Blastocyst environment and its influence on offspring cardiovascular health:the heart of the matter

The development of adult-onset diseases such as type II diabetes, obesity and cardiovascular disease is traditionally attributed to adult lifestyle characteristics such as a lack of physical exercise, poor diet and smoking. However, evidence from both human and animal model studies has demonstrated that environmental factors such as an imbalance or reduction in maternal nutrition during gestation can have adverse effects on offspring metabolism and cardiovascular health. The severity and nature of the phenotypic changes induced in offspring is influenced by the period of gestation manipulated. In particular, the mammalian preimplantation embryo in different animal models displays particular sensitivity to environmental factors, either in vivo (maternal diet) or in vitro (embryo culture) that is associated with the onset of cardiovascular dysfunction in adult life. The detailed mechanisms by which environmental conditions can alter postnatal cardiovascular physiology are poorly understood. However, various factors including endothelial function, vascular responsiveness, the renin-angiotensin system, kidney structure and early postnatal growth dynamics have all been recognize as potential contributors. Here, we review the relationship between preimplantation embryo environment and postnatal cardiovascular disease risk, and consider biochemical, molecular, genetic and physiological pathways implicated in this association. © 2009 The Authors Journal compilation © 2009 Anatomical Society of Great Britain and Ireland.

A qualitative study of English community pharmacists’ experiences of providing lifestyle advice to patients with cardiovascular disease

Background - Cardiovascular disease (CVD) progression is modifiable through lifestyle behaviors. Community pharmacists are ideally placed to facilitate self-management of cardiovascular health however research shows varied pharmacist engagement in providing lifestyle advice. Objective - This study explored community pharmacists' experiences and perceptions of providing lifestyle advice to patients with CVD. Methods - Semi-structured interviews were conducted with fifteen pharmacists (1 supermarket; 7 multiple; 7 independent) recruited through multiple methods from community pharmacies across the Midlands, England. A thematic analysis was conducted using a Framework approach. Results - Pharmacists categorized patients according to their perceptions of the patients' ability to benefit from advice. Many barriers to providing lifestyle advice were identified. Confidence to provide lifestyle advice varied, with pharmacists most comfortable providing lifestyle advice in conjunction with conversations about medicines. Some pharmacists felt lifestyle advice was an integral part of their role whilst others questioned whether pharmacists should give lifestyle advice at all, particularly when receiving no remuneration for doing so. Conclusion - Pharmacists viewed providing lifestyle advice as important but identified many barriers to doing so. Lifestyle advice provision was influenced by pharmacists' perceptions of patients. Professional identity and associated role conflict appeared to underpin many of the barriers to pharmacists providing lifestyle advice. Pharmacists may benefit from enhanced training to: increase their confidence to provide lifestyle advice; integrate lifestyle advice with regular pharmaceutical practice and challenge their perceptions of some patients' receptiveness to lifestyle advice and behavior change. Changes to the way UK pharmacists are remunerated may increase the provision of lifestyle advice.

Use of complementary and alternative medicine and self-tests by coronary heart disease patients

Background: Coronary heart disease patients have to learn to manage their condition to maximise quality of life and prevent recurrence or deterioration. They may develop their own informal methods of self-management in addition to the advice they receive as part of formal cardiac rehabilitation programmes. This study aimed to explore the use of complementary and alternative medicines and therapies (CAM), self-test kits and attitudes towards health of UK patients one year after referral to cardiac rehabilitation. Method: Questionnaire given to 463 patients attending an assessment clinic for 12 month follow up in four West Midlands hospitals. Results: 91.1% completed a questionnaire. 29.1% of patients used CAM and/or self-test kits for self-management but few (8.9%) used both methods. CAM was more often used for treating other illnesses than for CHD management. Self-test kit use (77.2%,) was more common than CAM (31.7%,) with BP monitors being the most prevalent (80.0%). Patients obtained self-test kits from a wide range of sources, for the most part (89.5%) purchased entirely on their own initiative. Predictors of self-management were post revascularisation status and higher scores on 'holism', 'rejection of authority' and 'individual responsibility'. Predictors of self-test kit use were higher `holism' and 'individual responsibility' scores. Conclusion: Patients are independently using new technologies to monitor their cardiovascular health, a role formerly carried out only by healthcare practitioners. Post-rehabilitation patients reported using CAM for self-management less frequently than they reported using self-test kits. Reports of CAM use were less frequent than in previous surveys of similar patient groups. Automatic assumptions cannot be made by clinicians about which CHD patients are most likely to self-manage. In order to increase trust and compliance it is important for doctors to encourage all CHD patients to disclose their self-management practices and to continue to address this in follow up consultations.

Maternal low-protein diet during mouse pre-implantation development induces vascular dysfunction and altered renin-angiotensin-system homeostasis in the offspring

Environmental perturbations during early mammalian development can affect aspects of offspring growth and cardiovascular health. We have demonstrated previously that maternal gestational dietary protein restriction in mice significantly elevated adult offspring systolic blood pressure. Therefore, the present study investigates the key mechanisms of blood pressure regulation in these mice. Following mating, female MF-1 mice were assigned to either a normal-protein diet (NPD; 18% casein) or an isocaloric low-protein diet throughout gestation (LPD; 9% casein), or fed the LPD exclusively during the pre-implantation period (3.5d) before returning to the NPD for the remainder of gestation (Emb-LPD). All offspring received standard chow. At 22 weeks, isolated mesenteric arteries from LPD and Emb-LPD males displayed significantly attenuated vasodilatation to isoprenaline (P=0.04 and P=0.025, respectively), when compared with NPD arteries. At 28 weeks, stereological analysis of glomerular number in female left kidneys revealed no significant difference between the groups. Real-time RT-PCR analysis of type 1a angiotensin II receptor, Na /K ATPase transporter subunits and glucocorticoid receptor expression in male and female left kidneys revealed no significant differences between the groups. LPD females displayed elevated serum angiotensin-converting enzyme (ACE) activity (P=0.044), whilst Emb-LPD males had elevated lung ACE activity (P=0.001), when compared with NPD offspring. These data demonstrate that elevated offspring systolic blood pressure following maternal gestational protein undernutrition is associated with impaired arterial vasodilatation in male offspring, elevated serum and lung ACE activity in female and male offspring, respectively, but kidney glomerular number in females and kidney gene expression in male and female offspring appear unaffected. © 2010 The Authors.

Cardiac induced localised motion of the human torso detected by a long period grating fibre optic sensing scheme

Cardiovascular health of the human population is a major concern for medical clinicians, with cardiovascular diseases responsible for 48% of all deaths worldwide, according to the World Health Organisation. Therefore the development of new practicable and economical diagnostic tools to scrutinise the cardiovascular health of humans is a major driver for clinicians. We offer a new technique to obtain seismocardiographic signals covering both ballistocardiography (below 20Hz) and audible heart sounds (20Hz upwards). The detection scheme is based upon an array of curvature/displacement sensors using fibre optic long period gratings interrogated using a variation of the derivative spectroscopy interrogation technique. © 2014 SPIE.

All-fiber loading sensor based on 45° and 81° tilted fiber gratings

Cardiovascular health of the human population is a major concern for medical clinicians, with cardiovascular diseases responsible for 48% of all deaths worldwide, according to the World Health Organisation. Therefore the development of new practicable and economical diagnostic tools to scrutinise the cardiovascular health of humans is a major driver for clinicians. We offer a new technique to obtain seismocardiographic signals covering both ballistocardiography (below 20Hz) and audible heart sounds (20Hz upwards). The detection scheme is based upon an array of curvature/displacement sensors using fibre optic long period gratings interrogated using a variation of the derivative spectroscopy interrogation technique. © 2014 SPIE.

Cardiac-induced localized thoracic motion detected by a fiber optic sensing scheme

The cardiovascular health of the human population is a major concern for medical clinicians, with cardiovascular diseases responsible for 48% of all deaths worldwide, according to the World Health Organization. The development of new diagnostic tools that are practicable and economical to scrutinize the cardiovascular health of humans is a major driver for clinicians. We offer a new technique to obtain seismocardiographic signals up to 54 Hz covering both ballistocardiography (below 20 Hz) and audible heart sounds (20 Hz upward), using a system based on curvature sensors formed from fiber optic long period gratings. This system can visualize the real-time three-dimensional (3-D) mechanical motion of the heart by using the data from the sensing array in conjunction with a bespoke 3-D shape reconstruction algorithm. Visualization is demonstrated by adhering three to four sensors on the outside of the thorax and in close proximity to the apex of the heart; the sensing scheme revealed a complex motion of the heart wall next to the apex region of the heart. The detection scheme is low-cost, portable, easily operated and has the potential for ambulatory applications.

Rho-kinase as a therapeutic target in vascular diseases:striking nitric oxide signaling

Rho GTPases are a globular, monomeric group of small signaling G-protein molecules. Rho-associated protein kinase/Rho-kinase (ROCK) is a downstream effector protein of the Rho GTPase. Rho-kinases are the potential therapeutic targets in the treatment of cardiovascular diseases. Here, we have primarily discussed the intriguing roles of ROCK in cardiovascular health in relation to nitric oxide signaling. Further, we highlighted the biphasic effects of Y-27632, a ROCK inhibitor under shear stress, which acts as an agonist of nitric oxide production in endothelial cells. The biphasic effects of this inhibitor raised the question of safety of the drug usage in treating cardiovascular diseases.

Pharmacist monitoring of patient health in the community

The Government has established essential principles in order to make significant improvements in the health of the people and has placed an emphasis on shifting care to the primary sening. This research has explored the potential role of the community pharmacist in health promotion in the pharmacy, and at general medical practices. The feasibility of monitoring patients' health status in the community was evaluated by intervention to assess and alter cardiovascular risk factors.68, hypertensive patients, monitored at one surgery, had a change in mean systolic blood pressure from 158.28 to 146.55 mmHg, a reduction of 7.4%, and a change in mean diastolic bood pressure from 90.91 to 84.85 mmHg, a reduction of 6.7%.120 patients, from a cohort of 449 at the major practice, with an initial serum total cholesterol of 6.0+mmol/L, experienced a change in mean value from 6.79 to 6.05 mmol/L, equivalent to a reduction of 10.9%. 86% of this patient cohort showed a decrease in cholesterol concentration. Patients, placed in a high risk category according to their coronary rank score, assessed at the first health screening, showed a consistent and significant improvement in coronary score throughout the study period of two years. High risk and intermediate risk patients showed improvements in coronary score of 52% and 14% respectively. Patients in the low risk group maintained their good coronary score. In some cases, a patient's improvement was effected in liaison with the GP, after a change or addition of medication and/or dosage.Pharmacist intervention consisted of advice on diet and lifestyle and adherence to medication regimes. It was concluded that a pharmacist can facilitate a health screening programme in the primary care setting, and provide enhanced continuity of care for the patient.

Dietary enrichment by almond supplementation: effects on risk factors for cardiovascular disease

Cardiovascular disease (CVD) is the leading cause of death in Europe responsible for more than 4.3 million deaths annually. The World Health Organisation funded the Monica project (1980s-1990s) which monitored ten million subjects aged 22-6Syrs, and demonstrated that coronary heart disease (CHD) mortality declined over 10 years, was due in two thirds of cases to reduced incidence of CHD (reduced risk behaviours e.g. poor diet and smoking) and one third by improved treatments. Epidemiological evidence suggests diets rich in antioxidants decrease incidence of CVD. Regular consumption of nuts, rich in vitamin E and polyphenols reduces atherosclerosis, an important risk for heart disease. Intervention studies to date using alpha tocopherol (an active component of vitamin E) have not consistently proved beneficial. This thesis aims to investigate the effect of almond supplementation on vascular risk factors in healthy young males (18-3Syrs); mature males and female(>SOyrs); and males considered at increased risk of CVD (18-3Syrs) in a cohort of 67 subjects. The effects of almond intake were assessed after 2Sg/d for four weeks followed by SOg/d for four weeks and compared to a control group which did not consume almonds or change their diet. Cardiovascular risk was assessed by plasma lipid profiles, apolipoprotein A1, plasma nitrates/nitrates, vascular flow, BMl, blood pressure, sVCAM-1 and protein oxidation. Systolic and diastolic blood pressures were reduced in almond supplemented volunteers but not in controls. Dietary monounsaturated fatty acids, polyunsaturated fatty acid content and total dietary fats were increased by almond supplementation. Neither sVCAM-1, venous occlusion plethysmography nor plasma nitrite levels were affected by almond intake in any independent group. No significant changes in plasma lipids, and apolipoprotein A1 were observed. In conclusion almonds supplementation caused a reduction in blood pressure that may be due to increased sensitivity of the baroreceptors after increased monounsaturated fatty acid intake.

Paternal low protein diet affects adult offspring cardiovascular and metabolic function in mice

Although the association between maternal periconceptional diet and adult offspring health is well characterised, our understanding of the impact of paternal nutrition at the time of conception on offspring phenotype remains poorly defined. Therefore, we determined the effect of a paternal preconception low protein diet (LPD on adult offspring cardiovascular and metabolic health in mice. Male C57BL/6 mice were fed either normal protein diet (NPD; 18% casein or LPD (9% casein for 7 wk before mating. At birth, a reduced male-to-female ratio (P = 0.03 and increased male offspring weight (P = 0.009 were observed in litters from LPD compared with NPD stud males with no differences in mean litter size. LPD offspring were heavier than NPD offspring at 2 and 3 wk of age (P <0.02. However, no subsequent differences in body weight were observed. Adult male offspring derived from LPD studs developed relative hypotension (decreased by 9.2 mmHg and elevated heart rate (P <0.05, whereas both male and female offspring displayed vascular dysfunction and impaired glucose tolerance relative to NPD offspring. At cull (24 wk, LPD males had elevated adiposity (P = 0.04, reduced heart-to-body weight ratio (P = 0.04, and elevated circulating TNF-α levels (P = 0.015 compared with NPD males. Transcript expression in offspring heart and liver tissue was reduced for genes involved in calcium signaling (Adcy, Plcb, Prkcb and metabolism (Fto in LPD offspring (P <0.03. These novel data reveal the impact of suboptimal paternal nutrition on adult offspring cardiovascular and metabolic homeostasis, and provide some insight into the underlying regulatory mechanisms.

Metabolic induction and early responses of mouse blastocyst developmental programming following maternal low protein diet affecting life-long health

Previously, we have shown that a maternal low protein diet, fed exclusively during the preimplantation period of mouse development (Emb-LPD), is sufficient to induce by the blastocyst stage a compensatory growth phenotype in late gestation and postnatally, correlating with increased risk of adult onset cardiovascular disease and behavioural dysfunction. Here, we examine mechanisms of induction of maternal Emb-LPD programming and early compensatory responses by the embryo. Emb-LPD induced changes in maternal serum metabolites at the time of blastocyst formation (E3.5), notably reduced insulin and increased glucose, together with reduced levels of free amino acids (AAs) including branched chain AAs leucine, isoleucine and valine. Emb-LPD also caused reduction in the branched chain AAs within uterine fluid at the blastocyst stage. These maternal changes coincided with an altered content of blastocyst AAs and reduced mTORC1 signalling within blastocysts evident in reduced phosphorylation of effector S6 ribosomal protein and its ratio to total S6 protein but no change in effector 4E-BP1 phosphorylated and total pools. These changes were accompanied by increased proliferation of blastocyst trophectoderm and total cells and subsequent increased spreading of trophoblast cells in blastocyst outgrowths. We propose that induction of metabolic programming following Emb-LPD is achieved through mTORC1signalling which acts as a sensor for preimplantation embryos to detect maternal nutrient levels via branched chain AAs and/or insulin availability. Moreover, this induction step associates with changes in extra-embryonic trophectoderm behaviour occurring as early compensatory responses leading to later nutrient recovery. © 2012 Fleming et al.

Maternal periconceptional and gestational low protein diet affects mouse offspring growth, cardiovascular and adipose phenotype at 1 year of age

Human and animal studies have revealed a strong association between periconceptional environmental factors, such as poor maternal diet, and an increased propensity for cardiovascular and metabolic disease in adult offspring. Previously, we reported cardiovascular and physiological effects of maternal low protein diet (LPD) fed during discrete periods of periconceptional development on 6-month-old mouse offspring. Here, we extend the analysis in 1 year aging offspring, evaluating mechanisms regulating growth and adiposity. Isocaloric LPD (9% casein) or normal protein diet (18% casein; NPD) was fed to female MF-1 mice either exclusively during oocyte maturation (for 3.5 days prior to mating; Egg-LPD, Egg-NPD, respectively), throughout gestation (LPD, NPD) or exclusively during preimplantation development (for 3.5 days post mating; Emb-LPD). LPD and Emb-LPD female offspring were significantly lighter and heavier than NPD females respectively for up to 52 weeks. Egg-LPD, LPD and Emb-LPD offspring displayed significantly elevated systolic blood pressure at 52 weeks compared to respective controls (Egg-NPD, NPD). LPD females had significantly reduced inguinal and retroperitoneal fat pad: body weight ratios compared to NPD females. Expression of the insulin receptor (Insr) and insulin-like growth factor I receptor (Igf1r) in retroperitoneal fat was significantly elevated in Emb-LPD females (P&0.05), whilst Emb-LPD males displayed significantly decreased expression of the mitochondrial uncoupling protein 1 (Ucp1) gene compared to NPD offspring. LPD females displayed significantly increased expression of Ucp1 in interscapular brown adipose tissue when compared to NPD offspring. Our results demonstrate that aging offspring body weight, cardiovascular and adiposity homeostasis can be programmed by maternal periconceptional nutrition. These adverse outcomes further exemplify the criticality of dietary behaviour around the time of conception on long-term offspring health. © 2011 Watkins et al.

Be SMART:examining the experience of implementing the NHS Health Check in UK primary care

Background: The NHS Health Check was designed by UK Department of Health to address increased prevalence of cardiovascular disease by identifying risk levels and facilitating behaviour change. It constituted biomedical testing, personalised advice and lifestyle support. The objective of the study was to explore Health Care Professionals' (HCPs) and patients' experiences of delivering and receiving the NHS Health Check in an inner-city region of England. Methods: Patients and HCPs in primary care were interviewed using semi-structured schedules. Data were analysed using Thematic Analysis. Results: Four themes were identified. Firstly, Health Check as a test of 'roadworthiness' for people. The roadworthiness metaphor resonated with some patients but it signified a passive stance toward illness. Some patients described the check as useful in the theme, Health check as revelatory. HCPs found visual aids demonstrating levels of salt/fat/sugar in everyday foods and a 'traffic light' tape measure helpful in communicating such 'revelations' with patients. Being SMART and following the protocolrevealed that few HCPs used SMART goals and few patients spoke of them. HCPs require training to understand their rationale compared with traditional advice-giving. The need for further follow-up revealed disparity in follow-ups and patients were not systematically monitored over time. Conclusions: HCPs' training needs to include the use and evidence of the effectiveness of SMART goals in changing health behaviours. The significance of fidelity to protocol needs to be communicated to HCPs and commissioners to ensure consistency. Monitoring and measurement of follow-up, e.g., tracking of referrals, need to be resourced to provide evidence of the success of the NHS Health Check in terms of healthier lifestyles and reduced CVD risk.

Do little embryos make big decisions? How maternal dietary protein restriction can permanently change an embryo's potential, affecting adult health

Periconceptional environment may influence embryo development, ultimately affecting adult health. Here, we review the rodent model of maternal low-protein diet specifically during the preimplantation period (Emb-LPD) with normal nutrition during subsequent gestation and postnatally. This model, studied mainly in the mouse, leads to cardiovascular, metabolic and behavioural disease in adult offspring, with females more susceptible. We evaluate the sequence of events from diet administration that may lead to adult disease. Emb-LPD changes maternal serum and/or uterine fluid metabolite composition, notably with reduced insulin and branched-chain amino acids. This is sensed by blastocysts through reduced mammalian target of rapamycin complex 1 signalling. Embryos respond by permanently changing the pattern of development of their extra-embryonic lineages, trophectoderm and primitive endoderm, to enhance maternal nutrient retrieval during subsequent gestation. These compensatory changes include stimulation in proliferation, endocytosis and cellular motility, and epigenetic mechanisms underlying them are being identified. Collectively, these responses act to protect fetal growth and likely contribute to offspring competitive fitness. However, the resulting growth adversely affects long-term health because perinatal weight positively correlates with adult disease risk. We argue that periconception environmental responses reflect developmental plasticity and 'decisions' made by embryos to optimise their own development, but with lasting consequences.