title: Independent risk for cardiovascular disease predicted by modified continuous score electrocardiographic criteria for 6-year incidence and regression of left ventricular hypertrophy among clinically disease free men: 16-year follow-up for the multiple risk factor intervention trial. Limited clinical value of exercise stress test for the screening of coronary artery disease in young, asymptomatic adult men. Assessing the Value of Risk Predictions by Using Risk Stratification Tables Exercise workload, cardiovascular risk factor evaluation and the risk of stroke in middle-aged men. Enhanced Risk Assessment in Asymptomatic Individuals With Exercise Testing and Framingham Risk Scores Association of Exercise-Induced, Silent ST-Segment Depression With the Risk of Stroke and Cardiovascular Diseases in Men Scintigraphic and electrocardiographic evidence of silent coronary artery disease in asymptomatic hypertension: a case-control study. Impaired heart rate response to graded exercise. Prognostic implications of chronotropic incompetence in the Framingham Heart Study. Global risk scores and exercise testing for predicting all-cause mortality in a preventive medicine program. Major risk factors as antecedents of fatal and nonfatal coronary heart disease events. Detecting Occult Coronary Disease in a High-Risk Asymptomatic Population Cardiorespiratory fitness as a predictor of nonfatal cardiovascular events in asymptomatic women and men. Prognostic value of ECG findings for total, cardiovascular disease, and coronary heart disease death in men and women Prognostic value of exercise EKG testing in asymptomatic normotensive subjects. A prospective matched study. Coronary heart disease morbidity and mortality in hypercholesterolemic men predicted from an exercise test: the Lipid Research Clinics Coronary Primary Prevention Trial. Symptom-limited exercise testing, ST depressions and long-term coronary heart disease mortality in apparently healthy middle-aged men Impact of minor electrocardiographic ST-segment and/or T-wave abnormalities on cardiovascular mortality during long-term follow-up. Diagnostic value of the maximal ST segment/heart rate slope in asymptomatic factory populations. Major and minor ECG abnormalities in asymptomatic women and risk of cardiovascular events and mortality. Is exercise testing useful to improve the prediction of coronary events in asymptomatic subjects? Long-term prognostic significance of isolated minor electrocardiographic T-wave abnormalities in middle-aged men free of clinical cardiovascular disease (The Multiple Risk Factor Intervention Trial [MRFIT]). Sensitivity of exercise electrocardiography for acute cardiac events during moderate and strenuous physical activity. The Lipid Research Clinics Coronary Primary Prevention Trial. Predictors of congestive heart failure in the elderly: the Cardiovascular Health Study. Electrocardiographic Minnesota code findings predicting short-term mortality in asymptomatic subjects. The Italian RIFLE Pooling Project (Risk Factors and Life Expectancy). Heart Rate Recovery after Submaximal Exercise Testing as a Predictor of Mortality in a Cardiovascularly Healthy Cohort Usefulness of ventricular premature complexes to predict coronary heart disease events and mortality (from the Atherosclerosis Risk In Communities cohort). Prognostic value of the duke treadmill score in asymptomatic women. Exercise workload, coronary risk evaluation and the risk of cardiovascular and all-cause death in middle-aged men Left ventricular hypertrophy on electrocardiogram: prognostic implications from a 10-year cohort study of older subjects: a report from the Bronx Longitudinal Aging Study. Electrocardiographic findings and incident coronary heart disease among participants in the Atherosclerosis Risk in Communities (ARIC) study. Sudden unexpected cardiac death as a function of time since the detection of electrocardiographic and clinical risk factors in apparently healthy men: the Manitoba Follow-Up Study, 1948 to 2004.
abstract: Risk prediction for electrocardiographic ( ECG ) left ventricular hypertrophy related criteria , used in clinical trials , and epidemiologic studies of clinical ly healthy people , has depended in the past on dichotomous classification of ECG LVH criteria . Recent analyses have shown that more sensitive methods of LVH ECG classification without loss of specificity are needed to improve on dichotomous classification . This was done by relating six year incident significant change in continuous score criteria of ECG LVH to the 16 year ( 10 year post trial ) coronary heart disease ( CHD ) and cardiovascular disease ( CVD ) mortality among 12,866 men , free of clinical disease , aged 35 to 57 years at baseline in the Multiple Risk Factor Intervention Trial . It was found that significant change in continuous ECG LVH criteria was a stronger independent predictor of future CHD and CVD mortality than was use of dichotomous classification of the same criteria . It was also demonstrated that increase in continuous ECG LVH indexes , below previous dichotomous thresholds independently ( of st and ard CVD risk factors , including increase in obesity-indicated by an increase in adult BMI ) predicted excess CHD and CVD mortality and that combinations of continuous indices increases the specificity and relative risk in clinical ly disease-free middle-aged men 1 . Frei B , Engl and L , Ames BN . Ascorbate is an outst and ing antioxidant in human blood plasma . Proc Natl Acad Sci U S A 1989;86:6377–6381 . 2 . Ting HH , Timimi FK , Boles KS , Creager SJ , Ganz P , Creager MA . Vitamin C improves endothelium-dependent vasodilation in patients with non-insulindependent diabetes mellitus . J Clin Invest 1996;97:22–28 . 3 . Heitzer T , Just H , Munzel T. Antioxidant vitamin C improves endothelial dysfunction in chronic smokers . Circulation 1996;94:6–9 . 4 . Slakey D , Roza A , Pieper G , Johnson C , Adams M. Delayed cardiac allograft rejection due to combined cyclosporine and antioxidant therapy . Transplantation 1993;56:1305–1309 . 5 . Fish RD , Nabel EG , Selwyn AP , Ludmer PL , Mudge GH , Kirshenbaum JM , Schoen FJ , Alex and er RW , Ganz P. Responses of coronary arteries of cardiac transplant patients to acetylcholine . J Clin Invest 1988;81:21–31 . 6 . Davis SF , Yeung AC , Meredith IT , Charbonneau F , Ganz P , Selwyn AP , And erson TJ . Early endothelial dysfunction predicts the development of transplant coronary artery disease at 1 year posttransplant . Circulation 1996;93:457– 462 . 7 . Morrow JD , Roberts LJ II . Mass spectrometric quantification of F2-isoprostanes in biological fluids and tissues as measure of oxidant stress . Methods Enzymol 1999;300:3–12 . 8 . Watanabe H , Kakihana M , Ohtsuka S , Sugishita Y. R and omized , double-blind , placebo-controlled study of ascorbate on the preventive effect of nitrate tolerance in patients with congestive heart failure . Circulation 1998;97:886–891 Key Summary Points Risk prediction models are statistical models used to predict the probability of an outcome on the basis of the values of 1 or more risk factors ( markers ) . The accuracy of the model 's predictions is typically summarized with statistics that describe the model 's discrimination and calibration . Risk stratification tables are a more informative way to assess and compare the models . The tables illustrate the distribution of predictions across risk categories . That illustration allows users to assess 3 key measures of the models ' value for guiding medical decisions : the models ' calibration , ability to stratify people into clinical ly relevant risk categories , and accuracy at classifying patients into higher- and lower-risk categories . This information is contained in the margins of the risk stratification table rather than in its cells . The tables should only be used to compare risk prediction models when one of the models contains all of the markers that are contained in the other ( nested models ) ; they should not be used to compare models with different sets of markers ( nonnested models ) . The table predictions require corrections when casecontrol data are used . The recent epidemiologic and clinical literature is filled with studies evaluating statistical models that predict risk for disease or some other adverse event ( 15 ) . Because risk prediction models are intended to help patients and clinicians make decisions , evaluation of these models requires methods that differ from those used to assess models describing disease etiology . This is because the characteristics of the models are less important than their value for guiding decisions . Cook and colleagues ( 1 , 6 ) recently proposed a new approach to evaluate risk prediction models : a risk stratification table . This methodology appropriately focuses on the key purpose of a risk prediction model , which is to classify individuals into clinical ly relevant risk categories , and it has therefore been widely adopted in the literature ( 24 ) . We examine the risk stratification approach in detail in this article , identifying the relevant information that can be abstract ed from a risk stratification table and caution ing against misuses of the method that frequently occur in practice . We use a recently published study of a breast cancer risk prediction model by Tice and colleagues ( 2 ) to illustrate the concepts . Background A risk prediction marker is any measure that is used to predict a person 's risk for an event . It may be a quantitative measure , such as high-density lipoprotein cholesterol level , or a qualitative measure , such as family history of disease . Risk predictors are also risk factors , in the sense that they will necessarily be strongly associated with the risk for disease . But a large , significant association does not assure that the marker has value in predicting risk for many people . A risk prediction model is a statistical model that combines information from several markers . Common types include logistic regression models , Cox proportional hazard models , and classification trees . Each type of model produces a predicted risk for each person by using information in the model . Consider , for example , a model predicting breast cancer risk that includes age as the only predictor . The result ing risk prediction for a woman of a given age is simply the proportion of women her age who develop breast cancer . The woman 's predicted risk will change if more information is included in the model . For instance , if family history information is added , her predicted risk will be the proportion of women her age and with her family history who develop breast cancer . The purpose of a risk prediction model is to accurately stratify individuals into clinical ly relevant risk categories . This risk information can be used to guide clinical or policy decisions , for example , about preventive interventions for persons or disease screening for sub population s identified as high risk , or to select persons for inclusion in clinical trials . The value of a risk prediction model for guiding these kinds of decisions can be judged by the extent to which the risk calculated from the model reflects the fraction of persons in the population with actual events ( its calibration ) ; the proportions in which the population is stratified into clinical ly relevant risk categories ( its stratification capacity ) ; and the extent to which participants with events are assigned to high-risk categories and those without events are assigned to low-risk categories ( its classification accuracy ) . Risk prediction models are commonly evaluated by using the receiver-operating characteristic ( ROC ) curve ( 4 , 7 ) , which is a st and ard tool for evaluating the discriminatory accuracy of diagnostic or screening markers . This curve shows the true-positive rate plotted against the false-positive rate for rules that classify persons by using risk thresholds that vary over allpossible values . Receiver-operating characteristic curves are generally not helpful for evaluating risk prediction models because they do not provide information about the actual risks that the models predict or about the proportion of participants who have high or low risk values . Moreover , when comparing ROC curves for 2 risk prediction models , the models are aligned according to their false-positive rates ( that is , different risk thresholds are applied to the 2 models to achieve the same false-positive rate ) . This is clearly inappropriate . In addition , the area under the ROC curve or c-statistic , a commonly reported summary measure that can be interpreted as the probability that the predicted risk for a participant with an event is higher than that for a participant without an event , has little direct clinical relevance . Clinicians are never asked to compare risks for a pair of patients one who will eventually have the event and one who will not . Neither the ROC curve nor the c-statistic relates to the practical task of predicting risks for clinical decision making . Cook and colleagues ( 1 , 6 ) propose using risk stratification tables to evaluate the incremental value of a new marker , or the benefit of adding a new marker ( for example , C-reactive protein ) , to an established set of risk predictors ( for example , Framingham risk predictors , such as age , diabetes , cholesterol level , smoking , and low-density lipoprotein cholesterol levels ) . In these stratification tables , risks calculated from models with and without the new marker are cross-tabulated . This approach represents a substantial improvement over the use of ROC methodology because it displays the risks calculated by use of the model and the proportions of individuals in the population who are stratified into the risk groups . We will provide an example of this approach and show how information about model calibration , stratification capacity , and classification accuracy can be derived from a risk stratification table and used to assess the added value of a marker for clinical and health care policy decisions . Example Tice and colleagues ( 2 ) published a study that builds and evaluates a model for predicting breast cancer risk by using data from 1095484 women in a prospect i ve cohort and incidence data from the Surveillance , Epidemiology , and End Results data base . Age , race or ethnicity , family history , and history of breast biopsy were used to model risk with a Cox proportional hazard model . The study focused on the benefit of adding breast density information to the model . The hazard ratio for breast density in the multivariate model ( extremely dense vs. almost entirely fat ) was estimated as 4.2 for women younger than age 65 years and 2.2 for women age 65 years or older . This suggests that breast density is strongly associated with disease riskthat is , that breast cancer rates are higher among women with higher breast density . However , it does not describe the value of breast density for helping women make informed clinical decisions , which requires knowledge of the frequency distribution of breast density in the population . To evaluate the added value of breast density , Tice and colleagues defined 5-year breast cancer risk categories as low ( # # lt##1 % ) , low to intermediate ( 1 % to 1.66 % ) , intermediate to high ( 1.67 % to 2.5 % ) , and high ( # # gt##2.5 % ) . The 1.67 % cutoff for intermediate risk was presumably chosen on the basis of recommendations by the American Society of Clinical Oncology ( 8) and the Canadian Task Force on Preventive Health Care ( 9 ) to counsel women with 5-year risks greater than this threshold about considering tamoxifen for breast cancer prevention . Tice and colleagues used a risk stratification table ( Table 1 ) to compare risk prediction models with and without breast density . Table 1 . Five-Year Risks for Breast Cancer as Predicted by Models That Do and Do Not Include Breast Density Calibration Assessing model calibration is an important first step in evaluating any risk prediction model . Good calibration is essential ; it means that the model-predicted probability of an event for a person with specified predictor values is the same as or very close to the proportion of all persons in the population with those same predictor values who experience the event ( 10 ) . With many predictors , and especially with continuous predictors , we can not evaluate calibration at each possible predictor value because there are too few participants with exactly those values . Instead , the st and ard approach is to place persons within categories of predicted risk and to compare the category values with the observed event rates for participants in each category . The calibration of the risk prediction models for breast cancer can be assessed by comparing the proportions of events in the margins of Table 1 with the corresponding row and column labels . For the model without breast density , the proportions of observed events within each risk category are in the far-right Total column and they generally agree OBJECTIVE We investigated the prognostic significance of risk scores and exercise workload with respect to stroke . Background . There are no data on exercise workload combined with European Systematic Coronary Risk Evaluation ( SCORE ) in the prediction of stroke . METHODS  Exercise workload was measured by exercise test with an electrically braked cycle ergometer performed at baseline . The study is based on a r and om population -based sample of 1639 men ( 42 - 60 years ) without history of type 2 diabetes or atherosclerotic cardiovascular disease including coronary heart disease , stroke or claudication . RESULTS During an average follow-up of 16 years , a total of 97 strokes occurred , of which 71 were ischaemic strokes . Independent predictors for all strokes were European SCORE [ for 1 % increment , relative risk ( RR ) : 1.12 , 95 % CI : 1.02 to 1.22 , P=0.017 ) , maximal workload ( for 20 W increment , RR : 0.87 , 95 % CI : 0.80 to 0.95 , P=0.003 ) and body mass index ( for 5 kg m(-2 ) increment , RR : 1.08 , 95 % CI : 1.03 to 1.14 , P=0.004 ) , when adjusted for serum HDL , alcohol consumption , C-reactive protein , family history of coronary heart disease , exercise-induced ST changes and the use of medications for hypertension , dyslipidaemia or aspirin . The risk was 2.54-fold ( 95 % CI : 1.27 - 5.09 , P=0.008 ) for any strokes and 4.43-fold ( 95 % CI 1.69 - 11.78 , P=0.003 ) for ischaemic strokes amongst men with exercise capacity less than 162 W when compared with those with high exercise capacity over 230 W , after adjustment for risk factors . CONCLUSIONS Low exercise workload predicts an especially high risk for stroke in the presence of high risk SCORE Background —National Cholesterol Education Program Adult Treatment Panel III ( ATP III ) guidelines recommend the use of Framingham risk scores ( FRS ) for cardiovascular assessment of asymptomatic individuals . We hypothesized that risk prediction could be improved with 2 non-ECG exercise test measures , exercise capacity ( metabolic equivalents , or METs ) and heart rate recovery ( HRR ) . Methods and Results —An asymptomatic cohort with baseline treadmill tests ( n=6126 ; 46 % women , FRS < 20 % ) was followed up prospect ively for 20 years . Individuals with low ( median or less ) HRR or METs experienced 91 % of all cardiovascular disease ( CVD ) deaths ( 225/246 ) . After FRS adjustment , low HRR and METs individually were highly significant predictors of CVD death , but low HRR and METs together were associated with substantially higher risk ( adjusted hazard ratio compared with high HRR/high METs for women 8.51 , 95 % CI 3.65 to 19.84 ; for men , 3.53 , 95 % CI 2.03 to 6.15 ; P<0.001 for both ) . At 10-year follow-up , FRS-adjusted CVD death risk associated with low HRR/low METs was less than at 20 years but remained significant ( women 3.83 , 95 % CI 1.09 to 13.47 , and men 2.70 , 95 % CI 1.11 to 6.55 ) . The application of HRR/METs information to FRS assessment identified those at high risk ( > 0.5 % annual CVD mortality ) in half of women with FRS 6 % to 9 % and 10 % to 19 % and just under half of men with FRS 10 % to 19 % . Low HRR/low METs was also associated with an increased relative risk of CVD death in individuals with low-risk FRS ( FRS < 6 % in women and < 10 % in men ) , but absolute CVD mortality rates were low in this subgroup . Conclusions —Exercise testing may be a useful adjunct for clinical risk assessment in asymptomatic women with FRS 6 % to 19 % and men with FRS 10 % to 19 % Background and Purpose — There are few if any data on the prognostic importance of silent myocardial ischemia during exercise with regard to the risk of stroke and cardiovascular diseases ( CVDs ) among asymptomatic men . In this prospect i ve study , we investigated the relation of silent myocardial ischemia and the risk of stroke and CVD death in men with and without conventional risk factors . Methods — The study sample included 1726 middle-aged men with no history of stroke , coronary heart disease , or atrial fibrillation at baseline . Silent myocardial ischemia was defined as a horizontal or downsloping ST-segment depression ( ⪖1 mm ) during exercise electrocardiography . A total of 86 CVD-related deaths and 78 strokes occurred during an average follow-up of 10 years . Results — Men with silent ischemia during exercise  had a 3.5-fold increased risk of CVD death and a 2.2-fold increased risk of stroke compared with men without silent ischemia , after adjusting for conventional risk factors . Silent ischemia during exercise was associated with a 3.8-fold ( 95 % confidence interval [ CI ] , 1.5 to 9.5 ) increased risk for CVD in smokers , a 3.9-fold ( 95 % CI , 2.1 to 7.3 ) increased risk in hypercholesterolemic subjects , a 3.6-fold ( 95 % CI , 1.9 to 6.8 ) increased risk in the hypertensives , and 3.8-fold ( 95 % CI , 2.0 to 7.1 ) increased risk in overweight men . The respective relative risks for stroke were 3.8 ( 95 % CI , 1.1 to 12.5 ) , 3.5 ( 95 % CI , 1.7 to 7.4 ) , 3.4 ( 95 % CI , 1.6 to 7.1 ) , and 2.9 ( 95 % CI , 1.4 to 6.1 ) . Conclusions — Exercise-induced silent myocardial ischemia is an important indicator of increased risk of stroke and CVD in men with other risk factors , such as smoking , hypercholesterolemia , hypertension , and being overweight OBJECTIVES This study was conducted to determine the incidence of physiologically significant coronary artery disease in a group of asymptomatic high risk men with essential hypertension and to assess the validity of noninvasive tests in a subset of these patients undergoing coronary arteriography . METHODS Two hundred twenty-six asymptomatic men ( mean age 61 + /- 8 years ) with essential hypertension and no clinical evidence of coronary artery disease but with at least one additional coronary risk factor were studied prospect ively . Fifty age- and risk factor-matched normotensive subjects were evaluated as a control group . After a minimum of 4 days without medication , subjects underwent stress thallium-201 scintigraphy , exercise and 48-h ambulatory electrocardiography , and echocardiography . Coronary angiography was performed in a subset of 34 ( 40 % ) of 84 patients with one or more positive test results . RESULTS A positive  thallium-201 scintigram  ( 18 % vs. 6 % ; odds ratio 3.4 , confidence interval 0.95 to 10.8 , p = 0.056 ) ,  exercise electrocardiograms ( ECGs ) ( 37 % vs. 13 % ; odds ratio 4.1 , confidence interval 1.5 to 11.2 , p < 0.003 ) and ambulatory ECG  ( 15 % vs. 0 % , p < 0.05 ) were more common in the hypertensive group than in the control group . In the cohort undergoing coronary angiography , thallium-201 scintigraphy was both sensitive and specific for epicardial atherosclerotic coronary disease ( 90 % and 79 % , respectively ) , but positive exercise and ambulatory ECGs occurred frequently in the absence of significant coronary stenoses . In the 39 % of hypertensive patients who had mild to moderate left ventricular hypertrophy , positive exercise and ambulatory ECGs occurred at a higher rate . CONCLUSIONS These findings suggest that physiologically significant coronary artery disease occurs more frequently in asymptomatic hypertensive men than in comparable normotensive control subjects . In the subgroup undergoing coronary arteriography , reversible scintigraphic defects were both sensitive and specific for diagnosing epicardial coronary artery disease , but exercise and ambulatory ECGs appeared to yield frequent false positive results , especially when left ventricular hypertrophy was present . These results indicate that patients with " silent " coronary artery disease can be identified among high risk hypertensive patients , but the appropriate application of such screening in clinical practice remains to be determined BACKGROUND Previous reports have suggested that an attenuated exercise heart rate response may be associated with coronary heart disease risk and with mortality . These observations may parallel the association between reduced heart rate variability during normal activities and adverse outcome . This investigation was design ed to look at the prognostic implication s of exercise heart rate response in a population -based sample . METHODS AND RESULTS In this prospect i ve cohort investigation , 1575 male participants ( mean age , 43 years ) in the Framingham Offspring Study who were free of coronary heart disease , who were not taking beta-blockers , and who underwent submaximal treadmill exercise testing ( Bruce protocol )  were studied . Heart rate response was assessed in three ways : ( 1 ) failure to achieve 85 % of the age-predicted maximum heart rate , which has been the traditional definition of chronotropic incompetence ; ( 2 ) the actual increase in heart rate from rest to peak exercise ; and ( 3 ) the ratio of heart rate to metabolic reserve used by stage 2 of exercise ( " chronotropic response index " ) . Proportional hazards analyses were used to evaluate the associations of heart rate responses with all-cause mortality and with coronary heart disease incidence during 7.7 years of follow-up . Failure to achieve target heart rate occurred in 327 ( 21 % ) subjects . During follow-up there were 55 deaths ( 14 caused by coronary heart disease ) and 95 cases of incident coronary heart disease . Failure to achieve target heart rate , a smaller increase in heart rate with exercise , and the chronotropic response index were predictive of total mortality and incident coronary heart disease ( P < .01 ) . Failure to achieve target heart rate remained predictive of incident coronary heart disease even after adjusting for age , ST-segment response , physical activity , and traditional coronary disease risk factors ( adjusted hazard ratio , 1.75 ; 95 % confidence interval , 1.11 to 2.74 ; P=.02 ) . After adjusting for the same factors , the increase in exercise heart rate remained inversely predictive of total mortality ( P=.04 ) and coronary heart disease incidence ( P=.0003 ) . The chronotropic response index also was predictive of total mortality ( P=.05 ) and incident coronary heart disease ( P=.001 ) after adjusting for age and other risk factors . CONCLUSIONS An attenuated heart rate response to exercise , a manifestation of chronotropic incompetence , is predictive of increased mortality and coronary heart disease incidence CONTEXT The usefulness of exercise stress test results and global cardiovascular risk systems for predicting all-cause mortality in asymptomatic individuals seen in clinical setting s is unclear . OBJECTIVES To determine the validity for prediction of all-cause mortality of the Framingham Risk Score and of a recently described European global scoring system Systematic Coronary Risk Evaluation ( SCORE ) for cardiovascular mortality among asymptomatic individuals evaluated in a clinical setting and to determine the potential prognostic value of exercise stress testing once these baseline risks are known . DESIGN , SETTING , AND PARTICIPANTS Prospect i ve cohort study of 3554 asymptomatic adults between the ages of 50 and 75 years who underwent exercise stress testing as part of an executive health program between October 1990 and December 2002 ; participants were followed up for a mean of 8 years . MAIN OUTCOME MEASURES Global risk based on the Framingham Risk Score and the European SCORE . Prospect ively recorded exercise stress test result abnormalities included impaired physical fitness , abnormal heart rate recovery , ventricular ectopy , and ST-segment abnormalities . The primary end point was all-cause mortality . RESULTS There were 114 deaths . The c-index , which corresponds to receiver operating characteristic curve values , and the Akaike Information Criteria found that the European SCORE was superior to the Framingham Risk Score in estimating global mortality risk . In a multivariable model , independent predictors of death were a higher SCORE ( for 1 % predicted increase in absolute risk , relative risk [ RR ] , 1.07 ; 95 % confidence interval [ CI ] , 1.04 - 1.09 ; P<.001 ) , impaired functional capacity ( RR , 2.95 ; 95 % CI , 1.98 - 4.39 ; P<.001 ) , and an abnormal heart rate recovery ( RR , 1.59 ; 95 % , 1.04 - 2.41 ; P = .03 ) . ST-segment depression did not predict mortality . Among patients in the highest tertile from the SCORE , an abnormal exercise stress test result , defined as either impaired functional capacity or an abnormal heart rate recovery , identified a mortality risk of more than 1 % per year . CONCLUSION Exercise stress testing when combined with the European global risk SCORE may be useful for stratifying risk in asymptomatic individuals in a comprehensive executive health screening program CONTEXT A frequently cited concept is that individual major risk factors for coronary heart disease ( CHD ) are absent in many patients ( perhaps > 50 % ) with CHD . However , prior studies have not systematic ally evaluated the extent to which CHD patients have previous exposure to at least 1 risk factor , including diabetes , cigarette smoking , or clinical ly elevated levels of cholesterol or blood pressure . OBJECTIVE To determine the frequency of exposure to major CHD risk factors . DESIGN , SETTING , AND PARTICIPANTS Three prospect i ve cohort studies were included : the Chicago Heart Association Detection Project in Industry , with a population sample of 35 642 employed men and women aged 18 to 59 years ; screenees for the Multiple Risk Factor Intervention Trial , including 347 978 men aged 35 to 57 years ; and a population -based sample of 3295 men and women aged 34 to 59 years from the Framingham Heart Study ( FHS ) . Follow-up lasted 21 to 30 years across the studies . MAIN OUTCOME MEASURES Fatal CHD in all cohorts and nonfatal myocardial infa rct ion ( MI ) in the FHS , compared by exposure to major CHD risk factors , defined as total cholesterol of at least 240 mg/dL ( > or = 6.22 mmol/L ) , systolic blood pressure of at least 140 mm Hg , diastolic blood pressure of at least 90 mm Hg , cigarette smoking , and diabetes . Participants were stratified by sex and age ( 18 - 39 vs 40 - 59 years ) . RESULTS For fatal CHD ( n = 20 995 ) , exposure to at least 1 clinical ly elevated major risk factor ranged from 87 % to 100 % . Among those aged 40 to 59 years at baseline with fatal CHD ( n = 19 263 ) , exposure to at least 1 major risk factor ranged from 87 % to 94 % . For nonfatal MI , prior exposure was documented in 92 % ( 95 % CI , 87%-96 % ) ( n = 167 ) of men aged 40 to 59 years at baseline and in 87 % ( 95 % CI , 80%-94 % ) ( n = 94 ) of women in this age group . CONCLUSIONS Antecedent major CHD risk factor exposures were very common among those who developed CHD , emphasizing the importance of considering all major risk factors in determining CHD risk estimation and in attempting to prevent clinical CHD . These results challenge cl aims that CHD events commonly occur in persons without exposure to at least 1 major CHD risk factor Background —Exercise stress testing alone or with perfusion imaging is the st and ard screening method to determine the presence of obstructive coronary artery disease ( CAD ) in people with chest pain . In asymptomatic individuals with a family history of premature CAD , it is unclear whether abnormalities on these functional exercise tests represent significant coronary disease . Methods and Results —An abnormal exercise test , thallium scan , or both occurred in 153 ( 21 % ) of 734 asymptomatic siblings of persons with documented CAD , of whom 105 underwent coronary angiography with quantitative analysis of stenosis severity . Overall , 95 % had coronary atherosclerosis , but only 39 % had 1 or more stenoses with ≥50 % narrowing . Of 30 siblings in whom the exercise test and perfusion scan were both abnormal , 70 % had ≥50 % stenoses . The mean stenosis in arteries that fed perfusion defects was only 43±31 % , and 68 % of such stenoses were < 50 % . However , in 71 % of all defects , the location matched arteries with the most severe stenoses . Conclusions —In asymptomatic persons with a family history of CAD , abnormal exercise scintigraphy identifies predominantly mild coronary atherosclerosis . Perfusion defects may be caused by coronary vasomotor dysfunction in addition to atherosclerotic plaque Prospect i ve data relating cardiorespiratory fitness ( CRF ) with nonfatal cardiovascular disease ( CVD ) events are limited to studies in men or studies of combined fatal and nonfatal CVD endpoints . The authors examined the association between CRF and nonfatal CVD events in 20,728 men and 5,909 women without CVD at baseline . All participants performed a maximal treadmill exercise test  and completed a follow-up health survey in the Aerobics Center Longitudinal Study ( Dallas , Texas ) between 1971 and 2004 . There were 1,512 events in men and 159 events in women during an average follow-up of 10 years . Across incremental CRF groups , age- and examination year-adjusted event rates per 10,000 person-years were 107.9 , 75.2 , and 50.3 in men ( p(trend ) < 0.001 ) and 41.9 , 27.7 , and 20.8 in women ( p(trend ) = 0.002 ) . After further adjustment for smoking , alcohol intake , family history of CVD , and abnormal exercise electrocardiogram responses , hazard ratios were 1.00 ( referent ) , 0.82 ( 95 % confidence interval ( CI ) : 0.72 , 0.94 ) , and 0.61 ( 95 % CI : 0.53 , 0.71 ) in men , p(trend ) < 0.001 , and were 1.00 ( referent ) , 0.74 ( 95 % CI : 0.49 , 1.13 ) , and 0.63 ( 95 % CI : 0.40 , 0.98 ) in women , p(trend ) = 0.05 . After adjustment for other CVD predictors , the association remained significant in men but not in women Objective To study abnormalities in the resting ECG as independent predictors for all cause , cardiovascular disease ( CVD ) , and coronary heart disease ( CHD ) mortality in a population based r and om sample of men and women , and to explore whether their prognostic value is different between sexes . Design and subjects An age and sex stratified r and om sample was selected from the total Belgian population aged 25 to 74 years .  Baseline data were gathered and resting ECGs were classified according to Minnesota code criteria . The sample was then followed for at least 10 years with respect to cause specific death . Results are based on observations from 5208 men and 4746 women free from prevalent CHD at the start of the follow up period . Results Although the prevalence of major abnormalities in general was comparable between sexes , women had more ischaemic findings , ST segment changes , and abnormal T waves on their baseline ECG , while men showed more arrhythmias , bundle branch blocks , and left ventricular hypertrophy . Fitting the multiplicative effect on subsequent mortality between all ECG classifications under study and sex indicated that the prognostic value of ECG changes was equal in women and men . Independently of other risk factors and other major ECG changes , almost all ECG classifications were significantly related to all cause , CVD , and CHD mortality . The most predictive ECG findings for CVD death were ST segment depression ( risk ratio ( RR ) 4.71 ) , major ECG findings ( RR 3.26 ) , left ventricular hypertrophy ( RR 2.79 ) , bundle branch blocks ( RR 2.58 ) , T wave flattening ( RR 2.47 ) , ischaemic ECG findings ( RR 2.35 ) , and arrhythmias ( RR 2.15 ) . The prognostic value of major ECG findings for CVD and CHD death was more powerful than well established cardiovascular risk factors . Conclusions Abnormalities in the baseline ECG are strongly associated with subsequent all cause , CVD , and CHD mortality . Their predictive value was similar for men and women We prospect ively studied 135 asymptomatic normotensive subjects with exercise-induced ST ischemic depression of 1 mm or more and compared them with 379 controls . At least two controls with negative responses on the exercise electrocardiographic ( EKG ) test  were selected for each case and were matched for age , sex , work , community , and coronary-risk-factors index . The end points considered were the following coronary events : angina pectoris , myocardial infa rct ion , and sudden death . After a median follow-up period of 6.0 years for the cases and 6.4 years for the controls , the relative risk was 5.55 ( 95 per cent confidence limits , 2.75 to 11.22 ) . Coronary events occurred significantly earlier in the cases than in the controls . Our data also suggest that the  exercise EKG response is a particularly good prognostic indicator for myocardial infa rct ion . In addition , our analysis has confirmed the predictive roles of age , smoking , blood pressure , and the coronary-risk-factors index and suggests that the  exercise EKG response is an additional independent risk indicator for coronary events A positive exercise electrocardiogram ( ECG ) has been proved to predict cardiovascular events in asymptomatic normolipidemic men . To study whether it is also predictive for hypercholesterolemic men , data from 3,806 asymptomatic hypercholesterolemic men in the Lipid Research Clinics Coronary Primary Prevention Trial were analyzed . All the men had performed a submaximal treadmill exercise test at baseline , before they were assigned to the cholestyramine or placebo treatment group . Because of missing or inconclusive data , 31 men were excluded from the analyses . A test was positive if the ST segment was displaced by greater than or equal to 1 mm ( visual code ) or there was greater than or equal to 10 microV-s change in the ST integral ( computer code ) , or both . The prevalence of a positive test was 8.3 % . During the 7 to 10 year ( mean 7.4 ) follow-up period , the mortality rate from coronary heart disease was 6.7 % ( 21 of 315 ) in men with a positive test and 1.3 % ( 46 of 3,460 ) in men with a negative test ( placebo and cholestyramine groups combined ) . The age-adjusted rate ratio for a positive test , compared with a negative test , was 6.7 in the placebo group and 4.8 in the cholestyramine group . With use of Cox 's proportional hazards models , it was found that the risk of death from coronary heart disease associated with a positive test was 5.7 times higher in the placebo group and 4.9 times higher in the cholestyramine group after adjustment for age , smoking history , systolic blood pressure , high density lipoprotein cholesterol and low density lipoprotein cholesterol . A positive test was not significantly associated with nonfatal myocardial infa rct ion . ( ABSTRACT TRUNCATED AT 250 WORDS Background Previous studies have shown that ST depressions ≤ 1.0 mm during or post-exercise increase long-term risk of dying from coronary heart disease ( CHD ) , the need for coronary artery bypass grafting ( CABG ) or the development of acute myocardial infa rct ion ( AMI ) in healthy men . In the present prospect i ve cohort study we investigate whether less marked ST depressions may influence CHD mortality , incidence of AMI , the need for a CABG or having a non-fatal stroke . Methods During 1972–75 , 2014 men aged 40–59 years , free from somatic diseases and not using any drugs , underwent an  examination programme including case history , clinical examination , various blood tests and a symptom-limited exercise ECG-test . ECG was registered during exercise and at 30 s , 1 , 2 , 3 and 5 min post-exercise . The possible prognostic impact of ST-changes of 0.50–0.99 mm and ≤ 1.00 mm compared with normal ST-segments were studied separately and combined . Horizontal , down-sloping and slowly up-sloping ST-segment patterns were combined . Results After adjustment for age , smoking , blood pressure , cholesterol , maximal heart rate , left ventricular hypertrophy and physical fitness ST depressions ≤ 0.50 mm - during and /or post-exercise - were associated with a 1.47-fold [ 95 % confidence interval ( CI ) 1.10–1.95 ] , and 1.54-fold ( 95 % CI of 1.17–2.04 ) increased 26 years risk of CHD-mortality , respectively . The same ST-changes also increased 22 years risk of developing non-fatal AMI or needing CABG but not developing non-fatal stroke . Conclusions Even an ST depression ≤ 0.50 mm during and /or after exercise increases the long-term risk of CHD-death , developing an AMI or needing CABG . No association was found between ST-changes and incidence of non-fatal strokes Minor ST-T abnormalities are common on the resting electrocardiogram of otherwise healthy persons , but the long-term importance of these findings has not been extensively evaluated , especially in women . In a prospect i ve study , 7,985 women and 9,630 men ( aged 40 to 64 years at baseline ) without other electrocardiographic abnormalities and free of previous coronary heart disease ( CHD ) were studied using Cox regression for 22-years of follow-up . Primary outcomes were death from CHD and total cardiovascular disease ( CVD ) ; total mortality was a secondary outcome . Minnesota Code was employed to assess the presence or absence of  electrocardiographic abnormalities . Analyses compared persons with  minor Minnesota Code ST-segment ( codes 4 - 3 or 4 - 4 ) or  T-wave findings  ( codes 5 - 3 or 5 - 4 ) to those with normal electrocardiographic findings . In combined analyses of men and women adjusted for age , isolated minor T-wave abnormality , minor ST-segment depression , or a combination of minor ST-segment and T-wave abnormalities were each associated with increased mortality risks . For CHD mortality , hazard ratios ( HRs ) ranged from 1.60 to 2.10 ; for CVD mortality , HRs ranged from 1.50 to 1.95 ; and for total mortality , HRs ranged from 1.31 to 1.50 ( p < 0.05 for all HRs ) . In separate analyses by gender adjusted for age , increased risks were observed for combined ST-T-wave abnormalities in both genders for CHD and CVD mortality ( HR 1.72 to 1.75 for men , p < 0.05 ; HR 2.07 to 2.51 for women , p < 0.001 ) . These data indicate that nonspecific ( minor ) ST-segment depression and /or T-wave abnormalities have a long-term prognostic impact for CHD and CVD death in middle-aged women and men and can be considered markers of heightened CHD and CVD risk In Leeds in hospital population s of patients with angina the maximal ST/HR slope was found to be a reliable index of myocardial ischemia as assessed by coronary angiography . Subsequent studies in Leeds and elsewhere in population s of patients with cardiac enlargement or following myocardial infa rct ion have shown that the slope is affected by myocardial scarring , ventricular enlargement and aneurysm . These findings implied that the slope had features in common with other usual exercise tests ; studies in Leeds and elsewhere , however , have shown a superior diagnostic reliability using the maximal ST/HR slope in patients with angina . The present report involves the use of the slope in asymptomatic population s. Trials are being undertaken in two factory population s , which respectively comprised all volunteers or asymptomatic men over the age of 30 who were r and omly chosen by computer . Subjects with slope values indicating , according to previous experience , myocardial ischemia equivalent to coronary heart disease were referred for cardiological investigations which included angiocardiography ; blind comparisons were performed between results of investigations and the slope . So far 1194 subjects have been examined . In 68 subjects the maximal ST/HR slope indicated myocardial ischemia , and in 24 of these cardiological investigations were completed . In nine of the 24 subjects the slope corresponded to the number of significantly narrowed coronary arteries ( greater than 75 % reduction in luminal diameter ) ; in 12 of the remaining 15 subjects who had no coronary narrowing , there were cardiac lesions which included cardiac enlargement , aortic valve disease , myocarditis , pericarditis , myocardial bridging and conduction defects . ( ABSTRACT TRUNCATED AT 250 WORDS CONTEXT Data are sparse regarding the prevalence , incidence , and independent prognostic value of minor and /or major electrocardiographic ( ECG ) abnormalities in asymptomatic postmenopausal women . There is no information on the effect , if any , of hormonal treatment on the prognostic value of the ECG . OBJECTIVE To examine association of minor and major baseline and incident ECG abnormalities with long-term cardiovascular morbidity and mortality . DESIGN , SETTING , AND PARTICIPANTS Post-hoc analysis of the estrogen plus progestin component of the Women 's Health Initiative study , a r and omized controlled primary prevention trial of 14 749 postmenopausal asymptomatic women with intact uterus who received 1 daily tablet containing 0.625 mg of oral conjugated equine estrogen and 2.5 mg of medroxyprogesterone acetate or a matching placebo . Participants were enrolled from 1993 to 1998 , and the estrogen plus progestin trial was stopped on July 7 , 2002 . MAIN OUTCOME MEASURES The Novacode criteria were used to define minor , major , and incident ECG abnormalities . Cardiovascular end points included incident coronary heart disease ( CHD ) and cardiovascular disease ( CVD ) events . RESULTS Among women with absent ( n = 9744 ) , minor ( n = 4095 ) , and major ( n = 910 )  ECG abnormalities  , there were 118 , 91 , and 37 incident CHD events , respectively . The incident annual CHD event rates per 10 000 women with absent , minor , or major ECG abnormalities were 21 ( 95 % confidence interval [ CI ] , 18 - 26 ) , 40 ( 95 % CI , 32 - 49 ) , and 75 ( 95 % CI , 54 - 104 ) , respectively . After 3 years of follow-up , 5 % of women who had normal ECG at baseline developed new ECG abnormalities with an annual CHD event rate of 85 ( 95 % CI , 44 - 164 ) per 10 000 women . The adjusted hazard ratios for CHD events were 1.55 ( 95 % CI , 1.14 - 2.11 ) for minor baseline , 3.01 ( 95 % CI , 2.03 - 4.46 ) for major baseline , and 2.60 ( 95 % CI , 1.08 - 6.27 ) for incident ECG abnormalities . There were no significant interactions between hormone treatment assignment and ECG abnormalities for risk prediction of cardiovascular end points . For prediction of CHD events , the addition of ECG findings to the Framingham risk score increased from 0.69 to 0.74 the area under the receiver operating characteristic curve . Similar findings were found for incident CVD events . CONCLUSIONS Among asymptomatic postmenopausal women , clinical ly relevant baseline and incident ECG abnormalities are independently associated with increased risk of cardiovascular events and mortality , and the information is incremental to the established method of risk stratification . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00000611 Objective The value of exercise testing ( ET ) in asymptomatic subjects remains controversial and is unknown in countries with a low coronary heart disease ( CHD ) incidence . The aim of this study was to investigate the ability of ET to improve the prediction of a first coronary event in such a population . Methods Using a prospect i ve cohort study , 1051 consecutive healthy asymptomatic adults were enrolled in a cardiovascular screening program including ET .  The pre-test risk of CHD was evaluated by the 10-year Framingham risk function . Positive ET was defined as a horizontal or downsloping ST-segment depression ≥ 1.0 mm . The primary outcome was total coronary events ( CE ) occurrence , including cardiac deaths , acute myocardial infa rct ion and stable or unstable angina . The mean follow-up period was 6 years . Results Subjects were aged 18 - 79 years and 36 % were women . A total of 89 subjects ( 8.5 % ) had a positive ET .  Positive exercise testing was associated with CE occurrence in a univariate analysis only in subjects with higher pre-test risk , defined by a 10-year Framingham risk > 10.4 % [ hazards ratio ( HR ) = 2.61 ; 95 % confidence interval ( CI ) ( 1.07 - 6.40 ) ] . In this risk category , ET was able to provide incremental information over the major risk factors in both men and women [ risk factor-adjusted HR for positive ET = 2.86 ; 95 % CI ( 1.14 - 7.20 ) ] . This risk excess in subjects with positive ET persisted even when a coronary revascularization was performed . Subjects with intermediate pre-test probability ( 10 - 15 % ) and positive ET had a post-test probability of CE largely equivalent to the probability in subjects with known CHD . Conclusion Additional informátion provided by ET in subjects with a pre-test risk at 10-years > 10 % should lead to a more efficient use of risk-reducing therapies than it would be the case in this risk category with the analysis of traditional risk factors only 1996;3:213–219 . 5 . Rubins HB , Robins SJ , Collins D , Fye CL , And erson JW , Elam MB , Faas FH , Linares E , Schaefer EJ , Schectman G , Wilt TJ , Wittes J. Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol . Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial Study Group . N Engl J Med 1999;341 : 410 –418 . 6 . Bloomfield Rubins H , Davenport J , Babikian V , Brass LM , Collins D , Wexler L , Wagner S , Papademetriou V , Rutan G , Robins SJ . Reduction in stroke with gemfibrozil in men with coronary heart disease and low HDL cholesterol : the Veterans Affairs HDL Intervention Trial ( VA-HIT ) . Circulation 2001;103:2828– 2833 . 7 . Frick MH , Elo O , Haapa K , Heinonen OP , Heinsalmi P , Helo P , Huttunen JK , Kaitaniemi P , Koskinen P , Manninen V , et al. Helsinki Heart Study : primary prevention trial with gemfibrozil in middle-aged men with dyslipidemia  . Safety of treatment , changes in risk factors , and incidence of coronary heart disease . N Engl J Med 1987;317:1237–1245 We determined whether the exercise electrocardiogram predicted acute cardiac events during moderate or strenuous physical activity among 3617 asymptomatic , hypercholesterolemic men ( age range , 35 to 59 years ) who were followed up in the Coronary Primary Prevention Trial .  Submaximal exercise test results were obtained at entry and at annual follow-up visits in years 2 through 7 . ST-segment depression or elevation ( greater than or equal to 1 mm or 10 microV-sec ) was considered to be a positive test result . The circumstances that surrounded each nonfatal myocardial infa rct ion and coronary heart disease death were determined through a record review . The cumulative incidence of activity-related acute cardiac events was 2 % during a mean follow-up period of 7.4 years . The risk was increased 2.6-fold in the presence of clinical ly silent , exercise-induced , ST-segment changes at entry ( 95 % confidence interval [ Cl ] , 1.3 to 5.2 ) after adjustment for 11 other potential risk factors . Of 62 men who experienced an activity-related event , 11 had a positive test result at entry ( sensitivity , 18 % ; 95 % Cl , 8 to 27 ) . The specificity of the entry exercise test was 92 % ( 95 % Cl , 91 to 93 ) . The sensitivity and specificity were similar when the length of follow-up was restricted to 1 year after testing . For a newly positive test result on a follow-up visit , the sensitivity was 24 % ( 95 % Cl , 12 to 36 ) , and the specificity was 85 % ( 95 % Cl , 84 to 86 ) ; for any positive test result during the study ( mean number of tests per subject , 6.2 ) , the sensitivity was 37 % ( 95 % Cl , 25 to 49 ) , and the specificity was 79 % ( 95 % Cl , 77 to 80 ) . Our findings suggested that the presence of clinical ly silent , exercise-induced , ischemic ST-segment changes on a submaximal test was associated with an increased risk of activity-related acute cardiac events . However , this test was not sensitive when used to predict the occurrence of activity-related events among asymptomatic , hypercholesterolemic men . For this reason , the utility of the submaximal exercise test to assess the safety of physical activity among asymptomatic men at risk of coronary heart disease is likely to be limited OBJECTIVES We sought to characterize the predictors of incident congestive heart failure ( CHF ) , as determined by central adjudication , in a community-based elderly population . BACKGROUND The elderly constitute a growing proportion of patients admitted to the hospital with CHF , and CHF is a leading source of morbidity and mortality in this group . Elderly patients differ from younger individuals diagnosed with CHF in terms of biologic characteristics . METHODS We analyzed data from the Cardiovascular Health Study , a prospect i ve population -based study of 5,888 elderly people > 65 years old ( average 73 + /- 5 , range 65 to 100 ) at four locations . Multiple laboratory measures of cardiovascular structure and function , blood chemistries and functional assessment s were obtained . RESULTS During an average follow-up of 5.5 years ( median 6.3 ) , 597 participants developed incident CHF ( rate 19.3/1,000 person-years ) . The incidence of CHF increased progressively across age groups and was greater in men than in women . On multivariate analysis , other independent predictors included prevalent coronary heart disease , stroke or transient ischemic attack at baseline , diabetes , systolic blood pressure ( BP ) , forced expiratory volume 1 s , creatinine > 1.4 mg/dl , C-reactive protein , ankle-arm index < 0.9 , atrial fibrillation , electrocardiographic ( ECG ) left ventricular ( LV ) mass , ECG ST-T segment abnormality , internal carotid artery wall thickness and decreased LV systolic function . Population -attributable risk , determined from predictors of risk and prevalence , was relatively high for prevalent coronary heart disease ( 13.1 % ) , systolic BP > or = 140 mm Hg ( 12.8 % ) and a high level of C-reactive protein ( 9.7 % ) , but was low for subnormal LV function ( 4.1 % ) and atrial fibrillation ( 2.2 % ) . CONCLUSIONS The incidence of CHF is high in the elderly and is related mainly to age , gender , clinical and sub clinical coronary heart disease , systolic BP and inflammation . Despite the high relative risk of subnormal systolic LV function and atrial fibrillation , the actual population risk of these for CHF is small because of their relatively low prevalence in community-dwelling elderly people Aim of the study was to analyze the predictive power on short term mortality of electrocardiographic findings in asymptomatic subjects belonging to sample s of the general population . In the Italian RIFLE Pooling Project ( Risk Factors and Life Expectancy ) 12 180 men and 10 373 women aged 30 to 69 years had a resting electrocardiogram ( ECG ) recorded at baseline examination . All of them were free from clinical ly symptomatic heart disease and represented 23 cohorts spread all over Italy .  ECGs were read by the Minnesota Code using 5 large categories of abnormalities , i.e. Q-QS abnormalities , ST-T abnormalities , high R. waves , major arrhythmias , and blocks . Some clinical ly relevant ECG combination of abnormalities were also analyzed . Six-year mortality from coronary heart disease ( CHD ) , cardiovascular diseases ( CVD ) and all-cause mortality ( ALL ) were the end-point . Those ECG findings were relatively common and covered the majority ( 80 to 90 % ) of all abnormalities found in the general population before excluding subjects with symptomatic heart disease . Most ECG findings on most occasions were associated with an excess mortality from the three end-points in both men and women and among relatively young ( age 30 - 49 ) and mature ( age 50 - 69 ) adults . The strongest predictor of fatal events were Q-QS items and blocks . The most consistent predictors were ST-T findings , although this was true for men and not for women . Relative risk against the absence of abnormalities ( one by one and all together ) were adjusted by multivariate analysis feeding in the models some possible confounders , i.e. age , systolic blood pressure , serum cholesterol , cigarette consumption and body mass index . Relative risks in cells with more than 20 events ( cells being separately made by men , women , the 5 ECG findings categories and the 3 end-points ) were ranging 1.00 to 9.88 for Q-QS abnormalities , 1.03 to 3.76 for ST-T abnormalities , 1.28 to 5.14 for high R waves , 0.81 to 2.28 for arrhythmias and 0.79 to 3.59 for blocks . Most of these relative risks were statistically significant . Combinations of clinical ly relevant ECG findings in the same individual ( LVH , possible and definite myocardial infa rct ion ) were rare but carried a severe prognosis with high and statistically significant relative risks among men ( ranging between 3.19 and 7.24 ) while they could not be properly tested in most cells for women due to the small numbers involved . It is concluded that in the general population high rates of prevalent ignored ECG abnormalities in asymptomatic subjects are associated with significant excess mortality from CHD , CVD and all-cause mortality , suggesting a high prevalence of silent heart disease We previously reported on the prognostic importance of heart rate recovery after symptom-limited exercise in an intermediate-risk group of patients who were referred for exercise testing with thallium single-photon emission computed tomography in a tertiary-care center ( 1 ) . It is unknown , however , whether these findings can be generalized to healthy adults undergoing submaximal exercise .  Our goal was to examine heart rate recovery as a predictor of long-term mortality in a population -based cohort of adults without evidence of cardiovascular disease who underwent submaximal exercise testing .  All-cause mortality was the outcome of interest because of its relevance and its objective and unbiased nature ( 2 ) . Methods The study cohort was derived from the Lipid Research Clinics Prevalence Study , the selection of which has been described in detail elsewhere ( 3 - 6 ) . Briefly , that study was design ed to determine the prevalence of lipid abnormalities among North Americans . Of the 68 317 population -based persons recruited from 10 primary care centers , those with lipid abnormalities ( approximately 10 % of the population ) and an additional r and omly selected 15 % were invited to undergo more extensive investigation ( 3 ) . Of the 13 852 who appeared for this second visit , 8681 underwent exercise testing .  Reasons for exclusion from exercise testing included  resting systolic blood pressure less than 90 or greater than 200 mm Hg , resting diastolic blood pressure greater than 120 mm Hg , inability to complete a treadmill test on the basis of physician examination , or participant request ( 5 , 6 ) . To assure selection of a cardiovascularly healthy asymptomatic cohort similar to that in previous population -based studies ( 7 ) , persons were excluded if they were younger than 30 years of age ( n=131 [ 2 % ] ) ; were taking -blockers , digoxin , antiarrhythmic agents , or nitrates ( n=356 [ 4 % ] ) ; had a history of cardiovascular disease ( defined as previous heart surgery or history of angina , myocardial infa rct ion , claudication , stroke , previous vascular surgery , congenital disease , or arrhythmia ) ( n=2413 [ 28 % ] ) ; or were unable to reach stage 2 of exercise ( n=1620 [ 19 % ] ) . Before testing , participants underwent a detailed medical and family history that elicited information about medical conditions , alcohol use , smoking , education level , socioeconomic status , exercise habits , and medications . Lipid profiles were obtained in all patients . The treadmill exercise protocol used was the Bruce or modified Bruce protocol ( 5 , 6 ) . Participants exercised until they attained at least 85 % to 90 % of their age- and fitness-predicted maximum heart rate for 1 minute or until fatigue or medical contraindications to continued exercise were observed . Data on symptoms , heart rate , and blood pressure were collected and  electrocardiography  was done before exercise , at the end of each stage , immediately after exercise , and 2 minutes into recovery . Estimated workload , expressed in metabolic equivalents , was based on total treadmill time . Chronotropic response during exercise was assessed by using the chronotropic indexthe ratio of heart rate to metabolic reserve usedduring stage 2 of exercise ( 8 , 9 ) . We used a cutoff value ( 0.86 ) that maximized the log-rank chi-square statistic ( 10 ) . Immediately after exercise , participants were helped to chairs , and recovery data were obtained . Heart rate recovery was defined as the change from peak heart rate to that measured after 2 minutes of recovery ( that is , heart rate recovery = heart ratepeak heart rate2-min recovery ) . An abnormal value for heart rate recovery was determined by finding the maximum value for the log-rank chi-square test statistic for all possible cutoff points between the 10th and 90th percentiles ( 10 ) ; this turned out to be 42 beats/min or less . This cutoff value differed from and could not be validly compared to that of our previous study ( 1 ) because 2-minute values ( rather than 1-minute values ) were used and because exercise was submaximal , not symptom-limited . We also considered indexing the 2-minute heart rate recovery by the maximum heart rate , but this result ed in a substantially lower maximum log-rank chi-square value ( 44 compared with 77 ) . Mean follow-up time was 12 years . The primary end point was all-cause mortality , which was determined through annual telephone interviews with study participants or their families or employers . Cause of death was assessed by review of death certificates and interviews of physicians or next of kin ( 6 ) . If the patient could not be contacted , registries were search ed for mortality information . For assessment of vital status , follow-up was 100 % complete . All analyses were performed by using version 6.12 of the SAS statistical package ( SAS Institute , Inc. , Cary , North Carolina ) . For descriptive purpose s , patients were divided into two groups based on heart rate recovery . Continuous variables are presented as the mean SD . Differences between groups were compared by using the Student t-test , Wilcoxon rank-sum test , and chi-square test , as appropriate . Heart rate recovery was related to all-cause mortality  by using univariable and multivariable Cox regression analyses . Stratified analyses were performed on prespecified subgroups according to age , sex , exercise patterns , smoking , cholesterol level , resting blood pressure and heart rate , chronotropic response to exercise , and medication use . Logarithmic and quadratic transformations and potential interactions were assessed for improvement of fit ; the strata option of PROC PHREG was used to allow for accurate estimation of main effects relative risks . The Cox proportional-hazards assumption was confirmed by inspection of log ( log [ survival ] ) curves . Attributable risk was calculated as P ( RR 1)/[P ( RR 1 ) + 1 ] , where P is prevalence and RR is relative risk . The estimated actuarial survival rate for the population was estimated on the basis of data from 1985 U.S. life tables ( 11 ) . According to the policy at our institution , this research was considered exempt from institutional review board approval because it used existing , publically available data . In addition , the data were recorded in such a manner that participants could not be identified directly or through identifiers linked to them . Results Baseline and Exercise Characteristics A total of 5234 adults met all inclusion criteria . The median value for heart rate recovery was 49 beats/min ( 25th and 75th percentiles , 39 and 59 beats/min ) . An abnormal heart rate recovery of 42 beats/min or less was seen in 1715 participants ( 33 % ) . Baseline and exercise characteristics of the study participants according to heart rate recovery are summarized in Table 1 . Table 1 . Baseline and Exercise Characteristics according to Heart Rate Recovery after Exercise Heart Rate Recovery and Mortality During 12 years of follow-up , 325 patients ( 6.2 % ) died . According to U.S. life tables , the actuarial predicted death rate was 7 % . Abnormal heart rate recovery was strongly predictive of death ( 10 % compared with 4 % among participants with normal heart rate recovery ; relative risk , 2.58 [ 95 % CI , 2.06 to 3.20 ] ) ( P<0.001 ) . The sensitivity , specificity , and positive and negative predictive values of an abnormal heart rate recovery for prediction of death over 12 years were 54 % , 69 % , 10 % , and 96 % , respectively . Of the participants who died , 116 ( 36 % ) were thought to have died of cardiovascular causes . An abnormal heart rate recovery was even more strongly predictive of cardiovascular death than of death in general ( 4 % compared with 1 % ; relative risk , 3.06 [ CI , 2.10 to 4.44 ] ) ( P<0.001 ) . Results of analyses stratified by age , sex , chronotropic response to exercise , regular exercise , smoking , resting hemodynamics , cholesterol level , and use of vasodilator medication are shown in Table 2 . Abnormal heart rate recovery was predictive of death in all subgroups except participants taking vasodilators . Table 2 . Association of Abnormal Heart Rate Recovery with Mortality according to Prespecified Subgroups Multivariable Cox Regression Analyses After adjustment for age , sex , body mass index , ethnicity , resting systolic blood pressure , use of vasodilators , exercise habits , physical fitness , smoking , diabetes , lipid profiles , ST-segment response , resting heart rate , chronotropic index , and educational and socioeconomic status and after consideration of interaction terms , a slower decrease in heart rate remained predictive of death ( adjusted relative risk , 1.55 [ CI , 1.22 to 1.98 ] ) ( P<0.001 by chi-square test ) . The adjusted attributable risk for death related to abnormal heart rate recovery was 15 % ( CI , 7 % to 24 % ) . Abnormal heart rate recovery was also predictive of cardiovascular death after adjustment for potential confounders and interactions ( adjusted relative risk , 1.95 [ CI , 1.11 to 3.42 ] ) ( P=0.02 ) . Discussion Heart rate recovery after submaximal exercise was a powerful predictor of mortality in a population -based cohort of adults without clinical ly evident cardiovascular disease , even after we adjusted for multiple , potentially confounding factors . These findings confirm the results of our previous study ( 1 ) and exp and them by demonstrating the prognostic importance of heart rate recovery in healthy persons undergoing submaximal , as opposed to symptom-limited , exercise testing . Heart rate recovery may therefore be a clinical ly relevant predictor of risk among patients undergoing screening exercise testing . Furthermore , because an abnormal heart rate recovery accounted for 15 % of deaths , this measure may be useful for insurance underwriting assessment s. It has been suggested that the link between heart rate recovery and mortality may be related to vagal tone and physical fitness ( 12 ) . We also noted an association between fitness levels and recovery heart rate ;  participants with abnormal heart rate recovery were less likely to exercise regularly and to participate in strenuous exercise ( Table 1 ) . It should be noted that heart rates The clinical relevance of ventricular premature complexes ( VPCs ) in apparently healthy patients is not clear and is typically not considered when evaluating risk . We conducted a prospect i ve longitudinal study of the population -based Atherosclerosis Risk In Communities ( ARIC ) study of 15,070 Caucasians and African-Americans , 45 to 64 years of age , to assess the risks of coronary heart disease ( CHD ) events and mortality associated with  VPCs among participants with and without prevalent CHD at baseline .  VPCs  on a single 2-minute electrocardiogram  were identified in 940 participants ( 6.2 % ) . After a follow-up of > 10 years , 1,762 participants died , with 366 deaths related to CHD , and 1,736 had cardiac events . The percentage of participants with CHD mortality was > 3 times greater for those with VPCs compared with those without VPCs . After controlling for cardiovascular risk factors and therapy with proportional hazards regression , participants with VPCs were > 2 times as likely to die due to CHD than were those without VPCs . Increased risk was found for participants with and without baseline CHD . In conclusion , a clinical finding of VPCs on electrocardiography of even apparently healthy patients may warrant a heightened awareness of and attention to cardiovascular risk assessment and management The Duke Treadmill Score ( DTS ) has been shown to predict mortality in women who have symptomatic heart disease , but its ability to do so in asymptomatic women is unknown , as is its comparative advantage to exercise capacity . We investigated whether a decreased DTS is associated with increased mortality in a prospect i ve cohort of 5,636 asymptomatic women . A symptom-limited exercise treadmill test using Bruce 's protocol was performed at baseline . DTS was calculated using exercise time , exercise-induced angina , and ST-segment depression . Exercise capacity was measured in METs . Deaths and cause of death were identified from 1992 to 2000 . After adjusting for the Framingham Risk Score , the risk of death decreased by 9 % for each unit increase in DTS and by 17 % for every 1-MET increase ( p < 0.001 ) . Those who had a DTS < 5 ( moderate or high risk ) had hazard ratios for death and cardiac death that were 2.2 and 2.5 times greater , respectively , than did those who had a DTS > or = 5 ( low risk ) , after adjusting for Framingham Risk Score ( p < 0.001 ) . Receiver-operating characteristic curves for the DTS model and the exercise capacity model were not significantly different . In conclusion , we have demonstrated that , although the DTS is an independent predictor of mortality and cardiac mortality in asymptomatic women , it does not appear to be a better predictor than exercise capacity alone . The role of ST-segment changes and symptoms with stress testing in asymptomatic women does not provide additional prognostic information Background No data exist on exercise workload combined with European Systematic Coronary Risk Evaluation ( SCORE ) with respect to death from cardiovascular diseases and other causes . We therefore investigated the prognostic significance of risk scores and exercise capacity with respect to cardiovascular diseases . Design A population -based follow-up study . Methods Exercise workload was measured by exercise test with an electrically braked cycle ergometer . The study is based on a r and om population -based sample of 1639 men ( 42–60 years ) without history of type II diabetes or atherosclerotic cardiovascular disease including coronary heart disease , stroke or claudication . Results During an average follow-up of 16 years , a total of 304 overall deaths and 116 cardiovascular deaths occurred . Relative risk ( RR ) was 2.50 [ 95 % confidence intervals ( CI ) : 1.71–3.68 , P < 0.001 ] for all-cause death and 2.04 ( 95 % CI : 1.14–3.65 , P = 0.016 ) for cardiovascular death among men with exercise capacity less than 162W as compared with those with exercise capacity over 230 W , after adjustment for risk factors . Independent predictors for all-cause death were European SCORE ( for 1 % increment , RR : 1.15 , 95 % CI : 1.10–1.20 , P < 0.001 ) , exercise workload ( for 20W increment , RR : 0.86 , 95 % CI : 0.82–0.91 , P < 0.001 ) , C-reactive protein and alcohol consumption , when adjusted for serum high-density lipoprotein , body mass index , family history of coronary heart disease , exercise-induced ST changes and the use of medications for hypertension , dyslipidemia or aspirin . Conclusion Low  exercise  workload predicts an especially high risk for death from cardiovascular and any other cause when combined with high risk SCORE OBJECTIVE The objective of this study was to report on the prevalence , incidence and prognosis of left ventricular hypertrophy ( LVH ) on the electrocardiogram ( ECG ) in a cohort of ambulatory older men and women . DESIGN A prospect i ve , longitudinal study of 10 years duration with ECGs obtained at baseline and on an annual basis . SETTING AND PATIENTS A community-based cohort study consisting of 459 subjects ( aged 75 - 85 , mean age 79 years ) . MEASUREMENTS Baseline and follow up ECGs  were interpreted using the Minnesota Code . Prevalence and incidence of  LVH  and  ECG  were determined as well as regression of ECG LVH . Clinical event rates measured were incidence of total mortality , myocardial infa rct ion ( MI , fatal and non-fatal ) , cardiovascular mortality , cardiovascular disease ( fatal and non-fatal ) , stroke ( fatal and non-fatal ) , all-cause dementia , and multi-infa rct dementia . Differences in event rates between groups ( those subjects with and without LVH ) were compared as tests between proportions . A Cox Proportional Hazards Regression Analysis was performed to compare the relative independent predictive values of different competing factors , including age , gender , serum cholesterol , digitalis use , body mass , index , Blessed Dementia Scale , cigarette smoking , LVH at baseline , LVH ar baseline ( persisting ) , new LVH , new LVH ( persisting ) , new LVH ( regressed ) , previous MI by history of ECG , hypertension by history , and cardiomegaly by X-ray ( cardiothoracic ratio > or = 50 % ) . RESULTS At baseline , 9.2 % of subjects ( n = 42 ) had LVH on ECG and a mortality rate of 11.7/100 persons years versus 4.9/100 persons years for subjects without baseline LVH ( P < .0001 ) , and MI rate of 7.5/100 persons years with LVH versus 2.6/100 persons years without LVH ( P < .0001 ) , and a cardiovascular mortality rate of 7.2/100 persons years without LVH versus 2.7/100 person years without LVH . Subjects who developed new LVH on ECG ( n = 39 ) had a mortality rate of 14.4/100 person-years compared with 4.4/100 person-years for those without LVH ( P < .0001 ) , a cardiovascular mortality rate of 11.1/100 person years versus 2.0/100 person years without LVH ( P < .0001 ) , and an MI rate of 6.1/100 person years versus 2.0/100 person years without LVH ( P < .01 ) . Subjects in whom the ECG LVH pattern disappeared over time had fewer cardiovascular mortal and morbid events than those with persistent LVH . According to the regression analyses , persistent LVH from baseline was an independent predictor of MI , overall cardiovascular disease , and total mortality . Newly developing LVH with subsequent regression was an independent predictor of overall cardiovascular disease and death . CONCLUSIONS An increased prevalence and incidence of LVH on ECG , irrespective cause , is associated with a poor prognosis in very old men and women . Regression of ECG LVH in older people , irrespective of cause , may confer improvement in risk for cardiovascular disease The associations of many electrocardiographic ( ECG ) abnormalities at rest with incident coronary heart disease ( CHD ) are not completely established , and whether individual ECG abnormalities convey similar risk across gender and race is uncertain . We studied the independent association of several ECG findings with incident CHD , testing for effect modification by gender and race , in a large , population -based , prospect i ve cohort study . Findings from the baseline 12-lead electrocardiograms in 1987 to 1989 were classified according to the Minnesota Code in 12,987 black and white men and women , aged 45 to 64 years , who were initially free of CHD and the use of specific cardiac medications . The incidence of CHD was ascertained through 2000 . After adjustment for multiple cardiovascular risk factors , the ECG findings that had the highest hazard rate ratios ( HRRs ) for incident CHD , when considered singly , were left ventricular hypertrophy with ST-T strain pattern in white men ( HRR 6.50 ) and in black women ( HRR 2.31 ) and , in the whole cohort , major ( HRR 2.27 ) and minor ( HRR 2.47 ) ST depression and major T-wave abnormalities ( HRR 2.12 ) . Statistically significant associations were also found in the whole cohort for minor Q waves and left ventricular hypertrophy by the Cornell definition , but not for a prolonged QTc interval , major ventricular conduction defects , or ST elevation . In conclusion , several 12-lead ECG findings were independently associated with incident CHD in middle-aged adults . With only a few exceptions , the associations were similar for blacks and whites PURPOSE As the first and only manifestation of ischemic heart disease , sudden unexpected cardiac death ( SUCD ) is a serious clinical and epidemiological concern . Prospect i ve population studies permit the identification of risk factors for SUCD . Knowledge of the short- and long-term risks for SUCD are key to underst and ing the basis of any intervention . The present paper explores the effect of time since the detection of factors on the risk for SUCD . SUBJECTS AND METHODS The Manitoba Follow-Up Study is a longitudinal , prospect i ve study of 3983 originally healthy young men who have been followed with routine medical examinations since 1948 . During 56 years of follow-up , SUCD occurred in 171 men . This analysis examined 21 possible risk factors for SUCD , including  clinical findings , social variables  and  electrocardiographic abnormalities . Time-dependent covariate Cox proportional hazard models were used to estimate age-adjusted relative risks for SUCD . In multivariate models , the relative risk of SUCD was estimated as a function of time since the documentation of each risk factor . RESULTS Excess alcohol consumption and T wave changes were associated with a high short-term risk for SUCD . Arterial hypertension and ST/T changes had sustained excess risk over both the short and long term . Newly developed left bundle branch block was a highly significant short-term risk that diminished with time . CONCLUSION These findings add new information for the clinical management of risk factors . The identification of time since the detection of these risk factors is an important consideration to reduce SUCD
target: Evidence on harms was limited , but direct harms seemed minimal ( for resting ECG ) or small ( for exercise ECG ) .
background: BACKGROUND Coronary heart disease is the leading cause of death in adults .
  Screening for abnormalities by using resting or exercise electrocardiography ( ECG ) might help identify persons who would benefit from interventions to reduce cardiovascular risk .
  PURPOSE To up date the 2004 U.S. Preventive Services Task Force evidence review on screening for  resting or exercise ECG abnormalities in asymptomatic adults .