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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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14-Day Ketone Supplementation Lowers Glucose and Improves Vascular Function in Obesity: A Randomized Crossover Trial.
Walsh, JJ, Neudorf, H, Little, JP
The Journal of clinical endocrinology and metabolism. 2021;(4):e1738-e1754
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CONTEXT Postprandial hyperglycemia increases systemic inflammation and is a risk factor for cardiovascular disease. A ketone monoester (KME) drink containing β-hydroxybutyrate (β-OHB) rapidly lowers plasma glucose, which may be a strategy protecting against postprandial hyperglycemia. OBJECTIVE We hypothesized that KME would attenuate 2-hour postprandial glucose, lower systemic inflammation, and improve vascular function in adults with obesity. METHODS In a randomized crossover design, 14 participants with obesity (age = 56 ± 12 years; body mass index = 32.8 ± 7.7 kg/m2) consumed KME (12 g β-OHB) or placebo 15 minutes prior to each meal for 14 days with all meals provided and matched between conditions. Postprandial glycemia was assessed by continuous glucose monitoring. Vascular function and inflammation were assessed before and after treatment periods. RESULTS Postprandial glucose was 8.0% lower in KME versus placebo (g = 0.735; P = 0.011) and 24-hour average glucose reduced by 7.8% (g = 0.686; P = 0.0001). Brachial artery flow-mediated dilation increased from 6.2 ± 1.5% to 8.9 ± 3.3% in KME (g = 1.05; P = 0.0004) with no changes in placebo (condition × time interaction, P = 0.004). There were no changes in plasma cytokines; however, lipopolysaccharide-stimulated monocyte caspase-1 activation was lower following KME supplementation versus placebo (stimulation × condition × time interaction; P = 0.004). The KME supplement was well tolerated by participants and adherence to the supplementation regimen was very high. CONCLUSIONS In adults with obesity, 14 days of premeal KME supplementation improves glucose control, enhances vascular function, and may reduce cellular inflammation. KME supplementation may be a viable, nonpharmacological approach to improving and protecting vascular health in people with heightened cardiometabolic risk.
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Impact of prolonged sitting and physical activity breaks on cognitive performance, perceivable benefits, and cardiometabolic health in overweight/obese adults: The role of meal composition.
Wanders, L, Cuijpers, I, Kessels, RPC, van de Rest, O, Hopman, MTE, Thijssen, DHJ
Clinical nutrition (Edinburgh, Scotland). 2021;(4):2259-2269
Abstract
BACKGROUND & AIMS Physical activity (PA) breaks may effectively attenuate the detrimental impact of prolonged sitting on acute cognitive performance, perceivable benefits (e.g. mood), vascular function, and metabolic health. To date, the impact of meal composition on the effects of sedentary behavior and/or PA breaks on health has been scarcely studied. Therefore, our aim was to investigate whether meal composition alters how sedentary behavior and PA breaks affect these acute health outcomes. METHODS A total of 24 overweight and obese, sedentary adults completed four conditions in randomized order in a cross-over design: [a] high-protein, low-fat breakfast (HPLF) + 4hrs uninterrupted sitting (SIT), [b] HPLF + 4hrs interrupted sitting (ACT; 5-min cycling every 30 min), [c] Western breakfast (WEST; higher in fats/simple sugars, lower in protein/fiber) + SIT, [d] WEST + ACT. WEST and HPLF were isocaloric. Linear mixed models were used to examine changes in cognitive performance (Test of Attentional Performance), perceivable benefits (Likert-scales, Profile of Mood States questionnaire), vascular health (carotid artery reactivity, blood pressure), and metabolic health (post-breakfast glucose, insulin, lipids). RESULTS Independent of meal composition, we did not observe any effect of PA breaks on cognitive performance, vascular health and post-breakfast lipid responses. PA breaks delayed post-breakfast mood and vigor decrements, as well as increases in fatigue and sleepiness (all p < 0.05), but effects were independent of meal composition (p > 0.05). WEST resulted in higher post-breakfast glucose levels compared to HPLF (p < 0.05), while PA breaks did not impact this response (p > 0.05). PA breaks reduced post-breakfast insulin (p < 0.05), which did not differ between meals (p > 0.05). CONCLUSIONS The acute impact of PA breaks and/or prolonged sitting on cognitive performance, perceivable benefits, and vascular and metabolic health was not altered by the composition of a single meal in overweight/obese, sedentary adults. Possibly, breaking up prolonged sitting, rather than meal composition, is a more potent strategy to impact acute health outcomes, such as perceivable benefits and insulin levels.
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Acute cardiometabolic effects of brief active breaks in sitting for patients with rheumatoid arthritis.
Pinto, AJ, Meireles, K, Peçanha, T, Mazzolani, BC, Smaira, FI, Rezende, D, Benatti, FB, Ribeiro, ACM, Pinto, ALS, Lima, FR, et al
American journal of physiology. Endocrinology and metabolism. 2021;(6):E782-E794
Abstract
Exercise is a treatment in rheumatoid arthritis, but participation in moderate-to-vigorous exercise is challenging for some patients. Light-intensity breaks in sitting could be a promising alternative. We compared the acute effects of active breaks in sitting with those of moderate-to-vigorous exercise on cardiometabolic risk markers in patients with rheumatoid arthritis. In a crossover fashion, 15 women with rheumatoid arthritis underwent three 8-h experimental conditions: prolonged sitting (SIT), 30-min bout of moderate-to-vigorous exercise followed by prolonged sitting (EX), and 3-min bouts of light-intensity walking every 30 min of sitting (BR). Postprandial glucose, insulin, c-peptide, triglycerides, cytokines, lipid classes/subclasses (lipidomics), and blood pressure responses were assessed. Muscle biopsies were collected following each session to assess targeted proteins/genes. Glucose [-28% in area under the curve (AUC), P = 0.036], insulin (-28% in AUC, P = 0.016), and c-peptide (-27% in AUC, P = 0.006) postprandial responses were attenuated in BR versus SIT, whereas only c-peptide was lower in EX versus SIT (-20% in AUC, P = 0.002). IL-1β decreased during BR, but increased during EX and SIT (P = 0.027 and P = 0.085, respectively). IL-1ra was increased during EX versus BR (P = 0.002). TNF-α concentrations decreased during BR versus EX (P = 0.022). EX, but not BR, reduced systolic blood pressure (P = 0.013). Lipidomic analysis showed that 7 of 36 lipid classes/subclasses were significantly different between conditions, with greater changes being observed in EX. No differences were observed for protein/gene expression. Brief active breaks in sitting can offset markers of cardiometabolic disturbance, which may be particularly useful for patients who may find it difficult to adhere to exercise.NEW & NOTEWORTHY Exercise is a treatment in rheumatoid arthritis but is challenging for some patients. Light-intensity breaks in sitting could be a promising alternative. Our findings show beneficial, but differential, cardiometabolic effects of active breaks in sitting and exercise in patients with rheumatoid arthritis. Breaks in sitting mainly improved glycemic and inflammatory markers, whereas exercise improved lipidomic and hypotensive responses. Breaks in sitting show promise in offsetting aspects of cardiometabolic disturbance associated with prolonged sitting in rheumatoid arthritis.
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Effects of Linagliptin on Cardiovascular and Kidney Outcomes in People With Normal and Reduced Kidney Function: Secondary Analysis of the CARMELINA Randomized Trial.
Perkovic, V, Toto, R, Cooper, ME, Mann, JFE, Rosenstock, J, McGuire, DK, Kahn, SE, Marx, N, Alexander, JH, Zinman, B, et al
Diabetes care. 2020;(8):1803-1812
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OBJECTIVE Type 2 diabetes is a leading cause of kidney failure, but few outcome trials proactively enrolled individuals with chronic kidney disease (CKD). We performed secondary analyses of cardiovascular (CV) and kidney outcomes across baseline estimated glomerular filtration rate (eGFR) categories (≥60, 45 to <60, 30 to <45, and <30 mL/min/1.73 m2) in Cardiovascular and Renal Microvascular Outcome Study With Linagliptin (CARMELINA), a cardiorenal placebo-controlled outcome trial of the dipeptidyl peptidase 4 inhibitor linagliptin (NCT01897532). RESEARCH DESIGN AND METHODS Participants with CV disease and/or CKD were included. The primary outcome was time to first occurrence of CV death, nonfatal myocardial infarction, or nonfatal stroke (three-point major adverse CV event [3P-MACE]), with a secondary outcome of renal death, end-stage kidney disease, or sustained ≥40% decrease in eGFR from baseline. Other end points included progression of albuminuria, change in HbA1c, and adverse events (AEs) including hypoglycemia. RESULTS A total of 6,979 subjects (mean age 65.9 years; eGFR 54.6 mL/min/1.73 m2; 80.1% albuminuria) were followed for 2.2 years. Across eGFR categories, linagliptin as compared with placebo did not affect the risk for 3P-MACE (hazard ratio 1.02 [95% CI 0.89, 1.17]) or the secondary kidney outcome (1.04 [0.89, 1.22]) (interaction P values >0.05). Regardless of eGFR, albuminuria progression was reduced with linagliptin, as was HbA1c, without increasing risk for hypoglycemia. AEs were balanced among groups overall and across eGFR categories. CONCLUSIONS Across all GFR categories, in participants with type 2 diabetes and CKD and/or CV disease, there was no difference in risk for linagliptin versus placebo on CV and kidney events. Significant reductions in risk for albuminuria progression and HbA1c and no difference in AEs were observed.
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The Effect of a Single Dose of Dark Chocolate on Cardiovascular Parameters and Their Reactivity to Mental Stress.
Regecova, V, Jurkovicova, J, Babjakova, J, Bernatova, I
Journal of the American College of Nutrition. 2020;(5):414-421
Abstract
Objective: This study investigated the effect of a single administration of dark or milk chocolate on blood pressure (BP), heart rate (HR), and double product (DP) in young healthy women at rest and during acute mental stress.Method: Measurements consisted of anthropometry, BP, and HR. Mean arterial BP (MAP) and DP were computed. The relative reactivity of individual variables was quantified as to their percentage change during the rest or test of mental arithmetic (MA) with respect to the respective baseline value. All subjects underwent two tests of MA-one before chocolate administration and the second one 2 hours after chocolate (1 mg/g of body weight) ingestion.Results: Two hours after ingestion at rest, dark chocolate administration resulted in a significant increase in relative values of systolic BP and DP by 5.1% ± 1.4% and 13.7% ± 3.2%, respectively, compared to the responses in the milk chocolate group (-2.4% ± 1.6% and 0.6% ± 3.4%, respectively, p < 0.04 for both comparisons) without changes in diastolic BP, HR, and MAP. During MA-induced acute stress, the relative magnitude of the reactivity of diastolic BP, HR, MAP, and DP decreased by about 10, 16, 8, and 23 percentage points, respectively, 2 hours after ingestion of dark chocolate compared to the relative reactivity determined before dark chocolate ingestion. Milk chocolate failed to affect any of the above-mentioned parameters at rest or during stress.Conclusions: The single oral intake of 85% dark chocolate increased relative values of systolic BP and DP at rest but buffered the reactivity of diastolic BP, HR, MAP, and DP during mental stress, which was not found after ingestion of milk chocolate. Thus, dark chocolate might have a beneficial effect during acute stress due to its ability to buffer cardiovascular reactivity in young healthy women.
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Avocado (Persea americana) pulp improves cardiovascular and autonomic recovery following submaximal running: a crossover, randomized, double-blind and placebo-controlled trial.
Sousa, FH, Valenti, VE, Pereira, LC, Bueno, RR, Prates, S, Akimoto, AN, Kaviani, M, Garner, DM, Amaral, JAT, de Abreu, LC
Scientific reports. 2020;(1):10703
Abstract
Previous studies have demonstrated that regular avocado consumption presents advantageous effects on cardiovascular system. However, little attention has been paid to the use of avocado as a dietary supplement, in particular, for individuals involved in physical exercise training. Therefore, this study aims to evaluate the effect of acute avocado pulp intake on cardiovascular and autonomic recovery subsequent to moderate exercise. Using a crossover, randomized, double-blind and placebo-controlled trial design, 16 healthy female adults underwent two protocols: Avocado pulp (600 mg in capsule) and placebo (600 mg starch in capsule). After the ingestion of Avocado pulp or placebo, the subjects were seated for 60 min at rest, followed by running on a treadmill at a submaximal level and then remained seated for 60 min during recovery from the exercise. Heart rate (HR), heart rate variability (HRV) [rMSSD, SD1, HF (ms2)] and skin conductance were evaluated before and during exercise, as well as during recovery. HR, systolic blood pressure, HRV and skin conductance recovered faster when subjects were given avocado pulp prior to exercise. In conclusion, avocado pulp improved cardiovascular and autonomic recovery after exercise, suggesting a reduced risk of cardiovascular events after exertion. The current results support the beneficial effects of ingestion of avocado prior to submaximal treadmill running.
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Effects of Low-Energy Diet or Exercise on Cardiovascular Function in Working-Age Adults With Type 2 Diabetes: A Prospective, Randomized, Open-Label, Blinded End Point Trial.
Gulsin, GS, Swarbrick, DJ, Athithan, L, Brady, EM, Henson, J, Baldry, E, Argyridou, S, Jaicim, NB, Squire, G, Walters, Y, et al
Diabetes care. 2020;(6):1300-1310
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OBJECTIVE To confirm the presence of subclinical cardiovascular dysfunction in working-age adults with type 2 diabetes (T2D) and determine whether this is improved by a low-energy meal replacement diet (MRP) or exercise training. RESEARCH DESIGN AND METHODS This article reports on a prospective, randomized, open-label, blinded end point trial with nested case-control study. Asymptomatic younger adults with T2D were randomized 1:1:1 to a 12-week intervention of 1) routine care, 2) supervised aerobic exercise training, or 3) a low-energy (∼810 kcal/day) MRP. Participants underwent echocardiography, cardiopulmonary exercise testing, and cardiac magnetic resonance (CMR) at baseline and 12 weeks. The primary outcome was change in left ventricular (LV) peak early diastolic strain rate (PEDSR) as measured by CMR. Healthy volunteers were enrolled for baseline case-control comparison. RESULTS Eighty-seven participants with T2D (age 51 ± 7 years, HbA1c 7.3 ± 1.1%) and 36 matched control participants were included. At baseline, those with T2D had evidence of diastolic dysfunction (PEDSR 1.01 ± 0.19 vs. 1.10 ± 0.16 s-1, P = 0.02) compared with control participants. Seventy-six participants with T2D completed the trial (30 routine care, 22 exercise, and 24 MRP). The MRP arm lost 13 kg in weight and had improved blood pressure, glycemia, LV mass/volume, and aortic stiffness. The exercise arm had negligible weight loss but increased exercise capacity. PEDSR increased in the exercise arm versus routine care (β = 0.132, P = 0.002) but did not improve with the MRP (β = 0.016, P = 0.731). CONCLUSIONS In asymptomatic working-age adults with T2D, exercise training improved diastolic function. Despite beneficial effects of weight loss on glycemic control, concentric LV remodeling, and aortic stiffness, a low-energy MRP did not improve diastolic function.
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Effect of Canagliflozin on Renal and Cardiovascular Outcomes across Different Levels of Albuminuria: Data from the CANVAS Program.
Neuen, BL, Ohkuma, T, Neal, B, Matthews, DR, de Zeeuw, D, Mahaffey, KW, Fulcher, G, Li, Q, Jardine, M, Oh, R, et al
Journal of the American Society of Nephrology : JASN. 2019;(11):2229-2242
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BACKGROUND If SGLT2 inhibitors protect the kidneys by reducing albuminuria as hypothesized, people with type 2 diabetes mellitus (T2DM) with higher albuminuria should benefit more. METHODS We conducted a post-hoc analysis of data from the CANagliflozin cardioVascular Assessment Study (CANVAS) Program, which randomized 10,142 participants with T2DM and high cardiovascular risk to canagliflozin or placebo. We assessed effects of canagliflozin on renal, cardiovascular, and safety outcomes by baseline albuminuria. The trial included 2266 participants (22.3%) with moderately increased albuminuria (urinary albumin/creatinine ratio [UACR] 30-300 mg/g) and 760 (7.5%) with severely increased albuminuria (UACR >300 mg/g) at baseline. RESULTS Canagliflozin lowered albuminuria with greater proportional reductions in those with moderately and severely increased albuminuria (P heterogeneity<0.001). After week 13, canagliflozin slowed the annual loss of kidney function across albuminuria subgroups, with greater absolute reductions in participants with severely increased albuminuria (placebo-subtracted difference 3.01 ml/min per 1.73 m2 per year; P heterogeneity<0.001). Heterogeneity for the renal composite outcome of 40% reduction in eGFR, ESKD, or renal-related death was driven by lesser effects in participants with moderately increased albuminuria (P heterogeneity=0.03), but no effect modification was observed when albuminuria was fitted as a continuous variable (P heterogeneity=0.94). Cardiovascular and safety outcomes were mostly consistent across albuminuria levels including increased risks for amputation across albuminuria subgroups (P heterogeneity=0.66). Greater absolute risk reductions in the renal composite outcome were observed in participants with severely increased albuminuria (P heterogeneity=0.004). CONCLUSIONS The proportional effects of canagliflozin on renal and cardiovascular outcomes are mostly consistent across patients with different levels of albuminuria, but absolute benefits are greatest among those with severely increased albuminuria.
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Effects of curcumin on cardiovascular risk factors in obese and overweight adolescent girls: a randomized clinical trial.
Saraf-Bank, S, Ahmadi, A, Paknahad, Z, Maracy, M, Nourian, M
Sao Paulo medical journal = Revista paulista de medicina. 2019;(5):414-422
Abstract
BACKGROUND Obese adolescents are at higher risk of development of cardiovascular risk factors and obesity in later life. Dietary intake of antioxidants, particularly curcumin, as an active ingredient of turmeric extract, may have noticeable effects on obesity and its important complications such as cardiovascular risk factors. Therefore, the aim of this study was to assess the effects of curcumin supplementation on cardiovascular risk factors among overweight and obese female adolescents. DESIGN AND SETTING Randomized placebo-controlled clinical trial; Pediatric Cardiovascular Research Center, Isfahan, Iran. METHODS 60 adolescent girls (aged 13-18 years) were randomly assigned to receive either placebo or intervention. The adolescents were asked to consume one 500 mg tablet per day, containing either standardized 95% turmeric extract or placebo, and to undergo a weight maintenance or a mild weight loss diet for 10 weeks. Anthropometric and biochemical indices were assessed at the baseline and the end of the intervention. RESULTS Curcumin supplementation had beneficial effects on body mass index (P = 0.019), waist circumference (P = 0.008), hip circumference (P = 0.030), high-density lipoprotein levels (P = 0.042) and triglyceride/high-density lipoprotein ratio (P = 0.021). However, in univariate analysis of covariance, no significant differences were found between the intervention and placebo groups after 10 weeks of supplementation (P > 0.05). CONCLUSIONS Prescription of curcumin supplementation along with use of a slight weight loss diet might have beneficial effects on some cardiovascular risk factors among overweight and obese female adolescents. Larger clinical trials with higher curcumin doses and longer duration are needed to confirm the results from the current study. CLINICAL TRIAL REGISTRATION IRCT20171107037302N1.