Dynamic cardiovascular risk assessment in elderly people. The role of repeated N-terminal pro-B-type natriuretic peptide testing

Abstract

Objectives: This study sought to determine whether serial measurement of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in community-dwelling elderly people would provide additional prognostic information to that from traditional risk factors.

Background: Accurate cardiovascular risk stratification is challenging in elderly people.

Methods: NT-proBNP was measured at baseline and 2 to 3 years later in 2,975 community-dwelling older adults free of heart failure in the longitudinal CHS (Cardiovascular Health Study). This investigation examined the risk of new-onset heart failure (HF) and death from cardiovascular causes associated with baseline NT-proBNP and changes in NT-proBNP levels, adjusting for potential confounders.

Results: NT-proBNP levels in the highest quintile (>267.7 pg/ml) were independently associated with greater risks of HF (hazard ratio [HR]: 3.05; 95% confidence interval [CI]: 2.46 to 3.78) and cardiovascular death (HR: 3.02; 95% CI: 2.36 to 3.86) compared with the lowest quintile (<47.5 pg/ml). The inflection point for elevated risk occurred at NT-proBNP 190 pg/ml. Among participants with initially low NT-proBNP (<190 pg/ml), those who developed a >25% increase on follow-up to >190 pg/ml (21%) were at greater adjusted risk of HF (HR: 2.13; 95% CI: 1.68 to 2.71) and cardiovascular death (HR: 1.91; 95% CI: 1.43 to 2.53) compared with those with sustained low levels. Among participants with initially high NT-proBNP, those who developed a >25% increase (40%) were at higher risk of HF (HR: 2.06; 95% CI: 1.56 to 2.72) and cardiovascular death (HR: 1.88; 95% CI: 1.37 to 2.57), whereas those who developed a >25% decrease to <or=190 pg/ml (15%) were at lower risk of HF (HR: 0.58; 95% CI: 0.36 to 0.93) and cardiovascular death (HR: 0.57; 95% CI: 0.32 to 1.01) compared with those with unchanged high values.

Conclusions: NT-proBNP levels independently predict heart failure and cardiovascular death in older adults. NT-proBNP levels frequently change over time, and these fluctuations reflect dynamic changes in cardiovascular risk.

Figure 1. Flow diagram of cardiovascular health study participants

Cardiovascular health study participants (CHS) with blood samples available for amino terminal pro-B-type natriuretic peptide (NT-proBNP) at baseline and follow-up visits. HF, heart failure.

Figure 2. Hazard ratios for new onset heart failure by decile of NT-proBNP

Demographic adjusted hazard ratios for developing new onset heart failure by decile of baseline amino terminal pro-B-type natriuretic peptide (NT-proBNP) level.

Figure 3. Kaplan Meier plots based on quintile of NT-proBNP

Unadjusted Kaplan Meier plots for (A) time to new onset heart failure diagnosis and (B) time to cardiovascular death based on the quintile of the baseline visit amino terminal pro-B-type natriuretic peptide (NT-proBNP) level.

Figure 4. Incident rates for cardiovascular outcomes based on change of NT-proBNP level

Incident rates for (A) new onset heart failure (HF) and (B) cardiovascular (CV) death based on change or absence of change between baseline and follow-up amino terminal pro-B-type natriuretic peptide (NT-proBNP) levels. Change in NT-proBNP level is defined among those with a baseline NT-proBNP <190 pg/mL as either a decrease in NT-proBNP of at least 25% or an increase of at least 25% to a level ≥ 190 pg/mL. Change in NT-proBNP level is defined among those with a baseline NT-proBNP ≥190 pg/mL as either a decline of at least 25% to a level <190 pg/mL or an increase of >25%.

Figure 4. Incident rates for cardiovascular outcomes based on change of NT-proBNP level

Incident rates for (A) new onset heart failure (HF) and (B) cardiovascular (CV) death based on change or absence of change between baseline and follow-up amino terminal pro-B-type natriuretic peptide (NT-proBNP) levels. Change in NT-proBNP level is defined among those with a baseline NT-proBNP <190 pg/mL as either a decrease in NT-proBNP of at least 25% or an increase of at least 25% to a level ≥ 190 pg/mL. Change in NT-proBNP level is defined among those with a baseline NT-proBNP ≥190 pg/mL as either a decline of at least 25% to a level <190 pg/mL or an increase of >25%.