Bias, precision and heritability of self-reported and clinically measured height in Australian twins

Many studies of quantitative and disease traits in human genetics rely upon self-reported measures. Such measures are based on questionnaires or interviews and are often cheaper and more readily available than alternatives. However, the precision and potential bias cannot usually be assessed. Here we report a detailed quantitative genetic analysis of stature. We characterise the degree of measurement error by utilising a large sample of Australian twin pairs (857 MZ, 815 DZ) with both clinical and self-reported measures of height. Self-report height measurements are shown to be more variable than clinical measures. This has led to lowered estimates of heritability in many previous studies of stature. In our twin sample the heritability estimate for clinical height exceeded 90%. Repeated measures analysis shows that 2-3 times as many self-report measures are required to recover heritability estimates similar to those obtained from clinical measures. Bivariate genetic repeated measures analysis of self-report and clinical height measures showed an additive genetic correlation > 0.98. We show that the accuracy of self-report height is upwardly biased in older individuals and in individuals of short stature. By comparing clinical and self-report measures we also showed that there was a genetic component to females systematically reporting their height incorrectly; this phenomenon appeared to not be present in males. The results from the measurement error analysis were subsequently used to assess the effects of error on the power to detect linkage in a genome scan. Moderate reduction in error (through the use of accurate clinical or multiple self-report measures) increased the effective sample size by 22%; elimination of measurement error led to increases in effective sample size of 41%.

Diabetic heart disease

Diabetes mellitus is responsible for a spectrum of cardiovascular disease. The best known complications arise from endothelial dysfunction, oxidation, inflammation, and vascular remodelling and contribute to atherogenesis. However, the effects on the heart also relate to concurrent hypertensive heart disease, as well as direct effects of diabetes on the myocardium. Diabetic heart disease, defined as myocardial disease in patients with diabetes that cannot be ascribed to hypertension, coronary artery disease, or other known cardiac disease, is reviewed.

Reduced nephron number and glomerulomegaly in Australian Aborigines: A group at high risk for renal disease and hypertension

Aborigines in remote areas of Australia have much higher rates of renal disease, as well as hypertension and cardiovascular disease, than non-Aboriginal Australians. We compared kidney findings in Aboriginal and non-Aboriginal people in one remote region. Glomerular number and mean glomerular volume were estimated with the disector/fractionator combination in the right kidney of 19 Aborigines and 24 non-Aboriginal people undergoing forensic autopsy for sudden or unexpected death in the Top End of the Northern Territory. Aborigines had 30% fewer glomeruli than non-Aborigines-202000 fewer glomeruli per kidney, or an estimated 404000 fewer per person (P=0.036). Their mean glomerular volume was 27% larger (P=0.016). Glomerular number was significantly correlated with adult height, inferring a relationship with birthweight, which, on average, is much lower in Aboriginal than non-Aboriginal people. Aboriginal people with a history of hypertension had 30% fewer glomeruli than those without-250000 fewer per kidney (P=0.03), or 500000 fewer per person, and their mean glomerular volume was about 25% larger. The lower nephron number in Aboriginal people is compatible with their susceptibility to renal failure. The additional nephron deficit associated with hypertension is compatible with other reports. Lower nephron numbers are probably due in part to reduced nephron endowment, which is related to a suboptimal intrauterine environment. Compensatory glomerular hypertrophy in people with fewer nephrons, while minimizing loss of total filtering surface area, might be exacerbating nephron loss. Optimization of fetal growth should ultimately reduce the florid epidemic of renal disease, hypertension, and cardiovascular disease.

Cardiovascular risk estimation by professionally active cardiovascular nurses: Results from the Basel 2005 Nurses Cohort

Background Nurses play a key role in the prevention of cardiovascular disease (CVD) and one would, therefore, expect them to have a heightened awareness of the need for systematic screening and their own CVD risk profile. The aim of this study was to examine personal awareness of CVD risk among a cohort of cardiovascular nurses attending a European conference. Methods Of the 340 delegates attending the 5th annual Spring Meeting on Cardiovascular Nursing (Basel, Switzerland, 2005), 287 (83%) completed a self-report questionnaire to assess their own risk factors for CVD. Delegates were also asked to give an estimation of their absolute total risk of experiencing a fatal CVD event in the next 10 years. Level of agreement between self-reported CVD risk estimation and their actual risk according to the SCORE risk assessment system was compared by calculating weighted Kappa (κw). Results Overall, 109 responders (38%) self-reported having either pre-existing CVD (only 2%), one or more markedly raised CVD risk factors, a high total risk of fatal CVD (≥ 5% in 10 years) or a strong family history of CVD. About half of this cohort (53%) did not know their own total cholesterol level. Less than half (45%) reported having a 10-year risk of fatal CVD of < 1%, while 13% reported having a risk ≥ 5%. Based on the SCORE risk function, the estimated 10-year risk of a fatal CVD event was < 1% for 96% of responders: only 2% had a ≥ 5% risk of such an event. Overall, less than half (46%) of this cohort's self-reported CVD risk corresponded with that calculated using the SCORE risk function (κw = 0.27). Conclusion Most cardiovascular nurses attending a European conference in 2005 poorly understood their own CVD risk profile, and the agreement between their self-reported 10-year risk of a fatal CVD and their CVD risk using SCORE was only fair. Given the specialist nature of this conference, our findings clearly demonstrate a need to improve overall nursing awareness of the role and importance of systematic CVD risk assessment.

The effect of innate compliance on the performance of a counterpulsation device

Cardiovascular disease (CVD) continues to be one of the top causes of mortality in the world. World Heart Organization (WHO) reported that in 2004, CVD contributed to almost 30% of death from estimated worldwide death figures of 58 million[1]. Heart failure treatment varies from lifestyle adjustment to heart transplantation; its aims are to reduce HF symptoms, prolong patient survival and minimize risk [2]. One alternative available in the market for HF treatment is Left Ventricular Assist Device (LVAD). Chronic Intermittent Mechanical Support (CIMS) device is a novel (LVAD) heart failure treatment using counterpulsation similar to Intra Aortic Balloon Pumps (IABP). However, the implantation site of the CIMS balloon is in the ascending aorta just distal to aortic valve contrasted with IABP in the descending aorta. Counterpulsation coupled with implantation close to the aortic valve enables comparable flow augmentation with reduced balloon volume. Two prototypes of the CIMS balloon were constructed using rapid prototyping: the straight-body model is a cylindrical tube with a silicone membrane lining with zero expansive compliance. The compliant-body model had a bulging structure that allowed the membrane to expand under native systolic pressure increasing the device’s static compliance to 1.5 mL/mmHg. This study examined the effect of device compliance and vascular compliance on counterpulsating flow augmentation. Both prototypes were tested on a two-element Windkessel model human mock circulatory loop (MCL). The devices were placed just distal to aortic valve and left coronary artery. The MCL mimicked HF with cardiac output of 3 L/min, left ventricular pressure of 85/15 mmHg, aortic pressure of 70/50 mmHg and left coronary artery flow rate of 66 mL/min. The mean arterial pressure (MAP) was calculated to be 57 mmHg. Arterial compliance was set to be1.25 mL/mmHg and 2.5 mL/mmHg. Inflation of the balloon was triggered at the dicrotic notch while deflation was at minimum aortic pressure prior to systole. Important haemodynamics parameters such as left ventricular pressure (LVP), aortic pressure (AoP), cardiac output (CO), left coronary artery flowrate (QcorMean), and dP (Peak aortic diastolic augmentation pressure – AoPmax ) were simultaneously recorded for both non-assisted mode and assisted mode. ANOVA was used to analyse the effect of both factors (balloon and arterial compliance) to flow augmentation. The results showed that for cardiac output and left coronary artery flowrate, there were significant difference between balloon and arterial compliance at p < 0.001. Cardiac output recorded maximum output at 18% for compliant body and stiff arterial compliance. Left coronary artery flowrate also recorded around 20% increase due to compliant body and stiffer arterial compliance. Resistance to blood ejection recorded highest difference for combination of straight body and stiffer arterial compliance. From these results it is clear that both balloon and arterial compliance are statistically significant factors for flow augmentation on peripheral artery and reduction of resistance. Although the result for resistance reduction was different from flow augmentation, these results serves as an important aspect which will influence the future design of the CIMS balloon and its control strategy. References: 1. Mathers C, Boerma T, Fat DM. The Global Burden of disease:2004 update. Geneva: World Heatlh Organization; 2008. 2. Jessup M, Brozena S. Heart Failure. N Engl J Med 2003;348:2007-18.

Effectiveness and uptake of screening programmes for coronary heart disease and diabetes:a realist review of design components used in interventions

Objective - To evaluate behavioural components and strategies associated with increased uptake and effectiveness of screening for coronary heart disease and diabetes with an implementation science focus. Design - Realist review. Data sources - PubMed, Web of Knowledge, Cochrane Database of Systematic Reviews, Cochrane Controlled Trials Register and reference chaining. Searches limited to English language studies published since 1990. Eligibility criteria - Eligible studies evaluated interventions designed to increase the uptake of cardiovascular disease (CVD) and diabetes screening and examined behavioural and/or strategic designs. Studies were excluded if they evaluated changes in risk factors or cost-effectiveness only. Results - In 12 eligible studies, several different intervention designs and evidence-based strategies were evaluated. Salient themes were effects of feedback on behaviour change or benefits of health dialogues over simple feedback. Studies provide mixed evidence about the benefits of these intervention constituents, which are suggested to be situation and design specific, broadly supporting their use, but highlighting concerns about the fidelity of intervention delivery, raising implementation science issues. Three studies examined the effects of informed choice or loss versus gain frame invitations, finding no effect on screening uptake but highlighting opportunistic screening as being more successful for recruiting higher CVD and diabetes risk patients than an invitation letter, with no differences in outcomes once recruited. Two studies examined differences between attenders and non-attenders, finding higher risk factors among non-attenders and higher diagnosed CVD and diabetes among those who later dropped out of longitudinal studies. Conclusions - If the risk and prevalence of these diseases are to be reduced, interventions must take into account what we know about effective health behaviour change mechanisms, monitor delivery by trained professionals and examine the possibility of tailoring programmes according to contexts such as risk level to reach those most in need. Further research is needed to determine the best strategies for lifelong approaches to screening.

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.

Fetal growth restriction results in remodeled and less efficient hearts in children

Background— Fetal growth restriction (FGR) affects 5% to 10% of newborns and is associated with increased cardiovascular mortality in adulthood. The most commonly accepted hypothesis is that fetal metabolic programming leads secondarily to diseases associated with cardiovascular disease, such as obesity, diabetes mellitus, and hypertension. Our main objective was to evaluate the alternative hypothesis that FGR induces primary cardiac changes that persist into childhood. Methods and Results— Within a cohort of fetuses with growth restriction identified in fetal life and followed up into childhood, we randomly selected 80 subjects with FGR and compared them with 120 normally grown fetuses, matched for gender, birth date, and gestational age at birth. Cardiovascular assessment was performed in childhood (mean age of 5 years). Compared with control subjects, children with FGR had a different cardiac shape, with increased transversal diameters and more globular cardiac ventricles. Although left ejection fraction was similar among the study groups, stroke volume was reduced significantly, which was compensated for by an increased heart rate to maintain output in severe FGR. This was associated with subclinical longitudinal systolic dysfunction (decreased myocardial peak velocities) and diastolic changes (increased E/E' ratio and E deceleration time). Children with FGR also had higher blood pressure and increased intima-media thickness. For all parameters evaluated, there was a linear increase with the severity of growth restriction. Conclusions— These findings suggest that FGR induces primary cardiac and vascular changes that could explain the increased predisposition to cardiovascular disease in adult life. If these results are confirmed, the impact of strategies with beneficial effects on cardiac remodeling should be explored in children with FGR.

An almond-enriched diet increases plasma α-tocopherol and improves vascular function but does not affect oxidative stress markers or lipid levels

Vascular dysfunction is one of the major causes of cardiovascular (CV) mortality and increases with age. Epidemiological studies suggest that Mediterranean diets and high nut consumption reduce CV disease risk and mortality while increasing plasma α-tocopherol. Therefore, we have investigated whether almond supplementation can improve oxidative stress markers and CV risk factors over 4 weeks in young and middle-aged men. Healthy middle-aged men (56 ± 5.8 years), healthy young men (22.1 ± 2.9 years) and young men with two or more CV risk factors (27.3 ± 5 years) consumed 50 g almond/day for 4 weeks. A control group maintained habitual diets over the same period. Plasma α-tocopherol/cholesterol ratios were not different between groups at baseline and were significantly elevated by almond intervention with 50 g almond/day for 4 weeks (p < 0.05). Plasma protein oxidation and nitrite levels were not different between groups whereas, total-, HDL- and LDL-cholesterols and triglycerides were significantly higher in healthy middle-aged and young men with CV risk factors but were not affected by intake. In the almond-consuming groups, flow-mediated dilatation (FMD) improved and systolic blood pressure reduced significantly after 50 g almonds/day for 4 weeks, but diastolic blood pressure reduced only in healthy men. In conclusion, a short-term almond-enriched diet can increase plasma α-tocopherol and improve vascular function in asymptomatic healthy men aged between 20 and 70 years without any effect on plasma lipids or markers of oxidative stress. © 2014 Informa UK, Ltd.

Ocular signs of systemic hypertension:a review

Cardiovascular disease and stroke continue to be the chief causes of death in developed countries and one of the leading causes of visual impairment. The individual with systemic hypertension may remain asymptomatic for many years. Systemic mortality and morbidity are markedly higher for hypertensives than normotensives, but can be significantly reduced by early diagnosis and then efficient management. However, the ability of Optometrists to detect and appropriately refer systemic hypertensives remains generally poor. This review examines the disease, its effects and detection by observation of the retinal signs, particularly those considered to be pre-malignant. Previous methods of classifying retinal hypertensive signs are discussed along with more recent image analysis techniques. The role of the optometrist in detecting, monitoring and appropriate referral of systemic hypertensives is discussed in relation to current research. (C) 2001 The College of Optometrists. Published by Elsevier Science Ltd. All rights reserved.

What factors influence concordance with medications? Findings from the UK Asian Diabetes study

Aims: To investigate concordance with medication, as assessed at baseline and at 1- and 2-year follow-up, and to examine factors associated with non-concordance in a UK-resident South-Asian population. Methods: Data from the UK Asian Diabetes Study were analysed. Concordance with medications was assessed and recorded at three time points during the study. Multiple logistic regression was used to investigate the factors associated with non-concordance; the associations of baseline factors with year 1 concordance and baseline plus year 1 factors with year 2 concordance. Results: Data for 403 patients from seven practices participating in the UK Asian Diabetes Study were analysed. The numbers of patients who were non-concordant were: 63 (16%) at baseline 101 (25%) at year 1; and 122 (30%) at year 2. The baseline-measured variables that were significantly associated with year 1 non-concordance included diabetes duration, history of cardiovascular disease, components of the EuroQol quality of life questionnaire, the EQ-5D score, and number of medications prescribed. In multivariable analyses, the most important determinant of year 1 non-concordance was baseline non-concordance: odds ratio 13.6 (95% confidence limits 4.7, 39.9). Number of medications prescribed for blood pressure control was also significant: odds ratio 1.8 (95% confidence limits 1.4, 2.4). Similar results were observed for year 2 non-concordance. Conclusions: Non-concordance with medications was common and more likely in people prescribed more medications. The current target-driven management of risk factor levels may lead to increasing numbers and doses of medications. Considering the high cost of medications and the implications of poor health behaviours on morbidity and mortality, further investigation of prescribing behaviours and the factors affecting patient concordance are required.

Entropy Based Approach to Finding Interacting Genes Responsible for Complex Human Disease

2000 Mathematics Subject Classification: 62P10, 92D10, 92D30, 94A17, 62L10.

Retinal vascular function and cardiovascular risk factors

The current platform of conventional cardiovascular risk assessments tends to forsake the importance of endothelial function - a key biological mechanism by which cardiovascular risk factors exert their propensity for adverse vascular events. Moreover, the presence and severity of endothelial dysfunction in ‘low-risk’ individuals suggests considerable variability in pre-clinical risk that could potentially be detected well before the onset of disease. The aim of the present thesis was to investigate the presence and impact of retinal vascular dysfunction, as a barometer of endothelial function, in otherwise healthy individuals with one or more cardiovascular risk factors, but low to moderate cardiovascular risk. Systemic circulatory influences on retinal vascular function were also evaluated. The principle sections and findings of this work are: 1. Ageing effect on retinal vascular function • In low-risk individuals, there are age differences in retinal vascular function throughout the entire functional response curve for arteries and veins. Gender differences mainly affect the dilatory phase and are only present in young individuals. 2. Retinal vascular function in healthy individuals with a family history of cardiovascular disease • In low-risk individuals with a family history of cardiovascular disease, impairments in microvascular function at the retinal level correlate with established plasma markers for cardiovascular risk. 3. Ethnic differences in retinal vascular function • When compared to age-matched White Europeans, in low-risk middle-aged South Asians, there are impairments in retinal vascular function that correlate with established cardiovascular risk indicators. 4. Systemic circulatory influences on retinalµvascular function • Systemic antioxidant capacity (redox index) and plasma markers for cardiovascular risk (lipids) influence retinal microvascular function at both arterial and venous levels. 5. Retinal vascular function in individuals with obstructive sleep apnoea: a preliminarystudy • Patients with moderate to severe sleep apnoea exhibit attenuated retinal vascular function.

Diabetes in the very elderly:need for an individualised approach

Background: Intensive risk factor management is recommended for individuals with diabetes. However, it is not known if such an approach is appropriate in the elderly with multiple comorbidities and limited life expectancy. The aim of this study was to characterise a cohort of very elderly individuals with diabetes and assess the impact of known risk factors on mortality. Methods: This was a retrospective audit approved by the clinical audit lead. All patients aged >80 years who attended diabetes outpatient clinics 2 years prior to the date of the audit (April 2012) were identified from clinic records. A detailed history including demographics, comorbidities and treatment were collected. Blood pressure readings, HbA1c, cholesterol and renal function were extracted and the mean of these readings was recorded. Survival status at 2 years was recorded for all patients. Statistical analysis was performed using SPSS19. Results: Data were available for 864 (381 male, 483 female) patients. The majority (75%) lived in their own home. More than 60% had multiple comorbidities and 25% had a prior history of cardiovascular disease. Two-thirds of the patients had more than one hospital admission in 2 years and a third had more than three admissions. 60% were on either insulin or a sulfonylurea. Mean HbA1c was 7.6%, cholesterol 4.2mmol/l, systolic blood pressure 145mmHg and eGFR 53ml/min. Over 2 years, 174 (20%)had died. Age, creatinine and previous coronary heart disease were significant predictors of death. Conclusion: The benefits of intensive diabetes management appear to be uncertain in very elderly patients. The need for intensive treatment must therefore be individualised to each patient.