A Review of Frailty Syndrome and Its Physical, Cognitive and Emotional Domains in the Elderly

Peer reviewedPublisher PD

The Roles of PPARs in the Fetal Origins of Metabolic Health and Disease

Beyond the short-term effects on fertility, there is increasing evidence that obesity or the consumption of an inappropriate diet by the mother during pregnancy adversely affects the long-term health of her offspring. PPAR and RXR isotypes are widely expressed in reproductive tissues and in the developing fetus. Through their interactions with fatty acids, they may mediate adaptive responses to the changes in the maternal diet. In the maturing follicle, PPAR-γ has an important role in the granulosa cells that surround the maturing oocyte. After fertilisation, PPAR-γ and PPAR-β/δ are essential regulators of placentation and the subsequent development of key metabolic tissues such as skeletal muscle and adipose cells. Activation of PPAR-γ and PPAR-β/δ during fetal development has the potential to modify the growth and development of these tissues. PPAR-α is expressed at low levels in the fetal liver, however, this expression may be important, as changes in the methylation of DNA in its promoter region are reported to take place during this period of development. This epigenetic modification then programmes subsequent expression. These findings suggest that two separate PPAR-dependent mechanisms may be involved in the fetal adaptations to the maternal diet, one, mediated by PPAR-γ and PPAR-β/δ, regulating cell growth and differentiation; and another adapting long-term lipid metabolism via epigenetic changes in PPAR-α to optimise postnatal survival

Age at quitting smoking as a predictor of risk of cardiovascular disease incidence independent of smoking status, time since quitting and pack-years

BACKGROUND Risk prediction for CVD events has been shown to vary according to current smoking status, pack-years smoked over a lifetime, time since quitting and age at quitting. The latter two are closely and inversely related. It is not known whether the age at which one quits smoking is an additional important predictor of CVD events. The aim of this study was to determine whether the risk of CVD events varied according to age at quitting after taking into account current smoking status, lifetime pack-years smoked and time since quitting. FINDINGS We used the Cox proportional hazards model to evaluate the risk of developing a first CVD event for a cohort of participants in the Framingham Offspring Heart Study who attended the fourth examination between ages 30 and 74 years and were free of CVD. Those who quit before the median age of 37 years had a risk of CVD incidence similar to those who were never smokers. The incorporation of age at quitting in the smoking variable resulted in better prediction than the model which had a simple current smoker/non-smoker measure and the one that incorporated both time since quitting and pack-years. These models demonstrated good discrimination, calibration and global fit. The risk among those quitting more than 5 years prior to the baseline exam and those whose age at quitting was prior to 44 years was similar to the risk among never smokers. However, the risk among those quitting less than 5 years prior to the baseline exam and those who continued to smoke until 44 years of age (or beyond) was two and a half times higher than that of never smokers. CONCLUSIONS Age at quitting improves the prediction of risk of CVD incidence even after other smoking measures are taken into account. The clinical benefit of adding age at quitting to the model with other smoking measures may be greater than the associated costs. Thus, age at quitting should be considered in addition to smoking status, time since quitting and pack-years when counselling individuals about their cardiovascular risk.This research was supported by an NHMRC health services research grant (no. 465130), an NHMRC/NHF PhD scholarship and a Vichealth Fellowship

The association between polypharmacy and late life deficits in cognitive, physical and emotional capability : a cohort study

Open via Springer Compact Agreement Acknowledgements We thank the participants of the Aberdeen Birth Cohort of 1936. Funding ABC1936 was funded (1999–2009) by Biotechnology and Biological Sciences Research Council, Scottish Health Department, Wellcome Trust, Medical Research Council, Alzheimer Research UK, Alzheimer Society and University of Aberdeen Development Trust. This work was supported by the Roland Sutton Academic Trust, Morningfield Association and the Rabin Ezra Scholarship Trust, which provides salary cost and consumables to MK.Peer reviewedPublisher PD

An overview of prevalence, determinants and health outcomes of polypharmacy

Peer reviewedPublisher PD

Increased diastolic blood pressure is associated with MRI biomarkers of dementia-related brain pathology in normative ageing

Background hypertension is a risk for brain ageing, but the mechanisms underlying this effect remain unclear. Magnetic resonance imaging (MRI) detected biomarkers of brain ageing include white matter hyperintensities (WMHs), a marker of cerebrovascular disease, and hippocampal volume, a marker of Alzheimer’s disease pathology. Objective to examine relationships between blood pressure (BP) components and brain pathology in older adults. Subjects two hundred and twenty-seven members of the Aberdeen 1936 Birth Cohort between ages 64 and 68 years. Methods BP was assessed biennially between 64 and 68 years and brain MRI performed at 68 years. The risk factors of interest were diastolic and systolic BP and their visit-to-visit variability. Outcomes were WMH abundance and hippocampal volume. Regression models, controlling for confounding factors, examined their relationships. Results higher diastolic BP predicted increased WMH (β = 0.13, P = 0.044) and smaller hippocampi (β = −0.25, P = 0.006). In contrast, increased systolic BP predicted larger hippocampi (β = 0.22, P = 0.013). Variability of diastolic BP predicted lower hippocampal volume (β = −0.15, P = 0.033). These relationships were independent of confounding life-course risk factors. Anti-hypertensive medication did not modify these relationships, but was independently associated with increased WMH (β = 0.17, P = 0.011). Conclusion increased diastolic BP is associated with biomarkers of both cerebrovascular and Alzheimer’s diseases, whereas the role of systolic BP is less clear, with evidence for a protective effect on hippocampal volume. These differing relationships emphasise the importance of considering individual BP components with regard to brain ageing and pathology. Interventions targeting diastolic hypertension and its chronic variability may provide new strategies able to slow the accumulation of these harmful pathologies

Comparing trends in BMI and waist circumference

The nature of excess body weight may be changing over time to one of greater central adiposity. The aim of this study is to determine whether BMI and waist circumference (WC) are increasing proportionately among population subgroups and the range of bodyweight, and to examine the public health implications of the findings. Our data are from two cross-sectional surveys (the US National Health and Nutrition Examination Studies (NHANES) in 1988-1994 (NHANES III) and 2005-2006), from which we have used samples of 15,349 and 4,176 participants aged ≥20 years. Between 1988-1994 and 2005-2006 BMI increased by an average of 1.8kg/m2 and WC by 4.7cm (adjusted for sex, age, race-ethnicity, and education). The increase in WC was more than could be attributed simply to increases in BMI. This independent increase in WC (of on average, 0.9cm) was consistent across the different BMI categories, sexes, education levels, and race-ethnicity groups. It occurred in younger but not older age groups. Overall in each BMI category, the prevalence of low-risk WC decreased and the prevalence of increased-risk or substantially increased-risk WC increased. These results suggest that the adverse health consequences associated with obesity may be increasingly underestimated by trends in BMI alone. Since WC is closely linked to adverse cardiovascular outcomes, it is important to know the prevailing trends in both of these parameters

Aspirin moderates the association between cardiovascular risk, brain white matter hyperintensity total lesion volume and processing speed in normal ageing

ABC1936 was funded (1999-2009) by the Biotechnology and Biological Sciences Research Council, Scottish Health Department, Wellcome Trust, Medical Research Council, Alzheimer Research UK, Alzheimer Society and University of Aberdeen Development Trust. This work was supported by the Elphinstone Scholarship, Roland Sutton Academic Trust, the Morningfield Association and the Rabin Ezra Scholarship Trust, which provides salary cost and consumables to MK.Peer reviewedPostprin

Development of a percutaneous coronary intervention patient level composite measure for a clinical quality registry

© 2020 The Author(s). Background: Composite measures combine data to provide a comprehensive view of patient outcomes. Despite composite measures being a valuable tool to assess post-intervention outcomes, the patient perspective is often missing. The purpose of this study was to develop a composite measure for an established cardiac outcome registry, by combining clinical outcomes following percutaneous coronary interventions (PCI) with a patient-reported outcome measure (PROM) developed specifically for this population (MC-PROM). Methods: Two studies were undertaken. Study 1: Patients who had undergone a PCI at one of the three participating registry hospital sites completed the 5-item MC-PROM. Clinical outcome data for the patients (e.g. death, myocardial infarction, repeat vascularisation, new bleeding event) were collected 30 days post-intervention as part of routine data collection for the cardiac registry. Exploratory factor analysis of clinical outcomes and MC-PROM data was conducted to determine the minimum number of constructs to be included in a composite measure. Study 2: Clinical experts participated in a Delphi technique, consisting of three rounds of online surveys, to determine the clinical outcomes to be included and the weighting of the clinical outcomes and MC-PROM score for the composite measure. Results: Study 1: Routine clinical outcomes and the MC-PROM data were collected from 266 patients 30 days post PCI. The MC-PROM score was not significantly correlated with any clinical outcomes. Study 2: There was a relatively consistent approach to the weighting of the clinical outcomes and MC-PROM items by the expert panel (n = 18) across the three surveys with the exception of the clinical outcome of 'deceased at 30 days'. The final composite measure included five clinical outcomes within 30 days weighted at 90% (new heart failure, new myocardial infarction, new stent thrombosis, major bleeding event, new stroke, unplanned cardiac rehospitalisation) and the MC-PROM score (comprising 10% of the total weighting). Conclusions: A single patient level composite score, which incorporates weighted clinical outcomes and a PROM was developed. This composite score provides a more comprehensive reported measure of individual patient wellbeing at 30 days post their PCI-procedure, and may assist clinicians to further assess and address patient level factors that potentially impact on clinical recovery

Nutritional B vitamin deficiency alters the expression of key proteins associated with vascular smooth muscle cell proliferation and migration in the aorta of atherosclerotic apolipoprotein E null mice.

Low B vitamin status is linked with human vascular disease. We employed a proteomic and biochemical approach to determine whether nutritional folate deficiency and/or hyperhomocysteinemia altered metabolic processes linked with atherosclerosis in ApoE null mice. Animals were fed either a control fat (C; 4 % w/w lard) or a high-fat [HF; 21 % w/w lard and cholesterol (0/15 % w/w)] diet with different B vitamin compositions for 16 weeks. Aorta tissue was prepared and global protein expression, B vitamin, homocysteine and lipoprotein status measured. Changes in the expression of aorta proteins were detected in response to multiple B vitamin deficiency combined with a high-fat diet (P < 0.05) and were strongly linked with lipoprotein concentrations measured directly in the aorta adventitia (P < 0.001). Pathway analysis revealed treatment effects in the aorta-related primarily to cytoskeletal organisation, smooth muscle cell adhesion and invasiveness (e.g., fibrinogen, moesin, transgelin, vimentin). Combined B vitamin deficiency induced striking quantitative changes in the expression of aorta proteins in atherosclerotic ApoE null mice. Deregulated expression of these proteins is associated with human atherosclerosis. Cellular pathways altered by B vitamin status included cytoskeletal organisation, cell differentiation and migration, oxidative stress and chronic inflammation. These findings provide new insight into the molecular mechanisms through which B vitamin deficiency may accelerate atherosclerosis