Pulse pressure—a review of mechanisms and clinical relevance

AbstractThe goal of this study was to review the origin, clinical relevance and treatment of pulse pressure (PP). Elevated PP is increasingly being recognized as a risk factor for cardiovascular, particularly coronary, disease. Pulse pressure is discussed in terms of both Windkessel and distributive models of the arterial circulation. Pulse pressure arises from the interaction of cardiac ejection (stroke volume) and the properties of the arterial circulation. An increased stiffness of the aorta and large arteries leads to an increase in PP through a reduction in arterial compliance and effects on wave reflection. A number of factors are known to influence arterial wall behavior and, therefore, PP. In addition to the effects of aging and blood pressure on arterial wall elasticity, there is some evidence that atherosclerosis, per se, amplifies these effects. Thus, the relationship between PP and coronary disease may be bidirectional. A number of dietary and lifestyle interventions have been shown to modify large artery behavior. These include aerobic exercise training and consumption of n-3 fatty acids. Conversely, strength training is associated with an increase in arterial stiffness and a higher PP. The effects of antihypertensive medication have been extensively studied, but many studies are difficult to interpret because of concomitant change in blood pressure, and to a lesser degree, heart rate. However a number of studies do suggest direct arterial wall effects, particularly for angiotensin-converting enzyme inhibitors. A distributed compliance model of the arterial circulation provides a framework for understanding the causes, effects and potential treatment of elevations in PP

Sitting Less and Moving More: Implications for Hypertension.

Through a hypertension lens, this review focuses on the serious health implications and potential counter-measures for the high volumes of uninterrupted sitting that characterises modern lifestyles. Reducing and breaking up sitting may represent a viable clinical and population health strategy to reduce blood pressure and related cardiovascular risk factors, which in contrast to moderate-vigorous physical activity, may have significant potential for widespread uptake. This review synthesises findings on the specific relationships of sedentary behaviour with BP - which primarily are from observational and acute experimental studies - including a discussion on the relevant cardiovascular mechanisms. It also considers what will need to be better understood as a basis for evidence-based recommendations on sedentary time in the context of BP control, and identify evidence gaps for future research

MicroRNA-194 modulates glucose metabolism and its skeletal muscle expression is reduced in diabetes

BACKGROUND: The regulation of microRNAs (miRNAs) at different stages of the progression of type 2 diabetes mellitus (T2DM) and their role in glucose homeostasis was investigated. METHODS: Microarrays were used to assess miRNA expression in skeletal muscle biopsies taken from healthy individuals and patients with pre-diabetes or T2DM, and insulin resistant offspring of rat dams fed a high fat diet during pregnancy. RESULTS: Twenty-three miRNAs were differentially expressed in patients with T2DM, and 7 in the insulin resistant rat offspring compared to their controls. Among these, only one miRNA was similarly regulated: miR-194 expression was significantly reduced by 25 to 50% in both the rat model and in human with pre-diabetes and established diabetes. Knockdown of miR-194 in L6 skeletal muscle cells induced an increase in basal and insulin-stimulated glucose uptake and glycogen synthesis. This occurred in conjunction with an increased glycolysis, indicated by elevated lactate production. Moreover, oxidative capacity was also increased as we found an enhanced glucose oxidation in presence of the mitochondrial uncoupler FCCP. When miR-194 was down-regulated in vitro, western blot analysis showed an increased phosphorylation of AKT and GSK3β in response to insulin, and an increase in expression of proteins controlling mitochondrial oxidative phosphorylation. CONCLUSIONS: Type 2 diabetes mellitus is associated with regulation of several miRNAs in skeletal muscle. Interestingly, miR-194 was a unique miRNA that appeared regulated across different stages of the disease progression, from the early stages of insulin resistance to the development of T2DM. We have shown miR-194 is involved in multiple aspects of skeletal muscle glucose metabolism from uptake, through to glycolysis, glycogenesis and glucose oxidation, potentially via mechanisms involving AKT, GSK3 and oxidative phosphorylation. MiR-194 could be down-regulated in patients with early features of diabetes as an adaptive response to facilitate tissue glucose uptake and metabolism in the face of insulin resistance

Sugar-and intense-sweetened drinks in Australia: a systematic review on cardiometabolic risk

Sugar-sweetened beverages (SSBs) are consumed globally, and have been associated with adverse health outcomes, including weight gain, high blood pressure, type 2 diabetes (T2D), and cardiovascular disease (CVD). There is global variation in beverage formulation in terms of glucose and fructose concentration, which may pose unique health risks linked to glycemic control for Australian consumers. However, previous systematic reviews have overlooked Australian-based literature. A systematic review was performed to synthesise evidence for the associations between consumption of SSBs and intense-sweetened beverages with clinical cardiometabolic risk factors in the Australian population. Articles were sourced from Global Health, Health Source: Nursing/Academic Edition, Medline, and Culmative Index to Nursing and Allied Health Literature. To be eligible for review, studies had to report on the consumption of sugar-sweetened (including fruit juice and fruit drinks) and/or intense-sweetened beverages, and at least one clinical cardiometabolic risk factor. Eighteen studies were included in this review. Research has mostly focused on the relationship between SSB consumption and adiposity-related outcomes. No studies have examined indices of glycaemic control (glucose/insulin), and the evidence for the health impact of intense-sweetened drinks is limited. In addition, studies have primarily been of cross-sectional design, and have examined children and adolescents, as opposed to adult populations. In the Australian population, there is modest but consistent evidence that SSB consumption has adverse associations with weight, but there is insufficient data to assess relationships with cardiometabolic outcomes. View Full-Tex

Sex-Specific Associations in Nutrition and Activity-Related Risk Factors for Chronic Disease: Australian Evidence from Childhood to Emerging Adulthood

Global assessments of burden of disease suggests there are sex differences in risk factors for chronic disease, including overweight/obesity, dietary patterns and habitual physical activity. Given that prevention efforts aim to target such factors to reduce disease risk, the age at which sex differences may occur is of particular interest. Early life to young adulthood is the optimal time for intervention, with lifestyle habits typically forming during this period. This study aimed to identify the sex differences in risk factors for chronic disease during childhood (5–9 years), adolescence (10–17 years) and emerging adulthood (18–25 years) in a large population-representative Australian sample. Among children in this study (n = 739), no sex-related differences were observed. Among adolescents (n = 1304), females were more likely than males to meet daily fruit and vegetable recommendations (12.9% vs. 7.5%; OR = 1.84, 95% CI = 1.16, 2.93, p < 0.05). Among emerging adults (n = 909), females were less likely to be overweight/obese (30.1% vs. 39.8%; OR = 0.65, 95% CI = 0.44, 0.95, p < 0.05) and more likely to meet physical activity recommendations (52.1% vs. 42.3%; OR = 1.44, 95% CI = 1.01, 2.06, p < 0.05). These findings suggest that sex differences for risk factors of chronic disease occur during adolescence and emerging adulthood, although the differences are not consistent across age periods. From adolescence onwards, it appears that females exhibit lower risk factors than males and a life span approach to risk factor monitoring is warranted

Cardio-metabolic impact of changing sitting, standing, and stepping in the workplace

According to cross-sectional and acute experimental evidence, reducing sitting time should improve cardio-metabolic health risk biomarkers. Furthermore, the improvements obtained may depend on whether sitting is replaced with standing or ambulatory activities. Based on data from the Stand Up Victoria multi-component workplace intervention, we examined this issue using compositional data analysis - a method that can examine and compare all activity changes simultaneously.Participants receiving the intervention (n=136 ≥0.6 full-time equivalent desk-based workers, 65% women, mean±SD age=44.6 ±9.1 years from seven worksites) were asked to improve whole-of-day activity by standing up, sitting less and moving more. Their changes in the composition of daily waking hours (activPAL-assessed sitting, standing, stepping) were quantified, then tested for associations with concurrent changes in cardio-metabolic risk (CMR) scores and 14 biomarkers concerning body composition, glucose, insulin and lipid metabolism. Analyses were by mixed models, accounting for clustering (3 months, n=105-120; 12 months, n=80-97).Sitting reduction was significantly (

Sex-Specific Lifestyle and Biomedical Risk Factors for Chronic Disease Among Early-Middle, Middle and Older Aged Australian Adults

Evidence suggests age and sex differences in risk factors for chronic disease. This study examined lifestyle and biomedical risk factors among men (m) and women (w) in early-middle (25–51 years), middle (52–64) and older (65+) adulthood. Cross-sectional data from the 2011–2012 Australian Health Survey (n = 3024) were analysed. Self-reported dietary, activity, sleep behaviours and collected biomedical data were analysed. Early-middle adults failed to meet fruit, vegetable (95.3%) and sugar-sweetened beverage (SSB, 34.9%) recommendations. Older adults had higher prevalence of overweight/obesity (70%), high blood pressure (38.0%) and fewer met physical activity guidelines (36.3%). Prior to older adulthood, more men consumed SSBs (early-middle m 45.6%, w 24.4%; middle m 26.0%, w 19.3%), and fewer met sedentary behaviour recommendations (early-middle m 43.2%, w 62.1%; middle m 46.4%, w 63.9%). Differences in overweight/obese women in early-middle (44.8%) to middle adulthood (64.7%) were significant. Biomedical risk was greatest in middle age; abnormal cholesterol/lipids increased specifically for women (total cholesterol early-middle 24.9% middle 56.4%; abnormal LDL-cholesterol early-middle 23.1% middle 53.9%). Adherence to lifestyle guidelines was low; particularly among men. While men exhibited greater clinical risk overall, this significantly increased among women in middle-adulthood. Public health strategies to improve lifestyle, monitor and intervene among middle-aged women are warranted

Fasting Plasma Glucose, Self-Appraised Diet Quality and Depressive Symptoms: A US-Representative Cross-Sectional Study

Depression and type 2 diabetes (T2D) contribute significantly to global burden of disease and often co-occur. Underpinning type 2 diabetes is poor glycaemic control and glucose is also an obligatory substrate for brain metabolism, with potential implications for cognition, motivation and mood. This research aimed to examine the relationships between fasting plasma glucose and depressive symptoms in a large, population representative sample of US adults, controlling for other demographic and lifestyle behavioural risk factors. Using the 2013–2014 National Health and Nutrition Examination Survey (NHANES) data, this study first investigated the relationship between fasting plasma glucose and mental disorders at a population-level, accounting for demographic, health behavioural and weight-related factors known to co-occur with both type 2 diabetes and mental disorders. Depressive symptoms were derived from the 9-item Patient Health Questionnaire. Fasting plasma glucose was obtained through medical examination and demographic (age, household income, sex) and health characteristics (perceived diet quality, daily time sedentary) were self-reported. Body mass index was calculated from objectively measured height and weight. In the univariate model, higher fasting plasma glucose was associated with greater depressive symptoms among females (b = 0.24, 95% CI = 0.05, 0.43, p < 0.05), but not males. In the final fully adjusted model, the relationship between fasting plasma glucose and depressive symptoms was non-significant for both males and females. Of all independent variables, self-appraised diet quality was strongly and significantly associated with depressive symptoms and this remained significant when individuals with diabetes were excluded. Although diet quality was self-reported based on individuals’ perceptions, these findings are consistent with a role for poor diet in the relationship between fasting plasma glucose and depressive symptoms

Role of IL-6 in Exercise Training- and Cold-Induced UCP1 Expression in Subcutaneous White Adipose Tissue

Expression of brown adipose tissue (BAT) associated proteins like uncoupling protein 1 (UCP1) in inguinal WAT (iWAT) has been suggested to alter iWAT metabolism. The aim of this study was to investigate the role of interleukin-6 (IL-6) in exercise training and cold exposure-induced iWAT UCP1 expression. The effect of daily intraperitoneal injections of IL-6 (3 ng/g) in C57BL/6 mice for 7 days on iWAT UCP1 expression was examined. In addition, the expression of UCP1 in iWAT was determined in response to 3 days of cold exposure (4°C) and 5 weeks of exercise training in wild type (WT) and whole body IL-6 knockout (KO) mice. Repeated injections of IL-6 in C57BL/6 mice increased UCP1 mRNA but not UCP1 protein content in iWAT. Cold exposure increased iWAT UCP1 mRNA content similarly in IL-6 KO and WT mice, while exercise training increased iWAT UCP1 mRNA in WT mice but not in IL-6 KO mice. Additionally, a cold exposure-induced increase in iWAT UCP1 protein content was blunted in IL-6 KO mice, while UCP1 protein content in iWAT was lower in both untrained and exercise trained IL-6 KO mice than in WT mice. In conclusion, repeated daily increases in plasma IL-6 can increase iWAT UCP1 mRNA content and IL-6 is required for an exercise training-induced increase in iWAT UCP1 mRNA content. In addition IL-6 is required for a full induction of UCP1 protein expression in response to cold exposure and influences the UCP1 protein content iWAT of both untrained and exercise trained animals