Roger Chou, MD; Bhaskar Arora, MD; Tracy Dana, MLS; Rongwei Fu, PhD; Miranda Walker, MA; Linda Humphrey, MD
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.
To update the 2004 U.S. Preventive Services Task Force evidence review on screening for resting or exercise ECG abnormalities in asymptomatic adults.
MEDLINE (2002 through January 2011), the Cochrane Library database (through the fourth quarter of 2010), and reference lists.
Randomized, controlled trials and prospective cohort studies.
Investigators abstracted details about the study population, study design, data analysis, follow-up, and results and assessed quality by using predefined criteria.
No study evaluated clinical outcomes or use of risk-reducing therapies after screening versus no screening. No study estimated how accurately resting or exercise electrocardiography classified participants into high-, intermediate-, or low-risk groups, compared with traditional risk factor assessment alone. Sixty-three prospective cohort studies evaluated abnormalities on resting or exercise ECG as predictors of cardiovascular events after adjustment for traditional risk factors. Abnormalities on resting ECG (ST-segment or T-wave abnormalities, left ventricular hypertrophy, bundle branch block, or left-axis deviation) or exercise ECG (ST-segment depression with exercise, chronotropic incompetence, abnormal heart rate recovery, or decreased exercise capacity) were associated with increased risk (pooled hazard ratio estimates, 1.4 to 2.1). Evidence on harms was limited, but direct harms seemed minimal (for resting ECG) or small (for exercise ECG). No study estimated harms from subsequent testing or interventions, although rates of angiography after exercise ECG ranged from 0.6% to 2.9%.
Only English-language studies were included. Statistical heterogeneity was present in several of the pooled analyses.
Abnormalities on resting or exercise ECG are associated with an increased risk for subsequent cardiovascular events after adjustment for traditional risk factors, but the clinical implications of these findings are unclear.
Agency for Healthcare Research and Quality.
What are the potential benefits of screening electrocardiography (ECG)?
Studies included in this systematic review showed that some abnormalities found on resting or exercise ECG were independent predictors of future cardiovascular events. No study compared clinical outcomes or use of risk-reducing therapies between persons who did and did not receive screening ECG. No studies assessed whether ECG findings better classified patients into meaningful risk groups than did traditional risk factor assessment alone.
Some abnormalities on ECG are risk factors for cardiovascular events, but the benefits and clinical implications of routine ECG screening are not clear.
CAD = coronary artery disease; CHD = coronary heart disease; ECG = electrocardiography; KQ = key question.
What are the benefits of screening for abnormalities on resting or exercise electrocardiography compared with no screening on coronary heart disease outcomes?
How does the identification of high-risk persons via resting or exercise electrocardiography affect use of treatments to reduce cardiovascular risk?
What is the accuracy of resting or exercise electrocardiography for stratifying persons into high-, intermediate- and low-risk groups?
What are the harms of screening with resting or exercise electrocardiography?
ECG = electrocardiography; KQ = key question.
* Includes the Cochrane Central Register of Controlled Trials and the Cochrane Database of Systematic Reviews.
† Includes studies identified from reference lists or suggested by experts.
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Mohammadreza, Bozorgmanesh, MD
Prevention of Metabolic Disorders Research Center, Research Institute for Endocrine Sciences, Shahid
November 8, 2011
Screening Asymptomatic Adults with Resting and Exercise Electrocardiography
To the editor:
Chou and colleagues have recently argued, that the clinical implications of the associations observed between ECG and CVD are unclear since there were only two studies showing ECG to improve discrimination capacity (1). Attention would be brought to indelible fingerprint of flawed methodology in these studies:
1. The sample of study conducted by Denes et al. was limited with respect to age and sex. Moreover as the authors appreciated the follow-up length was short and comparisons with the Framingham Risk Score was performed on a small subgroup of participants. The transportability of the Framingham Risk Score to the study sample, and consequently the validity of utilizing it as a surrogate of CVD risk in order to adjust for the confounding effects of its components could not be verified. The discriminatory capacity of the Framingham Risk Score was conspicuously low (Harrell's C of 0.690) and effect size of its components were not re- estimated and calibration of estimated risk was not assessed. No data was presented for the incidence of endpoints or the distributions of risk factors of the Framingham Risk Score in the study sample, as such no recalibration could be done.
2. Several limitations mentioned above apply to the study conducted by Atkas and colleagues. Still other methodological infringements deserve mentioning (2). The SCORE algorithm predicts 10-year risk of CVD while duration of follow-up of study allowed 9-year risk prediction. No adjustment, however, has been implemented to account for this difference. The endpoint for which the SCORE algorithm has been developed was different from those of the study under the investigation.
Finding no study to examine how ECG can help improve reclassification of participants compared with traditional risk factors assessment alone, Chuo et al. calls for future study to consider reclassification while evaluating the usefulness of the ECG. As recently noted by Tzoulaki et al. reclassification studies would benefit from more rigorous methodological standards; otherwise claims for improved reclassification may remain spurious. Attempt should be done to provide the state-of-the art while modeling currently available predictors (3). Cutpoint-free net reclassification improvement indices (NRIs) or meaningful thresholds of risk (3) with different therapeutic intervention implications should be used. Original NRI described by Pencina et al. applies to the logistic regression modeling (4, 5) and may not be applicable to survival data where censoring matters (5) or to matched case-control studies.
1. Chou R, Arora B, Dana T, Fu R, Walker M, Humphrey L. Screening Asymptomatic Adults With Resting or Exercise Electrocardiography: A Review of the Evidence for the U.S. Preventive Services Task Force. Annals of Internal Medicine. 2011;155(6):375-85.
2. Aktas MK, Ozduran V, Pothier CE, Lang R, Lauer MS. Global risk scores and exercise testing for predicting all-cause mortality in a preventive medicine program. JAMA. 2004;292(12):1462-8.
3. Tzoulaki I, Liberopoulos G, Ioannidis JP. Use of reclassification for assessment of improved prediction: an empirical evaluation. Int J Epidemiol. 2011;40(4):1094-105.
4. Pencina MJ, D'Agostino RB, Sr., D'Agostino RB, Jr., Vasan RS. Evaluating the added predictive ability of a new marker: from area under the ROC curve to reclassification and beyond. Stat Med. 2008;27(2):157-72; discussion 207-12.
5. Pencina MJ, D'Agostino RB, Sr., Steyerberg EW. Extensions of net reclassification improvement calculations to measure usefulness of new biomarkers. Stat Med. 2011;30(1):11-21.
Chou R, Arora B, Dana T, Fu R, Walker M, Humphrey L. Screening Asymptomatic Adults With Resting or Exercise Electrocardiography: A Review of the Evidence for the U.S. Preventive Services Task Force. Ann Intern Med. 2011;155:375-385. doi: 10.7326/0003-4819-155-6-201109200-00006
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Published: Ann Intern Med. 2011;155(6):375-385.
Cardiac Diagnosis and Imaging, Cardiology, Prevention/Screening, Pulmonary/Critical Care.
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