Orthostatic hypotension and symptomatic subclinical orthostatic hypotension increase risk of cognitive impairment: an integrated evidence review and analysis of a large older adult hypertensive cohort.

Aims: Systematically reviewing the literature found orthostatic hypotension (OH) to be associated with an increased risk of incident dementia but limited data were available in those at highest risk, the hypertensive oldest-old. Our aim was to analyse the relationship between OH and incident cognitive decline or dementia in this group and to synthesize the evidence base overall. Method and results: Participants aged ≥80 years, with hypertension, were from the Hypertension in the Very Elderly Trial (HYVET) cohort. Orthostatic hypotension was defined as a fall of ≥15 mmHg in systolic and or ≥7 mmHg in diastolic pressure after 2 min standing from a sitting position. Subclinical orthostatic hypotension with symptoms (SOH) was defined as a fall <OH but with unsteadiness, light-headedness, or faintness in the week before blood pressure measurement. Proportional hazard regression was used to examine the relationship between baseline OH, SOH, and cognitive outcomes. There were 3121 in the analytical sample, 538 with OH. Orthostatic hypotension was associated with increased risk of cognitive decline (906 events), hazard ratio (HR) 1.36 (95% confidence interval 1.14-1.59). For incident dementia (241 events), HR 1.34 (0.98-1.84). When competing risk of cardiovascular events were taken into account results were HR 1.39 (1.19-1.62) and HR 1.34 (1.05-1.73), respectively. Subclinical orthostatic hypotension was associated with an increased risk of cognitive decline HR 1.56 (1.12-2.17) and dementia HR 1.79 (1.00-3.20). Combining the results from the HYVET cohort in a meta-analysis with the existing published literature in this area found a 21% (9-35%) increased risk of dementia with OH. Conclusion: Orthostatic hypotension indicates an increased risk of dementia and cognitive decline. SOH may also be considered a risk factor, at least in older hypertensive adults. Questions remain regarding the mechanisms and whether interventions to reduce impact of OH could protect cognition

SCORE2-OP risk prediction algorithms: estimating incident cardiovascular event risk in older persons in four geographical risk regions

Aims The aim of this study was to derive and validate the SCORE2-Older Persons (SCORE2-OP) risk model to estimate 5- and 10-year risk of cardiovascular disease (CVD) in individuals aged over 70 years in four geographical risk regions.Methods and results Sex-specific competing risk-adjusted models for estimating CVD risk (CVD mortality, myocardial infarction, or stroke) were derived in individuals aged over 65 without pre-existing atherosclerotic CVD from the Cohort of Norway (28 503 individuals, 10 089 CVD events). Models included age, smoking status, diabetes, systolic blood pressure, and total- and high-density lipoprotein cholesterol. Four geographical risk regions were defined based on country-specific CVD mortality rates. Models were recalibrated to each region using region-specific estimated CVD incidence rates and risk factor distributions. For external validation, we analysed data from 6 additional study populations {338 615 individuals, 33 219 CVD validation cohorts, C-indices ranged between 0.63 [95% confidence interval (CI) 0.61-0.65] and 0.67 (0.64-0.69)}. Regional calibration of expected-vs.-observed risks was satisfactory. For given risk factor profiles, there was substantial variation across the four risk regions in the estimated 10-year CVD event risk.Conclusions The competing risk-adjusted SCORE2-OP model was derived, recalibrated, and externally validated to estimate 5- and 10-year CVD risk in older adults (aged 70 years or older) in four geographical risk regions. These models can be used for communicating the risk of CVD and potential benefit from risk factor treatment and may facilitate shared decision-making between clinicians and patients in CVD risk management in older persons.Cardiolog

is augmentation index a good measure of vascular stiffness in the elderly?

Objectives: we investigated the exact relationship between age and gender on augmentation pressure (AG) and augmentation index (AI) measured over the radial (muscular) and carotid (elastic) arteries. Design and Methods: AG is the contribution that wave reflection makes to systolic arterial pressure. AI is an indirect measure of arterial stiffness and is calculated as AG divided by pulse pressure (PP) 7100. AG and AI both increase with age. AG and AI were measured in 458 subjects using SphygmoCor. A total of 755 readings were obtained (302 carotid, 453 radial). The mean age was 57.5 \ub1 13.7 years. Diabetic subjects were excluded. Among the subjects, 13.5% were hypertensive. Results: statistically, women had mean values of AI significantly higher than men in both radial and carotid arteries. These differences were less marked with AG. Quadratic equations better described the relationship between AI and age but not AG and age. Thus, AI increased with age up to our median age of 55 years but plateaued thereafter, whereas the AG continued to increase steadily with age. A multiple regression analysis demonstrated that both AI and AG were negatively related to height and positively related to diastolic blood pressure (DBP). Conclusions: AG continues to increase in the elderly over the age of 55, but not AI. AI is higher in women and higher when measured over the carotid than the radial. AI is positively related to DBP and negatively to height. AG is proposed as a more suitable measure of arterial stiffness than AI

From gene expression to gene regulatory networks in Arabidopsis thaliana

Background: The elucidation of networks from a compendium of gene expression data is one of the goals of systems biology and can be a valuable source of new hypotheses for experimental researchers. For Arabidopsis, there exist several thousand microarrays which form a valuable resource from which to learn. Results: A novel Bayesian network-based algorithm to infer gene regulatory networks from gene expression data is introduced and applied to learn parts of the transcriptomic network in Arabidopsis thaliana from a large number (thousands) of separate microarray experiments. Starting from an initial set of genes of interest, a network is grown by iterative addition to the model of the gene, from another defined set of genes, which gives the 'best' learned network structure. The gene set for iterative growth can be as large as the entire genome. A number of networks are inferred and analysed; these show (i) an agreement with the current literature on the circadian clock network, (ii) the ability to model other networks, and (iii) that the learned network hypotheses can suggest new roles for poorly characterized genes, through addition of relevant genes from an unconstrained list of over 15,000 possible genes. To demonstrate the latter point, the method is used to suggest that particular GATA transcription factors are regulators of photosynthetic genes. Additionally, the performance in recovering a known network from different amounts of synthetically generated data is evaluated. Conclusion: Our results show that plausible regulatory networks can be learned from such gene expression data alone. This work demonstrates that network hypotheses can be generated from existing gene expression data for use by experimental biologists

Detecting chronic kidney disease in older people; what are the implications?

BACKGROUND: national policy is focused on early identification, referral and management of chronic kidney disease (CKD) to prevent both progression to endstage renal failure and cardiovascular disease. However, the significance of identifying CKD in older people is unclear. OBJECTIVE: to determine the frequency of CKD in older people using estimated glomerular filtration rate (eGFR), and its associations with morbidity and functional measures. DESIGN: observational cross-sectional analysis of baseline data from a large cluster randomised trial of health and social assessment of older people in the community. SETTING: included 53 general practices in Great Britain. SUBJECTS: subjects were people aged 75 and over, living in the community participating in the trial arm where systematic blood testing was undertaken. METHODS: the response rate for participation at baseline assessment of those eligible was 73% (15,536/20,934), of whom 13,109 (86%) participants had a serum creatinine measured, and an eGFR derivable using the Modification of Diet in Renal Disease formula (MDRD) in ml/min/1.73 m(2). Key outcomes were the prevalence of CKD stages and their associations with morbidity and functional status. RESULTS: prevalence of CKD was 56.1% (95% CI 55.3-57.0) for eGFR 45 need to be determine