Long-term prognostic value of N-Terminal Pro-Brain Natriuretic Peptide (NT-proBNP) changes within one year in patients with coronary heart disease
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1 Long-term prognostic value of N-Terminal Pro-Brain Natriuretic Peptide (NT-proBNP) changes within one year in patients with coronary heart disease D. Dallmeier 1, D. Rothenbacher 2, W. Koenig 1, H. Brenner 3 Dhayana Dallmeier, MD 1 Dept. of Internal Medicine II - Cardiology, University of Ulm Medical Center, Germany 2 Institute of Epidemiology and Medical Biometry, 3 German Cancer Research Center, Division of Clinical Epidemiology & Aging Research 1
2 I have nothing to disclose. 2
3 Every year worldwide 7 million people experience a myocardial infarction (MI) Among survivors about 20% will suffer a recurrent cardiovascular event during the first 5 years after the initial event N-TERMINAL PRO-BRAIN NATRIURETIC PEPTIDE 3 3
4 N-TERMINAL PRO-BRAIN NATRIURETIC PEPTIDE Single measurements have shown strong prognostic value for cardiovascular events, all-cause mortality or heart failure NT-proBNP guided therapy has been associated with a reduced number of cardiovascular events among patients with heart failure Longitudinal NT-proBNP measurements are recommended for further risk assessment among patients with heart failure Longitudinal changes have been evaluated for time periods < 1 year Less is known about the prognostic value of longitudinal measurements among patients with stable coronary heart disease (CHD) 4 4
5 Objective To evaluate the prognostic value of a NT-proBNP 12-months change on subsequent cardiovascular disease events in patients with stable CHD Relative Change Absolute Change Cutoff of ±30% change from baseline level* Quartiles Across a set of threshold values from 100 to 1000 pg/ml NT-proBNP *Thygesen K et al. Recommendations for the use of natriuretic peptides in acute cardiac care: A position statement from the Study Group on Biomarkers in Cardiology of the ESC Working Group on Acute Cardiac Care. Eur Heart J
6 Baseline Study Population 1206 patients with CHD participating in a cardiac rehabilitation program between January 1999 April year 3 years 4.5 years 6 years 8 years 10 years All secondary cardiovascular events NT-proBNP 6 6
7 1206 Participants Time to follow-up < 365 days (n=145) Missing values for NT-proBNP at baseline (n=16) at one year follow-up (n=106) at baseline and one year follow-up (n=8) Missing left ventricular function at baseline (n=98) Missing creatinine at baseline (n=98) 826 Participants (121 events) 7 7
8 Statistical Analysis Cox proportional hazard model Outcome All secondary cardiovascular events Covariates at baseline Age Sex Body Mass Index Creatinine Total cholesterol HDL cholesterol Medication Type of treatment Left ventricular function History of MI History of diabetes History of hypertension Smoking status 8 8
9 Results Table 1. Baseline participants characteristics (n=826) Age (mean, SD) 59 ± 8 Male (n (%)) 696 (84.3) Body Mass Index (kg/m 2 ) (mean, SD) 27.0 ± 3.5 Smoking Never Smoker (n (%)) 273 (33.1) Ex-smoker (n (%)) 519 (62.8) Current smoker (n (%)) 34 (4.1) History of Hypertension n (%) 457 (55.3) History of Myocardial Infarction n (%) 426 (51.6) Coronary Artery Bypass Graft n (%) 403 (48.8) History of Diabetes n (%) 132 (15.9) Left Ventricular Function Normal (n (%)) 451 (54.6) Mild depression (n (%)) 200 (24.2) Moderate depression (n (%)) 127 (15.4) Severe depression (n (%)) 48 (5.8) Serum Creatinine (mg/dl) (mean, SD) 0.93 ± 0.3 Total Cholesterol (mg/dl) (mean, SD) 168 ± 32 HDL Cholesterol (mg/dl) (mean, SD) 40 ±
10 Table 2. NT-proBNP median levels (pg/ml) stratified by sex n Male 696 Female 130 Baseline (Q1, Q3) (274, 1030) (345.9, 1634) 1 year follow-up (Q1, Q3) 177 (86.5, 371) 266 (113, 491) 10 10
11 Relative Change Table 3. Multivariable analysis for NT-proBNP relative change No. of events/ No. of subjects HR (95% CI) P value < -30% 99/ ( ) Cutoff of 30% change from baseline level [-30%, 30%] 19/89 Reference > 30% 3/ ( ) 0.25 Quartiles of relative change [IQR] Q1 [-96.93; ] Q2 [ ; ] Q3 [-66.4; ] 18/ ( ) < / ( ) / ( ) Q4 [-47.2; 438.4] 39/206 Reference Adjusted for baseline NT-proBNP (log), age, sex, left ventricular function and history of diabetes 11 11
12 NT-proBNP (pg/ml) Absolute Change High High High Low Low High Low Low Table 4. Model performances across NT-proBNP threshold levels from 600 to 1000 pg/ml Threshold Level (pg/ml) AIC SBC P value Global Model Adjusting for baseline NT-proBNP (log), age, sex, left ventricular function and history of diabetes. AIC Akaike s Information Criterion, SBC Schwarz-Bayes Criterion 12 12
13 Strengths Long-term follow-up with a high completeness rate Limitations Mostly male, white patients Insufficient case number to allow separate analyses (sex, ethnicity) Composite outcome fatal and non-fatal cardiovascular events Generalizability may be affected by low cardiac rehab participation rates 13 13
14 Conclusions The observed high baseline levels of NT-proBNP tended to normalize at one year follow-up A relative change <-30% at one year follow-up was associated with a strong reduction of the risk for a secondary cardiovascular event A threshold value of 700 pg/ml seemed the most suitable one for the prognostic assessment in stable CHD patients 14 14
15 Among those who survived the first year after an acute event, 12-month follow-up measurements of NT-proBNP can provide additional prognostic information with respect to the onset of secondary cardiovascular events 15
16 16
17 Baseline Study Population 1206 patients with CHD participating in a cardiac rehabilitation program between January 1999 April year 3 years 4.5 years 6 years 8 years 10 years All secondary cardiovascular events NT-proBNP Mean time from primary event to blood withdrawal 46.3 days (SD 13.6) 17
18 Supplementary Table 1. Absolute changes between baseline and one year follow-up across different threshold levels Categories of Absolute Change Events/Subjects HR 95% CI P value P value Global Model From < 1000 to < /591 Reference From 1000 to < / [ ] 0.74 From < 1000 to / [ ] 0.25 From 1000 to / [ ] 0.04 From < 900 to < /560 Reference From 900 to < / [ ] 0.23 From < 900 to 900 2/ [ ] 0.16 From 900 to / [ ] 0.01 From < 800 to < /526 Reference From 800 to < / [ ] 0.26 From < 800 to 800 1/ [ ] 0.49 From 800 to / [ ] From < 700 to < /489 Reference From 700 to < / [ ] 0.13 From < 700 to 700 2/ [ ] 0.09 From 700 to / [ ] From < 600 to < /428 Reference From 600 to < / [ ] From < 600 to 600 1/ [ ] 0.66 From 600 to / [ ] Adjusted for baseline NT-proBNP (log), age, sex, left ventricular function and history of diabetes 18
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