Diagnostic coronary angiography induces a systemic inflammatory response in patients with stable angina

doi:10.1016/S0002-8703(03)00407-1

American Heart Journal

Volume 146, Issue 5, November 2003, Pages 819-823

https://doi.org/10.1016/S0002-8703(03)00407-1 Get rights and content

Abstract

Background

Systemic markers of inflammation increase after percutaneous coronary intervention (PCI). The rise in inflammatory markers after PCI is frequently attributed to the inflammatory stimulus associated with coronary artery injury during balloon inflation and coronary stent implantation. The aim of this study was the determine whether diagnostic coronary angiography performed in patients with stable angina triggers a systemic inflammatory response.

Methods

We prospectively studied patients with chronic stable angina undergoing either coronary angiography (n = 13) or coronary angiography followed by PCI (n = 13). Peripheral blood samples were obtained before and 24 hours, 48 hours, and 4 weeks after the procedure and analyzed for C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). Patients with periprocedural myocardial necrosis were excluded.

Results

There was a significant increase in CRP levels at 24 and 48 hours in both the coronary angiography (P <.05) and PCI (P <.01) groups. IL-6 levels peaked at 24 hours in both the coronary angiography (median, 2.5–9.5 pg/mL; P = .01) and PCI (median, 3.0–8.2 pg/mL; P <.005) groups. At 4 weeks, both CRP and IL-6 returned to baseline levels. TNF-α levels were unchanged with either coronary angiography or PCI. The magnitude of the rise of CRP and IL-6 levels was not significantly different between the groups. There was a fair correlation between baseline and peak postprocedural levels of CRP (r = 0.67, P = .008) and IL-6 (r = 0.48, P = .016).

Conclusion

Uncomplicated diagnostic coronary angiography triggers a systemic inflammatory response in patients with stable angina. The contribution of coronary angiography should be considered in interpreting the significance of the systemic inflammatory response observed after PCI.

Section snippets

Patients

We prospectively studied patients with chronic stable angina who were referred to our institute for coronary angiography. Exclusion criteria included: 1) known inflammatory, neoplastic, or infectious disease; 2) treatment with steroids, immunosuppressive drugs, or non-steroidal anti-inflammatory drugs, with the exception of low-dose aspirin; 3) myocardial infarction or unstable angina pectoris within the previous month; 4) coronary angiography with or without PCI within the previous month; and

Results

A total of 34 patients with chronic stable angina who were admitted for elective cardiac catheterization were enrolled. In 21 patients (62%), the diagnostic angiography was immediately followed by an interventional procedure. In the PCI group, 8 patients were excluded from subsequent analysis because of IIb/IIIa inhibitors use (n = 6), postprocedural CK-MB and troponin T level elevations (n = 1), and groin hematoma (n = 1). The baseline clinical characteristics of the remaining 26 patients are

Discussion

This study shows that uncomplicated coronary angiography is sufficient to induce a substantial systemic inflammatory response, as evidenced by the elevation of plasma CRP levels and its chief stimulator, interleukin-6. Furthermore, the magnitude of the inflammatory response after diagnostic coronary angiography appears to be close to that induced by PCI. To the best of our knowledge, this study is the first to provide evidence that diagnostic coronary angiography, without any coronary artery

Conclusion

Uncomplicated diagnostic coronary angiography triggers a systemic inflammatory response in patients with stable angina. The magnitude of the inflammatory response after coronary angiography is close to that induced by PCI, suggesting that the inflammatory response to PCI is primarily caused by the diagnostic, rather than the interventional, procedure. The contribution of coronary angiography should be considered in interpreting the significance of the systemic inflammatory response observed

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The prevention of contrast-induced nephropathy by simultaneous hemofiltration during coronary angiographic procedures: A comparison with periprocedural hemofiltration
2014, International Journal of Cardiology
Citation Excerpt :
Accordingly, simultaneous hemofiltration could exert a beneficial effect, especially on hemodynamically unstable patients undergoing coronary interventions. Third, acute coronary syndrome is, in part, an acute inflammatory disorder, and coronary angiography or the stenting procedure itself is known to trigger a systemic inflammatory response [16–18]. Hemofiltration has been used to modulate inflammatory mediators in acute kidney injury and sepsis [14,19].
Periprocedural (6 h pre- and 24 h post-angiography) hemofiltration appears to effectively prevent contrast-induced nephropathy (CIN) in chronic kidney disease (CKD) patients undergoing coronary angiography. However, this procedure over-uses medical resources, and the cessation of hemofiltration during coronary angiography results in persistent renal injury. In comparison, simultaneous hemofiltration performed only during coronary angiography requires fewer medical resources and can provide instantaneous protection against CIN.
Sixty-eight CKD patients (serum creatinine, 2.51 ± 1.15 mg/dL) undergoing coronary angiography were randomized in a 1:2 ratio to receive either periprocedural (n = 23) or simultaneous (n = 45) hemofiltration. The expected CIN rate was similar for the two groups (41.3% versus 40.0%, p = 0.769).
On day 3 after contrast exposure, four and seven patients in the periprocedural and simultaneous groups, respectively experienced CIN (17.4% versus 15.6%, p = 0.846). On days 5–30, seven and three patients in the periprocedural and simultaneous groups, respectively experienced CIN (30.4% versus 6.7%, p = 0.009). The serum creatinine levels of patients in the periprocedural group transiently decreased on day 1 and persistently increased during days 5–30 compared with the simultaneous group. This difference between the two groups in terms of creatinine levels over time was statistically significant (F statistic = 6.830; p = 0.001, by ANCOVA). The cost of hemofiltration was doubled in the periprocedural group ($1066 ± 83 versus $504 ± 40, p < 0.001).
Simultaneous hemofiltration provide equal early (day 3) and better late-stage (days 5–30) renal protection against CIN at a significantly lower cost compared with periprocedural hemofiltration.
Eosinophil count predicts mortality following percutaneous coronary intervention
2012, Thrombosis Research
Citation Excerpt :
An emerging role for eosinophils is regulation of the inflammatory response. PCI has consistently been shown to produce a significant inflammatory response resulting in the elevation of post-procedural IL-6 and CRP [23,24]. Regulation of the inflammatory response may be protective by limiting additional myocardial tissue injury following PCI.
Several inflammatory markers have been shown to be independent predictors for both the development of clinically significant atherosclerosis and for adverse outcome in patients with symptomatic coronary artery disease (CAD). We investigated the prognostic role of eosinophil count in low to intermediate risk patients with CAD.
We studied 909 patients admitted for elective or urgent percutaneous coronary intervention (PCI) from April 2002 to December 2004, and measured pre-procedural total and differential white blood cell (WBC) counts. Inter-tertile WBC differences in short (6 months) and long term (up to 74 months) mortality were analysed after adjusting for differences in baseline characteristics.
Over a median period of 54 months (inter-quartile range 47–65), a total of 138 deaths (15.2%) occurred, of which 24 were in the first 6 months of follow-up. Cox regression analysis showed that high pre-procedural eosinophil count (top tertile) was associated with improved outcome within the first 6 months (OR = 0.23 [0.06–0.84]; p = 0.03) but after this period there was an increased risk of mortality (OR = 2.21, [1.26–3.88]; p = 0.006).
Eosinophil count is a novel biomarker for risk stratification of CAD patients, which was associated initially with reduced mortality, but after 6 months with increased mortality.
Inhibition of sPLA <inf>2</inf> and Endothelial Function: A Substudy of the SPIDER-PCI Trial
2012, Canadian Journal of Cardiology
Inflammation plays an important role in the pathophysiology of atherosclerosis and endothelial dysfunction, and occurs after percutaneous coronary intervention (PCI). We evaluated whether endothelial function is attenuated after PCI and if inhibition of secretory phospholipase A₂ (sPLA₂) activity augments endothelial function and coronary flow reserve (CFR) in these patients.
In the sPLA₂ Inhibition to Decrease Enzyme Release After Percutaneous Coronary Intervention (SPIDER-PCI) study, patients undergoing elective PCI were randomized to receive Varespladib (Anthera Pharmaceuticals Inc, San Mateo, CA), an inhibitor of sPLA₂, or placebo 3-5 days prior to PCI and for 5 days after PCI. In this substudy, endothelial function was assessed in 31 patients by flow-mediated dilation (FMD) before treatment and on the day after PCI, while taking study medication. During the PCI procedure, CFR was assessed using a Doppler guide wire.
Baseline and procedural characteristics were comparable in both groups and sPLA2 activity was similar at baseline. After PCI, sPLA₂ activity decreased only in the Varespladib group (2.9 ± 0.9 to 0.5 ± 0.4 ng/mL), and high-sensitivity C-reactive protein (hsCRP) increased by more than 100% in both groups. FMD at baseline was 3.66 ± 2.45% (Varespladib) and 3.37 ± 1.73% (placebo) with nonsignificant increase in both groups after PCI. The effect of Varespladib on FMD, adjusted for pre-PCI FMD by linear regression, was −1.16 ± 1.68%; P = 0.5. CFR was 2.45 ± 0.66 and 2.77 ± 0.85 in the Varespladib and placebo groups, respectively (P = 0.36).
Systemic endothelial function is not reduced after elective PCI despite eliciting acute inflammatory response. Acute inhibition of sPLA₂ activity with Varespladib does not affect endothelial or microvascular function after PCI.
L'inflammation joue un rôle important dans la pathophysiologie de l'athérosclérose et du dysfonctionnement endothélial, et survient après l'intervention coronarienne percutanée (ICP). Nous avons évalué si le fonctionnement endothélial était atténué après l'ICP et si l'inhibition de l'activité de la phospholipase sécrétoire A₂ (sPLA₂) augmentait le fonctionnement endothélial et la réserve coronarienne (RC) chez ces patients.
Dans l'étude sPLA₂ Inhibition to Decrease Enzyme Release after Percutaneous Coronary Intervention (SPIDER-PCI), les patients devant subir une ICP élective ont été choisis au hasard pour recevoir le varespladib (Anthera Pharmaceuticals, Inc., San Mateo, CA), un inhibiteur de la sPLA_2, ou un placebo de 3 à 5 jours avant l'ICP et 5 jours après l'ICP. Dans cette sous-étude, le fonctionnement endothélial a été évalué chez 31 patients par la dilatation induite par le flux (DIF) avant le traitement et le jour suivant l'ICP, tout en prenant le médicament de l'étude. Durant l'ICP, la RC a été évaluée en utilisant un fil-guide Doppler.
Les caractéristiques initiales et procédurales ont été comparables dans les deux groupes, et l'activité de la sPLA₂ a été similaire au début. Après l'ICP, l'activité de la sPLA₂ a diminué seulement dans le groupe prenant le varespladib (2,9 ± 0,9 à 0,5 ± 0,4 ng/ml) et la protéine C-réactive à haute sensibilité (hsCRP : high-sensitivity C-reactive protein) a augmenté à plus de 100 % dans les deux groupes. La DIF initiale a été de 3,66 ± 2,45 % (varespladib) et de 3,37 ± 1,73 % (placebo) avec une augmentation non significative dans les deux groupes après l'ICP. L'effet du varespladib sur la DIF, ajusté par la régression linéaire pour une DIF pré-ICP, a été de −1,16 ± 1,68 %; P = 0,5. La RC a été de 2,45 ± 0,66 et de 2,77 ± 0,85 dans les groupes prenant le varespladib et le placebo, respectivement (P = 0,36).
Le fonctionnement endothélial systémique n'est pas réduit après l'ICP élective malgré la réponse inflammatoire aiguë obtenue. L'inhibition aiguë de l'activité de la sPLA₂ avec l'administration du varespladib ne nuit pas au fonctionnement endothélial ou microvasculaire après l'ICP.
The double-faced metabolic and inflammatory effects of standard drug therapy in patients after percutaneous treatment with drug-eluting stent
2011, Atherosclerosis
Citation Excerpt :
The major shortcoming of this study is the limited external validity to other stents, such as bare metal stent (BMS), Taxus DES, or other new DES. Although it has been reported that CRP and IL-6 levels rose to peak after BMS implanted 48 h and returned to baseline levels at 4 weeks [27], and similar local artery inflammation and unendothelializion were also observed in Taxus DES [3,28], these indirect evidences cannot be used to prove the advantage of different type of stents. Recently, the efficacy and safety has been directly compared between two types of DES [29], suggesting that comparative studies are needed to further address the differential proinflammatory responses among stent types.
The inflammatory responses after percutaneous coronary intervention (PCI) with drug-eluting stent (DES) remain poorly understood; therefore, this study aims to investigate the changes of metabolic parameters and systematic inflammatory status of circulating mononuclear cells (MNC) in patients after percutaneous treatment with DES implantation.
Twenty-seven patients with acute coronary syndrome who would undergo PCI with DES implantation were consecutively recruited and treated with standard drug therapy from the start of hospitalization. Metabolic parameters including total cholesterol, triglycerides, high-density lipoprotein, low-density lipoprotein improved significantly after 12 weeks of standard medication, whereas the plasma levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), macrophage migration inhibitory factor (MIF), and matrix metalloproteinase-9 (MMP-9) increased (P = 0.012, 0.035, 0.062 and 0.112, respectively, compared to the baseline). The NF-κB DNA binding activity in MNC increased significantly compared to the baseline (P = 0.015), whereas IκB-β and PPAR-γ were significantly suppressed (P = 0.046 and 0.002, respectively). There were strong correlations among the changes of metabolic parameters and the changes of proinflammatory factors; however, none of them is statistically significant.
Standard drug therapy can improve the metabolic parameters but fail to restrain the proinflammatory state after PCI with DES implantation. Longer term endpoint-based studies are still needed for further exploration of the relationship between inflammatory factors and clinical cardiovascular events in the era of DES.
Diagnostic coronary angiography is related to decreased TNF-α production after ex-vivo whole blood stimulation with LPS
2010, Cytokine
Background: Several studies showed serum markers elevation as a result to coronary angiography. We investigated the effect of diagnostic coronary angiography (DCA) on the development of systemic inflammatory response syndrome (SIRS) and on whole blood cytokine production capacity after ex-vivo LPS stimulation. Methods: In this observational study, clinical characteristics and serum cytokines of the patients were recorded at baseline and at 2, 6, 12, and 24 h after DCA. Peripheral blood was collected at baseline and at 2, and 24 h for complete blood count, coagulation profile and ex-vivo (100 μl) stimulation with LPS (500 pg) for subsequent cytokine measurement. Values are expressed as median ± IQR and were compared using Wilcoxon’s signed rank test with Bonferroni adjustment. Results: We included 23 male patients (mean age 52.0 ± 18.0 years) undergoing DCA. None of the patients developed clinical or laboratory signs of SIRS. Serum IL-6 significantly increased at 12 h. There was a significant decrease in TNF-α production after ex-vivo LPS stimulation of whole blood at 2 and 24 h compared to baseline (median ± IQR; 716.0 ± 319.0; 576.0 ± 715.0 vs. 1154 ± 844.0 pg/ml; respectively) suggesting that DCA may cause transient endotoxin tolerance. Conclusions: DCA is related to increased serum IL-6 levels but does not cause clinical SIRS. Development of SIRS after DCA is indicative of other in origin complication. DCA is associated with immune cells hyporesponsiveness, possibly through monocyte depression, expressed as decreased TNF-α production after whole blood stimulation with LPS ex vivo.
Co-release of cytokines after drug-eluting stent implantation in acute myocardial infarction patients with PCI
2024, Scientific Reports

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Clinical investigationDiagnostic coronary angiography induces a systemic inflammatory response in patients with stable angina

Abstract

Background

Methods

Results

Conclusion

Section snippets

Patients

Results

Discussion

Conclusion

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FEBS Lett

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Abciximab suppresses the rise in levels of circulating inflammatory markers after percutaneous coronary revascularization

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Enhanced inflammatory response to coronary angioplasty in patients with severe unstable angina

Circulation

Plasma levels of C-reactive protein after coronary stent implantation

Eur Heart J

Pathology of acute and chronic coronary stenting in humans

Circulation

Clinical investigation
Diagnostic coronary angiography induces a systemic inflammatory response in patients with stable angina