Uncontrolled Arterial Hypertension Research Articles

Renal denervation for uncontrolled hypertension: a systematic review and meta-analysis examining multiple subgroups.

This systematic review and meta-analysis was conducted to assess the randomized controlled trial (RCT) evidence available for renal denervation (RDN) in uncontrolled arterial hypertension. Twenty-five RCTs met the eligibility criteria for the systematic review, and 16 RCTs were included in the meta-analysis. The results of the random effects meta-analysis estimated a mean difference of -8.5 mmHg [95% confidence interval (CI) -13.5 to -3.6] for office SBP, -3.6 mmHg (95% CI -5.2 to -2.0) for 24 h SBP and -3.9 mmHg (95% CI -5.6 to -2.2) for ambulatory daytime SBP in favour of RDN compared with control (medication and/or sham-only) at primary follow-up. Similarly favourable results were observed across a range of prespecified subgroup analyses, including treatment-resistant hypertension. This meta-analysis suggests that the use of RDN in uncontrolled hypertension leads to consistent reductions in blood pressure. Reductions appear to be statistically consistent in the presence or absence of medications and in populations resistant to the use of three medications.

Intracranial hemorrhage caused by dabrafenib and trametinib therapy for metastatic melanoma.

Although generally well tolerated compared with chemotherapy, molecular targeted therapy used in metastatic melanoma may be associated with life-threatening toxicity. We report the case of a patient with metastatic melanoma treated by dabrafenib plus trametinib who developed intracranial hemorrhage. Physicians should be aware of this rare but life-threatening adverse event of B-rapidly accelerated fibrosarcoma (BRAF) and mitogen-activated protein kinase kinase (MEK). However, they should be careful about the bleeding origin, which can prove to be a new onset of melanoma metastasis or anticoagulation overdose, or even an uncontrolled arterial hypertension.

Controlled and uncontrolled arterial hypertension: comparison of clinical and demographic characteristics in patients (according to the National Registry of Hypertension, 2019-2022)

Aim: to study the clinical and demographic characteristics of patients in a sample of patients with arterial hypertension observed in primary healthcare (20192022). To compare data from patients with uncontrolled and controlled hypertension.Materials and methods. An analysis of medical data of 4543 patients was carried out (history, clinical and laboratory data, concomitant cardiovascular diseases, type 2 diabetes mellitus, chronic kidney disease, revascularization (coronary bypass grafting, transluminal balloon angioplasty of the coronary arteries). For statistical data processing, the SPSS statistical software package was used.Results. The patients in the study sample were middle-aged and elderly. 51,5% of patients did not achieve target blood pressure values. More than 90% of patients in the studied sample are high and very high risk patients. The ratio of groups of patients with controlled and uncontrolled arterial hypertension among patients of different ages did not differ. Higher values of low-density lipoprotein cholesterol, a higher frequency (1,3 times) of failure to achieve target values of low-density lipoprotein cholesterol <2,6 mmol/l, and obesity (1,3 times) were identified in patients with uncontrolled arterial hypertension. More than 80% of patients had low-density lipoprotein cholesterol values higher than recommended. Patients with controlled arterial hypertension were more likely to have coronary heart disease, myocardial infarction and a history of coronary angioplasty and coronary artery bypass grafting.Сonclusions. In hypertensive patients, more careful monitoring of cardiovascular risk factors is required, including blood pressure levels and achieving target LDL cholesterol levels. The association of a higher incidence of obesity, type 2 diabetes mellitus and the severity of dyslipidemia with uncontrolled hypertension may indicate less adherence of patients to both drug and non-drug treatment methods. While the presence of coronary heart disease, surgical interventions performed on the coronary arteries can serve as an illustration of increased adherence to therapy when hypertension is combined with coronary heart disease.

Patients Living with Arterial Hypertension in Mexico: First Insights of The Mexican Registry of Arterial Hypertension (RIHTA Study).

Arterial hypertension is a significant cause of morbidity and mortality in Mexico. However, there is limited data available to understand blood pressure management and cardiometabolic profiles. To assess the prevalence of controlled and uncontrolled blood pressure, as well as the prevalence of cardiometabolic risk factors among patients from the Mexican Registry of Arterial Hypertension (RIHTA). We conducted a cross-sectional analysis of participants living with arterial hypertension registered on RIHTA between December 2021 and April 2023. We used both the 2017 ACC/AHA and 2018 ESC/ESH thresholds to define controlled and uncontrolled arterial hypertension. We considered eleven cardiometabolic risk factors, which include overweight, obesity, central obesity, insulin resistance, diabetes, hypercholesterolemia, hypertriglyceridemia, low-HDL-C, high-LDL-C, low-eGFR, and high CVD risk. In a sample of 5,590 participants (female: 61%, n=3,393; median age: 64 [IQR: 56-72] years), the prevalence of uncontrolled hypertension varied significantly, depending on the definition (2017 ACC/AHA: 59.9%, 95% CI: 58.6-61.2 and 2018 ESC/ESH: 20.1%, 95% CI: 19.0-21.2). In the sample, 40.43% exhibited at least 5-6 risk factors, and 32.4% had 3-4 risk factors, chiefly abdominal obesity (83.4%, 95% CI: 82.4-84.4), high-LDL-C (59.6%, 95% CI: 58.3-60.9), high-CVD risk (57.9%, 95% CI: 56.6-59.2), high triglycerides (56.2%, 95% CI: 54.9-57.5), and low-HDL-C (42.2%, 95% CI: 40.9-43.5). There is a high prevalence of uncontrolled hypertension interlinked with a high burden of cardiometabolic comorbidities in Mexican adults living with arterial hypertension, underscoring the urgent need for targeted interventions and better healthcare policies to reduce the burden of the disease in our country.

Association of inflammatory and hematological indices with left ventricular hypertrophy in hypertensive patients

Objective. To identify an associative relationship between inflammatory indicators, hematological indices and left ventricular hypertrophy (LVH) in patients with uncontrolled arterial hypertension (HTN). Design and methods. We examined 130 patients with uncomplicated essential HTN I–II with ineffective blood pressure (BP) control (≥ 140/90 mmHg). All patients underwent a clinical examination with determination of risk factors, indicators of inflammation — high-sensitivity C-reactive protein (hs-CRP), interleukin‑1β (IL‑1β), interleukin‑6 (IL‑6), interleukin‑8 (IL‑8), tumor necrosis factor α (TNF-α), hematological indices — systemic immune inflammation index (SII), the monocyte to high density lipoprotein cholesterol ratio (MHR), the platelet to lymphocyte ratio (PLR), the neutrophil to lymphocyte ratio (NLR), and echocardiography. Results. The positive correlations were found between the indicators of nonspecific inflammation and signs of LVH — MHR and left ventricular myocardial mass index (LVMI) (r = 0,448; p < 0,001), the posterior wall thickness (PWT) of left ventricle (LV) in the diastole (r = 0,256; p = 0,003), the interventricular septum (IVS) thickness in the diastole (r = 0,311; p ≤ 0,001); the level of hs-CRP and the relative wall thickness (RWT) (r = 0,283; p = 0,002), PWT of LV in the diastole (r = 0,202; p = 0,043), IVS thickness in the diastole (r = 0,231; p = 0,011); the level of IL‑6 and the PWT of LV in the diastole (r = 0,215; p = 0,018); SII and IVS thickness in the diastole (r = 0,230; p = 0,009), the RWT (r = 0,205; p = 0,016); NLR and IVS thickness in the diastole (r = 0,227; p = 0,009), PWT of LV in the diastole (r = 0,205; p = 0,029), RWT (r = 0,206; p = 0,016). Using multiple linear regression, independent factors associated with increased LVMI in HTN patients were male sex (β = 0,201), waist circumference (WC) (β = 0,258) and MHR (β = 0,236) (p = 0,029). Independent factors for increasing PWT of LV in the diastole in HTN patients were WC (β = 0,354) and male sex (β = 0,266) (p = 0,003); increase of IVS thickness in the diastole — SII (β = 0,254), WC (β = 0,392) and male sex (β = 0,219) (p = 0,021); and an increase of RWT — hs-CRP (β = 0,333) (p = 0,001). Conclusions. In patients with uncontrolled HTN increased levels of hs-CRP, IL‑6, SII, MHR and NLR were associated with echocardiographic LVH criteria—LVMI, PWT and IVS thickness in the diastole, RWT. Independent factors for increasing LVMI were WC, male sex and MHR; IVS thickness in the diastole — SII, WC and male; RWT — hs-CRP.

Resistant arterial hypertension: modern view of the problem

In clinical practice, uncontrolled arterial hypertension remains a difficult but solvable task, given the available arsenal of antihypertensive drugs. However, resistant arterial hypertension is diagnosed in 10%–15% of these cases. A significantly higher risk of cardiovascular complications indicates the extreme importance of the successful treatment of this pathology. Resistant hypertension is defined as above-goal high blood pressure in a patient despite concurrent use of three antihypertensive drug classes, commonly including a long-acting calcium channel blocker, a renin–angiotensin blocker (angiotensin-converting enzyme inhibitor or angiotensin receptor blocker), and a diuretic. All antihypertensive drugs should be administered at maximum or maximally tolerated doses. Resistant hypertension also includes cases in which blood pressure targets are achieved with ≥4 antihypertensive medications. The diagnosis of resistant hypertension requires assurance of antihypertensive medication adherence and exclusion of the “white-coat effect” (office blood pressure above goal but out-of-office blood pressure at or below the target). Once antihypertensive medication adherence is confirmed and out-of-office blood pressure recordings exclude a white-coat effect, the evaluation includes the identification of contributing lifestyle issues, detection of drugs interfering with antihypertensive medication effectiveness, screening for secondary hypertension, and assessment of target organ damage. The management of resistant hypertension includes the maximization of lifestyle interventions, correction of sleep disorders, use of long-acting thiazide-like diuretics (chlorthalidone or indapamide), addition of a mineralocorticoid receptor antagonist (spironolactone or eplerenone), and stepwise addition of antihypertensive drugs with complementary mechanisms of action to lower blood pressure if blood pressure remains high.

Фармакокинетика амлодипина у пациентов с артериальной гипертензией

Aim. To evaluate the pharmacokinetics of amlodipine in patients with arterial hypertension. Design. Open cohort study. Materials and methods. The study included 183 patients, 98 of them with uncontrolled arterial hypertension and 85 with controlled hypertension. All patients regularly took any two antihypertensive drugs (AHD) (lisinopril, amlodipine, valsartan, metoprolol) in combination with indapamide for a month. In the morning, fasting, before taking AHD and 2 hours after taking amlodipine, venous blood samples were taken from all patients to test the concentration of the analyte using high-performance liquid chromatography with tandem mass spectrometry. Results. In terms of the main concomitant diseases, the patients of the two groups were comparable to each other. Only angina pectoris (p = 0.02) and overweight (p = 0.02) were statistically significantly more common in the pressure–controlled group, and less often — grade 2 obesity (p = 0.002) and acute cerebrovascular accident (p = 0.05). The daily dose of amlodipine in patients with controlled hypertension was significantly (13.9%) lower (p < 0.05) than in participants with uncontrolled hypertension. Both the steadystate concentration of amlodipine and the concentration 2 hours after administration in patients with uncontrolled hypertension were not statistically significantly different from those in patients with controlled hypertension (p > 0.05). In 65.6% of patients with uncontrolled and in 49.4% with controlled hypertension, the concentration of amlodipine was within the therapeutic range (p = 0.03), in 5.2% and 16.5%, respectively, it was above the therapeutic range (p = 0.016), in 29.2% and 34.1%, respectively, — below the therapeutic range (p > 0.05). Conclusion. Conducting therapeutic drug monitoring and assessing the pharmacokinetics of amlodipine in clinical practice may be useful to improve the effectiveness and safety of therapy. Keywords: arterial hypertension, antihypertensive drugs, amlodipine, high-performance liquid chromatography with tandem mass spectrometry.

Efficacy of Consolidation Therapy with Ponatinib 15mg on Treatment-Free Remission Rate in Patients with Chronic Myeloid Leukemia. Results of the Ponazero Trial

Introduction: Discontinuation of tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia (CML) has become part of routine clinical practice in recent years, thanks to growing evidence on their feasibility and safety. However, and despite adequate patient selection based on current recommendations, loss of response is observed in approximately 50% of patients. In this scenario, efforts are focused on finding strategies to increase the rate of successful discontinuations. Ponatinib has shown to induce deeper molecular responses compared with imatinib, but its risk of arterial occlusive events (AOE) limits its use in first line at its standard dose of 45mg. The risk of AOEs appears to be dose-related and following the results of the OPTIC study, dose reduction to 15mg in patients with good response is an increasingly popular strategy. Under these premises it has been postulated that a consolidation with ponatinib 15mg may increase the proportion of patients who could discontinue treatment successfully. Our aim is to evaluate the efficacy and safety of one year of consolidation therapy with ponatinib 15mg on treatment-free remission (TFR) rate in patients with CML who have achieved a deep molecular response with imatinib. Material and Methods: A multicenter open-label, single-arm, phase II, exploratory, prospective clinical trial (NCT 04043676) was conducted including patients with philadelphia-positive CML who met discontinuation criteria according to European LeukemiaNet recommendations, had received 4 years or more of imatinib therapy, with a documented grade 4 molecular response (MR4) at least 12 months prior to study entry. Uncontrolled arterial hypertension, active cardiovascular disease, or concomitant medication with potential for QTc prolongation were exclusion criteria. The study has two main phases: ponatinib consolidation (48 weeks), and ponatinib TFR phase (48 weeks); where patients remain without treatment. During the TFR phase, patients with a confirmed loss of MR4 or a single value above major molecular response (MMR) were scheduled to restart treatment with a TKI at investigator's discretion. The present abstract reports the results of the primary endpoint of the study; the proportion of patients with no loss of MR4 at the end of the TFR phase. Results: A total of 23 patients started treatment with ponatinib 15mg. One patient subsequently failed screening due to a major protocol deviation. Baseline patient characteristics were as follows: median age was 51.8 years (range 26-74), 65.2% were male. Ninety-five percent were Caucasian and 5% were Hispanic, ECOG was 0 in 83% and 1 in 17%, Sokal was low in 69.5%, intermediate in 17.5% and unknown in 13%. Eighteen patients were receiving imatinib 400mg daily (82%) at study entry, 2 patients 800mg and two 200mg. Median time on prior imatinib was 10 years (range 4-17), with a median time on MR4 of 3.6 years (range 1.9-13.3). Prior to initiation 13 patients (56.5%) had a grade 5 molecular response, 4 had a 4.5 molecular response (26%) and the remainder had a MR4. The adverse events (AEs) reported with ponatinib are summarized in Table 1, the most frequent being constipation (30%), asthenia (26%), myalgias and arthralgias (26% respectively) and skin rash (17%). A high rate of SARS-CoV2 infections was reported during the treatment period (26%), which should be interpreted considering that the study took place during the COVID-19 pandemic. Three patients out of 22 (13.6%) had serious AEs with ponatinib leading to treatment discontinuation; thrombophlebitis, erectile dysfunction, and intermittent claudication. Of the patients who entered the TFR phase, 14/19 (74%) continue with MMR without requiring treatment after a median follow-up of 12 months (68% with MR4) (table 1). Six patients (31%) lost MR4, five of them required reintroduction of an TKI (4 imatinib, 1 dasatinib; median time to reintroduction 5.4 months). All patients with MR4 loss were receiving the 400 mg dose of imatinib at study entry. All patients who restarted treatment recovered MMR. The sixth patient lost MR4 while maintaining an MMR without requiring treatment reinduction to date. Conclusions: Consolidation with 12 months of ponatinib 15mg in this study shows a high discontinuation success rate with an adequate safety profile, although not free of AEs. The results make this approach attractive for the design of further randomized clinical trials.

Antihypertensive therapy and medication adherence in patients with uncontrolled arterial hypertension

Aim. To evaluate the antihypertensive therapy and adherence to treatment in patients with uncontrolled arterial hypertension.Materials and Мethods. The study included 297 patients hospitalized at the E.I. Chazov National Medical Research Center of Cardiology over the period from September 2019 to March 2022. Patients were spread into two groups depending on the increase in the frequency of BP: group 1 (n=149) – increase in BP above 140/90 mm Hg 1 or more per week while taking antihypertensive therapy with clinical manifestations, and group 2 (n=148) – increase in blood pressure more than 140/90 mm Hg less than 1 per week while taking antihypertensive therapy clinical manifestations. Antihypertensive therapy and medication adherence were assessed at hospital discharge and after 12 months.Results. Initially, the number of antihypertensive drugs was greater in patients with group 1 versus the patients with group 2 (p<0,001). The frequency of taking antihypertensive therapy initially and after 12 months was greater in group 1 (p<0,001). After 12 months, the number of antihypertensive drugs decreased in the group 1, and remained the same in group 2. When comparing the different classes of antihypertensive drugs, all classes, except angiotensin-converting enzyme inhibitors were most frequently prescribed in group 1 (p<0,05). After 12 months, a lower level of adherence was observed in group 1 patients compared to group 2 (6 [5-8] points vs. 8 [6-9] points) (p<0,001), as evidenced in the reduced intake of different classes of antihypertensive therapy.Conclusion. Uncontrolled arterial hypertension is a release of hypertension associated with more antihypertensive medications to be prescribed and adherence to be monitored more closely.

The relationship of asymmetric dimethylarginine levels with uncontrolled arterial hypertension and hypertension disease stage

Background: Patients with treatment-resistant hypertension have a worse cardiovascular prognosis compared to those who achieve their target levels of blood pressure (BP). One of biochemical and clinical markers of a decreased response to antihypertensive therapy can be asymmetric dimethylarginine (ADMA), a molecule that reduces formation of nitric oxide and promotes endothelial dysfunction and vasoconstriction.
 Aim: To assess the status of the nitrogen oxide synthesis system and clinical and laboratory profile in patients, depending on the hypertensive disease stage, who achieved or not achieved their target BP levels during hospitalization.
 Materials and methods: We performed аn observational retrospective uncontrolled study in a consecutive sample of 192 patients aged 45–65 years who were admitted to the City Clinical Hospital No. 25 (city of Novosibirsk) with a diagnosis of uncomplicated hypertensive crisis. On the day of discharge, the patients were retrospectively divided into 2 groups. Group 1 included patients who achieved their target BP during hospitalization (target BP group, n = 116). Group 2 included patients with uncontrolled hypertension, in whom the administration of three antihypertensive drugs including a diuretic in optimal or maximal tolerated doses did not result in the achievement of the target BP below 140 and/or 90 mm Hg during hospitalization (non-target BP group, n = 76).
 The following parameters were measured: ADMA, symmetrical dimethylarginine (SDMA), N-monomethyl-L-arginine (NMMA), and total nitric oxide.
 Results: Serum ADMA concentrations (Me [Q25%; Q75%] were increasing with the stage of hypertension: stage I, 0.75 µmol/L [0.66; 0.78], stage II, 1.14 µmol/L [0.87; 1.39], stage III, 1.38 µmol/L [1.22; 1.49] (p 0.0001, Kruskal-Wallis test). In the pairwise comparison, the difference between all these subgroups was significant at p 0.01. In the patients with uncontrolled arterial hypertension ADMA levels were increased compared to those in the target BP group: 1.2 µmol/L [0.99; 1.47] vs 1.07 [0.79; 1.34] µmol/L (p = 0.002). The proportion of patients with type 2 diabetes mellitus among those with uncontrolled arterial hypertension was 31.2% (24/76), while in the target BP group there were only 3.5% of such patients (4/116) (odds ratio 12.57, 95% confidence interval 4.15–38.05; p = 0.00001).
 Conclusion: ADMA measurement may help identify patients with a potential poor response to antihypertensive therapy. This should be taken into account when choosing a treatment regimen and BP monitoring. In addition, ADMA seems to be a promising target for the development of new drug classes.

Assessment of disturbed functions in patients with chronic heart failure using International classification of functioning ICF categories

BACKGROUND: The evaluation of impaired functions in patients with cardiac diseases is traditionally based on the clinical signs of the disease and instrumental hemodynamic parameters, without affecting all other disorders that occur with this pathology. The International classification of functioning is based on the functioning of the patient in his/her environment; therefore, a consistent assessment of the entire complex of impaired functions of the patient is appropriate, allowing for a more accurate formulation of the goals of rehabilitation and controlling the main stages of rehabilitation.
 AIM: To evaluate the International classification of functioning for assessing all impaired functions in patients with chronic heart failure.
 MATERIALS AND METHODS: The study included 68 patients with decompensated chronic heart failure. The analyzed sample included patients with chronic heart failure stages 2B and 3 (NYHA classes IIIIV). The average patient age was 63.9 years, and the average disease duration was approximately 7 years. The sample was predominantly men (66.5%). The etiology of chronic heart failure was represented by uncontrolled arterial hypertension (92%), post-infarction cardiosclerosis (74%), ischemic cardiomyopathy (25%), and chronic obstructive pulmonary disease (12%). Radiation diagnostic methods were used to confirm the severity of cardiac decompensation. The study assessed impaired functions in accordance with the domains of the International classification of functioning, mainly in functions of the cardiovascular system.
 RESULTS: In this study, 68 patients had decompensated chronic heart failure stages 2B and 3 (NYHA classes IIIIV). Group 1 included 40 patients, and group 2 included 28 patients. The instrumental examination revealed a more pronounced decrease in left-ventricular ejection fraction in group 1 compared with group 2 (42.84.4 and 49.25.6, respectively), showing a significant difference (p 0.05). Other hemodynamic parameters did not differ significantly in the groups. In the analysis of a basic set of the International classification of functioning domains for patients with chronic heart failure, the following domains turned out to be the most significant: heart function (b410), forced myocardial contraction (b4102); heart rate (b4100); blood supply to the heart (b4103); blood pressure functions (b420): increase (b4200), decrease (b4201), maintenance (b4202); functions of the respiratory system (b440) including the respiratory rate (b4400); additional functions and sensations from the cardiovascular and respiratory systems (b450-469); exercise tolerance functions (b455); water balance (b5450), including water retention (b45500), characterizing the presence of edematous syndrome; and muscle strength functions (b730). The indicated domains were also supplemented with Section d (activity and participation) walking long distances (d4501) and doing housework (d640); and Domain e (environmental factors), i.e., help from the next of kin (e310).
 CONCLUSIONS: A set of domains of the International classification of functioning for patients with decompensated heart failure has been developed and proposed, which makes it possible to more effectively identify the key problems of people with disability and more objectively form a plan for complex rehabilitation, which largely determines the prognosis in these patients.

Blood Pressure Variability: Marker or Predictor of Cardiovascular Risk?

Background: Regardless of the mean blood pressure value, short-term and long-term BP variability (BPV) are associated with the development and progression of target organ damage and predictors of cardiovascular complications and mortality. The purpose of the present study was to evaluate the prognostic significance of increased BPV in patients with arterial hypertension (AH). Methods and Results: The study consisted of two stages. In the first stage, a retrospective analysis of 365 ABPM results was carried out. As a result of the analysis, 271 patients aged 56.1±10.0 years with uncontrolled AH Grades 1-3 (ESC/ESH, 2018) were included in this study. Depending on the values of BPV, AH patients were divided into two groups: Group 1 consisted of patients with normal BPV (n=145), and Group 2 consisted of patients with increased BPV (n=126). The second stage included 91 patients with uncontrolled hypertension without permanent antihypertensive therapy who had increased BPV. We found statistically significant differences in BP between the AH patients with normal BPV and increased BPV. Thus, in the group with normal BPV, compared with increased BPV, the parameters of the average 24-h systolic BP (SBP), daytime SBP, and nighttime SBP were statistically lower (141±14.6 vs. 147.2±20.2 mmHg, P<0.004; 142.8±15.1 vs. 148.4±20.7 mmHg, P<0.01; and 136.2±15.5 vs. 143.8±21.4 mmHg, P<0.001; respectively). A statistically significant moderate direct correlation was found between the average 24-h SBP and the average 24-h and daytime SBP variability (SBPV) (rs=0.49 and rs=0.40 respectively, P<0.001 in all cases). A statistically significant moderate to weak direct correlation also was found between the average daytime SBP, and the average 24-h and daytime SBPV (rs=0.45 and rs=0.37, respectively, P<0.001 in all cases). A moderate direct correlation was found between nighttime SBP and 24-hour SBPV (rs=0.52, P<0.001) and between nighttime SBP and daytime SBPV (rs=0.42, P<0.001). Weak direct correlations were found between the average 24-h SBPV and central SBP (SBPc) (rs=0.34, P<0.001), as well as between the average 24-h and daytime SBPV and central pulse pressure (PPc) (rs=0.33 and rs=0.32, respectively, P<0.001 in all cases). A weak direct correlation was found between carotid intima-media thickness (CIMT) and the average 24-h and daytime SBPV (rs=0.37 [P<0.001] and rs=0.3 [P=0.04]). Conclusion: The increased BPV is associated with impaired diurnal blood pressure profile (DBPP) and structural and functional changes in blood vessels, in particular, an increase in SBPc and PP in the aorta, and CIMT thickening, which characterizes increased BPV as a predictor of vascular remodeling in patients with uncontrolled AH.

Renal Denervation as a Complementary Treatment Option for Uncontrolled Arterial Hypertension: A Situation Assessment.

Uncontrolled arterial hypertension is a major global health issue. Catheter-based renal denervation has shown to lower blood pressure in sham-controlled trials and represents a device-based, complementary treatment option for hypertension. In this situation assessment, the authors, who are practicing experts in hypertension, nephrology, general practice and cardiology in the Republic of Ireland, discuss the current evidence base for the BP-lowering efficacy and safety of catheter-based renal denervation with different modalities. Although important questions remain regarding the identification of responders, and long-term efficacy and safety of the intervention, renal denervation has the potential to provide much-needed help to address hypertension and its adverse consequences. The therapeutic approach needs to be multidisciplinary and personalised to take into account the perspective of patients and healthcare professionals in a shared decision-making process.

Acute kidney injury, uncontrolled arterial hypertension and resulting chronic kidney disease after severe COVID-19 infection

Acute kidney injury, uncontrolled arterial hypertension and resulting chronic kidney disease after severe COVID-19 infection

Therapeutic Drug Monitoring in Uncontrolled Arterial Hypertension: Result of the Pilot Part of Study

INTRODUCTION: Despite the recently established evidence-based and systemic approach to treatment for arterial hypertension (AH), not in all cases its control can be achieved.
 AIM: To conduct a comparative analysis of the concentration of antihypertensive drugs (AHTDs) in blood serum of patients with controlled and uncontrolled AH.
 MATERIALS AND METHODS: Fifty six patients were included. Inclusion criteria: age 18 years, signing of informed consent, established diagnosis of AH, regular intake of any two of study antihypertensive drugs (lisinopril, amlodipine, valsartan) and also of indapamide at stable doses, for women adequate contraception. According to the results of daily monitoring of the arterial pressure (AP), patients were divided into two groups: the first group controlled hypertension (AP 140/90 mmHg; n = 39), the second uncontrolled hypertension (AP 140/90 mmHg; n = 17). The mean age of patients in the first group was 65.03 10.80 years, in the second 63.50 8.31 (p = 0.576). In the first group, women prevailed (64.1% vs. 35.3%, p = 0.047) and the mean body mass index was lower (26.30 1.38 kg/m2 vs. 32.20 4.15 kg/m2, p = 0.02). In patients of both groups, venous blood was taken in fasting condition in the morning and 2 hours after intake of AHTDs to assess their concentration by high-performance liquid chromatography. The analytical range for lisinopril, indapamide, amlodipine was 5500 ng/ml, for valsartan 1010,000 ng/ml.
 RESULTS: In the first group, equilibrium concentration of lisinopril was 2.67 times higher (p = 0.053), and concentration of indapamide in 2 hours after intake was 1.83 times higher (р = 0,084); when normalized to the dose, the differences were leveled out (p 0.05). Concentrations of amlodipine and valsartan did not differ between the groups both before and 2 hours after intake (p 0.05). In 3 of 39 (7.7%) patients with controlled hypertension and in one of 17 patients (5.9%, p = 1.0) with uncontrolled hypertension, AHTDs were detected in blood serum, which were not administered to them.
 CONCLUSIONS: Results of the pilot part of the study (n = 56) demonstrated the absence of difference between the mean concentrations of the study AHTDs in the blood serum of patients with controlled and uncontrolled AH, and in some cases the presence of traces of AHTDs not administered by the doctor.

#6682 RENAL ARTERY STENOSIS: A SINGLE CENTRE STUDY

Abstract Background and Aims Renal artery stenosis (RAS) is present from 1% to 5% in people affected by arterial hypertension and it is often associated with peripheral artery disease and coronary artery disease; as the matter of fact, it is commonly found in people undergoing cardiac catheterization (18-20%) or angiography for aorto-iliac and lower extremities diseases. The major cause of renal artery stenosis is an atherosclerotic lesion localized in the proximal segment or to the ostium. Clinical presentations are renovascular hypertension and ischemic nephropathy. The aim of the study is to define either endovascular treatment gives a significant benefit on renal function and blood pressure control, when associated to medical therapy. Method This is a retrospective study focused on patients who underwent renal artery angioplasty and stenting in the last ten years, from November 2011 to April 2021 in the Nephrology Department, at Sant'Andrea Hospital, La Spezia (Italy). The primary outcome was kidney function, while secondary outcomes were blood pressure and the number of antihypertensive drugs one year after the revascularization. Patients included in the study had uncontrolled and refractory arterial hypertension (PA ≥140/90 mmHg) and/or progressive worsening of renal function, secondary to bilateral or unilateral stenosis in one functional kidney, that was identified at the color-doppler ultrasound examination by a peak systolic velocity (PSV) >200 ml/min and an aortic-renal ratio >3,5. We found 36 patients who had these characteristics. They were all affected by chronic kidney disease (CKD) (mean±SD eGFR 25,3±15,3 ml/min/1,73 m2) equally divided into stage 3 (33%, eGFR 30-60 ml/min/1,73 m2), stage IV (31% eGFR 15-29 ml/min/1,73 m2) and stage V (36%, eGFR <15 ml/min/1,73 m2). Results Kidney function, measured as serum creatinine (SCr) (mg/dl), improved immediately after the revascularization (mean ± SD SCr after vs before 2,52 ± 1,61 vs 3,31 ± 2,47 mg/dl p<0.05), after 30 days (mean ± SD SCr after vs before creat. 2,36 ± 1,53 vs 3,19 ± 2,39 mg/dl p<0.05) and after one year (mean ± SD SCr after vs before creat. 2,04 ± 1,16 vs 2,99 ± 2,40 mg/dl p<0.05) (Fig. 1). Regarding arterial hypertension, a significant reduction of both systolic (SBP) and diastolic (DBP) blood pressure was detected in the subgroup of people under 75 years old (mean ± SD SBP after vs before, 144,62 ± 12,55 vs 168,18 ± 36,40 mmHg, p< 0,01; after one year vs before, 143,95 ± 21,10 vs 167,83 ± 38,16 mmHg, p<0.05) (mean ± SD DBP after vs before, 73,62 ± 9,62 vs 83,07 ± 21,75 mmHg, p< 0,05; after one year vs before 75,20 ± 9,02 vs 83,33 ± 23,10 mmHg, p = 0.07) (Fig. 2). The number of antihypertensive drugs dropped immediately after the angioplasty (mean ± SD tablets after vs before 2,28 ± 1,11 vs 3,21 ± 1,43, p<0.01), while after one year there was not a significant increase of therapy (mean ± SD tablets after one year vs before, 3,00 ± 1,41 vs 3,23 ± 1,42, p = 0,47), even if blood pressure was better controlled than before the procedure with the same amount of tablets (Fig. 3). Conclusion Although our population was quite small, we demonstrated the advantages of renal artery revascularization in atherosclerotic renovascular disease, as demonstrated by kidney function and blood pressure control. Our results contrast the larger studies considered, that found no relevant clinical benefit on renal function and incidence of major adverse cardiovascular and renal events by comparing patients treated with medical therapy alone or with medical therapy plus angioplasty. The different conclusions are probably due to our strict adhesion to the endovascular treatment indications, which consider the revascularization as the optimal strategy for a well-defined population.

Arterial hypertension management in patients with confirmed coronary heart disease: how far are we from meeting prevention goals?

Abstract Funding Acknowledgements Type of funding sources: None. Introduction International registry studies offer useful information on the state of the cardiovascular risk factor management. The SURF CHD (Survey of Risk Factors in Coronary Heart Disease) II study is a clinical audit of the recording and management of major cardiovascular (CV) risk factors in patients with established coronary heart disease (CHD). CV risk factors’ control varies by countries and is typically insufficient, according to the prior studies. Purpose This study aimed to assess adherence to European Society of Cardiology (ESC) recommendations for secondary prevention of cardiovascular diseases based on the measurement of blood pressure (BP) control and its therapeutic management in patients with confirmed CHD at different hospitals in one of the regions at high risk for cardiovascular disease. Methods Eight public and private health care centres of Azerbaijan participated in the SURF CHD II study between November 2019 and April 2022. A one-page standard questionnaire of the study was used to collect information electronically on demographics, diagnostic category, risk factors, physical and laboratory data, and prescribed medications from consecutive patients aged ≥18 years with established CHD during outpatient visits. Uncontrolled arterial hypertension (AH) is identified as follows: systolic blood pressure (SBP) ≥140 mmHg or diastolic blood pressure (DBP) ≥90 mmHg. Results Data from 949 patients with CHD (the mean age 59.6±9.58 years; 27.3% female) were included in the study. Only 11.7% of participants were involved in a cardiac rehabilitation program. Previous history of AH was registered in 73,1% of participants, while uncontrolled SBP was detected in 59.6% of them. Regarding medications, 82.4% of patients were taking antihypertensive drugs: 52.2% were taking beta-blockers, 51.2% ACE inhibitors, 7.9% ARBs, and 31.7% calcium antagonists. Only 11.7% of participants were involved in a cardiac rehabilitation program. Conclusion The study results have shown that the implementation of the current ESC recommendations for CHD secondary prevention and in particular the control rate of BP is insufficient. Given the fact that patients are at very high risk with different comorbid pathologies, this is of great importance in the management of such patients. This should be taken into account by healthcare organizers when planning secondary prevention activities and public health protection measures, especially in the regions at high risk for cardiovascular disease.

Therapeutic Drug Monitoring in Arterial Hypertension.

(1) Background: This study was planned to assess the concentration of antihypertensive drugs (AHD) in the blood serum in patients with controlled and uncontrolled arterial hypertension (AH). (2) Methods: We assessed 46 patients with AH. Based on the results of 24 h blood pressure monitoring (ABPM), the patients were randomized into two groups. The first group consisted of the patients with controlled AH; the second group consisted of the patients with uncontrolled AH. Venous blood was taken in both groups of patients in the morning before and 2 h after taking drugs to assess the concentration of lisinopril, amlodipine, valsartan, and indapamide. (3) Results. The first group included 27 patients, and the second group 19 patients. In patients with uncontrolled AH, the median concentrations of lisinopril, indapamide, amlodipine, and valsartan before and after taking the drugs did not differ from patients who reached the target BP values. (p > 0.05). In some patients with uncontrolled and controlled (shown for the first time) AH the concentration of AHD was below the limit of quantitative determination. (4) Conclusions. The obtained results indicate that the pharmacokinetics of AHD, apparently, does not play a significant role in the development of ineffectiveness of the ongoing therapy for AH. Therapeutic drug monitoring can be used to test adherence to the treatment.

Hypertensive response to exercise, hypertension and heart failure with preserved ejection fraction (HFpEF)-acontinuum of disease?

Heart failure with preserved ejection fraction (HFpEF) has been shown to be along-term consequence of uncontrolled arterial hypertension (aHT). Other than that, hypertensive response to exercise (HRE) precedes aHT. We aim to evaluate the available evidence for acontinuum of HRE, aHT and HFpEF. Aliterature search on PubMed was conducted to assembly the most recent data on the topic. After collecting the data, aqualitative analysis was instrumented. 10studies including 16,165 subjects were analyzed with respect to the association between HRE and the future risk of developing aHT. With the exception of one study, all reported on apositive association between HRE and the future development of aHT despite methodological issues related to different definitions for HRE. Furthermore, HRE was associated with an increased risk of coronary artery disease. Moreover, we analysed 6studies including overall 1366 subjects investigating the association between HRE and HFpEF. In these studies, increased left atrial volume index (LAVI), elevatedE/e' (as surrogate parameters of increased LV end-diastolic filling pressure and of diastolic dysfunction) and higher LV mass index have been proposed as independent predictor of HRE in patients with no known HFpEF diagnosis. The literature search revealed suggestive data on aconnection of HRE, aHT and HFpEF. HRE seems to be an independent risk factor for aHT and aHT in turn is one of the main risk factors for HFpEF. However, further research is needed to improve our knowledge of apossible continuum of disease.

Impact of corticosteroids on the duration of ventilatory support during severe acute exacerbations of chronic obstructive pulmonary disease in patients in the intensive care unit: a study protocol for a multicentre, randomized, placebo-controlled, double-blind trial

BackgroundPatients who are admitted to the intensive care unit (ICU) for severe acute exacerbations of chronic obstructive pulmonary disease (COPD) have poor outcomes. Although international clinical practice guidelines cautiously recommend the routine use of systemic corticosteroids for COPD exacerbations, data are scarce and inconclusive regarding their benefit for most severe patients who require mechanical ventilation in the ICU. Furthermore, corticosteroids may be associated with an increased risk of infection, ICU-acquired limb weakness, and metabolic disorders.Methods and analysisThis study is an investigator-initiated, multicentre, randomized, placebo-controlled, double-blind trial comparing systemic corticosteroids to placebo during severe acute exacerbations of COPD in patients who require mechanical ventilation in French ICUs. A total of 440 patients will be randomized 1:1 to methylprednisolone (1 mg/kg) or placebo for 5 days, and stratified according to initial mechanical ventilation (non-invasive or invasive), pneumonia as triggering factor, and recent use of systemic corticosteroids (< 48 h). The primary outcome is the number of ventilator-free days at day 28, defined as the number of days alive and without mechanical invasive and/or non-invasive ventilation between randomization and day 28. Secondary outcomes include non-invasive ventilation (NIV) failure rate, duration of mechanical ventilation (invasive and/or NIV), circulatory support (vasopressor), outcomes related to corticosteroid adverse events (severe hyperglycaemia, gastrointestinal bleeding, uncontrolled arterial hypertension, ICU-acquired weakness, ICU-acquired infections, and delirium), lengths of ICU and hospital stay, ICU and hospital mortality, day 28 and day 90 mortality, number of new exacerbation(s)/hospitalization(s) between hospital discharge and day 90, and dyspnoea and comfort at randomization, ICU discharge, and day 90. Subgroup analyses for the primary outcome are planned according to stratification criteria at randomization.