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Predictors for coronary artery disease in patients with paradoxical systolic blood pressure elevation during recovery after graded exercise
International Journal of Cardiology 119 (2007) 274 – 276 www.elsevier.com/locate/ijcard
Letter to the Editor
Predictors for coronary artery disease in patients with paradoxical systolic blood pressure elevation during recovery after graded exercise Jung-Cheng Hsu a,d , Pei-Song Chu a , Ta-Chen Su a,b,⁎, Lian-Yu Lin a , Wen-Jone Chen c , Jing-Shiang Hwang e , Ming-Fong Chen a , Chiau-Suong Liau a , Yuan-Teh Lee a a Department of Internal Medicine, Taiwan Department of Environmental and Occupational Medicine, Taiwan c Department of Emergency Medicine, National Taiwan University Hospital, Taiwan Division of Cardiovascular Medicine, Cardiovascular Center, Far-Eastern Memorial Hospital, Pan-Chiao, Taipei County, Taiwan e Institute of Statistical Science, Academia Sinica, Taipei, Taiwan b
d
Received 5 April 2006; received in revised form 24 July 2006; accepted 29 July 2006 Available online 13 October 2006
Abstract The predictors for coronary artery disease (CAD) in patients with delayed systolic blood pressure (SBP) recovery after graded exercise are unclear. We studied 672 patients with preceding positive symptom-limited exercise treadmill testing (ETT) and underwent their first coronary angiography within 90 days to determine the high‐risk profiles for angiographic CAD in patients with paradoxical SBP elevation (the SBP at 3‐min of recovery was equal to or higher than that at 1‐min of recovery). Among them, 356 patients were diagnosed as CAD, of which 173 were severe CAD. Among 208 patients with paradoxical SBP elevation, 158 (76%) were CAD, and 101 (48.6%) were severe CAD. Multivariate logistic regression analyses identified male gender and hyperlipidemia as positive predictors and maximal heart rate and exercise time as negative predictors for CAD or severe CAD. In conclusion, patients with both positive ETT for ischemia and paradoxical SBP elevation during recovery have a high prevalence of CAD and severe CAD. The high-risk patients for the presence of CAD or severe CAD were those of male, with hyperlipidemia, low achievable maximal heart rate, and short exercise time after graded exercise. © 2006 Elsevier Ireland Ltd. All rights reserved.
Keywords: Exercise treadmill testing; Coronary artery disease; Paradoxical systolic blood pressure elevation
Exercise treadmill testing (ETT) was recommended as an initial evaluation for patients with suspected coronary artery disease (CAD). The magnitude of ST depression during ETT itself was often not good enough for predicting the severity of coronary artery disease. On the other hand, an abnormal postexercise systolic blood pressure (SBP) ratio during recovery was associated with the presence of CAD [1–4].
Furthermore, a delayed decline in SBP during recovery was associated with a higher risk for severe angiographic CAD [4]. Reduced BP drop after exercise identifies a subgroup with higher cardiovascular risk [5]. However, information about who are at the high-risk for angiographic CAD or severe CAD in patients with delayed SBP recovery after ETT is still unknown [1–4]. 1. Methods
⁎ Corresponding author. Departments of Internal Medicine and Environmental and Occupational Medicine, National Taiwan University Hospital, 7, Chung-Shan South Road, Taipei 10020, Taiwan. Tel.: +886 2 23123456x6719; fax: +886 2 23712361. E-mail address: [email protected] (T.-C. Su). 0167-5273/$ - see front matter © 2006 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijcard.2006.07.160
We retrospectively studied the 3221 patients whose results of treadmill testing were positive (the standard ST criteria) in National Taiwan University Hospital from January 2000 through June 2002. Among them, 672 patients underwent
J.-C. Hsu et al. / International Journal of Cardiology 119 (2007) 274–276
275
Table 1 Multivariate logistic regression for coronary artery disease (CAD) or severe CAD with paradoxical SBP elevation during recovery Characteristics Age ≥60 years Male gender Hypertension Hyperlipidemia Diabetes mellitus Smoking B-blocker use Exercise time, min Max HR ach, %
CAD
Severe CAD
Univariate
Multivariate
Univariate
Multivariate
2.32(1.19–4.50)⁎ 4.27(2.16–8.44)‡ 2.09(1.02–4.29)⁎ 2.26(1.16–4.39)⁎ 2.58(1.13–5.88)⁎ 2.94(1.43–6.03)‡ 1.49(0.49–4.50) 0.76(0.64–0.91)‡ 0.94(0.91–0.97)‡
1.79(0.74–4.36) 7.36(2.81–19.31)‡ 1.79(0.73–4.39) 2.58(1.19–5.59)⁎ 2.02(0.73–5.62) 2.32(0.94–5.77) 1.35(0.36–5.02) 0.73(0.57–0.95)⁎ 0.94(0.90–0.98)‡
1.59(0.92–2.75) 5.71(2.74–11.92)‡ 1.10(0.57–2.13) 1.65(0.95–2.86) 2.11(1.14–3.90)⁎ 1.93(1.11–3.37)⁎ 0.94(0.34–2.61) 0.78(0.67–0.90)‡ 0.95(0.93–0.98)‡
1.01(0.49–2.08) 11.00(4.38–27.63)‡ 0.80(0.36–1.80) 2.20(1.12–4.31)⁎ 1.45(0.69–3.05) 1.12(0.56–2.25) 0.72(0.21–2.47) 0.69(0.55–0.86)‡ 0.95(0.92–0.98)‡
Abbreviations: Max HR ach, maximal heart rate achievable. p-value: ⁎b0.05, †b0.01, ‡b0.005.
their first coronary angiography within 90 days of exercise testing enrolled for analyses. Electrocardiograms were recorded using an exercise system (CASE Marquette 16, Marquette Electronics Inc., Milwaukee, Wisconsin). The Bruce standard protocols were used for symptom-limited treadmill testing while leaning or grasping on handrails was not allowed. Heart rate, blood pressure and 12-lead ECG with shift of ST segment were recorded during the standing preexercise period, 60 s before the end of each stage, peak exercise and 1, 3 and 5 min of recovery. The Tango exercise BP monitor (SunTech Medical, NC, USA) was used to automatically measure and display patient's systolic and diastolic BP along with heart rate. SBP ratio during recovery was defined as the ratio of SBP in 3 min to SBP in 1 min during recovery during ETT. Paradoxical SBP elevation during recovery was defined as the SBP at 3 min of recovery was equal to or higher than the SBP at 1 min of recovery during ETT. Percent of maximal heart rate achievable was defined as the ratio of maximal heart rate achieved to maximal heart rate predicted. Prevalent diabetes mellitus (DM) was defined as fasting glucose ≥ 6.99 mmol/L, and/or a history of DM with management. Patients with cholesterol levels ≥ 5.17 mmol/L or low-density lipoprotein cholesterol levels ≥ 3.36 mmol/L or on lipid-lowering agents were defined as hyperlipidemia. The diagnosis of CAD was made from the evidence of any localized coronary artery stenosis or diffuses coronary artery narrowing, which was defined as N 50% diameter stenosis in one or more of the coronary arteries. Severe CAD was defined as left main disease, triple-vessel disease, or two-vessel disease with involvement of the proximal LAD. 2. Results Among them, 316 patients were diagnosed as non-CAD, while 356 patients diagnosed as CAD, of which 173 were severe CAD. The group of severe CAD was higher in age, percent of male gender, diabetes, hypertension, hyperlipidemia, current smoking and higher percent of paradoxical SBP elevation during recovery than the group of non-CAD
or mild CAD (all p-values b 0.005). Compared with those in non-CAD or non-severe CAD groups, the SBP ratio during recovery also was higher in those of CAD or severe CAD groups respectively. Among the 208 patients who had paradoxical SBP elevation during recovery, 50, 57 and 101 patients diagnosed as non-CAD, mild CAD and severe CAD by angiographic findings respectively. Multivariate logistic regression analyses in Table 1 showed male gender and hyperlipidemia as positive predictors for CAD (or severe CAD) with odds ratio of 7.36 (or 11.0) and 2.58 (or 2.20) respectively. In addition, the shorter exercise time and the lower percent of maximal achievable heart rate were also associated with higher risk for CAD or severe CAD. 3. Discussion Patients were at high risk for angiographic CAD and even severe CAD when paradoxical SBP elevation during recovery after maximal exercise. Our study extended the finding of high-risk profile of presence of CAD or severe CAD to include those of male gender, with hyperlipidemia, low maximal heart rate achievable, and short exercise time during ETT in patients with paradoxical SBP elevation during recovery after graded exercise. Among all patients with positive ETT and having received the first coronary angiography as shown in this study, there was 58.4% of severe CAD if their hemodynamic response showed paradoxical SBP elevation during recovery after graded exercise test. The high specificity (78.6%) of this test also added the validity of using paradoxical SBP elevation as an independent predictor for angiographic severe CAD. This study confirmed SBP ratio during recovery is significant higher in patients with CAD or severe CAD as previous studies [1–4]. Amon et al. first demonstrated an association between the presence of CAD and post-exercise SBP response [1]. A progressive increase in the ratio of SBP at 3 min of recovery to SBP at maximal exercise was positively correlated with mild to severe CAD [3]. Accordingly, we identified the group with the highest SBP
276
J.-C. Hsu et al. / International Journal of Cardiology 119 (2007) 274–276
ratio during recovery, namely those of ratio equal to or higher than one, as a very high risk group for CAD or severe CAD. Left ventricular dysfunction developed during maximal exercise [6] and a rapid amelioration of left ventricular asynergy after cessation of exercise [7] ascribed as the possible mechanisms of abnormal SBP response after maximal exercise. In patients with CAD, mechanisms of abnormal SBP response post-exercise have been studied by using pulmonary artery catheterization [6,8]. A paradoxical increase in stroke volume and systemic vascular resistance with exaggerated sympathetic activity were also demonstrated after exercise [8]. An increase in SBP after exercise is associated with impaired endothelial function [9]. These studies supported hypotheses that mechanisms of paradoxical SBP elevation during recovery phase might be due to recovery from transient myocardial ischemia, exaggerated sympathetic activity and impaired endothelial function at, and immediately after maximal exercise testing. Further studies to answer the mechanism of high-risk profiles in patients with paradoxical SBP elevation during recovery are recommended. This study provides a new insight to the abnormal SBP response during recovery phase in ETT. These findings may also provide a powerful and practical recommendation for those who are at high-risk for severe CAD and those who have to receive coronary angiography immediately if their ETT showed both positive for ischemia and paradoxical SBP elevation during recovery.
References [1] Amon KW, Richards KL, Crawford MH. Usefulness of the postexercise response of systolic blood pressure in the diagnosis of coronary artery disease. Circulation 1984;70:951–6. [2] Taylor AJ, Beller GA. Postexercise systolic blood pressure response: association with the presence and extent of perfusion abnormalities on thallium-201 scintigraphy. Am Heart J 1995;129:227–34. [3] Tsuda M, Hatano K, Hayashi H, Yokota M, Hirai M, Saito H. Diagnostic value of postexercise systolic blood pressure response for detecting coronary artery disease in patients with or without hypertension. Am Heart J 1993;125:718–25. [4] Mcham SA, Marwick TH, Pashkow FJ, Lauer MS. Delayed systolic blood pressure recovery after graded exercise. J Am Coll Cardiol 1999;34:754–9. [5] Yosefy C, Jafari J, Klainman E, Brodkin B, Handschumacher MD, Vaturi M. The prognostic value of post-exercise blood pressure reduction in patients with hypertensive response during exercise stress test. Int J Cardiol Oct 17 2005 [Electronic publication ahead of print]. [6] Miyahara T, Yokota M, Iwase M, et al. Mechanism of abnormal postexercise systolic blood pressure response and its diagnostic value in patients with coronary artery disease. Am Heart J 1990;120:40–9. [7] Rozanski A, Elkayam U, Berman DS, Diamond GA, Prause J, Swan HJ. Improvement of resting myocardial asynergy with cessation of upright bicycle exercise. Circulation 1983;67:529–35. [8] Hashimoto M, Okamoto M, Yamagata T, et al. Abnormal systolic blood pressure response during exercise recovery in patients with angina pectoris. J Am Coll Cardiol 1993;22:659–64. [9] Aldo Ferrara L, Palmieri V, Limauro S, et al. Association between postischemic forearm blood flow and blood pressure response to maximal exercise in well trained healthy young men. Int J Cardiol Oct 30 2005 [Electronic publication ahead of print].
Letter to the Editor
Predictors for coronary artery disease in patients with paradoxical systolic blood pressure elevation during recovery after graded exercise Jung-Cheng Hsu a,d , Pei-Song Chu a , Ta-Chen Su a,b,⁎, Lian-Yu Lin a , Wen-Jone Chen c , Jing-Shiang Hwang e , Ming-Fong Chen a , Chiau-Suong Liau a , Yuan-Teh Lee a a Department of Internal Medicine, Taiwan Department of Environmental and Occupational Medicine, Taiwan c Department of Emergency Medicine, National Taiwan University Hospital, Taiwan Division of Cardiovascular Medicine, Cardiovascular Center, Far-Eastern Memorial Hospital, Pan-Chiao, Taipei County, Taiwan e Institute of Statistical Science, Academia Sinica, Taipei, Taiwan b
d
Received 5 April 2006; received in revised form 24 July 2006; accepted 29 July 2006 Available online 13 October 2006
Abstract The predictors for coronary artery disease (CAD) in patients with delayed systolic blood pressure (SBP) recovery after graded exercise are unclear. We studied 672 patients with preceding positive symptom-limited exercise treadmill testing (ETT) and underwent their first coronary angiography within 90 days to determine the high‐risk profiles for angiographic CAD in patients with paradoxical SBP elevation (the SBP at 3‐min of recovery was equal to or higher than that at 1‐min of recovery). Among them, 356 patients were diagnosed as CAD, of which 173 were severe CAD. Among 208 patients with paradoxical SBP elevation, 158 (76%) were CAD, and 101 (48.6%) were severe CAD. Multivariate logistic regression analyses identified male gender and hyperlipidemia as positive predictors and maximal heart rate and exercise time as negative predictors for CAD or severe CAD. In conclusion, patients with both positive ETT for ischemia and paradoxical SBP elevation during recovery have a high prevalence of CAD and severe CAD. The high-risk patients for the presence of CAD or severe CAD were those of male, with hyperlipidemia, low achievable maximal heart rate, and short exercise time after graded exercise. © 2006 Elsevier Ireland Ltd. All rights reserved.
Keywords: Exercise treadmill testing; Coronary artery disease; Paradoxical systolic blood pressure elevation
Exercise treadmill testing (ETT) was recommended as an initial evaluation for patients with suspected coronary artery disease (CAD). The magnitude of ST depression during ETT itself was often not good enough for predicting the severity of coronary artery disease. On the other hand, an abnormal postexercise systolic blood pressure (SBP) ratio during recovery was associated with the presence of CAD [1–4].
Furthermore, a delayed decline in SBP during recovery was associated with a higher risk for severe angiographic CAD [4]. Reduced BP drop after exercise identifies a subgroup with higher cardiovascular risk [5]. However, information about who are at the high-risk for angiographic CAD or severe CAD in patients with delayed SBP recovery after ETT is still unknown [1–4]. 1. Methods
⁎ Corresponding author. Departments of Internal Medicine and Environmental and Occupational Medicine, National Taiwan University Hospital, 7, Chung-Shan South Road, Taipei 10020, Taiwan. Tel.: +886 2 23123456x6719; fax: +886 2 23712361. E-mail address: [email protected] (T.-C. Su). 0167-5273/$ - see front matter © 2006 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijcard.2006.07.160
We retrospectively studied the 3221 patients whose results of treadmill testing were positive (the standard ST criteria) in National Taiwan University Hospital from January 2000 through June 2002. Among them, 672 patients underwent
J.-C. Hsu et al. / International Journal of Cardiology 119 (2007) 274–276
275
Table 1 Multivariate logistic regression for coronary artery disease (CAD) or severe CAD with paradoxical SBP elevation during recovery Characteristics Age ≥60 years Male gender Hypertension Hyperlipidemia Diabetes mellitus Smoking B-blocker use Exercise time, min Max HR ach, %
CAD
Severe CAD
Univariate
Multivariate
Univariate
Multivariate
2.32(1.19–4.50)⁎ 4.27(2.16–8.44)‡ 2.09(1.02–4.29)⁎ 2.26(1.16–4.39)⁎ 2.58(1.13–5.88)⁎ 2.94(1.43–6.03)‡ 1.49(0.49–4.50) 0.76(0.64–0.91)‡ 0.94(0.91–0.97)‡
1.79(0.74–4.36) 7.36(2.81–19.31)‡ 1.79(0.73–4.39) 2.58(1.19–5.59)⁎ 2.02(0.73–5.62) 2.32(0.94–5.77) 1.35(0.36–5.02) 0.73(0.57–0.95)⁎ 0.94(0.90–0.98)‡
1.59(0.92–2.75) 5.71(2.74–11.92)‡ 1.10(0.57–2.13) 1.65(0.95–2.86) 2.11(1.14–3.90)⁎ 1.93(1.11–3.37)⁎ 0.94(0.34–2.61) 0.78(0.67–0.90)‡ 0.95(0.93–0.98)‡
1.01(0.49–2.08) 11.00(4.38–27.63)‡ 0.80(0.36–1.80) 2.20(1.12–4.31)⁎ 1.45(0.69–3.05) 1.12(0.56–2.25) 0.72(0.21–2.47) 0.69(0.55–0.86)‡ 0.95(0.92–0.98)‡
Abbreviations: Max HR ach, maximal heart rate achievable. p-value: ⁎b0.05, †b0.01, ‡b0.005.
their first coronary angiography within 90 days of exercise testing enrolled for analyses. Electrocardiograms were recorded using an exercise system (CASE Marquette 16, Marquette Electronics Inc., Milwaukee, Wisconsin). The Bruce standard protocols were used for symptom-limited treadmill testing while leaning or grasping on handrails was not allowed. Heart rate, blood pressure and 12-lead ECG with shift of ST segment were recorded during the standing preexercise period, 60 s before the end of each stage, peak exercise and 1, 3 and 5 min of recovery. The Tango exercise BP monitor (SunTech Medical, NC, USA) was used to automatically measure and display patient's systolic and diastolic BP along with heart rate. SBP ratio during recovery was defined as the ratio of SBP in 3 min to SBP in 1 min during recovery during ETT. Paradoxical SBP elevation during recovery was defined as the SBP at 3 min of recovery was equal to or higher than the SBP at 1 min of recovery during ETT. Percent of maximal heart rate achievable was defined as the ratio of maximal heart rate achieved to maximal heart rate predicted. Prevalent diabetes mellitus (DM) was defined as fasting glucose ≥ 6.99 mmol/L, and/or a history of DM with management. Patients with cholesterol levels ≥ 5.17 mmol/L or low-density lipoprotein cholesterol levels ≥ 3.36 mmol/L or on lipid-lowering agents were defined as hyperlipidemia. The diagnosis of CAD was made from the evidence of any localized coronary artery stenosis or diffuses coronary artery narrowing, which was defined as N 50% diameter stenosis in one or more of the coronary arteries. Severe CAD was defined as left main disease, triple-vessel disease, or two-vessel disease with involvement of the proximal LAD. 2. Results Among them, 316 patients were diagnosed as non-CAD, while 356 patients diagnosed as CAD, of which 173 were severe CAD. The group of severe CAD was higher in age, percent of male gender, diabetes, hypertension, hyperlipidemia, current smoking and higher percent of paradoxical SBP elevation during recovery than the group of non-CAD
or mild CAD (all p-values b 0.005). Compared with those in non-CAD or non-severe CAD groups, the SBP ratio during recovery also was higher in those of CAD or severe CAD groups respectively. Among the 208 patients who had paradoxical SBP elevation during recovery, 50, 57 and 101 patients diagnosed as non-CAD, mild CAD and severe CAD by angiographic findings respectively. Multivariate logistic regression analyses in Table 1 showed male gender and hyperlipidemia as positive predictors for CAD (or severe CAD) with odds ratio of 7.36 (or 11.0) and 2.58 (or 2.20) respectively. In addition, the shorter exercise time and the lower percent of maximal achievable heart rate were also associated with higher risk for CAD or severe CAD. 3. Discussion Patients were at high risk for angiographic CAD and even severe CAD when paradoxical SBP elevation during recovery after maximal exercise. Our study extended the finding of high-risk profile of presence of CAD or severe CAD to include those of male gender, with hyperlipidemia, low maximal heart rate achievable, and short exercise time during ETT in patients with paradoxical SBP elevation during recovery after graded exercise. Among all patients with positive ETT and having received the first coronary angiography as shown in this study, there was 58.4% of severe CAD if their hemodynamic response showed paradoxical SBP elevation during recovery after graded exercise test. The high specificity (78.6%) of this test also added the validity of using paradoxical SBP elevation as an independent predictor for angiographic severe CAD. This study confirmed SBP ratio during recovery is significant higher in patients with CAD or severe CAD as previous studies [1–4]. Amon et al. first demonstrated an association between the presence of CAD and post-exercise SBP response [1]. A progressive increase in the ratio of SBP at 3 min of recovery to SBP at maximal exercise was positively correlated with mild to severe CAD [3]. Accordingly, we identified the group with the highest SBP
276
J.-C. Hsu et al. / International Journal of Cardiology 119 (2007) 274–276
ratio during recovery, namely those of ratio equal to or higher than one, as a very high risk group for CAD or severe CAD. Left ventricular dysfunction developed during maximal exercise [6] and a rapid amelioration of left ventricular asynergy after cessation of exercise [7] ascribed as the possible mechanisms of abnormal SBP response after maximal exercise. In patients with CAD, mechanisms of abnormal SBP response post-exercise have been studied by using pulmonary artery catheterization [6,8]. A paradoxical increase in stroke volume and systemic vascular resistance with exaggerated sympathetic activity were also demonstrated after exercise [8]. An increase in SBP after exercise is associated with impaired endothelial function [9]. These studies supported hypotheses that mechanisms of paradoxical SBP elevation during recovery phase might be due to recovery from transient myocardial ischemia, exaggerated sympathetic activity and impaired endothelial function at, and immediately after maximal exercise testing. Further studies to answer the mechanism of high-risk profiles in patients with paradoxical SBP elevation during recovery are recommended. This study provides a new insight to the abnormal SBP response during recovery phase in ETT. These findings may also provide a powerful and practical recommendation for those who are at high-risk for severe CAD and those who have to receive coronary angiography immediately if their ETT showed both positive for ischemia and paradoxical SBP elevation during recovery.
References [1] Amon KW, Richards KL, Crawford MH. Usefulness of the postexercise response of systolic blood pressure in the diagnosis of coronary artery disease. Circulation 1984;70:951–6. [2] Taylor AJ, Beller GA. Postexercise systolic blood pressure response: association with the presence and extent of perfusion abnormalities on thallium-201 scintigraphy. Am Heart J 1995;129:227–34. [3] Tsuda M, Hatano K, Hayashi H, Yokota M, Hirai M, Saito H. Diagnostic value of postexercise systolic blood pressure response for detecting coronary artery disease in patients with or without hypertension. Am Heart J 1993;125:718–25. [4] Mcham SA, Marwick TH, Pashkow FJ, Lauer MS. Delayed systolic blood pressure recovery after graded exercise. J Am Coll Cardiol 1999;34:754–9. [5] Yosefy C, Jafari J, Klainman E, Brodkin B, Handschumacher MD, Vaturi M. The prognostic value of post-exercise blood pressure reduction in patients with hypertensive response during exercise stress test. Int J Cardiol Oct 17 2005 [Electronic publication ahead of print]. [6] Miyahara T, Yokota M, Iwase M, et al. Mechanism of abnormal postexercise systolic blood pressure response and its diagnostic value in patients with coronary artery disease. Am Heart J 1990;120:40–9. [7] Rozanski A, Elkayam U, Berman DS, Diamond GA, Prause J, Swan HJ. Improvement of resting myocardial asynergy with cessation of upright bicycle exercise. Circulation 1983;67:529–35. [8] Hashimoto M, Okamoto M, Yamagata T, et al. Abnormal systolic blood pressure response during exercise recovery in patients with angina pectoris. J Am Coll Cardiol 1993;22:659–64. [9] Aldo Ferrara L, Palmieri V, Limauro S, et al. Association between postischemic forearm blood flow and blood pressure response to maximal exercise in well trained healthy young men. Int J Cardiol Oct 30 2005 [Electronic publication ahead of print].