Serial Measurements of N-Terminal Pro-Brain Natriuretic Peptide in Patients with Coronary Heart Disease

<div><p>Objective</p><p>To assess the prognostic value of 12-months N-Terminal Pro-Brain Natriuretic Peptide (NT-proBNP) levels on adverse cardiovascular events in patients with stable coronary heart disease.</p><p>Methods</p><p>NT-proBNP concentrations were measured at baseline and at 12-months follow-up in participants of cardiac rehabilitation (median follow-up 8.96 years). Cox-proportional hazards models evaluated the prognostic value of log-transformed NT-proBNP levels, and of 12-months NT-proBNP relative changes on adverse cardiovascular events adjusting for established risk factors measured at baseline.</p><p>Results</p><p>Among 798 participants (84.7% men, mean age 59 years) there were 114 adverse cardiovascular events. 12-months NT-proBNP levels were higher than baseline levels in 60 patients (7.5%) and numerically more strongly associated with the outcome in multivariable analysis (HR 1.65 [95% CI 1.33–2.05] vs. HR 1.41 [95% CI 1.12–1.78], with a net reclassification improvement (NRI) of 0.098 [95% CI 0.002–0.194] compared to NRI of 0.047 [95% CI −0.0004–0.133] for baseline NT-proBNP levels. A 12-month 10% increment of NT-proBNP was associated with a HR of 1.35 [95% CI 1.12–1.63] for the onset of an adverse cardiovascular event. Subjects with a 12-month increment of NT-proBNP had a HR of 2.56 [95% CI 1.10–5.95] compared to those with the highest 12-months reduction.</p><p>Conclusions</p><p>Twelve-months NT-proBNP levels after an acute cardiovascular event are strongly associated with a subsequent event and may provide numerically better reclassification of patients at risk for an adverse cardiovascular event compared to NT-proBNP baseline levels after adjustment for established risk factors.</p></div

Measures of model accuracy.

<p>^aadjusted for age, sex, BMI, blood pressure, LV function, current smoking, history of diabetes, total cholesterol, HDL-cholesterol, GFR std, use of statins</p><p>^badjusted for baseline levels of ln NT-proBNP, age, sex, BMI, blood pressure, LV function, current smoking, history of diabetes, total cholesterol, HDL-cholesterol, GFR std, use of statins</p><p>Measures of model accuracy.</p

Sociodemographic, clinical and laboratory characteristics of participants (n = 798).

<p>Sociodemographic, clinical and laboratory characteristics of participants (n = 798).</p

Multivariable analyses between walking and sedentary duration with all-cause mortality for 24 hours as well as stratified by specific periods with time-specific quartiles.

<p>Multivariable analyses between walking and sedentary duration with all-cause mortality for 24 hours as well as stratified by specific periods with time-specific quartiles.</p

Study design.

<p>Study design.</p

Kaplan-Meier estimates of adverse cardiovascular events according to categories of relative changes (<i>P</i>-value of log rank test = 0.001).

<p>Kaplan-Meier estimates of adverse cardiovascular events according to categories of relative changes (<i>P</i>-value of log rank test = 0.001).</p

Manhattan plots for KORA (a) and LURIC (b).

<p>Manhattan plots for KORA (a) and LURIC (b).</p

Q-Q plots for KORA (a) and LURIC (b).

<p>Q-Q plots for KORA (a) and LURIC (b).</p

Description of the study population.

<p>Values denote %, in case of continuous variable, mean (standard deviation) is given.</p>*<p>only n = 1,477 subjects; ** Median (lower-upper quartile).</p

Association of the top SNP rs651007 with log-transformed sE-selectin, adjusted for age and sex (and additionally for survey in KORA).

<p> <i>Coding allele was the minor allele.</i></p>*<p> <i>For three subjects in KORA and in LURIC, information on rs651007 was missing.</i></p>**<p> <i>Change in R² of age- and sex-adjusted models (+ survey in KORA) with and without rs651007.</i></p