Physicians' Academy for Cardiovascular Education

NT-proBNP markedly improves prediction of recurrent cardiovascular events in very elderly

Literature - Van Peet et al., PLoS One 2013 - PLoS One. 2013 Nov 21;8(11):e81400

NT-proBNP Best Predictor of Cardiovascular Events and Cardiovascular Mortality in Secondary Prevention in Very Old Age: The Leiden 85-Plus Study

van Peet PG, Drewes YM, de Craen AJ, et al.
PLoS One. 2013 Nov 21;8(11):e81400. doi: 10.1371/journal.pone.0081400


Elderly people with previous cardiovascular disease (CVD) are known to be at high risk of recurrent CVD. Although secondary preventive treatment can be very effective in very old age, treatment is often far from optimal [1-3] and drug adherence is poor [4]. Identifying patients at highest risk can help clinicians to select those patients that may benefit most from intensified preventive lifestyle measures and drug treatment [5].
Traditional risk markers seem to have less predictive value for secondary prevention [6], although data on their value in the very elderly are scarce.
The authors tested the hypothesis that addition of information on the history of CVD or new biomarkers (markers of renal dysfunction (MDRD), C-reactive protein (CRP), homocysteine and NT-proBNP) to risk assessment based on traditional risk markers may have incremental value for predicting CV events and mortality. The Leiden 85-plus Study is a prospective population-based study that follows people from the moment that they turn 85 year-old. The composite endpoint ‘CV morbidity and mortality’ was defined as incident fatal and non-fatal myocardial infarction, incident fatal and non-fatal stroke or any other CV mortality.

Main results

  • Of the 282 participants, 157 (56%) died during the 5-year follow-up. Of these, 67 (43%) died from CV causes. 109 participants (39%) in total experienced the primary endpoint.
  • Univariate analyses of the new biomarkers showed significant associations with CVD risk for CRP (HR: 1.3, 95%CI: 1.03-1.5), homocysteine (HR: 1.4, 95%CI: 1.1-1.6) and NT-proBNP (HR: 1.7, 95%CI: 1.4-2.1), while MDRD was not associated with a higher risk (HR: 0.83, 95%CI: 0.68-1.01).
  • In a multivariable model with all traditional and new risk markers, NT-proBNP was the only new risk marker that was still independently associated with an increased CVD risk (HR: 1.6, 95%CI: 1.3-2.1). Current smoking (HR: 1.8, 95%CI: 1.1-2.9) and history of major CVD (HR: 1.5, 95%CI: 1.01-2.3) were also independently associated with CVD risk.
  • The C-statistic of the combination of traditional risk markers was 0.59 (95%CI: 0.52-0.66). When NT-proBNP was added to all traditional risk markers, the C-statistic increased to 0.67 (95%CI: 0.61-0.74, P(change of C-statistic)=0.023).
  • Net reclassification improvement was 39.0% (P=0.001) when NT-proBNP was added to the reference model with traditional risk markers, and 16.8% (P=0.17) for CRP and 24.7% (P=0.04) when homocysteine was added to the model.


In very old individuals with established CVD, adding the biomarker NT-proBNP substantially improved the predictive value of a risk assessment model based on traditional CVD risk factors.
This study shows that in secondary prevention in very old age, traditional risk markers indeed lose predictive value. Thus, these results call for incorporation of NT-proBNP in risk estimation in secondary prevention in the very elderly. Individuals at the highest risk will likely benefit most from intensified secondary preventive treatment and follow-up.
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