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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.
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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
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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.
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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.
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Efficacy of dulaglutide on vascular health indexes in subjects with type 2 diabetes: a randomized trial.
Tuttolomondo, A, Cirrincione, A, Casuccio, A, Del Cuore, A, Daidone, M, Di Chiara, T, Di Raimondo, D, Corte, VD, Maida, C, Simonetta, I, et al
Cardiovascular diabetology. 2021;(1):1
Abstract
BACKGROUND Recent cardiovascular outcome trials have shown significant reductions in major cardiovascular (CV) events with glucagon-like peptide (GLP)-1 receptor agonists. Additionally, adjunctive surrogates for cardiovascular risk validated by some studies include arterial stiffness and endothelial function indexes. To date, no randomized trial has addressed the possible effects of antidiabetic interventional drugs such as GLP1 agonists on endothelial and arterial stiffness indexes as surrogate markers of vascular damage. AIMS We aimed to evaluate metabolic efficacy and surrogate vascular efficacy endpoints of once-weekly dulaglutide (1.5 mg) plus traditional antidiabetic treatment compared with traditional antidiabetic treatment alone in subjects with type 2 diabetes. METHODS Men and women (aged ≥ 50 years) with established or newly detected type 2 diabetes whose HbA1c level was 9.5% or less on stable doses of up to two oral glucose- lowering drugs with or without basal insulin therapy were eligible for randomization. Subcutaneous dulaglutide was initiated at the full dose (1.5 mg/day weekly). Arterial stiffness (PWV: pulse wave velocity and augmentation index) and endothelial function (RHI: reactive hyperaemia index) were evaluated at baseline and at three-month and nine-month examination visits. At each visit (at 3 and 9 months), the subjects were also evaluated for glycaemic variables such as fasting plasma glucose (FPG) and HbA1c and lipid variables such as total cholesterol, LDL cholesterol, HDL cholesterol and triglyceride levels. RESULTS At the three-month follow-up, the subjects treated with dulaglutide showed significantly lower serum levels of FPG and HbA1c than control subjects treated with conventional therapy. At the 9-month follow-up, subjects treated with dulaglutide showed significant lower values of the mean diastolic blood pressure, BMI, total serum cholesterol, LDL cholesterol, FPG, HbA1c and PWV and higher mean RHI values than control subjects treated with conventional therapy. CONCLUSIONS Our randomized trial showed that subjects with type 2 diabetes treated with conventional therapy plus 1.5 mg/day of subcutaneous dulaglutide compared with subjects treated with conventional therapy alone showed favourable metabolic effects associated with positive effects on vascular health markers such as arterial stiffness and endothelial function markers. These findings are consistent with previous study findings indicating the strict relationship between cardiovascular risk factors such as systolic blood pressure, total serum cholesterol and LDL levels and cardiovascular events and vascular health surrogate markers.
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Dietary Approaches to Stop Hypertension Dietary Intervention Improves Blood Pressure and Vascular Health in Youth With Elevated Blood Pressure.
Couch, SC, Saelens, BE, Khoury, PR, Dart, KB, Hinn, K, Mitsnefes, MM, Daniels, SR, Urbina, EM
Hypertension (Dallas, Tex. : 1979). 2021;(1):241-251
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Abstract
This randomized control trial assessed the post-intervention and 18-month follow-up effects of a 6-month dietary approaches to stop hypertension (DASH)-focused behavioral nutrition intervention, initiated in clinic with subsequent telephone and mail contact, on blood pressure (BP) and endothelial function in adolescents with elevated BP. Adolescents (n=159) 11 to 18 years of age with newly diagnosed elevated BP or stage 1 hypertension treated at a hospital-based clinic were randomized. DASH participants received a take-home manual plus 2 face-to-face counseling sessions at baseline and 3 months with a dietitian regarding the DASH diet, 6 monthly mailings, and 8 weekly and then 7 biweekly telephone calls focused on behavioral strategies to promote DASH adherence. Routine care participants received nutrition counseling with a dietitian consistent with pediatric guidelines established by the National High Blood Pressure Education Program. Outcomes, measured pre- and post-intervention and at 18-months follow-up, included change in BP, change in brachial artery flow-mediated dilation, and change in DASH score based on 3-day diet recalls. Adolescents in DASH versus routine care had a greater improvement in systolic BP (-2.7 mm Hg, P= 0.03, -0.3 z-score, P=0.03), flow-mediated dilation (2.5%, P=0.05), and DASH score (13.3 points, P<0.0001) from baseline to post-treatment and a greater improvement in flow-mediated dilation (3.1%, P=0.03) and DASH score (7.4 points, P=0.01) to 18 months. The DASH intervention proved more effective than routine care in initial systolic BP improvement and longer term improvement in endothelial function and diet quality in adolescents with elevated BP and hypertension. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00585832.
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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.
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Effect of 1-year oral cholecalciferol on a metabolic profile and blood pressure in poor-controlled type 2 diabetes mellitus: an open-label randomized controlled pilot study.
Barale, M, Rossetto Giaccherino, R, Ghigo, E, Procopio, M
Journal of endocrinological investigation. 2021;(4):791-802
Abstract
PURPOSE Hypovitaminosis D has been associated with many cardio-metabolic disorders, although their pathogenetic link still remains unclear. Our aim was to evaluate whether 1-year vitamin D (D) supplementation could improve glycemic control, lipid profile, systolic (SBP) and diastolic (DBP) blood pressure levels and body composition. METHODS In an open-label randomized-controlled pilot study, thirty poor-controlled (HbA1c > 59 mmol/mol) type 2 diabetic patients (age 71.5 ± 3.2 years, M/F 21/9, BMI 29.8 ± 3.6 kg/m2) with hypovitaminosis D (25OHD 22.0 ± 11.3 nmol/l) were randomized to cholecalciferol supplementation (500 UI/kg p.o. weekly, + D) or observation (- D) for one year. Changes in parameters of glucose, lipid and blood pressure control at 3, 6, 9 and 12 months vs. baseline were assessed. RESULTS One-year D supplementation restored D status and had a beneficial effect on fasting glucose (FG, mean percentage changes ± SD, - 1.8% ± 23.1 vs. + 18.8% ± 30.0), glycosylated haemoglobin (HbA1c, - 13.7% ± 14.5 vs. - 4.2% ± 14.1), SBP (- 13.4% ± 8.5 vs. - 2.4% ± 12.6) and HDL-cholesterol levels (- 2.1% ± 14.0 vs. - 10.9% ± 12.9; p < 0.05 for all comparisons) in + D vs. - D patients, respectively. In the former, a reduction in HBA1c, SBP and DBP levels, BMI, fat mass index (FMI) and ratio (FMR) was observed after 1 year (p < 0.05 for all comparisons vs. baseline). We noticed a relationship between 1-year mean percentage changes of serum 25OHD and SBP levels (R = - 0.36, p < 0.05). CONCLUSION One-year cholecalciferol supplementation, able to restore D status, significantly improves FG, HbA1c, SBP and HDL-cholesterol levels in patients with poor-controlled type 2 diabetes mellitus and D deficiency.
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The wearable activity technology and action-planning trial in cancer survivors: Physical activity maintenance post-intervention.
Hardcastle, SJ, Maxwell-Smith, C, Hince, D, Bulsara, MK, Boyle, T, Tan, P, Levitt, M, Salama, P, Mohan, GRKA, Salfinger, S, et al
Journal of science and medicine in sport. 2021;(9):902-907
Abstract
OBJECTIVES The study objective was to assess whether moderate-to-vigorous intensity physical activity (MVPA) change in cancer survivors (n = 68, mean age = 64 years) was maintained 12-weeks following the Wearable Activity Technology and Action Planning (WATAAP) intervention. Secondary aims were to assess the effects of the intervention on blood pressure (BP) and body mass index (BMI), and to explore group differences between baseline and 24-weeks. DESIGN Randomized controlled trial. METHODS MVPA and sedentary behaviour were assessed using an accelerometer at baseline, the end of the intervention (12-weeks), and at 24-weeks. Generalised linear mixed models with random effects were used to examine between-group and within-group changes in MVPA, sedentary behaviour, BP and BMI. RESULTS MVPA was significantly higher in the intervention group compared with the control group at 24-weeks following adjustment for known confounders (141.4 min/wk. (95% CI = 9.1 to 273.8), p = 0.036). At 24-weeks participants in the intervention group had maintained their increased levels of MVPA (change from 12-weeks = 8.8 min/wk.; 95% CI = -43 to 61; p = 0.74). The reduction in MVPA in the control group over the first 12-weeks was also maintained at 24-weeks (5.4 min/wk.; 95% CI = -3.6 to 4.6; p = 0.80). Secondary outcomes did not differ between groups at 24-weeks. CONCLUSIONS Our results suggest distance-based interventions using wearable technology produce increases in MVPA that endure at least 12-weeks after the intervention is completed.
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Effectiveness of chlorthalidone/amiloride versus losartan in patients with stage I hypertension and diabetes mellitus: results from the PREVER-treatment randomized controlled trial.
Fuchs, FD, Scala, LCN, Vilela-Martin, JF, Whelton, PK, Poli-de-Figueiredo, CE, Pereira E Silva, R, Gus, M, Bortolotto, LA, Consolim-Colombo, FM, Schlatter, RP, et al
Acta diabetologica. 2021;(2):215-220
Abstract
AIMS: To compare the blood pressure (BP)-lowering efficacy of a chlorthalidone/amiloride combination pill with losartan, during initial management of JNC 7 Stage I hypertension in patients with type 2 diabetes mellitus. METHODS In an a priori subgroup analysis of a randomized, double-blind, controlled trial, volunteers aged 30-70 years, with stage I hypertension and diabetes mellitus, were randomized to 12.5/2.5 mg of chlorthalidone/amiloride (N = 47) or 50 mg of losartan (N = 50), and followed for 18 months in 21 clinical centers. If BP remained uncontrolled after three months, study medication dose was doubled, and if uncontrolled after six months, amlodipine (5 and 10 mg) and propranolol (40 and 80 mg BID) were added as open label drugs in a progressive fashion. RESULTS Systolic BP decreased to a greater extent in participants allocated to diuretics compared to losartan (P < 0.001). After 18 months of follow-up, systolic BP was 128.4 ± 10.3 mmHg in the diuretic group versus 133.5 ± 8.0 in the losartan group (P < 0.01). In the diuretic group, 36 out of 43 participants (83.7%) had a JNC 7 normal BP, compared to 31/47 (66%) in the losartan group (P = 0.089). Serum cholesterol was higher in the diuretic arm at the end of the trial. Other biochemical parameters and reports of adverse events did not differ by treatment. CONCLUSIONS Treatment of hypertension based on a combination of chlorthalidone and amiloride is more effective for BP lowering compared to losartan in patients with diabetes mellitus and hypertension. TRIAL REGISTRATION Clinical trials registration number: NCT00971165.
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Coconut Oil Supplementation Does Not Affect Blood Pressure Variability and Oxidative Stress: A Placebo-Controlled Clinical Study in Stage-1 Hypertensive Patients.
Júnior, FAO, Ruiz, CR, de Oliveira, Y, Barros, MAV, Silva, AS, Santos, MSB, Martins, VJB, Balarini, CM, Braga, VA
Nutrients. 2021;(3)
Abstract
Exploring an alternative to improve the clinical management of hypertension, we tested the hypothesis that food supplementation with coconut oil (EVCO), alone or combined with aerobic exercise training, could exert an antihypertensive effect (primary outcome) in patients with stage 1 hypertension. Forty-five hypertensive volunteers of both genders participated in a placebo-controlled clinical trial. The volunteers were submitted to 24-hour ambulatory blood pressure monitoring, analysis of blood pressure variability (BPV), measurement of serum malondialdehyde (MDA) and nutritional assessment. Results indicate that EVCO consumption had no adverse effects. The supplementation did not increase the caloric intake compared with placebo, and the dietary constituents were similar between groups, except for the saturated fats, especially lauric acid. The analysis of blood pressure indicated absence of antihypertensive effect of EVCO alone or combined with physical training. Furthermore, no effects on blood pressure variability and oxidative stress were observed in the supplemented hypertensive patients. Thus, despite the results observed in pre-clinical studies, the current clinical study did not provide evidence to support the use of coconut oil as an adjuvant in the management of hypertension in humans.