Aim. To study the influence of brain natriuretic peptide gene polymorphism (polymorphic locus Т-381С) on brain natriuretic peptide serum level and congestive heart failure onset risk and clinical features in patients with coronary heart disease. Methods. 412 patients with congestive heart failure were examined. Genotyping was performed by polymerase chain reaction. Brain natriuretic peptide N-terminal fragment level was assessed by ELISA. The control group included 211 healthy controls with no signs of cardiovascular pathology on examination. Results. In healthy people with C/C genotype the level of brain natriuretic peptide N-terminal fragment was significantly higher in comparison with people carrying T/T genotype. It was found that the T allele and T/T genotype of the T-381C natriuretic peptide gene polymorphic locus was associated with high risk, severity and unfavorable clinical course of congestive heart failure in patients with coronary heart disease. At the same time, the C allele and C/C genotype emerged as a protective factor regarding the risk, severity and clinical course of the disease. Conclusion. T/T genotype carriers of the of the T-381C natriuretic peptide gene polymorphic locus are a special subgroup associated with high risk of congestive heart failure onset and unfavorable clinical course. Therefore these patients with coronary heart disease should be considered as a group requiring an out-patient control and preventive measures targeted on congestive heart failure and premature mortality prevention.
Aim. To study the effectiveness of oral alendronate and ibandronate bisphosphonates for the prevention of cardiovascular complications in postmenopausal women with type 2 diabetes mellitus (DM) and osteoporosis during a 12-month prospective observation. Materials and methods. The study included 86 women with osteoporosis, chronic heart failure (CHF) and type 2 diabetes: the 1st group (n=52) included patients who received basic therapy for heart failure; the 2nd group (n=34) included patients who, in addition to the basic therapy of heart failure, were prescribed alendronic and ibandronic acid preparations for the treatment of osteoporosis. In order to identify the possibility of associating the studied factors with the nature of the course of heart failure, the patients were divided according to the results of a one - year follow - up into two subgroups: subgroup A (n=49) - patients with a favorable course of the disease and subgroup B (n=37) - patients with an unfavorable course of pathology. Results and discussion. After 12 months, a significant decrease in the levels of cerebral natriuretic peptide precursor (NT-proBNP), tumor necrosis factor-α, and interleukin-1β was found in the group of women treated with bisphosphonates compared to baseline. Significant associations of NT-proBNP levels (p=0.02) and the studied cytokines (p=0.01) with an unfavorable course of heart failure were revealed. A significant association of bisphosphonate therapy with a favorable course of heart failure (p=0.01) was also revealed. The probability of developing adverse cardiovascular events during the year in the treatment of heart failure with basic therapy drugs with additional therapy of osteoporosis with bisphosphonates is significantly (p=0.0025) lower than the treatment of patients with heart failure with only basic therapy and not taking bisphosphonates for the treatment of osteoporosis. Conclusion. In postmenopausal women with associated cardiovascular pathology (CHF, type 2 diabetes and osteoporosis), prophylactic therapy with oral alendronate and ibandronate oral bisphosphonates is effective, reduces the risk of progression of heart failure, inhibits inflammatory mediators, positively affects the combined endpoints of comorbid cardiovascular pathology.
Introduction. Diabetes mellitus, cardiovascular diseases and osteoporosis are linked by common pathophysiological mechanisms.Objective. To evaluate the effect of alendronate bisphosphonate on cardiovascular outcomes in comorbid patients with ischemic heart disease (CHD) associated with type 2 diabetes mellitus (type 2 diabetes) and osteoporosis during a two-year follow-up.Materials and methods. A total of 112 women with comorbid pathology including osteoporosis, coronary artery disease, and type 2 diabetes were examined. The patients' condition was assessed at baseline and prospectively for 24 months with a combined endpoint assessment, including: mortality, readmission for cardiovascular diseases, the development of myocardial infarction (MI), stroke, atrial fibrillation. Women were divided into groups: group 1 (n = 59) included patients who received basic therapy for IHD and type 2 diabetes, group 2 (n = 53) included patients who, in addition to basic therapy for coronary artery disease and diabetes Type 2 was prescribed alendronic acid preparation.Results and discussion. According to the results of two-year follow-up, the patients were divided into two subgroups: patients with a favorable (n = 61) and unfavorable course of coronary artery disease (n = 51). At the same time, during prospective observation, the following was assessed: the frequency of hospitalizations for cardiovascular diseases, the dynamics of the functional class (FC) of exertional angina, the development of MI, stroke, atrial fibrillation, and mortality. A significant association of alendronate therapy with a favorable course of ischemic heart disease (OR = 0.26; 95% CI = 0.18-0.57; p = 0.008), a decrease in the risk of MI (OR = 0.32; 95% CI = 0.11-0.87; p = 0.018) and worsening of FC of exertional angina (OR = 0.4; 95% CI = 0.17-0.91; p = 0.014).Conclusion. Long-term (24 months) use of alendronate is an effective and safe method for the treatment of associated cardiovascular pathology, represented by coronary artery disease, type 2 diabetes and osteoporosis in postmenopausal women, reducing the risk of MI, worsening of FC of exertional angina. These results suggest a more aggressive prescription of alendronate for osteoporotic patients at very high cardiovascular risk.
Highlights. Elevated levels of matrix metalloproteinases 2 and 9 are associated with the initiation and severity of CHF developed after breast cancer therapy with anthracyclines, which may contribute to cardiac remodeling and the progression of systolic dysfunction. Concentrations of matrix metalloproteinases-2 and -9 in blood serum serve as predictors of the unfavorable course of anthracycline-induced heart failure.Aim. To assess the role of matrix metalloproteinases-2 (MMP-2) and 9 (MMP-9) in the development and course of anthracycline-induced chronic heart failure (CHF) during 24 months of observation.Methods. The study included 114 women 12 months after completion of chemotherapy (CT) for breast cancer and developed CHF. The control group (n = 70) consisted of women (mean age 45.0 [42.0; 50.0] years old) who received doxorubicin as part of chemotherapy, but they did not develop CHF 12 months after completion of chemotherapy. The levels of biomarkers (MMP-2, MMP-9, NT-proBNP) in blood serum were determined using a sandwich immunoassay.Results. Patients with CHF had signs of cardiac remodeling and higher values of NT-proBNP, MMP-2 and MMP-9 (p<0.001) than women from the control group. After 24 months of observation, all patients with CHF were divided into 2 groups: group 1 – women with an unfavorable course of CHF (n = 54), group 2 – women with favorable course of pathology (n = 60). Criteria for the unfavorable course of CHF: the emergence of new or worsening of existing symptoms/signs of heart failure; and/or hospitalization due to HF decompensation; decrease in left ventricular ejection fraction by more than 10%; or an increase in the functional class of CHF by 1 or more. Baseline echocardiographic parameters and NT-proBNP values did not differ in groups 1 and 2. Levels of MMP-2 were higher by 8% (p = 0.017) and MMP-9 by 18.4% (p<0.001) in group 1. In 1 group the level of MMP-2 decreased after 24 months of observation. In group 2 the level of MMP-2 increased by the end of the observation period. MMP-2 levels ≥388.2 pg/ml (sensitivity 46%, specificity 80%; AUC = 0.64; p = 0.013) and MMP-9 ≥21.3 pg/ml (sensitivity 86%, specificity 84.4%; AUC = 0.9; p<0.001) were determined as predictors of an unfavorable course of CHF.Conclusion. Remodeling of the extracellular matrix may play an important role in the pathogenesis of CHF initiated by drugs of the anthracycline class. Elevated levels of MMP-2 and MMP-9 in the blood serum are associated with an unfavorable course of anthracycline-induced CHF and can be recommended when assessing the risk of an unfavorable course of pathology.
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