A quantitative feedback intervention to reduce binge drinking in young adults.

OBJECTIVE: Existing binge drinking reduction interventions such as brief intervention and personalized normative feedback have shown modest impact. The purpose of this study was to evaluate the feasibility (recruitment and retention rates), acceptability, and preliminary efficacy testing of a short-term "know your numbers (KYN)" intervention on motivating young adults to reduce their engagement in binge drinking. METHOD: Young adults (N=94, mean age 21 years) with a history of binge drinking received a 4-week KYN intervention that included information about their U.S. Alcohol Use Disorders Test (USAUDIT) scores and the alcohol biomarker phosphatidylethanol (PEth) level in relationship to different risk levels of alcohol use. At baseline and 4-weeks, measures included USAUDIT scores, PEth levels, motivation (Alcohol Contemplation Ladder) and other drinking measures. Focus groups were conducted at 4-weeks for feedback on the KYN approach. RESULTS: The recruitment rate was 82.26% (retention rate 76.9%). At 4-weeks there was a 62% increase in contemplation scores (indicating higher motivation), a decrease in USADUIT scores with an increase in the percent of participants classified as low-risk drinkers. No differences were found between baseline and 4-week PEth levels or number of binge episodes. Focus group results revealed satisfaction with the KYN approach but the need to understand how PEth levels and USAUDIT scores corresponded to health consequences and alcohol use levels. CONCLUSIONS: Results from this pilot study support the acceptability and potential use of a KYN approach in helping young adults understand their drinking levels.

Associations of online health information seeking with health behaviors of cancer survivors.

Objective: To examine the effects of online health information seeking (OHIS) behavior on five health behaviors (regular physical activity, less sedentary, calorie checking, no alcohol consumption, and no smoking) among adult cancer survivors in the United States. Methods: A cross-sectional analysis was conducted with adult cancer survivors (≥18 years old) from Cycles 2, 3, and 4 of the Health Information National Trends Survey (HINTS). The respondents self-reported OHIS, and the data on the five health behaviors were pooled to perform descriptive and multivariable logistic regression analyses using Stata 17.0. Results: Of the 1245 adult cancer survivors, approximately 74% reported OHIS behavior for themselves within the previous year of the survey. We found that OHIS was significantly and positively associated with the level of physical activity (odds ratio [OR] = 1.53, p = .002) and calorie checking (OR = 1.64, p = .001), but not with sedentary behavior, smoking, and alcohol consumption after adjusting for age, sex, race/ethnicity, education, income, body mass index (BMI), marital status, depression, and general health. Conclusions: Findings from this study suggest that most cancer survivors used various forms of digital tools and platforms to seek health information. The study also demonstrated an independent impact of OHIS behavior on physical activity and calorie checking. Healthcare professionals may need to encourage and guide cancer survivors to seek credible eHealth information and further utilize digital health tools as a platform for care delivery, promoting health behaviors and preventing adverse health outcomes among cancer survivors.

Gut-derived ammonia contributes to alcohol-related fatty liver development via facilitating ethanol metabolism and provoking ATF4-dependent de novo lipogenesis activation.

BACKGROUND & AIMS: Dysbiosis contributes to alcohol-associated liver disease (ALD); however, the precise mechanisms remain elusive. Given the critical role of the gut microbiota in ammonia production, we herein aim to investigate whether and how gut-derived ammonia contributes to ALD. METHODS: Blood samples were collected from human subjects with/without alcohol drinking. Mice were exposed to the Lieber-DeCarli isocaloric control or ethanol-containing diets with and without rifaximin (a nonabsorbable antibiotic clinically used for lowering gut ammonia production) supplementation for five weeks. Both in vitro (NH4Cl exposure of AML12 hepatocytes) and in vivo (urease administration for 5 days in mice) hyperammonemia models were employed. RNA sequencing and fecal amplicon sequencing were performed. Ammonia and triglyceride concentrations were measured. The gene and protein expression of enzymes involved in multiple pathways were measured. RESULTS: Chronic alcohol consumption causes hyperammonemia in both mice and human subjects. In healthy livers and hepatocytes, ammonia exposure upregulates the expression of urea cycle genes, elevates hepatic de novo lipogenesis (DNL), and increases fat accumulation. Intriguingly, ammonia promotes ethanol catabolism and acetyl-CoA formation, which, together with ammonia, synergistically facilitates intracellular fat accumulation in hepatocytes. Mechanistic investigations uncovered that ATF4 activation, as a result of ER stress induction and general control nonderepressible 2 activation, plays a central role in ammonia-provoked DNL elevation. Rifaximin ameliorates ALD pathologies in mice, concomitant with blunted hepatic ER stress induction, ATF4 activation, and DNL activation. CONCLUSIONS: An overproduction of ammonia by gut microbiota, synergistically interacting with ethanol, is a significant contributor to ALD pathologies.

Association of online health information seeking behavior with levels of knowledge about palliative care among older adults.

This study examined the knowledge, misconceptions, and predictors of palliative care among older adults using nationally representative data. A cross-sectional analysis was conducted with 1,390 respondents (≥ 50 years) from cycle 2 of the 2018 Health Information National Trends Survey (HINTS). Overall, 63.53% of older adults reported that they had never heard of palliative care. Among those who reported knowledgeable about palliative care, 33.33% thought palliative care is the same as hospice, and 41.42% automatically linked palliative care to death. Ordered logistic regression analysis revealed that online health information seeking behavior is a significant predictor of the level of knowledge about palliative care among older adults. Older adults who utilized the internet for health information were 2.16 (p < .001) times more likely to report being knowledgeable about palliative care than non-internet users. Findings from this study indicate that public health education efforts are needed to increase palliative care knowledge among older adults and the internet may be the key to improving health literacy in palliative care for them.

Alcohol Consumption: A New Risk Factor for Arterial Stiffness?

The relationship between alcohol consumption and cardiovascular disease risk is complex. Low-to-moderate daily alcohol consumption (1-2 drinks/day) is associated with reduced risk, whereas greater amounts of alcohol consumption and a "binge" pattern of drinking are associated with increased cardiovascular risk and mortality. Arterial stiffness may help explain the complex relationship. This integrated review summarizes data from studies examining the associations between alcohol consumption and pulse wave velocity, a gold standard measure of arterial stiffness. We also briefly review the concept and methodology of pulse wave velocity measurement as well as the mechanisms of alcohol-induced arterial stiffening. Findings among the different studies reviewed were inconsistent with methodological challenges related to alcohol use assessment. While making specific conclusions regarding this relationship is tenuous; the data suggest that excessive alcohol consumption or a binge drinking pattern is associated with increased arterial stiffness.

Effects of Exercise Mode on Improving Cardiovascular Function and Cardiorespiratory Fitness After Bariatric Surgery: A Narrative Review.

ABSTRACT: Obesity affects 600 million people globally and increases the risk of developing cardiovascular disease, stroke, diabetes, and cancer. Bariatric surgery is an increasingly popular therapeutic intervention for morbid obesity to induce rapid weight loss and reduce obesity-related comorbidities. However, some bariatric surgery patients, after what is considered a successful surgical procedure, continue to manifest obesity-related health issues, including weight gain, reduced physical function, persistent elevations in blood pressure, and reduced cardiorespiratory fitness. Cardiorespiratory fitness is a strong predictor of mortality and several health outcomes and could be improved by an appropriate exercise prescription after bariatric surgery. This review provides a broad overview of exercise training for patients after bariatric surgery and discusses cardiorespiratory fitness and other potential physiological adaptations in response to exercise training.

Cholesterol-Induced Suppression of Endothelial Kir Channels Is a Driver of Impairment of Arteriolar Flow-Induced Vasodilation in Humans.

Dyslipidemia-induced endothelial dysfunction is an important factor in the progression of cardiovascular disease; however, the underlying mechanisms are unclear. Our recent studies demonstrated that flow-induced vasodilation (FIV) is regulated by inwardly rectifying K+ channels (Kir2.1) in resistance arteries. Furthermore, we showed that hypercholesterolemia inhibits Kir2.1-dependent vasodilation. In this study, we introduced 2 new mouse models: (1) endothelial-specific deletion of Kir2.1 to demonstrate the role of endothelial Kir2.1 in FIV and (2) cholesterol-insensitive Kir2.1 mutant to determine the Kir2.1 regulation in FIV under hypercholesterolemia. FIV was significantly reduced in endothelial-specific Kir2.1 knock-out mouse mesenteric arteries compared with control groups. In cholesterol-insensitive Kir2.1 mutant mice, Kir2.1 currents were not affected by cyclodextrin and FIV was restored in cells and arteries, respectively, with a hypercholesterolemic background. To extend our observations to humans, 16 healthy subjects were recruited with LDL (low-density lipoprotein)-cholesterol ranging from 51 to 153 mg/dL and FIV was assessed in resistance arteries isolated from gluteal adipose. Resistance arteries from participants with >100 mg/dL LDL (high-LDL) exhibited reduced FIV as compared with those participants with <100 mg/dL LDL (low-LDL). A significant negative correlation was observed between LDL cholesterol and FIV in high-LDL. Expressing dominant-negative Kir2.1 in endothelium blunted FIV in arteries from low-LDL but had no further effect on FIV in arteries from high-LDL. The Kir2.1-dependent vasodilation more negatively correlated to LDL cholesterol in high-LDL. Overexpressing wild-type Kir2.1 in endothelium fully recovered FIV in arteries from participants with high-LDL. Our data suggest that cholesterol-induced suppression of Kir2.1 is a major mechanism underlying endothelial dysfunction in hypercholesterolemia.

The physiological benefits of sitting less and moving more: Opportunities for future research.

Sedentary behavior (SB) and physical activity (PA) are important risk factors of cardiovascular disease morbidity and mortality. In addition to increasing the amount of moderate-to-vigorous PA (MVPA), the current PA guidelines recommend that adults should reduce SB, or any waking activity performed while sitting, reclining, or lying, with low energy expenditure. While mounting evidence has emphasized the benefits of increasing MVPA, little has focused on the effect of SB on health. Therefore, this review discusses the pathophysiological effects of SB and the potential physiological benefits of reducing/breaking up SB at the levels below the current guidelines for PA. Such knowledge is important, given that the majority of the United States population performs insufficient or no MVPA and is at high risk of being negatively impacted by SB. Interventions targeting sedentary time, such as breaking up SB by standing and moving, may be safe, feasible, and applicable to execute daily for a wide range of the population. This review also discusses the importance of monitoring SB in the era of the coronavirus disease 2019 (COVID-19) pandemic and the clinical implications of sitting less and moving more.

Menstrual cycle effects on sympathetic neural burst amplitude distribution during orthostasis in young women.

PURPOSE: Fluctuations in ovarian hormones during the menstrual cycle impact muscle sympathetic nerve activity burst frequency and burst incidence at rest. The purpose of this study was to investigate menstrual cycle effects on sympathetic neural burst amplitude distribution during an orthostatic challenge in young women. METHODS: This study included 11 healthy women (33 ± 10 years [mean ± standard deviation]). Muscle sympathetic nerve activity was measured in the supine position as baseline measurement and during 5 min of 60° upright tilting, during the early follicular phase (low estrogen and progesterone) and mid-luteal phase (high estrogen and progesterone) of the menstrual cycle. Relative burst amplitude distribution of muscle sympathetic nerve activity was characterized by the mean, median, skewness, and kurtosis. RESULTS: From the supine to upright position, mean and median values of relative burst amplitude increased (both P < 0.05), regardless of phases of the menstrual cycle (P = 0.5 and P = 0.7, respectively). In comparison, during the early follicular phase, skewness and kurtosis remained unchanged (P = 0.6 and P = 0.3, respectively) and kurtosis decreased (1.25 ± 1.11 supine vs. - 0.03 ± 0.73 upright; P = 0.02); there was no change in skewness during the mid-luteal phase (P = 0.4). CONCLUSIONS: In response to orthostasis, while the symmetry and tailedness/peakness of burst amplitude distribution do not change during the early follicular phase, the distribution during the mid-luteal phase becomes flatter with a lower but broader peak. The latter result suggests that the firing probability of large axon action potentials in response to orthostatic challenge is higher when estrogen and progesterone levels are elevated. The role of changes in sympathetic neural burst amplitude distribution in orthostatic tolerance remains to be determined.

The effects of alcohol consumption on flow-mediated dilation in humans: A systematic review.

Changes in endothelial function may contribute to the positive and negative effects of alcohol consumption on cardiovascular conditions, such as hypertension and coronary artery disease. Numerous studies have used brachial artery flow-mediated dilation (FMD) to examine the effects of alcohol consumption on endothelial function in humans. However, the findings are inconsistent and may be due to multiple factors such as heterogeneity in subject characteristics, the alcohol use pattern, and amount/dose of alcohol consumed. Therefore, the aim of this systematic review was to investigate the effect of alcohol consumption on brachial artery FMD in humans considering the above-mentioned factors. This review found that while light to moderate alcohol consumption may have minimal effects on FMD, heavy alcohol consumption was associated with a decrease in FMD. However, most of the published studies included healthy, younger, and male individuals, limiting generalizability to other populations. Future studies should include more women, older subjects, and those from diverse and underrepresented backgrounds.

Differential responses of resistance arterioles to elevated intraluminal pressure in blacks and whites.

Black Americans have an earlier onset, higher average blood pressure, and higher rates of hypertension-related mortality and morbidity, compared to whites. The racial difference may be related to microvasculature, the major regulatory site of blood pressure. The goal of this study was to compare the response of resistance vessels to high intraluminal pressure between black and white participants. A total of 38 vessels were obtained from human fat samples [21 black, 17 white; mean age 32 ± 12 yr and body mass index (BMI) 26.9 ± 4.9; between-group P ≥ 0.05] and included in this study. Internal diameter was measured in response to the flow induced by various pressure gradients (Δ10, Δ20, Δ40, Δ60, and Δ100 cmH2O), and flow-induced dilation (FID) was calculated before and after high intraluminal pressure (150 cmH2O). Before high intraluminal pressure, FID was not different between blacks and whites (P = 0.112). After exposure to high intraluminal pressure, FID was reduced at every pressure gradient in vessels from blacks (P < 0.001), whereas FID did not change in white participants except at Δ100 cmH2O. When incubated with the hydrogen peroxide (H2O2) scavenger polyethylene glycol-catalase (PEG-catalase), the FID response in vessels from black, but not white, individuals was significantly reduced and the magnitude was higher at normal pressure relative to high pressure. Our findings suggest that the vessels from self-identified black individuals are more susceptible to microvascular dysfunction following transient periods of high intraluminal pressure compared to whites and show greater dependence on H2O2 as a main contributor to FID at normal pressures.NEW & NOTEWORTHY Microvascular function regulates blood pressure and may contribute to racial differences in the incidence and prevalence of hypertension and other cardiovascular diseases. Here, we show that using an ex vivo model of resistance arterioles isolated from human gluteal fat tissue, flow-induced dilation is not different between black and white participants. However, when exposed to transient increases in intraluminal pressure, the flow-induced dilation in resistance arterioles from black participants demonstrated greater reductions relative to their white counterparts, indicating a higher sensitivity to pressure change in the microvasculature.

Effects of Alcohol on the Cardiovascular System in Women.

Cardiovascular disease (CVD) is a leading cause of morbidity and mortality for women. This review summarizes the relationship between alcohol consumption and common CVDs in women and highlights potential differences from men. Except for risk of hypertension, no sex-related effects of alcohol consumption on the risk for coronary heart disease and stroke have been reported, and data on the sex-related effects on risk for peripheral arterial disease are limited. For women, alcohol consumption has a J-shaped relationship with hypertension. About 1 to 2 standard drinks per day is associated with lower risk for the development of hypertension, whereas for men, the relationship is relatively linear. In the area of alcoholic cardiomyopathy, the prevalence is greater for men, but women may develop alcoholic cardiomyopathy at a lower lifetime level of alcohol consumption. Overall, data support that 1 to 2 standard drinks per day for women and men is associated with a lower risk of CVD, and higher daily amounts may increase the risk of CVD.

More than a matter of the heart: the concept of intravascular multimorbidity in cardiac rehabilitation.

INTRODUCTION: Coronary artery disease (CAD) is the major cause of death of cardiovascular disease. It is initiated by atherosclerosis, which narrows the coronary arteries and limits blood flow and oxygen to the heart. Multiple pathophysiological conditions within the arteries, such as arterial wall thickening, endothelial dysfunction, and arterial stiffening, are associated with the development of atherosclerosis. AREAS COVERED: We introduce a new concept of 'intravascular multimorbidity,' the presence and integration of multiple pathophysiological conditions within the arteries. We also introduce some measurements of intravascular multimorbidity and discuss how these measurements can be utilized in cardiac rehabilitation (CR). EXPERT OPINION: We propose that the measures of intravascular multimorbidity in different arteries may provide information on disease severity and serve as unique prognostic 'barometers' to disease progression in patients with CAD. By measuring the underlying disease mechanisms within the arteries and understanding individual variability of disease progression/regression, these measures may also provide a unique prognostic window in CR. The window into intravascular multimorbidity can help guide clinical strategies, for example, assessing progress and appropriate titration of exercise. Intravascular multimorbidity may represent an important opportunity for more researchers and clinical professions to evaluate patients in CR.

The Effect of Low-Carbohydrate Diet on Macrovascular and Microvascular Endothelial Function is Not Affected by the Provision of Caloric Restriction in Women with Obesity: A Randomized Study.

Obesity impairs both macro- and microvascular endothelial function due to decreased bioavailability of nitric oxide. Current evidence on the effect of low-carbohydrate (LC) diet on endothelial function is conflicting and confounded by the provision of caloric restriction (CR). We tested the hypothesis that LC without CR diet, but not LC with CR diet, would improve macro- and microvascular endothelial function in women with obesity. Twenty-one healthy women with obesity (age: 33 ± 2 years, body mass index: 33.0 ± 0.6 kg/m2; mean ± SEM) were randomly assigned to receive either a LC diet (~10% carbohydrate calories) with CR (n = 12; 500 calorie/day deficit) or a LC diet without CR (n = 9) and completed the 6-week diet intervention. After the intervention, macrovascular endothelial function, measured as brachial artery flow-mediated dilation did not change (7.3 ± 0.9% to 8.0 ± 1.1%, p = 0.7). On the other hand, following the LC diet intervention, regardless of CR, blocking nitric oxide production decreased microvascular endothelial function, measured by arteriolar flow-induced dilation (p ≤ 0.02 for both diets) and the magnitude was more than baseline (p ≤ 0.04). These data suggest improved NO contributions following the intervention. In conclusion, a 6-week LC diet, regardless of CR, may improve microvascular, but not macrovascular endothelial function, via increasing bioavailability of nitric oxide in women with obesity.

Ethanol Induced Oxidative Stress in the Vasculature: Friend or Foe.

Oxidative stress is implicated in the etiology of many ethanol-induced pathologies. Oxidative stress has been shown to contribute to the development of endothelial dysfunction and cardiovascular disease, such as hypertension. This review details mechanisms of vascular function, the role of oxidative stress in vascular biology and how ethanol consumption may alter endothelial and smooth muscle cell function as well as microvascular function. Also reviewed are data from human investigations that have examined the association between alcohol consumption and changes in blood pressure and increased risk for hypertension.

The effects of repeated binge drinking on arterial stiffness and urinary norepinephrine levels in young adults.

OBJECTIVES: The aim of this study was to investigate the effect of repeated binge drinking and moderate alcohol consumption in young adults on arterial stiffness and sympathetic activity. METHODS: We enrolled 49 healthy young adults, free of cardiovascular diseases (25 men; age: 23.5 ±â€Š0.4 years; BMI: 23.4 ±â€Š0.4 kg/m; mean ±â€ŠS.E). Individuals included were those with a history of repeated binge drinking (>2 years duration; n = 20), drank at moderate levels (MODs, >5 years duration; n = 16) and abstained from alcohol (last 2-3 years; n = 13). Arterial stiffness was assessed using carotid to femoral pulse wave velocity (cfPWV) and sympathetic activity was assessed using 24-h urinary norepinephrine levels. Also measured was aortic SBP and augmentation index (AIx), a measure of wave reflection. RESULTS: Binge drinkers and MODs had higher cfPWV than alcohol abstainers (0.6 and 0.5 m/s, respectively; P ≤ 0.04). In addition, binge drinkers had higher urinary norepinephrine levels than MODs and alcohol abstainers (P < 0.05). Higher cfPWV were correlated with higher norepinephrine levels (r = 0.35. P = 0.02). Aortic SBP (P = 0.2) and AIx (P = 0.96) were similar among binge drinkers, MODs and alcohol abstainers. CONCLUSION: Our findings suggest that repeated exposure to alcohol, regardless of drinking pattern, may increase aortic arterial stiffness in healthy young adults. In addition, sympathetic activation, reflected by increased 24-h urinary norepinephrine levels, may contribute to alcohol-induced arterial stiffening in young adults.

Tetrahydrobiopterin Restores Microvascular Dysfunction in Young Adult Binge Drinkers.

BACKGROUND: Repeated binge drinking is associated with reduced microvascular function. However, microvascular responses to pathophysiological stimulus such as high pressure as well as potential mechanisms that underlie binge-induced microvascular dysfunction are unknown. Therefore, using an ex vivo experimental model, we examined microvascular responses following a brief period of high intraluminal pressure in isolated arterioles from young adults who have a history of repeated binge drinking. In addition, we examined whether the application of the endothelial nitric oxide synthase cofactor, tetrahydrobiopterin, would restore microvascular function in response to flow and high intraluminal pressure in young adult binge drinkers. METHODS: Isolated subcutaneous adipose arterioles were obtained from young adult binge drinkers (BD; n = 14), moderate drinkers (MODs; n = 10), and alcohol abstainers (ABs; n = 12; mean age: 23.7 ± 0.5 years; and body mass index: 23.4 ± 0.4 kg/m2 ). Arteriolar flow-induced dilation (FID, pressure gradient: ∆10 to 100 cm H2 O) was measured before and after acute high intraluminal pressure with and without tetrahydrobiopterin. RESULTS: Before high pressure, FID at Δ60 and Δ100 cm H2 O pressure gradient in BDs was 14% lower and 18% lower, respectively, than ABs (p < 0.05), while MODs and ABs had similar FID across all pressure gradients (p ≥ 0.2). After high pressure, FID in BDs was further reduced by 10% (p < 0.0005) and this impairment was ameliorated by the treatment of tetrahydrobiopterin (4 to 26% higher, p < 0.005). In contrast, FID after high pressure did not change in MODs and ABs (p ≥ 0.5). CONCLUSIONS: Microvascular dysfunction in young adult binge drinkers may be exacerbated with acute pathophysiological stimulus. These binge-induced dysfunctions may be reversed by tetrahydrobiopterin, which suggests a role of oxidative stress and/or uncoupled endothelial nitric oxide synthase in binge drinking.

Low-Fat Diet Designed for Weight Loss But Not Weight Maintenance Improves Nitric Oxide-Dependent Arteriolar Vasodilation in Obese Adults.

Obesity is associated with microvascular dysfunction. While low-fat diet improves cardiovascular risk, its contributions on microvascular function, independent of weight loss, is unknown. We tested the hypothesis that nitric oxide (NO)-dependent vasodilation in microvessels is improved by low-fat diets designed for weight loss (LFWL) compared to low-fat weight maintenance (LFWM) diet. Obese adults were randomly assigned to either a LFWL diet (n = 11) or LFWM diet (n = 10) for six weeks. Microvessels were obtained from gluteal subcutaneous fat biopsies before and after the intervention for vascular reactivity measurements to acetylcholine (Ach) and flow, with and without L-NAME or indomethacin. Vascular and serum NO and C-reactive protein (CRP) were also measured. LFWL diet increased flow-induced (FID) and ACh-induced dilation (AChID); an effect that was inhibited by L-NAME. Conversely, LFWM diet did not affect FID or AChID. Indomethacin improved FID and AChID in the baseline and this effect was minimized in response to both diets. Serum NO or CRP did not change in response to either diet. In conclusion, LFWL diet improves microvascular reactivity compared to LFWM diet and increased vascular NO contribution to the improved microvascular dilation. These data suggest that weight reduction on low fat diet is critical for microvascular health.