Cardio-ankle vascular index for predicting cardiovascular morbimortality and determinants for its progression in the prospective advanced approach to arterial stiffness (TRIPLE-A-Stiffness) study.

BACKGROUND: The cardio-ankle vascular index (CAVI) measure of arterial stiffness is associated with prevalent cardiovascular risk factors, while its predictive value for cardiovascular events remains to be established. The aim was to determine associations of CAVI with cardiovascular morbimortality (primary outcome) and all-cause mortality (secondary outcome), and to establish the determinants of CAVI progression. METHODS: TRIPLE-A-Stiffness, an international multicentre prospective longitudinal study, enrolled >2000 subjects ≥40 years old at 32 centres from 18 European countries. Of these, 1250 subjects (55% women) were followed for a median of 3.82 (2.81-4.69) years. FINDINGS: Unadjusted cumulative incidence rates of outcomes according to CAVI stratification were higher in highest stratum (CAVI > 9). Cox regression with adjustment for age, sex, and cardiovascular risk factors revealed that CAVI was associated with increased cardiovascular morbimortality (HR 1.25 per 1 increase; 95% confidence interval, CI: 1.03-1.51) and all-cause mortality (HR 1.37 per 1 increase; 95% CI: 1.10-1.70) risk in subjects ≥60 years. In ROC analyses, CAVI optimal threshold was 9.25 (c-index 0.598; 0.542-0.654) and 8.30 (c-index 0.565; 0.512-0.618) in subjects ≥ or <60 years, respectively, to predict increased CV morbimortality. Finally, age, mean arterial blood pressure, anti-diabetic and lipid-lowering treatment were independent predictors of yearly CAVI progression adjusted for baseline CAVI. INTERPRETATION: The present study identified additional value for CAVI to predict outcomes after adjustment for CV risk factors, in particular for subjects ≥60 years. CAVI progression may represent a modifiable risk factor by treatments. FUNDING: International Society of Vascular Health (ISVH) and Fukuda Denshi, Japan.

The associations of cytokines and gens polymorphisms of ß-adrenoceptors in patients with heart failure and some thyroid pathology (literature review and own observations).

OBJECTIVE: Aim: To analyze the role of cytokines in the progression of heart failure (HF) in patients with concomitant pathology of the thyroid gland. PATIENTS AND METHODS: Materials and Methods: The systematization of literature data on the role of cytokines in the progression of HF in patients with concomitant thyroid pathology (TP) was carried out. The results of our own research were presented. CONCLUSION: Conclusions: The final chapter in the history of the role of cytokines in the progression of HF has not yet been written. Further studies, including genetic ones, are necessary. The patients with HF have higher levels of TNFß and IL-6, and a lower concentration of IL-4, compared to the control group. Patients with a fatal outcome of the disease, in contrast to those who survived for two years, have an increased level of TNFß. In patients with concomitant TP, who had repeated hospitalization, a lower level was registered, compared to that under conditions of a more favorable course of heart failure. Concentrations of cytokines in the blood of patients with HF are associated with gene polymorphisms of the ß-adrenoreceptor system: the C-allele of the Gly389A polymorphism of the ß1-adrenoceptor gene leads to a decrease in the risk of increasing TNFα; IL-1α increases in the presence of the A-allele of the Ser49Gly polymorphism of this gene. In patients with HF and concomitant thyroid pathology, the risk of IL-6 growth increases in homozygous (C) patients for the Ser275 polymorphism of the ß3 subunit of the G-protein.

Use of beta-blockers in patients with heart failure - unresolved issues.

The analysis of literature data reflecting the issues of the mechanisms of action of beta-blockers in patients with heart failure are present. The heart failure has many variants. With each of these options, the concentration of catecholamines and the sensitivity of beta receptors change differently. The effectiveness of beta-blockers also differs in this. The beta-adrenergic receptors genes polymorphisms also affect the efficacy and safety of beta-blockers. The comorbidities also affect to the action and efficacy of beta-blockers in patients with heart failure. When using beta-blockers in patients with heart failure, there are still many unresolved questions: What is the best reference point for titration of drugs - dose or heart rate; what effects do these drugs have in heart failure with a preserved left ventricular ejection fraction? How do beta-blockers affect the course of heart failure in patients with comorbid thyroid pathology, taking into account their pharmacological properties and their effect on the activity of peripheral deidinases?

Influence of various risk factors on the level of ST2 biomarker in patients with heart failure and diabetes mellitus type 2.

Heart failure (HF) despite the progress in treatment remains the main health problem worldwide. Biomarker ST2 is currently being studied in patients with HF due to its high potential predictive value and promising prospects for use as a component of biomarker-controlled therapy. The factors that can impact on the ST2 biomarker level in diabetic patients with heart failure with preserved ejection fraction (HFpEF) are still not well known. AIM: The aim of the study was to determine the influence of various risk factors on ST2 levels in patients with HFpEF and diabetes mellitus type 2 (T2DM). MATERIALS AND METHODS: A total of one hundred and thirty-four patients (74 females and 60 males, 51 diabetic patients and 83 patients without T2DM with HFpEF were examined. Duration of HF and T2DM, common risk factors, such as smoking, overweight, clinical examination, parameters of carbohydrate and lipid metabolism, glomerular filtration rate (GFR) and M235T polymorphism of ATG have been used. Multivariate backward stepwise cox regression analysis was performed in Statistica 10,0. p<0,05 was considered statistically significant. RESULTS: ST2 level in patients with HFpEF associated with T2DM exceeded this value in patients with HFpEF without T2DM and was 23.26 ng/ml (18.5: 29.3) vs. 20.39 ng/ml (18.3: 24.6), respectively (p<0,05). To assess the cumulative effect of the studied factors on the ST2 level, we performed the Cox's stepwise multivariate regression analysis. Smoking, HOMA-IR (Homeostatic Model Assessment for Insulin Resistance), glucose, HbA1 and insulin levels were found to be the most significant factors influencing ST2 levels in patients with HF and T2DM, indicating a significant effect of DM type 2 on ST2 concentration. CONCLUSIONS: Smoking, HOMA-IR, glucose, HbA1, and insulin levels can significantly affect ST2 levels in patients with T2DM and HFpEF.

The effect of beta-blockers on a course of chronic heart failure in patients with a low triiodothyronine syndrome.

OBJECTIVE: The aim: The aim is to study the effect of ß-ABs in patients with LT3 S on the course of HF. PATIENTS AND METHODS: Materials and methods: 354 patients with HF on a background of post-infarction cardiosclerosis were included in the 2-yeared follow-up study. LT3 S was diagnosed at 89 (25.1%) patients. The levels of thyroid-stimulating hormone, free T3f and T4f, and reversible T3 were determined. The echocardioscopy was performed. RESULTS: Results: Patients with HF in combination with LT3 S have a heavier functional class by NYHA, greater dilatation of the left heart cavities, less myocardial contractility, a higher frequency of atrial fibrillation and re-hospitalization. The use of ß-ABs in patients with HF without LT3 S leads to a likely decrease in hospitalization frequency, while in patients with LT3 S it has an opposite effect. The frequency of rehospitalization increases with an excess of ß-ABs dose > 5 mg (equivalent to bisoprolol). At these patients a decrease in serum T3 level and negative dynamics of parameters of intracardiac hemodynamics are observed. CONCLUSION: Conclusions: The use of ß-ABs in patients with LT3 S leads to an increase in re-hospitalization at a dose over 5.0 mg (equivalent to bisoprolol). In these patients there is a decrease in serum T3, an increase in T4 level; and the ejection fraction decrease; and heart cavities size increase.

The association of polymorphisms of ß-adrenergic receptors genes with the low triiodothyronine syndrome in patients with a heart failure.

The course of heart failure (HF) and its progression is associated with comorbidities, genetic factors and a dynamics of a number of biomarkers. The low triiodothyronine syndrome (LT3S) is observed in some patients with HF. Extremely little data are available in the literature regarding the effect of ß-adrenoreceptors (ß-AR) genes polymorphisms on the development of LT3S and many contradictory results about their association with HF course. This encourages new research in this area. AIM: The aim of study was to evaluate the relationship of ß-adrenergic receptors gene polymorphisms with low triiodothyronine syndrome in patients with a heart failure. MATERIALS AND METHODS: 354 patients with HF on a background of postinfarction cardiosclerosis were included to the study. At 89 (25.1%) patients LT3S was diagnosed. The course of HF was studied for 2 years. Mean levels of thyroid stimulating hormone (TSH), free T3f and T4f were evaluated. Genotyping of 4 single nucleotide polymorphisms (Gly389Arg of ß1-AR gene, Ser49Gly of ß1-AR gene, Gln27Glu of ß2- AR gene and Ser275 of GNß3 gene) was performed by polymerase chain reaction. Genetic and epidemiological analysis was performed using the SNPStats program. RESULTS: The risk of LT3S in patients with HF increases with homozygous G/G variant of Gln27Glu polymorphism of the ß2-AR gene (OR=2.21, p=0.037), described as a recessive model of inheritance. There was a tendency to increase the risk of LT3S development in the presence of the genotype C/T of the Ser275 polymorphism of the GNb3 gene (OR=1.75, p=0.054), described as an over-dominant model. The genotype C/G of the Gln27Glu polymorphism of the ß2-AR gene was associated with a decreased risk of LT3S development (OR=0.54, p=0.037), described as over-dominant model. Patients with HF carriers the A allele (A/GA/A) of the Ser49Gly polymorphism of the ß1-AR gene have a lower risk of repeated hospitalization due to HF decompensation (OR=0.50, p=0.032), described as a dominant model. There was a tendency to increase the risk of re-hospitalization in the G-allele (C/GG/ G) variant of the Gln27Glu polymorphism of the ß2-AR gene (OR=1.68, p=0.057), described as a dominant heredity model. At patients with HF in combination with LT3S the risk of re-hospitalization increases at C/G variant of the Gln27Glu polymorphism of ß2-AR gene (OR=1.25, p=0.025), described as an over-dominant model. CONCLUSIONS: The results suggest that congenital genetic alterations in ß-adrenergic pathways may be associated with the development of LT3S in patients with HF and the features of the HF course.