, 36:9660 | Cite as

Plasma NT-proBNP as predictor of change in functional status, cardiovascular morbidity and mortality in the oldest old: the Leiden 85-plus study

  • Petra G. van Peet
  • Anton J.M. de Craen
  • Jacobijn Gussekloo
  • Wouter de Ruijter


In the aging society, it is important to identify very old persons at high risk of functional decline, cardiovascular disease and mortality. However, traditional risk markers lose their predictive value with age. We investigated whether plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels predict change in functional status, cardiovascular morbidity and mortality in very old age. Here we present an observational prospective cohort study (Leiden 85-plus Study, 1997–2004) in a population-based sample of 560 individuals aged 85 years with a 5-year complete follow-up for functional status, cardiovascular morbidity and cause-specific mortality. Median NT-proBNP for men was 351 pg/ml (cutoff values for low-medium tertiles 201 pg/ml and medium-high tertiles 649 pg/ml) and, for women, 297 pg/ml (cutoffs 204 and 519 pg/ml, respectively). During the 5-year follow-up, participants with high NT-proBNP had an accelerated cognitive decline and increase of activities of daily living (ADL) disability over time (all at p < 0.01) and an increased risk of incident heart failure [hazard ratio (HR) 3.3 (95 % confidence interval (CI) 1.8–6.1)], atrial fibrillation [HR 4.1 (2.0–8.7)], myocardial infarction [HR 2.1 (1.2–3.7)], stroke [HR 3.4 (1.9–6.3)], cardiovascular mortality [HR 5.5 (3.1–10)], non-cardiovascular mortality [HR 2.0 (1.4–3.0)] and all-cause mortality [HR 2.9 (2.1–4.0)], independent of other known risk markers. All results remained similar after exclusion of participants with heart failure at baseline. In very old age, high-NT-proBNP levels predict accelerated cognitive and functional decline, as well as cardiovascular morbidity and mortality. Results suggest that NT-proBNP can help clinicians to identify very old people at high risk of functional impairment and incident cardiovascular morbidity.


Aged 80 years and over Pro-brain natriuretic peptide Activities of daily living Cognition Cardiovascular disease Cardiovascular morbidity Cardiovascular mortality Prediction Prevention 



Activities of daily living


Atrial fibrillation


Area under the curve


B-type natriuretic peptide


Confidence interval


C-reactive protein


Cardiovascular disease


Geriatric Depression Scale




Heart failure


Hazard ratio


International Classification of Diseases


Estimated GFR (eGFR) using the Modification of Diet in Renal Disease formula


Myocardial infarction


Mini-Mental State Examination


Net reclassification improvement


N-terminal pro-B-type natriuretic peptide


Standard error


Transient ischemic attack



The Leiden 85-plus Study was partly funded by an unrestricted grant from the Dutch Ministry of Health, Welfare and Sports.

Conflict of interest

The funder played no role in study design, collection, analysis and interpretation of data, writing of the report, and in the decision to submit the article for publication. All researchers were independent from the funder and have no conflicts of interest.

Supplementary material

11357_2014_9660_MOESM1_ESM.docx (48 kb)
Table 5 (online supplementary table) Association between NT-proBNP at age 85 years and (changes in) functional status in participants aged 85 through 90 years (n=560) adjusted for blood pressure, total cholesterol, HDL-cholesterol, history of diabetes, current smoking, BMI, MDRD and medication for hypertension (upper 2 rows), and adjusted for all these plus for prevalent cardiovascular disease (middle 2 rows) and for prevalent cerebrovascular disease (lower 2 rows), respectively. (DOCX 48 kb)
11357_2014_9660_MOESM2_ESM.docx (21 kb)
Table 6 (Online supplementary table). Five-year risk of cardiovascular morbidity and mortality depending on plasma NT-proBNP level at 85 years (n=560), adjusted for blood pressure, total cholesterol, HDL-cholesterol, history of diabetes, current smoking, BMI, MDRD and medication for hypertension. (DOCX 21 kb)
11357_2014_9660_MOESM3_ESM.docx (22 kb)
Table 7 (Online supplementary table). Five-year risk of cardiovascular morbidity and mortality depending on plasma NT-proBNP level at 85 years (n=560), adjusted for blood pressure, total cholesterol, HDL-cholesterol, history of diabetes, current smoking, BMI, MDRD, medication for hypertension plus for prevalent cardiovascular disease (DOCX 21 kb)


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Copyright information

© American Aging Association 2014

Authors and Affiliations

  • Petra G. van Peet
    • 1
  • Anton J.M. de Craen
    • 2
  • Jacobijn Gussekloo
    • 1
  • Wouter de Ruijter
    • 1
  1. 1.Department of Public Health and Primary CareLeiden University Medical CenterLeidenThe Netherlands
  2. 2.Department of Gerontology and GeriatricsLeiden University Medical CenterLeidenThe Netherlands

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