Background Secondary Antiphospholipid Syndrome (APS) can develop in 20-30% of patients with Systemic Lupus Erythematosus (SLE). Renal damage in the form of Lupus nephritis (LN) develops in 50-70% of SLE patients. Thrombotic microangiopathy (TMA) in patients with APS adds to the renal damage. It is known that risk of thrombotic complications increases when defects in genes affecting haemostasis are present. Objectives To study prognostic role of the PAI-1 (4G/5G 675), Factor XIII (G485T), FBG G (-455)A), GPIa (C807T), GPIIIa (T196C), p22phox (C242T), eNOS (G894T), MTHFR (C677T) thrombophilia genes polymorphisms in development of clinical and laboratory manifestations of APS and LN in patients with SLE and APS. Methods The study involved 100 SLE patients of Caucasian race, 80 (80%) of which were females and 20 (20%) were males in the age from 16 to 73 years. Polymorphisms were analysed with molecular genetic analysis methods. SLE was diagnosed according to American College of Rheumatology's criteria. APS was diagnosed using clinical and laboratory criteria developed in 2006. Patients groups (comparable in age and sex) were as follows: first group of 50 patients with SLE and APS, and second group of 50 patients with SLE without APS. Frequency of allelic variations of studied genes were compared between groups. Analysis of frequency of clinical manifestations of APS and LN was performed taking patients' genotypes into account. Results When comparing patients with SLE with APS and SLE without APS statistically significant differences were not observed. Patients with APS-associated arterial and/or venous thromboses more frequently have minor allele (T) and genotype (TT) p22phox (C242T) compared to patients with APS without thromboses; T: 64.5% vs 34% (p=0.033), TT: 36% vs 7% (p=0.021, OR=2.1 (95% confidence interval (CI) 1.5-22.7). Patients with livedo reticularis and APS more frequently had minor allele (T) and genotype (TT) eNOS (G894T) compared to patients without livedo; T: 33% vs 10% (p=0.019), TT: 15% vs 0% (p=0.031, OR=2.49 (95% CI 1.2-28.9). Patients with APS and rapidly progressive lupus nephritis (RPLN) considerably more frequently had minor allele (T) and genotype (TT) MTHFR (C677T); T: 45% vs 27% (p=0.038), TT: 30% vs 0% (p=0.033, OR=3.1 (95% CI 1.4-32.7). In the group of patients without APS no correlation between studied polymorphisms and renal damage was found. Conclusions Having mutant allele of p22phox (C242T) subunit of NADPH-oxidase increases risk of developing arterial and venous thromboses in patients with SLE and APS. eNOS (G894T) gene polymorphism is associated with higher frequency of blood microcirculation disorders in organs and tissues of patients with SLE and APS. RPLN development risk in patients with SLE is probably related to mutation in MTHFR gene (C677T). Allelic contribution of PAI-1 (4G/5G 675), Factor XIII (G485T), FBG (G (-455)A), GPIa (C807T) and GPIIIa (T196C) is less pronounced in development of thrombotic complications within SLE with APS, probably because of existence ...
Aim To test a hypothesis that increased values of red cell distribution width (RDW) in patients with chronic heart failure (CHF) can be related with low exercise tolerance.Material and methods 102 patients were evaluated who had CHF with mid-range and reduced left ventricular ejection fraction (LV EF) without anemia (72% men, mean age 66±10.2 years). Cardiopulmonary stress test (CPST), echocardiography, 6‑min walk test (6MWT), blood count, and measurements of N-terminal pro-brain natriuretic peptide (NT-pro-BNP) and serum iron were performed.Results The average LV EF was 39±8.7 %; the peak oxygen consumption (VO2peak) was 13.7±4.8 ml /kg /min; and the median NT-pro-BNP was 595.3 pg /ml (Q1–3 1443–2401). RDW variables, including the RDW coefficient of variation (RDW-CV) and RDW standard deviation (RDW-SD), were not significantly related with serum iron or hemoglobin concentrations. A one-factor linear regression analysis showed a significant correlation of VO2peak with RDW-SD (р=0.039). A multivariate linear regression analysis with adjustments for LV EF, hemoglobin concentration, and age did not reveal any significant correlation of VO2peak with RDW variables. The distance covered in the 6MWT was significantly associated with RDW-CV both in the one-factor analysis and with adjustments for LV EF, hemoglobin and serum iron concentrations, and age.Conclusion This study showed that high RDW values in CHF patients without anemia predicted low exercise tolerance regardless of the age, LV systolic function, and hemoglobin and serum iron concentrations. A 16% increase in RDW-CV significantly decreased the likelihood of covering a distance longer than 360 m during 6 min.
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