Aleksander Danikiewicz

Serum interleukin-6 concentration reflects the extent of asymptomatic left ventricular dysfunction and predicts progression to heart failure in patients with stable coronary artery disease

BACKGROUND Left ventricular ejection fraction (LVEF) remains one of the strongest predictors of long-term prognosis in patients with stable coronary artery disease (CAD). Asymptomatic left ventricular systolic dysfunction (LVSD) often precedes clinically overt heart failure (HF) and is an area of extensive research nowadays. We studied the association between serum IL-6 concentrations and the extent of LV dysfunction in patients with asymptomatic LVSD. We aimed to investigate the diagnostic value of serum IL-6 concentrations in predicting the risk of progression to HF. Seventy-one patients entered the study and were divided into three groups based on LVEF: group 1 - patients with LVEF <30% (N=7), group 2 - patients with LVEF 30-50% (N=37) and group 3 - patients with LVEF >50% (N=27). RESULTS Demographics were similar in all three groups. IL-6 concentration was the highest in group 1 (median 8.6 pg/mL) and the lowest in group 3 (median 2.6 pg/mL), whereas IL-6 concentration in group 2 was intermediate (median 3.7 pg/mL) (P=0.002). We found a significant, inverse correlation between IL-6 concentration and ejection fraction. During 18-month follow-up clinically overt HF developed in 71.4% of patients in group 1 and in 37.5% of patients in group 2. None of the patients in group 3 manifested HF symptoms (P<0.001). ROC analysis revealed high diagnostic value of serum IL-6 and LVEF in predicting progression to HF. We also found a strong, inverse correlation between IL-6 and the time of progression to HF. CONCLUSIONS There is a strong correlation between IL-6 and the extent of asymptomatic LVSD in patients with documented CAD. Elevated IL-6 concentrations preceded progression to clinically overt HF. Moreover, the higher the IL-6 concentration the earlier the manifestation of HF symptoms.

Serum interleukin-6 concentration predicts contrast-induced nephropathy in patients undergoing percutaneous coronary intervention

BACKGROUND Contrast media are being widely applied for both diagnostic and therapeutic purposes. This has resulted in increasing incidence of contrast-induced nephropathy (CIN). METHODS We aimed to investigate the value of baseline serum IL-6 concentrations in predicting CIN before the rise of serum creatinine (SCr) in patients undergoing percutaneous coronary intervention. Seventy four Caucasian patients were enrolled. CIN was defined as an increase in SCr concentration of more than 44 micromol/L, or a 25% increase above baseline within 48 hours after contrast administration. RESULTS CIN developed in 16 out of 74 patients (21.6%). The median concentration of IL-6 was 3.2 pg/mL. The median IL-6 concentration on admission was lower in patients who subsequently did not develop CIN (2.7 pg/mL versus 8.3 pg/mL, p < 0.0001). Receiver operating characteristics analysis showed a high diagnostic value of baseline SCr and IL-6. The cut-off value to predict CIN for IL-6 was over 4.0 pg/mL (sensitivity 88%, specificity 76%, PPV 50%, NPV 96%). Multivariate logistic regression analysis revealed three independent predictors of CIN: IL-6 (OR 1.43; 95%CI: 1.17-1.76), serum creatinine (OR 1.79; 95%CI: 1.1-3.39), and ejection fraction (OR 0.86; 95%CI: 0.50-0.95). CONCLUSIONS Increased concentrations of IL-6 on admission are associated with subsequent CIN. Our study proposes that IL-6 be added to the list of potential markers that could be used, along with renal function parameters, in clinical practice.

Effect of omeprazole on the concentration of interleukin-6 and transforming growth factor-β1 in patients receiving dual antiplatelet therapy after percutaneous coronary intervention

BACKGROUND Dual antiplatelet therapy (aspirin plus clopidogrel) is recommended in patients undergoing percutaneous coronary intervention (PCI). Treatment with proton pump inhibitors (PPIs) decreases bleeding rate. Alarming reports have been made that PPIs may decrease the antiplatelet activity of clopidogrel. We sought to determine whether levels of interleukin-6 (IL-6) and transforming growth factor-β1 (TGF-β1) might help distinguish individuals at risk for adverse events. METHODS Thirty-eight patients on aspirin and clopidogrel were enrolled and divided into two groups: group 1 [patients receiving omeprazole (n = 18)] and group 2 [patients not receiving omeprazole (n = 20)]. Patients underwent PCI and were scheduled for twelve-month clinical follow-up. The major, adverse cardiac and cerebrovascular events (MACCE) include death, re-hospitalization for acute coronary syndromes, and stroke. RESULTS Median concentrations of IL-6 were higher in group 1 at 4.7 pg/mL, in comparison with group 2, 1.65 pg/mL (p = 0.003). Median concentrations of TGF-β1 were similar in both groups (p = 0.5). Patients in group 1 had a significantly higher leukocyte count [103/mm3] (median 7.5 vs 6.5; p = 0.04). There were no deaths during follow-up. The incidence of myocardial infarction was higher in group 1 (33.4% vs 5.0%; p = 0.03). MACCE at twelve months were more frequent in group 1 (55.6% vs 20.0%; p = 0.02). The cut-off value to predict MACCEs for IL-6 was > 3.6 pg/mL (sensitivity 64%, specificity 88%, positive predictive value 75%, negative predictive value 81%). INTERPRETATION We show here that concomitant omeprazole use is associated with an increased inflammatory reaction. Drug interactions may reduce the anti-inflammatory effect of clopidogrel. This mechanism maybe responsible for an increased risk of non-fatal, cardiovascular events, following stent placement.

Plasma Pentraxin 3 May Be a More Sensitive Marker of Inflammatory Response Than High-Sensitivity C-Reactive Protein After Bare-Metal Stent Compared to Drug-Eluting Stent Implantation

C-reactive protein (CRP) and pentraxin 3 (PTX3) are members of a highly conserved pentraxin superfamily. CRP is synthesized in the liver and may represent a systemic response to local inflammation. PTX3 is synthesized locally at the inflammatory sites and may represent a marker for local inflammation at sites of vessel injury. We compared plasma high-sensitivity CRP (hsCRP) and PTX3 concentrations after bare-metal stent (BMS) and drug-eluting stent (DES) implantation. Fifty-three patients with stable coronary artery disease who underwent percutaneous coronary intervention were divided into 2 groups: 1-24 patients (BMS group) and 2-29 patients (DES group). Patients were scheduled for an elective, 6-month clinical follow-up. Major adverse cardiovascular events (MACEs) (death, myocardial infarction, target vessel revascularization) were assessed. Baseline clinical characteristics were similar in both groups. Patients after BMS implantation had a higher median PTX3 concentration 1.02 ng/mL compared to patients after DES implantation 0.80 ng/mL, P=0.045. Median hsCRP concentrations were similar in both groups: 0.9 mg/L versus 0.89 mg/L, respectively. Six-month follow-up was available in 33 patients. Four out of 33 patients had MACEs during follow-up. The cut-off value to predict MACEs for PTX3 was >1.16 ng/mL (P=0.004) and for hsCRP was >0.95 mg/L (P<0.001). Patients after DES implantation showed significantly lower plasma PTX3 levels compared with patients after BMS implantation. hsCRP showed no difference between the study groups. PTX3 may be a more sensitive marker of local inflammatory response due to vessel injury by BMS than hsCRP. DES implantation may attenuate the early inflammatory response. Lower PTX3 levels may reflect potent anti-inflammatory properties of DES.

Pentraxin-3 concentrations in stable coronary artery disease depend on the clinical presentation

IntroductionPentraxin-3 (PTX3) is an acute-phase reactant that shares structural and functional homology with C-reactive protein (CRP). However, unlike CRP, which is synthesized mainly in the liver, PTX3 is produced at the site of inflammation. It has been suggested that PTX3 plays the same role in the periphery that CRP does in circulation. PTX3 may represent a rapid marker of local inflammation.MethodsFifty-one patients with stable coronary artery disease (CAD) were enrolled. Blood samples were collected on admission. Plasma concentration of PTX3 and high-sensitivity CRP (hsCRP) were determined.ResultsMedian PTX3 concentration was 0.92 μmol/L (0.58–1.40). Median hsCRP concentration was 0.90 mg/L (0.75–1.10). There was a positive correlation between PTX3 and total cholesterol (R = 0.34; P = 0.01), PTX3 and LDL cholesterol (R = 0.35; P = 0.01), and PTX3 and hsCRP (R = 0.46; P = 0.0005). We found no correlation between hsCRP and all laboratory parameters. We found higher PTX3 concentrations in patients with Canadian Cardiovascular Society (CCS) functional class 3 (compared to CCS functional class 2) and in patients taking nitrates. Lower PTX3 concentrations were reported in patients taking calcium channel blockers (amlodipine). hsCRP concentrations remained similar among these subgroups of patients.ConclusionsPTX3 is a marker of clinically more advanced CAD (CCS2 vs CCS3; nitrates vs no nitrates). PTX3 is also associated with other cardiovascular risk factors (total cholesterol, LDL cholesterol, and hsCRP). PTX3 may be a potential early marker of cardiovascular risk before the increase of systemic markers like hsCRP.

Relationship Between Plasma Pentraxin 3 Concentration and Platelet Indices in Patients With Stable Coronary Artery Disease

Few reports have analyzed the effect of pentraxin 3 (PTX3) on platelets and their activation. We explored the association between plasma PTX3 and platelet indices. Forty-nine patients with stable coronary artery disease (CAD) were enrolled. Based on median PTX3, the study population was divided into group 1 (n = 25; PTX3 ≤ 0.98 ng/mL) and group 2 (n = 24; PTX3 > 0.98 ng/mL). Platelet indices investigated included mean platelet volume (MPV), platelet distribution width (PDW), platelets and large cell ratio (P-LCR), MPV to platelet count ratio (MPV/PC), platelet to lymphocyte ratio (PLR), and MPV to lymphocyte ratio (MPVLR). Patients with lower PTX3 had a higher lymphocyte count. Platelet count was similar in both groups. Notwithstanding, patients with higher PTX3 concentrations had elevated MPV (8.3 vs 10.0 fL; P < .001) and PDW (9.4 vs 12.4 fL; P < .001). However, the MPV/PC ratio was similar in both groups. Thromboinflammatory biomarkers (PLR, MPVLR) were also elevated in group 2. Pentraxin 3showed a strong, positive correlation with MPV (r = .75, P < .01) and PDW (r = .80, P < .01), and weak to moderate correlation with MPVLR. In conclusion, PTX3 is associated with larger platelet size as assessed by platelet volume indices. There is a strong correlation between plasma PTX3 level and MPV and PDW.

Platelet Volume Measurements—EDTA, Citrate, or Both?

We appreciate the comments made by Dr Yildirim and colleagues. First, we agree that preanalytical factors play a key role in obtaining reliable results and that such errors can result in erroneous conclusions. Thus, all blood samples in our study were tested within 1 hour of collection. Second, we used ethylenediaminetetraacetic acid (EDTA) for whole blood anticoagulation. Some reports demonstrated that the mean platelet volume (MPV) increases with the use of EDTA due to platelet swelling, thus, suggesting the use of acid citrate as anticoagulant. However, most studies indicate that MPV can be measured accurately by both methods of anticoagulation—EDTA and citrate—if analysis is performed within 1 hour of sampling. Dastjerdi et al evaluated whether EDTAand citrate-based anticoagulated blood samples can be used interchangeably for MPV measurement. In the 61 patients, there was a close correlation between MPV as measured in EDTA and citrate, but MPV measured from EDTA samples was 0.66 fL (9%) greater than when collected in citrate. Both methods also showed a significant negative correlation between platelet count and MPV. The study indicates that MPV can be measured accurately by both methods of anticoagulation, EDTA and citrate, if the analysis is performed within 1 hour of sampling. Lance et al also demonstrated that platelets swell until 120 minutes in EDTA and until 60 minutes in citrate. So they suggest that optimal measuring time should not exceed 120 minutes. Interestingly, they demonstrated that the platelet count was most stable in EDTA. As to plateletcrit, it provides data regarding total platelet mass, whereas MPV and platelet larger cell ratio (P-LCR) are indicators of circulating larger platelets (>12 fL) and have also been used to monitor platelet activity. These are the reasons why we chose to study the associations of MPV and P-LCR with pentraxin 3 (PTX3) and C-reactive protein (CRP). Furthermore, there is paucity of data on the role of plateletcrit in stable coronary artery disease. Therefore, we did not record this variable in our study. Notwithstanding, the authors make an interesting point for future studies. Regarding correlation between CRP and platelet to lymphocyte ratio (PLR), and lack thereof between PTX3 and PLR, we speculate that different mechanisms underlie this phenomenon. One possibility might be the local nature of PTX3 actions in contrast to the systemic actions of CRP. However, we cannot exclude that our results are limited by a relatively small sample size.

Effects of trimetazidine on interleukin-2 and interleukin-8 concentrations in patients with coronary artery disease

Trimetazidine (TMZ) exhibits metabolic and cardioprotective effects. The aim of this study was to assess the effects of TMZ on interleukin-2 (IL-2) and interleukin-8 (IL-8) serum concentrations in 156 patients with stable coronary artery disease. They underwent a treadmill exercise test (TET) before and after 3 months of TMZ treatment. IL-2 and IL-8 concentrations were determined before and after each TET. Before treatment, TET did not influence IL-2 concentrations, whereas IL-8 concentrations increased. TMZ treatment led to a decrease in IL-2 concentrations before TET, as well as it prevented the increase of IL-8 following the second TET. Obtained results confirmed the improvement in TET performance during TMZ treatment and they revealed a significant influence of TMZ on IL-2 and IL-8 concentrations both before and after TET. These changes may reflect potential anti-inflammatory effects of TMZ.

Single nucleotide polymorphisms for genes encoding cytokines in the context of cardiac surgery. Part I: Heart transplantation.

Cardiovascular diseases remain the leading cause of death in Poland and other countries of the European Union. Patients with end-stage heart failure constitute a patient subgroup for whom the treatment of choice is heart transplantation. Despite advances in immunosuppressive therapy, acute or chronic graft rejection occurs in 20-30% of cases in the first six months after transplantation. The significance of the immune response and inflammation in graft rejection implies the important role of cytokines. Molecular markers are sought to facilitate risk assessment and improve patient care. At present, genetic tests are not used for this purpose, but studies aiming to rectify that have been conducted for years, including studies on single nucleotide polymorphisms of cytokine genes. This paper presents the results of research on the single nucleotide polymorphisms (SNPs) of the IL-2, IL-4, IL-6, IL-10, TGF-β1, PDGF, VEGF, and TNF-α genes in conjunction with heart transplantation. The analyzed data do not allow for reliable application of these genetic tests in clinical practice, but suggest that it is a promising direction which may improve the options of treatment individualization in the future.