Neuregulin-1β, Biomarkers of Inflammation and Myocardial Fibrosis in Heart Failure Patients

Neuregulin-1β (NRG-1) is an emerging biomarker of heart failure (HF). The mechanisms of its action in HF patients are yet  to be investigated. Cardioprotective and anti-inflammatory  effects of NRG-1 have been reported.Aim. To assess NRG-1 levels in HF patients and investigate the association between NRG-1 and biomarkers of inflammation and myocardial fibrosis.Material and Methods. NRG-1, biomarkers of inflammation and fibrosis (hsCRP, IL-6, sVCAM-1, MMP-9, Galectin-3, ST2, TGF-β) were assessed in 47 patients with HF and preserved ejection fraction (HFpEF); 39 patients with HF and reduced ejection  (HFrEF) and 40 healthy participants. The associations between  NRG-1 and biomarkers of inflammation and fibrosis, as well as  the composite outcomes of cardiovascular death and HF  hospitalisations were assessed.Results. Median NRG-1 levels in HFpEF were 0.969 (0.348; 1.932) ng/ml, in HFrEF – 0.63 (0.348; 1.932), in healthy participants 0.379 (0.195; 0.861) ng/ml, and was significantly higher in HFpEF compared to healthy volunteers (р=0.004). There was no  difference in NRG-1 concentration between HFpEF and HFrEF. In  HF patients, all biomarkers of inflammation and fibrosis were  higher than in controls. ST2, IL-6 and TGF-β were significantly higher in HFrEF compared to HFpEF patients, while hsCRP,  sVCAM-1, MMP-9, and Galectin-3 levels were comparable. In  HFpEF, NRG-1 was associated with hsCRP (rs=0.378, p=0.023) and IL-6 (rs=0.378, p=0.014). Median follow-up time in patients with HFpEF and in patients was 312 (236; 388) days, in HFrEF – 147 (98; 237) days. In HFpEF, 2 patients died and 19 were  hospitalized due to HF. In HFrEF, 10 deaths and 19  hospitalizations were registered. Kaplan-Mayer analysis showed that HFpEF patients with increased NRG-1 and IL-6 had higher  levels of HF hospitalisation (log rank test, р=0.046 and р=0.012, respectively). In a multivariable cox proportional hazard model,  the association between the NRG-1 and outcomes remained significant after adjustment for age, gender and NTproBNP but diminished when hsCRP and IL-6 were included in the model.Conclusion. NGR-1 level significantly higher in HFpEF compared to healthy participants, and comparable with NRG-1 concentrations in HFrEF. In HFpEF, NRG-1 was associated with biomarkers of inflammation and fibrosis. The prognostic value of NRG-1 in HF requires further investigations

Aromatic Amino Acids: Phenylalanine and Tyrosine in Patients with Hypertension and Coronary Artery Disease

Aim. To evaluate changes in the profile of aromatic amino acids (AAA) in patients with cardiovascular diseases (CVD): hypertension and coronary artery disease (CАD) in comparison with healthy study participants.Material and methods. One hundred and thirty-one participants were included in the study: 58 participants were included in the hypertension group, 46 in the CАD group, and 27 participants without signs of CVD in the control group. We used ultrahigh-performance liquid chromatography in combination with a triple quadrupole analyzer to measure plasma AAA: phenylalanine and tyrosine (Phe, Tyr) in all study participants. The association of AAA with biochemical blood test parameters, echocardiography (EchoCG) parameters, blood pressure level and clinical characteristics was analyzed.Results. A statistically significant difference in the level of concentration of Phe and Tyr was revealed (p=0,002 and p=0,024, respectively), comparing the three groups. Post-hoc analysis showed differences in the circulating level of both amino acids in patients with CAD vs the control group (Phe p=0,008 and Tyr p=0,020). Also a statistically significant difference in the level of Phe of the hypertension and CАD groups (p=0,017) was found. A negative correlation of low-density lipoproteins (LDL) with the level of Phe (r=-0,685, p<0,05) and Tyr (r=-0,583, p<0,05), as well as the level of Phe with total cholesterol (r=-0,461, p<0,05) was found in the group without CVD. In the hypertension group, only a weak positive correlation was found between very low-density lipoproteins and AAA levels (Phe r=0,326 and Tyr r=0,365, p<0,05), while in patients with CAD, the level of Phe and Tyr was negative correlated with high-density lipoprotein (r=-0,378 and r=-0,543, respectively, p<0,05), and the level of Tyr with LDL (r=0,349, p<0,05). When isolating the group with proven atherosclerosis of peripheral and/or coronary arteries, a statistically significant difference was revealed between the group of patients with CVD and clinical and instrumental signs of atherosclerosis and the group of patients with CVD without proven atherosclerosis in Phe level (p=0,019).Conclusion. Concentrations of AAA were higher in patients with CVD, comparing with the control group. At the same time, an increase of the Phe level was associated with the presence of peripheral or coronary atherosclerosis. The revealed correlations of AAA with EchoCG parameters and lipid spectrum parameters require further study to understand the involvement of AAA in pathogenesis of CVD and its potential role as treatment target

MINERAL METABOLISM AND BONE MINERAL DENSITY IN PATIENTS WITH CENTRAL HYPOGONADISM AS INDICATORS OF PREMATURE AGING

Aim of this study was to estimate the markers of mineral turnover and BMD in young women with the central hypogonadism, to compare them with healthy young women and healthy postmenopausal women of middle/advanced age. Materials and methods. One hundred seventy women were included in the study: 73 patients with the central hypogonadism (isolated hypogonadism n=35, hypopituitarism n=38), age of 25 [21.2; 30.5] y.o., amenorrhea duration 5 [2.3; 10.1] years; 47 healthy women with regular menstrual cycles, age 24 [23.1; 28.0] y.o., and 50 healthy women with natural menopause, age 56 [53; 58] y.o., menopause duration 6.0 [2.1; 10.0] years. Groups did not differ by age. Results. In patients with central female hypogonadism concentrations of calcium and alkaline phosphatase were significantly higher than in healthy women of similar age, however did not differ from the parameters in postmenopausal women. T-scores <-2.5 SD in lumbar spine were noted in 55% and 28% patients with central hypogonadism and in menopause respectively (р<0.001), and in a hip - 27% and 7%, respectively (r=0.002). The factors promoting lower values of BMD in young women with central hypogonadism were the amenorrhea duration, low level of total testosterone, primary amenorrhea. Distinctions of mineral turnover and BMD in isolated hypogonadism and a hypopituitarism were not revealed. Conclusions. Central hypogonadism in women at young age is a higher prognostic factor of low BMD than natural menopause, and might be considered as a marker of premature aging

Metabolic Syndrome: Development of the Issue, Main Diagnostic Criteria

Obesity is one of the leading and the most serious risk factors of cardiovascular diseases. Overweight provokes many metabolic and hemodynamic disorders.  About 30% of inhabitants of the planet have overweight and prevalence of obesity increases by 10% every 10 years according to the WHO data.  The probability of arterial hypertension in obese  patients is 50% higher than in people with normal body mass. Framingham study showed that obesity is an independent, significant risk factor  of ischemic heart  disease, myocardial infarction, cerebral stroke  and  diabetes mellitus. The most dangerous is the central obesity with the preferential fat deposition in the abdomen. Combination of visceral obesity, violation of carbohydrate and lipid metabolism, arterial hypertension, and close pathogenic relationship between these  factors  underlie the isolated symptom complex known  as metabolic syndrome. J. Vague was the first to describe relationship between abdominal obesity with cardiovascular disease and mortality in 1947. In our country G.F. Lang noticed common combination of arterial hypertension with obesity, lipid and carbohydrate metabolism disorders. Thus, metabolic syndrome significantly increases risk and  severity of cardiovascular disease. Within last decades criteria of metabolic syndrome stays constant. The factors  of insulin resistance and  endothelial dysfunction as stages of the pathogenesis of the metabolic syndrome have been  studied in detail. The mechanisms of insulin resistance and endothelial dysfunction are discussed in detail in this article as well as inflammatory markers and the significance of highly sensitive C-reactive protein