bluuebunny/crossref_metadata_2025 huggingface dataset:
ASSESSMENT OF ANGIOTENSIN RECEPTOR BLOCKERS THERAPY WHEN ASSOCIATED TO MINERALOCORTICOID RECEPTOR ANTAGONISTS OR TO HYDROCHLOROTHIAZIDE ACCORDING CENTRAL HAEMODYNAMIC PARAMETERS
Authors: Paterno Carlos Alberto
Published: April 2021

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.
A NOVEL PATHWAY FOR ENDOCYTOSIS OF OXIDIZED LDL VIA AN ALLOSTERIC ACTIVATION OF THE ANGIOTENSIN II TYPE 1 RECEPTOR
Authors: Huang Yibin , Yamamoto Koichi , Rakugi Hiromi
Published: April 2021

Objective:

Arrestin-dependent internalization of a G-protein-coupled receptor (GPCR) can intracellularly transport adjacent molecules. We previously proposed that a pattern recognition receptor (PRR), lectin-like oxidized LDL (oxLDL) receptor (LOX-1) physically interacts with the angiotensin II type 1 receptor (AT1) and the interaction mediates oxLDL-induced allosteric activation of AT1 and endothelial dysfunction. In this study, we analyzed direct downstream signaling pathways of AT1 by oxLDL, and investigated if the oxLDL-LOX-1 complex utilizes AT1-beta arrestin internalization to undergo endocytosis.

Design and method:

We used CHO-cells stably transfected with LOX-1 (CHO-LOX-1), AT1 (CHO-AT1), LOX-1 and AT1 (CHO-LOX-1-AT1), and LOX-1 and mutated AT1 that lacks ability to activate G protein or beta-arrestin pathway (CHO-LOX-1-mAT1). Activation of G(alpha)q and G(alpha)i were quantified by measuring the accumulation of IP1 and the inhibition of forskolin-induced cAMP production, respectively. Endocytosis of the oxLDL-LOX-1 complex through the AT1-beta-arrestin pathway was detected by an AT1-beta-arrestin BRET assay, real-time imaging of the membrane dynamics of LOX-1, and visualization of endocytosis of oxLDL. Endocytosis of oxLDL was assessed by the quantification of fluorescent intensity in cells with treatment and subsequent washout of Dil-labelled oxLDL.

Results:

Using genetically modified CHO cells, we found that oxLDL induced G(alpha)i-dependent inhibition of cAMP production only in the presence of both LOX-1 and AT1 with intact G protein binding. In contrast, oxLDL did not induce the accumulation of IP1, a downstream of G(alpha)q signaling, in CHO cells expressing both AT1 and LOX-1. The BRET signal between AT1-beta-arrestin was exerted by oxLDL only in the presence of LOX-1. Real-time imaging of cellular membrane revealed that oxLDL induced endocytosis of LOX-1 that depends on the intact beta-arrestin pathway of AT1. oxLDL accumulated in CHO cells expressing both LOX-1 and AT1 more prominently than those expressing LOX-1 or AT1 alone. This enhanced accumulation depended on the beta-arrestin-binding potency of AT1, and was abolished by dominant-negative or pharmacological inhibition of beta-arrestin. Accumulation of oxLDL was similarly attenuated by knockdown of AT1, beta-arrestin or LOX-1 in human vascular endothelial cells.

Conclusions:

oxLDL triggers selective G protein activation and beta-arrestin-dependent internalization of AT1 whereby the oxLDL-LOX-1 complex undergo endocytosis.
INFLUENCE OF ANTIHYPERTENSIVE TREATMENT ON RAAS PEPTIDES IN NEWLY DIAGNOSED HYPERTENSIVE PATIENTS
Authors: Vischer Annina , Kuster Gabriela , Twerenbold Raphael , Pfister Otmar , Zhou Qian , Villiger Andrea , Poglitsch Marko , Krähenbühl Stephan , Mayr Michael , Osswald Stefan , Haschke Manuel , Burkard Thilo
Published: April 2021

Objective:

Recently, the influence of antihypertensive treatment on the renin-angiotensin-aldosterone system (RAAS) gained increasing attention, especially since concerns were raised regarding a potential influence of RAAS inhibitors on Corona Virus Disease 2019 (COVID-19). Our objective was to study the effect of recently initiated antihypertensive drugs on Angiotensin (Ang) II (1–8) and Ang (1–7) as markers of the pro-inflammatory ACE/Ang II/Ang Type 1 receptor (AT1R) axis and the counteractive ACE2/Ang (1–7)/Mas R axis in patients with newly diagnosed hypertension.

Design and method:

Randomized, open-label trial investigating RAAS peptide profiles after initiation of antihypertensive treatment with either perindopril, olmesartan, amlodipine, or hydrochlorothiazide. Ang II and Ang (1–7) concentrations were measured at 8am and 12am at day of treatment initiation and after four weeks of treatment.

Results:

80 patients were randomized in a 1:1:1:1 fashion. Between the four substances, we found significant differences for the concentrations of Ang II (p < 0.0005 for 8 and 12am) and Ang (1–7) (p = 0.019 for 8am and <0.0005 for 12am) four weeks after treatment start. Ang II was decreased by perindopril (p = 0.002), and increased by olmesartan (p < 0.0005) and amlodipine (p = 0.012), and hydrochlorothiazide (p = 0.001) (Figure panel A). Ang (1–7) was increased by perindopril and olmesartan (p = 0.008 and 0.002), but not measurably altered by amlodipine and hydrochlorothiazide (p = 0.317 and 0.109) (Figure panel B).

Conclusions:

Initiation of antihypertensive therapy causes early and distinct alterations of equilibrium angiotensin levels. Given the additional AT1R blocking action of olmesartan, RAAS peptide shifts upon initiation of perindopril and olmesartan appear to work in favor of the anti-inflammatory axis compared to amlodipine and hydrochlorothiazide.
RESISTANT HYPERTENSION ON TREATMENT (RESHYPOT) TRIAL: SEQUENTIAL NEPHRON BLOCKADE COMPARED TO DUAL BLOCKADE OF THE RENIN- ANGIOTENSIN-ALDOSTERONE SYSTEM PLUS BISOPROLOL
Authors: Yugar-Toledo Juan Carlos , Cestari Elizabeth do Espirito Santo , Souza Maira Regina de , Rubio Tatiane de Azevedo , Mello Priscilla Galisteu de , Gonzales Elizangela Gianini , Uyemura Jéssia Rodrigues , Martin Luciana Nesves Cosenso , Tacito Lúcia Helena Buonalumi , J Heitor Moreno , Cunha Pedro , Vilela-Martin José Fernendo
Published: April 2021

Objective:

Resistant hypertension (RHTN) is a clinical entity, difficult to manage. To identify the contribution of the volume as well as the renin activity from the maintenance of blood pressure levels could individualize the treatment.

Objectives

: To demonstrate the efficacy of therapy of sequential nephron blocking (SNB) in relation to the double blockade of the renin-angiotensin system associated with beta-blockers (DBRAS) in patients with RHTN with > 85%-adherence rate after 20 weeks of treatment.

Design and method:

A prospective study was conducted, open, randomized, parallel comparison between two regimens for RHT: SNB versus DBRAS. SNB consists in a progressive increase of sodium depletion with thiazide, followed by a blockade of mineralocorticoid receptor, followed by progressive doses of loop diuretics and finally blocking sodium channels. DBRAS consists in reinforcing the effect of angiotensin receptor blocker (ARB) with an angiotensin converting enzyme inhibitors (ACEI), followed by betablockers to decrease the renin secretion. Seventy-two patients were randomized (35 to SNB 13 M/22F and 37 to RASDB 14 M/23F) coming from the tertiary outpatient clinic (HB-FAMERP). We used the criteria of the Brazilian VII Guidelines for Hypertension and V Guidelines for ABPM and HBPM. The BP was monitored with the SpaceLabs 90207.

Results:

Baseline clinical characteristics and laboratory parameters of the 72 RHTM randomized to SNB (n = 35) or DBRAS (n = 37) were similar across both study groups. At the end of the study, a significant reduction of the office pressure was observed (SBP and DBP) in both post-intervention groups (SNB group: initial SBP: 174.5 ± 21.08; final SBP: 127.0 ± 14.74; Initial DBP: 105.3 ± 15.5, final DBP: 78.11 ± 9.28 (p < 0.0001), RAASDB group: initial SBP: 178.4 ± 21.08, final SBP: 134.4 ± 23.25, initial DBP: 102.7 ± 11.07, final DBP: 77.33 ± 13.75 (p < 0.0001). No discontinuation due drug-related adverse events in both study groups.

Conclusions:

SNB and DBRAS associated with the beta-blocker in RHTN patients with full adherence to the treatment showed excellent therapeutic efficacy. However, the SNB group disclosed a greater absolute reduction of central blood pressure values.
LONG-TERM EFFICACY AND SAFETY OF SPIRONOLACTONE IN THE TREATMENT OF RESISTANT ARTERIAL HYPERTENSION
Authors: Vaclavik Jan , Jelinek Libor , Jarkovsky Jiri , Benesova Klara , Ramik Zdenek , Kamasova Monika , Kocianova Eva , Vykoupil Karel
Published: April 2021

Objective:

Spironolactone is recommended as a fourth line antihypertensive drug by current hypertension guidelines. However, data about its long-term efficacy and safety is limited.

Design and method:

We prospectively followed 274 patients with resistant arterial hypertension who started treatment with spironolactone between September 2007 and December 2016. Change of office and ambulatory blood pressure (BP) between baseline and the last clinical examination was recorded, as well as the duration of spironolactone use, its dose, changes of other antihypertensive medications, laboratory parameters and the incidence of adverse events.

Results:

Patients were followed for an average of 35 (± 29) months, the mean daily dose of spironolactone was 27.5 mg. Mean office BP decreased during follow-up from 149/87 mmHg to 136/80 mmHg by a mean 13/7 mmHg (P < 0.001 for both). Mean 24-hour, day-time and night-time ambulatory BP decreased by 12/6 mmHg, 11/6 mmHg and 14/9 mmHg respectively (P < 0.001 for all). Adverse effects occurred in 72 patients (26.3%) and in 61 (22.2%) lead to discontinuation of spironolactone. Adverse events occurred more frequently in patients using angiotensin receptor blockers (hazard ratio – HR 1.65, P = 0.040), in the elderly (HR 1.38, P = 0.007) and patients with higher baseline serum creatinine (HR 1.12, P = 0.035).

Conclusions:

Our data confirm good long-term antihypertensive efficacy of spironolactone in patients who tolerate it. However, in more than a quarter of patients the use of spironolactone leads to side effects, which usually necessitate its discontinuation.
ASSOCIATION OF HEMODYNAMIC AND NON-HEMODYNAMIC FACTORS WITH DIASTOLIC DYSFUNCTION IN PATIENTS WITH RESISTANT HYPERTENSION AND TYPE 2 DIABETES MELLITUS
Authors: Manukyan Musheg , Falkovskaya Alla , Mordovin Victor , Zyubanova Irina , Pekarski Stanislav , Lichikaki Valeriya , Ryabova Tamara , Gusakova Anna
Published: April 2021

Objective:

To identify factors associated with the development of diastolic dysfunction in diabetic patients with resistant hypertension (RHTN).

Design and method:

The study included 36 patients with RHTN and type 2 diabetes mellitus (DM) (mean age 61,4 ± 6,4 years, 14 men, mean 24-hour (24 h) blood pressure (BP) (systolic/diastolic) 158,6 ± 15,2/79,8 ± 12,7mmHg, mean HbA1c 7,2 ± 1,2%). Office BP, and 24 h ambulatory BP measurements (ABPM), renal Doppler ultrasound, tissue doppler echocardiography, lab tests (24 h urine volume, the plasma levels of metalloproteinases-9 (MMP-9)) were performed in all patients.

Results:

Average E/e‘ significantly correlated with the duration of diabetes (p = 0.005, R = 0.46), the level of daytime (p = 0.003, R = 0.48), nighttime (p = 0.007, R = 0.44 and average daily (p = 0.037, R = 0.35) pulse BP; the level of MMP- 9 (p = 0.016, R = 0.47), with renal resistive indices (RI) in the main renal arteries: right-sided R = 0.37, p = 0.034, left-sided R = 0.38, p = 0.029; in the segmental arteries - on the right R = 0.41, p = 0.020 and R = 0.35, p = 0.048 on the left. In a multiple regression analysis, average E / e ’ significantly correlated with nighttime pulse BP (b ∗ = 0.42; SE (b) = 0.041; p = 0.004), MMP -9 (b ∗ = - 0.47; SE (b) = 0.001; p = 0.002), 24 h urine volume (b ∗ = - 0.47; SE (b) = 0.001; p = 0.001). Final model R = 0.81, R2 = 0.65, adjusted R2 = 0.61, estimate standard error = 2.56, p = 0.00004. Residuals did not differ from the normal distribution (p = 0.09)

Conclusions:

Diastolic dysfunction in diabetic patients with RHTN depends from complex of hemodynamic and non-hemodynamic factors, including duration of DM, value both of pulse BP, MMP and 24 h urine volume, as well of renal resistive indexes.
HIGH RENAL RESISTANCE INDICES AND HIGH PULSE PRESSURE MAY LIMIT NEPHROPROTECTIVE EFFICACY OF RENAL DENERVATION IN PATIENTS WITH RESISTANT HYPERTENSION AND TYPE 2 DIABETES MELLITUS
Authors: Falkovskaya Alla , Mordovin V. , Pekarskiy S. , Manukyan M. , Zyubanova I. , Lichikaki V. , Ryabova T. , Baev A. , Shelemehov A. , Vtorushina A. , Moiseeva A. , Caraus A.
Published: April 2021

Objective:

The combination of diabetes mellitus (DM) and resistant hypertension (RHTN) is associated with an increased risk of development and progression of chronic kidney disease (CKD). It has been shown that renal denervation have nephroprotective efficacy by slowing the decline in renal function in some patients. The aim of the study was to identify factors limiting the nephroprotective effect of renal denervation in patients with RHTN and DM.

Design and method:

Twenty seven patients with RHTN and type 2 DM were included in single-arm prospective interventional study (protocol number NCT01499810 on ClinicalTrial.gov) (mean age 61.6 ± 7.3 years, mean office (systolic/diastolic) blood pressure (BP) 171.8 ± 21.9/87.7 ± 17.7mmHg, mean eGFR 72.1 ± 19.9 ml/min/1.73 m2, HbA1c 6.3 ± 1.1%, 7 patients (26%) with stage 3 CKD, 8 men). All patients were underwent to ambulatory 24-hour BP, renal Doppler ultrasound and assessment of eGFR (CKD-EPI formula) at baseline and 3 years follow-up. The patients were advised not to change their medication regimen during the study. Nineteen patients completed 3 years of follow-up. The renal outcomes were 1) a decrease in eGFR =  > 30% from baseline; 2) decrease in eGFR > 5 ml/min/1.73 m2/year; 3) their combination.

Results:

There was a significant decrease in mean 24-hour BP (SBP/DBP) (-14.3 ± 20.6 / -7.7 ± 10.6 mmHg, P = 0.02 /0.04). Six patients (32%) had renal outcomes at 3 years follow-up (5 pts (26%) with both outcomes, 5 patients (26%) had a decrease in eGFR = > 30% from baseline and 5 patients had a decrease in eGFR > 5 mL/min/1.73 m2/year). At baseline, patients with renal outcomes compared with patients without them had higher values of both 24-hour pulse BP (90.3 ± 7.1 vs 73.1 ± 12.5 mmHg, p = 0.007) and its variability (15.6 ± 2.6 versus 11.7 ± 3.0 mmHg, p = 0.01), as well as a higher mean value of renal resistive indices (RI) (RI in the trunk 0.79 ± 0.04 vs0.71 ± 0.06, p = 0.007; RI in segmental arteries 0.75 ± 0.08 vs 0.66 ± 0.08, p = 0.04).

Conclusions:

Our data indicate that a high value of pulse blood pressure and its variability, as well as high indices of renal resistance, can limit the nephroprotective efficacy of renal denervation, possibly due to chronic intrarenal barotrauma and irreversible changes in the kidneys.
SLEEP BLOOD PRESSURE AND SLEEP BLOOD PRESSURE SURGE IN PATIENTS WITH SLEEP DISORDERED BREATHING AND HEART FAILURE
Authors: Mizuno Hiroyuki , Hoshide Satoshi , Kario Kazuomi
Published: April 2021

Objective:

In patients with sleep disordered breathing (SDB), sleep apnea episode causes an acute transient blood pressure (BP) elevation (ie, BP surge). The SOMNO touch, a new full polysomnography device which can measure beat-to-beat BP by pulse transit time (PTT), can reveal whole of sleep BP and sleep BP surge non-invasively.

The aim of this study was to evaluate whether sleep BP and sleep BP surge in HF patients were higher or not compared with those in non-HF patients.

Design and method:

We enrolled 24 patients with SDB. Heart failure patients were defined as patients with past history of congestive heart failure. Office BP was the average of three consecutive brachial BP (Oscillometric). Full polysomnography and pulse transit time sleep BP (beat-to-beat BP) were measured by SOMNO touch.

Results:

We analyzed 13 HF patients (age 72.2 ± 14.2, BMI 24.1 ± 5.3) and 11 non-HF patients (age 66.6 ± 9.9, BMI 25.8 ± 3.4). There was no significant difference in age and BMI between the two groups. Left ventricular ejection fraction (47.8 ± 13.5 vs. 64.3 ± 13.4, p = 0.007) was significantly lower, and NT-proBNP (2971.7 (1821.0 to 4848.4) vs. 697.9 (307.5 to 1584.1), p = 0.002) was significantly higher in the HF group compared with the non-HF group. Concerning SDB, there was no significant difference in obstructive apnea index (AI) (10.2 ± 7.9 vs. 10.4 ± 5.1, p = 0.956), central AI (5.5 ± 8.7 vs. 5.6 ± 6.0, p = 0,965), apnea hypopnea index (AHI) (22.5 ± 15.9 vs. 23.2 ± 11.0, p = 0.904), and the lowest oxygen saturation (84.5 ± 6.4 vs. 84.2 ± 4.0, p = 0.874) between the two groups.

Office systolic BP (SBP) (111.0 ± 19.8 vs. 106.8 ± 13.6, p = 0.560) was similar. Concerning PTT BP, the highest sleep SBP (138.9 ± 10.2 vs. 132.5 ± 14.7, p = 0.217) and the largest increase in sleep SBP (20.6 ± 9.2 vs. 29.1 ± 15.6, p = 0.137) were similar, whereas mean sleep SBP (116.7 ± 10.0 vs. 105.3 ± 8.0, p = 0.006) and the lowest sleep SBP (104.3 ± 13.3 vs. 87.2 ± 13.7, p = 0.008) were significantly higher in the HF group compared with the non-HF group.

Conclusions:

The highest sleep SBP and the largest sleep BP surge were similar, whereas the mean sleep SBP and the minimum sleep SBP were significantly higher in the HF group compared with those in the non-HF group.
A HYPERTENSIVE RESPONSE TO EXERCISE IS ASSOCIATED WITH ALTERED CARDIAC STRUCTURE: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Moore Myles , Climie Rachel , Otahal Petr , Sharman James , Schultz Martin
Published: April 2021

Objective:

A hypertensive response to exercise (HRE) is a risk factor for cardiovascular disease and may reveal high blood pressure (BP) not detected by standard assessment at rest. Structural cardiac disease may underlie the association between HRE and cardiovascular risk, although this has not been fully elucidated. This study aimed to assess the relationship between HRE and cardiac structure via systematic review and meta-analysis of previously published literature.

Design and method:

Three online databases were searched from inception to July 2019 for studies that included associations between exercise BP and cardiac structural variables including left ventricular mass index (LVMI), relative wall thickness (RWT) and left atrial (LA) diameter. Pooled correlations between exercise BP and cardiac variables were calculated using random effects. Pooled mean differences (random effects) in LVMI, RWT and LA size between individuals with and without HRE were also calculated. Univariable meta-regressions were performed to assess differences in pooled mean differences by resting hypertension status, health status, exercise intensity at the time BP was measured and exercise modality.

Results:

A total of 47 studies with 23,090 participants (aged 44 ± 4 years; 62% male) were included. Exercise systolic BP had a moderate association with LVMI (22 studies, pooled r = 0.4, p < 0.001) and RWT (3 studies, r = 0.4, p < 0.001). On average, those with HRE had higher LVMI (24 studies, pooled mean difference 9.34 ± 1.7 g/m2; p < 0.001), RWT (13 studies, 0.02 ± 0.004, p < 0.001) and LA diameter (10 studies, 1.97 ± 0.49 mm, p < 0.001) compared to those without HRE. Meta-regression for pooled mean difference in LVMI indicated results were similar irrespective of resting hypertension status, health status and exercise intensity at BP measurement, but was greater among studies using treadmill testing (n = 18) compared to cycling (n = 6, p = 0.003). Meta-regression for pooled mean difference in RWT were similar irrespective of resting hypertension status, health status and test modality, but were greater during submaximal compared to peak intensity exercise (p = 0.02).

Conclusions:

HRE is associated with altered cardiac structure, including increased LVMI, RWT and LA diameter. Whilst associations varied across exercise intensity and testing modality, these results highlight potential mechanisms underlying cardiovascular risk associated with HRE.
HIGHER PREVALENCE OF EXAGGERATED EXERCISE BLOOD PRESSURE IN PEOPLE WITH TYPE 2 DIABETES CAN BE EXPLAINED BY CARDIOVASCULAR RISK FACTORS: THE EXERCISE STRESS TEST COLLABORATION (EXERTION)
Authors: Schultz Martin , Kovacevic Ann-Marie , Otahal Petr , Roberts-Thomson Philip , Stanton Tony , Wahi Sudhir , La Gerche Andre , Hare James , Selvanayagam Joseph , Maiorana Andrew , Venn Alison , Sharman James
Published: April 2021

Objective:

Exaggerated exercise blood pressure (EEBP) during clinical exercise testing is associated with elevated cardiovascular disease (CVD) risk. Type-2 diabetes (T2DM) is thought to be associated with higher prevalence of EEBP, but this has never been determined in a large clinical population, which was the aim of this study.

Design and method:

Clinical exercise test records were analysed from 15,994 people (mean age 53 ± 13 years, 59% male) referred for the Bruce treadmill protocol (stages 1–4 + peak) at 4 Australian public hospitals. Exercise records including blood pressure (BP) were linked to administrative datasets (hospital and emergency admissions) to define clinical characteristics and classify prior history of T2DM (n = 1,345) vs. no-T2DM (n = 14,649). EEBP was defined > 90th centile for each exercise stage. Exercise BP was regressed on T2DM history, adjusted to consider CVD risk factors.

Results:

EEBP prevalence (stage-1: + 4.1%; stage-2: + 4.4%; stage-3: + 4.9%; stage-4: + 4.8%; peak: + 1.9%, P < 0.05 respectively) and exercise systolic BP (stage-1: + 4.25, stage-2: + 4.52, stage-3: + 4.43, stage-4: + 3.08, peak: + 0.75 mmHg, P < 0.05 respectively) were higher across all exercise stages in T2DM vs. no-T2DM. However, all differences were abolished by adjustment for either: age, sex, peak workload, CVD history, or pre-exercise BP. Restricting analyses to those with normal pre-exercise BP (<140/90 or < 130/90 mmHg) revealed no differences in exercise BP or EEBP prevalence between T2DM and no-T2DM.

Conclusions:

This is the first study to confirm higher prevalence of EEBP in T2DM, but this is explained by accompanying CVD risk factors. Identification of EEBP should prompt aggressive CVD risk factor modification in T2DM.
HOW TO MAXIMIZE POST-EXERCISE HYPOTENSION? IS A BOUT OF HIGH INTENSITY EXERCISE BETTER THAN A BOUT OF MODERATE CONTINUOUS EXERCISE?
Authors: Marçal Isabela Roque , Goessler Karla F. , Buys Roselin , Casonatto Juliano , Ciolac Emmanuel G. , Cornelissen Véronique A.
Published: April 2021

Objective:

Post-exercise hypotension (PEH) is an important tool in the daily management of patients with hypertension. Varying the exercise parameters is likely to change the blood pressure (BP) response following a bout of exercise. In recent years, high-intensity interval exercise (HIIE) has gained significant popularity in exercise-based prevention and rehabilitation of clinical populations. Yet, to date, it is not known whether a single session of HIIE maximizes PEH more than a bout of moderate-intensity continuous exercise (MICE). We aimed to compare the effect of HIIE vs. MICE on PEH by means of a systematic review and meta-analysis.

Design and method:

A systematic search in the electronic databases MEDLINE, Embase, and SPORTDiscus was conducted from the earliest date available until February 24, 2020. Randomized clinical trials comparing the transient effect of a single bout of HIIE to MICE on office and/or ambulatory BP in humans (> 18 years) were included. Data were pooled using random-effects models with summary data reported as weighted means and 95% confidence interval (CIs).

Results:

Data from 14 trials were included, involving 18 comparisons between HIIE and MICE and 276 (193 males) participants. The immediate effects, measured as office BP at 30- and 60-minutes post-exercise, were similar for a bout of HIIE and MICE (p > 0.05 for systolic and diastolic BP). However, HIIE elicited a more pronounced BP reduction than MICE [(-5.3 mmHg (-7.3 to -3.3)/ -1.63 mmHg (-3.00 to -0.26)] during the subsequent hours of ambulatory daytime monitoring. No differences were observed for ambulatory nighttime BP (p > 0.05).

Conclusions:

HIIE promoted a larger PEH than MICE on ambulatory daytime BP. However, the number of studies was small, patients were mostly young to middle-aged individuals and only a few studies included patients with hypertension. Therefore, there is a need for studies that involve older individuals with hypertension and use ambulatory BP monitoring to confirm HIIE's superiority as a safe BP lowering intervention in today's clinical practice.
EFFECTS OF FIXED DOSE COMBINATION AZILSARTAN MEDOXOMIL/CHLORTALIDONE ON THE CENTRAL BP IN HYPERTENSIVE PATIENTS WITH HFPEF
Authors: Gudieva Khyadi , Medovschikov Vadim , Eshniyazov Nurlan , Kravchenko Alina , Safarova Ayten , Kobalava Zhanna
Published: April 2021

Objective:

We aimed to study the effects of a fixed AZL-M/CLD combination on central BP in patients with AH and HFpEF.

Design and method:

This 12-week study evaluated effects of a fixed-dose combination AZL-M/CLD (n = 30) vs non-fixed-dose combinations of iACE/ARB and thiazide/ thiazide-like diuretics (n = 30) on central BP (cBP), arterial stiffness and pulse wave velocity (PWV) in patients with AH and HFpEF. Patients with EF < 50%, significant valvular disease, ACS, permanent AF, neoplasm, eGFR < 30 ml/min/1.73 m2, BMI > 40 kg/m2 were not included. The initial doses could be titrated to meet BP targets during weeks 4 to 12: in 1 group to 40/25 mg, in the control group up to the maximum daily dose.

Results:

The mean age in the study group was 67 ± 11 years (M ± SD), 36% (10 /30) males, SBP/DBP 140 ± 12/84 ± 9 mmHg (M ± SD), DM 30% (9/30), obesity 61,2% (18/30), paroxysmal AF 20% (6/30), CKD 57% (16/30), eGFR 63 [44.1;72.8]. In the control group: 66 ± 10 years (M ± SD), 40% (12 /30) males, SBP/DBP was 141 ± 11/82 ± 10 mmHg (M ± SD), DM 30% (9/30), obesity 55 % (16/30), paroxysmal AF 26% (7/30), CKD 61% (18/30), eGFR 65 [46.3;76.1]. During observation, the level of pBP in the study group decreased from 140 ± 12/84 ± 9 mmHg to 120 ± 15/71 ± 12 mmHg (p < 0.05); cBP from 131 ± 15/84 ± 10 to 117 ± 14/78 ± 9 mmHg (p < 0.05) and PWV from 11.7 (9.4;13.4) to 10.1 (8.7;12.3) m/s (p < 0.05). The levels of pBP in the control group decreased from 141 ± 11/82 ± 11 mmHg to 128 ± 16/79 ± 9 mmHg (p < 0.05), cBP from 132 ± 14/85 ± 9 to 127 ± 16/82 ± 13 mmHg (p < 0.05), PWV from 11.5 (9.5; 13.6) to 10.2 (9.2.;12.8) m/s p < 0.05. The t-test indicated significant differences between this two groups in peripheral BP, cBP and PWV (p = 0.004, p < 0.01, p < 0,05 respectively).

Conclusions:

There is significant antihypertensive effect and reduction of arterial stiffness in patients with AH and HFpEF treated with AZL-M/CLD.
HYPERTENSION CONTROL IN RUSSIAN RESIDENTS WITH MULTICOMPONENT ANTIHYPERTENSIVE THERAPY
Authors: Tolkunova Kristina , Rotar Oxana , Alieva Asiyat , Boiarinova Maria , Erina Anastasia , Solntsev Vladislav , Konradi Aleksandra
Published: April 2021

Objective:

To assess the hypertension control depending on the number of antihypertensive drugs in Russian sampling in terms of MMM19 screening.

Design and method:

An opportunistic cross-sectional survey of volunteers the age of 18 from 21 Russian Regions (n = 5274) was performed in terms of international campaign MMM19. 1,834 of the residents were men (34.8%). 49.2% of the respondents were younger than 25 years, therefore, considering significant differences in age, further analysis of the data was performed among participants over 25 years (n = 2681). The questionnaire was being completed on presence of diabetes mellitus, history of cardiovascular complications, smoking and drinking. Information regarding intake and omission of antihypertensive medication were clarified. Blood pressure (BP) was measured three times with automated and manual sphygmomanometers.

Results:

Average age of the participants was 49.3 ± 16.2 years (17–96 years old). 51.5% of the participants had history of hypertension (n = 1343), while 73.6% (n = 989) received antihypertensive therapy. 44.8% of patients (n = 444) achieved target BP of less than 140/90 mm Hg, and only 20.5% (n = 203) - less than 130/80 mm Hg. The percentage of achieving the target BP depending on medication number is illustrated in Figure 1.

Conclusions:

In Russian screening sample older 25 years the level of hypertension control remains low, especially when the criteria of target blood pressure is tightened. Half of patients achieved blood pressure level of less than 140/90 mm Hg and only one fifth of the participants achieved blood pressure level of less than 130/80 mm Hg. Despite multicomponent therapy, only 20–30% of patients in this category achieved target blood pressure level even they were less likely to miss medication.
IMPLEMENTATION OF URINARY DRUG DETECTION FOR ASSESSMENT OF ADHERENCE TO ANTIHYPERTENSIVE DRUGS IN DAY-TO-DAY CARE IN A TERTIARY HYPERTENSION CLINIC IN PARIS AREA
Authors: Kably Benjamin , Billaud Eliane M , Belmihoub Ines , Madjalian Anne-Marie , Lorthioir Aurélien , Amar Laurence , Boutouyrie Pierre , Azizi Michel
Published: April 2021

Objective:

Non-adherence to antihypertensive drug (AHD) therapy is a major health challenge contributing to uncontrolled/resistant hypertension and major adverse cardiovascular events. We report here the results of implementation of AHD screening in spot urine samples in day-to-day care of patients with severe resistant hypertension (RHTN) in a tertiary hypertension clinic of Paris area.

Design and method:

Urine AHD screening was performed using ultrahigh performance LC-MS/MS in patients with apparent RHTN (office BP>140/90 mmHg despite 3 AHD including a diuretic) when poor adherence was clinically suspected. Full adherence (FA) was defined as the presence of all prescribed AHD, and partial adherence (PA) or complete nonadherence (NA) as the absence of at least one or all prescribed AHD, respectively.

Results:

We included 119 patients with RHTN (53.8% men), aged 54.9 years, with office SBP/DBP of 168/96 mmHg despite prescription of a median of 4.0 AHD. There were 58 (48.7%) FA patients, 41 (34.5%) PA patients, and 20 (16.8%) NA patients. In decreasing order of prescription, we detected ARB/ACEI in 60.4% of the patients (n = 58/96), CCB in 55.4% (n = 46/80), thiazides in 50.0% (n = 40/80), alpha-blockers in 66.7% (n = 34/51), beta-blockers in 72.9% (n = 35/48), spironolactone in 51.1% (n = 23/45), centrally acting AHD in 78.0% (32/41), furosemide in 76.2% (16/21) and amiloride in 81.8% of the patients (n = 9/11). Poor adherence (PA+NA, n = 61) was associated with younger age (53 vs. 58 yrs, p = 0.09), female sex (54% vs. 38%, p = 0.08), higher SBP/DBP (174/102 vs. 162/90mmHg, p = 0.001/0.02), higher eGFR (79 vs. 66 ml/min, p = 0.02), more AHD (5 vs. 4, p < 0.001) but not to less single pill combination prescription (66% vs. 57%, ns) compared to full adherence.

Conclusions:

Urine AHD screening allows to detect that < 50% of the patient with RHTN are FA and 16.8% are completely NA. The AHD recommended by the ESH guidelines for RHTN (ACEI/ARB, thiazides, CCB and spironolactone) were only detected in 50 to 60% of the patients which explains the persistence of uncontrolled severe hypertension. However, in FA patients, BP remained high suggesting inadequate use of AHD by physicians or white coat adherence by patients.
FACTORS AFFECTING ADHERENCE TO MEDICAL APPOINTMENT AMONG HYPERTENSIVE PATIENTS OF PUBLIC HEALTH FACILITIES IN PUNJAB, INDIA
Authors: Das Bidisha , Neupane Dinesh , Kunwar Abhishek , Kaur Prabhdeep , Mukhtar Qaiser
Published: April 2021

Objective:

Objective: Regular visit to health facilities is important for hypertension control. Under India Hypertension Control Initiative, hypertensive patients are enrolled in public hospitals and provided with patient-specific monthly medication for regular treatment at home and advised to return to the health facility after a month. However, at least 50% -60% of registered patients were not visiting the health facility for 3 to 6 months following their last visits. This article aims to document the major reasons for missed appointments and to characterize the patient and health system barriers.

Design and method:

We used a telephonic interview for collecting information from the patients who missed the appointments for more than 3 consecutive months. Out of 300 randomly selected patients, 206 were interviewed with a pre-structured questionnaire to explore patients’ experiences along with medical record reviews from the patient database. Interviews were conducted during the last quarter of 2019 and analyzed in both descriptive statistics and textual descriptions.

Results:

Not feeling sick or not experiencing any bodily symptoms due to hypertension (18.4%) followed by far distance between the health facility and the patient's home (16.5%) were the major reasons reported by the patients. Among other reasons, lack of proper instructions/guidance from the facility (11%), acute health conditions of patients (6%) and long waiting time at the public health facilities (5%) are also documented as the reasons for poor follow up. These factors cumulatively shifting a patient towards private sectors as 54% patients who were continuing their treatment are preferring private sectors.

Conclusions:

The results suggest the need for a more patient-centric care model such as guiding the patient properly at the health facility, saving patients time in the clinic, personalized care for acutely ill and aged patient and addressing the distance barriers between a patient's home and the health facility. Further, introducing reminder system by means of phone calls/SMS/visit may help to retain the higher follow-up of the patient.
STATIN THERAPY IS ASSOCIATED WITH BETTER 24-HOUR AND NIGHT-TIME BLOOD PRESSURE CONTROL IN HYPERTENSIVE PATIENTS
Authors: Spannella Francesco , Filipponi Andrea , Giulietti Federico , di Pentima Chiara , Sarzani Riccardo
Published: April 2021

Objective:

Hypertension and dyslipidemia often coexist. Statin therapy was associated with lower blood pressure (BP) in some but not all studies. Aim: to evaluate the association between statin therapy and 24-hour BP in a large hypertensive population, using propensity score matching analysis.

Design and method:

Retrospective study on 1827 consecutive essential hypertensives evaluated with 24 h ambulatory BP monitoring. Anti-hypertensive treatment intensity (ATI) was calculated to compare different drug associations. We used a propensity score matching to compare two equally-sized cohorts of patients (369 patients in each group) with similar characteristics according to statin therapy (age, sex, body mass index, smoking habit, diabetes mellitus, total cholesterol, high-density lipoprotein cholesterol, triglycerides, low-density lipoprotein cholesterol, estimated glomerular filtration rate, glycaemia, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, calcium channel blocker, diuretic, mineralocorticoid receptor antagonist, beta-blocker, alfa-blocker, ATI, 24 h pulse pressure). Matching was performed on log-transformed propensity score in a 1:1 fashion with a caliper of 0.1, in order to account for the different baseline characteristics between statins and non-statins groups.

Results:

Mean age: 58.1 ± 13.8 years; male sex: 55%. Patients on statin therapy: 402 (22%). The different statins were taken as follows: atorvastatin (39.8%), simvastatin (35.8%), rosuvastatin (15.7%), pravastatin (5.6%), lovastatin (2.3%) and fluvastatin (0.8%). Patients on statins showed lower 24 h BP (-2.8/-7.1 mmHg), daytime (-3.3/-7.6 mmHg) and night-time BP (-2.5/-6.0 mmHg, all p < 0.001). They also showed better ambulatory BP control, even after adjustment for confounders. The analyses on the groups derived from the propensity score matching (369 patients in each group) confirmed these results (OR 1.8 for 24 h BP control; OR = 1.6 for daytime BP control; OR = 1.7 for night-time BP control, all p < 0.001).

Conclusions:

Conclusions: Statin therapy is associated with lower ABPM values in hypertensive patients. This result is not affected by the anti-hypertensive treatment intensity or by the several cofactors analyzed, but may depend on greater adherence to prescribed drug therapies as suggested by the assumption of a nocebo-tainted drug class. The cardiovascular benefit of statins is due to the reduction of blood cholesterol and effects on blood pressure may be just indirect.
ADDITIVE BLOOD-PRESSURE LOWERING EFFECT OF AEROBIC TRAINING ON ANTIHYPERTENSIVE MEDICATION IN METABOLIC SYNDROME INDIVIDUALS
Authors: Jimenez Miguel Ramirez , Morales-Palomo Felix , Moreno-Cabañas Alfonso , Alvarez-Jimenez Laura , Ortega Juan F. , Mora-Rodriguez Ricardo
Published: April 2021

Objective:

In hypertensive individuals with metabolic syndrome (MetS), antihypertensive medications (AHM) are prescribed in conjunction with lifestyle advice (i.e., exercise) to reduce blood pressure (BP). However, if the combination of both treatments results in better BP control remains unknown. The objective of this study was to analyze the separated and combined effects of AHM and exercise training on ambulatory blood pressure (ABP).

Design and method:

Thirty-six hypertensive individuals with MetS under long-term prescription with AHM targeting the renin-angiotensin-aldosterone system (RAAS) were recruited. Before and after a 4-month aerobic interval training their AHM prescription was withdrawn during 3 days (i.e., PLAC trials) and 24-h ABP compared to when individuals held their habitual dose of medication (i.e., AHM trial) using a double-blind, randomized design. Plasma renin activity (PRA) and aldosterone concentration were measured to confirm withdrawal effects on RAAS. Urine albumin and creatinine ratio (UACR) was measured to assess kidney function.

Results:

Before the intervention AHM reduced 24-h mean arterial pressure (MAP) by -5 ± 5 mmHg (P < 0.001, Figure 1). After 4-months of aerobic training AHM reduced MAP an additional -3 ± 5 mmHg (92 ± 9 to 89 ± 8 mmHg; P = 0.014). However, BP lowering effect was not observed when AHM was withdrawn after training (97 ± 8 vs 96 ± 8 mmHg; P = 507). AHM increased PRA before and after training (P < 0.005) whilst had no effect on plasma aldosterone concentration (P = 1.000). Aerobic training did not significantly reduced RAAS hormones or the UACR.

Conclusions:

Aerobic training and AHM in conjunction reduce BP to a higher extent than each treatment in isolation. These findings support the combination of habitual AHM with exercise training with the goal to reduce BP in hypertensive MetS individuals.
SODIUM HYDROGEN SULFIDE IMPROVES RENOVASCULAR HYPERTENSION-INDUCED MALADAPTIVE CARDIAC REMODELING AND DIASTOLIC DYSFUNCTION BY REDUCING OXIDATIVE STRESS AND MMP ACTIVITY
Authors: Pernomian Laena , de Mello Marcela Blascke , de Castro Michele Mazzaron
Published: April 2021

Objective:

To evaluate whether treatment with sodium hydrogen sulfide (NaHS) improves cardiac function and remodeling of two kidney-one clip (2K-1C) rats through inhibition of matrix metalloproteinase (MMP) activity and oxidative stress.

Design and method:

2K-1C hypertension was surgically induced in male Wistar rats (200 g; ethics commitee #118/2019) by an implantation of a silver clip (0.2 mm) in the left renal artery. Control rats (2K) was submitted to laparotomy. SBP and echocardiograph were registered. The NaHS (0.24 mg/Kg/day; i.p.) treatment or vehicle (0.6% DMSO in saline; i.p.) was initiated in the second week after the surgeries and lasted for 28 days. Hearts were collected and western blotting to MMP-2, Nox2 and Nox4 were performed in the left ventricles. MMPs localization and activity were also evaluated by in situ zymography. Reactive oxygen species (ROS) were investigated by dihydroethidium (10 μM). Data are presented as mean ± S.E.M. of different experimental n. Two-way ANOVA with Bonferroni correction was used (P < 0.05).

Results:

SBP values of 2K-1C (165.47 ± 3.98mmHg, n = 12) were increased compared to 2K rats (133.28 ± 2.48mmHg, n = 10; P < 0.0001) in the first week after the surgery. NaHS treatment decreased SBP of 2K-1C NaHS (155.60 ± 5.72mmHg, n = 5) compared to 2K-1C vehicle (202.13 ± 5.57mmHg, n = 7; P = 0.0003). Isovolumetric relaxation time analysis showed increases in values from 2K-1C rats (40.31 ± 2.97ms, n = 7) and NaHS treatment (28.04 ± 1.05ms, n = 5) normalized this parameter (P = 0.0018). 2K-1C rats (2.30 ± 0.11 mm, n = 7) presented increased interventricular septum thickness and NaHS treatment (1.99 ± 0.0 mm, n = 5) reduced this parameter (P = 0.028). MMP-2, Nox2 or Nox4 expression was not different in all groups. The gelatinolytic activity of MMPs was higher in 2K-1C vehicle rats (18,029.31 ± 1,225.42U, n = 3) and NaHS (12,092.70 ± 868.22U, n = 3) reduced it (P = 0.021). In 2K-1C rats (33,868.95 ± 2,103.74U, n = 3), ROS were higher compared to control and NaHS treatment (22,019.50 ± 914.08 U, n = 3) decreased this value (P = 0.0021).

Conclusions:

Our results showed beneficial effects of NaHS treatment in 2K-1C rats, thus leading to SBP decrease, cardiac function improvement and reduction in both MMPs activity and oxidative stress.
ARTERIAL STIFFNESS PARAMETERS AS INDICATORS OF CORONARY ARTERY DISEASE IN YOUNG PATIENTS
Authors: Oleynikov Valentin , Khromova Angelina , Salyamova Lyudmila
Published: April 2021

Objective:

To assess the state of the arterial bed in patients with CAD with varying degrees of coronary artery injuries (CA) and healthy peers.

Design and method:

The study included 92 patients with CAD (mean age 41.3 ± 8.2 years). Inclusion criteria: CAD verified by coronary angiography (CAG), ECG and/or biomarkers, hospitalization for unstable angina. After CAG, the patients were divided into 3 groups: the first - 30 people without hemodynamically significant stenoses (HSS1 < 50%) of CA, the second - 37 patients with HSS of 1 CA (HSS1 > 50%), the third group - 35 patients with HSS 2 or more CA (HSS2 > 50%). The control (C) group consisted of 28 healthy individuals. Regional arterial stiffness was assessed by volume sphygmography (Fukuda Denshi, Japan): R/L–PWV - PWV in elastic arteries, L-/CAVI-1 - cardio-ankle vascular index. Applanation tonometry (AtCorMedical, Australia) was used to record carotid-femoral PWV (cfPWV) and indicators of central aortic pressure: systolic (SBPao), pulse (PPao).

Results:

The lowest R/L-PWV values were in control - 10.1 ± 1.9 m/s; in patients with CAD, an increase in R/L-PWV was revealed in the HSS1 < 50% group - 11.9 ± 1.5 m/s and in the group HSS1 > 50% - 13.9 ± 0.9 m/s. The highest values were found in the group HSS2 > 50% - 13.9 (9.6;14.7) m/s (p < 0.05). The L-/CAVI-1 index in control was 6.4 (5.6;7.3), in group 1 - 7.2 (6.2;8.4), in group 2 - 8.3 (6.7;9.4) in group 3 - 9.5 (7.1;10.4) (p < 0.05). According to the applanation tonometry, in healthy people HSS1 < 50%, HSS1 > 50%, and HSS2 > 50%, a comparable level of central BP was recorded: SBPao - 100.9 ± 8.1mmHg, 100.5 ± 9.7mmHg, 100.3 ± 8.4mmHg 101.3 ± 7.7mmHg, PPao - 26.8 ± 6.1mmHg, 27.0 ± 5.9mmHg, 29.0 ± 5.3mmHg, 28.7 ± 6.4mmHg, respectively (p > 0.05), which is probably due to the examination in pharmacotherapy. The smallest cfPWV values were recorded in control - 6.5 ± 0.9 m/s compared with group 1 - 7.4 (6.2;8.7) m/s, in the group 2 - 8.5 ± 1.1 m/s, group 3 - 9.6 ± 1.4 m/s (p < 0.05).

Conclusions:

In patients with CAD, a significant violation of the vascular stiffness parameters was diagnosed, more pronounced in people with stenosis of two or more CA. The study results confirm that the CAD in young adult is a clinical manifestation of the widespread process of early vascular aging.