Biomarkers screening and high risk populations? Patrick Jourdain Unité thérapeutique d insuffisance cardiaque CH R DUBOS

Transcription

1 Biomarkers screening and high risk populations? Patrick Jourdain Unité thérapeutique d insuffisance cardiaque CH R DUBOS

2 Déclaration de transparence Honorarium (last 3 years) from: Servier,,, MSD, Schering,, Novartis, Daichi, Lilly, Roche, Boston,. Research (last 3 years): Servier, Novartis,,CAS, Amgen, MSD, Schering MSD,, Janssen, pfizer.

3 2014. Screening and biomarkers?

4 A diabetic profile is

5 A risk.

6

7 NT pro BNP et screening de la dysfonction VG BNP levels were compared to echocardiographic findings in 263 patients. Patients were divided into two groups: clinical indication for echocardiography (CIE) (n = 172) and those without clinical indication for echocardiography (no-cie) (n = 91). Cardiologists making the assessment of left ventricular function were blinded when measuring plasma levels of BNP.

8 Seuils et DVG

9 BNP et echographie

10 BNP et performance?

11 Screen HF study 3550 subjects at high risk for incident HF ( 60 years plus 1 HF risk factor), but without pre-existing HF or left ventricular dysfunction Participants at highest risk (n = 664) (NT-proBNP highest quintile; N30.0 pmol/l) and a sample (n = 51) from the lowest NT-proBNP quintile underwent echocardiography.

12 Design

13 Results

14 NP and HF detection in an echographist perspective The original ECHOES study screened a total of 6162 participants from 16 practices in central England. ECHOES included four separate cohorts: 3960 patients randomly sampled from the general population over age 45; 782 patients with a previous label of HF recorded in general practitioner (GP) notes; 928 patients on diuretic therapy and 1062 with known risk factors for heart disease (hypertension, diabetes, angina, history of myocardial infarction (MI)). The four cohorts were stipulated prior to the study and searches were carried out to find patients in each of these groups using general practice records. NT-proBNP levels were measured in 594 participants during the ECHOES study. An HF diagnosis was confirmed for 7 (8%) of those in the general population

15 Impact of an elevated NT pro BNP level

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19 NT PRO BNP ET EVENEMENTS CARDIOVASCULAIRES HORS IC

20 NT-proBNP and stable angina

21 Stable angina and survival

22 Graham S. Hillis case-cohort study was performed in 3,862 patients who participated in the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial. Follow up 5 years

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24 Et en NRI, le NT pro BNP sort encore

25 Impact sur les évènements cardiovasculaires (A) et mortalité (B)

26 Diabète, NT pro BNP et angor stable A total of 1,034 consenting patients with angina pectoris, or evidence of ischemia on exercise electrocardiography or myocardial radionuclide imaging, were included in this analysis. At baseline, selective coronary angiography and left ventriculography were performed in all patients. A thorough medical history of previous CV disease, diabetes, was recorded. Diabetes was defined as a history of diabetes, on antidiabetic treatment, or fasting glucose (FPG) >7 mmol/l. A total of 197 patients (19%) had diabetes. Median (interquar- tile range) NT-proBNP level was increased in patients with diabetes (230 ng/l [78 632]) compared with patients with- out diabetes (161 ng/l [61 423]) (P < 0.015).

27 Interaction Diabète et NT PRo BNP

28 Impact du dosage de NT pro BNP chez les patients agés.

29 Results After a median follow up of 9.2 years, 288 (28%) patients had died, including 206 (25%) nondiabetic patients and 82 (43%) diabetic patients By multivariable Cox regression analysis, the HR was 1.8 (95% CI , P < 0.02) for the group of patients with low NT-proBNP levels and diabetes, 1.6 ( , P < 0.004) for the group of patients with high NT-proBNP without diabetes, and 2.8 ( , P < ) for the group of patients with high NT-proBNP and diabetes

30 Design The prospective study included 1,825 type 2 diabetic patients from the population-based cohort of the Casale Monferrato study. CV risk factors, preexisting CVD, and NT-proBNP levels were evaluated at baseline. All-cause and CV mortality were assessed 5.5 years after baseline examination. Multivariate Cox proportional hazards modeling was used to estimate mortality hazard ratios (HRs).

31 Results During the follow-up period, 390 people died (175 for CVD) out of 9,101 person- years of observations. A significantly increased mortality risk by quartiles of NTproBNP was observed (test for trend, P, 0.001). NT-proBN P values.91 pg/ml conferred HRs of 2.05 (95% CI ) for all-cause and 4.47 ( ) for CV mortality, independently of CV risk factors, including CRP and albumin excretion rate (AER). The association was also significant for modest rises in NTproBNP levels and in patients without microalbuminuria and CVD at baseline

32 Population et NT pro BNP

33 Quartile de NT pro BNP et mortalité toutes causes

34 La valeur pronostique du NT pro BNP existe de façon indépendante à la microalbuminurie

35 A prospective observational study was conducted in 631 diabetic patients. The composite endpoint consisted of unplanned hospitalization for cardiovascular events or death within the observation period of 12 months. NT pro BNP et pronostic

36 Valeur prédictive positive, negative ou «accuracy?

37 Le cut off pronostic à 125 pg/ml est identifié

38 NT pro BNP élevé dans un contexte de population à risque un argument de traitement préventif? L étude PONTIAC 300 patients with type 2 diabetes, elevated NT-proBNP (>125pg/ml) but free of cardiac disease were randomized. Cardiac disease-based exclusion criteria were one or more of the following: history of cardiac disease; signs of cardiac disease in the electrocardiogram; abnormal echocardiography (with the exception of diastolic dysfunction), defined as low ejection fraction; wall motion abnormalities, significant valve dysfunction, or other significant alteration.

39 Work flow The control group was cared as usual the intensified group was additionally treated at a cardiac outpatient clinic for the up- titration (patient up titration ) of RAS-antagonists and beta-blockers. The primary endpoint was hospitalization/death due to cardiac disease after two years. Physicians increased the dosage of the medications until either NT-proBNP concentrations decreased by 50% or below normal values or a maximum recommended or tolerated dose was reached. Patients went for scheduled visits over a period of one year in the intensified group. The observation period for all patients was two years.

40 Baseline characteristics J Am Coll Cardiol 2013;62:

41 Mean NT pro BNP 256 pg/ml

42 Results J Am Coll Cardiol 2013;62:

43 Primary end point J Am Coll Cardiol 2013;62:

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45 The Saint Vincents Screening To Prevent Heart Failure (STOP-HF) Study Etude randomisée de screening sur les peptides natriurétiques pour réduire la prévalence des dysfonction VG et des insuffisances cardiaques (IC) STOP-HF Investigators St. Vincent s / St. Michael s Hospitals and Collaborative GP Group Dublin, Ireland

46 STOP-HF Inclusion / Exclusion Critères d entrée (> 40 ans) avec Hypertension Hyperlipidemie Exclusion IC ou dysfonction VG connue Maladie grave altérant le pronostic Refus Diabete Maladie vasculaire Arrhythmia Obesité Critère primaire Prévalence d insuffisance cardiaque (IC) (hospitalisations) et dysfonction VG Dysfonction Systolique (DS VG): FEVG < 50% Dysfonction Diastolique (DD VG) : E / E > 15 Critère secondaire Hospitalisation pour événement cardiovasculaire IC, Arrhythmie, SCA, AIT/AVC, thormbose périphérique, embolie pulmonaire

47 STOP-HF Intervention Prise en charge de Routine Prise en charge basée sur le BNP BNP annuel résultats non donnés au médecin Prise en charge de routine + Dosage annuel du BNP et Au moins 1 visite au médecin généraliste (MG) par an Avis cardio seulement sur demande du MG si BNP > 50pg/ml : Avis cardio Echo-Doppler Autres investigations cv si nécessaire Coaching par une infirmière de cardiologie Suivi régulier cardio

48 Critère primaire IC et dysfonction VG 20,0% 18,0% 16,0% 14,0% 12,0% 10,0% 8,0% 6,0% 4,0% 2,0% 0,0% OR 0.46 [0.27, 0.77], p=0.003 N=44 6,4% OR 0.59 [0.38, 0.90], p=0.01 N=59 N=25 N=39 7,2% 3,8% 3,0% 2,0% 4,6% 2,8% 2,3% 5,1% 2,1% 1,0% 1,9% Control Intervention Control Intervention Population All patients totale Any BNP > >= 50 pg/ml DDVG DSVG IC

49 Meta analysis based on usefulness of NP during non cardiac surgery Studies were considered eligible if they measured B-type natriuretic peptide (BNP) or N-terminal fragment of probnp (NT-proBNP) preoperatively and postoperatively (i.e., <8 days after noncardiac surgery) on the same patient. Our primary outcome was a composite of mortality or non fatal MI. NRI methodology

50 Risk analysis

51 Apport du BNP pré opératoire

52 Apport supplémentaire du dosage post op

53 584 consecutive patients with acute ischemic stroke within 24 hours of onset. Patients with AF on admission 12-lead electrocardiography (ECG) or with histories of AF were excluded. Patients with dialysisdependent chronic renal failure were also excluded from the present study Diagnosis of acute ischemic stroke was made by stroke neurologists and confirmed by computed tomography or magnetic resonance imaging Am J Cardiol 2012;109:

54 Population

55 Résultats Cut off 65 pg/ml AUC 0,82 sensibilité 80% spécificité 70%

56 Prévalence de la détection d une FA selon le taux de NP

57 Conclusion Le dosage du NT pro BNP apparait comme utile chez le diabétique. C est le marqueur de choix car stable et dosage reproductible à faible taux. L existence d un diabète ne modifie pas ses seuils diagnostiques ou pronostiques Le dosage du NT Pro BNP est utile en tant que marqueur de screning et marqueur pronostic tant pour la dysfonction VG que pour les évènements et la mortalité. Seuil pg/ml car la on n est pas dans le cadre de l IC sysmptomatique Le NT pro BNP est un biomarqueur de PARCOURS!

58 On ne peut pas mettre tout le monde sur le même plan nous devons être éclairés pour faire les bon choix