Eskisehir Osmangazi University, Cardiology Department Eskisehir, Turkey

1. Heart Failure Matters The Invisible Part of the Iceberg: Stage A and B Heart Failure Prof. Dr. Yüksel ÇAVUŞOĞLU, MD, FESC Board Member of the Working Group of Heart Failure of Turkish Society of Cardiology Eskisehir Osmangazi University, Cardiology Department Eskisehir, Turkey Joint Session UKBIH - TKD 5th Congress of the UKBIH, Bosnia and Herzegovina, 27 May 2010

2. Heartfailure is a majorpublichealth problem thataffectsmillions of people Davis RC et al. BMJ 2002; 325: 1156. Lloyd-Jones D et al. Circulation 2009;119:e21-e181.

3. HF is a progressivediseasewith a poorprognosis The 1-year mortality rate for HF is estimated as 21% in men and 17% in women Roger VL et al. JAMA 2004;292:344-50. Heart Disease and Stroke Statistics 2010 update.

4. Hospitaldischargesforheartfailure n=1 106 000 n=399 000 175% ↑ “From 1979 to 2006, hospital discharges for HF have increased by 175%” “HF causes a substantial economic burden on the healthcare system” Heart Disease and Stroke Statistics 2010 update. Circulation published online Dec 17, 2009

5. The risk of HF incidenceincreaseswitholderage The elderly population (≥65 y) is expected to grow in the community. Even if HF incidence remains constant, the total number of people with HF is expected to double during the next two decades Heart Disease and Stroke Statistics 2010 update. Circulation published online Dec 17, 2009

6. ClinicalHF increases in prevalencewithadvancingage The prevalence of HF will likely continue to increase in developed and developing countries Heart failure will become a major public health burden Heart Disease and Stroke Statistics 2010 update. Circulation published online Dec 17, 2009

7. Symptomatic disease is only the tip of the iceberg Death Visible Part Refractory HF Symptomatic HF Systolic/diastolicdysfunction LV Dilatation Valvularheartdisease LVH MI Invisible Part Atherosclerozis Diabetes Toxins Dyslipidemia Obesity Smoking Hypertension Aging Genes Themajority of peopleare in a preclinicalstage of thedisease

8. Prevention of HeartFailure • Prevention programs targeting this growing population will likely reduce HF incidence • Essential strategies for prevention of HF should focus on modification of risk factors for HF development • Objectives include: • Early idendification of patients at high risk • Early detection of asymptomatic LV dysfunction • Optimal treatment plan for each individuals • Agressive therapeutic lifestyle changes • Targeted pharmacological intervention • Persistent follow-up

9. New ApproachtotheClassification of Heart Failure Hunt, S. A. et al. J Am Coll Cardiol 2009;53:e1-e90

10. Prevention of HeartFailure A ScientificStatementFrom AHA Stage A and stage B present ideal opportunities to intervene to prevent HF Schocken DD et al. Circulation 2008;117:2544-65.

11. EstablishedandPossible Risk Factorsfor HF A ScientificStatementFrom AHA Major Clinical Risk Factors Minor Clinical Risk Factors • Age, male sex • Hypertension, LVH • Myocardial infarction • Diabetes • Valvular heart disease • Obesity • Smoking • Dyslipidemia • Sleep-disordered breathing • Chronic kidney disease • Albuminuria • Homocysteine • Immune activation, IGF1, TNFα, IL-6, CRP • Natriuretic peptide • Anemia • Dietary risk factors • Increased HR • Sedentary lifestyle • Low socieconomic status • Phychological stress Schocken DD et al. Circulation 2008;117:2544-65.

12. EstablishedandPossible Risk Factorsfor HF A ScientificStatementFrom AHA Toxic Risk Precipitants Morphological Risk Predictors • Chemotherapy • Anthracyclines • Cyclophosphamide • 5-FU • trastuzumab • Cocaine • NSAIDs • Thiazolidinediones • Doxazosin • Alcohol • Increased LVID, mass • Asymptomatic LV dysfunction • LV diastolic dysfunction Genetic Risk Predictors • Single-nucleotide polymorphism • (eg, α2CDeI322-325, β1Arg389) Schocken DD et al. Circulation 2008;117:2544-65.

13. Coronaryheartdisease is theleadingcause of HF NHANES I Epidemiologic Follow-up Study n= 13 643 19 years follow-up CAD is theunderlyingcause of HF in 62% of patients He, J. et al. Arch Intern Med 2001;161:996-1002.

14. Hypertension is a most common risk factor for HF • HT is associated with a 2- to 3-fold increase in the risk of HF • Seventy-five percent of HF cases have antecedent HT • The lifetime risk for people with BP >160/90 mmHg is double that of those with BP <140/90 mmHg Heart Disease and Stroke Statistics 2010 update. Circulation published online Dec 17, 2009

15. Heart Failure Event Rate in HT Trials Heart failure incidence may be higher than MI or stroke incidence

16. Risk of HF in Different HT Subgroups Tocci G et al Hypertension 2008

17. Results of Randomised Trials of Antihypertensive Drug Therapy Adequate BP controlreduces development of incidentHF Moser and Hebert J Am Coll Cardiol 1996 Collins R et al. Lancet 1990

18. Effect of Antihypertensive Therapy on CV EventsComparison of more or less intensive BP control BPLTTC Lancet 2003

19. Reduction in HF Risk by SBP Reduction 26% risk reduction per 10 mmHg decrease in SBP (p<0.001) 56% risk reduction per 10 mmHg decrease in SBP in diabetics

20. Diabetes is an independent risk factorfor HF • The Framingham study revealed a 2.4-fold increase in diabetic men and a 5-fold increase in diabetic women. • Approximately 12% of type 2 diabetics have established HF. • Approximately 3.3% of type 2 diabetics develop HF each year. • Incrementally increased risk for HF is seen at higher HbA1c levels

21. Abnormal Lipid Levels Increase Risk of HF Framingham Heart Study Patientswithhighnon-HDL-C have a 29% higher HF risk. Patientswithlow HDL-C have a 40% higher HF risk. Velagaleti RS et al. Circulation 2009;120:2345-51.

22. BMI & Risk of heartFailure TheFinnish FINMONICA study 59,178 participants, free of HF at baseline, 18.4 yearsfollow-up The multivariable-adjusted (age, study year, smoking, education, alcohol consumption, history of myocardial infarction, history of valvular heart disease, systolic blood pressure, total cholesterol, history of diabetes and physical activity) hazard ratios (HRs) of HF Obesity and overweight are independently associated with an increased risk of HF Hu G. Circulation. 2010;121:237-244.

23. Physicalactivity & Risk of heartFailure TheFinnish FINMONICA study 59,178 participants, free of HF at baseline, 18.4 yearsfollow-up The multivariable-adjusted (age, study year, smoking, education, alcohol consumption, history of myocardial infarction, history of valvular heart disease, BMI, systolic blood pressure, total cholesterol, and history of diabetes) hazard ratios (HRs) of HF Physical activity is associated with a reduced risk of HF Hu G. Circulation. 2010;121:237-244.

24. Recommended Therapy for Stage A and B HF In patients at high risk for developing HF, risk factors should be controlled in accordance with contemporary guidelines

25. Conclusions • HF represents the final common pathway of many risk factors and cardiovascular diseases • Stage A and stage B HF confer ideal opportunities to intervene to prevent HF • Many risk factors and CV diseases can be prevented by aggressive lifestyle and pharmacologic interventions • Prevention of HF must begin with increasing public/professional awareness of HF and risk factors