Το πεπρωμένον φυγείν αδύνατον?

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1 ΠΡΟΛΗΨΗ ΚΑΡΔΙΑΓΓΕΙΑΚΩΝ ΝΟΣΗΜΑΤΩΝ Στεφανιαία νόσος Το πεπρωμένον φυγείν αδύνατον? Αθανάσιος Δρίτσας FESC Καρδιολόγος, Ωνάσειο ΚΚ

2 Υπάρχει πεπρωμένον στη στεφανιαία νόσο? ΓΕΝΕΤΙΚΗ vs ΠΡΟΛΗΨΗ No conflict of interest

3 Clinical mantra of 21 st century is PREVENTION via which coronary artery disease is likely to be markedly attenuated, if not eliminated (1961) FRAMINGHAM STUDY Ανακάλυψη παραγόντων κινδύνου της στεφ. Νόσου: Υπερ-χοληστερολαιμία Αρτηριακή υπέρταση (Σακχ.διαβήτης) Παχυσαρκία (1964) Surgeon General s announcement Κάπνισμα ως παράγων κινδύνου στεφ.νόσου (2007) Ανακάλυψη πρώτου γενετικού παράγοντα κινδύνου Genetic variant at 9p21

4 ΓΕΝΕΤΙΚΗ ΠΡΟΔΙΑΘΕΣΗ ΓΙΑ ΣΤΕΦΑΝΙΑΙΑ ΝΟΣΟ Αναφέρεται αδρά στο 50% της πιθανότητας ΣΝ (susceptibility) Οικογενειακό ιστορικό ΣΝ ή ΑΕΕ αυξάνει 2.4 φορές την πιθανότητα σε άνδρες Οικογενειακό ιστορικό υπάρχει στο 100% εκδήλωσης νόσου <46 ετών Οικογενειακό ιστορικό υπάρχει στο 15-30% εκδήλωσης νόσου >55 ετών Danish Twin Registry/ Υψηλή επίπτωση ΣΝ σε μονοζυγώτες σε σχέση με διζυγώτες διδύμους (44% vs 14%) Πρόσφατη μελέτη INTERHEART δείχνει ότι το οικογενειακό ιστορικό αυξάνει τον κίνδυνο κατά 1.45 μετά διόρθωση για άλλους παράγοντες κινδύνου PROCAM STUDY/Οικογενειακό ιστορικό εμφράγματος μυοκαρδίου αποτελεί ανεξάρτητο παράγοντα κινδύνου για στεφανιαία νόσο

5 Genetics of CAD in the 21 st Century Robert Roberts & Alexander Stewart (2012) Research recently has identified 36 genetic variants with increased risk for CAD. More than 50% of these variants occur in >50% of the population, with 10 occurring in >75% of the population. The challenge and the opportunity Lie in the observation that > 66% of these variants do not mediate their risk via conventional risk factors. These results suggest that genetic predisposition to CAD is conferred by common DNA variants and many factors contributing to The pathogenesis of CAD are yet to be determined. Αρα υπάρχει ακόμη σύγχυση όσον αφορά το γενετικώς πεπρωμένον στη στεφανιαία νόσο!

6 ΤΟ ΕΝΔΟΜΗΤΡΙΟ (ΩΣ ΠΕΠΡΩΜΕΝΟ) ΣΤΑ ΚΑΡΔΙΑΓΓΕΙΑΚΑ ΝΟΣΗΜΑΤΑ

7 Hungry in the womb: What are the consequences? Lessons from the Dutch famine Poor nutrition at the very beginning of life (before birth) leads to long term effects on mental and physical health Roseboom TJ et al, Maturitas 70(2011):

8 The Dutch Famine November 1944-May 1945 Smith et al 1947 Am J Obstetrics Gynaecology The effects of war time starvation in Holland on pregnancy and its product

9 Hungry in the womb: What are the consequences? Lessons from the Dutch famine People conceived during the famine: Had a more atherogenic lipid profile More responsive to stress and doubled the rate of CAD Had higher incidence of type II diabetes Were at increased risk of schizophrenia and depression They performed worse on cognitive tasks

10 Low birth weight as a risk factor for: Coronary heart disease, Diabetes type II, Hypertension, Cognitive decline, Depression

11 Low birth weight or length of gestation lead to cardiovascular disease Programming of physiological stress response as an important linking mechanism Alterations in arterial pressure Alterations in autonomic tone higher in females HPAA axis reactivity higher in males Early life predictors of the physiological stress response later in life Kajantie e et al, Neuroscience and Biobehavioral Reviews (2010)

12 Birth weight and the programming of disease STRESS!! Glucocorticoids during pregnancy Excess glucocorticoids and fetal development Maternal stress in pregnancy affects offspring brain Role of the placenta and hydroxysteroid dehydrogenase (HSD2) Reprogramming of the HPAA axis (Linked with) Low birth weight Hypertension Hyperglycemia Increased HPA axis reactivity Increased anxiety related behavior Platelet aggregation and thrombosis Harris a et al, Hormones and Behavior (2010)

13 IMPORTANCE OF INTRAUTERINE LIFE Maternal hypo-nutrition Maternal over-nutrition Thrifty Hypothesis Pathways linking early environment to long-term health, Progress in Biophysics and Molecular Biology 2011, Barnes SK

14 Epigenetics and Programming Life Span mechanisms

15 PREVENTIVE MEASURES Cholesterol Hypertension Diabetes Obesity Psychosocial aspects Exercise training only? Life style philosophy in preventing CVD

16 DETERMINANTS OF RETURN TO WORK AFTER ACS adj. OR 95% CI p Age Gender(M/F) GRACE Arrhythmia Heart failure Recurrence Antidepress use BDI depress.index Bhattacharyya et al Eur Heart Journal ACS=acute coronary event

17 Characteristics of patients working and not working at 12 months after ACS working (n=101) not working (n=25) p ======================================================= Gender M 88% M 87% 0.98 Age 55(8.2) 56(9.8) 0.47 Education pr 23.8% 24.0% 0.49 Education sec 39.6% Social deprivation high 17.5% 28% 0.13 Marital status 75.3% 68% 0.53 Smoking status 46.5% 64% 0.18 BMI Physical activity none 53% 72% Alcohol u/wk ======================================================== Eur Heart 2007, 28,

18 Cardioprotective mechanisms of exercise training as part of CR Improved endothelial function Reduced levels of C-reactive protein (CRP) Reduce body weight and adiposity Reduce TG and increase HDL Improve insulin sensitivity and glucose homeostasis Modify all components of metabolic syndrome Increase coronary flow via improving coronary compliance Promote angiogenesis Induce ischemic preconditioning of myocardium Enhanced vagal activity and reduce sympathetic activity Decreased platelet aggregation & enhanced fibrinolysis (+TPA)

19 PCI vs exercise training Hambrect et al 2004

20 Comparative effectiveness of exercise and drug interventions on mortality outcomes: metaepidemiological study (Published 1 October 2013) Cite this as: BMJ 2013;347:f5577 1LSE Health, London School of Economics and Political Science, London, UK 2Drug Policy Research Group, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA 3Stanford Prevention Research Center, Stanford University School of Medicine, Stanford, CA, USA Huseyin Naci, researcher1, fellow2, John P A Ioannidis, director3 Conclusions: Although limited in quantity, existing randomised trial evidence on exercise interventions suggests that exercise and many drug interventions are often potentially similar in terms of their mortality benefits in the secondary prevention of coronary heart disease, rehabilitation after stroke, treatment of heart failure, and prevention of diabetes.

21 BMJ 2013;347:f5577

22 INEQUALITIES AND HEALTH Poverty pays more to health, A report, September 2009 Prof. George Caplan, Dept. of Epidemiology, University of Mitchigan, USA

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27 The world today! Αυτός ο κόσμος δεν θα αλλάξει ποτέ! (Κεμάλ, Ν.Γκάτσος) Malnutrition vs Overnutrition One billion people worldwide go hunger everyday and at the same time More than one billion are obese or overweight (2011)