Background
Some experts have suggested that patients with exaggerated blood pressure responses during exercise echocardiography are more likely to have abnormal exercise echocardiographic findings and less likely to have angiographically significant coronary artery disease than patients with normal blood pressure responses. The aim of this study was to evaluate the impact of exercise blood pressure on exercise echocardiographic findings and subsequent angiographic results in men and women.
Methods
In this retrospective study, clinical, exercise, and echocardiographic characteristics of patients who underwent treadmill exercise echocardiography over a 2-year period were examined, and the angiographic findings of the subgroup of patients who subsequently underwent coronary angiography within 30 days were analyzed.
Results
Among the 7,015 patients (mean age, 61 ± 13 years), 3,992 were men (57%). The likelihood of patients’ having abnormal exercise echocardiographic results was similar at all levels of exercise blood pressure, except in men who had low peak systolic blood pressures (<120 mm Hg); they had the highest rate of abnormal exercise echocardiographic findings. Of the 3,225 patients without histories of hypertension or coronary artery disease, 3,098 had peak systolic blood pressures of 120 to 219 mm Hg (a “normal” blood pressure response), and 59 had peak systolic blood pressures ≥ 220 mm Hg (an exaggerated blood pressure response). These patients with exaggerated blood pressure responses were just as likely to have normal exercise echocardiographic results as those who had normal blood pressure responses (85% vs 83%, P > .99). A subgroup of 508 patients underwent coronary angiography. The rate of false-positive findings was similar for patients who had exaggerated blood pressure responses and those who had normal blood pressure responses. The false-positive rate tended to be lower in patients who had low blood pressure responses.
Conclusions
Patients who have exaggerated blood pressure responses to exercise are not more likely to have abnormal exercise echocardiographic findings than those with normal blood pressure responses. The majority of patients who have echocardiographic abnormalities and subsequently undergo coronary angiography have substantial (≥50% stenosis) coronary artery disease.
Exercise echocardiography is widely used for evaluating patients with established or suspected coronary artery disease (CAD). Two-dimensional echocardiography, when used in concert with treadmill exercise testing, improves the overall diagnostic accuracy of the test. Exercise-related echocardiographic regional wall motion abnormalities are not always associated with angiographically significant CAD. Potential causes of false-positive stress echocardiographic findings include the presence of left bundle branch block, cardiomyopathy, abnormalities of coronary vascular tone, small-vessel CAD, and overinterpretation of data by reviewing echocardiographers.
Some experts have suggested that patients who have excessively high blood pressure with exercise, commonly described as a hypertensive response or an exaggerated blood pressure response, are more likely to have abnormal exercise echocardiographic findings and that these abnormalities are less specific for the diagnosis of angiographically significant CAD. This viewpoint can influence the subsequent treatment of patients who have echocardiographic abnormalities in the clinical setting of an exaggerated blood pressure response to exercise.
The purpose of this retrospective study was to test the hypothesis that an exaggerated blood pressure response to exercise is more likely to be associated with abnormal exercise echocardiographic findings and false-positive results at subsequent coronary angiography.
Methods
Identification of Patients
All patients who underwent exercise echocardiography from November 3, 2003, to November 2, 2005, at the Mayo Clinic in Rochester, Minnesota, were candidates for the study. The patients’ clinical characteristics were abstracted from their medical records by specially trained registered nurses and were entered into a stress echocardiography research database at the time of the stress tests. Exercise data and rest and peak stress echocardiographic data also were gathered in the database.
Patients who underwent upright cycle or supine bike exercise testing or testing with the Naughton or modified Bruce protocol were excluded from the study. Patients who had valvular heart disease, defined as at least moderate aortic or mitral stenosis or at least moderately severe aortic or mitral regurgitation, also were excluded. Seventy-two patients did not give permission for their data to be used for research purposes. A total of 7,015 patients met the inclusion criteria of the study. All patients who underwent coronary angiography within 30 days after treadmill exercise echocardiography were identified every month by a research assistant.
Exercise Testing
All patients underwent symptom-limited treadmill exercise testing and evaluation with the Bruce protocol. Test end points were those recommended in the American College of Cardiology and American Heart Association exercise testing guidelines. Medications such as β-blockers were stopped before exercise testing only if the referring physician did so. Blood pressure measurements were taken at rest with patients in the supine and standing positions, during each stage of the Bruce protocol, near or at peak exercise, and in the recovery period. Specially trained registered nurses made these measurements with sphygmomanometry while they monitored the patients during the stress tests. The systolic blood pressure measurement obtained at or near peak exercise was defined as the peak systolic blood pressure. An exaggerated blood pressure response was defined as a peak systolic blood pressure ≥220 mm Hg. A low blood pressure response was defined as a peak systolic blood pressure <120 mm Hg. Change in systolic blood pressure was calculated by subtracting the rest systolic blood pressure from the peak systolic blood pressure. The exercise electrocardiographic results were considered positive for ischemia if there was ≥1-mm horizontal or down-sloping ST-segment depression at 80 ms after the J point in one or more leads.
Exercise Echocardiography
Two-dimensional echocardiographic images at rest and immediately after exercise were acquired and analyzed according to a previously published protocol. Digitized and videotaped images were used for interpretation by level 3 trained echocardiologists. The left ventricular (LV) ejection fraction was determined by either visual assessment or a modification of the Quinones method. A 16-segment LV model was used for semiquantitative scoring at rest and immediately after exercise. The LV wall motion score index was calculated by adding the scores and dividing the sum by 16. Increased LV wall thickness was defined by a diastolic thickness of >13 mm of the ventricular septum or posterior wall. Patients with normal exercise echocardiographic results had normal LV regional and global systolic function at rest and no exercise-induced wall motion abnormalities. Patients with abnormal exercise echocardiographic results had rest regional wall motion abnormalities (fixed), exercise-induced regional wall motion abnormalities (ischemic), or both (mixed). Exercise echocardiographic results were considered positive for ischemia if new or worsening regional wall motion abnormalities developed with exercise (ischemic or mixed). The overall change in LV end-systolic size was assessed visually by comparing the rest and postexercise digitized images side by side. The response of the LV end-systolic size to exercise was considered normal if the LV end-systolic size decreased and abnormal if it did not change appreciably or increased.
Coronary Angiography
Coronary angiography was performed for clinical reasons within 30 days after stress testing in a subgroup of patients. Coronary angiograms were interpreted by experienced invasive cardiologists and scored according to the Coronary Artery Surgery Study criteria. The definition of normal coronary arteries was the absence of luminal irregularities or any other CAD in any of the epicardial vessels. Angiographically mild, nonobstructive CAD was defined by the presence of <50% stenosis and angiographically significant CAD by the presence of ≥50% stenosis in one or more coronary arteries or major coronary branches.
Presentation of Data
Clinical and exercise echocardiographic data were summarized and presented according to peak systolic blood pressure. All patients were assigned to one of the following three blood pressure subgroups: exaggerated blood pressure response (peak systolic blood pressure ≥ 220 mm Hg), “normal” blood pressure response (peak systolic blood pressure, 120–219 mm Hg), and low blood pressure response (peak systolic blood pressure < 120 mm Hg). Exercise echocardiographic and angiographic findings also were stratified according to peak systolic blood pressure, in increments of 20 mm Hg.
Statistical Analysis
Categorical variables are summarized as numbers and percentages of patients and continuous variables as mean ± SD or median (interquartile range). Patient characteristics were compared using t tests and Wilcoxon’s rank-sum tests for continuous variables; the distribution of continuous variables was visually assessed for normality before the application of one of these two tests. Fisher’s exact tests and Pearson’s χ 2 tests were used for categorical variables. Pearson’s χ 2 test was used to compare blood pressure subgroups. Analyses were performed with JMP version 8.0.0 (SAS Institute Inc., Cary, NC).
Results
Clinical Characteristics
The study population was composed of 7,015 patients (mean age, 61 ± 13 years). There were 3,992 men (57%) and 3,023 women (43%). Overall, 10% of patients had diabetes mellitus, 50% had histories of hypertension, 8% had histories of myocardial infarction, and 15% had prior coronary revascularization. Among patients, 171 (2.4%) had exaggerated blood pressure responses, 156 (2.2%) low blood pressure responses, and 6,688 (95.4%) normal blood pressure responses. Clinical characteristics of the patients are given in Table 1 . Patients with exaggerated blood pressure responses were more likely to have histories of hypertension. Patients with low blood pressure responses were more likely to have histories of myocardial infarction or prior coronary revascularization and were more likely to be receiving β-blocker therapy.
| Characteristic | Peak exercise systolic BP (mm Hg) | P | ||
|---|---|---|---|---|
| <120 ( n = 156) | 120–219 ( n = 6,688) | ≥220 ( n = 171) | ||
| Age (y) | 61.9 ± 11 | 61.0 ± 13 | 59.9 ± 11 | .34 |
| Women | 78 (50%) | 2,883 (43%) | 62 (36%) | .05 |
| Hypertension | 74 (47%) | 3,292 (49%) | 111 (65%) | .001 |
| Diabetes mellitus | 18 (12%) | 687 (10%) | 21 (12%) | .62 |
| Hyperlipidemia | 95 (61%) | 4,276 (64%) | 108 (63%) | .69 |
| History of smoking | 72 (46%) | 2,910 (44%) | 87 (51%) | .13 |
| History of MI | 29 (19%) | 554 (8%) | 7 (4%) | <.001 |
| Prior coronary revascularization | 48 (31%) | 990 (15%) | 16 (9%) | <.001 |
| Medications | ||||
| ACE inhibitors | 42 (27%) | 1,625 (24%) | 48 (28%) | .41 |
| β-blockers | 75 (48%) | 1,933 (29%) | 42 (25%) | <.001 |
| Calcium channel blockers | 25 (16%) | 792 (12%) | 21 (12%) | .29 |
Exercise Echocardiographic Characteristics
Of the patients, 5,110 (73%) had normal treadmill exercise echocardiographic results, and 1,905 (27%) had abnormal results. The exercise echocardiographic characteristics of the study population are detailed in Table 2 . Significant differences were found among the three blood pressure subgroups. However, patients with exaggerated blood pressures responses were not more likely to have positive exercise electrocardiographic results or abnormal exercise echocardiographic findings. Patients with low blood pressure responses were least likely to have normal exercise echocardiographic results ( Figure 1 ). Patients with marked increases in systolic blood pressure were not more likely to have abnormal exercise echocardiographic results ( Figure 2 ). Also, the higher the peak rate-pressure product, the greater the likelihood that exercise echocardiographic findings would be normal ( Figure 3 ).
| Characteristic | Peak exercise systolic BP (mm Hg) | P | ||
|---|---|---|---|---|
| <120 ( n = 156) | 120–219 ( n = 6,688) | ≥220 ( n = 171) | ||
| Rest systolic BP (mm Hg) | 107 ± 17 | 128 ± 22 | 150 ± 21 | <.001 |
| Rest heart rate (beats/min) | 74 ± 15 | 77 ± 87 | 77 ± 13 | .92 |
| Exercise duration (min) | 7.3 ± 2.8 | 8.6 ± 3.2 | 8.3 ± 2.4 | <.001 |
| Peak systolic BP (mm Hg) | 106 ± 11 | 167 ± 21 | 228 ± 10 | <.001 |
| Peak heart rate (beats/min) | 132 ± 28 | 148 ± 23 | 153 ± 18 | <.001 |
| Peak rate-pressure product | 14,092 ± 3,528 | 24,818 ± 5,218 | 34,839 ± 4,377 | <.001 |
| Exercise electrocardiographic results positive for ischemia | 18 (12%) | 544 (8%) | 16 (9%) | .27 |
| Rest variables | ||||
| WMSI | 1.18 ± 0.3 | 1.06 ± 0.2 | 1.02 ± 0.1 | <.001 |
| LVEF (%) | 57 ± 9 | 60 ± 6 | 62 ± 6 | <.001 |
| Increased LV wall thickness | 13 (8%) | 322 (5%) | 26 (15%) | <.001 |
| Stress variables | ||||
| WMSI | 1.26 ± 0.4 | 1.12 ± 0.3 | 1.10 ± 0.4 | <.001 |
| LVEF (%) | 63 ± 12 | 69 ± 11 | 70 ± 9 | <.001 |
| Abnormal response of LV end-systolic size | 27 (17%) | 660 (10%) | 19 (11%) | <.001 |
| Exercise echocardiographic findings | ||||
| Normal | 89 (57%) | 4,895 (73%) | 126 (74%) | <.001 |
| Ischemia | 21 (13%) | 848 (13%) | 27 (16%) | .46 |
| Mixed | 25 (16%) | 515 (7%) | 11 (6%) | <.001 |
| Fixed | 21 (13%) | 430 (6%) | 7 (4%) | <.002 |
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