MonIToring surve Y - The cu Rrent stat E of Angina popuLation and heart rate
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Source: Fréquence des infarctus du myocarde Meyer K. et al., Kardiovask, Med. 2007;10:279–284 http://www.obsandaten.ch/indikatoren/8_3_11/2004
Qu’est qu’un facteur de risque cardiovasculaire ? “C’est une condition associée avec un risque augmenté de développer une maladie cardiovasculaire. L'association est au début toujours statistique. Ainsi le fait qu'une personne particulière ait un facteur particulier augmente simplement la probabilité de développer un certain type de maladie cardio-vasculaire. cela ne signifie en aucun cas qu’il ou elle soit sûre de développer la maladie cardiovasculaire. Réciproquement, le fait qu'un individu n'ait pas un facteur de risque cardio-vasculaire particulier ne garantit pas la protection contre une maladie cardiovasculaire” Dr. William KanneI, premier directeur de l’étude Framingham
FCR et mortalité chez l’ Homme Population générale Insuffisance cardiaque Mort subite 70.0 6.0 Evénements/1000 patients x 2 ans Evénements/1000 patients x 2 ans 66-94 35-84 52.5 4.5 35.0 3.0 17.5 1.5 15 25 48 63 1.1 2.5 3.1 4.7 5.9 0 0 < 64 65-74 75-84 >85/min 65 74-79 >88/min
Relationship between heart rate and cardiovascular mortality in the general and hypertensive population J Clin Epidemiol 2006
Pouls et pression artérielle humérale pendant examen final Facteurs de risque CV Syndrome métabolique Obésité Diabète sucré Dépôts Hypertension lipidiques Modifiables artérielle HDL, LDL, TGL Diète Tabac Inflammation Alcool Exercice physique Âge modifiables Contraintes de Sexe Non- cisaillement Hérédité Uexküll T, Wick E: Arch Kreislaufforsch 39: 236-271; 1962
Coronary Heart Atherosclerotic Plaque Rupture Plaque Plaque Growth Risk Factors for Plaque Rupture Risk Factors for Plaque Growth Diabetes mellitus Smoking Metabolic Dyslipidemia syndrome Inflammation/Apoptosis Obesity Lipid Diabetes mellitus deposition Endothelial dysfunction/Shear Can be changed Hypertension stress HDL, LDL, TGL High heart rate High-fat diet Hyperhomocysteinaemia/ Tobacco Lipoproteinaemia Sedentary lifestyle Inflammation Genetic protein defiencies (ATIII, High heart Protein C or S) rate Hypercoagulability/Fibrinolytic state Cannot be Age Tissue factor activity changed Gender Shear stress Heredity Coronary Event
Cardiovascular events during Soccer Coronary Worldcup in Germany Heart Atherosclerotic Plaque Rupture Plaque Plaque Growth Risk Factors for Plaque Rupture Risk Factors for Plaque Growth Diabetes mellitus Smoking Metabolic Dyslipidemia syndrome Inflammation/Apoptosis Obesity Lipid Diabetes mellitus deposition Endothelial dysfunction/Shear Can be changed Hypertension stress HDL, LDL, TGL High heart rate High-fat diet Hyperhomocysteinaemia/ Tobacco Lipoproteinaemia Sedentary lifestyle Inflammation Genetic protein defiencies (ATIII, High heart Protein C or S) rate Hypercoagulability/Fibrinolytic state Cannot be Age Tissue factor activity changed Gender Shear stress Heredity Coronary Event NEJM 2008
Increased heart rate may contribute to coronary plaque disruption 2002 2004 2004 2009 Heidland UE, Strauer BE. Circulation. 2001;104:1477-1482.
High resting heart rate: an independent predictor of mortality in the French general population c a r d ia q u e é le v é e Fréquence - s . F a c te u r d e r is q u e ? Marqueur de risque v Benetos A et al.Hypertension. 1999;33:44-52.
Ivabradine shifts the patients from high risk to low risk 8 HR >70 bpm in placebo (mean HR = 79 bpm) -36%* fatal or nonfatal MI (%) Hospitalization for 4 HR 70 bpm with Procoralan (mean HR = 66 bpm after treatment) 0 *P=0.001 **P=0.0066 0 0.5 1 1.5 2 Years Fox K et al. Lancet. 2008;372:807-816.
Cascade Stabilité ischémique de plaque Contrôle des Contrôle des symptômes événements Cook S & Hess OM, European Heart Journal, 2009
The cuRrent statE of Angina treatment in outpatient popuLation and heart rate monIToring surveY
Objectives of REALITY To characterize resting heart rate and medication of the population with stable angina pectoris in outpatient clinics To correlate angina pectoris events to heart rate. To evaluate the impact of angina pectoris on quality of life
Study design Cross-sectional epidemiological study Data acquisition by 33 Swiss cardiologists in clinical practice Mock Sigwart Grobéty Gillard-Berguer Reynard Bacchocchi-Suilen Jaussi Koerfer Burri Ricou Pasquier Perret Bérubé Vulliemin Bosquet Fiori Savcic Goy Depeursinge
Baseline data: Cardiovascular risk factors Total 283 coronary disease patients (202 male, 81 female) Mean heart rate at rest [bpm] 69 (min-max) (46-126) Smoker 45 (16%) Mean systolic blood pressure [mmHg] 140.0 (min-max) (98-202) Mean diasolic blood pressure [mmHg] 80.8 (min-max) (54-100) Hypertension 191 (67%) Mean BMI [kg/m2] 26.8 (min-max) (17.9-39.5) Diabetes Mellitus 74 (26%)
CAD Mean time since diagnosis of a stable 4.25 (0.02-36.7) angina pectoris [years] (min-max) Myocardial infarction 84 (30%) Coronary artery bypass graft (CABG) 35 (12%) Percutaneous coronary intervention 142 (50%) (PCI) PCI & CABG 23 (8%)
Cardiovascular risk factors Mean heart rate at rest [bpm] 69 (min-max) (46-126) resting resting heart rate heart rate 70 bpm
Association of resting heart rate with major cardiovascular risk factors 70 bpm (n=157) (n=126) Atrial fibrillation % 10 13 NS Heart failure % 8 10 NS Cerebrovascular diseases % 9 17 p < 0.05 Hypertension % 62 74 p < 0.05 Diabetes mellitus % 21 33 p < 0.05 Dyslipidemia % 83 90 NS Obesity, BMI > 27 kg/m2 % 37 52 p < 0.01 Patients with heart rate >70 bpm suffer significantly more from additional cardiovascular risks than patients with heart rate
FCR et mortalité chez Physiopathologie - l’ Homme Acquis Coronary Artery Surgery Study 24 913 patients avec maladie coronarienne suspecte ou prouvée Diaz A, et al., European Heart Journal (2005) 26, 967–974
How do angina pectoris events and heart rate correlate? Angina pectoris events per week Angina pectoris events/ week 4 3 3.8 3.3 2.8 2.7 2 n=86 n=71 n=62 n=62 ≤60 61-69 70-77 ≥77 Subgroups by bpm
FCR et mortalité chez Fréquence cardiaque et l’ Homme Espérance de vie après infarctus du myocarde Analyse de l’étude GUSTO-I * ECG à l’admission Admission pour infarctus aigu du 41’021 patients myocarde Mortalité à 30 jours * Hathaway WR,et al. Jama. 1998;279(5):387-391. GUSTO-I: Global Utilization of Streptokinase and t-PA (alteplase) for Occluded Coronary Arteries
Classification of severity of angina by the CCS: Canadian Cardiology Society Scale CCS IV = Inability to perform any activity without angina or angina at rest, i.e., severe 100% limitation CCS III = Symptoms with everyday 75% living activities, i.e., moderate limitation 50% CCS II = Slight limitation, with angina only during vigorous 25% physical activity 0% CCS I = Angina only during ≤60 61-69 70-77 ≥77 strenuous or prolonged physical activity Subgroups by bpm
Objective 2 How does angina pectoris influence habits and quality of life of CD patients?
Restenosis and Quality Bénéfices des DES of Life Functional Status No Revasc Repeat Revasc P=0.03 P=
Limitation of everyday living activities Whole p 70 bpm population difference (n=157 ) (n=126 ) (n=283 ) 70 Fear of angina pectoris events leads to limitation 26% 38% 31% p < 0.05 of physical activity (despite treatment) Regular physical activity 60% 47% 54% p < 0.05 •Fear from angina pectoris events leads to limitation of everyday living activities in many CD patients. Subgroup heart rate >70 bpm significantly more affected than subgroup 70 bpm are significantly less physically active than patients of the subgroup heart rate
Evaluation of CAD treatments in Switzerland Whole 70 bpm p Difference population (n=157) (n=126) 70 (n=283) Invasive treatments 75% 67% 72% NS Nitrates 51% 51% 51% NS Calcium antagonists 30% 40% 34% NS Coronary therapy 24% 25% 25% NS Beta-blockers 81% 67% 75% p < 0.01 No Beta-blockers because of 7% 18% 13% NS contraindication Antianginal therapy per 4.26 4.51 4.37 NS patient (11 months) Increase of heart rate 3% 17% 9% p < 0.001 since diagnosis
Heart rate reduction is associated with a decrease of post-MI cardiac deaths Meta-regression of 12 controlled studies 2.0 1.0 Odds ratio 0.5 0.2 β-Blockers P
Comparison Europe wide – cardiovascular risk factors EUROASPIRE II1 2000/2001 EUROASPIRE III1 REALITY CH Risk factors 1999-2000 Survey CH2 2006-2007 2008 n = 2975 n=565 n = 2392 n=283 Age (years) 59 68 60 69 Angioplasty % 28 62 50 72 Smoker % 21 18 18 16 Obesity % 33 - 38 44 Hypertension % 58 65 61 67 Dyslipidemia % 75 71 46 87 Diabetes % 20 22 28 26 1 Wood DA et coll. Abst. 316. Hot Line I, ESC 2007, Vienne, Autriche - 2 National survey on prescription of cardiovascular drugs among outpatients with coronary artery disease in switzerland. Swiss Med Wkly 2003;133:88-92
Comparison Europe wide - treatment EUROASPIRE II1 2000/2001 EUROASPIRE III1 REALITY CH Treatment 1999-2000 Umfrage CH2 2006-2007 2008 n = 2975 n=565 n = 2392 n=283 Antithrombotic agents % 84 84 93 99 Beta blockers % 69 71 85 75 ACE-blockers & Sartans % 49 47 74 65 Statins % 57 - 87 84 1 Wood DA et coll. Abst. 316. Hot Line I, ESC 2007, Vienne, Autriche - 2 National survey on prescription of cardiovascular drugs among outpatients with coronary artery disease in switzerland. Swiss Med Wkly 2003;133:88-92
Latéral Inférieur Latéral Inférieur Latéral Antérieur
Aspirine 100 mg/d CK 3250 U/l Plavix 75 mg/d LVEF @ D3: 45 % Coversum 5 mg/d Torem 5mg/d Medicaments ? Concor 5mg/d Crestor 10 mg/d FCR 74 bpm Concor 10mg ou Procoralan 5mg/d ?
Merci
Multiple cardiac effects of heart rate MVO Neurohormonal Myocardial systems perfusion Ion fluxes Autonomous Myocardial nervous system Heart rate relaxation Arterial Myocardial compliance contraction Plaque Myocardial rupture gene expression
The Bowditch phenomenon Contractile force of frog heart increases when paced at increasing frequency. Henry Pickering Bowditch (1840 – 1911) Bowditch HP. Ueber die Eigenthuemlichkeiten der Reizbarkeit, welche die Muskelfasern des Herzens zeigen. Ber Sachs Ges Akad Wiss 1871; 23: 652-689. Courtesy of R. Lerch, MD
Effect of long-term therapy with β-blocker on EF 1936 patients enrolled in 15 placebo-controlled trials Packer et al, Am Heart J 2001; 141: 899-907 Courtesy of R. Lerch, MD
Force-Frequency relationship in normal and failing myocardium Trabecula from human hearts Stimulation frequency (/min) "negative staircase" Schillinger, Hasenfuss et al, Basic Res Cardiol 1998; 93 (Suppl. 1): 38-45 Courtesy of R. Lerch, MD
Ivabradine shifts the patients from high risk to low risk 8 HR >70 bpm in placebo (mean HR = 79 bpm) -36%* fatal or nonfatal MI (%) Hospitalization for 4 HR 70 bpm with Procoralan (mean HR = 66 bpm after treatment) 0 *P=0.001 **P=0.0066 0 0.5 1 1.5 2 Years Fox K et al. Lancet. 2008;372:807-816.
IVA
Fréquence cardiaque et Espérance de vie après infarctus du myocarde 432 patients avec infarctus aigu ECG à l’admission et Holter 24 heures fin hosp. 343 hommes, 89 femmes;58 “Endpoints”: Mortalité et événements arrythmiques ±11 ans (Mort subite, fibrillation ventriculaire, tachycardie ventriculaire soutenue). Suivi: 41 mois Mortalité à 30 jours Mauss O, et al. J Electrocardiol. 2005; 38_106-112
The effects of a reduction in heart rate Lower oxygen consumption Improved diastolic coronary flow Anti-ischemic effects Increased ventricular fibrillation threshold Antithromboatherosclerotic effects Prevention of plaque rupture Prevention of cardiomyopathy Slower development and progression of IHD Prevention of acute and chronic ischemic events (CV death, sudden death, angina, AMI, CHF)
Implication of heart rate as a simple tool for mortality risk estimation Simple (part of routine clinical examination) Predictive (demonstrated in large number of epidemiological trials) Cheap (does not request special equipment) Easily interpreted Useful to monitor improvement of management
Conclusions CAD patients suffer from angina pectoris despite intensive treatments. Number and severity of angina pectoris events in patients with heart rate >70 is significantly higher than in subgroup heart rate 70 suffering significantly more the patients with 70 than
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