Barbara Zubelewicz-Szkodzinska

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.

Radiocontrast-induced thyroid dysfunction: is it common and what should we do about it?

There has been a substantial increase in the use of radiocontrast‐enhanced imaging studies in the past two decades (particularly computed tomography and coronary angiography). Sudden exposure to high levels of iodide may result in thyroid dysfunction (hyperthyroidism and hypothyroidism alike). Although the adverse‐event rate is not very high, the condition is notable considering the large number of contrast‐enhanced radiographic studies performed. Clinicians often have to decide on the most suitable diagnostic modality and the safest contrast medium when it comes to certain patients. In this study, we stress that the thyroid function of the patients should also be taken into consideration while making such decisions. We discuss in detail the prevalence and types (hypothyroidism and hyperthyroidism) of radiocontrast‐induced thyroid dysfunction. We list the subsets of the population that are at a higher risk of radiocontrast‐induced thyroid dysfunction and summarize the necessary prophylaxis and possible treatment. The presented principles apply to intravenous, intra‐arterial and enteral (endoscopic retrograde cholangiopancreatography) routes of iodinated contrast medium administration.

Obesity, adipose tissue function and the role of vitamin D

Introduction Obesity is not just a cosmetic problem. Pathological accumulation of body fat can cause many health problems: insulin resistance, impaired glucose tolerance, and diabetes mellitus type 2. It may also increase morbidity and mortality. Adipose tissue plays an important role in body homeostasis by producing and secreting several bioactive proteins known as adipokines: adiponectin, leptin, resistin, visfatin, and apelin, which are involved in the regulation of food intake, glucose and lipid metabolism, and insulin action. There can be observed nutritional deficiencies, despite increased food intake, in morbidly obese people. Data concerning concentrations of serum 25(OH)D3 presented an inverse correlation with obesity parameters like: BMI (body mass index), waist circumference, fat mass or percentage of body fat. Also, higher insulin sensitivity was associated with higher concentrations of vitamin D. Conclusions Studies published up to now suggest that vitamin D plays an important role in adipose tissue function and could be involved in the synthesis and modulation of adipokine production. This article is a review of the literature on fatty tissue function and the role of vitamin D in obesity.

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.

Effect of HMG-CoA (3-hydroxy-3-methyl-glutaryl-CoA) reductase inhibitors on the concentration of insulin-like growth factor-1 (IGF-1) in hypercholesterolemic patients

UNLABELLED Studies have shown that HMG-CoA reductase inhibitors (statins) play an important role in the prevention and treatment of atherosclerosis and hyperlipidemia. The aim of this study was to investigate the effect of 3-month treatment with simvastatin on serum levels of Insulin-Like Growth Factor-1 (IGF-1) in patients with diagnosed hypercholesterolemia. In total, 156 patients with hypercholesterolemia were recruited for the study. The inclusion criteria for this study were designed to allow the enrollment of a representative group of patients for cytokine studies. The patients were divided into two groups: (1) patients with a mild-to-moderate risk of heart disease, who had total cholesterol (TC) < 300 mg/dl (7.8 mmol/l), LDL-cholesterol < 210 mg/dl (5.4 mmol/l), and who lacked risk factors for coronary artery disease (CAD) after treatment with a diet for 3 months; (2) patients with a high-to-very high risk of CAD, who had TC > 300 mg/dl (7.8 mmol/l), LDL-cholesterol > 210 mg/dl (5.4 mmol/l), and at least two risk factors for CAD after treatment with a diet and administration of simvastatin (20 mg/day) for a three month period. The control group consisted of ten healthy volunteers who each had a normal lipid profile. Total cholesterol, LDL-cholesterol and IGF-1 concentrations were measured at baseline and either after six months of dietary supplementation (first group) or after three months of dietary supplementation and three months of simvastatin treatment (second group). CONCLUSIONS In patients with mild-to-moderate risk of CAD, a decreased serum concentration of IGF-1 was observed three months after beginning a low-fat diet. However, no changes in the serum concentration of IGF-1 were noted in patients with high-to-very high risk of CAD. Additional three-month treatment with simvastatin decreased the serum concentration of IGF-1.

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.

Amiodarone-related thyroid dysfunction

Nowadays, amiodarone is the most commonly used antidysrhythmic drug in clinical practice. It is highly effective in the management of recurrent ventricular dysrhythmias, paroxysmal supraventricular dysrhythmias, including atrial fibrillation and flutter, and in the maintenance of sinus rhythm after electrical cardioversion of atrial fibrillation. Moreover, it has the added benefit of being well tolerated in patients with both normal and impaired left ventricular systolic function. Despite amiodarone’s potent antidysrhythmic actions, its use is hampered by numerous adverse effects on various organs, including the thyroid. Adverse effects are becoming more prevalent given the increasing incidence of dysrhythmias and wider amiodarone use. Thus, physicians and patients should both be aware of the potential thyroid-specific sequelae. However, amiodarone is likely to remain a significant problem for endocrinologists as concerns exist over the use of the new alternative antiarrhythmic agent, dronedarone, especially in patients with heart failure and left ventricular dysfunction because of the risk of hepatic injury and increased mortality. The final diagnostic and therapeutic approaches must be discussed among the patient, the general practitioner, the cardiologist, and the endocrinologist.

No predictive value of serum interleukin-6 and transforming growth factor-β1 in identifying patients with a first restenosis, recurrent restenosis or a history of restenosis

BACKGROUND The efficacy of percutaneous coronary intervention (PCI) is limited by the need for repeat revascularization resulting from restenosis. The restenosis rate after treatment for in-stent restenosis (recurrent restenosis) is high (> 30%). Numerous studies have suggested the predictive value of interleukin 6 (IL-6) and transforming growth factor beta1 (TGF-beta1). METHODS We sought to determine whether serum levels of IL-6 and TGF-beta1 could help identify individuals with recurrent restenosis. Thirty seven patients with a history of stent implantation were enrolled and divided into three groups: (1) patients with a current, first restenosis (n = 9); (2) patients with current restenosis and at least one prior restenosis (recurrent restenosis) (n = 11), and (3) patients with a history of restenosis, but without current restenosis (n = 17). RESULTS The baseline profile was similar in all three groups. The median (25th-75th percentile) concentrations of IL-6 were: group 1 - 2.8 (1.4-5.5); group 2 - 2.6 (0.6-8.6); group 3 - 2.4 (0.9-4.7) p = 0.69 and TGF-beta1: group 1 - 3.6 (0.2-14.4); group 2 - 4.2 (1.8-57.6); group 3 - 6.6 (2.8-30.0) p = 0.57. Moreover we found no correlation, either between diameter stenosis and IL-6 (R = 0.10; p = 0.38) or TGF-beta1 (R = 0.10; p = 0.57). Both IL-6 (AUC 0.59 p = 0.4 and AUC 0.51 p = 0.9) and TGF-beta1 (AUC 0.64 p = 0.2 and AUC 0.50 p = 0.9) failed to provide significant results in receiver-operating characteristic analysis. CONCLUSION We report that there is no association between the severity of diameter stenosis (restenosis) and IL-6 or TGF-beta1 concentrations. Our findings might suggest that levels of IL-6 and TGF-beta1 have no predictive value for identifying patients with recurrent restenosis.