THE ROLE OF ACTIVATION OF SOLUBLE TUMOR NECROSIS FACTOR-Α RECEPTORS IN THE DEVELOPMENT OF COMORBID PATHOLOGY: CHRONIC HEART FAILURE ASSOCIATED WITH TYPE 2 DIABETES AND OSTEOPOROSIS
Shilov S.N., Berezikova E.N., Uzakov O.J., Samsonova E.N., Safronov I.D., Popova A.A., Yakovleva I.V., Efremov A.V., Schmidt G.,Teplyakov A.T., Grakova E.V.
Objective. To study the clinical and pathogenetic relationship between the risk of developing heart failure (CHF), type 2 diabetes mellitus (DM), and osteoporosis with the level of activation of soluble tumor necrosis factor-α 1 and type 2 receptors (TNF-α-SR1 and SR2) and osteoprotegerin, as well as to evaluate the effectiveness of bisphosphonate therapy in postmenopausal women.
Materials and methods. The study included 178 women aged 50 to 65: 48 women with CHF and type 2 diabetes (group 1), 93 patients with osteoporosis and CHF (group 2), 37 women with osteoporosis, CHF and type 2 diabetes type (group 3). The control group consisted of 35 postmenopausal women aged 50 to 65 years old, without clinical and instrumental signs of the pathology of the cardiovascular system and osteoporotic process. To determine the bone mineral density, an X-ray study was used by the method of dual-energy X-ray absorptiometry of the lumbar spine and the proximal femur. Determination of the concentration of TNF-α-SR1 and TNF-α-SR2 receptors, osteoprotegerin in the blood serum was carried out by the method of enzyme-linked immunosorbent analysis. Women with osteoporosis (n = 48) received bisphosphonates.
Results. Concentrations of TNF-α-SR1 and TNF-α-SR2 in groups 1-3 were higher (p <0.01) than levels in the control group. It was also found that the levels of both receptors were significantly higher in group 3 compared to patients in groups 1 and 2. TNF-α-SR1 levels TNF-α-SR2 were divided into quartiles (Q1-Q4) according to the increase in the concentration of these markers. For TNF-α-SR2, there was an increasing gradient in risk, with the odds ratio (OR) of cardiovascular events increasing from 1.43 to 7.50, but the risk was statistically significant only for Q3-Q4. OR increased for TNF-α-SR1 levels significantly for Q2-Q4 compared to Q1. The cumulative incidence of the combined endpoint of adverse cardiovascular events decreased with bisphosphonate therapy by 24% (p=0.01), reflecting the beneficial effect of these on the regression of associated cardiovascular pathology.
Conclusion. Postmenopausal women with elevated levels of soluble TNF-α-SR1 and SR2 receptors are diagnosed with an increased risk of developing unfavorable cardiovascular pathology associated with impaired bone mineral density. The purpose of bisphosphonates prevents bone metabolic disturbances, reducing the risk of adverse cardiovascular events.
Keywords: tumor necrosis factor-α receptors; osteoprotegerin; comorbidity; heart failure; diabetes; osteoporosis; bisphosphonates.