Pēteris Tretjakovs, Juris Hofmanis, Dace Hofmane, Gita Krieviņa, Leons Blumfelds, Vitolds Mackēvičs, Aivars Lejnieks and Guntis Bahs
The aim of the present study was to evaluate plasma levels of chemerin, myeloperoxidase (MPO), fibroblast growth factor-21 (FGF-21), thioredoxin reductase-1 (TrxR1), and matrix metallopeptidase-9 (MMP-9) in acquired aortic valve (AoV) stenosis patients to determine correlations between the studied cellular factors, and also clarify the predictive values of these factors as biomarkers in AoV stenosis. AoV stenosis patients were classified into three groups: 17 patients with mild AoV stenosis; 19 with moderate and 15 with severe AoV stenosis. Twenty-four subjects without AoV stenosis were selected as a control group. Our findings suggest that AoV stenosis might be associated with increased chemerin, TrxR1, MPO, and FGF-21 levels in plasma. Moreover, these factors and also MMP-9 already reached statistically significantly elevated levels in the early stages of AoV stenosis, but MPO levels were more pronounced in patients with moderate and severe AoV stenosis. Chemerin was correlated with all of the studied cytokines; TrxR1 and MMP-9 were correlated with several other cellular factors. Our findings (by ROC analysis) suggest that MPO and chemerin might serve as specific and sensitive biomarkers for AoV stenosis without grading the severity, but, in relation to mild AoV stenosis, TrxR1, FGF-21, and MMP-9 also reached good or moderate levels as biomarkers. The cellular factors might serve as novel diagnostic and prognostic biomarkers in AoV stenosis patients, while chemerin and MPO may be more powerful.
Astra Zviedre, Arnis Eņģelis, Pēteris Tretjakovs, Irisa Zīle and Aigars Pētersons
The aim of the study was to determine whether the Alvarado score (AS) together with laboratory tests could be used to distinguish patients with acute appendicitis (AA) from acute mesenteric lymphadenitis (AML). Fifty-seven patients (7–18 years) with suspected AA were included in the prospective study (October 2010 – October 2013). Thirty-one patients underwent surgery for AA and 26 were not treated surgically and were diagnosed AML on ultrasonography. AS, white blood cell count (WBC), C – reactive protein (CRP) and serum cytokines (EGF, IL-10, IL-12(p70), IL-1β, IL-4, IL-6, IL-8, IL-17, MCP-1, TNF-α) were obtained on admission and were compared between groups. Mean age of the 57 patients was 12.9 (SD 3.2). Accuracy (AR) for AS ≥ 7 alone was 73.7% for AA. Modified AS with certain serum cytokines seemed to be a reliable tool for initial differential diagnosis between AA and AML in school-age children. Based on these results, AS ≥ 7, WBC ≥ 10.7 × 103/µL and serum IL-6 ≥ 4.3 pg/mL assessed altogether will yield more sensitivity for AA. Also for further advanced diagnostics, we propose to take into account the serum IL-6, IL-8, MCP-1, CRP cut-off levels in the differential diagnosis between complicated and uncomplicated AA to decide whether the treatment should be conservative or surgical.
Inga Stuķēna, Andrejs Kalvelis, Guntis Bahs, Uldis Teibe, Pēteris Tretjakovs and Aivars Lejnieks
Association between Inflammatory Markers and Clinical and Metabolic Risk Factors for Cardiovascular Diseases
The inflammatory reaction plays an important role in the development of atherosclerosis. The clinical significance of the main inflammatory markers — C-reactive protein (CRP), interleukin 6 (IL6), tumour necrosis factor alpha (TNF-α), plasminogen activator inhibitor 1 (PAI1), etc. — has not been fully established. CRP, IL6, TNF-α, and PAI1 were assessed in 100 patients in terms of certain clinical indicators (sex, obesity indicators, blood pressure, and heart rate), total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), triglycerides (TG), glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), adiponectin, and leptin levels. CRP and PAI1 levels were elevated in subjects with increased body mass index (BMI) and waist circumference. CRP correlated positively with indicators of carbohydrate metabolism and negatively with TC, HDL-C, and adiponectin. PAI1 correlated positively with insulin levels, HOMA-IR, leptin, and TG, but negatively with HDL-C. IL6 correlated negatively with TC, but TNF-α correlated negatively with HDL-C. Both IL6 and TNF-α correlated positively with leptin levels. TNF-α correlated with TG levels and the indicators of carbohydrate metabolism only in women. CRP and PAI1 are the most sensitive inflammatory markers; their levels were higher in adipose subjects.
Inga Stuķēna, Andrejs Kalvelis, Guntis Bahs, Uldis Teibe, Pēteris Tretjakovs and Aivars Lejnieks
Characteristics of Cardiovascular Risk Factors and Their Correlation with the Sex and Age of Patients in the Latvian Population
Various cardiovascular risk factors (RFs) were determined in 773 out-patients (mean age 55.8 ± 14.5 years). Male individuals had a larger waist circumference (WC) than did female patients (99.1 ± 13.6 cm vs 93.3 ± 15.2 cm), higher diastolic blood pressure (DBP) (83.6 ± 9.6 mmHg vs 81.8 ± 9.6 mmHg), and higher levels of blood glucose (5.73 ± 1.4 mmol/L vs 5.49 ± 1.3 mmol/L) and triglycerides (TG) (1.89 ± 1.3 mmol/L vs 1.60 ± 1.0 mmol/L), but lower levels of total cholesterol (TC) (5.54 ± 1.2 mmol/L vs 5.79 ± 1.2 mmol/L) and high-density lipoprotein cholesterol (HDL-C) (1.21 ± 0.4 mmol/L vs 1.44 ± 0.4 mmol/L). Compared with the younger age group (i.e., males, < 7 years; females, < 65 years), patients in the older age group had a larger WC (98.4 ± 14.2 cm vs 92.8 ± 15.1 cm), higher systolic blood pressure (SBP) (144.2 ± 19.2 mmHg vs 131.6 ± 18.5 mmHg), higher DBP (84.5 ± 8.8 mmHg vs 80.9 ± 9.8 mmHg), higher blood glucose level (5.74 ± 1.3 mmol/L vs 5.46 ± 1.3 mmol/L), and higher low-density lipoprotein cholesterol level (LDL-C) (3.68 ± 1.0 mmol/L vs 3.52 ± 1.0 mmol/L), but lower HDL-C level (1.3 ± 0.4 mmol/L vs 1.41 ± 0.4 mmol/L). Age was significantly correlated with all RFs, with the exception of the level of C-reactive protein. In conclusion, analysis of cardiovascular RFs in different age subgroups of both sexes clearly showed individual peculiarities of risk profile. This conclusion challenges the usual way of risk calculation using "universal" markers like adiposity or dyslipidemia in all population. The new approach requires individual attention depending on sex and age also in management of risk.
Pēteris Tretjakovs, Antra Jurka, Inga Bormane, Indra Miķelsone, Dace Reihmane, Gita Krieviņa, Iveta Marksa, Karlīna Elksne, Jurijs Verbovenko and Guntis Bahs
Neopterin, cellular adhesion molecules and myeolperoxidase in patients with stable and unstable angina pectoris
Recent data indicate that the serum level of neopterin, a marker of inflammation and immune modulator secreted by monocytes/macrophages, is elevated in patients with acute coronary syndrome (ACS) and seems to be a prognostic marker for major cardiovascular events. Soluble cellular adhesion molecules (sCAMs) and myeloperoxidase (MPO) levels are also related to ACS. The aim of the present study was to evaluate differences in serum levels of neopterin, sCAMs and MPO between coronary artery disease and metabolic syndrome (CAD-MetS) patients with stable and unstable angina pectoris (SAP, UAP), and to clarify the relationships between neopterin and other biomarkers. The study included 60 patients with CAD-MetS who were classified into two groups, 30 patients with SAP and 30 patients with UAP. Twenty healthy subjects were selected as controls (C). Serum soluble vascular cell adhesion molecule-1 (sVCAM-1), intercellular cell adhesion molecule-1 (sICAM-1), sE-selectin and MPO levels were measured by Luminex xMAP technology, and serum neopterin concentrations were measured by radioimmunoassay. Results: Serum levels of neopterin, MPO, sVCAM-1, sICAM-1, and sE-selectin were significantly higher in patients with UAP in comparison with the group of healthy controls (P < 0.05). Patients with SAP also had higher levels of these biomarkers than those in healthy controls (P < 0.05), except for sE-selectin. The biomarker level did not differ between the two patient groups, except for MPO, which was significantly higher in the USP group (P < 0.05). Neopterin was significantly correlated only with sVCAM-1 (P < 0.05). In conclusion, CAD-Met patients with SAP had more apparent raised levels of serum sICAM-1 and sVCAM-1, simultaneously with higher MPO and neopterin concentrations, in comparison to those in healthy subjects. However, UAP is also associated with more substantial changes in MPO and significantly increased sE-selectin levels. Neopterin concentration was had a close correlation only with sVCAM-1.
Ieva Kalere, Ilze Konrāde, Anna Proskurina, Sabīne Upmale, Tatjana Zaķe, Normunds Limba, Gita Krieviņa, Aivars Lejnieks and Pēteris Tretjakovs
There is a close relationship between melatonin as a circadian regulator and insulin, glucagon and somatostatin production. This study aimed to describe subgroups of type 2 diabetes mellitus (T2DM) patients that may benefit from melatonin clock-targeting properties. The study involved 38 participants: 26 T2DM patients, and 12 participants without diabetes in the control group. Subjects were asked to complete the questionnaire of Pittsburgh Sleep Quality Index (PSQI). Standard biochemical venous sample testing was performed, and a sample of saliva was collected for melatonin testing. Melatonin concentration in participants without obesity (body mass index (BMI) < 30 kg/m2) was significantly higher than in obese participants: 13.2 (6.4; 23.50) pg/ml vs 5.9 (0.78; 13.1) pg/ml, p = 0.035. Subjects with BMI 30 kg/m2 had a significantly higher PSQI score than non-obese subjects: 7 (4.5; 10) vs 5.5 (3; 7), p = 0.043. T2DM patients showed significantly lower levels of melatonin than the control group: 6.1 (0.78; 12.2) pg/ml vs 17.8 (8.2; 25.5) pg/ml, p = 0.003. T2DM patients using short-acting insulin analogues showed a significantly higher PSQI score than patients not using insulin: 9 (6; 10) vs 6 (3; 8), respectively (p = 0.025). Poor sleep quality was more prevalent in patients with diabetic retinopathy than in those without this complication (p = 0.031). Lower melatonin levels were detected in T2DM and obese patients. Furthermore, poor sleep quality was observed in T2DM patients using short-acting insulin analogues and those with diabetic retinopathy, and obese individuals.
Pēteris Tretjakovs, Antra Jurka, Inga Bormane, Indra Miķelsone, Dace Reihmane, Līga Balode, Inta Jaunalksne, Vitolds Mackēvičs, Inga Stuķēna, Guntis Bahs, Aivars Lejnieks, Juris Aivars and Valdis Pīrāgs
Relation of Endothelial Dysfunction and Adipokines Levels to Insulin Resistance in Metabolic Syndrome Patients
Obese metabolic syndrome (MS) patients were categorised into three groups: 44 with type 2 diabetes mellitus (T2DM)(D); 20 with T2DM and coronary artery disease (CAD) (DC), and 26 with MS alone (M). Eighteen healthy subjects were selected as controls (C). Insulin resistance (IR) was assessed by HOMA-IR. Adiponectin, tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and interleukin-8 (IL-8) concentrations were measured by xMAP technology. Endothelin-1 (ET-1) was determined by ELISA. We used laser Doppler imaging for evaluating cutaneous endothelium-dependent vasodilatation in the hand. D and DC groups had significantly elevated IR compared with M or C group (P < 0.01). TNF-α, IL-6, IL-8, MCP-1 and ET-1 levels in DC were significantly elevated compared with other groups (P < 0.001). IL-6, IL-8, MCP-1 and ET-1 in D group were higher than those in C group (P < 0.05). TNF-α, IL-6, IL-8, MCP-1 and ET-1 concentrations were correlated with HOMA-IR indexes and adiponectin levels. All patients had lower adiponectin concentrations than controls (P < 0.001), but there were no differences between the patient groups. Only D and DC groups demonstrated a significant and similar decrease in LDI-Ach marker compared to C group (P < 0.001). LDI-Ach values were significantly correlated with HOMA-IR indexes and adiponectin levels (P < 0.001). Our findings show that obese MS patients have significantly increased HOMA-IR, TNF-α, IL-6, MCP-1 and IL-8 levels, decreased adiponectin concentration, and endothelial dysfunction, but the presence of T2DM and CAD in these patients is associated with more pronounced endothelial dysfunction and increased production of inflammatory cytokines and chemokines.