B-Type Natriuretic Peptide as a Marker of Different Forms of Systemic Sclerosis

Background: Systemic sclerosis (SSc) is an autoimmune connective tissue disease which affects various tissues and organs, including skin, lungs, kidneys, gastrointestinal tract and cardiovascular system. Cardiac involvement is the most commonly recognized problem and a significant cause of morbidity. The brain natriuretic peptide (BNP) is a previously known marker of elevated cardiovascular risk in SSc, but the levels of BNP in various forms of SSc have not been investigated so far. Aim: The aim of our study was to evaluate the influence of SSc on the function of the right ventricle and the right atrium using the echocardiographic parameters. Moreover, we examined the levels of BNP in different forms of SSc as well as the association of disease severity with the plasma concentrations of BNP. Methods: We included 42 patients with newly diagnosed SSc and patients whose disease had been diagnosed earlier. SSc patients and non-SSc control patients were examined by using echocardiography and the concentrations of BNP were determined. Results: We analyzed differences in the parameters of right ventricle (RV) function and right atrium (RA) function between SSc patients and healthy controls. The two groups had similar distribution of gender, but SSc patients were significantly older than controls. RV wall thickness was increased in SSc patients (p lt 0.001), while right ventricular end-systolic area (RVEDA; p=0.408) and right ventricular end-diastolic area (RVEDA; p=0.368) did not differ among the examinees. In contrast, RA minor-axis dimension (p=0.001) and the tricuspid annular plane systolic excursion (TAPSE) (p=0.001) were significantly higher in SSc patients. Also, we analyzed differences in brain natriuretic peptide (BNP) concentrations between diffuse cutaneous systemic sclerosis (DSSc) and limited cutaneous systemic sclerosis (LSSc) patients. DSSc patients had significantly higher concentrations of BNP. We found that levels of BNP were in significant positive correlations with age (p=0.007), disease duration (p=0.023), C reactive protein (CRP) (p=0.032), right ventricle fractional area change (FAC) (p=0.022), pulmonary vascular resistance (PVR) and Rodnan score (p=0.019). Conclusions: Given the obtained results, the laboratory determination of BNP could be useful in differentiating different forms of systemic sclerosis as well as in predicting the severity of the disease and future cardiovascular complications

HDL Subclasses and the Distribution of Paraoxonase-1 Activity in Patients with ST-Segment Elevation Acute Myocardial Infarction

The aim of this multicentric study was to assess the impacts of oxidative stress, inflam- mation, and the presence of small, dense, low-density lipoproteins (sdLDL) on the antioxidative function of high-density lipoprotein (HDL) subclasses and the distribution of paraoxonase-1 (PON1) activity within HDL in patients with ST-segment elevation acute myocardial infarction (STEMI). In 69 STEMI patients and 67 healthy control subjects, the lipoproteins’ subclasses were separated using polyacrylamide gradient (3–31%) gel electrophoresis. The relative proportion of sdLDL and each HDL subclass was evaluated by measuring the areas under the peaks of densitometric scans. The distribution of the relative proportion of PON1 activity within the HDL subclasses (pPON1 within HDL) was estimated using the zymogram method. The STEMI patients had significantly lower proportions of HDL2a and HDL3a subclasses (p = 0.001 and p < 0.001, respectively) and lower pPON1 within HDL3b (p = 0.006), as well as higher proportions of HDL3b and HDL3c subclasses (p = 0.013 and p < 0.001, respectively) and higher pPON1 within HDL2 than the controls. Independent positive associations between sdLDL and pPON1 within HDL3a and between malondialdehyde (MDA) and pPON1 within HDL2b were shown in the STEMI group. The increased oxidative stress and increased proportion of sdLDL in STEMI are closely related to the compromised antioxidative function of small HDL3 particles and the altered pPON1 within HDL

Telomere-telomerase system status in patients with acute myocardial infarction with ST-segment elevation – relationship with oxidative stress

Introduction: Telomeres are protective chromosomal ends. Short telomeres are a proven biomarker of biological aging. We aimed to find an association of telomere length and telomerase activity in circulating leukocytes and thromboaspirates of patients with acute myocardial infarction. Furthermore, association of the telomere-telomerase system with oxidative stress markers (as common risk factors for coronary artery disease (CAD)) was tested. Material and methods: Patients were selected from the patients admitted to the intensive care unit with acute myocardial infarction with ST-segment elevation (STEMI), with the following inclusion criteria – STEMI patients between 18 and 80 years old of both genders and candidates for primary percutaneous coronary intervention, with infarction pain present for a maximum of 12 h. In all the patients leukocyte telomere length, telomerase activity and scores related to oxidative-stress status (Protective, Damage and OXY) were evaluated. Results: Patients were divided into different groups: with stable angina pectoris (AP) (n = 22), acute myocardial infarction with: STEMI (n = 93), non-obstructive coronary arteries (MINOCA) (n = 7), blood vessel rupture (n = 6) at three time points, and compared to the group of 84 healthy subjects. Telomerase activity was significantly higher in all CAD sub-groups compared to the control group (AP = 0.373 (0.355–0.386), STEMI = 0.375 (0.349–0.395), MINOCA = 0.391 (0.366–0.401), blood vessel rupture = 0.360 (0.352–0.385) vs. CG = 0.069 (0.061–0.081), p < 0.001), while telomeres were significantly shorter in STEMI, MINOCA and blood vessel rupture groups compared to the control group (STEMI = 1.179 (0.931–1.376), MINOCA = 1.026 (0.951–1.070), blood vessel rupture = 1.089 (0.842–1.173) vs. CG = 1.329 (1.096–1.624), p = 0.030]. Values of OXY score were significantly higher in STEMI and MINOCA patients compared to the control group and AP patients (5.83 (4.55–7.54) and 10.28 (9.19–10.72) vs. 4.94 (3.29–6.18) and 4.18 (2.58–4.86), p < 0.001). Longer telomeres and higher telomerase activity were found in thromboaspirates, compared to the peripheral blood leukocytes in the same patients (1.25 (1.01–1.84) vs. 1.18 (0.909–1.516), p = 0.036; and 0.366 (0.367–0.379) vs. 0.366 (0.367–0.379), p < 0.001, respectively). In addition, telomere length and telomerase activity had good diagnostic ability to separate STEMI patients from healthy persons. Conclusions: Leukocyte telomere length and telomerase activity can differentiate CAD patients from healthy persons, and relate CAD to oxidative stress

The influence of systemic sclerosis on the function of the right ventricle and the right atrium by examining echocardiographic and electrocardiographic parameters

Apstrakt: Uvod. Sistemska skleroza(SC) je autoimuna bolest vezivnog tkiva koja utiče na različita tkiva i organe, uključujući kožu, pluća, bubrege, gastrointestinalni trakt i kardiovaskularni sistem. Komplikacije na srcu su najčešće prepoznat problem i značajan uzrok morbiditeta. Pacijenti i metode istraživanja: Studijsku populaciju čini 42 bolesnika oba pola, sa novootkrivenom sistemskom sklerozom, kao i bolesnike kod kojih je bolest ranije dijagnostikovana, a dolazili su tokom 2016. godine na kontrolne preglede. Pored njih, obavio se ultrazvučni pregled srca jednakom broju ispitanika odgovarajućeg pola i godina, koji su do trenutka ispitivanja bili potpuno zdravi (kontrolna grupa). Rezultati: Naši rezultati nisu pokazali korelaciju težine bolesti sa većinom ehokardiografskih parametara funkcije desne komore i desne pretkomore. Dobijeni rezultati sugerišu da bi BNP mogao biti čak i osetljiviji na procenu mogućih kardiovaskularnih komplikacija u različitim oblicima SSc. S obzirom na dobijene rezultate u našoj studiji, laboratorijsko određivanje BNP- a može biti korisno za diferenciranje različitih oblika sistemske skleroze, kao i za predviđanje težine bolesti i budućih kardiovaskularnih komplikacija. Elektrokardiografske promene u našem radu nisu pokazale značajnost u smislu pokazatelja težine bolesti i poremećaja funkcije desne komore i pretkomore, iako je postojao trend porasta QTc intervala i nastanak inkompletnog bloka desne grane kod pacijenata sa difuznim oblikom SSc. U našoj studiji zaključili smo da nije bilo značajne razlike u parametrima plućne funkcije kod pacijenata sa SSc i opstruktivnim nalazom na plućima i bez opstruktovnog nalaza na plućima registrovanim spirometrijom. U našoj studiji koncentracije CRP-a bile su značajan prediktor zahvaćenosti pluća kod pacijenata SSc. Zaključak: Bez obzira na veliki napredak u lečenju pacijenata sa sistemskom sklerozom, procenat kardiovaskularnih komplikacija kod ovih pacijenata je i dalje relativno visok. Rano otkrivanje SSc u periodu pre značajnih promena na određenim organima ili sistemima je u fokusu mnogih istraživača. SSc je doživotna bolest i ne može se izlečiti, ali znajući da disfunkcija srca značajno pogoršava prognozu, rano otkrivanje srčanih komplikacija i odgovarajuća terapija može poboljšati kvalitet života pacijenata. Naši preliminarni podaci mogu biti polazna tačka za veće studije sa dužim praćenjem, kako bi se bolje definisala prognoza srčanih komplikacija kod pacijenata sa sistemskom sklerozom. Rano otkrivanje komplikacija će nam omogućiti da poboljšamo kvalitet života i dugovečnost kod pacijenata sa kardiološkim manifestacijama u SSc.Abstract: Introduction: Systemic sclerosis (SSc) is an autoimmune connective tissue disease which affects various tissues and organs, including skin, lungs, kidneys, gastrointestinal tract and cardiovascular system. Cardiac involvement is the most commonly recognized problem and a significant cause of morbidity. Patiens and methods: The study population included 42 patients with both sexes, with newly diagnosed systemic sclerosis, as well as patients in whom the disease was diagnosed earlier, and came in 2016 for screening. In addition, echocardiographic examination was performed with an equal number of subjects of the appropriate sex and age, who were completely healthy (control group) until the time of the examination. Results: Our results did not show a correlation of the severity of the disease with most echocardiographic parameters of the right ventricular function and right atrium. The obtained results suggest that BNP could be even more sensitive to the assessment of possible cardiovascular complications in different forms of SSc. Laboratory determination of BNP can be useful for differentiating different forms of systemic sclerosis, as well as for predicting the severity of the disease and future cardiovascular complications. Electrocardiographic changes in our study did not show significance in terms of the severity of the disease and the disorder of the right ventricle and right atrial, although there was a trend of QTc interval growth and the incidence of an incomplete right bundle branch block in patients with diffuse SSc. In our study, we concluded that there was no significant difference in in the SSc patients with the obstructive pulmonary pattern revealed by spirometry and without obstructive pulmonary pattern. CRP concentrations were a significant predictor of lung involvement in SSc patients. Conclusion: Regardless of the great progress in the treatment of patients with systemic sclerosis, the percentage of cardiovascular complications in these patients is still relatively high. Early detection of SSc in the period prior to significant involvement on certain organs or systems is in the focus of many researchers. SSc is a lifelong illness and can not be cured, but knowing that heart dysfunction significantly worsens prognosis, early detection of cardiac complications and appropriate therapy can improve the quality of life of patients. Our preliminary data may be the starting point for larger studies with longer follow-up, in order to better define the prognosis of cardiac complications in SSC patients. Early detection of complications will allow us to improve quality of life and longevity in patients with cardiac manifestations in SSc

Oxidative Stress and Inflammatory Markers PTX3, CypA, and HB-EGF: How Are They Linked in Patients With STEMI?

We investigated circulating levels of inflammatory biomarkers pentraxin-3 (PTX3), cyclophilin A (CypA), and heparin-binding epidermal growth factor-like growth factor (HB-EGF); oxidative stress; and antioxidant status markers in the patients with ST-segment elevation acute myocardial infarction (STEMI) to better understand a relationship between inflammation and oxidative stress. We examined the impact of oxidative stress on high values of inflammatory parameters. The study included 87 patients with STEMI and 193 controls. We observed a positive correlation between PTX3 and HB-EGF (ρ = 0.24, P = .027), CyPA, and sulfhydryl (SH) groups (ρ = 0.25, P = .026), and a negative correlation between PTX3 and SH groups (ρ = −0.35, P = .001) in patients with STEMI. To better understand the effect of the examined parameters on the occurrence of high concentrations of inflammatory parameters, we grouped them using principal component analysis. This analysis identified the 4 most contributing factors. Optimal cutoff values for discrimination of patients with STEMI from controls were calculated for PTX3 and HB-EGF. An independent predictor for PTX3 above the cutoff value was a “metabolic-oxidative stress factor” comprised of glucose and oxidative stress marker prooxidant-antioxidant balance (odds ratio = 4.449, P = .030). The results show that higher PTX3 values will occur in patients having STEMI with greater metabolic and oxidative stress status values

Redox Status and Telomere–Telomerase System Biomarkers in Patients with Acute Myocardial Infarction Using a Principal Component Analysis: Is There a Link?

In the present study, we examined redox status parameters in arterial and venous blood samples, its potential to predict the prognosis of acute myocardial infarction (AMI) patients assessed through its impact on the comprehensive grading SYNTAX score, and its clinical accuracy. Potential connections between common blood biomarkers, biomarkers of redox status, leukocyte telomere length, and telomerase enzyme activity in the acute myocardial infarction burden were assessed using principal component analysis (PCA). This study included 92 patients with acute myocardial infarction. Significantly higher levels of advanced oxidation protein products (AOPP), superoxide anion (O2•−), ischemia-modified albumin (IMA), and significantly lower levels of total oxidant status (TOS) and total protein sulfhydryl (SH-) groups were found in arterial blood than in the peripheral venous blood samples, while biomarkers of the telomere–telomerase system did not show statistical significance in the two compared sample types (p = 0.834 and p = 0.419). To better understand the effect of the examined biomarkers in the AMI patients on SYNTAX score, those biomarkers were grouped using PCA, which merged them into the four the most contributing factors. The “cholesterol–protein factor” and “oxidative–telomere factor” were independent predictors of higher SYNTAX score (OR = 0.338, p = 0.008 and OR = 0.427, p = 0.035, respectively), while the ability to discriminate STEMI from non-STEMI patients had only the “oxidative–telomere factor” (AUC = 0.860, p = 0.008). The results show that traditional cardiovascular risk factors, i.e., high total cholesterol together with high total serum proteins and haemoglobin, are associated with severe disease progression in much the same way as a combination of redox biomarkers (pro-oxidant-antioxidant balance, total antioxidant status, IMA) and telomere length