Yvonne M. Drewes

The effect of cognitive impairment on the predictive value of multimorbidity for the increase in disability in the oldest old: the Leiden 85-plus Study

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.

Homocysteine Levels and Treatment Effect in the Prospective Study of Pravastatin in the Elderly at Risk

To assess the effect of preventive pravastatin treatment on coronary heart disease (CHD) morbidity and mortality in older persons at risk for cardiovascular disease (CVD), stratified according to plasma levels of homocysteine.

Assessment of Appropriateness of Screening Community-Dwelling Older People to Prevent Functional Decline

To identify appropriate screening conditions, stratified according to age and vulnerability, to prevent functional decline in older people.

NT-proBNP best predictor of cardiovascular events and cardiovascular mortality in secondary prevention in very old age: the Leiden 85-plus Study.

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.

Risk stratification and treatment effect of statins in secondary cardiovascular prevention in old age: Additive value of N-terminal pro-B-type natriuretic peptide

Background To date, no validated risk scores exist for prediction of recurrence risk or potential treatment effect for older people with a history of a cardiovascular event. Therefore, we assessed predictive values for recurrent cardiovascular disease of models with age and sex, traditional cardiovascular risk markers, and ‘SMART risk score’, all with and without addition of N-terminal pro-B-type natriuretic peptide (NT-proBNP). Treatment effect of pravastatin was assessed across low and high risk groups identified by the best performing models. Design and methods Post-hoc analysis in 2348 participants (age 70–82 years) with a history of cardiovascular disease within the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) study. Composite endpoint was a recurrent cardiovascular event/cardiovascular mortality. Results The models with age and sex, traditional risk markers and SMART risk score had comparable predictive values (area under the curve (AUC) 0.58, 0.61 and 0.59, respectively). Addition of NT-proBNP to these models improved AUCs with 0.07 (p for difference ((pdiff)) = 0.003), 0.05 (pdiff = 0.009) and 0.06 (pdiff < 0.001), respectively. For the model with age, sex and NT-proBNP, the hazard ratio for the composite endpoint in pravastatin users compared with placebo was 0.67 (95% confidence interval 0.49–0.90) for those in the highest third of predicted risk and 0.91 (0.57–1.46) in the lowest third, number needed to treat 12 and 115 (pdiff = 0.038) respectively. Conclusion In secondary cardiovascular prevention in old age addition of NT-proBNP improves prediction of recurrent cardiovascular disease, cardiovascular mortality and treatment effect of pravastatin. A minimal model including age, sex and NT-proBNP predicts as accurately as complex risk models including NT-proBNP.

Change in calculated cardiovascular risk due to guideline revision: A cross-sectional study in the Netherlands

Background: Guidelines and accompanying risk charts concerning cardiovascular risk management (CVRM) are regularly revised worldwide. Objective: To evaluate whether revision of the Dutch CVRM guideline has led to the reclassification of patients and, accordingly, to changes in drug recommendations. Methods: All medical records (year 2011) of patients aged 40–65 years with no history of cardiovascular disease (CVD) but using antihypertensive and/or lipid-lowering drugs, were selected from the Registration Network of General Practices associated with Leiden University Medical Center. Multiple imputation techniques for missing determinants were used. The individual cardiovascular risk was calculated and the resulting drug recommendation was assessed according to both the 2006 and 2012 versions of the guideline. Results: In total, 2075 patients were selected, of whom 1248 fulfilled the guideline criteria (systolic blood pressure 115–180 mmHg and total cholesterol/high-density-lipoprotein-cholesterol ratio 3.5–8). According to the 2012 guideline, 58.2% of the patients had low risk and 249 patients (20.0%) shifted to a different risk category. For 150 of these patients (12.0%), this category shift implied a shift in drug recommendation. The probability of shifting in drug recommendation increased with increasing age, cholesterol level, and blood pressure, and by being male. Conclusion: Guideline revision may have important implications: based on identical values for risk factors, according to the latest revision of the Dutch CVRM guideline 20% of patients shifted in risk category and 12% of the patients shifted in drug recommendation.

Incidental findings in research: A focus group study about the perspective of the research participant

To explore the experiences and preferences of population‐based research participants to whom an incidental finding was communicated.

Effectiveness and cost-effectiveness of proactive and multidisciplinary integrated care for older people with complex problems in general practice: an individual participant data meta-analysis

Abstract Purpose to support older people with several healthcare needs in sustaining adequate functioning and independence, more proactive approaches are needed. This purpose of this study is to summarise the (cost-) effectiveness of proactive, multidisciplinary, integrated care programmes for older people in Dutch primary care. Methods design individual patient data (IPD) meta-analysis of eight clinically controlled trials. Setting primary care sector. Interventions combination of (i) identification of older people with complex problems by means of screening, followed by (ii) a multidisciplinary integrated care programme for those identified. Main outcome activities of daily living, i.e. a change on modified Katz-15 scale between baseline and 1-year follow-up. Secondary outcomes quality of life (visual analogue scale 0–10), psychological (mental well-being scale Short Form Health Survey (SF)-36) and social well-being (single item, SF-36), quality-adjusted life years (Euroqol-5dimensions-3level (EQ-5D-3L)), healthcare utilisation and cost-effectiveness. Analysis intention-to-treat analysis, two-stage IPD and subgroup analysis based on patient and intervention characteristics. Results included were 8,678 participants: median age of 80.5 (interquartile range 75.3; 85.7) years; 5,496 (63.3%) women. On the modified Katz-15 scale, the pooled difference in change between the intervention and control group was −0.01 (95% confidence interval −0.10 to 0.08). No significant differences were found in the other patient outcomes or subgroup analyses. Compared to usual care, the probability of the intervention group to be cost-effective was less than 5%. Conclusion compared to usual care at 1-year follow-up, strategies for identification of frail older people in primary care combined with a proactive integrated care intervention are probably not (cost-) effective.