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Background: Falls and consequent injuries are prevalent in older adults. In this group, half of injury-related hospitalizations are associated with falls and the rate of falls increases with age. The evidence on the role of blood pressure and the use of antihypertensive treatment on the risk of falls remains unclear in oldest-old adults (≥85 years)., Objectives: To examine the association between systolic blood pressure (SBP) and incident falls with medical consequences in oldest-old adults and to analyse whether this association is modified by the use of antihypertensive treatments or the presence of cardiovascular disease., Methods: We analysed data from the Leiden 85-plus Study, a prospective, population-based cohort study with adults aged ≥85 years and a 5-year follow-up. Falls with medical consequences were reported by the treating physician of participants. We assessed the association between time-updated systolic blood pressure and the risk of falling over a follow-up period of five years using generalized linear mixed effects models with a binomial distribution and a logit link function. Subgroup analyses were performed to examine the role of antihypertensive treatment and the difference between participant with and without cardiovascular disease., Results: We analysed data from 544 oldest-old adults, 242 (44.4%) of which used antihypertensives. In 81 individuals (15%) ≥1 fall(s) were reported during the follow-up period. The odds for a fall decreased by a factor of 0.86 (95% CI 0.80 to 0.93) for each increase in blood pressure by 10 mmHg. This effect was specific to blood pressure values above 130mmHg. We did not find any evidence that the effect would be modified by antihypertensive treatment, but that there was a tendency that it would be weaker in participants with cardiovascular disease (OR 0.81, 95% CI 0.72 to 0.90 per 10mmHg) compared to those without cardiovascular disease (OR 0.94, 95% CI 0.84 to 1.05 per 10mmHg)., Conclusion: Our results point towards a possible benefit of higher blood pressure in the oldest-old with respect to falls independent of the use of antihypertensive treatments., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2023 Röthlisberger et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Disturbed cognitive function is associated with several causes of mortality; however, the association between cognitive function and the risk of cancer death has not been extensively investigated yet. We aimed to evaluate the association of cognitive function with the risk of cancer death and all-cause mortality in the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) and Leiden 85-plus Study. Additionally, a systematic review and meta-analysis of longitudinal studies were conducted to evaluate the association of cognitive function and risk of cancer death., Methods: Risk of cancer death and all-cause mortality were reported using hazard ratios (HRs) with 95% confidence interval (CI) in tertiles of cognitive function of PROSPER and Leiden85-Plus Study. Additionally, PubMed, Embase, Web of Science, Cochrane, PsycINFO, Academic Search Premier, CINHAL, and Emcare were searched up to November 1st, 2020 to perform a systematic review and meta-analysis. The relative risks (RRs) with 95%CI of cancer death per each standard deviation lower performance in cognitive measurements were calculated., Results: Participants of PROSPER had 1.65-fold (95%CI 1.11-2.47) greater risk of cancer death (P for trend = 0.016) and 1.85-fold (95%CI 1.46-2.34) higher risk of all-cause mortality (P for trend<0.001), in multivariable models. Results of the Leiden-85 Plus Study showed that subjects with MMSE score below 24 had a lower chance of cancer death (HR 0.79, 95%CI 0.36-1.70, P for trend = 0.820) but had 2.18-fold (95%CI 1.57-3.02) higher risk of all-cause mortality compared to the reference group (P for trend<0.001). Besides, the results of systematic review and meta-analysis showed that per each standard deviation lower performance in cognitive function, individuals were at a 10% higher chance of cancer death (RR 1.10, 95%CI 1.00-1.20, P-value = 0.044)., Conclusions: Lower cognitive function performance is associated with a marginally increased risk of cancer death, in line with a significantly greater risk of all-cause mortality., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Multimorbidity and polypharmacy are current challenges when caring for the older population. Both have led to an increase of potentially inappropriate medication (PIM), illustrating the need to assess patients' attitudes towards deprescribing. We aimed to assess the prevalence of PIM use and whether this was associated with patient factors and willingness to deprescribe., Method: We analysed data from the LESS Study, a cross-sectional study on self-reported medication and on barriers and enablers towards the willingness to deprescribe (rPATD questionnaire). The survey was conducted among multimorbid (≥3 chronic conditions) participants ≥70 years with polypharmacy (≥5 long-term medications). A subset of the Beers 2019 criteria was applied for the assessment of medication appropriateness., Results: Data from 300 patients were analysed. The mean age was 79.1 years (SD 5.7). 53% had at least one PIM (men: 47.8%%, women: 60.4%%; p = 0.007). A higher number of medications was associated with PIM use (p = 0.002). We found high willingness to deprescribe in both participants with and without PIM. Willingness to deprescribe was not associated with PIM use (p = 0.25), nor number of PIMs (p = 0.81)., Conclusion: The willingness of older adults with polypharmacy towards deprescribing was not associated with PIM use in this study. These results suggest that patients may not be aware if they are taking PIMs. This implies the need for raising patients' awareness about PIMs through education, especially in females, in order to implement deprescribing in daily practice., Competing Interests: The authors have declared that no competing interests exist.

Background: The best management of hypertension in frail oldest-old (≥80 years of age) remains unclear and we still lack guidelines that provide specific recommendations. Our study aims to investigate guideline use in general practitioners (GPs) and to examine if guideline use relates to different decisions when managing hypertension in frail oldest-old., Design/setting: Cross-sectional study among currently active GPs from 29 countries using a case-vignettes survey., Methods: GPs participated in a survey with case-vignettes of frail oldest-olds varying in systolic blood pressure (SBP) levels and cardiovascular disease (CVD). GPs from 26 European countries and from Brazil, Israel and New Zealand were invited. We compared the percentage of GPs reporting using guidelines per country and further stratified on the most frequently mentioned guidelines. To adjust for patient characteristics (SBP, CVD and GPs' sex, years of experience, prevalence of oldest-old and location of their practice), we used a mixed-effects regression model accounting for clustering within countries., Results: Overall, 2,543 GPs from 29 countries were included. 59.4% of them reported to use guidelines. Higher guideline use was found in female (p = 0.031) and less-experienced GPs (p<0.001). Across countries, we found a large variation in self-reported guideline use, ranging from 25% to 90% of the GPs, but there was no difference in hypertension treatment decisions in frail oldest-old patients between GPs that did not use and GPs that used guidelines, irrespective of the guidelines they used., Conclusion: Many GPs reported using guidelines to manage hypertension in frail oldest-old patients, however guideline users did not decide differently from non-users concerning hypertension treatment decisions. Instead of focusing on the fact if GPs use guidelines or not, we as a scientific community should put an emphasis on what guidelines suggest in frail and oldest-old patients., Competing Interests: The authors declare that they have no competing interests.

Patient satisfaction with the general practitioner (GP) is lower in older persons with a higher level of complexity of health problems. This study investigates whether, in these older persons, changes in satisfaction with their GP, on receiving improved integrated care, is related to their perceived health state.Using the Integrated Systematic Care for Older People (ISCOPE) trial (aimed at improving person- centered integrated care) this study compared changes in satisfaction with the GP in older persons (aged ≥75 years) with a high level of complex health problems on receiving integrated care, stratified for perceived health state at baseline. Satisfaction with the GP was registered on a 5-point Likert scale. Perceived health state was estimated with the Older Persons and Informal Caregivers Survey-Composite End Point (TOPICS-CEP) at baseline, stratified into 33% percentiles. Differences in satisfaction change between the intervention and usual care/control groups (overall and stratified for perceived health state) are presented by percentages of 'very satisfied' participants and improving or deteriorating 1 or more points on the Likert scale. At baseline, the intervention (n = 151) and control group (n = 603) were mainly female (75%) and living alone (62%); mean age was 83 years. Medical status, perceived health state and characteristics of participants were similar. Overall, at baseline 44.4% of respondents in the intervention group were 'very satisfied' compared with 37.1% at follow-up, (difference -7.3%). In the control group, 'very satisfied' at baseline was 32% and at follow up 29.2% (difference -2.8%). The p-value for this difference in change is 0.56. After stratification for TOPICS-CEP the results were the same. In older persons with a high level of complexity of health problems, implementation of person- centered integrated healthcare did not influence their satisfaction with the GP, also not among those with the highest or lowest perceived health state., Competing Interests: The authors have declared that no competing interests exist.

Background: Clinical medication reviews (CMRs) are increasingly performed in older persons with multimorbidity and polypharmacy to reduce drug-related problems (DRPs). However, there is limited evidence that a CMR can improve clinical outcomes. Little attention has been paid to patients' preferences and needs. The aim of this study was to investigate the effect of a patient-centred CMR, focused on personal goals, on health-related quality of life (HR-QoL), and on number of health problems., Methods and Findings: This study was a randomised controlled trial (RCT) performed in 35 community pharmacies and cooperating general practices in the Netherlands. Community-dwelling older persons (≥70 years) with polypharmacy (≥7 long-term medications) were randomly assigned to usual care or to receive a CMR. Randomisation was performed at the patient level per pharmacy using block randomisation. The primary outcomes were HR-QoL (assessed with EuroQol [EQ]-5D-5L and EQ-Visual Analogue Scale [VAS]) and number of health problems (such as pain or dizziness), after 3 and 6 months. Health problems were measured with a self-developed written questionnaire as the total number of health problems and number of health problems with a moderate to severe impact on daily life. Between April 2016 and February 2017, we recruited 629 participants (54% females, median age 79 years) and randomly assigned them to receive the intervention (n = 315) or usual care (n = 314). Over 6 months, in the intervention group, HR-QoL measured with EQ-VAS increased by 3.4 points (95% confidence interval [CI] 0.94 to 5.8; p = 0.006), and the number of health problems with impact on daily life decreased by 12% (difference at 6 months -0.34; 95% CI -0.62 to -0.044; p = 0.024) as compared with the control group. There was no significant difference between the intervention group and control group for HR-QoL measured with EQ-5D-5L (difference at 6 months = -0.0022; 95% CI -0.024 to 0.020; p = 0.85) or total number of health problems (difference at 6 months = -0.30; 95% CI -0.64 to 0.054; p = 0.099). The main study limitations include the risk of bias due to the lack of blinding and difficulties in demonstrating which part of this complex intervention (for example, goal setting, extra attention to patients, reducing health problems, drug changes) contributed to the effects that we observed., Conclusions: In this study, we observed that a CMR focused on personal goals improved older patients' lives and wellbeing by increasing quality of life measured with EQ-VAS and decreasing the number of health problems with impact on daily life, although it did not significantly affect quality of life measured with the EQ-5D. Including the patient's personal goals and preferences in a medication review may help to establish these effects on outcomes that are relevant to older patients' lives., Trial Registration: Netherlands Trial Register; NTR5713., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: SV, HFK, and MB declare that their institution received unconditional grants from KNMP and Service Apotheek for the PhD project of SV, which this study is part of. JB and JG declare that they have no competing interests.

Introduction: Community-dwelling older persons often experience hindering health complaints that disturb daily activities. If general practitioners (GPs) are unaware of such complaints, this could lead to a mismatch in provided care and needed or expected care. In this qualitative study with community-dwelling older persons we investigated how older persons experience hindering health complaints, how they deal with them, and what they expect from their GP., Methods: Participants (aged ≥80 years) with pain and/or problems with walking/standing were invited to participate in a (group)interview about hindering health problems and expectations from general practice. Data were analysed using the framework method and results were discussed with a client panel., Results: Participants experienced various hindering health complaints in addition to pain and/or problems with walking/standing. Complaints affecting social activities were experienced as the most hindering. Participants actively tried to remain independent and, to achieve this, GPs were expected to be involved and be easily accessible. However, they did not expect specific help from their GP for pain or problems with walking/standing. Suggestions for improvement of care from GPs included optimisation of accessibility (continuous availability by telephone), a yearly check including medication review, open communication, and empathy and support during major life events., Conclusions: According to older persons with hindering health complaints, GPs could improve their accessibility/relationship with patients by: 1) continuous telephonic availability, 2) initiating regular contact with medication reviews, and 3) initiating support during major life events. This might lower the reported barriers to contact the GP for hindering health complaints., Competing Interests: The authors have declared that no competing interests exist.

Purpose: Statins are widely used by older persons in primary and secondary prevention of cardiovascular disease. Although serious adverse events are rare, many statin users report mild muscle pain and/or muscle weakness. It's unclear what impact statins exert on a patient's daily life. Research on statin related side effects in older persons is relatively scarce. We therefore investigated the relation between statin use and self-reported hindering muscle complaints in older persons in the general population., Methods: The present research was performed within the Integrated Systematic Care for Older Persons (ISCOPE) study in the Netherlands (Netherlands trial register, NTR1946). All registered adults aged ≥ 75 years from 59 participating practices (n = 12,066) were targeted. Information about the medical history and statin use at baseline and after 9 months was available for 4355 participants from the Electronic Patient Records of the general practitioners. In the screening questionnaire at baseline we asked participants: 'At the moment, which health complaints limit you the most in your day-to-day life?' Answers indicating muscle or musculoskeletal complaints were coded as such. No specific questions about muscle complaints were asked., Results: The participants had a median age of 80.3 (IQR 77.6-84.4) years, 60.8% were female and 28.5% had a history of CVD. At baseline 29% used a statin. At follow-up, no difference was found in the prevalence of self-reported hindering muscle complaints in statin users compared to non-statin users (3.3% vs. 2.5%, OR 1.39, 95% CI 0.94-2.05; P = 0.98). Discontinuation of statin use during follow-up was independent of self-reported hindering muscle complaints., Conclusion: Based on the present findings, prevalent statin use in this community-dwelling older population is not associated with self-reported hindering muscle complaints; however, the results might be different for incident users., Competing Interests: The authors have declared that no competing interests exist.

Background: Integrated care for older persons with complex care needs is widely advocated. Particularly professionals and policy makers have positive expectations. Care outcome results are ambiguous. Receiver and provider satisfaction is relevant but still poorly understood., Methods: During implementation of integrated care in residential homes (The MOVIT project), we compared general satisfaction and satisfaction with specific aspects of General Practitioner (GP) care in older persons and GPs before (cohort I) and after at least 12 months of implementation (cohort II)., Results: The general satisfaction score for GP care given by older persons does not change (Cohort I (n = 762) mean score 8.0 (IQR:7.0-9.0) vs. Cohort II (n = 505) mean score 8.0 (IQR:7.0-8.0);P = 0.01). Expressions of general satisfaction in GPs do not show consistent change (Cohort I (n = 87) vs Cohort II (n = 66), percentage satisfied about; role as GP, 56% vs 67%;P = 0.194, ability to provide personal care, 60% vs 67%;P = 0.038, quality of care, 54% vs 62%;P = 0.316). Satisfaction in older persons about some specific aspects of care do show change; GP-patient relationship, points 61.6 vs 63.3;P = 0.001, willingness to talk about mistakes, score 3.47 vs 3.73;P = 0.001, information received about drugs, score 2.79 vs 2.46;P = 0.002. GPs also report changes in specific aspects: percentage satisfied about multidisciplinary meetings; occurrence, 21% vs 53%;P = <0.001, GP presence, 12% vs 41%;P = <0.001, and participation, 29% vs.51%;P = 0.046., Conclusion: General satisfaction about care received and provided shows no consistent change in older persons and GPs during the implementation of integrated care. Specific changes in satisfaction are found. These show an emphasis on inter-personal aspects in older persons and organizational aspects in GPs., Competing Interests: The authors have declared that no competing interests exist.

Self-rated health is routinely used in research and practise among general populations. Older people, however, seem to change their health perceptions. To accurately understand these changed perceptions we therefore need to study the correlates of older people's self-ratings. We examined self-rated, nurse-rated and physician-rated health's association with common disabilities in older people (the geriatric giants), mortality hazard and life satisfaction. For this, we used an age-representative population of 501 participant aged 85 from a middle-sized city in the Netherlands: the Leiden 85-plus Study. Participants with severe cognitive dysfunction were excluded. Participants themselves provided health ratings, as well as a visiting physician and a research nurse. Visual acuity, hearing loss, mobility, stability, urinal and faecal incontinence, cognitive function and mood (depressive symptoms) were included as geriatric giants. Participants provided a score for life satisfaction and were followed up for vital status. Concordance of self-rated health with physician-rated (k = .3 [.0]) and nurse-rated health (k = .2 [.0]) was low. All three ratings were associated with the geriatric giants except for hearing loss (all p < 0.001). Associations were equal in strength, except for depressive symptoms, which showed a stronger association with self-rated health (.8 [.1] versus .4 [.1]). Self-rated health predicted mortality less well than the other ratings. Self-rated health related stronger to life satisfaction than physician's and nurse's ratings. We conclude that professionals' health ratings are more reflective of physical health whereas self-rated health reflects more the older person's mental health, but all three health ratings are useful in research., Competing Interests: The authors have declared that no competing interests exist.

Purpose: Proactive care for community-dwelling older persons targeting self-reported hindering health complaints might prevent a decline in function. We investigated the spectrum of self-reported hindering complaints of community-dwelling older persons, the association with functional outcomes, and help-seeking behavior for these complaints., Methods: Within the ISCOPE trial, participants (aged ≥75 years) received the ISCOPE screening questionnaire, including the open-ended question "At the moment, which health complaints limit you the most in your day-to-day life?". After coding the answers with the ICPC-1-NL, we examined the prevalence and the association between the number and type of complaints and functional outcomes (Groningen Activities Restriction Scale, quality of life measured on Cantril's Ladder, Mini-Mental State Examination, Geriatric Depression Scale-15, and De Jong Gierveld Loneliness Scale). Electronic patient registers were searched for the most reported complaints., Results: 7285 participants (median age: 81.0 years [IQR 77.8-85.3], 38.6% males) reported 13,524 hindering complaints (median 1, range 0-18); 32.7% reported no complaints. Participants mostly reported problems with walking/standing (22.1%), pain (20.8%) or weakness/tiredness (8.5%). These complaints were mentioned in the electronic patient registers in 28.3%, 91.3% and 55.5%, respectively. Higher numbers of hindering complaints were related to poorer scores on the number of domains with problems, Cantril's Ladder for quality of life, Groningen Activities Restriction Scale, Geriatric Depression Scale, and De Jong Gierveld Loneliness Scale. Self-reported weakness, problems with walking/standing, visual limitations, cognitive problems, dyspnea and back complaints were associated with poorer scores on the number of domains with problems, Groningen Activities Restriction Scale, MMSE or Geriatric Depression Scale., Conclusion: One third of the participants reported no hindering complaints. Problems with walking/standing, pain, and weakness/tiredness were most reported, but not always found in electronic patient registers. A higher number of, and specific self-reported hindering complaints, were associated with poorer scores on functional outcomes. It may be helpful for general practitioners to ask about these complaints and their influence on daily life.

Unlabelled: This study explores the combination of four common health problems in older people and whether problems on four domains result in an additional effect on indicators of poor health. For this purpose, a total of 2681 participants (32% male, mean age 82 years) of the Integrated Systematic Care for Older People (ISCOPE) study were screened on the presence of health problems on four domains (functional, somatic, mental, social) with the postal ISCOPE questionnaire. Extensive interview data on health indicators were obtained at baseline and at 12-months follow-up, including disability (Groningen Activities Restriction Scale, GARS), cognitive function (Mini-Mental State Examination, MMSE), depressive symptoms (Geriatric Depression Scale-15, GDS), loneliness (loneliness scale of De Jong Gierveld), and health-related quality of life (EQ-5D). General practitioner (GP) contact time (min/year) was estimated via GP electronic medical records. Of the study population, 9% had no health problems according to the screening, 8% had problems on one domain, 27% on two, 38% on three and 18% on four domains. At baseline, the number of health domains with problems was associated with poorer scores on the GARS, the MMSE, the GDS-15, the loneliness scale, the EQ-5D and with more GP contact time (p <0.001). Problems on all four domains had an additional negative effect on these health indicators (all pinteraction <0.001). At follow-up, an increased number of domains with problems was associated with an increased decline in health indicators (all p<0.001) and with an additional negative effect on GP contact time of the presence of problems on all four domains (pinteraction <0.001). We conclude that combinations of functional, somatic, mental and social problems are associated with poor health indicators in community-dwelling older people. Since problems on four domains have an additional effect on health, individuals with combined functional, somatic, mental and social problems could benefit from integrated care., Trial Registration: Netherlands Trial Register: NTR1946.

Background: In clinical practice, GPs appeared to have an internalized concept of "vulnerability." This study investigates the variability between general practitioners (GPs) in their vulnerability-assessment of older persons., Methods: Seventy-seven GPs categorized their 75-plus patients (n = 11392) into non-vulnerable, possibly vulnerable, and vulnerable patients. GPs personal and practice characteristics were collected. From a sample of 2828 patients the following domains were recorded: sociodemographic, functional [instrumental activities in daily living (IADL), basic activities in daily living (BADL)], somatic (number of diseases, polypharmacy), psychological (Mini-Mental State Examination, 15-item Geriatric Depression Scale; GDS-15) and social (De Jong-Gierveld Loneliness Scale; DJG). Variability in GPs' assessment of vulnerability was tested with mixed effects logistic regression. P-values for variability (pvar) were calculated by the log-likelihood ratio test., Results: Participating GPs assessed the vulnerability of 10,361 patients. The median percentage of vulnerable patients was 32.0% (IQR 19.5 to 40.1%). From the somatic and psychological domains, GPs uniformly took into account the patient characteristics 'total number of diseases' (OR 1.7, 90% range  = 0, p var = 1), 'polypharmacy' (OR 2.3, 90% range  = 0, p var = 1) and 'GDS-15' (OR 1.6, 90% range  = 0, p var = 1). GPs vary in the way they assessed their patients' vulnerability in the functional domain (IADL: median OR 2.8, 90% range 1.6, p var < 0.001, BADL: median OR 2.4, 90% range 2.9, p var < 0.001) and the social domain (DJG: median OR 1.2, 90% range  = 1.2, p var < 0.001)., Conclusions: GPs seem to share a medical concept of vulnerability, since they take somatic and psychological characteristics uniformly into account in the vulnerability-assessment of older persons. In the functional and social domains, however, variability was found. Vulnerability assessment by GPs might be a promising instrument to select older people for geriatric care if more uniformity could be achieved., Trial Registration: Netherlands Trial Register NTR1946.

Background: Satisfaction is widely used to evaluate and direct delivery of medical care; a complicated relationship exists between patient satisfaction, morbidity and age. This study investigates the relationships between complexity of health problems and level of patient satisfaction of older persons with their general practitioner (GP) and practice., Methods and Findings: This study is embedded in the ISCOPE (Integrated Systematic Care for Older Persons) study. Enlisted patients aged ≥75 years from 59 practices received a written questionnaire to screen for complex health problems (somatic, functional, psychological and social). For 2664 randomly chosen respondents (median age 82 years; 68% female) information was collected on level of satisfaction (satisfied, neutral, dissatisfied) with their GP and general practice, and demographic and clinical characteristics including complexity of health problems. Of all participants, 4% was dissatisfied with their GP care, 59% neutral and 37% satisfied. Between these three categories no differences were observed in age, gender, country of birth or education level. The percentage of participants dissatisfied with their GP care increased from 0.4% in those with 0 problem domains to 8% in those with 4 domains, i.e. having complex health problems (p<0.001). Per additional health domain with problems, the risk of being dissatisfied increased 1.7 times (95% CI 1.4-2.14; p<0.001). This was independent of age, gender, and demographic and clinical parameters (adjusted OR 1.4, 95% CI 1.1-1.8; p = 0.021)., Conclusion: In older persons, dissatisfaction with general practice is strongly correlated with rising complexity of health problems, independent of age, demographic and clinical parameters. It remains unclear whether complexity of health problems is a patient characteristic influencing the perception of care, or whether the care is unable to handle the demands of these patients. Prospective studies are needed to investigate the causal associations between care organization, patient characteristics, indicators of quality, and patient perceptions.

Background: In the aging population cardiovascular disease (CVD) is highly prevalent. Identification of very old persons at high risk of recurrent CVD is difficult, since traditional risk markers loose predictive value with age., Methods: In a population-based sample of 282 85-year old participants with established CVD from the Leiden 85-plus Study, we studied predictive values of traditional cardiovascular risk markers, a history of major CVD (myocardial infarction, stroke or arterial surgery), and new cardiovascular biomarkers (estimated glomerular filtration rate (MDRD), C-reactive protein (CRP), homocysteine and N-terminal pro B-type natriuretic peptide (NT-proBNP)) regarding 5-year risk of recurrent cardiovascular events and mortality (composite endpoint)., Results: During complete 5-year follow-up 157 (56%) participants died. 109 (39%) had a cardiovascular event or died from cardiovascular causes. Individually related to the composite endpoint were: a history of major CVD (HR 1.5 (95%CI 1.03-2.3)), CRP (HR 1.3 (95%CI 1.03-1.5)), homocysteine (HR 1.4 (95%CI 1.2-2.6)) and NT-proBNP (HR 1.7 (95%CI 1.4-2.1)). A prediction model including all traditional risk markers yielded a C-statistic of 0.59 (95%CI 0.52-0.66). Of all five new markers only addition of NT-proBNP improved the C-statistic (0.67 (95%CI 0.61-0.74, p=0.023)). The categoryless net reclassification improvement for NT-proBNP was 39% (p=0.001), for a history of major CVD 27.2% (p=0.03) and for homocysteine 24.7% (p=0.04)., Conclusions: Among very old subjects with established CVD, NT-proBNP was the strongest risk marker for cardiovascular events and cardiovascular mortality. When estimating risk in secondary prevention in very old age, use of NT-proBNP should be considered.

Background: Subclinical thyroid dysfunction has been implicated as a risk factor for cognitive decline in old age, but results are inconsistent. We investigated the association between subclinical thyroid dysfunction and cognitive decline in the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER)., Methods: Prospective longitudinal study of men and women aged 70-82 years with pre-existing vascular disease or more than one risk factor to develop this condition (N = 5,154). Participants taking antithyroid medications, thyroid hormone supplementation and/or amiodarone were excluded. Thyroid function was measured at baseline: subclinical hyper- and hypothyroidism were defined as thyroid stimulating hormones (TSH) <0.45 mU/L or >4.50 mU/L respectively, with normal levels of free thyroxine (FT4). Cognitive performance was tested at baseline and at four subsequent time points during a mean follow-up of 3 years, using five neuropsychological performance tests., Results: Subclinical hyperthyroidism and hypothyroidism were found in 65 and 161 participants, respectively. We found no consistent association of subclinical hyper- or hypothyroidism with altered cognitive performance compared to euthyroid participants on the individual cognitive tests. Similarly, there was no association with rate of cognitive decline during follow-up., Conclusion: We found no consistent evidence that subclinical hyper- or hypothyroidism contribute to cognitive impairment or decline in old age. Although our data are not in support of treatment of subclinical thyroid dysfunction to prevent cognitive dysfunction in later life, only large randomized controlled trials can provide definitive evidence.

Background: Various questionnaires and performance tests predict mortality in older people. However, most are heterogeneous, laborious and a validated consensus index is not available yet. Since most older people are regularly monitored by laboratory tests, we compared the predictive value of a profile of seven routine laboratory measurements on mortality in older persons in the general population with other predictors of mortality; gait speed and disability in instrumental activities of daily living (IADL)., Methodology/principal Findings: Within the Leiden 85-plus Study, a prospective population-based study, we followed 562 participants aged 85 years for mortality over five years. At baseline (age 85 years) high-density lipoprotein cholesterol, albumin, alanine transaminase, hemoglobin, creatinin clearance, C-reactive protein and homocysteine were measured. Participants were stratified based on their number of laboratory abnormalities (0, 1, 2-4 and 5-7). The predictive capacity was compared with gait speed (6-meter walking test) and disability in IADL (Groningen Activity Restriction Scale) by C-statistics. At baseline, 418 (74%) 85-year old participants had at least one laboratory abnormality. All cause mortality risk increased with increasing number of laboratory abnormalities to a hazard ratio of 5.64 [95% CI 3.49-9.12] for those with 5-7 laboratory abnormalities (p<0.001) compared to those without abnormalities. The c-statistic was 0.66 [95% CI 0.59-0.69], similar to that of gait speed and disability in IADL., Conclusions/significance: In the general population of oldest old, the number of abnormalities in seven routine laboratory measurements predicts five-year mortality as accurately as gait speed and IADL disability.

Variability in blood pressure predicts cardiovascular disease in young- and middle-aged subjects, but relevant data for older individuals are sparse. We analysed data from the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) study of 5804 participants aged 70-82 years with a history of, or risk factors for cardiovascular disease. Visit-to-visit variability in blood pressure (standard deviation) was determined using a minimum of five measurements over 1 year; an inception cohort of 4819 subjects had subsequent in-trial 3 years follow-up; longer-term follow-up (mean 7.1 years) was available for 1808 subjects. Higher systolic blood pressure variability independently predicted long-term follow-up vascular and total mortality (hazard ratio per 5 mmHg increase in standard deviation of systolic blood pressure = 1.2, 95% confidence interval 1.1-1.4; hazard ratio 1.1, 95% confidence interval 1.1-1.2, respectively). Variability in diastolic blood pressure associated with increased risk for coronary events (hazard ratio 1.5, 95% confidence interval 1.2-1.8 for each 5 mmHg increase), heart failure hospitalisation (hazard ratio 1.4, 95% confidence interval 1.1-1.8) and vascular (hazard ratio 1.4, 95% confidence interval 1.1-1.7) and total mortality (hazard ratio 1.3, 95% confidence interval 1.1-1.5), all in long-term follow-up. Pulse pressure variability was associated with increased stroke risk (hazard ratio 1.2, 95% confidence interval 1.0-1.4 for each 5 mmHg increase), vascular mortality (hazard ratio 1.2, 95% confidence interval 1.0-1.3) and total mortality (hazard ratio 1.1, 95% confidence interval 1.0-1.2), all in long-term follow-up. All associations were independent of respective mean blood pressure levels, age, gender, in-trial treatment group (pravastatin or placebo) and prior vascular disease and cardiovascular disease risk factors. Our observations suggest variability in diastolic blood pressure is more strongly associated with vascular or total mortality than is systolic pressure variability in older high-risk subjects.

Objective: The objective of this trial, the Leiden 85-Plus Occupational Therapy Intervention Study (LOTIS), was to assess whether unsolicited occupational therapy, as compared to no therapy, can decelerate the increase in disability in high-risk elderly people., Design: This was a randomised controlled trial with 2-y follow-up., Setting: The study took place in the municipality of Leiden in the Netherlands., Participants: The participants were 402 community-dwelling 85-y-old people, with a Mini-Mental State Examination score of >18 points at baseline., Interventions: Participants in the intervention group were visited by an occupational therapist who provided training and education about assistive devices that were already present and who gave recommendations and information about procedures, possibilities, and costs of assistive devices and community-based services. Control participants were not visited by an occupational therapist., Outcome Measures: The primary outcome measure was the score achieved on the Groningen Activity Restriction Scale. Secondary outcome measures included self-evaluations of well-being and feelings of loneliness., Results: THE PARTICIPANTS WERE EVENLY DIVIDED BETWEEN THE TWO GROUPS: 202 participants were allocated to the intervention group and 200 participants to the control group. Of the 202 participants randomised to occupational therapy, 55 participants declined the proposed intervention. An occupational therapist indicated that of the remaining 147 participants, 66 (45%) needed an occupational therapy intervention. A total of 44 new assistive devices and five community-based services were implemented. During follow-up there was a progressive increase in disability in the intervention group (mean annual increase, 2.0 points; SE 0.2; p < 0.001) and control group (mean annual increase, 2.1 points; SE 0.2; p < 0.001). The increase in disability was not significantly different between study groups (0.08 points; 95% CI, -1.1-1.2; p = 0.75). There was also no difference between study groups for any of the secondary outcome measures., Conclusion: Unsolicited occupational therapy in high-risk elderly participants does not decelerate the increase in disability over time.