Wouter de Ruijter

Use of Framingham risk score and new biomarkers to predict cardiovascular mortality in older people: population based observational cohort study.

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.

High Blood Pressure and Resilience to Physical and Cognitive Decline in the Oldest Old: The Leiden 85-Plus Study

To evaluate the association between various blood pressure (BP) measures at age 85 and future decline in physical and cognitive function the oldest old.

Blood Pressure Variability and Cardiovascular Risk in the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER)

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.

High Blood Pressure, Physical and Cognitive Function, and Risk of Stroke in the Oldest Old: The Leiden 85-Plus Study

Background and Purpose— Epidemiological studies have shown mixed findings on the association between hypertension and stroke in the oldest old. Heterogeneity of the populations under study may underlie variation in outcomes. We examined whether the level of physical and cognitive function moderates the association between blood pressure and stroke. Methods— We included 513 subjects aged 85 years old from the population-based Leiden 85-plus Study. Systolic blood pressure, diastolic blood pressure, mean arterial pressure, and pulse pressure were measured at baseline. Activities of daily living and Mini-Mental State Examination were assessed to estimate level of physical and cognitive function, respectively. Five-year risk of stroke was estimated with Cox regression analysis. Results— In the entire cohort, there were no associations between various measures of blood pressure and risk of stroke except for the inverse relation between pulse pressure and stroke risk (hazard ratio [HR], 0.80 [95% confidence interval [CI], 0.66–0.98]). Among subjects with impaired physical functioning, higher systolic blood pressure (HR, 0.74 [95% CI, 0.59–0.92]), mean arterial pressure (HR: 0.68 [95% CI, 0.47–0.97]), and pulse pressure (HR, 0.71 [95% CI, 0.55–0.93]) were associated with reduced risk of stroke. Likewise, among subjects with impaired cognitive functioning, higher systolic blood pressure was associated with reduced risk of stroke (HR, 0.80 [95% CI, 0.65–0.98]). In subjects with unimpaired cognitive functioning, higher diastolic blood pressure (HR: 1.98 [95% CI, 1.21–3.22]) and mean arterial pressure (HR, 1.70 [95% CI, 1.08–2.68]) were associated with higher risk of stroke. Conclusions— Our findings suggest that impaired physical and cognitive function moderates the association between blood pressure and stroke.

Effect of Discontinuation of Antihypertensive Treatment in Elderly People on Cognitive Functioning—the DANTE Study Leiden: A Randomized Clinical Trial

IMPORTANCE Observational studies indicate that lower blood pressure (BP) increases risk for cognitive decline in elderly individuals. Older persons are at risk for impaired cerebral autoregulation; lowering their BP may compromise cerebral blood flow and cognitive function. OBJECTIVE To assess whether discontinuation of antihypertensive treatment in older persons with mild cognitive deficits improves cognitive, psychological, and general daily functioning. DESIGN, SETTING, AND PARTICIPANTS A community-based randomized clinical trial with a blinded outcome assessment at the 16-week follow-up was performed at 128 general practices in the Netherlands. A total of 385 participants 75 years or older with mild cognitive deficits (Mini-Mental State Examination score, 21-27) without serious cardiovascular disease who received antihypertensive treatment were enrolled in the Discontinuation of Antihypertensive Treatment in Elderly People (DANTE) Study Leiden from June 26, 2011, through August 23, 2013 (follow-up, December 16, 2013). Intention-to-treat analyses were performed from January 20 through April 11, 2014. INTERVENTIONS Discontinuation (n=199) vs continuation (n=186) of antihypertensive treatment (allocation ratio, 1:1). MAIN OUTCOMES AND MEASURES Change in the overall cognition compound score. Secondary outcomes included changes in scores on cognitive domains, the Geriatric Depression Scale-15, Apathy Scale, Groningen Activity Restriction Scale (functional status), and Cantril Ladder (quality of life). RESULTS Compared with 176 participants undergoing analysis in the control (continuation) group, 180 in the intervention (discontinuation) group had a greater increase (95% CI) in systolic BP (difference, 7.36 [3.02 to 11.69] mm Hg; P=.001) and diastolic BP (difference, 2.63 [0.34 to 4.93] mm Hg; P=.03). The intervention group did not differ from the control group in change (95% CI) in overall cognition compound score (0.01 [-0.14 to 0.16] vs -0.01 [-0.16 to 0.14]; difference, 0.02 [-0.19 to 0.23]; P=.84). The intervention and control groups did not differ significantly in secondary outcomes, including differences (95% CIs) in change in compound scores of the 3 cognitive domains (executive function, -0.07 [-0.29 to 0.15; P=.52], memory, 0.08 [-0.12 to 0.29; P=.43], and psychomotor speed, -0.85 [-1.72 to 0.02; P=.06]), symptoms of apathy (0.17 [-0.65 to 0.99; P=.68]) and depression (0.14 [-0.20 to 0.48; P=.41]), functional status (-0.72 [-1.52 to 0.09; P=.08]), and quality-of-life score (-0.09 [-0.34 to 0.16; P=.46]). Adverse events were equally distributed. CONCLUSIONS AND RELEVANCE In older persons with mild cognitive deficits, discontinuation of antihypertensive treatment did not improve cognitive, psychological, or general daily functioning at the 16-week follow-up. TRIAL REGISTRATION trialregister.nl Identifier: NTR2829.

Vitamin B12 and folate and the risk of anemia in old age: the Leiden 85-Plus Study.

BACKGROUND Screening for deficiencies in vitamin B(12) and folate is advocated to prevent anemia in very elderly individuals. However, the effects of vitamin B(12) and folate deficiency on the development of anemia in old age have not yet been established. METHODS The current study is embedded in the Leiden 85-Plus Study, a population-based prospective study of subjects aged 85 years. Levels of vitamin B(12), folate, and homocysteine were determined at baseline. Hemoglobin levels and mean corpuscular volume (MCV) were determined annually during 5 years of follow-up. RESULTS We analyzed data from 423 subjects who did not use any form of cyanocobalamin, hydroxocobalamin, or folic acid supplementation, neither at baseline nor during follow-up. Folate deficiency (<7 nmol/L; n = 34) and elevated homocysteine levels (>13.5 mumol/L; n = 194) were associated with anemia at baseline (adjusted odds ratio [OR], 2.44; 95% confidence interval [CI], 1.06-5.61; and adjusted OR, 1.82; 95% CI, 1.08-3.06, respectively), but vitamin B(12) deficiency (<150 pmol/L; n = 68) was not (adjusted OR, 1.51; 95% CI, 0.79-2.87). Furthermore, vitamin B(12) deficiency was not associated with the development of anemia during follow-up (adjusted HR, 0.92; 95% CI, 0.46-1.82) or with changes in MCV (adjusted linear mixed model; P = .77). Both folate deficiency and elevated homocysteine levels were associated with the development of anemia from age 85 years onward (adjusted HR, 3.33; 95% CI, 1.55-7.14; and adjusted HR, 1.70; 95% CI, 1.01-2.88, respectively), but not with an increase in MCV over time (P > .30). CONCLUSION In the general population of very elderly individuals, anemia in 85-year-old subjects is associated with folate deficiency and elevated homocysteine levels but not with vitamin B(12) deficiency.

Clinical relevance of a raised plasma N-terminal pro-brain natriuretic peptide level in a population-based cohort of nonagenarians.

OBJECTIVES: To investigate whether plasma N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) remains a specific marker of cardiac illness in very old age and can be used to identify very elderly people at high risk for death independent of the presence of known cardiac diagnoses.

The routine electrocardiogram for cardiovascular risk stratification in old age : The leiden 85-plus study

OBJECTIVES: To explore the prognostic value of signs of prior myocardial infarction (MI) and atrial fibrillation (AF) on routine electrocardiograms (ECGs) at the age of 85 with respect to mortality and changes in functional status.

Low blood pressure predicts increased mortality in very old age even without heart failure: the Leiden 85-plus Study

To investigate whether low systolic blood pressure is predictive for increased mortality risk in 90‐year‐old subjects without heart failure, defined by low levels of NT‐proBNP, as well as in 90‐year‐old subjects with high levels of NT‐proBNP.

Framingham Stroke Risk Score and Cognitive Impairment for Predicting First-Time Stroke in the Oldest Old

Background and Purpose— Predictive value of the conventional risk factors for stroke attenuates with age. Cognitive impairment has been implicated as a potential predictor for stroke in older subjects. Our aim was to compare the Framingham stroke risk score with cognitive functioning for predicting first-time stroke in a cohort of the oldest old individuals. Methods— We included 480 subjects, aged 85 years, from the Leiden 85-plus Study. At baseline, data on the Framingham stroke risk score and the Mini-Mental State Examination (MMSE) score were obtained. Risk of first-time stroke was estimated in tertiles of Framingham and MMSE scores. Receiver operating characteristic curves with corresponding areas under the curves (AUCs) and 95% confidence intervals (CIs) were constructed for both Framingham and MMSE scores. Results— Subjects with high Framingham risk score compared with those with low Framingham risk score did not have a higher risk of stroke (hazard ratio, 0.77; 95% CI, 0.39–1.54). Conversely, subjects with high levels of cognitive impairment compared with those with low levels of cognitive impairment had a higher risk of stroke (hazard ratio, 2.85; 95% CI, 1.48–5.51). In contrast to the Framingham risk score (AUCs, 0.48; 95% CI, 0.40–0.56), MMSE score had discriminative power to predict stroke (AUCs, 0.65; 95% CI, 0.57–0.72). There was a significant difference between AUCs for Framingham risk score and MMSE score (P=0.006). Conclusions— In the oldest old, the Framingham stroke risk score is not predictive for first-time stroke. In contrast, cognitive impairment, as assessed by MMSE score, identifies subjects at higher risk for stroke.