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Title:
Etiopathogenesis of hypertension
Author:
Subject:
arterial hypertension ; interleukins ; inflammatory factors ; urocortin 2 ; arterial stiffness
Abstract:
Introduction Hypertension is one of the most common diseases in the world. Among the established classic factors involved in the development of primary hypertension are the excessive activity of the renin-angiotensin-aldosterone system and the sympathetic nervous system. The involvement of the immune system in the development of hypertension and its complications is also increasingly emphasized. Despite abundant evidence in preclinical studies of the effects of inflammation on vascular endothelium and blood pressure values, there is a lack of work evaluating the association of inflammatory interleukins with blood pressure values in both chronic inflammatory diseases and hypertension itself. In addition to inflammatory interleukins, new factors such as urocortin 2 may also influence the development of hypertension and the regulation of blood pressure values. Aims of the study The purpose of this study was to evaluate the relationship between markers and blood pressure values, and to determine the relationship between inflammation and hypertension and vascular stiffness in chronic inflammatory diseases using rheumatoid arthritis and ankylosing spondylitis as examples. In addition, we also wanted to determine the relationship between blood pressure values and levels of Ucn2, a peptide with postulated vasodilatory effects. Materials and Methods: A total of 177 patients were st ; udied in two distinct populations. The first group consisted of patients with inflammatory joint diseases such as rheumatoid arthritis (26 patients) and ankylosing spondylitis (45 patients) and a control group (29 patients). The second group consisted of newly diagnosed hypertension patients (38 patients) and the control group (29 patients). Information about concomitant diseases, medications, smoking, family history of cardiovascular disease, physical examination, anthropometric measurements and vital signs were obtained from each patient in both groups. Patients with inflammatory joint diseases had an additional disease activity assessment performed: patients with RA - DAS 28; patients with AS - BASDAI; while patients with hypertension had an additional 24-hour blood pressure monitoring performed. Additionally, vascular stiffness was assessed and laboratory tests were performed, including evaluation of inflammatory interleukins and indices of vascular endothelial dysfunction. The levels of IL-6, IL-18, TNFα, fibrinogen, pentraxin 3, sICAM, sVCAM, E-selectin, vWF, tissue plasminogen activator, fibrinogen were evaluated in the group of patients with inflammatory joint disease and in the control group. The levels of ITAC, GM-CSF, Fractaline, IFNγ, IL-10, MIP-3α, IL-12, IL-13, IL-17A, IL-1β, IL-2, IL-21, IL-23, IL-5, IL-6, IL-7, IL-8, MIP-1α, MIP-1β, TNFα, IL-15, Ucn2 were eval ; uated in the group of patients with newly diagnosed hypertension and in the control group. Statistical analysis was performed using Statistica version12 and 13 and SPSS IBM version 28 software. Results: The population of patients with rheumatoid arthritis, ankylosing spondylitis, and the control group. The values of office blood pressure and central pressure in all groups were comparable. There were no statistically significant differences between the groups in arterial stiffness as assessed by pulse wave velocity, aortic pulse wave augmentation and pulse wave augmentation index. The patients in each group differed in HDL cholesterol, creatinine, and HbA1c levels. Furthermore, inflammatory markers, that is, ESR, hsCRP, IL-6, fibrinogen, and TNFα were elevated in patients with RA and AS (TNFα level, after adjustment to age and sex, ultimately did not differ between the groups). Additionally, some parameters of vascular endothelial function, like PTX-3, vWF, sVCAM were elevated in patients with inflammatory arthritis; while IL-18 and tPA levels did not differ between groups. The population of patients with newly diagnosed hypertension and the control group. Hypertensive patients had lower logUcn2 levels (2.09±0.63) than healthy volunteers (2.44±0.70; p=0.04). LogUcn2 in the hypertensive group correlated negatively with values of nocturnal diastolic blood pressure, while no ; relationship was shown between blood pressure values and Ucn2 in the group of healthy volunteers. An analogous relationship between logUcn2 and nocturnal diastolic blood pressure was confirmed in multivariate regression analysis with gender and age in the whole group. Furthermore, there was no association of logUcn2 with the presence of obesity, metabolic syndrome, or insulin resistance. However, a negative relationship was observed between logUcn2 and total and LDL cholesterol in the healthy group; a similar relationship was not found in the hypertensive group. The relationship between logUcn2 and total cholesterol persisted when age, sex, and the presence of hypertension were included in the analysis. Despite differences in blood pressure values, the groups did not differ in pulse wave velocity (hypertensive patients versus healthy volunteers: 9.6 [8.6-10.3] m/s versus 8.75 [7.9 - 10.5]ms; p=0.167) or the level of inflammatory factors such as: TNFα, INFγ, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-8, IL-10, IL-12, IL-13, IL-15, IL-17A, IL-21, IL-23, hs-CRP, MIP-1α, MIP-1β, MIP-3α, GM-CSF, fractalkine, ITAC. There was a correlation between IL-5, IL-8, hs-CRP, and ITAC levels and blood pressure values, but after adjusting for age, sex and BMI the association were no longer statistically significant. Two factors were created: Factor 1- pro-inflammatory (containing IL-1β, ; IL-2, IL-6, IL-7, IL-12, IL-6, IL21, TNFα, INFγ) and Factor 2 anti-inflammatory (containing IL-13 and IL-5). We found no association between the Factors and the blood pressure values. Conclusions The levels of inflammatory makers in patients with newly diagnosed hypertension are comparable to those in healthy control group. We do not find any relation between inflammatory indices and blood pressure values. Patients with short duration chronic inflammatory joint diseases, despite higher values of inflammatory indices and the presence of endothelial dysfunction markers, do not differ in blood pressure values or vascular stiffness compared to healthy subjects. Subjects with newly diagnosed hypertension have reduced urocortin 2 levels compared to healthy subjects, and Ucn2 levels exhibit an age- and sex-independent association with diastolic nocturnal blood pressure values in hypertensive patients.
Place of publishing:
Level of degree:
Degree discipline:
Degree grantor:
Rada Dyscypliny Nauki medyczne
Promoter:
Grodzicki, Tomasz ; Walczewska, Jolanta