Optimal Antihypertensive Therapy Research Articles

Comparison of the Efficacy of Labetalol and Nifedipine in Preeclampsia: A Prospective Interventional Study

Introduction: Hypertensive disorders of pregnancy constitute the most widely analysed conditions in pregnancy. Previously, methyldopa was the most commonly used drug, which nowadays has been largely replaced by T. labetalol and T. nifedipine due to the slower onset of action of methyldopa. Chronic hypertension is associated with more maternal and perinatal adverse events, so it is important to determine the optimal antihypertensive therapy. Aim: To compare drug side effects, obstetric complications, and mode of delivery between Group A (T. labetalol administered) and Group B (T. nifedipine administered). Materials and Methods: A prospective interventional study was conducted in the Department of Obstetrics and Gynaecology, Dhiraj Hospital and SBKS Medical Institute and Research Centre, Vadodara, Gujrat, India from December 2022 to May 2023 at Dhiraj Hospital, involving 200 pregnant women with hypertension or Blood Pressure (BP) readings ≥140 mmHg Systolic Blood Pressure (SBP) or ≥90 mmHg Diastolic Blood Pressure (DBP) after 20 weeks gestation. They were randomly divided into two groups: Group A (n=100) with T. labetalol administered and Group B (n=100) with T. nifedipine. The two groups were compared with variables like age, side effects of respective drugs, pregnancy complications, and outcomes, including vaginal or caesarean delivery. The Chi-square and t-test were used to compare variables between the two groups. Results: The mean age in Group A was 25.52±4.10 years, and in Group B, it was 25.95±4.47 years. In Group A (T. labetalol), the majority of cases, i.e., 34 (34%), required a 200 mg dose, followed by 300 mg in 26 (26%) of cases. In Group B (T. nifedipine), the majority of cases, i.e., 48 (48%), required a 30 mg dose, followed by 20 mg in 28 (28%) and 40 mg in 24 (24%) of cases. In Group A (T. labetalol), 2 (1%) cases had Intrauterine Growth Restriction (IUGR), 4 (2%) had oligohydramnios, and 2 (1%) had Intrauterine Demise (IUD). In Group B (T. nifedipine), 6 (3%) cases had IUGR, 6 (3%) had oligohydramnios, and 0 (0%) mmHg had IUD. No significant difference was found between Group A and B (p=0.213). In Group A (T. labetalol), 76 (38%) cases had vaginal delivery, 14 (7%) had emergency caesarean sections, and 10 (5%) had elective caesarean sections. In Group B (T. nifedipine), 70 (35%) cases had vaginal delivery, 18 (9%) had emergency caesarean sections, and 12 (6%) had elective caesarean sections. No significant difference was found between groups A and B (p=0.628). Post-intervention SBP in Group A was 126.06±6.6 mmHg, and in Group B, it was 126.96±8.17 mmHg with no statistically significant difference (p=0.3925). Post-intervention DBP in Group A was 80.6±2.38 mmHg, and in Group B, it was 80.2±1.40 mmHg with no statistically significant difference (p=0.14). Conclusion: Both T. labetalol and T. nifedipine were found to be equally effective. However, with respect to drug side effects and tolerability, T. labetalol was found to be significantly better compared to T. nifedipine.

Adherence to ESC guidelines for antihypertensive drug therapy: real-world survey from an EU country

Abstract Background Achieving optimal BP control in hypertensive patients (pts) remains a continuous challenge worldwide. Multiple factors are responsible for the low rates of BP control with suboptimal drug choice playing a key role. Practice guidelines should serve as evidence based foundation for optimal antihypertensive drug therapy but their impact in the real-world is variable. Purpose This retrospective study aimed: 1. To assess the prescription pattern of main classes of antihypertensive drugs and its association with comorbidities. 2. To compare prescription before and after the publication of the 2018 ESC/ESH guidelines for management of arterial hypertension, translated into local language (in 2019). Thus, prescriptions in the years 2018 and 2020 were compared. Dual combination of ACEi/ARB + CCB/thiazide-like diuretics (THI) or triple combination of ACEi/ARB + CBB + THI were considered as guidelines directed first line drugs (FLAD) i.e. adherence to guideline. Spironolactone (MRA) was considered as recommended drug for patients requiring ≥4 drugs. Methods We analysed prescribed drug therapy in a large patient cohort from the years 2018 and 2020 with 264 237 and 272 934 hypertensive pts, respectively. Pts were considered hypertensive after meeting at least one of two criteria: 1. Having been prescribed ≥ 121 standard drug doses of antihypertensive drugs in the year before the studied period. 2. Having at least 2 medical visits with the diagnosis of hypertension within 2 years before the studied period. Following comorbidities were considered as potential modifiers of drug therapy: ischemic heart disease (IHD), chronic heart failure (CHF), atrial fibrillation (AF), diabetes (DM) and chronic kidney disease (CKD). Results Overall, first line therapy was prescribed to 21.5% and 22.4% of pts in the year 2018 and 2020, respectively (p<0.0001). In pts taking ≥3 drugs 30.4% did not use THI, in those taking ≥4 drugs only 10.7% used spironolactone (MRA). Selected results are in the attached table. Conclusion Adherence to guideline recommended FLAD in this large survey improved but remained low during the first year after publishing ESC 2018 guidelines: only 22.4% of pts received FLAD in this cohort where 58.6% were free of comorbidities. In pts with AF, the use of FLAD was the lowest with 7.3%. Preferred use of BB and low use of THI and MRA were mostly behind this trend. BB (alone or in combination) were the most prescribed drug group – to 57.3% of pts both in 2018 and 2020. Their prescription was high in all pts with comorbidities, notably worrisome for diabetic pts (66.0%). Continuous efforts to improve dissemination of knowledge of FLAD according to guidelines appear mandatory.Attached table

The role of stress and sleep disorders in the development of cardiovascular complications in patients with arterial hypertension: what is important for an internist to know? A review

This publication discusses the mechanisms underlying the development of arterial hypertension on the background of stress, discusses the current problems of blood pressure control in patients with stress-induced sleep disorders, the clinical features of patients with hypersympathicotonia as the main mechanism for the development of arterial hypertension and blood pressure variability in patients with comorbid pathology, a diagnostic algorithm, as well as presenting current recommendations in the strategy for choosing the optimal antihypertensive therapy with the possibility of personalized choice in various clinical situations.

Pharmacological treatment in patients with aortic dissection

ObjectivesTo describe medical management in aortic dissection (AD) and to analyse the possible associations between antihypertensive, antithrombotic, anticoagulant and statin agents, respectively, and long-term survival.MethodsFrom Swedish medical registers, all patients...

Resistant arterial hypertension: is it really so or have we missed something?

This publication discusses the relevance of the problem of blood pressure control in patients with resistance to drug therapy in real clinical practice. Data on the prevalence of true resistant arterial hypertension and clinical features of patients are presented. At the same time, taking into account the wider prevalence of patients with pseudo resistant arterial hypertension, special attention is paid to diagnostic algorithms in the publication, and the criteria for excluding pseudo resistant arterial hypertension are analyzed in detail. Presented are modern ideas about the most common secondary causes of arterial hypertension, such as obstructive sleep apnea syndrome, the possibility of correcting this condition and the choice of drug therapy. For this publication, modern recommendations were used in the strategy for choosing the optimal antihypertensive therapy, taking into account the pharmacokinetic properties and the possibility of personalized choice in various clinical situations. We analyzed data on the benefits of antihypertensive therapy using fixed combinations to increase adherence to therapy with a blood pressure control strategy and reduce the risk of cardiovascular risks. Various search engines were used to search for data and material: PubMed, Google Academy, Elsevier, information resources of the Russian Society of Cardiology and the European Society of Cardiology.

Hypertensive Emergency in Heart Failure: Trends, Risk factors and Outcomes from a Nationwide Analysis 2005-2014.

Heart failure (HF) patients may be susceptible to complications of hypertensive emergency (HTNE). Large registries have found that these patients are not on optimal antihypertensive therapy. To date, little investigation has been done on HF patients with HTNE, and their clinical risk factors/outcomes have not been well defined. We reviewed the National Inpatient Sample database to collect data on HF patient hospitalizations from 2005 to 2014. HF patients with and without a primary diagnosis of HTNE were included in the analysis. Risk factors and outcomes of HF patients with a primary diagnosis of HTNE were compared to those without HTNE. HF patients with a primary diagnosis of shock of any etiology were excluded. Of 8,265,792 patients hospitalized with HF, 39,170 (0.5%) had HTNE. There was a threefold increase in the incidence of HTNE in HF patients over a 10-year period. The increase was more evident in females, Blacks and those <40 years of age. There was also an increasing trend in modifiable risk factors. HF patients with HTNE had significantly higher major in-hospital complications compared to those without HTNE. However, this association did not reflect an increase in short-term in-hospital mortality, irrespective of age. HF patients with HTNE represent a unique population that requires a different approach to treatment. Further research is needed to identify barriers preventing adequate therapy of hypertension and other modifiable risk factors in HF patients and assess their effects on long-term outcomes.

Choosing the optimal antihypertensive therapy

The article considers approaches to the selection of optimal antihypertensive therapy in order to achieve the target blood pressure in patients with hypertension in accordance with the latest Recommendations on hypertension of the European Society of Hypertension (ESH) and the European Society of Cardiology; ESC), as well as the circadian rhythm of blood pressure. Fixed combinations of renin-angiotensin-aldosterone system blockers, which include angiotensin II receptor blockers and angiotensin-converting enzyme inhibitors, with calcium antagonists should be preferred. Taking such a fixed combination at night can prevent the morning rise in blood pressure, when patients with hypertension usually have cardiovascular accidents.

Drug therapy of arterial hypertension: assessment of the physicians’ basic knowledge. Final results of the PHYSTARH project

Background. Arterial hypertension is a multifactorial disease accompanied by an increase in systolic and/or diastolic blood pressure above the established values. Uncontrolled blood pressure can cause various complications, which will lead to either disability or death of the patient.&#x0D; Aim. To assess the compliance of the level of doctors knowledge with current clinical guidelines in the treatment of arterial hypertension.&#x0D; Materials and methods. Within the framework of the PHYSTARH multicenter study, we presented the results of an anonymous prospective survey to assess the level of physicians knowledge and pharmacotherapeutic preferences in the treatment of arterial hypertension.&#x0D; Results. The study involved 425 physicians from 9 regions of Russia: Belgorod, Voronezh, Lipetsk, Chelyabinsk, Moscow, Krasnodar Territory, Primorye Territory, the Republic of Adygea and Tatarstan. In the course of the analysis, we revealed an insufficiently high level of the respondents knowledge in the treatment of arterial hypertension. Less than half of the respondents chose the indication of combination therapy as a therapeutic intervention in which the effectiveness of lowering blood pressure increases about 5 times more than when the dose of the original drug is doubled; correctly indicated the pharmacological group for the proposed drug (methyldopa), determined the indication for the use of aspirin in patients with hypertension, selected the optimal antihypertensive therapy for the proposed clinical situations, indicated absolutely contraindicated antihypertensive drugs in pregnancy and chronic obstructive pulmonary disease.&#x0D; Conclusion. The need for additional educational activities among physicians was established to improve the quality of knowledge on the basic aspects of hypertension, because a significant number of key questions on this topic cause difficulties for respondents.

Primary aldosteronism: from diagnosis to therapy in clinical practice

Primary aldosteronism (PA) is the single most common cause of secondary hypertension and is associated with increased target organ injury. It can be can either surgically cured or treated with targeted pharmacotherapy. PA is frequently undiagnosed and untreated, leading to aldosterone-specific cardiovascular morbidity and nephrotoxicity. Thus, clinicians should perform case detection testing for PA at least once in all patients with hypertension. The diagnostic work-up of PA is a sequence of three phases comprising screening tests, confirmatory tests and the differentiation of unilateral from bilateral forms. With appropriate surgical expertise, laparoscopic unilateral adrenalectomy is safe, efficient and curative in patients with unilateral adrenal disease. In patients who have bilateral aldosterone hypersecretion, the optimal management is a low sodium diet and lifelong treatment with a mineralocorticoid receptor antagonist administered at a dosage to maintain a high-normal serum potassium concentration without the aid of oral potassium supplements. In patients with PA, specific treatment provides prognostic benefit over optimal antihypertensive therapy and is therefore crucial to reduce mortality and morbidity in this subgroup of patients with hypertension.

Clinical and functional predictors that cause a decrease of indicators of morning blood pressure profile in antihypertensive telmisartan-based therapy

Background: Blood pressure (BP) monitoring is an important aspect in the treatment of arterial hypertension (AH), namely the morning BP increase which is associated with an increased risk of cardiovascular and cerebrovascular incidents as well as sudden death. The study herein revealed clinical and functional predictors which decrease the morning BP rise in the case of optimal antihypertensive therapy with telmisartan, based on results of daily blood pressure monitoring (DBPM).&#x0D; Methods: A single-center open-label study in parallel groups was conducted. The study included 50 patients with AH who had previously received antihypertensive therapy but did not achieve a reduction in BP according to DBPM. Telmisartan (40 - 80 mg per day) was added to the treatment regimen of all patients. All patients underwent a general clinical examination, measurement of glucose and creatinine levels, assessment of lipid profile, ECG recording in 12 leads, echocardiography (EchoCG), and DBPM before treatment and after 12 weeks of treatment. Statistical data analyses were performed.&#x0D; Results: Twelve-week antihypertensive telmisartan-based therapy led to a decrease in mean systolic blood pressure (SBP) from 134.3 ± 5.0 to 126.2 ± 4.3 mm Hg (p = 0.008), and a decrease in mean diastolic blood pressure (DBP) from 79.8 ± 1.5 to 73.0 ± 1.4 mm Hg (p &lt; 0.001). There was a decrease in the index of variability of DBP from 22.4 ± 2.8 to 16 ± 2.4 mm Hg (p &lt; 0.001), and a decrease in the daily index of SBP from 15.7 ± 4.7 to 13.1 ± 4.7 mm Hg (p = 0.014). In the study, a connection was found between the decrease of the average morning index and the following indicators: presence of left ventricular (LV) hypertrophy on ECG, final diastolic size of the LV over 6.0 cm, LV ejection fraction below 52.3%, total cholesterol level over 5.5 mmol/L, LDL level greater than 3.3 mmol/L, and triglyceride level greater than 2.0 mmol/L.&#x0D; Conclusion: These values could be used as predictors of a decrease in the morning index during 12-week telmisartan therapy.

THERAPY OF ENDOCRINE DISEASE: Medical treatment of primary aldosteronism.

In patients with primary aldosteronism, specific treatment provides prognostic benefit over optimal antihypertensive therapy and is therefore crucial to reduce mortality and morbidity in this subgroup of patients with hypertension. Prognostic relevance has been shown for adrenalectomy in unilateral disease and for medical treatment with mineralocorticoid receptor antagonists in bilateral adrenal hyperplasia. Collectively, evidence points to the superiority of surgical treatment compared to medical treatment. The causal approach of removing the mineralocorticoid excess, as well as the often-accompanying glucocorticoid excess, might provide one biologically plausible explanation for the observation of slightly better outcomes with surgical therapy. However, in patients living with primary aldosteronism, medical treatment is often insufficient for three major reasons. First and foremost, no marker of sufficient aldosterone blockade has yet been established and therefore adequate treatment of the aldosterone excess is often dismissed as a treatment goal. Second, side effects often limit patient compliance. Third, as recommendations differ from other indications like heart failure, drug dosing is often inadequate. The aim of this review is first to provide an overview over medical treatment options and second to review potential markers for treatment surveillance in patients with primary aldosteronism.

THE BEST WAY FOR DETECTING THE DELAYED INEFFICIENCY OF ANTIHYPERTENSIVE THERAPY

Objective: To determine the best way for detecting the delayed inefficiency of an antihypertensive therapy (AHT). Design and method: The AHT (2–3 drugs from various 1st line groups) was assigned to 102 hypertensive patients (52 men, age 54.2 ± 9.8 years). Antihypertensive agents and their dosages were selected during 2–3 weeks of ambulatory management, with the possibility of a single correction initially prescribed AHT. In all participants were achieved the target BP levels at the stage of inclusion, which were confirmed by office blood pressure monitoring (OBPM) (<130/80 mmHg, oscillometric method, OMRON, Japan), and by ambulatory blood pressure monitoring (ABPM) (24-hour BP < 130/80 mmHg, oscillometric method, BpLab, Russia). 1 and 3 months after the inclusion stage the evaluation of the efficacy of AHT was carried out by OBPM, ABPM, and by assessment of home blood pressure monitoring (HBPM) data. Results: During the first three months of taking recently prescribed AHT, 34 patients (33.3%) demonstrated the escape phenomenon in according to a data at least of one of the measurement methods. There were identified: 22 cases (64.7%) of the escape phenomenon by OBPM, 28 cases (82.4%) - by HBPM, and 32 cases (94.1%) - by ABPM. The sensitivity and specificity for the OBPM were 46.1% and 93.6% respectively, for the HBPM - 78% and 88% resp., and for the ABPM - 82% and 92% resp. Conclusions: It is recommended to carry out the ABPM, and to assess HBPM data after 1 and 3 months of taking recently prescribed optimal AHT to identify the escape phenomenon, prevent cardiovascular events, and to reduce a number of the repeated hospitalizations.

Effects of direct renin inhibition versus angiotensin II receptor blockade on angiotensin profiles in non-diabetic chronic kidney disease

Background: Direct renin inhibition (DRI) is clinically inferior to other blockers of the renin–angiotensin system (RAS). Thus far, the underlying molecular causes of this finding remain unknown.Methods: Twenty four patients with non-diabetic chronic kidney disease (CKD) stages III–IV and albuminuria were randomized to DRI or angiotensin receptor blocker (ARB). Employing a novel mass-spectrometry method, the concentrations of renin, aldosterone and plasma angiotensin peptides [Ang I, Ang II, Ang-(1-7), Ang-(1-5), Ang-(2-8), Ang-(3-8)] were quantified before and after an 8-week treatment.Results: While blood pressure, renal function and albuminuria decreased comparably in both groups, profound RAS component differences were observed: DRI led to a massive renin increase, while suppressing both vasoconstrictive (Ang I and Ang II) and vasodilatory RAS metabolites (Ang-(1-7) and Ang-(1-5)). In contrast, ARB led to a four-fold increase of Ang I and Ang II, while Ang-(1-7) and Ang-(1-5) increased moderately but significantly. With ARB treatment, a decreased aldosterone-to-Ang II ratio suggested efficacy in blocking AT1 receptor.Conclusions: DRI therapy abolishes all RAS effector peptides. ARB increases both vasoconstrictive and vasodilative angiotensins, while this is accompanied by efficient blockade of vasoconstrictive effects. These differential molecular regulations should be considered when selecting optimal antihypertensive and disease-modifying therapy in CKD patients.Key messagesDirect renin inhibition leads to a complete and lasting abolition of both classical and alternative RAS components.Angiotensin receptor blockade leads to effective receptor blockade and up-regulation of alternative RAS components.Differential molecular regulations of the RAS should be considered when selecting optimal antihypertensive and disease-modifying therapy in CKD patients.

The Effectiveness of Combination Antihypertensive Therapy in Women With Hypothyroidism and the Metabolic Syndrome

Evaluating the effectiveness of the various options of combination antihypertensive therapy (AHT) in women with arterial hypertension (AH) and metabolic syndrome (MS) and hypothyroidism. The study included 163 women with hypertension, metabolic syndrome, and hypothyroidism, the median age of 53.5 (48-60) years; in 73 (44.8%) women were diagnosed with subclinical hypothyroidism (SH), 90 (55.2%) - overt hypothyroidism (OH). Patients with both SH and OH, depending on the source of the heart rate (HR) was appointed as one of the following combination of AHT. If heart rate <75 beats/min, patients (n=100) received a combination of the dihydropyridine calcium antagonist (AA) amlodipine 5 mg/day, and angiotensin receptor blockers II (ARB) losartan 50 mg/day, with heart rate >75 beats/min (n=63) - a combination of amlodipine 5 mg/day and imidazoline receptor agonist (IRA) moxonidine 200 micrograms/day. The failure to achieve target blood pressure (BP) after 4 weeks of dose drugs doubled with subsequent evaluation of the effectiveness even after 4 weeks. At baseline and after 6 months of therapy, all patients underwent daily blood pressure monitoring (DBPM). At 8 weeks, the use of a combination of AA+ARB target BP level was registered in 26 (59%) of 44 women with SH and 34 (60.7%) of the 56 - OH. In the group of women who took the AA+IRA, after 8 weeks of the target blood pressure was observed in 24 (82.8%) of 29 patients with SH and 28 (82.4%) of 34 - to OH. Register the target blood pressure was observed significantly more frequently (p<0,05) when using a combination of AA+IRA compared with AA+ARBs as with SH and OH. As a result of the combination of DBPM AA and ARBs in patients with SH and OG provided a significant reduction in average daily, daytime and nighttime systolic and diastolic blood pressure (SBP and DBP), the time index of SBP and DBP during the day and night hours. The therapy of AA and IRA regardless of the severity of hypothyroidism, there was a significant improvement in all indicators DBPM: average daily, daytime and nighttime SBP and DBP, time index and variability in SBP and DBP during the day and at night. Furthermore, as in the SH and OH significantly more pronounced positive changes most DBPM parameters were recorded using IRA in combination with AA compared with a combination AA+ARB. Significant increase in the number of women with optimal BP daily profile "dipper" observed only when using amlodipine and moxonidine. In women with hypertension, hypothyroidism and MS, regardless of the severity of decline of thyroid function and combination of the dihydropyridine AA IRA had an advantage over the AA combination with ARBs, since most patients provided achieving target blood pressure and clinically significant positive impact on BPM indicators. The results can be used in selecting the optimal AHT in patients with hypertension, MS, and the manifest subclinical hypothyroidism.

Autosomal polycystic kidney disease

Autosomal dominant polycystic kidney disease (ADPKD) is the most common monogenetic kidney disease. The clinical course is highly variable, association to certain genetic mutations only weak. Great progress has been made in recent years in determining the pathophysiology of the disease. Diagnosis of ADPKD is almost always possible by ultrasound, genetic examination is confined to selected cases. In addition, imaging is important for prognosis where MRI and computer tomography are superior for determination of total kidney volume. Until recently, supportive therapy has been the only available therapeutic option. This includes optimal antihypertensive therapy with a goal blood pressure below 110/75 mm mercury, at least with normal renal function and without any other contraindication. In addition, fluid intake should be increased to 2.5-4 l per day. Finally, tolvaptan is available as a specific therapy in selected countries. This therapy should be restricted to cases with rapid progressive and early renal failure due to costs and side effects. The value of this agent in later stages of chronic renal failure is currently being evaluated in clinical studies. Additional specific therapies are in early clinical evaluations.

OP.7C.10] IDENTIFICATION OF GENE VARIANTS ASSOCIATED WITH ANTIHYPERTENSIVE RESPONSES TO BETA BLOCKERS AND LOSARTAN

Objective: A genome-wide association study on Genetics of Drug Responsiveness in Essential Hypertension (GENRES) identified four single nucleotide polymorphisms (SNPs) associated with blood pressure (BP) response to bisoprolol and three SNPs associated with BP response to losartan in Finnish men. Here we replicate these results using the Finnish subjects of the Losartan Intervention For Endpoint Reduction in Hypertension Study (LIFE). Design and method: The LIFE study subcohort included 927 men and women with hypertension that were randomized to atenolol (N = 467) or losartan (N = 460) based treatment. We analysed the BP response at the two months’ visit when the subjects were using a monotherapy with 50 mg of atenolol or 50 mg of losartan, or a combination therapy with 12.5 mg of hydrochlorothiazide added to the monotherapy (approximately half of the subjects). The DNA samples were genotyped using Illumina HumanOmniExpress-12 BeadChip. We used an additive genetic model and linear regression with appropriate covariates to analyze the associations of the four bisoprolol-associated SNPs (GENRES) with BP responses to atenolol-based treatment (LIFE), and the three losartan-associated GENRES SNPs with BP responses to losartan in LIFE. Separate analysis was performed in men if SNP*sex interaction was significant (P < 0.05). Results: rs2514036 on chromosome 11 within the ACY3 gene was associated with systolic (beta = -5.5 mmHg, P = 0.005) and diastolic (beta = -1.9 mmHg, P = 0.05) BP responses to atenolol in men. The effect was in the same direction as the effect on bisoprolol response in GENRES. rs3814995 on chromosome 19 in the NPHS1 gene was associated with diastolic BP response to losartan (beta = -0.9 mmHg, P = 0.04), again with the same direction of effect. Conclusions: This replication study supports earlier findings that rs2514036 within the ACY3 gene is associated with BP response to beta blockers and that rs3814995 in NPHS1 gene coding for nephrin is associated with BP response to losartan. The findings suggest these SNPs could be used as genetic markers for selecting optimal antihypertensive therapy. The findings also encourage further research on the role of ACY3 and NPHS1 genes in the antihypertensive effect of beta blockers and losartan, respectively.

The Role of Immunosuppressive Medications in the Pathogenesis of Hypertension and Efficacy and Safety of Antihypertensive Agents in Kidney Transplant Recipients

The purpose of this review is to summarize current data on the role of immunosuppressants in the pathogenesis of hypertension and the efficacy and tolerability of major antihypertensive classes in kidney transplant recipients. Arterial hypertension is a common complication after kidney transplantation and a major risk factor for adverse outcome and graft rejection due to blood pressure elevation by immunosuppressive medications. Calcineurin inhibitors induce hypertension by a mechanism related to the imbalance of vasoactive substances endothelin and nitric oxide, and probably by causing overactivity of thiazide-sensitive sodium-chloride-cotransporter. Corticosteroids are well known for their hypertensive effects. The interactions of calcineurin inhibitors and mammalian target of rapamycin inhibitor sirolimus also promote hypertension. Management of arterial hypertension is a complex problem in the care of kidney transplant recipients. Target blood pressure values of <130/80 mm Hg are suggested by the National Kidney Foundation/ Kidney Disease Outcomes Quality Initiative. Calcium channel blockers may be useful in antagonizing the vasoconstrictive effects of calcineurin inhibitors. The renin-angiotensin system inhibitors seem a good option, especially in patients with proteinuria, however their effects on long-term graft and patient survival are controversial. β-Blockers could be beneficial in patients with coronary heart disease, but caution is required due to metabolic adverse effects. Thiazide diuretics could be the reasonable option for patients with glomerular filtration rate ≥30 mL/min/1.73 m2, also with caution regarding hypokalemia and glycemia. Until more evidence is provided, the choice of optimal antihypertensive therapy in kidney transplant recipients should be based on previous individual antihypertensive tolerability and efficacy, comorbidities, concomitant medications and post-transplant kidney function.

Association Between Hypertension and Residual Renal Function in Hemodialysis Patients

AbstractIntroduction.Cardiovascular diseases are the leading cause of death in hemodialysis patients. The decline of residual renal function increases the prevalence and severity of risk factors of cardiovascular morbidity and mortality in these patients. Hypertension is common in dialysis patients and represents an important independent factor of survival in these patients.Methods.The study included 77 patients who are on chronic HD for longer than 3 months. Depending on the measured residual diuresis patients were divided into two groups. The study group consisted of patients with residual diuresis &gt;250 ml/day, while patients from control group had residual diuresis &lt;250 ml/day. All patients had their blood pressure measured before 10 consecutive hemodialysis treatments. Collected data were statistically analyzed using SPSS 16.0.Results.The study included 77 hemodialysis patients, mean age of 56.56±14.6 years and mean duration of hemodialysis treatment of 24.0 months. Of the total number of patients, 39(50.6%) had preserved residual renal function. Hypertension was more common in the group of patients who did not have preserved residual renal function (68.4% vs 25.6%). There was statistically significant negative linear correlation between the volume of residual urine output and the residual clearance of urea and values of systolic blood pressure [(rho=−0.388; p&lt;0.0001); (rho=−0.392; p&lt;0.0005)], values of mean arterial pressure [(rho =−0.272; p&lt;0.05); (rho=−0.261; p=0.023; p&lt;0.05)] and values of pulse pressure in hemodialysis patients [(rho =−0.387; p&lt;0.001); (rho=−0.400; p&lt;0.0005)].Conclusions.Residual renal function plays an important role in controlling blood pressure in patients on hemodialysis. More attention should be directed to preserve residual renal function, and after the start of hemodialysis by avoiding intensive ultrafiltration with optimal antihypertensive therapy.

Anti-hypertensive Drug Treatment of Patients with and the Metabolic Syndrome and Obesity: a Review of Evidence, Meta-Analysis, Post hoc and Guidelines Publications

Epidemiological studies have shown an increasing prevalence of obesity and the metabolic syndrome worldwide. Lifestyle modifications that include dietary changes, weight reduction, and exercise are the cornerstones in the treatment of this pathology. However, adherence to this approach often meets with failure in clinical practice; therefore, drug therapy should not be delayed. The ideal pharmacological antihypertensive regimen should target the underlying mechanisms involved in this syndrome, including sympathetic activation, increased renal tubular sodium reabsorption, and overexpression of the renin-angiotensin-aldosterone system by the adipocyte. Few prospective trials have been conducted in the search of the ideal antihypertensive regimen in patients with obesity and the metabolic syndrome. We summarize previously published ad hoc studies, prospective studies, and guideline publications regarding the treatment of hypertension in patients with obesity and the metabolic syndrome. We conclude that the optimal antihypertensive drug therapy in these patients has not been defined. Though caution exists regarding the use of thiazide diuretics due to potential metabolic derangements, there is insufficient data to show worsened cardiovascular or renal outcomes in patients treated with these drugs. In regard to beta blockers, the risk of accelerating conversion to diabetes and worsening of inflammatory mediators described in patients treated with traditional beta blockers appears much less pronounced or absent when using the vasodilating beta blockers. Renin-angiotensin-aldosterone system (RAAS) inhibition with an ACE or an ARB and treatment with calcium channel blockers appears safe and well tolerated in obesity-related hypertension and in patients with metabolic syndrome. Future prospective pharmacological studies in this population are needed.

Perioperative acute hypertension-role of Clevidipine butyrate.

Arterial hypertension (AH) is one of the most common pathological conditions affecting the general population which contributes to pathogenesis of various diseases and worsens the treatment outcome (James et al., 2014). It increases the perioperative morbidity and mortality, frequently result in cancelation of surgical procedures and increases treatment-associated costs (Handler, 2006). Perioperative hypertension may occur in patients with pre-existing arterial hypertension or manifest as a de novo phenomenon (Vuylsteke et al., 2000; Varon and Marik, 2008). Induction of general anesthesia is related with significant stress and sympathetic over-activation. The systolic blood pressure (SBP) in normotensive patients may increase by up to 20–30 mm Hg, while hypertensive patients may have an exaggerated reaction—SBP in these patients may increase up to 90 mm Hg (Ahuja and Charap, 2010). On the other hand, anesthesia-induced sympathetic suppression with diminished baroreceptor reflex takes place during the maintenance phase which frequently causes sustained arterial hypotension. Postoperatively, these patients present with labile BP, frequent and rebound hypertension, and have an increased risk of postoperative complications (Goldman and Caldera, 1979; Wolfsthal, 1993). Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC-7 and JNC-8) classifications and guidelines are currently applicable to perioperative patients as well (James et al., 2014; Chobanian et al., 2003). According to JNC-7 guidelines for evaluation and treatment of hypertensive emergencies, an immediate intervention is required in cases of hypertensive emergencies to reduce the SBP by 10–15% (no more than 25%) within the first hour. Reduction of the absolute BP to 160/110 mmHg should be done gradually over the following 2–6 h (Aggarwal and Khan, 2006; Flanigan and Vitberg, 2006; Pollack and Varon, 2008; Varon, 2008; De Gaudio et al., 2009; Hays and Wilkerson, 2010; Kuppasani and Reddi, 2010; Smithburger et al., 2010; Polly et al., 2011). Only in patients with aortic dissection, the SBP should be reduced to less than 120 mmHg within 20 min. In hypertensive emergencies associated with ischemic stroke, BP must be decreased to less than 180/110 before thrombolytic therapy may be administered (Pollack and Varon, 2008; Varon, 2008; De Gaudio et al., 2009; Hays and Wilkerson, 2010; Polly et al., 2011). Abrupt BP reduction should be avoided as it can result in critical blood flow reduction and ischemic end organ damage (Varon, 2008; De Gaudio et al., 2009; Smithburger et al., 2010; Polly et al., 2011). Since overshooting a target BP in hypertensive patients is associated with worse outcome, many treatment protocols require invasive arterial blood pressure monitoring during anesthesia in high risk cases (Pollack and Varon, 2008; Rhoney and Peacock, 2009). Hypertensive emergencies should be treated aggressively, using quick-onset intravenous medications, whereas hypertensive urgencies do not always require such aggressive treatment. Longer acting oral medications (labetalol, clonidine, etc.) may be more appropriate in situations of hypertensive urgency. However, caution should be exercised when using antihypertensive agents in the acute setting. An overly aggressive treatment approach may lead to organ hypoperfusion (Rodriguez et al., 2010). Once the immediate threat of organ damage is diminished, BP should be gradually brought to baseline level within a period of 24–48 h (Peacock et al., 2009). Characteristics of an ideal intravenous hypertensive agent are rapid onset and offset of action, low risk of hypotension, minimal drug interaction with other medications, lack of adverse reactions, wide therapeutic window, ease of titration, preservation of renal and hepatic functions, selectivity, low cost, possibility of easy transition to oral therapy, predictable response, and lack of effects on intracranial pressure (Levy, 1999; Oparil et al., 1999). Multiple intravenous medications are currently used to control the BP in the perioperative period, and all these medications have specific advantages and limitations (Kurnutala et al., 2013). Selection of an optimal antihypertensive therapy for the perioperative period depends on the patient’s individual characteristics and locally adopted guidelines (Pollack and Varon, 2008; Belsha, 2013). Clevidipine butyrate is a Ca2+-channel antagonist that acts on the L-type Ca2+