Degree Of Blood Pressure Reduction Research Articles

New data from a subanalysis of the TRICOLOR study: antihypertensive effectiveness of the triple single-pill combination of amlodipine/indapamide/perindopril and predictors of effectiveness and blood pressure control in young patients

Aim. To describe the antihypertensive efficacy of triple fixed­dose combination of amlodipine/indapamide/perindopril and assess the predictors of efficacy in young patients (<50 years).Material and methods. The TRICOLOR study (NCT03722524) is an observational prospective study (n=1247) that demonstrated high antihypertensive effectiveness and good tolerability of the triple single­pill combination (SPC) of amlodipine/ indapamide/perindopril. This subgroup analysis was performed on 199 patients aged <50 years (16% of the total population), and the comparison group consisted of 925 patients (82,3% of the total population) aged 50 years or older.Results. In young patients, during triple therapy with SPC amlodipine/indapa­ mide/perindopril, a positive trend in blood pressure (BP) reduction was observed compared to the baseline: an average decrease in BP after 12 weeks was 32,6 (11,0)/14,8 (8,5) mm Hg (p<0,0001), comparable to patients over 50 years of age in terms of reduction in systolic blood pressure (SBP) and diastolic blood pressure (DBP) after 2, 4 and 12 weeks of follow­up. A greater number of young patients achieved a reduction in blood pressure <140/90 mm Hg after 2 weeks of therapy compared to patients 50 years of age and older (49,7% vs 38,8%, p=0,004), and blood pressure <130/80 mm Hg – after 4 and 12 weeks (51,3% vs 43,5% (p=0,041) and 74,9% vs 67,5% (p=0,038), respectively). Left ventricular hypertrophy was a significant negative predictor of SBP reduction by 12 weeks of therapy, and the presence of grade 2 hypertension (HTN) and statin use, on the contrary, were positive predictors of changes in SBP by the end of observation. More adherent younger patients were significantly more likely to have a decrease in DBP by 12 weeks of follow-up. In addition, in young patients, male sex and the presence of dyslipidemia significantly increased the chances of blood pressure control at the end of observation. Waist circumference, body mass index, and grade 2 HTN were negative predictors of achieving the target blood pressure level.Conclusion. Thus, in young patients, good antihypertensive effectiveness of amlodipine/indapamide/perindopril was observed, comparable in the degree of blood pressure reduction with the older age group of 50 years and older.

Predictors for success of renal denervation in patients with resistant arterial hypertension

Objective. Development of principles for personalized selection of patients for renal denervation (RD) based on the evaluation of procedural response predictors. Design and methods. In the period from 2016 to 2022, 91 patients with resistant arterial hypertension (RHTN) underwent a RD procedure using 2 types of catheters — monopolar and spiral. All patients were assessed for basic demographic, clinical, functional, and laboratory characteristics. The reassessment was carried out on the 7th day, then after 6 and 12 months. A predictive model for determining the probability of response to RD was constructed using the logistic regression method. Results. The final analysis included data from 91 RHTN patients, the mean age was 57,79 ± 9,5 years. At baseline, patients received 4,5 ± 1,4 antihypertensive drugs. Initial office systolic blood pressure (SBP) was 190 (interquartile range (IQR) 100; 140, 240) mm Hg, diastolic blood pressure (DBP) — 100 (IQR 60; 80, 140) mm Hg. Among the responders, a significant reduction in blood pressure (BP) was achieved, with maintenance of the antihypertensive effect during 1 year of follow-up (p < 0,001 for SBP and DBP). The multivariate regression analysis showed that the initial DPB (p < 0,001), the diameter of the right (p = 0,049) and left renal arteries (RA) (p = 0,038) were significant predictors. Based on these data, a prognostic model was developed (p < 0,001). Conclusions. Our results confirmed effectiveness and safety of RD. The stability of the clinical effect is important. However, there was a high variability in the degree of BP reduction after the procedure. The initial DBP, the diameter of the left and right RA, and the use of drugs that reduce the activity of the sympathetic nervous system can be used as possible predictors of response to RD.

S-50-6: HOW TO ASSESS BENEFICIAL EFFECTS OF ANTIHYPERTENSIVE TREATMENTS

Most hypertensive patients could have hypertension mediated organ damage (HMOD) at the moment of the diagnosis. Even in low 10-year cardiovascular risk patients HMOD is frequent. The presence of HMOD is related to increased cardiovascular risk and mortality, so, at the same time HMOD should be considered as a therapeutic target and a surrogate marker of blood pressure un/controlled. The effects of impaired renal function and left-ventricular hypertrophy could identify patients at a mortality very high risk. Guidelines considered arterial stiffening evaluated as high carotid-femoral pulse wave velocity a factor influencing cardiovascular risk, and a documented carotid artery stenosis > 50 % as a marker of very high cardiovascular risk. The Shiga Epidemiological Study of Subclinical Atherosclerosis (SESSA) showed that 50% of the participants at risk category one had a mean of one atherosclerotic plaque, and 80.7 % of individuals at category two had a mean of 2.2 atherosclerotic plaques. The hazard ratio of having a vascular event could increase by 50% in the presence of one HMOD and by 3.8 times when three HMOD are present. In this scenario, to prevent that at least some patients could be misclassified as low risk, screening of HMOD as modifiers of cardiovascular risk estimated by different scores could be recommended in hypertensive patients. The non-significant net reclassification improvement of cardiovascular risk and the lack of evidence suggesting a relationship between vascular images biomarkers regression independently of blood pressure lowering and a reduction in cardiovascular events precludes the routine search of arterial stiffness or carotid atherosclerotic plaques out of research scenarios. A reduction in left ventricular mass during treatment is a favorable prognostic marker that predicts lesser risk for subsequent cardiovascular morbidity and mortality. The association between left ventricular mass regression and cardiovascular outcomes is independent of baseline left ventricular mass, baseline clinic and ambulatory blood pressure, and degree of blood pressure reduction. Suboptimal blood pressure control is a significant covariate of persistent left ventricular hypertrophy, independent of the number and class of antihypertensive drugs. RAS blockade is recommended as the initial treatment of hypertension in patients with reduced glomerular filtration rate or albuminuria since they are the most effective at reducing progression to end stage kidney disease, but a combination with calcium channel blockers or diuretics is recommended due to the difficulties to achieve the targets with monotherapy.

Association of Blood Pressure Within 6 h After Endovascular Thrombectomy and Functional Outcomes in Ischemic Stroke Patients With Successful Recanalization.

Background and PurposeBlood pressure in the days following endovascular thrombectomy (EVT) can influence functional outcomes of patients who have suffered an acute ischemic stroke, but whether the same is true of blood pressure during the first few hours after EVT is unclear.MethodsSeveral blood pressure parameters were retrospectively analyzed in acute ischemic stroke patients who underwent EVT at West China Hospital from March 2016 to December 2019. Baseline blood pressure, speed of blood pressure reduction, postoperative blood pressure, degree of blood pressure reduction, and quality of blood pressure management were evaluated during the first 24 h after EVT. We explored whether these parameters during different time windows correlated significantly with patients' modified Rankin Scale (mRS) score at 90 days.ResultsAnalysis of 163 patients showed that poor functional outcome (mRS scores 3–6) correlated significantly with higher postoperative blood pressure and worse blood pressure management during the first 6 h after EVT. Postoperative systolic blood pressure at 37 min after EVT was significantly higher in patients with poor outcome (141 mmHg) than in those with good outcome (mRS scores 0–2; 122 mmHg, p = 0.006), and systolic pressure >136 mmHg at this time point was associated with a significantly higher risk of poor outcome, before and after adjusting for other risk factors (adjusted OR 0.395, 95% CI 0.20–0.79).ConclusionsAmong acute ischemic patients who successfully undergo recanalization, adequate blood pressure management during the first 30–40 min after EVT may be important for ensuring good 90-day functional outcomes.

Low-degree inflammation is a mediator of target organ damage and a target for renal denervation in diabetic patients with resistant hypertension

Abstract Introduction Sympathetic activity is involved in low-degree inflammation, which is seen as a new cardiovascular risk factor and a possible therapeutic target. Resistant hypertension (RH) and diabetes mellitus (DM) are associated with increased sympathetic and pro-inflammatory activity, and renal denervation (RDN) is sympatholytic procedures with anti-inflammatory potential. Objective To investigate the relationship of inflammatory markers with target organ damage in patients with RH and type 2 DM, as well as the relationship between changes in organ damage after renal denervation with the anti-inflammatory effect of the procedure. Materials and methods We studied 74 patients with RH and type 2 DM (28 men (38%), mean age 59.1±8.6 years, office blood pressure (BP) (systolic/diastolic) 168.5/90.4 mm Hg, HbA1c 7.0±1.3%), of which 58 patients were included in single-arm prospective interventional study and underwent RDN (registration numbers NCT01499810 and NCT02667912 at ClinicalTrial.gov). Office and ambulatory BP measurement, laboratory tests (hsCRP, TNF-α, IL-6, sICAM-1, GDF-15 (ELISA)), echocardiography, renal Doppler ultrasound, and 1.5 Tesla MRI (assessment of white matter hyperintensity (WMH) of the brain and the enhancement index (IE) of the wall of the renal arteries (RA) after contrast enhancement with gadodiamide) were performed. Twelve months follow up were completed by 45 patients. Patients were instructed not to change the regimen of antihypertensive and hypoglycemic therapies throughout the study. Results At baseline there was a direct relation of left ventricular mass (LVM) with the level of sICAM-1 (r=0.72, p=0.003) and GDF-15 (r=0.53, p=0.036); values of renal resistive indices (RI) and severity of WMH of the brain correlated with levels of TNF-α (r=0.33, p=0.03 and r=0.55, p=0.01, respectively) and hsCRP (r=0.64 p=0.045 and r=0.64, p=0.045 respectively). IE of the wall of RA had positive relationship with hsCRP (R=0.51, p=0.04) and IL-6 (R=0.57, p=0.003). RDN significantly reduced BP (−12.4/−7.2 mm Hg, p=0.01), level of TNF-α (from 6.8±3.1 to 6.2±3.1 pg/mL, p=0.004) and hsCRP (from 4.6±3.8 to 3.1±2.3 mg/L, p=0.02) as well as values of IE of the wall of the RA from trunk to segmental branches (p<0.05). The effect of RDN on severity of WMH, renal RI, and LVM was not significant; however, 51% patients had regression of LVM. The changes in LVM and IE of the wall of RA did not depend on the degree of BP reduction. At the same times, there were relationships between changes of IE of the wall of RA and the changes in inflammatory markers (r=0.62, p=0.03 for hsCRP and r=0.56, p=0.04 for TNF-α). Changes of LVM correlated with changes in TNF-α too (r=0.43, p=0.01). Conclusion The severity of target organ damage in diabetic patients with RH are closely associated with chronic low-intensity inflammation, the suppression of which may by one of the mechanisms of beneficial effects of RDN on cardiovascular organs. Funding Acknowledgement Type of funding sources: None.

Независимые факторы сердечно-сосудистого риска: гипергомоцистеинемия и жесткость сосудов у больных с артериальной гипертензией

Актуальность. Определение факторов риска и проведение предварительной оценки общего сердечно-сосудистого риска (ССР) у пациентов с артериальной гипертензией (АГ) — самая важная задача в клинической практике. У большинства пациентов, помимо повышенного артериального давления (АД), отмечаются и другие факторы ССР, усиливающие друг друга, что приводит к увеличению общего ССР. Одним из факторов ССР является жесткость артерий. Определение жесткости артерий проводят с помощью метода определения скорости распространения пульсовой волны (СРПВ). Вторым независимым фактором риска развития сердечно-сосудистых заболеваний является повышенный уровень гомоцистеина (ГЦ) в крови. Цель: оценить связь гипергомоцистеинемии (ГГц) с жесткостью сосудов у пациентов с АГ. Материалы и методы. Наше исследование было выполнено в рамках исследования ХИПСТЕР в Украине. В исследование было включено 40 пациентов с I и II степенью АГ (средний уровень офисного систолического (САД)/диастолического АД — 155,88/92,60 ± 1,63/1,43 мм рт.ст.), частота сердечных сокращений — 71,40 ± 1,29 уд/мин. Средний возраст больных составил 55,85 ± 2,09 года (26–74). Пациентов с уровнем ГЦ ≥ 10 мкмоль/л определяли как пациентов с ГГц (Н-тип АГ). Жесткость сосудов определяли по СРПВ. Результаты. Нами выявлено, что в начале исследования 75% (30 пациентов с мягкой и умеренной АГ) имели Н-тип АГ с повышенным уровнем ГЦ. Пациенты с Н-типом АГ (ГГц) и АГ без ГГц не отличались по возрасту, длительности АГ. При этом пациенты с Н-типом АГ имели большие массу тела, индекс массы тела (ИМТ). Офисное САД у пациентов с Н-типом АГ в начале и через 6 месяцев лечения было выше по сравнению с пациентами без ГГц (156,45 ±1,04 мм рт.ст. против 152,55 ± 1,41 мм рт.ст. в начале (р < 0,05) и 130,65 ± 0,96 мм рт.ст. против 126,97±1,08мм рт.ст. через 6 месяцев (р < 0,05)). ИМТ в начале исследования с Н-типом АГ — 30,72 ± 0,39 кг/м2 против 28,34 ± 0,69 кг/м2 без ГГц (р < 0,05). Пациенты с Н-типом АГ хуже достигали целевых уровней АД на фоне лечения, и у них изначально были высокие показатели АД. Пациенты с Н-типом АГ по сравнению с пациентами без ГГц имели более выраженную степень инсулинорезистентности (по уровню индекса НОМА), меньшую скорость клубочковой фильтрации как в начале, так и в конце лечения. По данным суточного мониторирования АД до начала лечения пациенты с Н-типом АГ по сравнению с пациентами с АГ без ГГц имели достоверно более высокий уровень САД. После регрессионного анализа уровень гомоцистеина ассоциировался со СРПВ по артериям эластичного типа (СРПВэл) независимо от степени снижения АД (СРПВэл (6 месяцев), м/с, β = 0,307, Р = 0,001). Выводы. Мужской пол, индекс массы тела, скорость клубочковой фильтрации, уровень глюкозы крови, уровень офисного и центрального артериального давления ассоциировались с повышением уровня гомоцистеина крови у пациентов с артериальной гипертензией.

Age-specific cerebral haemodynamic effects of early blood pressure lowering after transient ischaemic attack and non-disabling stroke.

IntroductionThere is limited knowledge of the effects of blood pressure (BP) lowering on cerebral haemodynamics after transient ischaemic attack (TIA) and non-disabling stroke, particularly at older ages. We aimed to evaluate changes in transcranial Doppler (TCD) haemodynamic indices in patients undergoing early blood pressure lowering after TIA/non-disabling stroke, irrespective of age.Patients and methodsAmong consecutive eligible patients attending a rapid-access clinic with suspected TIA/non-disabling stroke and no evidence of extra/intracranial stenosis, hypertensive ones underwent intensive BP-lowering guided by daily home telemetric blood pressure monitoring (HBPM). Clinic-based BP, HBPM, End-tidal CO2 and bilateral middle cerebral artery (MCA) velocity on TCD were compared in the acute setting versus one-month follow-up; changes were stratified by baseline hypertension (clinic-BP≥140/90) and by age (<65, 65–79 and ≥80).ResultsIn 697 patients with repeated TCD measures, mean/SD baseline systolic-BP (145.0/21.3 mmHg) was reduced by an average of 11.3/19.9 mmHg (p < 0.0001) at one-month (133.7/17.4 mmHg), driven by patients hypertensive at baseline (systolic-BP change = −19.0/19.2 mmHg, p < 0.001; vs −0.5/15.4, p = 0.62 in normotensives). Compared with baseline, a significant change was observed at one-month only in mean/SD MCA end diastolic velocity (EDV) (0.77/7.26 cm/s, p = 0.005) and in resistance index (RI) (−0.005/0.051, p = 0.016), driven by hypertensive patients (mean/SD EDV change: 1.145/6.96 cm/s p = 0.001, RI change −0.007/0.06, p = 0.014). Findings were similar at all ages (EDV change – ptrend=0.357; RI change – ptrend=0.225), including 117 patients aged ≥80. EDV and RI changes were largest in 100 patients with clinic systolic-BP decrease ≥30 mmHg (mean/SD EDV change = 2.49/7.47 cm/s, p = 0.001; RI change −0.024/0.063, p < 0.0001).ConclusionThere was no evidence of worsening of TCD haemodynamic indices associated with BP-lowering soon after TIA/non-disabling stroke, irrespective of age and degree of BP reduction. In fact, EDV increase and RI decrease observed after treatment of hypertensive patients suggest a decrease in distal vascular resistance.

ASSESSMENT OF ANGIOTENSIN RECEPTOR BLOCKERS THERAPY WHEN ASSOCIATED TO MINERALOCORTICOID RECEPTOR ANTAGONISTS OR TO HYDROCHLOROTHIAZIDE ACCORDING CENTRAL HAEMODYNAMIC PARAMETERS

Objective: OBJECTIVE: The goal of antihypertensive therapy is to prevent complications. The harmful effects of aldosterone are innumerable: induced cardiac/renal fibrosis, sodium and water retention, inflammation, oxidative stress, among others, that are involved in arterial/myocardium stiffness, remodelling, heart failure and new onset atrial fibrillation. Thiazide diuretics can activate the neurohormonal system, impair glucose metabolism, increase new-onset diabetes, and are potentially arrhythmogenic. Protective effect of Angiotensin Receptor Blockers (ARBs) on major cardiovascular events might be partly independent of the degree of blood pressure reduction. Mineralocorticoid Receptor Antagonists (MRAs) therapy reduce arterial stiffness, plasma volume, collagen/elastin ratio and vascular/myocardial fibrosis. The objective is to assess the levels reached in central haemodynamic parameters (CHPs) when thiazide is replaced by MRA, and associated with ARBs, during the treatment of hypertensive patients with normal kidney function. Design and method: DESIGN AND METHOD: For this cross-sectional retrospective study, data were registered from 70 hypertensive patients, female/male: 39/31 (average age: 66/62), while being treated with hydrochlorothiazide (Hctz) combined to ARBs, and after changing to MRAs+ARBs therapy in the same patients. The average dose of Hctz among female/male were 14/15 mg and the duration of the Hctz+ARB therapy were 35/34 months, while the MRA+ARB therapy were 13/14 months. The CHPs (Central Aortic Pressure, End-Systolic Pressure, Mean Arterial Pressure, Pulse Pressure, Augmentation Pressure, Augmentation Index) were measured by the SphygmoCor System PVX (AtCor-Medical, Australia), according system's standard methods. Also was measured the difference between the normal levels, and the observed values of Augmentation Index (Diff-AIx) according age. Results: RESULTS: The results of CHPs, Diff-AIx, systolic and diastolic blood pressure during association of ARBs+MRAs therapy compared to ARBs+Hctz, both genders, showed the lowest values with a highly statistically significant difference, except augmentation pressure and pulse pressure among male. No hyperkalaemia was observed in this sample. Conclusions: CONCLUSIONS: These findings suggest that the dual block with MRA+ARB therapy giving better central haemodynamic parameters, reducing the stress to arterial-ventricular coupling, it could be helpful to prevent, in the short- and long-term, the harmful effects of angiotensin-aldosterone system such as the development of heart failure and atrial fibrillation.

Sodium-glucose cotransporter2 inhibitor-induced reduction in the mean arterial pressure improved renal composite outcomes in type2 diabetes mellitus patients with chronic kidney disease: A propensity score-matched model analysis in Japan.

Aims/IntroductionLarge‐scale clinical trials have reported that, in patients with type 2 diabetes mellitus, sodium–glucose cotransporter 2 (SGLT2) inhibitor treatment affords favorable renal outcomes; the underlying mechanisms, however, remain unclear. Thus, this study investigated how SGLT2 inhibitor‐induced changes in the mean arterial pressure (MAP; denoted as ΔMAP) are associated with renal outcomes in type 2 diabetes mellitus patients with chronic kidney disease (CKD).Materials and MethodsWe retrospectively assessed the data of 624 Japanese type 2 diabetes mellitus patients with CKD who had been using SGLT2 inhibitors for >1 year. For propensity score matching (1:1 nearest neighbor match, with caliper value = 0.053, no replacement), patients were categorized into two groups based on the ΔMAP (>−4 mmHg [n = 329] and ≤−4.0 mmHg [n = 295]). Composite albuminuria progression or a ≥15% annual reduction in the estimated glomerular filtration rate was regarded as the end‐point.ResultsPer group, 173 propensity‐matched patients were compared. Patients with ΔMAP ≤−4 mmHg had a significantly lower incidence of composite renal outcomes than those with ΔMAP ≥−4 mmHg (5.8% [n = 10] vs 15.6% [n = 27], P = 0.003). Although the between‐group differences in the estimated glomerular filtration rates were non‐significant, patients with a ΔMAP ≤−4 mmHg had significantly larger reductions in the logarithmic urine albumin‐to‐creatinine ratio (P = 0.005).ConclusionsThe degree of blood pressure reduction after SGLT2 inhibitor treatment influenced renal composite outcomes in Japanese type 2 diabetes mellitus patients with CKD, confirming the importance of blood pressure management in type 2 diabetes mellitus patients with CKD, even when they are under SGLT2 inhibitor treatment.

Опыт применения фиксированной комбинации рамиприла и индапамида в клинической практике

Relevance. Arterial hypertension is one of the most common cardiovascular diseases in the adult population, but much has already been achieved in its treatment. The advantages of combination therapy, according to the clinical recommendations "Arterial Hypertension in Adults" in 2020, are as follows: an increase in the degree of blood pressure reduction is much stronger than an increase in the dose of a single drug; the possibility of physiological and pharmacological synergy between drugs of different classes, which may underlie a more pronounced reduction in blood pressure and better tolerability of treatment; suppression of the opposite mechanisms of increasing blood pressure. Aim. Aim of the study was to study the effect of the antihypertensive drug – Konsilar-D24 on the clinical picture, HRV data, and hemodynamic parameters in patients with stage II hypertension of the 2nd degree. Materials and methods. 40 patients with stage II AH and grade 2 AH were examined. During the outpatient examination, all patients were evaluated for HRV, SCAD, SMAD, ECHO-KG, ECG, GFR, laboratory and biochemical examination (UAC, OAM, blood bch-creatinine, urea, glucose, ASAT, ALAT), and the SF-36 quality of life questionnaire. Results. An increase in SVVR, a decrease in blood pressure, and an increase in the quality of life of the patient. Discussion: Konsilar-D24 is an effective antihypertensive agent for grade 2 hypertension in the complex treatment of stage II hypertension. Against the background of therapy, there is a persistent achievement of target figures, an increase in vagal tone. There is a metabolic neutrality of the drug, as well as nephro and cardioprotective effects. Keywords: arterial hypertension, ramipril, indapamide For citation: Kochetkovа I.V. Experience of using a fixed combination of ramipril and indapamide in clinical practice. Consilium Medicum. 2021; 23 (1): 103–108. DOI: 10.26442/20751753.2021.1.200759

Angiotensin receptor blockers and mineralocorticoid receptor antagonists therapy reaches better central haemodynamic parameters and avoid the episodes of atrial fibrillation

Abstract Introduction The goal of antihypertensive therapy is to prevent complications. The harmful effects of aldosterone are innumerable: induced cardiac/renal fibrosis, sodium and water retention, inflammation, oxidative stress, among others, that are involved in arterial/myocardium stiffness, remodelling, heart failure and new-onset atrial fibrillation (AF). Thiazide diuretics can activate the neurohormonal system, impair glucose metabolism, increase new-onset diabetes, and are potentially arrhythmogenic. Protective effect of Angiotensin Receptor Blockers (ARB) on major cardiovascular events might be partly independent of the degree of blood pressure reduction. Mineralocorticoid Receptor Antagonists (MRA) therapy reduce arterial stiffness, plasma volume, collagen/elastin ratio and vascular/myocardial fibrosis. Purpose The objective was to assess the levels reached in central haemodynamic parameters (CHP) and the presence of episodes of AF during ARB+hydrochlorothiazide (Hct) versus ARB+MRA therapy in hypertensive patients with normal kidney function. Methods For this cross-sectional retrospective study, data were entered from 108 hypertensive patients, female 62 (ARBs+MRA/ARB+Hctz average age 67/71), male 46 (average age ARB+MRA/ARB+Hctz 67/71), both p=ns). The average doses of Hct among female/male were 16/19 mg and the duration of the ARB+Hctz therapy were 37/47 months, while the ARB+MRA therapy were 36/49 months. 24-hours Holter monitoring was used in all patients. The group ARB+MRA before therapy had a history of AF episodes. The CHP (Central Aortic Pressure, End-Systolic Pressure, Mean Arterial Pressure, Pulse Pressure, Augmentation Pressure, Augmentation Index) were registered by the SphygmoCor System PVX (AtCor-Medical, Australia), according system's standard methods. Also was measured the difference between the normal levels, and the observed values of Augmentation Index (Diff-AIx) according age. Results The results of CHP, Diff-AIx, systolic and diastolic blood pressure during association of ARB+MRA therapy compared to ARB+Hct, both genders, showed the lowest values with a highly statistically significant difference. The episodes of AF during 24-hours Holter monitoring in the group ARB+Hct therapy in female/male were 55%/71%; instead, in the ARB+MRA treated they were not found. Conclusions These findings suggest that the dual block with ARB+MRA therapy giving better CHP, reducing the stress to arterial-ventricular coupling, it could be helpful to prevent, the harmful effects of angiotensin-aldosterone system such as the development of heart failure and atrial fibrillation. Funding Acknowledgement Type of funding source: None

How to Choose the Optimal Single-Pill Combination of the First-Line Antihypertensive Drugs? The Benefits of Amlodipine and Telmisartan Combination

In patients with arterial hypertension (AH), an extremely important measure of the effectiveness of antihypertensive drugs (AHD) is not only a direct decrease in blood pressure (BP), but also its stable control throughout the 24 hours, preventing excessive morning surge and increased BP variability, which in turn are recognized cardiovascular risk factors. Currently, in the vast majority of hypertensive patients, the main antihypertensive therapy approach is using single-pill combinations (SPC) of AHD. Among the first-line combinations for a wide range of patients with AH and no special clinical conditions is amlodipine/telmisartan SPC. Distinctive features of these drugs, on the one hand, are unique pharmacological properties, consisting in an ultra-long antihypertensive effects, superior to other AHD in their classes; and on the other hand, there is an large body of evidence from numerous clinical trials confirming their high antihypertensive and target-organ protective potential as well as excellent capabilities in cardiovascular risk reduction. To assess the AHD effectiveness extent, several parameters have been proposed, of which the most rational and useful is the smoothness index, calculated using the ambulatory blood pressure monitoring data. Smoothness index describes both the degree of BP reduction and its distribution during the monitoring period. This index inversely associates with the changes in BP variability, and has predictive value in relation to the hypertension-mediated organ damage regression during different antihypertensive regimens. Amlodipine/telmisartan SPC has also been studied in many trials, including comparative ones with other AHD. In these works its direct powerful antihypertensive effect and a pronounced beneficial impact on the smoothness index have been proved, demonstrating stable BP control throughout the 24 hours (especially in the most dangerous morning hours), and also a decrease in BP variability. Therefore, amlodipine/telmisartan SPC can effectively reduce cardiovascular risk and improve prognosis in patients with AH.

Gender differences in left ventricular hypertrophy regression after renal denervation in patients with resistant hypertension

Purpose . To study the regression of left ventricular hypertrophy (LVH) in men and women with resistant hypertension (RH) after renal denervation (RDN). Material and Methods . A total of 84 patients (50% men) with RH were enrolled in the study after signing informed consent. Renal denervation was performed in all patients. Initially and at 6 and 12 months after treatment, patients underwent careful examination. These analyses included office blood pressure (BP) measurement, transthoracic echocardiography (TTE) study with assessments of the left ventricular (LV) wall thickness and LV mass (LVM), and cardiac magnetic resonance (CMR) imaging. Results. Groups of men and women were comparable in regard to office BP, age, number of administered antihypertensive drugs, and the number of radiofrequency energy applications for RDN. The LVM in the male group was significantly higher than in women due to anatomy differences. According to echocardiography data, the rate of LVH was insignificantly higher in women: 90% in women versus 76% in men, χ 2 = 0.079. In the presence of a significant and comparable BP reduction, significant regression in the values interventricular wall thickness (by 4.4%, р =0.039) and LVM (by 9.5%, р =0.044) was found in men one year after RND according to data of echocardiography. According to CMR according to CMR, LVM decreased by 11.9% at six months ( р =0.039) and by 22.9% at 12 months ( р =0.026) after RND. However, no significant changes in LVM were found in women. The extent of LVM regression did not depend on the antihypertensive effect of RDN in either group. Conclusion. The frequency of LVH was insignificantly higher in women than in men: 90% in women versus 76% in men. One year after RDN, LVH significantly regressed in men, but not in women, and did not depend on degree of BP reduction.

The effectiveness of a specialist Hypertension Clinic in reducing blood pressure: Factors determining blood pressure response.

ObjectivesWe retrospectively assessed both blood pressure response to management in a specialist Hypertension Clinic and the predictors of response.DesignRetrospective data audit.SettingHypertension Clinic at Guy’s and St Thomas’ Hospitals, London, UK.ParticipantsOne hundred and twenty-two sequential patients attending the clinic between January 2017 and October 2018. Patients were excluded if they had previously been seen in the clinic, failed to attend their initial appointment or did not return after their initial appointment.Outcome measureChange in blood pressure readings between first and last recorded appointments.ResultsSystolic blood pressure decreased from 149 ± 20 mmHg to 140 ± 17 mmHg, and diastolic blood pressure from 92 ± 13 to 86 ± 1 mmHg, between the first and last recorded appointments (P < 0.05 for each). Those patients who reached target blood pressure were significantly younger than those who did not (age 45 ± 14 versus 52 ± 17 years, P = 0.0171); however, the degree of blood pressure reduction was independent of age, and younger subjects had a baseline blood pressure significantly lower than older subjects. Sex, body mass index and lifestyle interventions had an important effect on blood pressure reduction; however, these were not associated with attainment of target blood pressure.ConclusionSpecialist hypertension input is effective in helping patients to achieve target blood pressure, especially so in younger as compared to older hypertensive patients, but this appears to be related to the fact that blood pressure in younger patients is already closer to target at baseline. Blood pressure reduction is greater in women, those with higher body mass index and those who receive lifestyle interventions.

Sacubitril/Valsartan Inhibits Cardiomyocyte Hypertrophy in Angiotensin II-Induced Hypertensive Mice Independent of a Blood Pressure-Lowering Effect.

BackgroundHypertensive left ventricular hypertrophy is associated with the risk of heart failure, coronary heart disease and cerebrovascular disease. Although sacubitril/valsartan (SAC/VAL), a first-in-class angiotensin receptor neprilysin inhibitor, reduces the risks of death and hospitalization for patients with heart failure, its mechanism of action is not fully understood. We hypothesized that SAC/VAL is superior to other conventional drugs in reducing cardiac hypertrophy.MethodsMale C57BL/6J mice were implanted with an osmotic pump containing angiotensin II (Ang II). After 7 days of Ang II infusion, mice were also treated with either SAC/VAL, valsartan, enalapril or vehicle alone each day for 2 weeks. Blood pressure measurement was done weekly, and echocardiography was performed before and 3 weeks after infusion of Ang II. Histological analyses were done using extracted heart to investigate cardiac hypertrophy and fibrosis.ResultsAng II markedly elevated blood pressures in all of the treatment groups, and there were no differences in the degree of blood pressure reduction among the SAC/VAL-, valsartan- and enalapril-treated groups. Echocardiography showed that SAC/VAL significantly suppressed the increase in left ventricular (LV) wall thickness and tended to decrease LV mass. In a histological analysis, SAC/VAL inhibited Ang II-induced cardiomyocyte hypertrophy, and individual cardiomyocytes in the SAC/VAL group were smaller than those in the valsartan and enalapril groups. Although previous studies using animal models of heart failure have indicated that SAC/VAL attenuates cardiac fibrosis, we found no supporting evidence in this setting.ConclusionsSAC/VAL, valsartan and enalapril all attenuated cardiomyocyte hypertrophy in a mouse model of Ang II-induced cardiac hypertrophy. Of note, SAC/VAL most strongly suppressed hypertrophy in spite of similar blood pressure-lowering effects as valsartan and enalapril. The present study suggests that SAC/VAL may have a beneficial effect on the early stage of hypertensive heart disease.

P4559Assess of angiotensin receptor blockers therapy associated to mineralocorticoid receptor antagonists or to calcium channel blockers plus hydrochlorothiazide according central haemodynamic parameters

Abstract Background Protective effect of Angiotensin-II Receptor Blockers (ARBs) on major cardiovascular events might be partly independent of the degree of blood pressure reduction. Calcium channel blockers (CCBs), lower arterial pressure by decreasing total peripheral resistance without reducing cardiac output. Hydrochlorothiazide (Hctz) is one of the most commonly prescribed antihypertensive drugs worldwide, but associated with more frequent adverse effects, such as hypokalaemia, hyponatraemia, hyperuricaemia and may increase the glycaemia, It sensitizes the endothelium to the action of angiotensin II, might act on the aldosterone release. The phenomenon of “aldosterone escape” occurs even in the presence of combination therapy with ARBs. The harmful effects of aldosterone are innumerable: induced cardiac and renal fibrosis, sodium and water retention, inflammation, oxidative stress, arrhythmias, glucose intolerance, insulin resistance, among others, that are involved in arterial and myocardium remodelling. Mineralocorticoid Receptor Antagonists (MRAs) therapy improve diastolic function, decrease plasma volume and vascular/myocardial fibrosis. Purpose This study aimed to assess the responses of two groups of therapy such as ARBs associated to MRAs or to CCBs+Hctz according to central haemodynamic parameters (CHPs) in hypertensive patients, both genders, with normal kidney function. Methods For this cross-sectional retrospective study, data were collected from 391 hypertensive patients who were assisted in the hypertension centre. Female/male 239/152, each gender divided into two groups of therapy: ARB+MRA/ARB+CCB+Hctz. Female 210/29 (average age 57/70) and male 125/27 (average age 55/61). The CHPs were measured with a SphygmoCor System PVX (AtCor-Medical Australia), a validated device employing the high-fidelity technique of applanation tonometry according to established protocols. Also, the difference of Augmentation Index (Diff-AIx) between the observed values and the expected levels was assessed according to normal range by age. No patients had cardiovascular, endocrine, renal and metabolic decompensated diseases. Results After measuring the body mass index, waist circumference and heart rate, the two therapy groups were confronted, both genders, had not found the statistically significant difference. The results of CHPs (Central Aortic Pressure, End-Systolic Pressure, Mean Arterial Pressure, Pulse Pressure, Augmentation Pressure), systolic and diastolic blood pressure during association of ARBs+MRAs therapy compared to ARBs+CCBs+Hctz, both genders, showed the lowest values with a highly statistically significant difference. In the female/male the Diff-AIx was found p=0.05/0.04. Conclusion These findings suggest that ARBs+MRAs treatment reaches the best haemodynamic conditions because improve the levels of CHPs and arterial stiffness (Diff-AIx) giving an adequate reduction of the stress to the arterial-ventricular coupling.

IMPACT OF AGGRESSIVE BLOOD PRESSURE REDUCTION ON KIDNEY FUNCTION AFTER RENAL DENERVATION

Objective: Renal denervation (RDN) seems to be safe in patients with true resistant hypertension (RHTN). However long-term effect of significant decrease of blood pressure (BP) level on renal function is lacking. We aimed to investigate renal safety of the procedure depending on the degree of BP reduction. Design and method: A total of 22 patients (age 56,1 ± 10.2 years, 9 males) with true RHTN underwent bilateral RDN procedure (Symplicity RDN System, Medtronic, USA). Office BP, ambulatory BP monitoring, applanation tonometry with the calculation of systolic and diastolic central aortic pressure (sCAP and dCAP), urine levels of NGAL, KIM-1, L-FABP, serum levels of Cystatin C (sCys) and creatinine (sCr) were obtained at baseline, 6-month, 12-month and 24-month follow-up. Renal function was analyzed using CKD-EPI sCr (GFR_CKD-EPI_sCr) and CKD-EPI sCys (GFR_CKD-EPI_sCys) equation. Results: All patients were divided into 3 groups according BP reduction: 1 – BP increase above 0 mmHg; 2 – BP reduction from 0 to −30 mmHg; 3 - BP reduction below 31 mmHg. There were an increased urine KIM-1 level associated with decreased 24-dBP at 12-month follow-up (r = −0,962, p = 0,009). An increased sCr level was registered in a group with decreased dCAP (83,4 ± 8,24; 82,00 ± 7,95; 142,00 ± 9,37; F = 23,476; p = 0,01) and 24-hour sBP (78,3 ± 3,7; 88,2 ± 6,78; 142,00 ± 8,76; F = 61,987; p = 0,004) at 6-month follow-up, also sCr level was associated with decreased 24-hour sBP at 12-month follow-up (r = −0,437, p = 0,04). An increased sCys was registered in a group with decreased sCAP (1,39 ± 0,19; 0,88 ± 0,10; 1,01 ± 0,17; F = 6,156; p = 0,01) and an increased urine L-FABP level – in a group with decreased office dBP (3531,33 ± 1795,04; 997,51 ± 1096,83; 7351,66 ± 3296,97; F = 12,103; p = 0,002) at 6-month follow up. Increased sCys level was registered in a group with decreased 24-hour sBP (0,95 ± 0,16; 0,98 ± 0,12; 1,56 ± 0,15; F = 8,476; p = 0,02) and 24-hour dBP (0,91 ± 0,13; 1,02 ± 0,10; 1,56 ± 0,45; F = 11,121; p = 0,01), decreased GFR_CKD-EPI_sCr was associated with decreased 24-hour dBP (r = 0,691, p = 0,01) at 24-month follow up. Conclusions: Renal function worsening in long-term follow-up may be due to significant decrease of BP as a result of RDN. Therefore, we can suggest the occurrence of the J-curve phenomenon in relation to the kidneys and a further increase of cardiovascular risk.

Achieving Rapid Blood Pressure Control With Digital Therapeutics: Retrospective Cohort and Machine Learning Study.

BackgroundBehavioral therapies, such as electronic counseling and self-monitoring dispensed through mobile apps, have been shown to improve blood pressure, but the results vary and long-term engagement is a challenge. Machine learning is a rapidly advancing discipline that can be used to generate predictive and responsive models for the management and treatment of chronic conditions and shows potential for meaningfully improving outcomes.ObjectiveThe objectives of this retrospective analysis were to examine the effect of a novel digital therapeutic on blood pressure in adults with hypertension and to explore the ability of machine learning to predict participant completion of the intervention.MethodsParticipants with hypertension, who engaged with the digital intervention for at least 2 weeks and had paired blood pressure values, were identified from the intervention database. Participants were required to be ≥18 years old, reside in the United States, and own a smartphone. The digital intervention offers personalized behavior therapy, including goal setting, skill building, and self-monitoring. Participants reported blood pressure values at will, and changes were calculated using averages of baseline and final values for each participant. Machine learning was used to generate a model of participants who would complete the intervention. Random forest models were trained at days 1, 3, and 7 of the intervention, and the generalizability of the models was assessed using leave-one-out cross-validation.ResultsThe primary cohort comprised 172 participants with hypertension, having paired blood pressure values, who were engaged with the intervention. Of the total, 86.1% participants were women, the mean age was 55.0 years (95% CI 53.7-56.2), baseline systolic blood pressure was 138.9 mmHg (95% CI 136.6-141.3), and diastolic was 86.2 mmHg (95% CI 84.8-87.7). Mean change was –11.5 mmHg for systolic blood pressure and –5.9 mmHg for diastolic blood pressure over a mean of 62.6 days (P<.001). Among participants with stage 2 hypertension, mean change was –17.6 mmHg for systolic blood pressure and –8.8 mmHg for diastolic blood pressure. Changes in blood pressure remained significant in a mixed-effects model accounting for the baseline systolic blood pressure, age, gender, and body mass index (P<.001). A total of 43% of the participants tracking their blood pressure at 12 weeks achieved the 2017 American College of Cardiology/American Heart Association definition of blood pressure control. The 7-day predictive model for intervention completion was trained on 427 participants, and the area under the receiver operating characteristic curve was .78.ConclusionsReductions in blood pressure were observed in adults with hypertension who used the digital therapeutic. The degree of blood pressure reduction was clinically meaningful and achieved rapidly by a majority of the studied participants. Greater improvement was observed in participants with more severe hypertension at baseline. A successful proof of concept for using machine learning to predict intervention completion was presented.

Effectiveness and Adherence to Treatment with Perindopril/Indapamide/Amlodipine Single-Pill Combination in a Greek Population with Hypertension

Despite the overwhelming evidence and the established benefits of antihypertensive treatment, adherence to treatment remains low. To assess the adherence to treatment with a perindopril/indapamide/amlodipine single-pill combination (SPC), its effectiveness on blood pressure (BP) reduction, as well as the safety and tolerability of this SPC over a 4-month treatment period. This multicenter, non-interventional study prospectively included 2285 hypertensive patients on perindopril/indapamide/amlodipine SPC. The data were recorded at baseline, 1month, and 4months. Of the 2285 hypertensive patients included in the study, 50.5% were at "high/very high risk". Mean systolic (SBP)/diastolic (DBP) decreased from 162.3 ± 13.3/93.1 ± 9.3mmHg at baseline to 129.7 ± 8.3/78.6 ± 7.1mmHg at 4months (p < 0.001). Patients with higher baseline BP levels showed greater BP reduction. Patients with hypertension stages 1, 2, and 3 showed mean SBP/DBP reductions of 21.5/10.4mmHg, 34.2/14.7mmHg, and 51.2/22.5mmHg, respectively, at study end (p < 0.001). Only 26 patients (1.1%) prematurely discontinued treatment (0.58% due to an adverse reaction or event). Perindopril/indapamide/amlodipine SPC decreased BP levels rapidly and significantly. The degree of BP reduction was associated with the severity of hypertension and/or with total cardiovascular risk at baseline. Simplifying the drug regimen by using this SPC improved adherence and showed excellent tolerability.

Prospective, randomized double blind comparative study of safety and efficacy of carvedilol versus atenolol in patients of mild to moderate hypertension

Background: Carvedilol is a new cardiovascular compound with the combined pharmacologic properties of nonselective ß-blockade and vasodilation. The Aim of the study was to compare the safety and antihypertensive efficacy of 25mg Carvedilol once daily with 50mg atenolol once daily in patients with mild to moderate essential hypertension.Methods: This was a single center study conducted in Rangaraya Medical College, Kakinada. 80 eligible patients with mild to moderate hypertension were randomized to receive 25mg Carvedilol once daily (40 patients) or 50mg atenolol (40 patients) in a double-blind 12-week treatment phase. At each visit 0, 4, 8 and 12 weeks of treatment, sitting Blood Pressure (BP) and heart rate were measured. The effect on BP reduction within the group is compared by paired “t”test and the effect on reduction of BP between two study groups compared by unpaired “t”test.Results: After 12 weeks of treatment, the mean reduction of SBP (Systolic Blood Pressure) with carvedilol is 22.33±8.31mmHg with no Significant difference (p &gt;0.05) compared to atenolol group mean reduction in SBP of 21.37±10mm Hg. The mean reduction in DBP (Diastolic Blood Pressure) after completion of the study in carvedilol group is 6.75±4.82mm Hg with no Significant difference (p &gt;0.05) compared to atenolol group mean reduction in DBP of 8.55±5.25mm Hg. No significant difference seen in the efficacy parameters of both the drugs. The incidence of adverse effects such as bradycardia, headache, nausea, vomiting, hypotension and rash is less with carvedilol.Conclusions: In patients with mild to moderate hypertension, there was no statistically significant difference between efficacy of carvedilol or atenolol with regard to the degree of reduction in BP or the percentage of patients achieving a response to therapy but carvedilol showed a better safety profile when compared to atenolol.