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"Cardiovascular Physiological Phenomena"
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The influence of adjuvant therapy on cardiorespiratory fitness in early-stage breast cancer seven years after diagnosis: the Cooper Center Longitudinal Study
We examined cardiorespiratory fitness (CRF) levels in early stage breast cancer patients and determined whether CRF differs as a function of adjuvant therapy regimen. A total of 180 early breast cancer patients representing three treatment groups (surgery only, single-, and multi-modality adjuvant therapy) in the Cooper Center Longitudinal Study (CCLS) were studied. A non-cancer control group (
n
= 180) matched by sex, age, and date of the CCLS visit was included. All subjects underwent an incremental exercise tolerance test to symptom limitation to assess CRF (i.e., peak metabolic equivalents [METs] and time to exhaustion). The mean time from breast cancer diagnosis to exercise tolerance testing was 7.4 ± 6.2 years. In adjusted analyses, time to exhaustion and peak METs were incrementally impaired with the addition of surgery, single-, and multi-modality adjuvant therapy compared to those of matched controls (
p
= 0.006 and 0.028, respectively). CRF was lowest in the multi-modality group compared to all other groups (all
p
’s < 0.05). Despite being 7 years post-diagnosis, asymptomatic early breast cancer survivors have marked reductions in CRF. Patients treated with multi-modal adjuvant therapy have the greatest impairment in CRF.
Journal Article
14-Day Ketone Supplementation Lowers Glucose and Improves Vascular Function in Obesity: A Randomized Crossover Trial
Abstract
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.
Journal Article
Black Soybean Improves Vascular Function and Blood Pressure: A Randomized, Placebo Controlled, Crossover Trial in Humans
Vascular dysfunction and injurious stimuli such as oxidative stress are closely related to the risk of cardiovascular diseases (CVD). Dietary polyphenols are reported to exert beneficial effects in reducing the risk of CVD. Black soybean has been used as a nutritionally rich food and contains abundant polyphenols in its seed coat and grain. Black soybean has many beneficial physiological activities, and its prevention effects on CVD risk were reported mainly in animal experiments. In this study, we performed a randomized, single blind, placebo controlled, crossover trial to investigate the effect of black soybean consumption on the vascular function in healthy humans. Twenty-two healthy adults aged from 30 to 60 completed the four week trial with daily consumption of about a 40 g test material cookie containing 20 g roasted black soybean powder. Body composition, vascular function, biomarkers for oxidative stress, and polyphenol contents in the urine and the plasma were measured. After ingestion of the black soybean cookie, vascular function, which was evaluated by plethysmogram using a Pulse Analyzer®, was improved and systolic blood pressure was decreased. Moreover, nitric oxide levels in plasma and urine were increased, while an oxidative stress biomarker, 8-hydroxy-2′-deoxyguanosine level, in the plasma was decreased accompanied by an increase in the concentration of polyphenols derived from black soybean in plasma and urine. These results suggest that the antioxidant activity of black soybean polyphenols and an increase in the nitric oxide level may contribute to the improvement of vascular function. Thus, black soybean is an attractive food material for improvement of vascular function through decreasing oxidative stress by its potent antioxidant activity and increasing the nitric oxide level in healthy humans.
Journal Article
Avocado (Persea americana) pulp improves cardiovascular and autonomic recovery following submaximal running: a crossover, randomized, double-blind and placebo-controlled trial
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 (ms
2
)] 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.
Journal Article
Hemodynamic, Autonomic, and Vascular Effects of Exposure to Coarse Particulate Matter Air Pollution from a Rural Location
Fine particulate matter (PM) air pollution is associated with numerous adverse health effects, including increased blood pressure (BP) and vascular dysfunction. Coarse PM substantially contributes to global air pollution, yet differs in characteristics from fine particles and is currently not regulated. However, the cardiovascular (CV) impacts of coarse PM exposure remain largely unknown.
Our goal was to elucidate whether coarse PM, like fine PM, is itself capable of eliciting adverse CV responses.
We performed a randomized double-blind crossover study in which 32 healthy adults (25.9 ± 6.6 years of age) were exposed to concentrated ambient coarse particles (CAP; 76.2 ± 51.5 μg/m(3)) in a rural location and filtered air (FA) for 2 hr. We measured CV outcomes during, immediately after, and 2 hr postexposures.
Both systolic (mean difference = 0.32 mmHg; 95% CI: 0.05, 0.58; p = 0.021) and diastolic BP (0.27 mmHg; 95% CI: 0.003, 0.53; p = 0.05) linearly increased per 10 min of exposure during the inhalation of coarse CAP when compared with changes during FA exposure. Heart rate was on average higher (4.1 bpm; 95% CI: 3.06, 5.12; p < 0.0001) and the ratio of low-to-high frequency heart rate variability increased (0.24; 95% CI: 0.07, 0.41; p = 0.007) during coarse particle versus FA exposure. Other outcomes (brachial flow-mediated dilatation, microvascular reactive hyperemia index, aortic hemodynamics, pulse wave velocity) were not differentially altered by the exposures.
Inhalation of coarse PM from a rural location is associated with a rapid elevation in BP and heart rate during exposure, likely due to the triggering of autonomic imbalance. These findings add mechanistic evidence supporting the biological plausibility that coarse particles could contribute to the triggering of acute CV events.
Journal Article
An indoor air filtration study in homes of elderly: cardiovascular and respiratory effects of exposure to particulate matter
Background
Exposure to particulate air pollution increases respiratory and cardiovascular morbidity and mortality, especially in elderly, possibly through inflammation and vascular dysfunction.
Methods
We examined potential beneficial effects of indoor air filtration in the homes of elderly, including people taking vasoactive drugs.
Forty-eight nonsmoking subjects (51 to 81 years) in 27 homes were included in this randomized, double-blind, crossover intervention study with consecutive two-week periods with or without the inclusion of a high-efficiency particle air filter in re-circulating custom built units in their living room and bedroom. We measured blood pressure, microvascular and lung function and collected blood samples for hematological, inflammation, monocyte surface and lung cell damage markers before and at day 2, 7 and 14 during each exposure scenario.
Results
The particle filters reduced the median concentration of PM
2.5
from approximately 8 to 4 μg/m
3
and the particle number concentration from 7669 to 5352 particles/cm
3
. No statistically significant effects of filtration as category were observed on microvascular and lung function or the biomarkers of systemic inflammation among all subjects, or in the subgroups taking (n = 11) or not taking vasoactive drugs (n = 37). However, the filtration efficacy was variable and microvascular function was within 2 days significantly increased with the actual PM
2.5
decrease in the bedroom, especially among 25 subjects not taking any drugs.
Conclusion
Substantial exposure contrasts in the bedroom and no confounding by drugs appear required for improved microvascular function by air filtration, whereas no other beneficial effect was found in this elderly population.
Journal Article
Artery Wall Assessment Helps Predict Kidney Transplant Outcome
Kidney transplant recipients have high cardiovascular risk, and vascular inflammation may play an important role. We explored whether the inflammatory state in the vessel wall was related to carotid intima-media thickness (c-IMT) and patient survival following kidney transplantation.
In this prospective observational cohort study we measured c-IMT and expression of proinflammatory cytokines and adhesion molecules in the inferior epigastric artery in 115 kidney transplant candidates. Another c-IMT measurement was done 1-year post-transplantation in 107. By stepwise multiple regression analysis we explored factors associated with baseline c-IMT and their changes over time. Multivariate Cox regression analysis was constructed to identify risk factors for mortality.
A worse cardiovascular profile (older age, smoker, diabetic, carotid plaque, systolic blood pressure and vascular calcification) and higher VCAM-1 levels were found in patients in the highest baseline c-IMT tertile, who also had a worse survival. Factors independently related to baseline c-IMT were age (β=0.369, P<0.0001), fasting glucose (β=0.168, P=0.045), smoking (β=0.228, P=0.003) and VCAM-1 levels (β=0.244, P=0.002). Independent factors associated with c-IMT measurement 1-year post-transplantation were baseline c-IMT (β=-0.677, P<0.0001), post-transplant diabetes (β=0.225, P=0.003) and triglycerides (β=0.302, P=0.023). Vascular VCAM-1 levels were associated with increased risk of mortality in bivariate and multivariate Cox regression. Notably, nearly 50% of patients showed an increase or maintenance of high c-IMT 1 year post-transplantation and these patients experienced a higher mortality (13 versus 3.5%; P=0.021).
A worse cardiovascular profile and a higher vascular VCAM-1 protein levels at time of KT are related to subclinical atheromatosis. This could lead to a higher post-transplant mortality. Pre-transplant c IMT, post-transplant diabetes and triglycerides at 1-year post-transplantation may condition a high c-IMT measurement post-transplantation, which may decrease patient survival.
Journal Article
Safety and Efficacy of Once-Weekly Exenatide Compared With Insulin Glargine Titrated to Target in Patients With Type 2 Diabetes Over 84 Weeks
OBJECTIVE: We recently reported that after 26 weeks, exenatide once weekly (EQW) resulted in superior A1C reduction, reduced hypoglycemia, and progressive weight loss compared with daily insulin glargine (IG) in patients with type 2 diabetes who were taking metformin alone or with sulfonylurea. This 84-week extension study assessed the long-term safety and efficacy of EQW versus IG. RESEARCH DESIGN AND METHODS: This multicenter, open-label, randomized, two-arm, parallel trial assessed change in A1C, proportions of patients achieving A1C <7.0 and ≤6.5%, body weight, incidence of hypoglycemia, and overall safety. RESULTS: Of 415 patients who completed 26 weeks, 390 (194 EQW and 196 IG patients) entered the extension study. At 84 weeks, A1C decreased from baseline (8.3%) by –1.2% for EQW vs. –1.0% for IG (P = 0.029). The proportions of patients who achieved end point A1C targets <7.0 and ≤6.5% were 44.6% for EQW patients vs. 36.8% for IG patients (P = 0.084) and 31.3% for EQW patients vs. 20.2% for IG patients (P = 0.009), respectively. Patients taking EQW lost 2.1 kg of body weight, whereas those taking IG gained 2.4 kg (P < 0.001). Among patients taking metformin plus sulfonylurea, the incidence of minor hypoglycemia was 24% for EQW patients vs. 54% for IG patients (P < 0.001); among patients taking metformin alone, it was 8% for EQW patients vs. 32% for IG patients (P < 0.001). Among adverse events occurring in ≥5% of patients, diarrhea and nausea occurred more frequently (P < 0.05) in the EQW group than in the IG group (12 vs. 6% and 15 vs. 1%, respectively). CONCLUSIONS: After 84 weeks, patients treated with EQW continued to experience better glycemic control with sustained overall weight loss and a lower risk of hypoglycemia than patients treated with IG.
Journal Article
Dynamics of the vascular system
Recent advances in vascular biology and vascular engineering have led to the understanding and integration of the two fields. A feature that is fundamental to both is the dynamic aspects of the vascular system. Although the basic principles governing blood flow and the circulatory function are known, new approaches to examining the interaction of different parts of the vascular system have emerged. These include measurement techniques and quantitative methods with greater use of modern technology and computer modeling. An obvious need therefore exists for a book that deals specifically with the dynamics of the vascular system. This book begins with the historical discoveries of the features of the vascular system and its importance in the overall circulatory function. Modern aspects of vascular biology in terms of structure and function are then described, followed by the introduction of physical principles and basic fluid mechanics for quantitative analysis. The hemodynamics of large arteries, the optimal structure of vascular branching and the pulsatile energy transmission and modeling aspects are elaborated. These are extended to analyze the function of the venous system and the microcirculation. Finally, the integrated vascular system and its response and adaptation to diseased conditions, such as aging, stenosis, hypertension, myocardial ischemia, atheroslerosis and stroke are explained. The overall emphasis is on the dynamic nature of the vascular system.
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