scholarly journals Effect of esaxerenone on nocturnal blood pressure and natriuretic peptide in different dipping phenotypes

Author(s):  
Kazuomi Kario ◽  
Sadayoshi Ito ◽  
Hiroshi Itoh ◽  
Hiromi Rakugi ◽  
Yasuyuki Okuda ◽  
...  

AbstractThere are limited data on the nighttime blood pressure (BP)-lowering effect of esaxerenone and its effect on N-terminal pro b-type natriuretic peptide (NT-proBNP), a predictor of cardiovascular risk, according to different dipping patterns of nocturnal BP. This was a post hoc analysis of a multicenter, open-label, long-term phase 3 study of esaxerenone, a new highly selective mineralocorticoid receptor blocker, in patients with essential hypertension. Patients were classified by dipping pattern (extreme dippers, dippers, non-dippers, risers). Mean changes in BP, changes in dipping pattern, mean NT-proBNP levels, and percentage of patients with normal NT-proBNP levels (<55 pg/mL) at baseline and Weeks 12 and 28 were evaluated. Nighttime systolic BP decreased in all dipping pattern groups at Week 28, with the riser group showing the greatest change (−25.5 mmHg). A significant shift in dipping pattern and riser/non-dipper pattern changes to dipper/extreme dipper pattern were found from baseline to Week 28 (p < 0.0001). The prevalence of the riser pattern decreased from 14.4% to 9.8%, and that of the non-dipper pattern from 44.7% to 39.2%. The decrease in NT-proBNP from baseline to Week 28 was statistically significant in risers, non-dippers, dippers, and extreme dippers (p < 0.001, respectively). At baseline, the proportion of patients with NT-proBNP <55 pg/mL was lowest in risers versus the other dipping pattern types, but after reductions in NT-proBNP in all groups to Week 28, these differences disappeared. Long-term administration of esaxerenone may be a useful treatment option for nocturnal hypertension, especially in patients with a riser pattern.

Author(s):  
Xiaoyong Xu ◽  
Xianghong Meng ◽  
Shin-ichi Oka

Abstract Objective Our work aimed to investigate the association between vigorous physical activity and visit-to-visit systolic blood pressure variability (BPV). Methods We conducted a post hoc analysis of SPRINT (Systolic Blood Pressure Intervention Trial), a well-characterized cohort of participants randomized to intensive (&lt;120 mmHg) or standard (&lt;140 mmHg) SBP targets. We assessed whether patients with hypertension who habitually engage in vigorous physical activity would have lower visit-to-visit systolic BPV compared with those who do not engage in vigorous physical activity. Visit-to-visit systolic BPV was calculated by standard deviation (SD), average real variability (ARV), and standard deviation independent of the mean (SDIM) using measurements taken during the 1-, 2-, 3-, 6-, 9- and 12-month study visits. A medical history questionnaire assessed vigorous physical activity, which was divided into three categories according to the frequency of vigorous physical activity. Results A total of 7571 participants were eligible for analysis (34.8% female, mean age 67.9±9.3 years). During a follow-up of 1-year, vigorous physical activity could significantly reduce SD, ARV, and SDIM across increasing frequency of vigorous physical activity. There were negative linear trends between frequency of vigorous physical activity and visit-to-visit systolic BPV. Conclusions Long-term engagement in vigorous physical activity was associated with lower visit-to-visit systolic BPV.


2002 ◽  
Vol 30 (6) ◽  
pp. 543-552 ◽  
Author(s):  
J Amerena ◽  
S Pappas ◽  
J-P Ouellet ◽  
L Williams ◽  
D O'Shaughnessy

In this multicentre, prospective, randomized, open-label, blinded-endpoint (PROBE) study, the efficacy of 12 weeks' treatment with once-daily telmisartan 40–80 mg and enalapril 10–20 mg was evaluated using ambulatory blood pressure monitoring (ABPM) in 522 patients with mild-to-moderate essential hypertension. Patients were titrated to the higher dose of study drug at week 6 if mean seated diastolic blood pressure (DBP) was ≥ 90 mmHg. The primary endpoint was the change from baseline in ambulatory DBP in the last 6 h of the 24-h dosing interval after 12 weeks' treatment. Telmisartan and enalapril produced similar reductions from baseline in DBP and systolic blood pressure (SBP) over all ABPM periods evaluated (last 6 h, 24-h, daytime and night-time). Telmisartan produced a significantly greater reduction in mean seated trough DBP, measured unblinded with an automated ABPM device in the clinic, amounting to a difference of −2.02 mmHg ( P < 0.01). A significantly greater proportion of patients achieved a seated diastolic response with telmisartan than enalapril (59% versus 50%; P < 0.05), also measured with the same ABPM device. Both treatments were well tolerated. Compared with telmisartan, enalapril was associated with a higher incidence of cough (8.9% versus 0.8%) and hypotension (3.9% versus 1.1%). Therefore, telmisartan may provide better long-term compliance and, consequently, better blood pressure control than enalapril.


1999 ◽  
Vol 87 (6) ◽  
pp. 2025-2031 ◽  
Author(s):  
Holger Kraiczi ◽  
Jarkko Magga ◽  
Xiang Ying Sun ◽  
Heikki Ruskoaho ◽  
Xiaohe Zhao ◽  
...  

We investigated whether the effect of long-term intermittent hypoxia (LTIH) on cardiovascular function may be modified by preexisting genetic traits. To induce LTIH experimentally, cycles of 90-s hypoxia (nadir 6%) followed by 90-s normoxia were applied to six Wistar-Kyoto and six spontaneously hypertensive rats during 8 h daily. Comparison with the same number of control animals after 70 days revealed no alteration of intra-arterial blood pressure or heart rate. Blood pressure responsiveness to a brief hypoxic stimulus was enhanced in the LTIH animals, regardless of strain, whereas the hypoxia-induced increase in heart rate was abolished. In the spontaneously hypertensive but not the Wistar-Kyoto rats, LTIH increased left ventricular weight-to-body weight ratio and content of atrial natriuretic peptide mRNA. Expression of B-type natriuretic peptide was unchanged (Northern blot). Slightly increased right ventricular weight-to-body weight ratios in the LTIH animals were associated with higher right ventricular atrial natriuretic peptide and B-type natriuretic peptide mRNA amounts. Consequently, the effects of LTIH on different components of cardiovascular function appear incompletely related to each other and differentially influenced by constitutional traits.


2009 ◽  
Vol 3 (3) ◽  
pp. 97
Author(s):  
Yang Qian ◽  
Jiang Xiongjing ◽  
Zhang Yuqing ◽  
Liu Lisheng

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Arshed Quyyumi ◽  
Susan Zieman ◽  
Emil Kakkis ◽  
John Hopkins ◽  
Martha Nicholson

BACKGROUND: Tetrahydrobiopterin (6R-BH4) is a cofactor for nitric oxide (NO) synthesis. Reduced BH4 bioavailability uncouples NO synthase, decreases NO production, increases superoxide production, and may contribute to hypertension. 6R-BH4 administration has been shown to lower blood pressure (BP) and improve endothelial function in animal models and in two small, open-label clinical studies. A randomized, placebo-controlled, multicenter, parallel study was designed (‘CONTROL’) to evaluate the antihypertensive effects of 6R-BH4 in patients with treated, but poorly controlled, hypertension. METHODS: A total of 116 subjects with hypertension (SBP/DBP> 135/85) despite a stable regimen of at least two antihypertensive drugs were randomized 2:1 to oral 6R-BH4 (n=77) or placebo (n=39) and stratified by presence or absence of type 2 diabetes. Subjects received a daily dose of 10 mg/kg 6R-BH4 for 8 weeks. Endpoints were change from baseline in SBP and DBP over 8 weeks of treatment. Other measures of efficacy included change in insulin sensitivity, proteinuria, and biochemical markers of oxidative stress and NO production. RESULTS: 6R-BH4-treated subjects had a 4.4-mm Hg drop in SBP (baseline mean, 145 mm Hg) compared with a 6.4-mm Hg drop in placebo-treated subjects (baseline mean, 143 mm Hg; p=0.428). 6R-BH4-treated subjects had a 5.0-mm Hg drop in DBP (baseline mean, 90 mm Hg) compared with a 4.8-mm Hg drop in placebo-treated subjects (baseline mean, 93 mm Hg; p=0.907). No statistically significant differences in either endpoint were seen in subgroup analyses of subjects with or without diabetes, or in other measures of efficacy or safety. Post-hoc analyses in subjects with higher SBP at baseline (>150 mm Hg) showed a better SBP response to 6R-BH4 (−14.1 mm Hg) than to placebo (−5.9 mm Hg) however too few subjects with higher SBP were enrolled to reach statistical significance (6R-BH4, n=19; placebo, n=7: p=0.149). CONCLUSIONS: Oral 6R-BH4 at a dose of 10 mg/kg/day showed no anti-hypertensive effect in subjects already on a stable regimen of at least two antihypertensive drugs.


Pituitary ◽  
2019 ◽  
Vol 23 (2) ◽  
pp. 171-181 ◽  
Author(s):  
Stephan Petersenn ◽  
◽  
Aude Houchard ◽  
Caroline Sert ◽  
Philippe J. Caron

Abstract Purpose PRIMARYS (NCT00690898) was a 48-week, open-label, phase 3b study, evaluating treatment with the somatostatin receptor ligand lanreotide autogel (stable dose: 120 mg/28 days) in treatment-naïve patients with growth hormone (GH)-secreting pituitary macroadenoma. This post hoc analysis aimed to evaluate factors predictive of long-term responses. Methods Potential predictive factors evaluated were: sex, age, and body mass index at baseline; and GH, insulin-like growth factor-1 (IGF-1), and tumor volume (TV) at baseline and week 12, using univariate regression analyses. Treatment responses were defined as hormonal control (GH ≤ 2.5 µg/L and age- and sex-normalized IGF-1), tight hormonal control (GH < 1.0 µg/L and normalized IGF-1), or ≥ 20% TV reduction (TVR). Receiver-operating-characteristic (ROC) curves were constructed using predictive factors significant in univariate analyses. Cut-off values for predicting treatment responses at 12 months were derived by maximizing the Youden index (J). Results At baseline, older age, female sex, and lower IGF-1 levels were associated with an increased probability of achieving long-term hormonal control. ROC area-under-the curve (AUC) values for hormonal control were high for week-12 GH and IGF-1 levels (0.87 and 0.93, respectively); associated cut-off values were 1.19 μg/L and 110% of the upper limit of normal (ULN), respectively. Results were similar for tight hormonal control (AUC values: 0.92 [GH] and 0.87 [IGF-1]; cut-off values: 1.11 μg/L and 125% ULN, respectively). AUC and J values associated with TVR were low. Conclusions The use of predictive factors at baseline and week 12 of treatment could inform clinical expectations of the long-term efficacy of lanreotide autogel.


SLEEP ◽  
2020 ◽  
Vol 43 (Supplement_1) ◽  
pp. A399-A400
Author(s):  
R H Roth ◽  
H Bonner ◽  
J Logan ◽  
M Baruch ◽  
D Calhoun ◽  
...  

Abstract Introduction Abnormal nocturnal blood pressure(BP) such as non-dipping or nocturnal hypertension(reverse-dipping) represents a potent marker for cardiovascular risks. Standard cuff-based ambulatory nocturnal BP measurement yields limited data points potentially resulting in imprecise results, especially compared to continuously recorded BP. We hypothesized nocturnal BP based on periodic measurement would be different from true average beat-to-beat based BP. Methods We prospectively enrolled patients undergoing clinically indicated in-lab polysomnography, both CPAP and non-CPAP studies, for sleep apnea evaluation. Nocturnal BP was continuously monitored beat-to-beat by a noninvasive Caretaker™ device, which uses the Pulse Decomposition Analysis(PDA) algorithm. We compared BP recorded at 30-minute intervals with average BP continuously recorded over 30 minutes, both recorded by Caretaker™. We also looked at the differences between recording spot and continuous BP from an awake or sleeping state and BP variability(SD) based on continuously recorded BP. Using first 30 min as a reference, we determined dipping status (dipping: 10-20% reduction, level: 0-10% reduction, riser: any increase) by the two methods. Results A total of 18 patients were recruited(male:11, mean age:52.2). Among a total of 261 periodic BP measurements, 60 (30.0%) were obtained while awake. Mean nocturnal SBP by periodic BP measurement was higher compared with beat-to-beat-derived average BP(135.6mmHg[24.2] vs. 131.5[20.3], p&lt;0.0001). The difference between the two methods remained similar when continuous BP was derived from sleep vs. awake period(4.5mmHg[3.1] vs. 7.7[9.9], p=0.202). BP variability was more pronounced during awake compared with sleep period(6.7mmHg[8.1] versus 3.95[7.5], p=0.047). 8 patients were dippers by spot check measurement, but 11 were dippers by continuous BP. Conclusion Standard ambulatory periodic nocturnal BP recording may not yield true sleep BP patterns due to its spot-check nature and lack of sleep-awake information, which leads to inaccurate dipping measurements. Incorporation of beat-to-beat continuous BP measurement can provide more accurate and meaningful nocturnal BP information. Support N/A


Sign in / Sign up

Export Citation Format

Share Document