Onset Of Arterial Hypertension Research Articles

CD19-targeting CAR T-cell therapy in patients with diffuse systemic sclerosis: a case series

CD19-targeting chimeric antigen receptor (CAR) T-cell therapy has shown remarkable outcomes in patients with systemic lupus erythematosus. The effects of CD19-targeting CAR T cells on organ manifestations in patients with systemic sclerosis have yet to be characterised. B cells have a central role in the pathogenesis of systemic sclerosis. We present a detailed analysis of the effects of CD19-targeting CAR T-cell therapy in patients with systemic sclerosis. Six patients with severe diffuse systemic sclerosis with an insufficient response to at least two treatments were consecutively recruited at the Department of Internal Medicine 3, University Hospital Erlangen (Erlangen, Germany) to receive CD19-targeting CAR T-cell treatment (1 × 106 CAR T cells per kg bodyweight). Events were predefined by progression of interstitial lung disease, onset of congestive heart failure, onset of renal failure, onset of arterial hypertension, or initiation of new immunosuppressive or antifibrotic therapy. Event-free time or treatment intensification after study entry was the primary outcome. Key secondary outcomes included changes in the modified Rodnan Skin Score (mRSS), imaging (a component of the assessment of lung fibrosis), laboratory assessments, patient-reported outcomes, and a modified version of the American College of Rheumatology Composite Response Index in Systemic Sclerosis (ACR-CRISS), assessed at baseline, 3 months, 6 months, 9 months, and 12 months. Between April 20, 2022, and Nov 8, 2023, six patients with severe diffuse systemic sclerosis (median age 42 years [IQR 36-53]; four men and two women; all White European) were recruited and received CD19-targeted CAR T-cell therapy. The median follow-up time was 487 days (IQR 342-585). No events occurred within the observational period. Probability of improvement in the ACR-CRISS score increased to a median of 100% (IQR 100-100) at 6 months. Median mRSS decreased by 31% (IQR 29-38), corresponding to a median of 8 points (IQR 7-13) within 100 days. The extent of disease on CT scan decreased by a median of 4% (IQR 3-4) due to reduction of ground-glass opacities while the reticular pattern remained stable. Forced vital capacity improved by a median of 195 mL (IQR 18-275) at the latest observational timepoint. We provide the first evidence that CD19-targeting CAR T-cell therapy might intercept with the progression of fibrotic organ manifestations in patients with systemic sclerosis. Deutsche Forschungsgemeinschaft, Deutsche Krebshilfe, ELAN-Foundation Erlangen, IZKF Erlangen, and Bundesministerium für Bildung und Forschung.

The potential effect of natural antioxidants on endothelial dysfunction associated with arterial hypertension.

Arterial hypertension represents a leading cause of cardiovascular morbidity and mortality worldwide, and the identification of effective solutions for treating the early stages of elevated blood pressure (BP) is still a relevant issue for cardiovascular risk prevention. The pathophysiological basis for the occurrence of elevated BP and the onset of arterial hypertension have been widely studied in recent years. In addition, consistent progress in the development of novel, powerful, antihypertensive drugs and their appropriate applications in controlling BP have increased our potential for successfully managing disease states characterized by abnormal blood pressure. However, the mechanisms responsible for the disruption of endogenous mechanisms contributing to the maintenance of BP within a normal range are yet to be fully clarified. Recently, evidence has shown that several natural antioxidants containing active ingredients originating from natural plant extracts, used alone or in combination, may represent a valid solution for counteracting the development of arterial hypertension. In particular, there is evidence to show that natural antioxidants may enhance the viability of endothelial cells undergoing oxidative damage, an effect that could play a crucial role in the pathophysiological events accompanying the early stages of arterial hypertension. The present review aims to reassess the role of oxidative stress on endothelial dysfunction in the onset and progression of arterial hypertension and that of natural antioxidants in covering several unmet needs in the treatment of such diseases.

Characteristics of patients with non-specific aortoarteritis and arterial hypertension based on retrospective analysis

The aim was to study the medical history, laboratory and instrumental data, the trends of arterial hypertension (AH), risk factors for cardiovascular events, target organ damage (TOD), and the development of cardiovascular complications in patients with NSAA (Non-Specific Aortoarteritis).Materials and Methods. The study included 33 women with confirmed NSAA who had been treated at the 5th Cardiology Department of the E.I. Chazov National Medical Research Center of Cardiology since 2005. Complete blood count, biochemical blood analysis, urine analysis, the following instrumental examinations, such as, ECG, echocardiography, ultrasound of the brachial, femoral, aortic, and renal arteries, MRA or CT angiography with contrast, blood pressure measurement in the arms and legs were performed for all patients. Telephone interviews were conducted to assess some patient's condition over time.Results. The most common symptom (84% of patients) was AH, the average age of AH onset was 30 [19; 40] years and the AH average duration is 7,5 [2; 13] years. Nearly half of the patients (45%) had AH as the leading symptom that led them to perform the examination that helped to the diagnosis of NSAA. The average systolic and diastolic blood pressure values were 123±35 mmHg and 66±17 mmHg in the upper extremities, and 166±31 mmHg and 78±18 mmHg in the lower extremities, respectively. About half of patients (51%) had stage 3 AH, and almost all of them had type 3 according to E. Lupi-Herrera classification. The most common risk factors for cardiovascular events were dyslipidemia (82%), a family history of early cardiovascular events (51%), resting heart rate above 80 bpm (25%), and carbohydrate metabolism disorders (21%). When assessing cardiovascular risk, moderate risk of developing cardiovascular events was observed in 3 patients (10,7%), high risk in 16 patients (57,1%), and very high risk in 9 patients (32,1%). The most common TODs were nervous system damage (53%), including cerebrovascular ischemic events (14%) and left ventricular hypertrophy (42%). This group of patients was characterized by resistant hypertension, and combination with other risk factors for cardiovascular events, it leds to severe TOD and influenced survival rate. In terms of antihypertensive therapy, 61% of patients received combination therapy, with CCB, beta-blockers, and imidazoline receptor agonist being the most prescribed. Two fatal cases were identified in the long-term follow-up, and cardiovascular events, most frequently stroke, were the main complications observed. Additionally, AH progression and its uncontrolled course despite going through multiple drug therapy were characteristic.Conclusion: AH is often difficult to diagnostic in patients with NSAA, and it significantly contributes to the structure of complications and mortality in this patient cohort, progressively worsening over time. It is important to measure blood pressure in both arms and legs to detect elevated values early. The main goals of treatment are achieving NSAA remission and blood pressure control and preventing cardiovascular events.

INCREASED RISK OF NEW ONSET OF ARTERIAL HYPERTENSION IN PATIENTS WITH MULTIPLE MYELOMA TREATED WITH CARLFIZOMIB

Objective: Several new drugs are used nowadays to treat multiple myeloma (MM). Some drugs are loaded with an increased risk of developing cardiovascular diseases. Carfilzomib (K), a proteasome inhibitor, is well recognized to cause cardiovascular side effects. Also, arterial hypertension is a main factor leading to LV dysfunction. Purpose is to evaluate if patients who underwent the carfilzomib treatment may present an increased incidence of arterial hypertension. Design and method: We evaluated 34 patients (group K, 20M, 14F, aged 65.87±5.98) treated with carfilzomib: 25 patients were given 56 mg/m2 (group 1, 14M, 9F, aged 67.30±5.98) while 9 27 mg/m2 (group 2, 6M, 3F, aged 63.00±5.39). As controls, we recruited 34 patients (16M, 18F, aged 69.80±9.13) who underwent in the same period the MM treatment without carfilzomib. Hypertension was identified as new onset of disease or worsening of disease (need double the dose used, add a new drug, or no pressure control in at least 3 drugs treatments). Results: At baseline, the controls presented an increased arterial hypertension rate (76.47% vs group K 47.06%, p = 0.07). There was no difference in any other CVD risk factor. There was no difference in LV mass, volumes and ejection fraction. The group K experienced an increased incidence of arterial hypertension compared to controls (controls 0% vs group K 41.17 %, p = 0.001). This result was not related to the drug dose. Finally, there was no difference in mortality between the two groups also by analysing the CV death. Conclusions: Carfilzomib is a potent and effective drug in MM. Its cardiovascular toxicity relates to a vascular and endothelial damage leading to a new onset of arterial hypertension. This observation may be useful in preventing evolution of the CV dysfunction in survivors and long survivors MM patients. Also, it may be important for studies of vascular damage in arterial hypertension pathophysiology.

Parameters of cutaneous microvasculature in men of working age with newly diagnosed arterial hypertension.

To investigate structural and functional features of cutaneous microvasculature in men of working age with newly diagnosed arterial hypertension (AH). The study included 161 apparently healthy men from 30 to 60 years, who underwent a comprehensive examination of cardiovascular system "from the heart to the capillaries". Control group (CG) included 60 normotensive men. AH group included 101 men with elevated BP. There is no rarefaction of the capillary bed and latent fluid retention in the interstitial space in the skin in men with AH. No data were obtained for increased endothelial, neurogenic and myogenic tone of resistive cutaneous precapillary arterioles in AH group, but a decrease in the perfusion efficiency of the endothelial and myogenic mechanisms of tissue perfusion modulation was noted. Obtained results allow making the assumption that metabolic disorders at the level of capillaries that are of a systemic nature prevail in men with the onset of AH.

Posterior reversible encephalopathy syndrome due to arterial hypertension may mark the onset of the symptomatic phase in Huntington's disease.

Autonomic dysregulation of cardiovascular functions marks early Huntingtons disease (HD). Blood-brain barrier (BBB) is dysfunctional in HD. A 37-year-old female carrying 41 CAG triplets in the huntingtin gene acutely presented with a multifaceted syndrome attributable to posterior reversible encephalopathy syndrome (PRES). Syndrome was associated with arterial hypertension (AHT). The syndrome fully recovered both by imaging and clinical signs after normalization of arterial pressure during hospitalization. Immediately after hospital discharge, the patient developed a complex psychiatric syndrome and choreic movements that represented conversion to the symptomatic phase of HD. A one-year later follow up clearly showed the patient had developed the symptomatic stage of HD by presenting both psychiatric symptoms and choreic movements. Onset of AHT may represent an early premonitory signal of HD becoming manifested. Induction of PRES might be associated with BBB impairment in HD.

Acute congestive heart failure due to Bevacizumab in metastatic breast cancer: a case report

The addition of Bevacizumab to chemotherapy has shown its first-line interest in metastatic breast cancer by improving PFS but not OS. After a certain period of exposure, the appearance of side effects such as acute Congestive heart failure (CHF) has been described during clinical trials; manifested by a drop in LVEF and clinical signs which sometimes caused a hospitalization. We report the case of a patient in whom this exposure time was rather long with a very long survival under Bevacizumab. The onset of arterial hypertension appeared after 8 months of treatment with Bevacizumab in combination with metastatic first- line chemotherapy, while acute CHF occurred after approximately 10 years of treatment, which is at the 129th treatment. The evolution of CHF was favorable after adequate treatment and discontinuation of Bevacizumab as in most cases reported in the literature.

Performance of the sFLT-1 / PLGF Ratio in the Diagnosis of Preeclampsia in Four Hospitals in Brazzaville (Republic of Congo)

Preeclampsia is a serious obstetric situation, responsible for high maternal and perinatal morbidity and mortality. Its diagnosis is clinical and biological, with confirmation either by proteinuria on the urine dipstick or by 24-hour proteinuria constituting the gold standard. Current revisions to the definition of preeclampsia tend to free themselves from reliance on proteinuria for diagnosis. They are oriented towards a broader model where the involvement of a target organ concomitant with gestational hypertension is sufficient to make the diagnosis of preeclampsia. Late positivity of proteinuria after the onset of arterial hypertension (HTA) has been reported, contrasting with the precocity of angiogenic factors such as soluble Fms tyrosine kinase type 1 (sFlt-1) and placental growth factor (PlGF). <i>Objective.</i> To evaluate the performance of the sFLT-1/PLGF ratio in the diagnosis of preeclampsia. <i>Methods.</i> Cross-sectional multicenter analytical study conducted from October 17 to December 17, 2020 including hypertensive pregnant women, treated or not, with more than 20 weeks of amenorrhea. These all benefited from the Elisa assay of sFLT-1 and PlGF after carrying out the proteinuria on the urine dipstick during the consultation. Preeclampsia was defined by the double positivity of proteinuria on the urine dipstick associated with high blood pressure (Systolic blood pressure ≥ 140 mmHg and/or diastolic blood pressure ≥ 90 mmHg). SPSS software was used for statistical analysis and calculation of performance indices (Se; Sp; PPV; NPV; Youden “J” index, AUC). The p-value of the probability was considered significant for a value < 0.05. <i>Results.</i> Pregnant women were mostly multiparous with a median age of 31 years (24-35). Preeclampsia was noted in 69.2% of cases. sFLT-1 was significantly higher in preeclamptic pregnant women (409±18.9 vs 194.6±12.9; p<0.05). No significant difference was noted for PlGF (11.9 vs 13.6; p< 0.05). The sFlt-1/PlGF ratio was higher in case of preeclampsia (39.3 vs 14.6; p< 0.05). The threshold for the sFlt-/PlGF ratio retained was 18.5 (Se=86.4%; Sp=84.6%; PPV=90.5%; NPV=78.6%; J = 0.7; AUC =0.9). <i>Conclusion.</i> The sFlt-1/PlGF ratio was effective in the diagnosis of preeclampsia.

PHYSIOLOGICAL AND BIOCHEMICAL STUDIES OF AGEING RAT HEART WITH EXPERIMENTAL ARTERIAL HYPERTENSION

Abstract Objective: It has been shown that DOCA-NaCl dependent arterial hypertension appears before any kidney lesions and there are proofs which suggest the role of NaCl retention or sensitivity to this in etiology of essential arterial hypertension The aim of our study was concerned with evaluation of physiological and biochemical parameters of rat heart with arterial hypertension experimentally induced with (DOCA) as well as to investigate the antioxidant potential and lipid metabolism parameters. Design and method: 16 white male Wistar rats (180 + 20 g), aged 20 months old, fed on standard chew, have been divided into two groups of 8 rats each: group A Controls and group B treated with DOCA for 4 weeks with 2 (i.m.) injections /week) with 10 mg/kg b.w. and two weeks afterwards drinking water has been replaced by saline solution (0.9%NaCl + 0.2%KCl). Evaluation of physiological parameters: heart rate (H.R.), coronary flow (C.F.) and left ventricle systolic pressure (L.V.S.P.) of heart from controls and hypertensive rats has been achieved on isolated heart in Langendorff perfusion system with Krebs Hanseleit bicarbonate buffer at a constant pressure. Oxidative stress has been imposed by applying a 45 minutes ischemia which has been followed by 120 minutes reperfusion. Biochemical studies of antioxidant system have been performed on plasma and left ventricle tissue by evaluating: SOD, GGT, Lipid peroxides, CK, LDH, Cholesterol, LDL, HDL with standard biochemical methods. Results: Our data have pointed out that for about one hour (C.F.) presented higher values as well as (LVSP) and (H.R). in DOCA treated rats, above the values from Controls. These data account for an intense cardiac activity imposed by the onset of arterial hypertension following DOCA treatment. A reduction in GGT in myocardium due to hypoxia generated by cardiac insufficiency following DOCA treatment is accompanied by a reduction of antioxidant potential and both HDL and CK markers of myocardial lesion exhibited higher values. Conclusions: Following 4 weeks DOCA treatment a pathological state is achieved similar with Essential arterial hypertension found in humans, accounted for by the following changes: an intensification of contractile activity, cardiac hypertrophy and the increase in lipid peroxides level, LDH and CK activity.

Combination of increased situational anxiety and endothelial dysfunction in young athletes as a condition for microcirculation spasm: assessment methods and correction using a specialized honey bar-candy

Objective: study of psychoemotional-volitional sphere and endothelium-dependent factors of cardiovascular risk, the level of performance and recovery time in athletes before and after a 2-month intake of a specialized athlete’s nutrition product (SANP) honey bar-candy “Gold F25 ApiSpeis Light”.Materials and methods: the main group of 58 athletes (under the age of 18) used SANP for 2 months. Control group-1 included 32 schoolchildren and students, not athletes, to assess the age limits of endothelium-dependent vasodilation, blood composition and the presence of risk factors for atherosclerosis in young athletes. The control group-2 included 30 young athletes under 18 years old without the use of SANP to compare the indicators in the main group before and after taking the honey bar. The psycho-emotional sphere was studied using the Spielberger-Hanin scale of anxiety and WAM testing: Well-being, Activity and Mood. In addition, the maximum achieved load, maximum oxygen consumption, time to reach the threshold of anaerobic metabolism, systolic blood pressure, heart rate, neurovegetative stress index and recovery time after exercise were determined. Also, tests with reactive hyperemia (TRH) and hyperventilation (TGV) on the brachial artery were performed to assess endothelium-dependent vasodilation and vasoconstriction, conjunctival biomicroscopy on a slit lamp with calibrometry of arterioles and venules, general and biochemical blood tests.Results: the normalization of situational anxiety, psychoemotional stress and hyperfunction of the sympathoadrenal system was established. There was a decrease in the levels of cortisol, neurovegetative stress index, improvement of well-being, activity and mood against the background of elimination of endothelial dysfunction, improved performance and reduced recovery time after work. The analysis of multiple canonical correlations revealed a close relationship between the psychoemotional state, endothelial dysfunction and microcirculation spasm (R = 0.86; p &lt; 0.0001).Conclusion: it has been proven that a combination of increased situational anxiety, neurovegetative overexertion, hyperfunction of the sympathoadrenal system and endothelial dysfunction can form a spastic type of peripheral circulation and provoke the onset of arterial hypertension. It was found that the course intake of honey ingot has anti-stress, antioxidant, erythropoietic, vasodilating and antispastic effects, improves performance and recovery after stress. Ingot “Gold F25 ApiSpeis Light” is included in the FMBA Formulary as a specialized product for the nutrition of young athletes of the Russian national teams.

Effects of Caloric Restriction Diet on Arterial Hypertension and Endothelial Dysfunction.

The most common manifestation of cardiovascular (CV) diseases is the presence of arterial hypertension (AH), which impacts on endothelial dysfunction. CV risk is associated with high values of systolic and diastolic blood pressure and depends on the presence of risk factors, both modifiable and not modifiable, such as overweight, obesity, physical exercise, smoking, age, family history, and gender. The main target organs affected by AH are the heart, brain, vessels, kidneys, and eye retina. AH onset can be counteracted or delayed by adopting a proper diet, characterized by a low saturated fat and sodium intake, a high fruit and vegetable intake, a moderate alcohol consumption, and achieving and maintaining over time the ideal body weight. In this review, we analyzed how a new nutritional approach, named caloric restriction diet (CRD), can provide a significant reduction in blood pressure values and an improvement of the endothelial dysfunction. In fact, CRD is able to counteract aging and delay the onset of CV and neurodegenerative diseases through the reduction of body fat mass, systolic and diastolic values, free radicals production, and oxidative stress. Currently, there are few studies on CRD effects in the long term, and it would be advisable to perform observational studies with longer follow-up.

Rapidly progressive course of nonspecific aortoarteritis: a clinical case

Background. Nonspecific aortoarteritis, or Takayasus disease, is one of the most complex and rare pathologies in modern clinical practice. It is the orphan nature of the disease, along with non-specific clinical manifestations, that causes a large number of clinical and diagnostic errors that lead to an unfavorable prognosis and early disability of patients. Despite the development of modern methods of treatment of nonspecific aortoarteritis, in some cases it is not possible to achieve a stable remission, which leads to a steady progression of the pathological process. Clinical case description. The article presents a case of a rapidly progressing course of Takayasu's disease in a young woman with multiple arterial vascular lesions that developed during the first year after the onset of arterial hypertension, while the narrowing of the carotid arteries (7585%) was not accompanied by signs of cerebral ischemia. The follow-up period was 10 years. Conclusion. Given the peculiarities of this nosology, each identified case of Takayasus disease is of great clinical and practical interest. The disease peculiarity in thise patient is that during the first year from the onset of arterial hypertension, the main occlusive lesions of the aorta and arterial vessels were identified. At the same time, the narrowing of the carotid arteries (7585%) was not accompanied by signs of cerebral ischemia. It should be noted that often the symptoms of non-specific aortoarteritis appear under the masks of other diseases, which requires a careful differential search. A correct diagnosis and timely treatment can prevent the development of complications and slow the progression of the disease.

Histone Deacetylase Activity and the Renin-Angiotensin-Aldosterone System: Key Elements in Cardiorenal Alterations Provoked by Chronic Malnutrition in Male Adult Rats.

Chronic malnutrition (M) affects >1 billion people worldwide. Epidemiological data point to long-term renal and cardiovascular outcomes (e.g. arterial hypertension, cardiorenal syndromes). The renin-angiotensin-aldosterone system (RAAS) has been implicated in the physiopathology of these disturbances, but M-induced alterations in RAAS-modulated renal Na+ handling and their cardiovascular repercussions are not known. Moreover, altered tissue-specific histone deacetylases (HDAC) results in arterial hypertension and the use of sodium Valproate (Val; a HDAC inhibitor) reduces blood pressure. However, there are no reports regarding the renal and cardiovascular effects of HDAC inhibition in M, or on the signaling pathways involved. The central aim of our study has been to investigate whether alterations in the HDAC/RAAS axis underpin alterations in active Na+ transport in the kidney and heart, and affects blood pressure. Male rats aged 28 days were given either a control (C) or a multideficient diet (Regional Basic Diet, RBD), which mimics alimentary habits from developing countries. Subgroups received Losartan (Los), a blocker of type 1 Angiotensin II receptors. When the rats reached 70 days, new subgroups received Val until they were 90 days of age. Homogenates and enriched plasma membrane fractions from renal cortex corticis and cardiomyocytes were obtained by differential centrifugation of the tissues. The activity of renal and cardiac deacetylases was assayed by measuring - after incubation with the membranes - the amount of deacetylated lysines in a substrate containing an acetylated lysine side chain. Protein kinases activities were measured following the incorporation of the γ-phosphoryl group of [γ-32P]ATP into Ser/Thr residues of histone type III-S. The activity of Na+-transporting ATPases (kidney and heart) was quantified by measuring the release of Pi from ATP that was sensitive to ouabain ((Na++K+)ATPase), or sensitive to furosemide (Na+-ATPase). Tail-cuff plethysmography was used to measure systolic blood pressure and heart rate. M provoked HDAC downregulation, which was reversed by Los and Val, either alone or in combination, with selective upregulation of protein kinases C and A (PKC, PKA) in renal cortex corticis, but not in left ventricle cardiomyocytes. The 2 kinases were strongly inhibited by Los and Val in both organs. Malnourished rats developed elevated systolic arterial pressure (SAP) and heart rate (HR) at 70 days of age; Los and Val restored the control SAP, but not HR. Functional and the above biochemical alterations were associated with the deregulation of renal and cardiac Na+-transporting ATPases. (Na++K+)ATPase activities were downregulated in M rats in both organs, and were further inhibited by the pharmacological treatments in the renal cortex corticis (C and M groups) and the left ventricle (only in C rats). No additional effect was found in cardiac (Na++K+)ATPase from M rats. Ouabain-resistant Na+-ATPase was upregulated in renal cortex corticis and downregulated in cardiomyocytes, returning to C values after administration of Los and Val. The HDAC/RAAS axis appears to be a key regulator of Na+-transporting ATPases in renal cortex corticis and cardiomyocytes via an appropriate balance of PKC and PKA activities. Modifications within the HDAC/RAAS axis provoked by chronic M - with repercussions in renal and cardiac Na+ transport - underpin alterations in bodily Na+ homeostasis that culminate with the onset of arterial hypertension and potential cardiorenal syndrome.

P858 Cardiovascular toxicity induced by immunotherapy and tyrosine kinase inhibitors

Abstract Background in the recent years, survival of cancer patients increased enormously through the use of new anticancer drugs such as molecular target drugs (tyrosine kinase inhibitors- TKIs, immunotherapy). Immunotherapy includes anti-BRAF and anti-MEK drugs (although evidences are scarce, these drugs seem to be capable of causing cardiovascular toxicity too); TKIs includes inhibitors of VEGF, VEGFR and other kinases. Purpose to assess cardiovascular toxic effects of TKIs and immunotherapy, to identify early signs of cardiac and vascular toxicity using speckle tracking echocardiography and arterial stiffness measurement. Methods a prospective study was carried out evaluating 45 patients treated with immunotherapy or TKIs. Population was divided into 2 groups: Group A (17 patients with melanoma treated with anti- BRAF and anti-MEK) and Group B (28 patients with solid cancer treated with TKIs-anti VEGF). Cardiological evaluation including electrocardiogram, conventional echocardiogram with tissue Doppler imaging (TDI) and left ventricular global longitudinal strain (GLS) measurement and carotid ultrasound scan was carried out before starting therapy and at a follow-up time of 6 and 12 months. Cardiovascular events such as heart failure, arterial hypertension, arrhythmias, Qtc interval prolongation, stroke, arterial and venous thrombosis were assessed during follow-up. Results mean follow-up was 7 months for anti-BRAF and 13 months for TKI. Neither cardiovascular adverse events nor significant reductions in LVEF or other echocardiographic parameters during follow-up were observed in Group A: we did not observe significant changes in GLS (-18,4 [RI -19,9 a -15,8] vs. -18,3 [RI -18,9 a -16,1] or in vascular parameters (PWV 7,3 ± 1,4 vs. 6,7 ± 1,5, β mean wave 8,5 [RI 6,3-12] vs. 7,4 [RI 4,9-9,4]; α mean wave 6,8 [RI 3,1-6,2] vs. 9,6 [RI 2,4-4,6]). As regards Group B, new onset of arterial hypertension in 35% of population but no significant changes in LVEF or other echocardiographic parameters including GLS ( -18,6 ± 2,3 vs. -18,3 ± 3,3) were observed. Significant changes were furthermore found in vascular parameters with increased arterial stiffness during follow-up (PWV 7,82 ± 1,23 vs. 10,02 ± 2,73; p = 0,04, β mean wave 5,33 ± 1,98 vs. 8,43 ± 3,03; p = 0,02, α mean wave 10,79 ± 4,03 vs.16,82 ± 6,38; p = 0,03). Conclusions according to the literature data, immunotherapy seems to have a safe cardiovascular profile. Anti-VEGF drugs seem to predominantly cause vascular damage, early identifiable through arterial stiffness measurement.

Glucose Fluctuations Promote Aortic Fibrosis through the ROS/p38 MAPK/Runx2 Signaling Pathway

Aim: Glucose fluctuations may be responsible for, or further the onset of arterial hypertension, but the exact mechanisms remain unclear. The purpose of this study was to investigate the mechanisms behind and related to aortic fibrosis and aortic stiffening induced by glucose fluctuations. Methods: Sprague-Dawley rats were injected with streptozotocin (STZ) and randomly divided into three treatment groups: controlled STZ-induced diabetes (C-STZ); uncontrolled STZ-induced diabetes (U-STZ); and STZ-induced diabetes with glucose fluctuations (STZ-GF). After 3 weeks, rat blood pressure (BP) was tested, and aortic fibrosis was detected by using the Masson trichrome staining technique. Levels of p38 mitogen-activated protein kinase (p38 MAPK), runt-related transcription factor 2 (Runx2), collagen type 1 (collagen I), and NADPH oxidases were determined by Western blot.Rat vascular smooth muscle cells in vitro were used to explore underlying mechanisms. Results: The systolic BP of diabetic rats in the C-STZ, U-STZ, and STZ-GF groups was 127.67 ± 6.53, 150.03 ± 5.24, and 171.63 ± 3.53 mm Hg, respectively (p< 0.05). The mean BP of diabetic rats in the three groups was 91.20 ± 10.07, 117.29 ± 4.28, and 140.58 ± 2.14 mm Hg, respectively (p< 0.05). The diastolic BP of diabetic rats in the three groups was 73.20 ± 12.63, 101.93 ± 5.79, and 125.37 ± 4.62 mm Hg, respectively (p< 0.05). The ratios of fibrosis areas in the aortas of the three groups were 11.85 ± 1.23, 29.00 ± 0.87, and 48.36 ± 0.55, respectively (p< 0.05). The expressions of p38 MAPK, Runx2, and collagen I were significantly increased in the STZ-GF group. In vitro, applications of inhibitors of reactive oxygen species (ROS) and p38 MAPK successfully reversed glucose fluctuations that would have possibly induced aortic fibrosis. Conclusions: Blood glucose fluctuations aggravate aortic fibrosis via affecting the ROS/p38 MAPK /Runx2 signaling pathway.

Abstract P524: Vasoprotective Effect of Hesperidin in the Onset of Arterial Hypertension Induced by L-NAME

Hesperidin has been used to manage venous disease and has been shown to have vasodilator, antiinflammatory and antioxidant properties. The aim of this work was to evaluate the efects of acute treatment with hesperidin (HD) on the vascular reactivity of rats in the onset of arterial hypertension induced by L-NAME. Male Wistar rats were divided into 3 groups as follow: 1- Control (CTL); 2- L-NAME (LN); 3- L-NAME + Hesperidin (LNHD). LN was given by gavage at the dose of 75mg/Kg, concomitantly with HD at the dose of 0.5 mmol/Kg, 24 hours previously to the sacrifice. After sacrifice, the blood was collected and the aorta removed and mounted in a wire myograph to assess concentration response curves to acetylcholine (ACh) and sodium nitroprusside (SNP). ACh elicited concentration dependent relaxation in aorta of CTL rats, reaching a maximum relaxation of 89 ± 3%, which was significantly reduced in LN group (37 ± 7%). Treatment with HD partially prevented this decrease, reaching the maximum relaxation of 72 ± 2%. On the other hand, SNP induced relaxation was more potent on the aorta of LN (pEC 50 9.67 ± 0.11) when compared to CTL (pEC 50 8.51 ± 0.13) and LNHD rats (pEC 50 8.90 ± 0.09). The oxidative status was not changed by any treatment since SOD activity was 11 ± 1, 9 ± 2 and 12 ± 0.5 U/mL, for CTL, LN and LNHD, respectively and lipid peroxidation measured by TBARS assay showed a MDA concentration of 29 ± 8, 35 ± 7 and 23 ± 3 μM for CTL, LN and LNHD, respectively. Altogether, these data suggest that that Hesperidin prevents the impairment of endothelium-dependent vascular relaxation, through a mechanism not related to its antioxidant property.

Evidências da interrelação trabalho/ocupação e hipertensão arterial sistêmica: uma revisão integrativa

Objective: To identify in the literature evidence for the interrelationship between work/occupation and the onset of arterial hypertension. Methods: This is an integrative review. The databases used were: Latin American and Caribbean Health Sciences (LILACS) and Scientific Electronic Library Online (SciELO). There were 11 studies that met the search criteria. The analysis and synthesis of data were conducted in a descriptive way, and then the value of evidence adopted for elaboration of the integrative review was described. Results: After an integrative review of articles, value III was observed in almost all studies, which demonstrates intermediate evidence for the relation between work and the development of hypertension. Conclusion: Despite being addressed by a few studies, the deleterious effects of the work/occupation on the onset of systemic arterial hypertension were identified.

PROSPECTIVE STUDY OF TABLE SALT TASTE SENSITIVITY THRESHOLD INFLUENCE ON CARDIOVASCULAR COMPLICATIONS

Aim. To evaluate prognostic significance of TSTST in cardiovascular complications development. Material and methods. Totally 162 persons studied, of those 67 with arterial hypertension (AH) and 95 their close relatives of the 1 grade of relativity, healthy at the moment of the first examination in 1998. Second study of the group has been done in 16 years, in 2014. Totally 28 families studied. In 16 years, 101 person had arterial hypertension, and in 34 it had been developed during the observation period. Ischemic heart disease (IHD) was diagnosed in 38 patients, diabetes (DM) — in 21 (all had 2nd type). For 16 years, the brain stroke (BS) developed in 15 participants, in 6 cases it was fatal, and myocardial infarction (MI) — in 13 participants, in 10 cases fatal. Totally 15 patients died (9,3%), one — from melanoma. The participants at the baseline were studied for the TSTST by Henkin R. J. method under Konstantinov E. N. modification. For the second study in 16 years a protocol was created included the results of anthropometric and hemodynamic data, and the cases of AH, IHD, MI and BS, and the death. Results. In the group of those died comparing to the others, were higher levels of TSTST at the baseline (2,52±0,39 vs 1,38±0,16, р<0,05). During 16 years among 54 participants with high TSTST (more than 0,64) died 14 — 25,9%, and from 47 participants with normal TSTST died 1 — 2,13%. In analysis of the influence of TSTST on cardiovascular outcomes, it was shown that the risk of fatal and nonfatal cases of BS increased with TSTST, but the risk of MI did not differ significantly. In addition, the survival of the patients was significantly lower in the case of higher TSTST in BS, as in MI. In survival analysis for the influence of TSTST on nonfatal cases of MI and BS there were no such influence. Conclusion. High TSTST in AH patients increases the risk of fatal and nonfatal cases of BS, fatal MI during 16 years of study. High TSTST is followed by the increase of the risk of new onset of AH, and higher mean values of BP in AH. The decrease of general survival and 16-year survival of AH patients due to fatal cases of BS and MI is caused by higher TSTST.

4D.11

Objective:Arterial stiffness (AS) is an independent risk factor of cardiovascular mortality in general and haemodialysis (HD) population. Endemic (Balkan) nephropathy (EN) is a chronic tubulointerstitial salt wasting nephropathy characterized with later onset of arterial hypertension (AH) which coul

RISK FACTORS OF CARDIOVASCULAR DISEASES IN TEACHING STAFF AMONG PRIMARY SCHOOLS OF TOMSK CITY (THE DATA FROM MULTICENTER PROSPECTIVE PREVENTION STUDY)

Aim. To study the prevalence of risk factors (RF) of cardiovascular diseases (CVD) in the teaching staff of primary schools in Tomsk city. Material and methods. Totally 154 teachers studied (staff of 2 general education schools of Tomsk) at the age of 21-71 y. Mean age 46,6±10,9. Response — 84%. Results. Prevalence of arterial hypertension (AH) among the staff was 51,9%, and primary onset of AH — in 3,2%. Less than a half of teachers with AH took antihypertension therapy (42,8%) and just in 15% of those we found target levels of blood pressure during business day. Prevalence of smoking was 7,0%. We found a high prevalence of alimentary CVD risk factors. Two thirds of the staff were overweight (68,8%). Prevalence of excessive bodyweight was 33,1% and of obesity — 35,7%, of abdominal obesity — 40,2%. In teaching staff there was high level of hyperglycemia (12,1%), hypercholesterolemia (78,0%) and hypertriglyceridemia (32,0%). Insufficient physical activity was noted in 30% of teachers. Conclusion. The main points are found for the development and implementation of preventive strategies in the group — effective control over AH and correction of alimentary-dependent RF of CVD.