N-terminal B-type Natriuretic Peptide Predicts Extent of Coronary Artery Disease and Ischemia in Patients With Stable Angina Pectoris

Michael Weber, MD; Thorsten Dill, MD; Roman Arnold, MD; Matthias Rau, MD; Okan Ekinci, MD; Klaus D. Müller, MD; Alexander Berkovitsch; Veselin Mitrovic, MD; Christian Hamm, MD

Disclosures

Am Heart J. 2004;148(4)

Abstract and Introduction

Background: B-type natriuretic peptide (BNP) and its N-terminal fragment (NT-proBNP) are elevated in patients with acute coronary syndromes and are closely linked to prognosis. Because there is only a small amount of data available concerning NT-proBNP in patients with stable angina pectoris, we aimed to determine whether NT-proBNP is of additional diagnostic value in these patients.
Methods and Results: Ninety-four patients with stable angina pectoris were prospectively included. All patients underwent exercise testing and coronary angiography, and 91 patients received thallium-201 single-photon emission computed tomography myocardial scintigraphy. NT-proBNP was analyzed at rest and after exercise testing. NT-proBNP was elevated in patients with inducible myocardial ischemia shown by single-photon emission computed tomography (396 ± 80 pg/mL vs 160 ± 101 pg/mL; P < .01) closely linked to the extent of coronary artery disease (CAD) (no CAD, 148 ± 29 pg/mL; 1- or 2-vessel disease, 269 ± 50 pg/mL; 3-vessel disease 624 ± 186 pg/mL; P < .01). In a multivariate analysis, NT-proBNP was an independent predictor for CAD. The area under the curve of the receiver operating characteristic curve was 0.72 for NT-proBNP to predict CAD. Using an optimized cut off level of 214 pg/mL, CAD can be predicted with high accuracy. The total test efficiency of exercise testing can be improved from 1.46 to 1.52 when combined with NT-proBNP measurement.
Conclusion: NT-proBNP is elevated in patients with stable angina pectoris and has a close correlation to disease severity. Combining the measurement of NT-proBNP with exercise testing, the test accuracy for predicting severe CAD can be improved. Our data show an incremental value of NT-proBNP in the diagnostic process of stable angina pectoris.

Coronary artery disease (CAD) is the most common cardiovascular disease and accounts for the majority of deaths in the Western world. Whereas the benefits of an early invasive approach are well established in patients with an acute coronary syndrome,^[1] in patients with stable angina pectoris the indication for coronary angiography and interventional or surgical revascularization is linked to clinical symptoms and to the verification of inducible myocardial ischemia by exercise testing or imaging techniques.^[2,3] Imaging techniques such as thallium myocardial scintigraphy or stress echocardiography have proven to be highly sensitive and specific, but they are expensive and not generally available. In contrast, exercise testing is commonly available and cost-effective, but sensitivity and specificity are much lower. Since the presence of myocardial ischemia in addition to clinical symptoms is the fundamental component in the process of clinical decision making in patients with stable angina pectoris, the implementation of an additional, cost-effective, and generally available parameter would be desirable.

B-type natriuretic peptide (BNP) and its N-terminal fragment (NT-proBNP) are neurohormones synthesized and secreted from the ventricular myocardium. Stimulus for their release is an increase in left ventricular wall stress.^[4] These markers are known to be elevated in patients with acute coronary syndromes (ST-elevation myocardial infarction and non-ST-elevation myocardial infarction) and are closely linked to the prognosis.^[5,6] An increase in BNP immediately after transient myocardial ischemia during percutaneous transluminal coronary angioplasty has been shown in a smaller study.^[7] To date the only available data on BNP or NT-proBNP in patients with stable angina pectoris originates from a recently published study by Bibbins-Domingo et al. They showed that BNP was elevated in 112 patients with inducible myocardial ischemia assessed by stress echocardiography as compared to individuals without inducible ischemia. But no angiographic data was obtained in that study.^[8]

The aim of the present study is to determine whether NT-proBNP is of additional diagnostic value in patients with stable angina pectoris. Therefore, we investigated whether NT-proBNP is elevated in patients with stable angina pectoris in correlation with angiographic findings and inducible myocardial ischemia detected by exercise testing or by thallium myocardial scintigraphy and whether NT-proBNP increases after transient myocardial ischemia during exercise testing.

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Abstract and Introduction
Methods
Results
Discussion
Conclusions
References

Table 1. Baseline Characteristics
	No CAD	1/2 VD	3 VD	Total	P
No. (%)	36 (38%)	39 (41%)	19 (20%)	94
Sex (male/female)	23/13	31/8	17/2	71/23	.08
Age (y)	60.3 ± 7.6	62.6 ± 7.8	65.5 ± 11.7	62.3 ± 8.7	.10
BMI (kg/m²)	28.7 ± 3.5	28.1 ± 3.5	27.3 ± 3.1	28.2 ± 3.4	.34
Creatinine (mmol/L)	73.4 ± 15.9	82.2 ± 20.3	81.3 ± 14.1	78.7 ± 17.7	.59
LVMI (g/m²)	86.1 ± 30.3	98.8 ± 24.7	98.4 ± 22.3	93.1 ± 27.3	.16
Ejection fraction (%)	57.9 ± 4.8	58.3 ± 5.1	56.8 ± 5.1	57.9 ± 5.0	.58
LVEDP (mm Hg)	14.7 ± 6.0	14.2 ± 3.5	15.8 ± 4.9	14.7 ± 4.9	.54
Cardiovascular risk factors
Diabetes mellitus, n (%)	4 (11%)	7 (18%)	3 (16%)	14 (15%)	.70
Hyperlipidemia, n (%)	23 (64%)	30 (77%)	14 (74%)	67 (71%)	.46
Hypertension, n (%)	30 (83%)	30 (77%)	16 (84%)	76 (81%)	.72
Smoker, n (%)	8 (22%)	13 (33%)	4 (21%)	25 (27%)	.46
History
Myocardial infarction, n (%)	5 (14%)	10 (26%)	4 (21%)	19 (20%)	.45
PCI, n (%)	9 (25%)	12 (31%)	2 (11%)	23 (24%)	.24
Medical pretreatment
Beta-blocker, n (%)	23 (64%)	22 (56%)	13 (68%)	58 (62%)	.64
Nitrate, n (%)	6 (16%)	11 (28%)	12 (63%)	29 (31%)	<.01
ACE/AT antagonist, n (%)	18 (50%)	22 (56%)	6 (32%)	46 (49%)	.20
Statin, n (%)	14 (39%)	20 (51%)	7 (37%)	41 (44%)	.45

ACE/AT antagonist, Angiotensin-converting enzyme inhibitor or angiotensin-receptor antagonist; PCI, percutaneous coronary intervention.

Table 1. Baseline Characteristics
	No CAD	1/2 VD	3 VD	Total	P
No. (%)	36 (38%)	39 (41%)	19 (20%)	94
Sex (male/female)	23/13	31/8	17/2	71/23	.08
Age (y)	60.3 ± 7.6	62.6 ± 7.8	65.5 ± 11.7	62.3 ± 8.7	.10
BMI (kg/m²)	28.7 ± 3.5	28.1 ± 3.5	27.3 ± 3.1	28.2 ± 3.4	.34
Creatinine (mmol/L)	73.4 ± 15.9	82.2 ± 20.3	81.3 ± 14.1	78.7 ± 17.7	.59
LVMI (g/m²)	86.1 ± 30.3	98.8 ± 24.7	98.4 ± 22.3	93.1 ± 27.3	.16
Ejection fraction (%)	57.9 ± 4.8	58.3 ± 5.1	56.8 ± 5.1	57.9 ± 5.0	.58
LVEDP (mm Hg)	14.7 ± 6.0	14.2 ± 3.5	15.8 ± 4.9	14.7 ± 4.9	.54
Cardiovascular risk factors
Diabetes mellitus, n (%)	4 (11%)	7 (18%)	3 (16%)	14 (15%)	.70
Hyperlipidemia, n (%)	23 (64%)	30 (77%)	14 (74%)	67 (71%)	.46
Hypertension, n (%)	30 (83%)	30 (77%)	16 (84%)	76 (81%)	.72
Smoker, n (%)	8 (22%)	13 (33%)	4 (21%)	25 (27%)	.46
History
Myocardial infarction, n (%)	5 (14%)	10 (26%)	4 (21%)	19 (20%)	.45
PCI, n (%)	9 (25%)	12 (31%)	2 (11%)	23 (24%)	.24
Medical pretreatment
Beta-blocker, n (%)	23 (64%)	22 (56%)	13 (68%)	58 (62%)	.64
Nitrate, n (%)	6 (16%)	11 (28%)	12 (63%)	29 (31%)	<.01
ACE/AT antagonist, n (%)	18 (50%)	22 (56%)	6 (32%)	46 (49%)	.20
Statin, n (%)	14 (39%)	20 (51%)	7 (37%)	41 (44%)	.45

ACE/AT antagonist, Angiotensin-converting enzyme inhibitor or angiotensin-receptor antagonist; PCI, percutaneous coronary intervention.

Table 2. Association Between Clinical Characteristics and NT-proBNP
	NT-proBNP (pg/mL)	P
Male/female	310 ± 60 vs 247 ± 56	.83
Age <63 y/≥63 y (median)	292 ± 86 vs 296 ± 47	.14
Diabetes mellitus/no diabetes mellitus	237 ± 34 vs 622 ± 238	.01
History of AMI/no history of AMI	235 ± 35 vs 530 ± 181	.03
History of PCI/no history of PCI	297 ± 57 vs 286 ± 82	.82
CAD/no CAD	386 ± 72 vs 148 ± 29	<.01
Thallium scan positive/negative	396 ± 80 vs 160 ± 27	<.01
Exercise test positive/negative	312 ± 60 vs 281 ± 69	.15

Table 3. Test Performance for the Prediction of CAD
	Sensitivity (%)	Specificity (%)	NPV (%)	PPV (%)	Test efficiency	Likelihood ratio	P
Exercise test	60	86	57	88	1.46	22.7	<.01
Thallium scintigraphy	80	78	72	85	1.58	31.1	<.01
NT-proBNP (cutoff 214 pg/ml)	55	83	54	84	1.38	14.6	<.01
Exercise test + thallium scintigraphy	90	64	79	80	1.54	34.1	<.01
Exercise test + NT-proBNP	83	69	71	81	1.52	26.5	<.01
Thallium scintigraphy + NT-proBNP	82	69	71	80	1.51	24.8	<.01

Table 2. Association Between Clinical Characteristics and NT-proBNP
	NT-proBNP (pg/mL)	P
Male/female	310 ± 60 vs 247 ± 56	.83
Age <63 y/≥63 y (median)	292 ± 86 vs 296 ± 47	.14
Diabetes mellitus/no diabetes mellitus	237 ± 34 vs 622 ± 238	.01
History of AMI/no history of AMI	235 ± 35 vs 530 ± 181	.03
History of PCI/no history of PCI	297 ± 57 vs 286 ± 82	.82
CAD/no CAD	386 ± 72 vs 148 ± 29	<.01
Thallium scan positive/negative	396 ± 80 vs 160 ± 27	<.01
Exercise test positive/negative	312 ± 60 vs 281 ± 69	.15

Table 3. Test Performance for the Prediction of CAD
	Sensitivity (%)	Specificity (%)	NPV (%)	PPV (%)	Test efficiency	Likelihood ratio	P
Exercise test	60	86	57	88	1.46	22.7	<.01
Thallium scintigraphy	80	78	72	85	1.58	31.1	<.01
NT-proBNP (cutoff 214 pg/ml)	55	83	54	84	1.38	14.6	<.01
Exercise test + thallium scintigraphy	90	64	79	80	1.54	34.1	<.01
Exercise test + NT-proBNP	83	69	71	81	1.52	26.5	<.01
Thallium scintigraphy + NT-proBNP	82	69	71	80	1.51	24.8	<.01

Table 2. Association Between Clinical Characteristics and NT-proBNP
	NT-proBNP (pg/mL)	P
Male/female	310 ± 60 vs 247 ± 56	.83
Age <63 y/≥63 y (median)	292 ± 86 vs 296 ± 47	.14
Diabetes mellitus/no diabetes mellitus	237 ± 34 vs 622 ± 238	.01
History of AMI/no history of AMI	235 ± 35 vs 530 ± 181	.03
History of PCI/no history of PCI	297 ± 57 vs 286 ± 82	.82
CAD/no CAD	386 ± 72 vs 148 ± 29	<.01
Thallium scan positive/negative	396 ± 80 vs 160 ± 27	<.01
Exercise test positive/negative	312 ± 60 vs 281 ± 69	.15

Table 3. Test Performance for the Prediction of CAD
	Sensitivity (%)	Specificity (%)	NPV (%)	PPV (%)	Test efficiency	Likelihood ratio	P
Exercise test	60	86	57	88	1.46	22.7	<.01
Thallium scintigraphy	80	78	72	85	1.58	31.1	<.01
NT-proBNP (cutoff 214 pg/ml)	55	83	54	84	1.38	14.6	<.01
Exercise test + thallium scintigraphy	90	64	79	80	1.54	34.1	<.01
Exercise test + NT-proBNP	83	69	71	81	1.52	26.5	<.01
Thallium scintigraphy + NT-proBNP	82	69	71	80	1.51	24.8	<.01

Table 2. Association Between Clinical Characteristics and NT-proBNP
	NT-proBNP (pg/mL)	P
Male/female	310 ± 60 vs 247 ± 56	.83
Age <63 y/≥63 y (median)	292 ± 86 vs 296 ± 47	.14
Diabetes mellitus/no diabetes mellitus	237 ± 34 vs 622 ± 238	.01
History of AMI/no history of AMI	235 ± 35 vs 530 ± 181	.03
History of PCI/no history of PCI	297 ± 57 vs 286 ± 82	.82
CAD/no CAD	386 ± 72 vs 148 ± 29	<.01
Thallium scan positive/negative	396 ± 80 vs 160 ± 27	<.01
Exercise test positive/negative	312 ± 60 vs 281 ± 69	.15

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N-terminal B-type Natriuretic Peptide Predicts Extent of Coronary Artery Disease and Ischemia in Patients With Stable Angina Pectoris

Abstract and Introduction

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References

Authors and Disclosures

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