-
1.
Absence of effect of steady state bempedoic acid on cardiac repolarization: Results of a thorough QT/QTc study in healthy volunteers.
Amore, BM, Cramer, CT, MacDougall, DE, Sasiela, WJ, Emery, MG
Clinical and translational science. 2021;(6):2487-2496
-
-
Free full text
-
Abstract
Bempedoic acid is an inhibitor of adenosine triphosphate-citrate lyase approved for use in adults with hypercholesterolemia. Nonclinical studies assessed binding to the human ether-a-go-go-related gene (hERG) potassium channel in vitro and the effect of bempedoic acid on QT/QTc in cynomolgus monkeys. A randomized, double-blind, parallel-design clinical study assessed the effects of steady-state bempedoic acid at a supratherapeutic dose (240 mg/day, 33.3% higher the180 mg/day therapeutic dose), placebo, and moxifloxacin (400 mg) in healthy subjects. In vitro binding potency for bempedoic acid to the hERG potassium channel was weak, with half-maximal inhibition (IC50 ) estimated at greater than 1000 μM (>1670-fold the bempedoic acid 180 mg/day steady-state unbound maximum concentration). In monkeys, individual rate-corrected QT intervals showed no time- or dose-dependent changes up to 100 mg/kg of bempedoic acid. In human subjects, the upper 90% confidence interval (CI) for the difference in QTc interval, corrected using Fridericia's formula (QTcF), between bempedoic acid and placebo was less than 5 msec at all time points. Concentration-QTcF analysis showed that maximum bempedoic acid concentration at steady-state was attained at a median 2.1 h postdose, and the predicted mean change (90% CI) in QTcF at the observed mean bempedoic acid concentration 2 h postdose was -0.5 (-5.0, 4.0) msec. The lower bound of the moxifloxacin 90% CI exceeded 5 msec at prespecified time points, establishing study sensitivity. Steady-state bempedoic acid at a supratherapeutic dose of 240 mg was generally well-tolerated and not associated with QTc prolongation in healthy subjects.
-
2.
Effects of age on blood pressure and heart rate responses to whey protein in younger and older men.
Giezenaar, C, Oberoi, A, Jones, KL, Horowitz, M, Chapman, I, Soenen, S
Journal of the American Geriatrics Society. 2021;(5):1291-1299
Abstract
BACKGROUND Postprandial falls in blood pressure (BP) are more common in older compared to younger individuals. The effects of protein compared to carbohydrates and fat on postprandial BP, and the relation to gastric emptying rates, are poorly studied. OBJECTIVES To determine the effects of a whey protein compared to a control drink on systolic BP (SBP) and diastolic BP (DBP), and heart rate (HR) in healthy younger and older men, and to relate these effects to gastric emptying. DESIGN A pooled analyses of two randomized, double-blind, cross-over studies. SETTING Two acute clinical intervention studies with identical study design. PARTICIPANTS Nineteen older (age: 74 ± 1 years, body mass index: 26 ± 1 kg/m2 ) and 13 younger (23 ± 1 years, 24 ± 1 kg/m2 ) healthy men. INTERVENTION A 70 g/280 kcal whey-protein or control (water with diet cordial, ~2 kcal) drink (450 ml). MEASUREMENTS BP and HR were assessed with an automated device immediately before and at 3-min intervals after drink ingestion (0-180 min). Gastric emptying of the drinks was measured using 3D ultrasonography (0-180 min). RESULTS Older versus younger men exhibited a greater fall in SBP (-23 ± 2 vs -15 ± 2 mmHg, p = 0.001) after whey-protein versus control, as BP did not change after the two drinks in younger men (p > 0.05). The nadir in SBP occurred later in the older than younger men (114 ± 11 vs 62 ± 14 min; p < 0.001), with SBP still apparently declining 180 min after whey-protein ingestion in the older men. The magnitude of the rise in HR was greater (p < 0.05) in the younger than older men. CONCLUSION Following ingestion of 70 g whey protein, healthy older men exhibited a sustained fall in BP, despite an increase in HR, whereas in younger men there was no change in BP. BP may need to be monitored after high protein meals in older people at risk of postprandial hypotension.
-
3.
Nicotine supplementation enhances simulated game performance of archery athletes.
Hung, BL, Chen, LJ, Chen, YY, Ou, JB, Fang, SH
Journal of the International Society of Sports Nutrition. 2021;(1):16
Abstract
BACKGROUND Nicotine is beneficial to mood, arousal and cognition in humans. Due to the importance of cognitive functioning for archery athletes, we investigated the effects of nicotine supplementation on the cognitive abilities, heart rate variability (HRV), and sport performance of professional archers. METHODS Eleven college archers were recruited and given 2 mg of nicotine supplementation (NIC group) and placebo (PLA group) in a crossover design. RESULTS The results showed that at 30 min after the intake of nicotine gum, the "correct rejection" time in the NIC group was significantly lower than that of the PLA group (7.29 ± 0.87 vs. 8.23 ± 0.98 msec, p < 0.05). In addition, the NIC group completed the grooved pegboard test in a shorter time than the PLA group (48.76 ± 3.18 vs. 53.41 ± 4.05 s, p < 0.05), whereas motor reaction times were not different between the two groups. Saliva α-amylase activity was significantly lower after nicotine supplementation (p < 0.01) but increased immediately after the archery test in the NIC group (p < 0.05). In addition, nicotine supplementation significantly decreased HRV and increased the archery score (290.58 ± 10.09 vs. 298.05 ± 8.56, p < 0.01). CONCLUSIONS Nicotine enhances the performance of archery athletes by increasing cognitive function and stimulating the sympathetic adrenergic system.
-
4.
Effect of High Dietary Sodium Intake in Patients With Postural Tachycardia Syndrome.
Garland, EM, Gamboa, A, Nwazue, VC, Celedonio, JE, Paranjape, SY, Black, BK, Okamoto, LE, Shibao, CA, Biaggioni, I, Robertson, D, et al
Journal of the American College of Cardiology. 2021;(17):2174-2184
Abstract
BACKGROUND High sodium intake is recommended for the treatment of postural tachycardia syndrome (POTS) to counteract the hypovolemia and elevated plasma norepinephrine that contribute to excessive orthostatic tachycardia, but evidence of its efficacy is not available. OBJECTIVES This study tested whether a high sodium (HS) diet reduces orthostatic tachycardia (Δ heart rate) and upright heart rate compared with a low sodium (LS) diet in POTS patients, and secondarily its effect on plasma volume (PV) and plasma norepinephrine. METHODS A total of 14 POTS patients and 13 healthy control subjects (HC), age 23 to 49 years, were enrolled in a crossover study with 6 days of LS (10 mEq sodium/day) or HS (300 mEq sodium/day) diet. Supine and standing heart rate, blood pressure, serum aldosterone, plasma renin activity, blood volume, and plasma norepinephrine and epinephrine were measured. RESULTS In POTS, the HS diet reduced upright heart rate and Δ heart rate compared with the LS diet. Total blood volume and PV increased, and standing norepinephrine decreased with the HS compared with the LS diet. However, upright heart rate, Δ heart rate, and upright norepinephrine remained higher in POTS than in HC on the HS diet (median 117 beats/min [interquartile range: 98 to 121 beats/min], 46 beats/min [interquartile range: 32 to 55 beats/min], and 753 pg/ml [interquartile range: 498 to 919 pg/ml] in POTS vs. 85 beats/min [interquartile range: 77 to 95 beats/min], 19 beats/min [interquartile range: 11 to 32 beats/min], and 387 pg/ml [interquartile range: 312 to 433 pg/ml] in HC, respectively), despite no difference in the measured PV. CONCLUSIONS In POTS patients, high dietary sodium intake compared with low dietary sodium intake increases plasma volume, lowers standing plasma norepinephrine, and decreases Δ heart rate. (Dietary Salt in Postural Tachycardia Syndrome; NCT01547117).
-
5.
The effects of varying doses of caffeine on cardiac parasympathetic reactivation following an acute bout of anaerobic exercise in recreational athletes.
Sarshin, A, Naderi, A, da Cruz, CJG, Feizolahi, F, Forbes, SC, Candow, DG, Mohammadgholian, E, Amiri, M, Jafari, N, Rahimi, A, et al
Journal of the International Society of Sports Nutrition. 2020;(1):44
Abstract
BACKGROUND To examine the effects of varying doses of caffeine on autonomic reactivation following anaerobic exercise. METHODS Recreationally active males (N = 20; 24 ± 2y) participated in a randomized, double-blind, placebo-controlled, crossover study where participants ingested: [1] Control (CON; no supplement), [2] a non-caffeinated placebo (PLA), [3] 3-mg∙kg- 1 of caffeine (CAF3) or [4] 6-mg∙kg- 1 of caffeine (CAF6) prior to Wingate testing. Parasympathetic (lnRMSSD, primary outcome) and global HRV (lnSDNN, secondary outcome) were assessed at rest (i.e., pre-ingestion), 45-min post-ingestion, and 5-min and 35-min post-exercise recovery. We used a GLM to assess mean (95% CI) changes from pre-ingestion baseline. RESULTS Overall, we observed a significant trend for lnRMSSD and lnSDNN (both, p = 0.001, ηp2 = 0.745). Forty-five minutes after treatment ingestion, we observed a significant increase in lnRMSSD for CAF3 (0.15 ms, 95%CI, 0.07,0.24) and CAF6 (0.16 ms, 95%CI, 0.06,0.25), both being significant (both, p < 0.004) vs. CON (- 0.02 ms, 95%CI, - 0.09,0.04). Five-minutes after exercise, all treatments demonstrated significant declines in lnRMSSD vs. baseline (all, p < 0.001). After 35-min of recovery, lnRMSSD returned to a level not significantly different than baseline for CAF3 (0.03 ms, 95%CI, - 0.05, 0.12) and CAF6 (- 0.03 ms, 95%CI, - 0.17, 0.10), while PLA (- 0.16 ms, 95%CI, - 0.25, - 0.06) and CON (- 0.17 ms, 95%CI, - 0.28, - 0.07) treatments remained significantly depressed. A similar pattern was also observed for SDNN. CONCLUSION Caffeine ingestion increases resting cardiac autonomic modulation and accelerates post-exercise autonomic recovery after a bout of anaerobic exercise in recreationally active young men. However, no differences between caffeine doses on cardiac autonomic reactivity were observed.
-
6.
Effect of Moderate- Versus High-Intensity Interval Exercise Training on Heart Rate Variability Parameters in Inactive Latin-American Adults: A Randomized Clinical Trial.
Ramírez-Vélez, R, Tordecilla-Sanders, A, Téllez-T, LA, Camelo-Prieto, D, Hernández-Quiñonez, PA, Correa-Bautista, JE, Garcia-Hermoso, A, Ramírez-Campillo, R, Izquierdo, M
Journal of strength and conditioning research. 2020;(12):3403-3415
Abstract
Ramírez-Vélez, R, Tordecilla-Sanders, A, Téllez-T, LA, Camelo-Prieto, D, Hernández-Quiñonez, PA, Correa-Bautista, JE, Garcia-Hermoso, A, Ramírez-Campillo, R, and Izquierdo, M. Effect of moderate- versus high-intensity interval exercise training on heart rate variability parameters in inactive Latin-American adults: a randomized clinical trial. J Strength Cond Res 34(12): 3403-3415, 2020-We investigated the effect of moderate versus high-intensity interval exercise training on the heart rate variability (HRV) indices in physically inactive adults. Twenty inactive adults were randomly allocated to receive either moderate-intensity training (MCT group) or high-intensity interval training (HIT group). The MCT group performed aerobic training at an intensity of 55-75%, which consisted of walking on a treadmill at 60-80% of the maximum heart rate (HRmax) until the expenditure of 300 kcal. The HIT group ran on a treadmill for 4 minutes at 85-95% peak HRmax and had a recovery of 4 minutes at 65% peak HRmax until the expenditure of 300 kcal. Supine resting HRV indices (time domain: SDNN = SD of normal-to-normal intervals; rMSSD = root mean square successive difference of R-R intervals and frequency domain: HFLn = high-frequency spectral power; LF = low-frequency spectral power and HF/LF ratio) were measured at baseline and 12 weeks thereafter. The SDNN changes were 3.4 (8.9) milliseconds in the MCT group and 29.1 (7.6) milliseconds in the HIT group {difference between groups 32.6 (95% confidence interval, 24.9 to 40.4 [p = 0.01])}. The LF/HFLn ratio changes were 0.19 (0.03) milliseconds in the MCT group and 0.13 (0.01) milliseconds in the HIT group (p between groups = 0.016). No significant group differences were observed for the rMSSD, HF, and LF parameters. In inactive adults, this study showed that a 12-week HIT training program could increase short-term HRV, mostly in vagally mediated indices such as SDNN and HF/LFLn ratio power. Trial registration. ClinicalTrials.gov NCT02738385 https://clinicaltrials.gov/ct2/show/NCT01796275, registered on March 23, 2016.
-
7.
Snacking on Whole Almonds for Six Weeks Increases Heart Rate Variability during Mental Stress in Healthy Adults: A Randomized Controlled Trial.
Dikariyanto, V, Smith, L, Chowienczyk, PJ, Berry, SE, Hall, WL
Nutrients. 2020;(6)
Abstract
Cardiac autonomic regulation can be indirectly measured by heart rate variability (HRV). Low HRV, which can be induced by mental stress, is a predictor of risk of sudden cardiac death. Few studies have investigated cause-and-effect relationships between diet and HRV. Nut consumption is associated with CVD risk reduction, but the impact on HRV, particularly in response to stress, is unclear. Men and women (30-70 y) with above average risk of developing CVD were randomly assigned in a 6-week randomized, controlled, parallel arm trial to consume either whole almond or isocaloric control snacks (20% of daily estimated energy requirement). Control snacks contained the average nutrient profile of UK snacks. Five-minute periods of supine heart rate (HR) and HRV were measured at resting and during mental stress (Stroop color-word test) at baseline and six weeks. High frequency (HF) power, which reflects parasympathetic regulation of HR, was increased following almonds during the mental stress task relative to control (mean difference between groups 124 ms2; 95% CI 11, 237; p = 0.031, n = 105), but other indices were unaffected. Snacking on whole almonds instead of typical snacks may reduce risk of CVD partly by ameliorating the suppression of HRV during periods of mental stress.
-
8.
Cardiovascular and metabolic responses to passive hypoxic conditioning in overweight and mildly obese individuals.
Chacaroun, S, Borowik, A, Doutreleau, S, Belaidi, E, Wuyam, B, Tamisier, R, Pépin, JL, Flore, P, Verges, S
American journal of physiology. Regulatory, integrative and comparative physiology. 2020;(2):R211-R222
Abstract
Although severe intermittent hypoxia (IH) is well known to induce deleterious cardiometabolic consequences, moderate IH may induce positive effects in obese individuals. The present study aimed to evaluate the effect of two hypoxic conditioning programs on cardiovascular and metabolic health status of overweight or obese individuals. In this randomized single-blind controlled study, 35 subjects (54 ± 9.3 yr, 31.7 ± 3.5 kg/m2) were randomized into three 8-wk interventions (three 1-h sessions per week): sustained hypoxia (SH), arterial oxygen saturation ([Formula: see text]) = 75%; IH, 5 min [Formula: see text] = 75% - 3 min normoxia; normoxia. Ventilation, heart rate, blood pressure, and tissue oxygenation were measured during the first and last hypoxic conditioning sessions. Vascular function, blood glucose and insulin, lipid profile, nitric oxide metabolites, and oxidative stress were evaluated before and after the interventions. Both SH and IH increased ventilation in hypoxia (+1.8 ± 2.1 and +2.3 ± 3.6 L/min, respectively; P < 0.05) and reduced normoxic diastolic blood pressure (-12 ± 15 and -13 ± 10 mmHg, respectively; P < 0.05), whereas changes in normoxic systolic blood pressure were not significant (+3 ± 9 and -6 ± 13 mmHg, respectively; P > 0.05). IH only reduced heart rate variability (e.g., root-mean-square difference of successive normal R-R intervals in normoxia -21 ± 35%; P < 0.05). Both SH and IH induced no significant change in body mass index, vascular function, blood glucose, insulin and lipid profile, nitric oxide metabolites, or oxidative stress, except for an increase in superoxide dismutase activity following SH. This study indicates that passive hypoxic conditioning in obese individuals induces some positive cardiovascular and respiratory improvements despite no change in anthropometric data and even a reduction in heart rate variability during IH exposure.
-
9.
Ischemic preconditioning prevents impact of prolonged sitting on glucose tolerance and markers of cardiovascular health but not cerebrovascular responses.
Horiuchi, M, Thijssen, DHJ
American journal of physiology. Endocrinology and metabolism. 2020;(5):E821-E826
Abstract
Prolonged, uninterrupted sitting is demonstrated to acutely impair glucose homeostasis, but it also leads to detrimental cardiovascular health effects. We examined whether ischemic preconditioning (IPC) prevents the impact of prolonged sitting-induced glucose intolerance and measured related influencing factors such as (para)sympathetic nerve activity [assessed by heart rate variability (HRV)] and blood pressure during 2 h of prolonged sitting. In this randomized, controlled crossover study, 15 healthy participants (80% men) with a mean age of 21 ± 1 yr (means ± SD) and body mass index of 25.0 ± 2.4 kg/m2 performed IPC (IPC, 4 × 5-min 220-mmHg unilateral occlusion at the thigh muscle) or a sham intervention (sham, 4 × 5 min 20-mmHg), followed by 2 h of sitting. After IPC or sham intervention, fingertip blood glucose was measured before and after 30, 60, 90, and 120 min of 75 g of glucose ingestions. Blood glucose responses during an oral glucose tolerance test were significantly attenuated, resulting in a lower area under the curve when sitting was preceded by a bout of IPC than sham (P < 0.05). IPC increased high-frequency oscillations and decreased the ratio of low-frequency-to-high-frequency oscillations at 120 min in HRV (P < 0.05). Moreover, a lower blood pressure was observed with IPC compared with sham (P < 0.05). Prolonged sitting or IPC did not affect cerebrovascular responses (P > 0.05). Collectively, these results indicate that the application of IPC before prolonged, uninterrupted sitting bout was associated with a better glucose tolerance and prevented impairment in (para)sympathetic nerve activity and blood pressure in healthy young men and women.
-
10.
The Effect of Different Cadence on Paddling Gross Efficiency and Economy in Stand-Up Paddle Boarding.
Castañeda-Babarro, A, Santos-Concejero, J, Viribay, A, Gutiérrez-Santamaría, B, Mielgo-Ayuso, J
International journal of environmental research and public health. 2020;(13)
Abstract
Background: Due to the importance of energy efficiency and economy in endurance performance, it is important to know the influence of different paddling cadences on these variables in the stand-up paddleboarding (SUP). The purpose of this study was to determine the effect of paddling at different cadences on the energy efficiency, economy, and physiological variables of international SUP race competitors. Methods: Ten male paddlers (age 28.8 ± 11.0 years; height 175.4 ± 5.1 m; body mass 74.2 ± 9.4 kg) participating in international tests carried out two test sessions. In the first one, an incremental exercise test was conducted to assess maximal oxygen uptake and peak power output (PPO). On the second day, they underwent 3 trials of 8 min each at 75% of PPO reached in the first test session. Three cadences were carried out in different trials randomly assigned between 45-55 and 65 strokes-min-1 (spm). Heart rate (HR), blood lactate, perceived sense of exertion (RPE), gross efficiency, economy, and oxygen uptake (VO2) were measured in the middle (4-min) and the end (8-min) of each trial. Results: Economy (45.3 ± 5.7 KJ·l-1 at 45 spm vs. 38.1 ± 5.3 KJ·l-1 at 65 spm; p = 0.010) and gross efficiency (13.4 ± 2.3% at 45 spm vs. 11.0 ± 1.6% at 65 spm; p = 0.012) was higher during de 45 spm condition than 65 spm in the 8-min. Respiratory exchange ratio (RER) presented a lower value at 4-min than at 8-min in 55 spm (4-min, 0.950 ± 0.065 vs. 8-min, 0.964 ± 0.053) and 65 spm cadences (4-min, 0.951 ± 0.030 vs. 8-min, 0.992 ± 0.047; p < 0.05). VO2, HR, lactate, and RPE were lower (p < 0.05) at 45 spm (VO2, 34.4 ± 6.0 mL·kg-1·min-1; HR, 161.2 ± 16.4 beats·min-1; lactate, 3.5 ± 1.0 mmol·l-1; RPE, 6.0 ± 2.1) than at 55 spm (VO2, 38.6 ± 5.2 mL·kg-1·min-1; HR, 168.1 ± 15.1 beats·min-1; lactate, 4.2 ± 1.2 mmol·l-1; RPE, 6.9 ± 1.4) and 65 spm (VO2, 38.7 ± 5.9 mL·kg-1·min-1; HR, 170.7 ± 13.0 beats·min-1; 5.3 ± 1.8 mmol·l-1; RPE, 7.6 ± 1.4) at 8-min. Moreover, lactate and RPE at 65 spm was greater than 55 spm (p < 0.05) at 8-min. Conclusion: International male SUP paddlers were most efficient and economical when paddling at 45 spm vs. 55 or 65 spm, confirmed by lower RPE values, which may likely translate to faster paddling speed and greater endurance.