Screening for Asymptomatic Coronary Artery Disease: Table 3. Association between Abnormal ST-Segment Response to Exercise and Coronary Heart Disease Events in Asymptomatic Persons

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Table 3. Association between Abnormal ST-Segment Response to Exercise and Coronary Heart Disease Events in Asymptomatic Persons^a

Author, Year (Reference)	Sample	Exclusion Criteria	Mean Years of Followup	Test	Abnormal Test Result		Cumulative Event Rate	Adjusted Relative Risk (95% CI) for CHD Events with Abnormal ST-Segment Response	Sensitivity for CHD Events	Positive Predictive Value of Abnormal ST Response	Variables for Which Relative Risk Was Adjusted
Author, Year (Reference)	Sample	Exclusion Criteria	Mean Years of Followup	Test	Definition	Prevalence	Cumulative Event Rate		Sensitivity for CHD Events	Positive Predictive Value of Abnormal ST Response	Variables for Which Relative Risk Was Adjusted
Giagnoni et al., 1983³⁶	514 factory workers in Italy Age range: 18-65 y 73% men	Positive history and physical exam for CVD, resting blood pressure ≥160/95 mm Hg, abnormal resting electocard-iogram	6 y	Submaximal supine cycle ergometry	≥1 mm of horizontal/downsloping ST-segment depression during or after exercise	NR	Normal exercise test 3.4% Abnormal exercise test result 15.6%^b	5.5 (2.8-11.2)	62	15	Age, systolic blood pressure, smoking, coronary risk index
MRFIT Trial Research Group, 1985⁸ Rautaharju et al., 1986⁵⁰	6,205 men in the upper 10% to 15% Framingham risk score distribution Age range: 35-57 100% men	Clinical heart disease, life-limiting conditions, diastolic blood pressure ≥115 mm Hg, cholesterol ≥350 mg/dL	7 y	Submaximal	Computer code ST- segment depression 16 muV-s or more in leads CS5, aVL, aVF, V5 during or after exercise (in electrocard-iogram with less than 6 muV-s depression at rest)	12.2%	Normal exercise test result 2/1,000 person years^b Abnormal exercise test result 7.6/1,000 person years^b	3.5 (P <0.05)^b 1.61 (P <0.01)^c	NR	36	Age, diastolic blood pressure, cholesterol, number of cigarettes smoked daily
Gordon et al., 1986⁴¹ Ekelund et al., 1989²⁶	3,640 white men in Lipid Research Clinics Prevalence Survey in United States and Canada Mean age: 47 Age range: 35-59 y 100% men	Evidence of CHD by history, resting electrocardiogram, and physician exam. Secondary hyperlipidem-ia, BMI >32.1 kg/m², blood pressure ≥165/105 mm Hg with antihypertensive or cardiovascular medication; diabetes mellitus.	8.1 y	Submaximal modified Bruce	≥1 mm of ST-segment depression or elevation or computer- ST integral decreased or increased ≥10 muV-s from resting value	8.3%	Placebo group Normal exerciser test result 13/1,000 person years^b Abnormal exercise test result 1.9/1,000 person years^b	Placebo group 5.7 (2.7-12.2)^b 3.3 (1.8-5.9)^c	30	7.1	Age, LDL cholesterol level, HDL cholesterol level, systolic blood pressure, smoking, family history
Gordon et al., 1986⁴¹ Ekelund et al., 1989²⁶			8.1 y	Submaximal modified Bruce		8.3%	Cholestyramine group Normal exercise test result 7.2/1,000 person years^b Abnormal exercise test result 1.5/1,000 person years^b	Cholestyramine group 4.9 (2.2-10.8)^b 2.9 (1.6-5.2)^c	30	7.1
Fleg et al., 1990¹⁹	407 residents of Baltimore, Maryland (mainly white) Mean age ±SD 60 ±11 y Range: 40-90 y 71% men	NR	4.6 y	Maximal treadmill with thallium modified Balke	≥1 mm of horizontal/ downsloping ST-segment during or after exercise	Abnormal electro-cardiogram only 16.0% Abnormal thallium scan only 14% Both tests abnormal 6.0%	Both test results normal, 7% Abnormal electrocardiogram only, 12% Abnormal thallium scan, only 3% Both tests abnormal, 48%	1.0 2.4 (P <0.05) 1.4 (NS) 3.6 (1.6-8.1)	40 N/A 28	24 N/A 48	Age, sex, hypertension, fasting blood glucose, total cholesterol, BMI, smoking, exercise duration
Okin et al., 1991⁴⁰	3,168 participants in the Framingham Offspring Study Mean age ±SD, 44 ±10 y Age range: 17-70 y 48% male	Medical contraindica-tions to exercise, history of myocardial infarction, CHF, valvular disease, syncope, conduction abnormalities, digoxin use, atrial fibrillation	4.3 y	Standard Bruce	ST segment corrected for heart rate index >1.6 muV per beat per min or abnormal rate recovery loop	416/3168 13% (either test abnormal)	Both tests normal 1.6% Either test abnormal 4.1% Both tests abnormal 9.8%	1.0 1.6 (1.1-2.5) 2.7 (1.8-4.0)	23% 8%	4% 10%	Age, sex, smoking, diastolic blood pressure, total cholesterol level, fasting blood glucose, left ventricular hypertrophy on electrocardiography
Siscovick et al., 1991¹²	3,617 white men in the Lipid Research Clinics Prevalence Survey Mean age: NR Age range: 35-59 y 100% male	Clinical evidence of CHD or CHF on history, various resting electrocard-iogram abnormalities	7.4 y	Submaximal modified Bruce	Visual code ≥1 mm ST-segment depression or elevation or computer code ≥10 muV 1/N s	6.6%	Overall 2%^d	2.6 (1.3 - 5.2)^d	18%	5%	Age, LDL cholesterol level, HDL cholesterol level, smoking, physical activity, workload achieved, family history of CHD, BMI, alcohol consumption
Blumenthal et al., 1996³²	264 healthy siblings of individuals with CAD before age 60 in Baltimore, Maryland Mean age ±SD, 46 ± 8 Age range: 37-59 y 69% men	Known CAD, corti-costeriods, collagen vascular disease, decreased life expectancy, functional status limitations	6.2 y	Modified Bruce and thallium scintigraphy	≥1 mm (≥2 mm for women) of horizontal or downsloping depression in 3 consecutive beats during exercise or first 3 min of recovery	Abnormal exercise electrocard-iogram 5.4% Abnormal plus thallium scan 18.1% Abnormal exercise electrocard-iogram and scan 4.6%	Normal 3%	1.0			Age, sex
							Abnormal exercise electrocardiogram 7%	1.5 (0.2-12.5)	N/A	N/A
							Abnormal thallium scan 13%	3.6 (1.1-11.4)	63%	20%
							Abnormal exercise electrocard-iogram and scan 50%	14.5 (4.2-50.2)	32%	50%
Okin et al., 1996³⁹	5,940 men in the usual care group of MRFIT Mean age: NR Age range: 35-57 y 100% men	No evidence of CHD by history, physical examination, or resting electrocard-iography	7 y	Submaximal treadmill	ST segment corrected for heart rate index >1.6 muV per beats per min	729/5,940 (12.3%)	Normal exercise test result 1.3%^b Abnormal exercise test result 5.4%^b	3.6 (2.4-5.4)^b	36%	5%	Age. Diastolic blood pressure, cholesterol level, smoking
Katzel et al., 1999²⁹	170 healthy sedentary obese men living in the Baltimore-Washington, DC area (96% white) Mean age: NR Age range: 45-79 y 100% men	History or laboratory evidence of CAD, diabetes mellitus, hypertension, hyperlipidemia	7.3 y	Maximal Bruce	≥1 mm of horizontal or downsloping ST-segment depression in 2 or more leads	37/170 (22%)	Overall 18%	4.23 (2.03-8.83)	55%	46%	Age, BMI, maximal VO2, fasting glucose level
Gibbons et al., 2000³³	25,927 patients of a preventive medicine clinic in Texas (mainly white) Mean age: 42.9 Age range 20-82 y 100% men	Evident CHD, severe aortic stenosis, acute systemic illness, uncontrolled atrial or ventricular arrhythmias, pericarditis, myocarditis, thrombophlebitis or exercise- limiting orthopedic problems	8.4 y	Maximal treadmill modified Blake	Chest pain and ≥1mm ST-segment depression or elevation, exercise induced-decrease ≥10 mm in systolic blood pressure, systolic blood pressure >250 mm Hg, diastolic blood pressure >120 mm Hg, ventricular tachycar-dia, left bundle-branch block, right bundle branch block, super-ventricular tachycardia	No risk factors, 3.0%	No risk factors Normal exercise test result 0.08/1000 person years^b Abnormal ETT 2.8/1000 person years^b	21 (6.9-63.3)^b	60	2.2	Age
Gibbons et al., 2000³³			8.4 y	Maximal treadmill modified Blake		>1 risk factor, 7.1%	>1 risk factor Normal ETT 0.5/1000 person years^b Abnormal exercise test result 7.6/1000 person years^b	9^b	61	7.7
Josephson et al., 1990¹¹ Rywik et al., 2002²¹	1,083 participants in the Baltimore Longitudinal Study of Aging Mean age ±SD, 52 ±18 y 57% men	History of angina or heart failure, Q wave on resting electrocardio-graphy, valvular disease, use of anti-arrhythmic drugs, inability to achieve 85% of maximal heart rate	7.9	Modified Balke	Normal		Men 4% Women 3%	1.0^e	Men 74 Women 68	Men 16 Women 7	Age, cholesterol, sex, exercise duration
					Minnesota Code 11.1^e	20%	Men 17% Women 8%	2.7 (1.6-4.7)^f
					Minnesota Code 11.5^e	5.5%	Men 17% Women 11%	2.7 (1.05-7.10)^f
					Minnesota Code 11.2^e	7%	Men 10% Women 5%	OR 1.8^f (0.6-5.4)
					Minnesota Code 11.4^e	11.5%	Men 17% Women 3%	OR 1.3^f (0.6-2.9)
Jouven and Ducimetiere, 2000⁴⁵	6,101 Frenchmen in Paris Civil Service Age range: 42-53 y 100% men	Known or suspected CVD, resting systolic blood pressure ±180 mm Hg, resting Electrocard-iographic abnormality	23	Bicycle ergometry	J-point depression of at least 1 mm with a flat or downsloping ST segment during exercise or recovery	4.4%	Normal exercise test result, 6.4% Abnormal exercise test result 16.7%^b	2.6 (1.93-3.59)^b	10	17-25	Age, BMI, heart rate at rest, smoking, physical activity, diabetes mellitus, total cholesterol level, premature ventricular complex
Laukkanen et al., 2001²⁰	1,769 participants, population in Kupio Ischemic Heart Disease Study base sample of Finnish men Mean age ±SD, 52 ±5.2 y 100% men	Known CHD or symptoms suggestive of CHD	10	Maximal Bicycle ergometry	>1 mm ST-segment depression during exercise	10.7%	Normal exercise test result 9.2% 2.4%^b Abnormal 15.3% 7.9%^b	1.7 (1.1-2.6) 3.5 (1.9-6.5)^b	16	15	Age, examination year, smoking, systolic blood pressure, alcohol consumption, BMI, max oxygen uptake, diabetes mellitus, LDL cholesterol level, HDL cholesterol level
Rutter et al., 2002¹³	86 diabetic patients in the United Kingdom Mean age ±SD, 62 ±7 y Age range: 46-74 y 72% men	History of CAD	2.8	Treadmill	>1 mm of horizontal or downsloping ST-segment depression for 3 consecutive beats	52%	Both normal and abnormal exercise test results 17%	21 (2-204)	100%	20%	Ankle brachial index, microalbuminuria, Framingham 10-y CHD risk >30%, fibrinogen level
Mora et al., 2003⁴²	2994 women enrolled in the Lipid Research Clinics Prevalence Study Age range 30-80 0% men	Pregnancy or significant cardiovascu-lar disease	20.3	Maximal Bruce	≥1mm horizontal or downsloping ST-segment depression at 0.08 seconds after the J point during recovery or exercise	4.7%	Both normal and abnormal exercise tolerance test results 5%^b 14%^c	0.88 (0.48-1.61)^b 0.69 (0.45-1.04)^c			Age, smoking, diabetes, family history of premature heart disease, obesity, HDL cholesterol level, LDL cholesterol level, triglyceride level, hypertension

^aEvents are CHD events unless otherwise indicated. BMI = body mass index; CAD = coronary heart disease; CVD = cardiovascular disease; HDL = high-density lipoprotein; LDL = low-density lipoprotein; MRFIT = Multiple Risk Factor Intervention Trial Research Group; NA = not applicable; NR = not reported.
^bCHD death.
^cAll-cause death.
^dFor CHD events occurring during exercise.
^eMinnesota code 11.1 = ≥1 mm J-point depression with flat or downsloping ST segment in most complexes in any lead except aVR; Minnesota code 11.2 = horizontal or downsloping ST-segment depression of 0.5-1.0 mm; Minnesota code 11.4 = J-point depression of ≥1 mm with upsloping ST; Minnesota code 11.5 = ST-segment depression at rest that worsens to 11.1 during exercise.
^fValues are odds ratios (95% CI).

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Table 3. Association between Abnormal ST-Segment Response to Exercise and Coronary Heart Disease Events in Asymptomatic Personsa

Table 3. Association between Abnormal ST-Segment Response to Exercise and Coronary Heart Disease Events in Asymptomatic Persons^a