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.

Background: reduced telomere length in blood cells has been associated with increased risk of multiple age-related diseases and is widely regarded as a general biomarker of ageing. Therefore, it is important to know both the extent and limitations of this association. We investigated the relation between telomere length and anaemia in two independent cohorts, with the prior expectation of adding anaemia to the list of conditions for which telomere reduction is a risk factor.

Participants and methods: the present study is embedded in the Newcastle 85-plus Study and Leiden 85-plus Study, two population-based studies of inhabitants of Newcastle and North Tyneside, UK (n = 749) and Leiden, the Netherlands (n = 658) aged 85 and over. High-molecular-weight DNA was isolated from full fresh blood (Newcastle) and peripheral blood mononuclear cells samples (Leiden). Telomere length was measured as abundance of telomeric template versus a single gene by quantitative real-time polymerase chain reaction. Anaemia was defined according to World Health Organization criteria.

Results: in both studies, no differences in median telomere length were observed between participants with anaemia and participants without anaemia (Newcastle: 2,846 bp (interquartile range (IQR) 2,433–3,630) versus 2,920 bp (IQR 2,425–3,570), P = 0.63; Leiden: 4,136 bp (IQR 3,879–4,428) versus 4,167 bp (IQR 3,893–4,501), P = 0.41). Telomere length also did not correlate with any other haematological parameter in both men and women.

Conclusions: in contrast to other age-related diseases, telomere length is not associated with anaemia or any other haematological parameter in older individuals in the general population.

Background: prevention of disability is an important aim of healthcare for older persons. Selection of persons at risk is a first crucial step in this process.

Objectives: this study investigates the predictive value of multimorbidity for the development of disability in the general population of very old people and the role of cognitive impairment in this association.

Design: the Leiden 85-plus Study (1997–2004) is an observational prospective cohort study with 5 years of follow-up.

Setting: general population of the city of Leiden, the Netherlands.

Subjects: population based sample of 594 participants aged 85 years.

Methods: disability in activities of daily living (ADL) was measured annually for 5 years with the Groningen Activity Restriction Scale (range 9–36, 9 = optimal). Multimorbidity is defined as the presence of two or more chronic diseases at age 85 years. Cognitive function was measured at baseline with the mini-mental state examination (MMSE).

Results: at baseline participants with multimorbidity had higher ADL disability scores compared with those without [median 11 inter-quartile range (IQR 9–16) versus 9 (IQR 9–13) ADL points, Mann–Whitney U test P < 0.001]. Stratified into four MMSE groups, ADL disability increased over time in all groups, even in participants without multimorbidity (P trend <0.001). Multimorbidity predicted accelerated increase in ADL disability in participants with MMSE of 28–30 points (n = 205, 0.67 points/year, P < 0.001), but not in participants with lower MMSE scores (all P > 0.100).

Conclusion: the predictive value of multimorbidity for the increase in ADL disability varies with cognitive function in very old people. In very old people with good cognitive function, multimorbidity predicts accelerated increase in ADL disability. This relation is absent in very old people with cognitive impairment.

Background

The production of erythropoietin is triggered by impaired oxygen delivery to the kidney, either because of anemia or hypoxemia. High erythropoietin levels have been shown to predict the risk of death among patients with chronic heart failure. We investigated the prognostic value of elevated erythropoietin levels on mortality among very elderly people in the general population.

Methods

The Leiden 85-plus Study is a population-based prospective follow-up study involving 599 people aged 85 years in Leiden, the Netherlands, enrolled between September 1997 and September 1999. Erythropoietin levels were determined at age 86. For this analysis, we included 428 participants with a creatinine clearance of at least 30 mL/min. Mortality data, recorded until Feb. 1, 2008, were obtained from the municipal registry.

Results

During follow-up, 324 (75.7%) participants died. Compared with participants whose erythropoietin levels were in the lowest tertile (reference group), those whose levels were in the middle tertile had a 25% increased risk of death (hazard ratio [HR] 1.25, 95% confidence interval [CI] 0.95–1.64), and those whose levels were in the highest tertile had a 73% increased risk (HR 1.73, 95% CI 1.32–2.26) (p value for trend < 0.01). The association between erythropoietin levels and mortality remained largely unchanged after we adjusted for sex, creatinine clearance, hemoglobin level, comorbidity, smoking status and C-reactive protein level, and was similar for deaths from cardiovascular and noncardiovascular causes.

Interpretation

Among people aged 85 years and older, elevated erythropoietin levels were associated with an increased risk of death, independent of hemoglobin levels.

Background

There is limited insight into the attributable effect of anemia and comorbidity on functional status and mortality in old age.

Methods

The Leiden 85-plus Study is a population-based prospective follow-up study of 562 people aged 85 years. Anemia was defined according to World Health Organization criteria. We measured 3 parameters of functional status at baseline and annually thereafter for 5 years: disability in basic and instrumental activities of daily living, cognitive function and the presence of depressive symptoms. We obtained mortality data from the municipal registry.

Results

The prevalence of anemia at baseline was 26.7% (150/562). Participants who had anemia at baseline had more disability in activities of daily living, worse cognitive function and more depressive symptoms than participants without anemia at baseline (p ≤ 0.01). These differences disappeared after adjustment for comorbidity. After adjustment for comorbidity in the prospective analyses, anemia at baseline was associated with an additional increase in disability in instrumental activities of daily living during follow-up; incident anemia during follow-up (n = 99) was associated with an additional increase in disability in basic activities of daily living. Prevalent and incident anemia were both associated with an increased risk of death, even after we adjusted for sex, education level, income, residence in a long-term care facility, C-reactive protein level, creatinine clearance and the presence of disease (hazard ratio for prevalent anemia 1.41, 95% confidence interval [CI] 1.13 to 1.76; hazard ratio for incident anemia 2.08, 95% CI 1.60 to 2.70).

Interpretation

Anemia in very elderly people appears to be associated with an increased risk of death, independent of comorbidity. However, the associated functional decline appears to be attributed mainly to comorbidity.

Objectives To investigate the performance of classic risk factors, and of some new biomarkers, in predicting cardiovascular mortality in very old people from the general population with no history of cardiovascular disease.

Design The Leiden 85-plus Study (1997-2004) is an observational prospective cohort study with 5 years of follow-up.

Setting General population of the city of Leiden, the Netherlands.

Participants Population based sample of participants aged 85 years (215 women and 87 men) with no history of cardiovascular disease; no other exclusion criteria.

Main measurements Cause specific mortality was registered during follow-up. All classic risk factors included in the Framingham risk score (sex, systolic blood pressure, total and high density lipoprotein cholesterol, diabetes mellitus, smoking and electrocardiogram based left ventricular hypertrophy), as well as plasma concentrations of the new biomarkers homocysteine, folic acid, C reactive protein, and interleukin 6, were assessed at baseline.

Results During follow-up, 108 of the 302 participants died; 32% (35/108) of deaths were from cardiovascular causes. Classic risk factors did not predict cardiovascular mortality when used in the Framingham risk score (area under receiver operating characteristic curve 0.53, 95% confidence interval 0.42 to 0.63) or in a newly calibrated model (0.53, 0.43 to 0.64). Of the new biomarkers studied, homocysteine had most predictive power (0.65, 0.55 to 0.75). Entering any additional risk factor or combination of factors into the homocysteine prediction model did not increase its discriminative power.

Conclusions In very old people from the general population with no history of cardiovascular disease, concentrations of homocysteine alone can accurately identify those at high risk of cardiovascular mortality, whereas classic risk factors included in the Framingham risk score do not. These preliminary findings warrant validation in a separate cohort.