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CLINICAL STUDY

C-reactive protein, clinical presentation, and ischemic activity in patients with chest pain and normal coronary angiograms

^* Coronary Artery Disease Research Unit, Department of Cardiological Sciences, St. George’s Hospital Medical School, London, United Kingdom

Manuscript received September 11, 2002; revised manuscript received November 12, 2002, accepted December 12, 2002.

^* Reprint requests and correspondence: Dr. Juan Carlos Kaski, Coronary Artery Disease Research Unit, Department of Cardiological Sciences, St. George’s Hospital Medical School, Cranmer Terrance, London SW17 0RE, United Kingdom.
jkaski{at}sghms.ac.uk

	Abstract

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OBJECTIVES: We sought to investigate the relationship among C-reactive protein (hs-CRP), clinical characteristics, exercise stress test responses, and ST-segment changes during daily life in patients with typical chest pain and normal coronary angiograms (CPNCA).

BACKGROUND: Patients with CPNCA have coronary microvascular endothelial dysfunction and myocardial ischemia. Elevated hs-CRP levels have been related to atherogenesis and endothelial dysfunction. The relationship between hs-CRP and disease activity has not been previously investigated in CPNCA patients.

METHODS: We studied 137 consecutive CPNCA patients (mean age, 57 ± 9; 33 men). All completed standardized angina questionnaires, underwent exercise stress testing, 24-h ambulatory electrocardiogram (ECG) monitoring (Holter), and hs-CRP measurements at study entry.

RESULTS: C-reactive protein levels (mg/l) were higher in patients with frequent (2.9 ± 3.3) and prolonged (3.9 ± 4.1) chest pain episodes, and in those with ST-segment depression on exercise testing (2.6 ± 2.8) and Holter monitoring (3.4 ± 3.1) compared with patients with occasional (1.3 ± 1.2; p = 0.002) or shorter chest pain (1.5 ± 1.3; p < 0.001) episodes, negative exercise stress testing (1.1 ± 1.1; p < 0.001), and no ST-segment shifts on Holter monitoring (0.9 ± 0.7; p < 0.001). Moreover, we found a correlation between hs-CRP concentration and number of ischemic episodes during Holter monitoring (r = 0.65; p < 0.001) and with the magnitude of ST-segment depression on exercise testing (r = –0.43; p < 0.001). The hs-CRP was the only independent variable (multivariate logistic regression) capable of predicting positive findings on Holter monitoring (odds ratio [OR], 3.8; confidence interval [CI], 2.3 to 6.2) and exercise testing (OR, 1.7; CI, 1.2 to 2.2).

CONCLUSIONS: The hs-CRP correlates with symptoms and ECG markers of myocardial ischemia in CPNCA patients. Whether hs-CRP is related to the pathogenesis of angina in these patients deserves further investigation.

Abbreviations and Acronyms   CI = confidence interval   CPNCA = chest pain and normal coronary arteriogram   CRP = C-reactive protein   ECG = electrocardiogram   ET-1 = endothelin-1   hs-CRP = high-sensitivity C-reactive protein   ICAM-1 = intercellular cell adhesion molecule-1   OR = odds ratio   VCAM-1 = vascular cell adhesion molecule-1

Coronary microcirculation abnormalities have been shown to play a pathogenic role in cardiac syndrome X. Endothelial cell activation (4,5) and coronary endothelial dysfunction (6,7) have been reported in patients with syndrome X. These may be associated with an increased release of constricting factors and the production of proinflammatory cytokines, cell adhesion molecules, and growth factors, which, in turn, can induce inflammatory and proliferative changes in the vessel wall and cause microvascular dysfunction (8). Recently, we reported higher intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) levels in patients with cardiac syndrome X, compared with healthy individuals (9). Cox et al. (10) reported a relationship between coronary vasomotor abnormalities during rapid atrial pacing and endothelin-1 (ET-1) concentrations in CPNCA patients. Thus, increased ET-1 levels may be associated with coronary microvascular endothelial dysfunction and contribute to reduced vasodilatory reserve in patients with CPNCA.

C-reactive protein (CRP), a marker of systemic inflammation, has been shown to be elevated in patients with angina and to correlate with impaired systemic endothelial vascular reactivity (11). It has been also suggested that CRP contributes to the development of endothelial dysfunction and atherogenesis (12).

We sought to investigate whether CRP levels correlate with markers of disease activity, such as chest pain occurrence and duration, ST-segment shifts on Holter monitoring during daily life, and a positive response to exercise stress testing in patients with CPNCA.

	Methods

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Patients.   We studied 164 consecutive patients who were referred to our CPNCA clinic from September 1996 to February 2002. All had typical anginal chest pain on effort and/or at rest, and completely normal coronary angiograms. As part of their clinical characterization, all patients underwent clinical and risk factor assessment, baseline 12-lead electrocardiogram (ECG), M-mode and two-dimensional echocardiography, and provocative testing for coronary artery spasm with hyperventilation or ergonovine.

Ten patients with left bundle branch block on the baseline ECG, two with dilated cardiomyopathy, six with coronary artery spasm, five with systemic inflammatory conditions, and one with prostatitis were excluded. In addition, three patients who returned an incomplete angina questionnaire were also excluded from study.

We, thus, enrolled 137 patients (mean age, 57 ± 9 years; 33 men), all of whom completed a standardized angina and cardiovascular risk factor questionnaire and also underwent exercise treadmill stress testing and 24-h continuous ECG Holter monitoring. Venous blood samples were taken at study entry and kept frozen at –80°C for measurement of serum high-sensitivity C-reactive protein (hs-CRP) concentration at a later time.

The study protocol was approved by the local research ethics committee, and all subjects signed informed written consent before study entry.

Angina and cardiovascular risk factor questionnaires.   Temporal onset of pain, number of anginal episodes per week, average duration of episodes, triggers of chest pain, association of chest pain with exertion, presence of chest pain at rest, and classical risk factors such hyperlipidemia, diabetes mellitus, hypertension, and current or past smoking were investigated.

Chest pain weekly occurrence was subsequently grouped in three categories: <2, 2 to 4, and 5 episodes per week. Average duration of individual anginal episodes was also grouped in three categories: < 5, 5 to 20, and >20 min. The circumstance of occurrence of angina was also noted, that is, exertional chest pain, pain at rest, and their combination.

24-h continuous ambulatory ECG monitoring.   Three-channel 24-h Holter monitors with amplitude-modulated recording (Marquette 8500, Marquette Electronics Inc., Milwaukee, Wisconsin) were used to record ST-segment changes during patients routine daily activities; ST-segment analyses (Marquette 8000 laser Holter, version 5) were performed after each recording was completely edited and artifacts removed. Ischemic episodes were defined as horizontal or downsloping ST-segment depression >1.0 mm (0.1 mV) measured at 0.08 s after the J-point and persisting for 1 min. Holter recordings were analyzed independently by two investigators who were blind to the patients’ clinical data.

Treadmill exercise stress testing.   All treadmill exercise tests were carried out in the morning between 9:00 AM and 10:30 AM after patients discontinued cardiac medications for at least 48 h. The Bruce protocol was used in all patients (CASE Marquette 12, Marquette Electronics, Milwaukee, Wisconsin). Three ECG leads (V₂ to V₅ and aVF) were continuously monitored during the test. A standard 12-lead ECG was printed and blood pressure measured (cuff sphygmomanometer) at baseline, at the end of each stage, at peak exercise, as well as at the onset of chest pain and/or significant ST-segment depression. Time to 1-mm ST-segment depression and total exercise time were recorded. Patients’ recovery was continuously monitored until the return of ST-segment to baseline levels, or for up to 6 min when tests were negative.

The exercise test was terminated when one or more of the following end points were reached: physical exhaustion, progressive severe angina, ST-segment depression 3 mm, dyspnea, and severe arrhythmias.

A test was considered "positive" when 1 mm ST-segment (horizontal or downsloping) at 0.08 s from the J-point was observed in two contiguous leads. In patients with positive test results, duration of exercise, heart rate-blood pressure product at 1 mm ST-segment depression and at peak exercise, and total ST-segment depression (mm) were measured. In patients with negative tests results, duration of exercise and rate pressure product were measured at peak exercise.

Crp assessment.   Fasting blood samples were collected in tubes containing citrate, and were drawn and centrifuged immediately. Serum was then aliquoted and stored at –80°C until analysis. No specimen inadvertently thawed during storage. C-reactive protein measurements were performed on the COBAS Integra (Roche Diagnosis Limited, East Sussex, United Kingdom) using the CRP-latex assay in both the high-sensitivity application (analytical range, 0.2 to 12 mg/l) and the normal application (analytical range, 2 to 160 mg/l). Analytical precision of the hs-CRP–latex assay was 7.6% at a level of 1.02 mg/l, 3.3% at 1.79 mg/l, and 1.3% at a level of 4.36 mg/l. Samples outside the analytical range of the hs-CRP–latex assay were analyzed by the CRP-latex assay in the normal application. The analytical precision of the normal CRP-latex assay was 2.4% at a level of 29.5 mg/l and 1.3% at a level of 113 mg/l.

Statistical analysis.   Baseline demographic and biochemistry analytical information is presented as mean ± SD for continuous variables and as absolute number (percentage) for categorical variables. Comparison of hs-CRP levels among patients with different chest pain duration, different number of weekly episodes, and different circumstances of occurrence of angina was carried out with one-way analysis of variance. When this analysis showed statistical significance, post-hoc Bonferroni test was applied to assess individual differences. To evaluate whether cardiovascular risk factors would alter these results, univariate analysis of variance was carried out. Comparison of hs-CRP levels among patients with positive or negative exercise stress test or Holter monitoring was carried out using the Student t test. To assess the relationship of the results of exercise stress testing and 24-h ECG monitoring with the severity of anginal symptoms, the chi-square test was applied. The Spearman rank correlation test was used to assess the relation between hs-CRP concentration and ST-segment depression in the 24-h Holter, the maximal ST-segment depression and the heart rate-blood pressure product at 1-mm ST-segment depression in the exercise stress test. Logistic regression analysis was carried out to assess independent predictors for positive (1 mm ST-segment depression) or negative (<1 mm ST-segment depression) exercise stress test and Holter results.

Traditional risk factors used in the multivariable analyses included smoking history, diabetes, diagnosis of hypertension, and cholesterol levels. Statistical analysis was performed using SPSS for Windows (version 10.0, SPSS Inc., Chicago, Illinois). All p values are two-tailed, and confidence intervals (CI) have been calculated at the 95% level.

	Results

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Baseline demographic characteristics, classical risk factors, and medical treatment at study entry are shown in Table 1. The characteristics of chest pain in all 137 patients are presented in Table 2. Episodes of chest pain were often prolonged (72% of patients had chest pain episodes 5 min). All patients had exertional chest pain, but 53% of them also had chest pain at rest. Rest chest pain was the predominant symptom in only 10% of patients. Regarding weekly occurrence of chest pain, 39% of patients had 5 chest pain episodes per week.

We did not find a relationship between exercise stress test or 24-h ECG Holter monitoring results and the number of chest pain episodes per week or the duration of chest pain episodes (Table 3).

Patients with prolonged angina episodes (>20 min) had significantly higher hs-CRP levels (3.9 ± 4.1 mg/l) than patients with moderate (5 to 20 min) duration of pain (1.5 ± 1.4 mg/l; p < 0.001) and those with short-lasting (<5 min) episodes (1.5 ± 1.3 mg/l; p < 0.001). Similarly, patients with a greater number of chest pain episodes (5 per week) had significantly higher levels of hs-CRP (2.9 ± 3.3 mg/l) than patients with two to four episodes (1.6 ± 1.7 mg/l; p = 0.015) and those with <2 episodes of chest pain (1.3 ± 1.2 mg/l; p = 0.004), as shown in Figure 1. These significant differences were maintained after adjustment for traditional risk factors; hs-CRP concentration was nonsignificantly (p = 0.6) higher in patients with both exertional and rest pain (2.2 ± 2.5 mg/l) compared with patients with exertional chest pain only (1.8 ± 2.5 mg/l) or those with predominantly rest chest pain (1.7 ± 1.7 mg/l).

View larger version (15K): [in this window] [in a new window]   Figure 1 Error bars graph showing high-sensitivity C-reactive protein (hs-CRP) concentrations (mean ± 2 SE) compared with number of chest pain episodes per week (A) and duration of chest pain episodes (B).

The number of ischemic episodes during the 24-h ECG Holter monitoring was significantly correlated with hs-CRP concentration (Spearman r = 0.65; p < 0.001). When analysis was limited to the 86 patients with a positive exercise stress test result, both ST-segment depression at peak exercise and rate pressure product at 1-mm ST-segment depression correlated significantly with hs-CRP levels (Spearman r = –0.43; p < 0.001 and Spearman r = –0.42; p < 0.001, respectively) (Fig. 2).

View larger version (17K): [in this window] [in a new window]   Figure 2 Spearman correlations among high-sensitivity C-reactive protein (hs-CRP) concentrations, number of episodes of ST-segment depression during 24-h electrocardiogram Holter monitoring (A), ST-segment depression during exercise stress testing (B), and rate-pressure product (RPP) at 1-mm ST-segment depression during exercise stress testing (C).

	Discussion

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The present study showed, for the first time, that CRP levels are higher in CPNCA patients who have increased clinical activity, that is, more frequent and prolonged chest pain episodes, positive exercise stress test responses, and ischemic episodes during 24-h Holter recordings, compared with those with a reduced number and a shorter duration of chest pain episodes, negative exercise test responses, and absence of ST-segment changes on Holter monitoring. Findings in this study confirm and expand recent preliminary observations (13) that syndrome X patients have higher baseline CRP levels than healthy subjects. In the present study, CRP serum concentration was the only independent variable able to predict both a positive result of exercise ECG stress testing and the presence of ST-segment shifts on Holter monitoring. Of importance, syndrome X patients with lower ischemic thresholds, as assessed by heart rate-blood pressure product levels at 1-mm ST-segment depression on exercise and those with a larger number of episodes of ST-segment depression on Holter monitoring, had significantly higher CRP levels compared with patients with higher ischemic thresholds.

C-reactive protein is a sensitive, albeit nonspecific, marker of inflammation that increases in response to acute injury, infection, and other inflammatory stimuli. It may be, therefore, speculated that CRP levels in our study were elevated merely due to the presence of chest pain. However, this is unlikely to be the case, as CRP levels were increased in patients with ST-segment changes and positive exercise ECG responses irrespective of the presence or absence of chest pain. Moreover, chest pain duration or severity did not correlate significantly with ECG changes in our patients, further suggesting high hs-CRP levels were not simply a nonspecific response to pain. The observed relationship between ECG ischemic changes and hs-CRP levels in this study together with findings in large epidemiological trials that high CRP levels were a risk factor for cardiovascular events in both apparently healthy individuals (14) and angina patients (15,16) suggests that inflammation may have a pathogenic role in cardiac syndrome X.

C-reactive protein plasma levels have been shown to correlate with endothelial dysfunction (11,12,17), and increased levels of ET-1 and other markers of endothelial activation (4,5) and dysfunction (18–20) have been previously reported in these patients.

Crp, endothelial dysfunction, and myocardial ischemia in syndrome X.   Yudkin et al. (17) showed in a cross-sectional study of healthy subjects that CRP concentrations were related to biochemical markers of endothelial dysfunction. Fichtlscherer et al. (11) reported that elevated CRP levels in patients with coronary artery disease were associated with a profound impairment of systemic endothelial vascular reactivity. More importantly, they also reported that normalization of CRP levels over time was associated with a significant improvement of endothelium-dependent flow responses. Further data endorsing a role of CRP in endothelial dysfunction were gathered by Pasceri et al. (12), who reported that CRP induced the expression of ICAM-1 and VCAM-1 in both umbilical vein and coronary artery endothelial cells. These findings suggest that CRP was not merely an inflammatory marker but also a potential cause of impaired endothelial function.

We have previously shown that plasma ET-1, a powerful microvascular vasoconstrictor agent, is raised in patients with syndrome X and that "high" plasma ET-1 levels were associated with an earlier onset of chest pain during exercise (4) and with a reduced coronary flow response during rapid atrial pacing (10). Recently, Desideri et al. (5) found that syndrome X patients had an increased responsiveness of ET-1 to glucose loading, suggesting that these patients were more susceptible to releasing ET under stressful circumstances.

The mechanisms responsible for myocardial ischemia in patients with CPNCA remain poorly understood, but increased vasoconstrictor and abnormal vasodilator responses, due to endothelial dysfunction, have been suggested as possible candidates (6,7). Reversible myocardial perfusion defects in areas supplied by arteries showing endothelial dysfunction, the production of transmyocardial lactate (21), lipid hydroperoxides and conjugated dienes (22) during atrial pacing, and a decrease of pH and oxygen saturation (23) in the coronary sinus of patients with syndrome X undergoing atrial pacing, indicate that myocardial ischemia may indeed be responsible for chest pain and ECG changes in these patients. More recently, using cardiac magnetic resonance, Buchthal et al. (3) and Panting et al. (2) have objectively shown the presence of myocardial ischemia in syndrome X patients.

Previous studies from our group showed the occurrence of increased ICAM-1 and VCAM-1 levels in syndrome X patients that were comparable to elevations in coronary artery disease patients and significantly larger than levels found in healthy individuals (9). Taken together, these findings and the results of the present study suggest that inflammatory mechanisms may be responsible, at least in part, for endothelial dysfunction and increased disease activity in patients with cardiac syndrome X.

Conclusions.   High-sensitivity C-reactive protein correlates with symptoms and ECG markers of myocardial ischemia in CPNCA patients. Whether hs-CRP is related to the pathogenesis of angina in these patients deserves further investigation.

	Footnotes

 
Dr. Cosín-Sales is the recipient of a research scholarship from the Spanish Society of Cardiology.

	References

Top Abstract Methods Results Discussion References

 

1. Kaski JC, Rosano GM, Collins P, Nihoyannopoulos P, Maseri A, Poole-Wilson PA. Cardiac syndrome Xclinical characteristics and left ventricular function: long-term follow-up study. J Am Coll Cardiol. 1995;25:807–814[Abstract]
2. Panting J, Gatehouse P, Yang GZ, et al. Abnormal subendocardial perfusion in cardiac syndrome X detected by cardiovascular magnetic resonance imaging. N Engl J Med. 2002;346:1948–1953[Abstract/Free Full Text]
3. Buchthal SD, den Hollander JA, Merz CN, et al. Abnormal myocardial phosphorus-31 nuclear magnetic resonance spectroscopy in women with chest pain but normal coronary angiograms. N Engl J Med. 2000;342:829–835[Abstract/Free Full Text]
4. Kaski JC, Elliott PM, Salomone O, et al. Concentration of circulating plasma endothelin in patients with angina and normal coronary angiograms. Br Heart J. 1995;74:620–624[Abstract/Free Full Text]
5. Desideri G, Gaspardone A, Gentile M, Santucci A, Gioffre PA, Ferri C. Endothelial activation in patients with cardiac syndrome X. Circulation. 2000;102:2359–2364[Abstract/Free Full Text]
6. Egashira K, Inou T, Hirooka Y, et al. Evidence of impaired endothelium-dependent coronary vasodilatation in patients with angina pectoris and normal coronary angiograms. N Engl J Med. 1993;328:1659–1664[Abstract/Free Full Text]
7. Quyyumi AA, Cannon RO, Panza JA, et al. Endothelial dysfunction in patients with chest pain and normal coronary arteries. Circulation. 1992;86:1864–1871[Abstract/Free Full Text]
8. Vane JR, Anggard EE, Botting RM. Regulatory functions of the vascular endothelium. N Engl J Med. 1990;323:27–36[Medline]
9. Tousoulis D, Davies GJ, Asimakopoulos G, et al. Vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 serum level in patients with chest pain and normal coronary arteries (syndrome X). Clin Cardiol. 2001;24:301–304[Medline]
10. Cox ID, Botker HE, Bagger JP, Sonne HS, Kristensen BO, Kaski JC. Elevated endothelin concentrations are associated with reduced coronary vasomotor responses in patients with chest pain and normal coronary arteriograms. J Am Coll Cardiol. 1999;34:455–460[Abstract/Free Full Text]
11. Fichtlscherer S, Rosenberger G, Walter DH, Breuer S, Dimmeler S, Zeiher AM. Elevated C-reactive protein levels and impaired endothelial vasoreactivity in patients with coronary artery disease. Circulation. 2000;102:1000–1006[Abstract/Free Full Text]
12. Pasceri V, Willerson JT, Yeh ET. Direct proinflammatory effect of C-reactive protein on human endothelial cells. Circulation. 2000;102:2165–2168[Abstract/Free Full Text]
13. Mollichelli N, Zouridakis E, Mwansa V, et al. Early atherosclerosis and raised markers of inflammation in patients with cardiac syndrome X. (abstr)Heart. 2002;87:54[Abstract/Free Full Text]
14. Tracy RP, Lemaitre RN, Psaty BM, et al. Relationship of C-reactive protein to risk of cardiovascular disease in the elderly: results from the Cardiovascular Health study and the Rural Health Promotion Project. Arterioscler Thromb Vasc Biol. 1997;17:1121–1127[Abstract/Free Full Text]
15. Liuzzo G, Biasucci LM, Gallimore JR, et al. The prognostic value of C-reactive protein and serum amyloid A protein in severe unstable angina. N Engl J Med. 1994;331:417–424[Abstract/Free Full Text]
16. Anzai T, Yoshikawa T, Shiraki H, et al. C-reactive protein as a predictor of infarct expansion and cardiac rupture after a first Q-wave acute myocardial infarction. Circulation. 1997;96:778–784[Abstract/Free Full Text]
17. Yudkin JS, Stehouwer CD, Emeis JJ, Coppack SW. C-reactive protein in healthy subjectsassociations with obesity, insulin resistance, and endothelial dysfunction: a potential role for cytokines originating from adipose tissue? Arterioscler Thromb Vasc Biol. 1999;19:972–978[Abstract/Free Full Text]
18. Bellamy MF, Goodfellow J, Tweddel AC, Dunstan FD, Lewis MJ, Henderson AH. Syndrome X and endothelial dysfunction. Cardiovasc Res. 1998;40:410–417[Abstract/Free Full Text]
19. Egashira K, Mohri M, Takeshita A. Endothelial dysfunction in cardiac syndrome X microvascular angina. Kaski JC. Chest Pain With Normal Coronary Angiograms. Norwell, MA: Kluwer; 1999. p. 91–99
20. Zeiher A, Krause T, Schechinger V, Minners J, Moser E. Impaired endothelium dependent vasodilatation of coronary resistance vessels is associated with exercise induced myocardial ischemia. Circulation. 1995;91:2345–2352[Abstract/Free Full Text]
21. Boudoulas H, Cobb TC, Leighton RF, Wilt SM. Myocardial lactate production in patients with angina-like chest pain and angiographically normal coronary arteries and left ventricle. Am J Cardiol. 1974;34:501–505[CrossRef][Medline]
22. Buffon A, Rigattieri S, Santini SA, et al. Myocardial ischemia-reperfusion damage after pacing-induced tachycardia in patients with cardiac syndrome X. Am J Physiol Heart Circ Physiol. 2000;279:H2627–2633[Abstract/Free Full Text]
23. Rosano GM, Kaski JC, Arie S, et al. Failure to demonstrate myocardial ischaemia in patients with angina and normal coronary arteries: evaluation by continuous coronary sinus pH monitoring and lactate metabolism. Eur Heart J. 1996;17:1175–1180[Abstract/Free Full Text]

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This Article Abstract Figures Only Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Cosín-Sales, J. Articles by Kaski, J. C. Search for Related Content PubMed PubMed Citation Articles by Cosín-Sales, J. Articles by Kaski, J. C.