The combination of hypertension and type 2 diabetes revealed a stronger effect of type 2 diabetes on a significant increase in the level of GDF-15 due to the correlation with the level of glycemia and, in addition, the non-inflammatory mechanism of action of GDF-15 and metformin. In addition, the increase in the level of GDF-15 was influenced by the age of patients, blood pressure and the presence of concomitant coronary heart disease and AF. Increased levels of galectin-3 were observed in patients with signs of fibrosis, in particular in stage 3 hypertension, as well as increased levels of P-selectin, which reflected the activation of the platelet component and increased risk of atherothrombosis. A significant decrease in the level of P-selectin in patients with AF was due to the simultaneous use of anticoagulants and antiplatelet agents.
GDF-15 and galectin-3 levels showed an association with LVH, but a stronger relationship was observed between GDF-15 levels and GFR and albuminuria levels.
The relationship between the level of GDF-15 and diastolic blood pressure (r=0.251 p =0.023) was found. The weak reliable correlation between P-selectin and SBP and DBP (r =0.192, p=0.035 and r=0.181, p=0.047, respectively) is due to the fact that the increase in blood pressure, on the one hand, leads to the activation of P-selectin synthesis, as a compensatory response aimed at reducing the pressor effects of angiotensin II, which, in turn, activates the cellular mechanisms of atherosclerosis progression.
The highest level of GDF-15 was associated with correlation analysis and linear regression analysis with the average SBP at night, and due to this, with the average SBP per day. The connection of P-selectin with the level of DBP at night was also revealed, but the most probable is not the connection of P-selectin with DBP at night, but the coinciding circadian rhythm of P-selectin and DBP at night in patients with hypertension and type 2 diabetes with circadian BP by type "Nondipper".
Analysis of the total endpoint by comparison groups for the observation period of 36 months showed a tendency to a more unfavorable course of the combination of hypertension and type 2 diabetes compared with isolated hypertension and type 2 diabetes, while analysis of factors influencing the prognosis showed the impact on the total endpoint hypertension and type 2 diabetes, no decrease in blood pressure at night on the type of "Nondipper", left ventricular myocardial hypertrophy. Among the biomarkers of inflammation studied in the study, the greatest influence on the prognosis was the level of GDF-15 above the median at the time of inclusion in the study, for which there was a significant increase in additional risk (OR = 1.44; CI 95%: 1.06-1, 96).
The dependence of GDF-15 levels on the achievement of the "target" blood pressure level shown in our study can be explained by the positive effect on hemodynamics and structural changes in the cardiovascular system due to better blood pressure control, as one that finally correlates with reduced risk of cardiovascular events including mortality, development of heart failure and diabetes.
Analysis of the effect of antihypertensive drugs on the level of GDF-15 showed that RAS blockers had an effect on reducing the level of GDF-15, but this effect was largely due to the effects of ACE inhibitors, while ARBs had little effect. According to the analysis of the chances, calcium antagonists had the greatest influence on the reduction of GDF-15 levels, which was confirmed by a significantly lower level of GDF-15 in patients who were taking this group of antihypertensive drugs at the time of inclusion in the study.
None of the classes of antihypertensive drugs had a significant effect on the level of Galectin-3 and P-selectin, with a tendency to lower levels of CRP in patients taking PAC blockers and anticoagulants, and a tendency to higher levels of SBR in patients who took diuretics. P-selectin levels decreased significantly under the influence of antiplatelet drugs and anticoagulants.
Glycemic control at the target level did not significantly affect the level of biomarkers of inflammation, neither at the time of inclusion of patients in the study, nor after 12 months of treatment. Metformin was accompanied by a significant increase in the level of GDF-15 in patients (3109.76 ± 1231.88 and 2114.66 ± 754.14 ng / ml, p <0.05, respectively; OR = 1.76 (CI: 1,35-1, 93), however, at the level of P-selectin and Galectin-3 metformin was not significantly affected, as well as sulfonylurea, which did not significantly affect any of the analyzed biomarkers of inflammation.
