Inflammatory Markers, Angiographic Severity of Coronary Artery Disease, and Patient Outcome

doi:10.1016/j.amjcard.2006.11.032

The American Journal of Cardiology

Volume 99, Issue 7, 1 April 2007, Pages 879-884

https://doi.org/10.1016/j.amjcard.2006.11.032 Get rights and content

Serum levels of high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) have been shown to be predictors of adverse outcomes in patients with coronary artery disease (CAD). We hypothesized that measurement of inflammatory markers could predict atherosclerotic burden and major adverse cardiac events (MACEs). We prospectively measured hs-CRP, IL-6, and TNF-α in 249 patients who were admitted with acute chest pain and underwent coronary angiography. We analyzed the relation between serum levels of inflammatory markers and angiographic severity of CAD. A follow-up at 6 months was conducted to assess MACEs, defined as a cumulative of myocardial infarction, all-cause death, or coronary revascularization (percutaneous coronary intervention or coronary artery bypass surgery). After adjusting for conventional CAD risk factors (age, gender, diabetes, hypertension, smoking, and hypercholesterolemia), there was no association between inflammatory markers (hs-CRP, IL-6, and TNF-α) and angiographic severity of CAD. There was a significant positive correlation between age, male gender, diabetes mellitus, and hypercholesterolemia with atherosclerotic burden determined by angiography. There was no significant positive association between MACEs and hs-CRP, IL-6, or TNF-α level in unadjusted and adjusted models. In conclusion, in patients hospitalized with chest pain, we found no association of serum levels of hs-CRP, IL-6, or TNF-α with coronary atherosclerotic burden or MACEs at 6 months after adjustment for traditional CAD risk factors.

Section snippets

Methods

This prospective study consisted of a series of consecutive patients (men and women, ≥21 years of age) who had a diagnosis of acute chest pain suspected to be of cardiac cause and were admitted to a coronary care unit. We included patients with or without known CAD but excluded those with ST-elevation myocardial infarction. Patients were enrolled in the study within the first 24 hours of admission and evaluated during the index admission, at 6 weeks (±2 weeks) from enrollment, and again at 6

Results

All 249 patients underwent coronary angiography after admission for chest pain. The inflammatory markers hs-CRP, IL-6, and TNF-α were measured in all patients within 24 hours of admission. Patients were categorized into tertiles according to hs-CRP values <1.00, 1 to 2.99, and ≥3.00 mg/L. Patients were also categorized into 2 groups based on median values of IL-6 (<4.7 and ≥4.7 pg/ml) and TNF-α (<6.2 and ≥6.2 pg/ml).

Patient demographics, baseline characteristics, and conventional risk factors

Discussion

We embarked on this prospective study to establish a relation of inflammatory markers with angiographically documented coronary atherosclerosis. Because IL-6 and TNF-α induce CRP synthesis,¹³ we measured IL-6 and TNF-α levels in addition to hs-CRP levels in serum. We did an extensive, careful analysis of coronary angiograms and quantitation of atherosclerotic burden. Although hs-CRP and IL-6 were associated with some parameters of atherosclerotic burden in the unadjusted model, this association

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Identification of depression in patients with acute coronary syndrome using multiple serum biomarkers
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Biomarkers for depression in patients with acute coronary syndrome (ACS) have not been identified.
This study evaluated multiple serum biomarkers for depressive disorders after ACS. Thirteen serum biomarkers associated with seven functional systems, along with sociodemographic/clinical characteristics, were evaluated in 969 patients within 2 weeks after ACS onset (acute phase). In total, 711 patients were evaluated for depressive disorder using DSM-IV criteria 1 year later (chronic phase). Logistic regression was used for the analysis.
Depressive disorders were observed in 378 patients (39.0%) in the acute phase of ACS and 183 patients (25.7%) in the chronic phase. The weighted scores of five serum biomarkers (high-sensitivity C-reactive protein, interleukin-6, homocysteine, troponin I, and creatine kinase-MB) were significantly associated with depressive disorder diagnosis in the acute phase, and the weighted scores of three other biomarkers (tumor necrosis factor-alpha, interleukin-1 beta, and homocysteine) were significantly associated with depressive disorders in the chronic phase, in a dose-dependent manner after adjusting for relevant covariates (all P-values <0.001).
The combination of several serum biomarkers exhibited robust associations with depressive disorders in both the acute and chronic phases of ACS.
The utility of inflammation and platelet biomarkers in patients with acute coronary syndromes
2018, Saudi Journal of Biological Sciences
Citation Excerpt :
Moreover, which should be emphasized, this is the first study assessing the activity of β-TG in STEMI, NSTEMI, and UA subjects. Studies revealed that patients with CAD have increased concentrations of proinflammatory biomarkers, such as TNF-α, CRP, and IL-6 (Lindahl et al., 2000; Sukhija et al., 2007; Williams et al., 2014; Zhang et al., 2007). Our study also showed statistically significant elevation in chosen inflammation biomarkers (WBC, CRP, IL-6) in the whole group of ACS patients in comparison to controls.
Thrombotic and inflammatory mechanisms are involved in the pathophysiology of acute coronary syndrome (ACS). The aim of the study was the evaluation of inflammation (white blood cells count/WBC, C-reactive protein/CRP, interleukin-6/IL-6) and platelet (platelet count/PLT, mean platelet volume/MPV, large platelet/LPLT, beta-thromboglobulin/β-TG) biomarkers in the groups of ACS patients depending on the severity of signs and symptoms and compared to controls without coronary artery disease.
The study group included 93 patients categorized into 3 subgroups depending on the severity of signs and symptoms of ACS. PLT, MPV, LPLT, and WBC were determined on hematological analyzer, IL-6 and β-TG were measured using the ELISA method.
In the whole group of ACS patients WBC, CRP, IL-6, MPV, and β-TG were significantly higher as compared to controls. Analyzing the inflammation and platelet biomarkers depending on the severity of signs and symptoms in comparison to controls, statistically significant differences for above-mentioned parameters were also found. There were no significant differences between the advancement of coronary artery changes and inflammation as well as platelet parameters, except for CRP concentrations. The AUCs for all inflammation parameters tested were similar, however the highest AUCs showed WBC and CRP. Among platelet parameters the highest AUC revealed β-TG.
Markers of inflammation and platelet activation may be associated to myocardial ischemia and myocardial injury. WBC, CRP and IL-6 as inflammation parameters and MPV and β-TG as platelet biomarkers may be useful indicators of the presence of coronary artery disease.
The role of lnc-DC long non-coding RNA and SOCS1 in the regulation of STAT3 in coronary artery disease and type 2 diabetes mellitus
2018, Journal of Diabetes and its Complications
Coronary artery disease (CAD) can be classified as an inflammatory disease, which affected by type 2 diabetes mellitus (T2DM). Elevated levels of many inflammatory molecules were found in the serum of patients with CAD. STAT3 molecule as a transcription factor plays an important role in the cytokines expression. Here, we examined the expression levels of STAT3 and its important regulatory genes lnc-DC and SOCS1, in patients with CAD and T2DM.
Blood samples were obtained from 37 CAD + and 36 CAD- patients. These patients were enrolled in this study based on angiography findings and categorized based on T2DM status. The expression levels of STAT3, lnc-DC and SOCS1 genes were examined with Real time PCR method.
A significant increase was observed in expression of STAT3 and lnc-DC genes but not SOCS1 in CAD + versus CAD- patients. These results replicated partially in some groups categorized based on T2DM and CAD status. However, severity of CAD had no effect on expressions of these genes. Moreover, we found some significant correlations between expressions of lnc-DC with SOCS1 and STAT3, which confirmed by in silico analysis.
Our results shed further light to the inflammatory aspects of CAD and T2DM with emphasis to JAK/STAT pathway and the regulatory role of long non-coding RNAs in the physiopathology of these diseases.
HDL cholesterol, leptin and interleukin-6 predict high risk coronary anatomy assessed by CT angiography in patients with stable chest pain
2015, Atherosclerosis
Coronary computed tomography angiography (CTA) describes several features of coronary plaques, i.e. location, severity, and composition. Integrated CTA scores are able to identify individual patterns of higher risk. We sought to test whether circulating biomarkers related with metabolism and inflammation could predict high risk coronary anatomy at CTA in patients with stable chest pain.
We evaluated a panel of 17 biomarkers in 429 patients (60.3 ± 0.4 years, 268 males) with stable chest pain who underwent coronary CTA having been enrolled in the Evaluation of Integrated Cardiac Imaging (EVINCI) study. The individual CTA risk score was calculated combining plaque extent, severity, composition, and location. The presence and distribution of non-calcified, mixed and calcified plaques were analyzed in each patient.
After adjustment for age, sex and medical treatment, high-density lipoprotein (HDL) cholesterol, leptin, and interleukin-6 (IL-6) were independent predictors of CTA risk score at multivariate analysis (P = 0.050, 0.002, and 0.007, respectively). Integrating these biomarkers with common clinical variables, a model was developed which showed a better discriminating ability than the Framingham Risk Score and the Euro-SCORE in identifying the patients with higher CTA risk score (area under the receiver-operating characteristics curve = 0.81, 0.63 and 0.71, respectively, P < 0.001). These three biomarkers were significantly altered in patients with mixed or non-calcified plaques.
In patients with stable chest pain, low HDL cholesterol, low leptin and high IL-6 are independent predictors of high risk coronary anatomy as defined by an integrated CTA risk score.
Circulating cytokines in relation to the extent and composition of coronary atherosclerosis: Results from the ATHEROREMO-IVUS study
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Citation Excerpt :
Furthermore, Naranjo et al. [18] found that TNF-α therapy was associated with a lower incidence of cardiovascular events in patients with rheumatoid arthritis, who are known to be at high cardiovascular risk. On the other hand, Cherneva et al. [19] and Sukhija et al. [20] examined the prognostic abilities of TNF-α in patients with known coronary artery disease, but did not find any associations between TNF-α and patient outcome. In the current study, we found that higher TNF-α level are associated with both extent of atherosclerosis and with plaque vulnerability in patients with SAP, which is in line with the presumed proinflammatory nature of this cytokine.
We investigated whether concentrations of TNF-α, TNF-β, TNF-receptor 2, interferon-γ, IL-6, IL-8, IL-10 and IL-18 are associated with extent and composition of coronary atherosclerosis determined by grayscale and virtual histology (VH)- intravascular ultrasound (IVUS).
Between 2008 and 2011, IVUS(-VH) imaging of a non-culprit coronary artery was performed in 581 patients (stable angina pectoris (SAP), n = 261; acute coronary syndrome (ACS), n = 309) undergoing coronary angiography from the ATHEROREMO-IVUS study. Plaque burden, presence of VH-IVUS-derived thin-cap fibroatheroma (TCFA) lesions, and presence of VH-TCFA lesions with plaque burden ≥70% were assessed. Blood samples for cytokine measurement were drawn from the arterial sheath prior to the angiography procedure. We applied linear and logistic regression.
TNF-α levels were positively associated with plaque burden (beta (β) [95%CI]: 4.45 [0.99–7.91], for highest vs lowest TNF-α tertile) and presence of VH-TCFA lesions (odds ratio (OR) [95%CI] 2.30 (1.17–4.52), highest vs lowest TNF-α tertile) in SAP patients. Overall, an inverse association was found between IL-10 concentration and plaque burden (β [95%CI]: −1.52 [−2.49 to −0.55], per Ln (pg/mL) IL-10) as well as IL-10 and VH-TCFA lesions with plaque burden ≥70% (OR: 0.31 [0.12–0.80],highest vs lowest IL-10 tertile). These effects did not reach statistical significance in the separate SAP and ACS groups.
Higher circulating TNF-α was associated with higher plaque burden and VH-TCFA lesions in SAP patients. Lower circulating IL-10 was associated with higher plaque burden and large VH-TCFA lesions. These in-vivo findings suggest a role for these cytokines in extent and vulnerability of atherosclerosis.
Do platelet-derived microparticles play a role in depression, inflammation, and acute coronary syndrome?
2014, Psychosomatics
Major depression is an independent predictor of increased mortality in patients presenting with acute coronary syndromes (ACS). There have been several mechanisms proposed to explain the link between depression and ischemic heart disease. Both abnormal platelet physiology and inflammation have been suggested as potential confounding variables.
We set out to examine platelet activation, inflammation, and levels of depression in hospitalized patients presenting with ACS.
We enrolled 28 patients with ACS and assessed levels of depression by PHQ-9. Platelet activation was assessed by the measurement of platelet microparticle levels and platelet aggregation to adenosine diphosphate and serotonin. Inflammatory markers were assessed by the measurement of TNF alpha, IL-6, and CRP.
We found that ACS patients with moderate depressive symptoms who had higher TNF alpha, IL-6, and CRP levels had higher levels of platelet microparticles. We also found that ACS patients with PHQ-9 ≥ 10 had higher platelet aggregation to ADP.
Our results suggest that patients hospitalized for the treatment of an ACS who have moderate depression have increased platelet aggregation. These patients also have a positive association between elevated inflammatory markers and platelet activation, thus suggesting a pro-inflammatory component in ACS patients with depressive symptoms that may alter platelet function. These results are intriguing in that a potential pathway to explain the connection between depression, inflammation, and increased cardiovascular thrombosis might be found when both platelet activation and inflammation are measured.

View all citing articles on Scopus

: This study was supported by Grant M01 RR14288 from the University of Arkansas for Medical Sciences General Clinical Research Center, Little Rock, Arkansas.

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Coronary artery diseaseInflammatory Markers, Angiographic Severity of Coronary Artery Disease, and Patient Outcome

Section snippets

Methods

Results

Discussion

J Am Coll Cardiol

Atherosclerosis

J Am Coll Cardiol

Am Heart J

Am J Cardiol

J Am Coll Cardiol

Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men

N Engl J Med

Inflammation and long-term mortality after non-ST elevation acute coronary syndrome treated with a very early invasive strategy in 1042 consecutive patients

Circulation

Production of C-reactive protein and risk of coronary events in stable and unstable angina

Lancet

Elevation of tumor necrosis factor-alpha and increased risk of recurrent coronary events after myocardial infarction

Circulation

High attributable risk of elevated C-reactive protein level to conventional coronary heart disease risk factors: the Third National Health and Nutrition Examination Survey

Arch Intern Med

Is C-reactive protein an innocent bystander or proatherogenic culprit?The verdict is still out

Circulation

C-reactive protein and other circulating markers of inflammation in the prediction of coronary heart disease

N Engl J Med

Inflammatory markers and the risk of coronary heart disease in men and women

N Engl J Med

An assessment of incremental coronary risk prediction using C-reactive protein and other novel risk markers: the Atherosclerosis Risk In Communities study

Arch Intern Med

Coronary artery disease
Inflammatory Markers, Angiographic Severity of Coronary Artery Disease, and Patient Outcome