-
1.
Assessment of Omecamtiv Mecarbil for the Treatment of Patients With Severe Heart Failure: A Post Hoc Analysis of Data From the GALACTIC-HF Randomized Clinical Trial.
Felker, GM, Solomon, SD, Claggett, B, Diaz, R, McMurray, JJV, Metra, M, Anand, I, Crespo-Leiro, MG, Dahlström, U, Goncalvesova, E, et al
JAMA cardiology. 2022;(1):26-34
-
-
Free full text
-
Abstract
IMPORTANCE Heart failure with reduced ejection fraction is a progressive clinical syndrome, and many patients' condition worsen over time despite treatment. Patients with more severe disease are often intolerant of available medical therapies. OBJECTIVE To evaluate the efficacy and safety of omecamtiv mecarbil for the treatment of patients with severe heart failure (HF) enrolled in the Global Approach to Lowering Adverse Cardiac Outcomes Through Improving Contractility in Heart Failure (GALACTIC-HF) randomized clinical trial. DESIGN, SETTING, AND PARTICIPANTS The GALACTIC-HF study was a global double-blind, placebo-controlled phase 3 randomized clinical trial that was conducted at multiple centers between January 2017 and August 2020. A total of 8232 patients with symptomatic HF (defined as New York Heart Association symptom class II-IV) and left ventricular ejection fraction of 35% or less were randomized to receive omecamtiv mecarbil or placebo and followed up for a median of 21.8 months (range, 15.4-28.6 months). The current post hoc analysis evaluated the efficacy and safety of omecamtiv mecarbil therapy among patients classified as having severe HF compared with patients without severe HF. Severe HF was defined as the presence of all of the following criteria: New York Heart Association symptom class III to IV, left ventricular ejection fraction of 30% or less, and hospitalization for HF within the previous 6 months. INTERVENTIONS Participants were randomized at a 1:1 ratio to receive either omecamtiv mecarbil or placebo. MAIN OUTCOMES AND MEASURES The primary end point was time to first HF event or cardiovascular (CV) death. Secondary end points included time to CV death and safety and tolerability. RESULTS Among 8232 patients enrolled in the GALACTIC-HF clinical trial, 2258 patients (27.4%; mean [SD] age, 64.5 [11.6] years; 1781 men [78.9%]) met the specified criteria for severe HF. Of those, 1106 patients were randomized to the omecamtiv mecarbil group and 1152 to the placebo group. Patients with severe HF who received omecamtiv mecarbil experienced a significant treatment benefit for the primary end point (hazard ratio [HR], 0.80; 95% CI, 0.71-0.90), whereas patients without severe HF had no significant treatment benefit (HR, 0.99; 95% CI, 0.91-1.08; P = .005 for interaction). For CV death, the results were similar (HR for patients with vs without severe HF: 0.88 [95% CI, 0.75-1.03] vs 1.10 [95% CI, 0.97-1.25]; P = .03 for interaction). Omecamtiv mecarbil therapy was well tolerated in patients with severe HF, with no significant changes in blood pressure, kidney function, or potassium level compared with placebo. CONCLUSIONS AND RELEVANCE In this post hoc analysis of data from the GALACTIC-HF clinical trial, omecamtiv mecarbil therapy may have provided a clinically meaningful reduction in the composite end point of time to first HF event or CV death among patients with severe HF. These data support a potential role of omecamtiv mecarbil therapy among patients for whom current treatment options are limited. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT02929329.
-
2.
Low-dose fentanyl does not alter muscle sympathetic nerve activity, blood pressure, or tolerance during progressive central hypovolemia.
Huang, M, Watso, JC, Belval, LN, Cimino, FA, Fischer, M, Jarrard, CP, Hendrix, JM, Laborde, CH, Crandall, CG
American journal of physiology. Regulatory, integrative and comparative physiology. 2022;(1):R55-R63
Abstract
Hemorrhage is a leading cause of battlefield and civilian trauma deaths. Several pain medications, including fentanyl, are recommended for use in the prehospital (i.e., field setting) for a hemorrhaging solider. However, it is unknown whether fentanyl impairs arterial blood pressure (BP) regulation, which would compromise hemorrhagic tolerance. Thus, the purpose of this study was to test the hypothesis that an analgesic dose of fentanyl impairs hemorrhagic tolerance in conscious humans. Twenty-eight volunteers (13 females) participated in this double-blinded, randomized, placebo-controlled trial. We conducted a presyncopal limited progressive lower body negative pressure test (LBNP; a validated model to simulate hemorrhage) following intravenous administration of fentanyl (75 µg) or placebo (saline). We quantified tolerance as a cumulative stress index (mmHg·min), which was compared between trials using a paired, two-tailed t test. We also compared muscle sympathetic nerve activity (MSNA; microneurography) and beat-to-beat BP (photoplethysmography) during the LBNP test using a mixed effects model [time (LBNP stage) × trial]. LBNP tolerance was not different between trials (fentanyl: 647 ± 386 vs. placebo: 676 ± 295 mmHg·min, P = 0.61, Cohen's d = 0.08). Increases in MSNA burst frequency (time: P < 0.01, trial: P = 0.29, interaction: P = 0.94) and reductions in mean BP (time: P < 0.01, trial: P = 0.50, interaction: P = 0.16) during LBNP were not different between trials. These data, the first to be obtained in conscious humans, demonstrate that administration of an analgesic dose of fentanyl does not alter MSNA or BP during profound central hypovolemia, nor does it impair tolerance to this simulated hemorrhagic insult.
-
3.
A Comparative Study of Health Efficacy Indicators in Subjects with T2DM Applying Power Cycling to 12 Weeks of Low-Volume High-Intensity Interval Training and Moderate-Intensity Continuous Training.
Li, J, Cheng, W, Ma, H
Journal of diabetes research. 2022;:9273830
Abstract
This study is aimed at comparing the effects of different exercise intensities, namely, high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT), on body composition, heart and lung fitness, and blood glucose, and blood pressure indices in patients with type 2 diabetes mellitus (T2DM), using power cycling. A total of 96 T2DM volunteers who met the inclusion criteria were recruited from a hospital in Yangpu, Shanghai. Based on the blood index data of their medical examination results which comprised blood pressure, fasting blood glucose, hemoglobin A1c (HbA1c), and insulin, 37 volunteers were included in the study. Exercise prescription was determined based on T2DM exercise guidelines combined with medical diagnosis and exercise test results, and the patients were randomly assigned to three groups: HIIT group, MICT group, and control (CON) group. HIIT involved one-minute power cycling (80%-95% maximal oxygen uptake (VO2max)), one-minute passive or active rest (25%-30% VO2max), and two-minute rounds of eight groups. MICT required the use of a power bike for 30 minutes of continuous training (50%-70% VO2max) five times a week. The CON group was introduced to relevant medicine, exercise, and nutrition knowledge. The exercise interventions were completed under the supervision of an exercise instructor and hospital doctors. The same indicators were measured after 12 weeks of intervention, and the results of the two tests within and between groups were analyzed for comparison. The weight index of the MICT intervention showed statistically significant within-group differences (difference = 3.52, 95% CI = 2.11-4.92, p = 0.001 < 0.01); group differences for the MICT and CON groups were also statistically significant (difference = 3.52 ± 2.09, Cd1 = -0.39 ± 1.25, p = 0.004 < 0.01). Body mass index (BMI) analysis revealed that the overall means of BMI indicators were not statistically different between groups (F = 0.369, p = 0.694 > 0.05) and the before and after values of the MICT and CON (difference = -1.30 ± 0.79, Cd1 = -0.18 ± 0.45, p = 0.001 < 0.01). No statistically significant difference was observed in the overall mean VO2max index between the groups after the 12-week intervention (F = 2.51, p = 0.100 > 0.05). A statistically significant difference was found in the overall means of the data between the two groups (difference = 0.32, 95% CI = 0.23-0.40, p = 0.001 < 0.01). Analysis of fasting blood glucose (FBG) indicators revealed statistically significant differences between the MICT and control groups (p = 0.028 < 0.05). Analysis of HbA1c and fasting insulin (FI) indicators revealed no statistically significant difference in the overall HbA1c index after the 12-week exercise intervention (F = 0.523, p = 0.598 > 0.05), and the overall difference before and after the experiment between the groups was statistically significant (F = 6.13, p = 0.006 < 0.01). No statistically significant difference was found in the FI index overall after the 12-week exercise intervention (F = 2.50, p = 0.1 > 0.05). Analysis of systolic blood pressure (SBP) revealed statistically significant difference before and after the HIIT and CON interventions (Hd7 = -1.10 ± 1.79, Cd7 = 1.2 ± 1.31, p = 0.018 < 0.05) and statistically significant difference before and after the MICT and CON interventions (Md7 = -0.99 ± 0.91, Cd7 = 1.40 ± 1.78, p = 0.02 < 0.05). The diastolic blood pressure (DBP) revealed no statistically significant within-group differences before and after. Exercise interventions applying both low-volume HIIT and MICT, with both intensity exercises designed for power cycling, improved health-related indicators in the participants; low-volume HIIT had more time advantage. The current experiment compared HIIT with MICT in a safe manner: 50% of the exercise time produced similar benefits and advantages in the two indicators of VO2max and FI. However, MICT was superior to HIIT in the two indicators of body weight (weight) and BMI. The effect of power cycling on FI has the advantages of both aerobic and resistance exercise, which may optimize the type, intensity, and time of exercise prescription according to the individual or the type of exercise program. Our results provide a reference for the personalization of exercise prescription for patients with T2DM.
-
4.
Hypertensive Retinopathy and the Risk of Stroke Among Hypertensive Adults in China.
Chen, X, Liu, L, Liu, M, Huang, X, Meng, Y, She, H, Zhao, L, Zhang, J, Zhang, Y, Gu, X, et al
Investigative ophthalmology & visual science. 2021;(9):28
-
-
Free full text
-
Abstract
PURPOSE This study aimed to investigate the association between hypertensive retinopathy and the risk of first stroke, examine possible effect modifiers in hypertensive patients, and test the appropriateness of the Keith-Wagener-Barker (KWB) classification for predicting stroke risk. METHODS In total, 9793 hypertensive participants (3727 males and 6066 females) without stroke history from the China Stroke Primary Prevention Trial were included in this study. The primary outcome was first stroke. RESULTS Over a median follow-up of 4.4 years, 592 participants experienced their first stroke (509 ischemic, 77 hemorrhagic, and six unclassifiable strokes). In total, 5590 participants were diagnosed with grade 1 retinopathy (57.08%), 1466 with grade 2 retinopathy (14.97%), 231 with grade 3 retinopathy (2.36%), and three with grade 4 retinopathy (0.03%). Grades 1 and 2 were merged and classified as mild retinopathy, and grades 3 and 4 were merged and classified as severe retinopathy. There was a significant positive association between hypertensive retinopathy and the risk of first stroke and first ischemic stroke, and no effect modifiers were found. The hazard ratios (HRs) for first stroke were as follows: mild versus no retinopathy, 1.26 (95% confidence interval [CI], 1.01-1.58, P = 0.040), and severe versus no retinopathy, 2.40 (95% CI, 1.49-3.84, P < 0.001). The HRs for ischemic stroke were as follows: severe versus no retinopathy, 2.35 (95% CI, 1.41-3.90, P = 0.001), and nonsignificantly increased HRs for mild versus no retinopathy, 1.26 (95% CI, 0.99-1.60, P = 0.057). CONCLUSIONS There was a significant positive association between hypertensive retinopathy and the risk of first stroke in patients with hypertension, indicating that hypertensive retinopathy may be a predictor of the risk of stroke. A simplified two-grade classification system based on the KWB classification is recommended for predicting stroke risk.
-
5.
A Randomized, Double-Blind, Placebo-Controlled Trial to Determine the Effectiveness of a Polyphenolic Extract (Hibiscus sabdariffa and Lippia citriodora) for Reducing Blood Pressure in Prehypertensive and Type 1 Hypertensive Subjects.
Marhuenda, J, Pérez-Piñero, S, Arcusa, R, Victoria-Montesinos, D, Cánovas, F, Sánchez-Macarro, M, García-Muñoz, AM, Querol-Calderón, M, López-Román, FJ
Molecules (Basel, Switzerland). 2021;(6)
Abstract
Hypertension is an important factor of cardiovascular diseases and contributes to their negative consequences including mortality. The World Health Organization estimated that 54% of strokes and 47% of cases of ischemic heart illness are related to high blood pressure. Recently, Hibiscus sabdariffa (HS) and Lippia citriodora (LC) have attracted scientific interest, and they are recognized for their high content of polyphenols as these may prevent several disease factors, such as hypertension. The aim of the present study is to determine if supplementation with an HS-LC blend (MetabolAid®) may be effective for the treatment of type 1 hypertensive sedentary populations. A total of 80 type 1 hypertensive subjects of both sexes were included in the study and were treated with placebo or the HS-LC extract, and both groups were treated over 84 days. The blood pressure (diastolic, systolic, and pulse pressure) was measured throughout the day, for each of the days of the study duration and determined using Ambulatory Blood Pressure Monitoring (ABPM). Physical activity was determined throughout the study to ensure similar conditions related to exercise. The results showed the capacity for reducing the blood pressure parameters in the case of the HS-LC extract. The daily consumption of the HS-LC extract but not the placebo over 84 days was able to reduce the daytime parameters related to blood pressure. The most remarkable results were observed in the measurements performed during the daytime, especially in the systolic blood pressure showing statistically significant variation.
-
6.
Treatment effect of lacidipine and amlodipine on clinic and ambulatory blood pressure and arteria stiffness in a randomised double-blind trial.
Wang, Y, Li, Y, Huo, Y, Wang, JG
Blood pressure. 2021;(2):108-117
Abstract
PURPOSE In a randomised, double-blind trial, we investigated effects of lacidipine on clinic and ambulatory blood pressure (BP) and arterial stiffness in patients with mild-to-moderate hypertension, as compared with amlodipine. MATERIALS AND METHODS Previously untreated and treated patients (n = 269, 50-80 years of age) with clinic hypertension (a clinic systolic/diastolic BP 140-180/<110 mmHg and <160/100 mmHg, respectively) were randomly assigned to double-dummy treatment with lacidipine (4-6 mg/day) or amlodipine (5-7.5 mg/day) for 20 weeks. The primary efficacy variable was the change in 24-h ambulatory systolic BP at 20 weeks of treatment. Arterial stiffness was measured as brachial-ankle pulse wave velocity (PWV). RESULTS After 20 weeks of treatment, 24-h systolic BP decreased from 141.3 ± 14.0 and 138.3 ± 12.8 mmHg at baseline, respectively, in the lacidipine (n = 134) and amlodipine groups (n = 135), by a least square mean (±SE) change of 15.2 ± 1.3 and 15.5 ± 1.3 mmHg, respectively, with a between-group difference (95% confidence interval [CI]) of 0.3 mmHg (-3.4 to 4.1, p = 0.86). Similar results were observed for other ambulatory BP components and clinic BP. Clinic and ambulatory pulse rate did not significantly change in either group (p ≥ 0.21). PWV decreased significantly (p < 0.001) from baseline in both groups, with a non-significant between-group difference of 0.24 m/s (p = 0.45). The incidence rate of adverse events was 30.3% (n = 40) and 27.5% (n = 36) in the lacidipine and amlodipine groups, respectively (p = 0.61). No serious adverse event occurred in the trial. CONCLUSIONS Lacidipine effectively lowers clinic and ambulatory BP in patients with mild-to-moderate hypertension and significantly improves arterial stiffness, similarly as amlodipine.
-
7.
Short-Term RCT of Increased Dietary Potassium from Potato or Potassium Gluconate: Effect on Blood Pressure, Microcirculation, and Potassium and Sodium Retention in Pre-Hypertensive-to-Hypertensive Adults.
Stone, MS, Martin, BR, Weaver, CM
Nutrients. 2021;(5)
Abstract
Increased potassium intake has been linked to improvements in cardiovascular and other health outcomes. We assessed increasing potassium intake through food or supplements as part of a controlled diet on blood pressure (BP), microcirculation (endothelial function), and potassium and sodium retention in thirty pre-hypertensive-to-hypertensive men and women. Participants were randomly assigned to a sequence of four 17 day dietary potassium treatments: a basal diet (control) of 60 mmol/d and three phases of 85 mmol/d added as potatoes, French fries, or a potassium gluconate supplement. Blood pressure was measured by manual auscultation, cutaneous microvascular and endothelial function by thermal hyperemia, utilizing laser Doppler flowmetry, and mineral retention by metabolic balance. There were no significant differences among treatments for end-of-treatment BP, change in BP over time, or endothelial function using a mixed-model ANOVA. However, there was a greater change in systolic blood pressure (SBP) over time by feeding baked/boiled potatoes compared with control (-6.0 mmHg vs. -2.6 mmHg; p = 0.011) using contrast analysis. Potassium retention was highest with supplements. Individuals with a higher cardiometabolic risk may benefit by increasing potassium intake. This trial was registered at ClinicalTrials.gov as NCT02697708.
-
8.
Effect of Dietary Nori (Dried Laver) on Blood Pressure in Young Japanese Children: An Intervention Study.
Wada, K, Tsuji, M, Nakamura, K, Oba, S, Nishizawa, S, Yamamoto, K, Watanabe, K, Ando, K, Nagata, C
Journal of epidemiology. 2021;(1):37-42
Abstract
BACKGROUND Few studies have examined the association between seaweed intake and blood pressure in children. We conducted an intervention study to investigate whether seaweed intake affects blood pressure. METHODS Subjects were children aged 4 to 5 years attending a preschool in Aichi Prefecture, Japan, in 2010. Among 99 students, 89 (89.9%) were enrolled in our study. Nori (dried laver), an edible seaweed widely consumed in Japan, was used as a dietary intervention. Children in the intervention group were asked to consume 1.76 grams per day of roasted nori in addition to standard meals for 10 weeks. Children in the control group consumed their usual diet. Before the intervention and at the 10th week of the intervention, children's blood pressure was measured three times successively using an automated sphygmomanometer with subjects in a sitting position. Changes in systolic (SBP) and diastolic blood pressure (DBP) were compared between 55 children in the intervention group and 26 in the control group after adjustment for SBP and DBP before the intervention. RESULTS Changes in SBP were -8.29 mm Hg in the intervention group and +0.50 mm Hg in the control group (P for difference in change = 0.051). Changes in DBP were -6.77 mm Hg in the intervention group and -0.05 mm Hg in the control group (P = 0.031). In girls, no difference in blood pressure changes was found between the intervention and control groups. CONCLUSION Nori intake lowered DBP level in boys. Seaweed intake might have preventive effects on elevated blood pressure in childhood.
-
9.
Preoperative Amlodipine Is Efficacious in Preventing Intraoperative HDI in Pheochromocytoma: Pilot RCT.
Jaiswal, SK, Memon, SS, Lila, A, Sarathi, V, Goroshi, M, Garg, R, Barnabas, R, Hemantkumar, I, Patel, RD, Oak, S, et al
The Journal of clinical endocrinology and metabolism. 2021;(8):e2907-e2918
Abstract
CONTEXT Preoperative blockade with α-blockers is recommended in patients with pheochromocytoma/paraganglioma (PPGL). The data on calcium channel blockade (CCB) in PPGL are scarce. OBJECTIVE We aimed to compare the efficacy of CCB and α-blockers on intraoperative hemodynamic instability (HDI) in PPGL. METHODS In the interim analysis of this monocentric, pilot, open-label, randomized controlled trial, patients with solitary, secretory, and nonmetastatic PPGL were randomized to oral prazosin gastrointestinal therapeutic system (GITS) (maximum 30 mg, n = 9) or amlodipine (maximum 20 mg, n = 11). The primary outcomes were the episodes and duration of hypertension (systolic blood pressure ≥ 160 mmHg) and hypotension (mean arterial pressure < 60 mmHg) and duration of HDI (hypertension and/or hypotension) as a percentage of total surgical time (from induction of anesthesia to skin closure). RESULTS The median (IQR) episodes (2 [1-3] vs 0 [0-1]; P = 0.002) and duration of hypertension (19 [14-42] vs 0 [0-3] minutes; P = 0.001) and intraoperative HDI duration (22.85 ± 18.4% vs 2.44 ± 2.4%; CI, 8.68-32.14%; P 0.002) were significantly higher in the prazosin GITS arm than the amlodipine arm, whereas episodes and duration of hypotension did not differ between the 2 groups. There was no perioperative mortality. One patient had intraoperative ST depression on the electrocardiogram. The drug-related adverse effects were pedal edema (1 in amlodipine), dizziness (1 in prazosin GITS), and tachycardia (6 in prazosin GITS and 3 in amlodipine). CONCLUSION Preoperative blockade with amlodipine is an efficacious alternative to prazosin GITS in preventing intraoperative HDI in PPGL. Larger studies that compare preoperative blockade by amlodipine with other α-blockers like phenoxybenzamine and/or doxazosin in PPGL patients are warranted.
-
10.
Epigallocatechin gallate decreases plasma triglyceride, blood pressure, and serum kisspeptin in obese human subjects.
Chatree, S, Sitticharoon, C, Maikaew, P, Pongwattanapakin, K, Keadkraichaiwat, I, Churintaraphan, M, Sripong, C, Sririwichitchai, R, Tapechum, S
Experimental biology and medicine (Maywood, N.J.). 2021;(2):163-176
-
-
Free full text
-
Abstract
Obesity is one of major risk factors increasing chronic diseases including type II diabetes, cardiovascular diseases, and hypertension. The effects of epigallocatechin gallate (EGCG), the major active compound in green tea, on reduced obesity and improved metabolic profiles are still controversial. Furthermore, the effects of EGCG on human adipocyte lipolysis and browning of white adipocytes have not been elucidated. This study aimed to investigate the effects of EGCG on obesity, lipolysis, and browning of human white adipocytes. The results showed that, when compared to the baseline values, EGCG significantly decreased fasting plasma triglyceride levels (P < 0.05), systolic blood pressure (P < 0.05), diastolic blood pressure (P < 0.05), and serum kisspeptin levels (P < 0.05) after 8 weeks of supplement. On the other hand, supplement of EGCG in obese human subjects for 4 or 8 weeks did not decrease body weight, body mass index, waist and hip circumferences, nor total body fat mass or percentage when compared to their baseline values. The study in human adipocytes showed that EGCG did not increase the glycerol release when compared to vehicle, suggesting that it had no lipolytic effect. Furthermore, treatment of EGCG did not enhance uncoupling protein 1 (UCP1) mRNA expression in human white adipocytes when compared with treatment of pioglitazone, the peroxisome proliferator-activated receptor γ (PPAR-γ) agonist, suggesting that EGCG did not augment the browning effect of PPAR-γ on white adipocytes. This study revealed that EGCG reduced 2 metabolic risk factors which are triglyceride and blood pressure in the human experiment. We also showed a novel evidence that EGCG decreased kisspeptin levels. However, EGCG had no effects on obesity reduction in humans, lipolysis, nor browning of human white adipocytes.