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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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Black chokeberry Aronia melanocarpa extract reduces blood pressure, glycemia and lipid profile in patients with metabolic syndrome: a prospective controlled trial.
Tasic, N, Jakovljevic, VLJ, Mitrovic, M, Djindjic, B, Tasic, D, Dragisic, D, Citakovic, Z, Kovacevic, Z, Radoman, K, Zivkovic, V, et al
Molecular and cellular biochemistry. 2021;(7):2663-2673
Abstract
The aim of the study was to examine the effect of 4-week supplementation of Alixir 400 PROTECT® (Standardized Aronia L. Melanocarpa Extract Extract-SAE) on clinical and biochemical parameters in patients with confirmed metabolic syndrome (MetS). This study was designed as a prospective open-label clinical case-series study with 28 days of follow-up with cases selected and followed during the period from February 1, 2018 to November 2019. The study included 143 male and female patients with MetS who were subjected to SAE. SAE supplementation significantly altered SP, BP as well as HR values. After 2 weeks, CHOL levels significantly decreased in the fMetS-DM group compared to the baseline values in this group, while the LDL levels significantly decreased in the fMetS group. Triglycerides significantly decreased only after 4 weeks of SAE treatment in diabetic groups of patients (fMetS-DM and mMetS-DM) compared to the baseline, while in non-diabetic groups this marker was not significantly altered. Increased polyphenols or SAE consumption is correlated with a positive effect on body weight, total cholesterol, low and high-density lipoproteins, blood pressure and glycemia. Increasing consumption of polyphenol-rich foods could be a promising strategy to reduce cardiovascular risk.
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A Smartphone Intervention to Promote Time Restricted Eating Reduces Body Weight and Blood Pressure in Adults with Overweight and Obesity: A Pilot Study.
Prasad, M, Fine, K, Gee, A, Nair, N, Popp, CJ, Cheng, B, Manoogian, ENC, Panda, S, Laferrère, B
Nutrients. 2021;(7)
Abstract
The goal of this study was to test the feasibility of time restricted eating (TRE) in adults with overweight and obesity. Participants (n = 50) logged all eating occasions (>0 kcal) for a 2-week run-in period using a smartphone application. Participants with eating duration ≥14 h enrolled in an open label, non-randomized, prospective 90-day TRE intervention, with a self-selected reduced eating window of 10 h. No dietary counseling was provided. Changes in anthropometrics, eating patterns and adherence after TRE were analyzed using t-tests or Wilcoxon Rank-Sum Test. The mean duration of the baseline eating window was 14 h 32 m ± 2 h 36 m (n = 50) with 56% of participants with duration ≥14 h. TRE participants (n = 16) successfully decreased their eating window from 16 h 04 m ± 1 h 24 m to 11 h 54 m ± 2 h 06 m (p < 0.001), and reduced the number of daily eating occasions by half (p < 0.001). Adherence to logging and to the reduced eating window was 64% ± 22% and 47% ± 19%, respectively. TRE resulted in decreases in body weight (-2.1 ± 3.0 kg, p = 0.017), waist circumference (-2.2 ± 4.6 cm, p = 0.002) and systolic blood pressure (-12 ± 11 mmHg, p = 0.002). This study demonstrates the feasibility and efficacy of TRE administered via a smartphone, in adults with overweight and obesity.
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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.
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Changes in Central 24-h Ambulatory Blood Pressure and Hemodynamics 12 Months After Bariatric Surgery: the BARIHTA Study.
Oliveras, A, Goday, A, Sans, L, Arias, CE, Vazquez, S, Benaiges, D, Ramon, JM, Pascual, J
Obesity surgery. 2020;(1):195-205
Abstract
BACKGROUND Weight loss is associated to blood pressure (BP) reduction in obese patients. There is no information on central 24-h BP changes after bariatric surgery (BS). METHODS AND RESULTS In this study, we analyzed changes in 24-h BP 12 months following BS, with intermediate evaluations at 1, 3, and 6 months, in severely obese adults. The primary endpoint was aortic (central) 24-h systolic BP changes. Circadian BP patterns and hypertension resolution were also assessed. As secondary endpoints, we analyze changes in central 24-h diastolic BP as well as in all office and ambulatory peripheral BP parameters. Obese adults scheduled for BS as routine clinical care were recruited. We included 62 patients (39% with hypertension, 77% women, body mass index, 42.6 ± 5.5 kg/m2). Reduction in body weight was mean (IQR) 30.5% (26.2-34.4) 1 year after BS. Mean (95% CI) change in central 24-h systolic BP was - 3.1 mmHg (- 5.5 to - 0.7), p = 0.01 after adjustment for age, sex, and baseline hypertensive status. BP parameter changes were different between normotensives and hypertensives. Mean (95% CI) change in central 24-h systolic BP was - 5.2 mmHg (- 7.7 to - 2.7), p < 0.001, in normotensives and - 0.5 mmHg (- 5.1 to 4.0), p = 0.818, in hypertensives. There was a remission of hypertension in 48% of patients. Most patients had a reduced dipping pattern, similarly at baseline and 12 months after BS. CONCLUSIONS Among patients with severe obesity, there was a substantial central 24-h systolic BP decrease 12 months following BS. Importantly, this change was observed in those patients with normal BP at baseline. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT03115502.
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Mindfulness and cardiovascular health: Qualitative findings on mechanisms from the mindfulness-based blood pressure reduction (MB-BP) study.
Nardi, WR, Harrison, A, Saadeh, FB, Webb, J, Wentz, AE, Loucks, EB
PloS one. 2020;(9):e0239533
Abstract
BACKGROUND Mindfulness-based programs hold promise for improving cardiovascular health (e.g. physical activity, diet, blood pressure). However, despite theoretical frameworks proposed, no studies have reported qualitative findings on how study participants themselves believe mindfulness-based programs improved their cardiovascular health. With an emphasis on in-depth, open-ended investigation, qualitative methods are well suited to explore the mechanisms underlying health outcomes. The objective of this qualitative study was to explore the mechanisms through which the mindfulness-based program, Mindfulness-Based Blood Pressure Reduction (MB-BP), may influence cardiovascular health. METHODS This qualitative study was conducted as part of a Stage 1 single arm trial with one-year follow-up. The MB-BP curriculum was adapted from Mindfulness-Based Stress Reduction to direct participants' mindfulness skills towards modifiable determinants of blood pressure. Four focus group discussions were conducted (N = 19 participants), and seven additional participants were selected for in-depth interviews. Data analysis was conducted using the standard approach of thematic analysis. Following double-coding of audio-recorded transcripts, four members of the study team engaged in an iterative process of data analysis and interpretation. RESULTS Participants identified self-awareness, attention control, and emotion regulation as key mechanisms that led to improvements in cardiovascular health. Within these broader themes, many participants detailed a process beginning with increased self-awareness to sustain attention and regulate emotions. Many also explained that the specific relationship between self-awareness and emotion regulation enabled them to respond more skillfully to stressors. In a secondary sub-theme, participants suggested that higher self-awareness helped them engage in positive health behaviors (e.g. healthier dietary choices). CONCLUSION Qualitative analyses suggest that MB-BP mindfulness practices allowed participants to engage more effectively in self-regulation skills and behaviors lowering cardiovascular disease risk, which supports recent theory. Results are consistent with quantitative mechanistic findings showing emotion regulation, perceived stress, interoceptive awareness, and attention control are influenced by MB-BP.
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Hemodynamic and perceptual responses to blood flow-restricted exercise among patients undergoing dialysis.
Clarkson, MJ, Brumby, C, Fraser, SF, McMahon, LP, Bennett, PN, Warmington, SA
American journal of physiology. Renal physiology. 2020;(3):F843-F850
Abstract
End-stage kidney disease is associated with reduced exercise capacity, muscle atrophy, and impaired muscle function. While these may be improved with exercise, single modalities of exercise do not traditionally elicit improvements across all required physiological domains. Blood flow-restricted exercise may improve all of these physiological domains with low intensities traditionally considered insufficient for these adaptions. Investigation of this technique appeals, but is yet to be evaluated, in patients undergoing dialysis. With the use of a progressive crossover design, 10 satellite patients undergoing hemodialysis underwent three exercise conditions over 2 wk: two bouts (10 min) of unrestricted cycling during two consecutive hemodialysis sessions (condition 1), two bouts of cycling with blood flow restriction while off hemodialysis on 2 separate days (condition 2), and two bouts of cycling with blood flow restriction during two hemodialysis sessions (condition 3). Outcomes included hemodynamic responses (heart rate and blood pressure) throughout all sessions, participant-perceived exertion and discomfort on a Borg scale, and evaluation of ultrafiltration rates and dialysis adequacy (Kt/V) obtained post hoc. Hemodynamic responses were consistent regardless of condition. Significant increases in heart rate, systolic blood pressure, and mean arterial blood pressure (P < 0.05) were observed postexercise followed by a reduction in blood pressures during the 60-min recovery (12, 5, and 11 mmHg for systolic, diastolic, and mean arterial pressures, respectively). Blood pressures returned to predialysis ranges following the recovery period. Blood flow restriction did not affect ultrafiltration achieved or Kt/V. Hemodynamic safety and tolerability of blood flow restriction during aerobic exercise on hemodialysis is comparable to standard aerobic exercise.
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Serum levels of miR-199a-5p correlates with blood pressure in premature cardiovascular disease patients homozygous for the MTHFR 677C > T polymorphism.
Lynch, SM, Ward, M, McNulty, H, Angel, CZ, Horigan, G, Strain, JJ, Purvis, J, Tackett, M, McKenna, DJ
Genomics. 2020;(1):669-676
Abstract
This investigation profiled circulating serum concentrations of microRNAs (miRNAs) in premature cardiovascular disease (CVD) patients screened for the 677C > T polymorphism in methylenetetrahydrofolate reductase (MTHFR), a risk factor for hypertension. Serum samples from 75 premature CVD patients of known MTHFR genotype were analysed for CVD-related miRNA expression, to identify those that were associated with blood pressure. Samples were collected at baseline and following intervention with riboflavin as part of a randomized controlled trial. In patients with the MTHFR 677TT genotype, expression of miR-199a-5p in serum was inversely correlated with hypertension at baseline, and with change in blood pressure in TT genotype patients who responded to riboflavin intervention. These correlations were not observed in MTHFR 677CC genotype patients. In vitro experiments and in silico data analysis provided evidence that miR-199a-5p targets SMAD4. This is the first study to link miR-199a-5p expression with hypertension in a genetically at-risk cohort of premature CVD patients.
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Randomised, double-blind, placebo-controlled clinical trial investigating the effects of inorganic nitrate in hypertension-induced target organ damage: protocol of the NITRATE-TOD study in the UK.
Lau, CWZ, Hamers, AJP, Rathod, KS, Shabbir, A, Cooper, J, Primus, CP, Davies, C, Mathur, A, Moon, JC, Kapil, V, et al
BMJ open. 2020;(1):e034399
Abstract
INTRODUCTION Arterial stiffness and left ventricular (LV) hypertrophy are the key markers of hypertensive target organ damage (TOD) associated with increased cardiovascular morbidity and mortality. We have previously shown that dietary inorganic nitrate supplementation lowers blood pressure (BP) in hypertension, however, whether this approach might also improve markers of hypertensive TOD is unknown. In this study, we will investigate whether daily dietary inorganic nitrate administration reduces LV mass and improves measures of arterial stiffness. METHODS AND DESIGN NITRATE-TOD is a double-blind, randomised, single-centre, placebo-controlled phase II trial aiming to enrol 160 patients with suboptimal BP control on one or more antihypertensives. Patients will be randomised to receive 4 months once daily dose of either nitrate-rich beetroot juice or nitrate-deplete beetroot juice (placebo). The primary outcomes are reduction in LV mass and reduction in pulse wave velocity (PWV) and central BP.The study has a power of 95% for detecting a 9 g LV mass change by cardiovascular MRI (~6% change for a mildly hypertrophied heart of 150 g). For PWV, we have a power of >95% for detecting a 0.6 m/s absolute change. For central systolic BP, we have a>90% power to detect a 5.8 mm Hg difference in central systolic BP.Secondary end points include change in ultrasound flow-mediated dilation, change in plasma nitrate and nitrite concentration and change in BP. ETHICS AND DISSEMINATION The study was approved by the London-City and East Research Ethics Committee (10/H0703/98). Trial results will be published according to the Consolidated Standards of Reporting Trials statement and will be presented at conferences and reported in peer-reviewed journals. TRIAL REGISTRATION NUMBER NCT03088514.
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The Short-Term Effects of Roux-en-Y Gastric Bypass on Renal Excretion of Sodium and Its Association with Blood Pressure.
López-Martínez, JE, Chávez-Negrete, A, Rodríguez-González, AA, Molina-Ayala, MA, Villanueva-Recillas, S, Maravilla, P, Reséndiz-Barragán, AM, Rentería-Palomo, E, Rojano-Rodríguez, ME
Obesity surgery. 2020;(1):102-110
Abstract
INTRODUCTION Bariatric surgery has been shown to be effective in reducing weight and has benefits, such as lowering blood pressure. An increase in urinary sodium excretion has been suggested as a possible mechanism. This study explored changes in sodium excretion and their correlation with blood pressure after Roux-en-Y gastric bypass. MATERIALS AND METHODS This study was conducted on 28 obese participants with body mass index (BMI) of 44.54 ± 7.81 kg/m2 who underwent gastric bypass. Before surgery and at the third and sixth months after gastric bypass, blood pressure, urinary sodium concentration, 24-hour (24-h) urinary sodium excretion, and fractional excretion of sodium were evaluated. In addition, serum sodium and potassium levels were determined. Nonparametric tests were used to analyze the data. RESULTS Blood pressure decreased after surgery and remained at low levels over the 3- and 6-month periods. The urinary sodium concentration increased at 3 months after surgery; however, the 24-h urinary sodium excretion and urine volume decreased. Interestingly, although some associations between variables were observed, significant correlations between the 24-h urinary sodium excretion and the systolic, diastolic, and mean blood pressures were found. In addition, the urine volume was higher in the sixth month than in the third month following surgery. CONCLUSIONS In the months immediately following surgery, a low-salt and low-volume diet favors decreases in urine volume and 24-h urinary sodium excretion. In addition, in the sixth month after surgery, an association between blood pressure and 24-h urinary sodium excretion was observed.