognosis of asymptomatic or mildly symptomatic patients with coronary artery disease . Am J Cardiol 1982;;49:1823-1830.
10 +
Cohn PF, Harris P, Barry WH, et al:  Prognostic importance of angina symptoms in angiographic defined coronary artery disease . Am J Cardiol 1981;;47:233-237.
11 +
Hickman JR, Uhe GS, Cook RL, et al:  A natural history study of asymptomatic coronary disease, abstracted . Am J Cardiol 1980;;45:422.
12 +
Deanfield JE, Kensett M, Wilson RA, et al:  Silent myocardial ischaemia due to mental stress . Lancet 1984;;2:1001-1005.
13 +
Shea MJ, Deanfield JE, Wilson R, et al:  Transient ischemia in angina pectoris: Frequent silent events with every day activities . J Am Coll Cardiol 1985;;56:34E-38E.
14 +
Deanfield JE, Selwyn AP, Chierchia S, et al:  Myocardial ischaemia during daily life in patients with stable angina: Its relation to symptoms and heart rate changes . Lancet 1983;;2:753-758.
15 +
Schang SJ Jr, Pepine CJ:  Transient asymptomatic ST-depression during daily activity . Am J Cardiol 1977;;39:396-402.
16 +
Selwyn AP, Shea MJ, Deanfield JE, et al:  Clinical problems in coronary disease are caused by wide variety of ischemic episodes that affect patients out of hospital . Am J Med 1985;;79:12-17.
17 +
Chierchia S, Smith G, Morgan M, et al:  Role of heart rate in pathophysiology of chronic stable angina . Lancet 1984;;1:1353-1357.
18 +
Muller JE, Stone PH, Turi ZG, et al:  Circadian variation in the frequency of acute myocardial infarction . N Engl J Med 1985;;313:1315-1322.
19 +
Muller JE, Ludmer PL, Willich S, et al:  Circadian variation in the frequency of sudden cardiac death . Circulation 1987;;75:131-138.
20 +
Rocco MB, Barry J, Campbell S, et al:  Circadian variation of transient myocardial ischemia . Circulation 1987;;75:395-400.
21 +
Tzivoni D, Benhorn J, Gavish A, et al:  Holter recording during treadmill testing in assessing myocardial ischemic changes . Am J Cardiol 1985;; 55:1200-1203.
22 +
Campbell S, Barry J, Rocco MB, et al:  Features of the exercise test that indicate activity of ischemic heart disease during daily life . Circulation 1986;; 74:72-80.
23 +
Bonow RD, Kent KM, Rosing DR, et al:  Exercise-induced ischemia in mildly symptomatic patients with coronary artery disease and preserved left ventricular function: Identification of subgroups at risk of death during medical therapy . N Engl J Med 1984;;311:1339-1345.
24 +
Campbell S, Barry J, Rebecca GS, et al:  Active ischemia during daily life in asymptomatic patients with positive exercise tests and coronary artery disease . Am J Cardiol 1986;;57:1010-1016.
25 +
Malliani A:  Cardiovascular sympathetic afferent fibers . Rev Physiol 1982;;94:11-74.
26 +
Proccaci P, Zoppi M, Padeletti L, et al:  Myocardial infarction without pain: A study of the sensory function of the upper limbs . Pain 1976;;2:308-313.
27 +
Droste C, Roskamm H:  Experimental pain measurements in patients with asymptomatic myocardial ischemia . J Am Coll Cardiol 1983;;1:940-945.
28 +
Maseri A, Parodi O, Severi S, et al:  Transient transmural reduction of myocardial blood flow, demonstrated by thallium-201 scintigraphy, as a cause of variant angina . Circulation 1976;;54:280-288.
29 +
Chierchia S, Brunelli C, Simonetti I, et al:  Sequence of events in angina at rest: Primary reduction in coronary flow . Circulation 1980;;61:759-768.
30 +
Brown BG, Bolson EL, Dodge HT:  Dynamic mechanisms in human coronary stenosis . Circulation 1984;;70:917-922.
31 +
Selwyn AP, Allan RM, L'Abbate A, et al:  Relations between regional myocardial uptake of rubidium-82 and perfusion: Absolute reduction of cation uptake in ischemia . Am J Cardiol 1982;;50: 112-121
32 +
Selwyn AP, Shea M, Deanfield J, et al:  The character of transient myocardial ischemia: Clinical studies and progress using positron emission tomography . Int J Card Imag 1985;;1:61-72.
33 +
Deanfield JE, Shea MJ, Wilson R, et al:  Direct effect of cigarette smoking causes silent ischemia in patients with angina pectoris . Am J Cardiol 1986;; 57:1005-1010.
34 +
Selwyn AP, Shea MJ, Foale R, et al:  Regional myocardial and organ blood flow after myocardial infarction: Application of the microsphere principle in man . Circulation 1986;;73:433-443.
35 +
Ellis EF, Oelz O, Roberts LJ, et al:  Coronary arterial smooth-muscle contraction by a substance released from platelets: Evidence that it is thromboxane A2 . Science 1976;;193:1135-1137.
36 +
Hirsh PD, Mills LD, Campbell WB, et al:  Release of prostaglandins and thromboxane into the coronary circulation in patients with ischemic heart disease . N Engl J Med 1981;;304:685-691.
37 +
Sobel M, Salzman EW, Davies GC, et al:  Circulating platelet products in unstable angina pectoris . Circulation 1981;;63:300-306.
38 +
Furchgott RF:  Role of endothelium in responses of vascular smooth muscle . Circ Res 1983;; 53:557-573.
39 +
Vanhoutte PM, Houston DA:  Platelets, endothelium, and vasospasm . Circulation 1985;;72:728-734.
40 +
Ludmer PL, Selwyn AP, Shook TL, et al:  Paradoxical vasoconstriction induced by acetylcholine in atherosclerotic coronary arteries . N Engl J Med 1986;;315:1046-1051.
41 +
Furchgott RF, Zawaddzki JV:  The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine . Nature 1980;;288: 373-376.
42 +
Cherry PD, Furchgott RF, Zawadski JV, et al:  Role of endothelial cells in relaxation of isolated arteries by bradykinin . Proc Natl Acad Sci USA 1982;;79:2106-2110.
43 +
Berk BC, Brock TA, Webb RC, et al:  Epidermal growth factor, a vascular smooth-muscle mitogen, induces rat aortic contraction . J Clin Invest 1985;;75:1083-1086.
44 +
Holter NJ:  New method for heart studies: Continuous electrocardiography of active subjects over long periods is now practical . Science 1961;; 134:1214-1220.
45 +
Balasubramanian V, Lahirl A, Green HL, et al:  Ambulatory ST-segment monitoring: Problems, pitfalls, solutions and clinical application . Br Heart J 1980;;44:419-425.
46 +
Bragg-Remschel DA, Anderson CM, Winkle RA:  Frequency response characteristics of ambulatory ECG monitoring systems and their implications for ST-segment analysis . Am Heart J 1982;; 1:20-31.
47 +
Quyyumi AA, Wright C, Fox K:  Ambulatory electrocardiographic ST-segment changes in healthy volunteers . Br Heart J 1983;;50:460-464.
48 +
Tzivoni D, Stern Z, Keren A, et al:  Electrocardiographic characteristics of neurocirculatory asthenia during everyday activities . Br Heart J 1980;; 44:426-432.
49 +
Stern S, Tzivoni D:  Dynamic changes in the STT segment during sleep in ischemic heart disease . Am J Cardiol 1973;;32:17-20.
50 +
Deanfield JE, Ribeiro P, Oakley K, et al:  Analysis of ST-segment changes in normal subjects: Implications for ambulatory monitoring in angina pectoris . Am J Cardiol 1984;;54:1321-1325.
51 +
Califf RM, McKinnis RA, Burk J, et al:  Prognostic implications of ventricular arrhythmias during 24-hour ambulatory monitoring in patients undergoing cardiac catheterization for coronary artery disease . Am J Cardiol 1982;;50:23-31.
52 +
Hammermeister KE, DeRoven TA, Dodge HT:  Variables predictive of survival in patients with coronary disease . Circulation 1979;;59:421-430.
53 +
Takaro T, Hultgren HN, Detre KM, et al:  The Veterans Administration Cooperative Study of stable angina: Current status . Circulation 1982;;65: II60-II67.
54 +
Gottlieb SO, Weisfeldt ML, Ouyang P, et al:  Silent ischemia as a marker for early unfavorable outcomes in patients with unstable angina . N Engl J Med 1986;;314:1214-1219.

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Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature

Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal

1 +
Stern S, Tzivoni D:  Early detection of silent ischaemic heart disease by 24-hour electrocardiographic monitoring of active subjects . Br Heart J 1974;;36:481-486.
2 +
Selwyn AP, Fox K, Eves M, et al:  Myocardial ischaemia in patients with frequent angina pectoris . Br Med J 1978;;2:1594-1596.
3 +
Cecci AC, Dovellini EV, Marchi F, et al:  Silent myocardial ischemia during ambulatory electrocardiographic monitoring in patients with effort angina . J Am Coll Cardiol 1983;;1:934-939.
4 +
Deanfield JE, Shea M, Ribeiro P, et al:  Transient ST-segment depression as a marker of myocardial ischemia during daily life . Am J Cardiol 1984;;54:1195-1200.
5 +
Theroux P, Waters DD, Halphen C, et al:  Prognostic value of exercise testing soon after myocardial infarction . N Engl J Med 1979;;301:341-345.
6 +
Langou RA, Huang EK, Kelley MJ, et al:  Predictive accuracy of coronary artery calcification and abnormal exercise test for coronary artery disease in asymptomatic men . Circulation 1980;; 62:1196-1203.
7 +
Erikssen J, Thoulaw E:  Follow-up of patients with asymptomatic myocardial ischemia , in Rutishauser W, Roskamm H (eds): Silent Myocardial Ischemia . Berlin, Springer-Verlag, 1984;, pp 154-164.
8 +
Kannel WB, Abbott RD:  Incidence and prognosis of unrecognized myocardial infarction . N Engl J Med 1984;;311:1144-1147.
9 +
Kent KM, Rosing DR, Ewels CJ, et al:  Prognosis of asymptomatic or mildly symptomatic patients with coronary artery disease . Am J Cardiol 1982;;49:1823-1830.
10 +
Cohn PF, Harris P, Barry WH, et al:  Prognostic importance of angina symptoms in angiographic defined coronary artery disease . Am J Cardiol 1981;;47:233-237.
11 +
Hickman JR, Uhe GS, Cook RL, et al:  A natural history study of asymptomatic coronary disease, abstracted . Am J Cardiol 1980;;45:422.
12 +
Deanfield JE, Kensett M, Wilson RA, et al:  Silent myocardial ischaemia due to mental stress . Lancet 1984;;2:1001-1005.
13 +
Shea MJ, Deanfield JE, Wilson R, et al:  Transient ischemia in angina pectoris: Frequent silent events with every day activities . J Am Coll Cardiol 1985;;56:34E-38E.
14 +
Deanfield JE, Selwyn AP, Chierchia S, et al:  Myocardial ischaemia during daily life in patients with stable angina: Its relation to symptoms and heart rate changes . Lancet 1983;;2:753-758.
15 +
Schang SJ Jr, Pepine CJ:  Transient asymptomatic ST-depression during daily activity . Am J Cardiol 1977;;39:396-402.
16 +
Selwyn AP, Shea MJ, Deanfield JE, et al:  Clinical problems in coronary disease are caused by wide variety of ischemic episodes that affect patients out of hospital . Am J Med 1985;;79:12-17.
17 +
Chierchia S, Smith G, Morgan M, et al:  Role of heart rate in pathophysiology of chronic stable angina . Lancet 1984;;1:1353-1357.
18 +
Muller JE, Stone PH, Turi ZG, et al:  Circadian variation in the frequency of acute myocardial infarction . N Engl J Med 1985;;313:1315-1322.
19 +
Muller JE, Ludmer PL, Willich S, et al:  Circadian variation in the frequency of sudden cardiac death . Circulation 1987;;75:131-138.
20 +
Rocco MB, Barry J, Campbell S, et al:  Circadian variation of transient myocardial ischemia . Circulation 1987;;75:395-400.
21 +
Tzivoni D, Benhorn J, Gavish A, et al:  Holter recording during treadmill testing in assessing myocardial ischemic changes . Am J Cardiol 1985;; 55:1200-1203.
22 +
Campbell S, Barry J, Rocco MB, et al:  Features of the exercise test that indicate activity of ischemic heart disease during daily life . Circulation 1986;; 74:72-80.
23 +
Bonow RD, Kent KM, Rosing DR, et al:  Exercise-induced ischemia in mildly symptomatic patients with coronary artery disease and preserved left ventricular function: Identification of subgroups at risk of death during medical therapy . N Engl J Med 1984;;311:1339-1345.
24 +
Campbell S, Barry J, Rebecca GS, et al:  Active ischemia during daily life in asymptomatic patients with positive exercise tests and coronary artery disease . Am J Cardiol 1986;;57:1010-1016.
25 +
Malliani A:  Cardiovascular sympathetic afferent fibers . Rev Physiol 1982;;94:11-74.
26 +
Proccaci P, Zoppi M, Padeletti L, et al:  Myocardial infarction without pain: A study of the sensory function of the upper limbs . Pain 1976;;2:308-313.
27 +
Droste C, Roskamm H:  Experimental pain measurements in patients with asymptomatic myocardial ischemia . J Am Coll Cardiol 1983;;1:940-945.
28 +
Maseri A, Parodi O, Severi S, et al:  Transient transmural reduction of myocardial blood flow, demonstrated by thallium-201 scintigraphy, as a cause of variant angina . Circulation 1976;;54:280-288.
29 +
Chierchia S, Brunelli C, Simonetti I, et al:  Sequence of events in angina at rest: Primary reduction in coronary flow . Circulation 1980;;61:759-768.
30 +
Brown BG, Bolson EL, Dodge HT:  Dynamic mechanisms in human coronary stenosis . Circulation 1984;;70:917-922.
31 +
Selwyn AP, Allan RM, L'Abbate A, et al:  Relations between regional myocardial uptake of rubidium-82 and perfusion: Absolute reduction of cation uptake in ischemia . Am J Cardiol 1982;;50: 112-121
32 +
Selwyn AP, Shea M, Deanfield J, et al:  The character of transient myocardial ischemia: Clinical studies and progress using positron emission tomography . Int J Card Imag 1985;;1:61-72.
33 +
Deanfield JE, Shea MJ, Wilson R, et al:  Direct effect of cigarette smoking causes silent ischemia in patients with angina pectoris . Am J Cardiol 1986;; 57:1005-1010.
34 +
Selwyn AP, Shea MJ, Foale R, et al:  Regional myocardial and organ blood flow after myocardial infarction: Application of the microsphere principle in man . Circulation 1986;;73:433-443.
35 +
Ellis EF, Oelz O, Roberts LJ, et al:  Coronary arterial smooth-muscle contraction by a substance released from platelets: Evidence that it is thromboxane A2 . Science 1976;;193:1135-1137.
36 +
Hirsh PD, Mills LD, Campbell WB, et al:  Release of prostaglandins and thromboxane into the coronary circulation in patients with ischemic heart disease . N Engl J Med 1981;;304:685-691.
37 +
Sobel M, Salzman EW, Davies GC, et al:  Circulating platelet products in unstable angina pectoris . Circulation 1981;;63:300-306.
38 +
Furchgott RF:  Role of endothelium in responses of vascular smooth muscle . Circ Res 1983;; 53:557-573.
39 +
Vanhoutte PM, Houston DA:  Platelets, endothelium, and vasospasm . Circulation 1985;;72:728-734.
40 +
Ludmer PL, Selwyn AP, Shook TL, et al:  Paradoxical vasoconstriction induced by acetylcholine in atherosclerotic coronary arteries . N Engl J Med 1986;;315:1046-1051.
41 +
Furchgott RF, Zawaddzki JV:  The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine . Nature 1980;;288: 373-376.
42 +
Cherry PD, Furchgott RF, Zawadski JV, et al:  Role of endothelial cells in relaxation of isolated arteries by bradykinin . Proc Natl Acad Sci USA 1982;;79:2106-2110.
43 +
Berk BC, Brock TA, Webb RC, et al:  Epidermal growth factor, a vascular smooth-muscle mitogen, induces rat aortic contraction . J Clin Invest 1985;;75:1083-1086.
44 +
Holter NJ:  New method for heart studies: Continuous electrocardiography of active subjects over long periods is now practical . Science 1961;; 134:1214-1220.
45 +
Balasubramanian V, Lahirl A, Green HL, et al:  Ambulatory ST-segment monitoring: Problems, pitfalls, solutions and clinical application . Br Heart J 1980;;44:419-425.
46 +
Bragg-Remschel DA, Anderson CM, Winkle RA:  Frequency response characteristics of ambulatory ECG monitoring systems and their implications for ST-segment analysis . Am Heart J 1982;; 1:20-31.
47 +
Quyyumi AA, Wright C, Fox K:  Ambulatory electrocardiographic ST-segment changes in healthy volunteers . Br Heart J 1983;;50:460-464.
48 +
Tzivoni D, Stern Z, Keren A, et al:  Electrocardiographic characteristics of neurocirculatory asthenia during everyday activities . Br Heart J 1980;; 44:426-432.
49 +
Stern S, Tzivoni D:  Dynamic changes in the STT segment during sleep in ischemic heart disease . Am J Cardiol 1973;;32:17-20.
50 +
Deanfield JE, Ribeiro P, Oakley K, et al:  Analysis of ST-segment changes in normal subjects: Implications for ambulatory monitoring in angina pectoris . Am J Cardiol 1984;;54:1321-1325.
51 +
Califf RM, McKinnis RA, Burk J, et al:  Prognostic implications of ventricular arrhythmias during 24-hour ambulatory monitoring in patients undergoing cardiac catheterization for coronary artery disease . Am J Cardiol 1982;;50:23-31.
52 +
Hammermeister KE, DeRoven TA, Dodge HT:  Variables predictive of survival in patients with coronary disease . Circulation 1979;;59:421-430.
53 +
Takaro T, Hultgren HN, Detre KM, et al:  The Veterans Administration Cooperative Study of stable angina: Current status . Circulation 1982;;65: II60-II67.
54 +
Gottlieb SO, Weisfeldt ML, Ouyang P, et al:  Silent ischemia as a marker for early unfavorable outcomes in patients with unstable angina . N Engl J Med 1986;;314:1214-1219.

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