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Lowering cholesterol – The earlier the better, the lower the better

Lowering cholesterol – The earlier the better, the lower the better . Contents. Relevance of LDL reduction in the prevention of CVD The earlier the better The lower the better Diet as a key factor in LDL-C lowering and CVD prevention

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Lowering cholesterol – The earlier the better, the lower the better

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  1. Lowering cholesterol –The earlier the better, the lower the better

  2. Contents • Relevance of LDL reduction in the prevention of CVD • The earlier the better • The lower the better • Diet as a key factor in LDL-C lowering and CVD prevention • Plant stanol ester – a dietary tool for effective LDL-C lowering

  3. CVD - a preventable burden • CVDs, especially atherosclerotic CHD and stroke, are the leading cause of death globally. However, 80% of premature heart disease and stroke is preventable • By the time that heart problems are detected, the atherosclerosis is usually quite advanced, having progressed for decades. Therefore, there is increased emphasis on preventing atherosclerosis by modifying lifestyle factors such as diet AHA 2009 WHO, Fact Sheet 137, 2009 European Cardiovascular Disease Statistics, 2008

  4. Hypercholesterolemia in key rolein the development of CVD • Research has indisputably established the crucial role of hypercholesterolemia in the development of CVD1 • Reducing plasma LDL-C unequivocally reduces the risk of CVD1,2 • Latest research shows that even individuals with a low risk of vascular events benefit greatly from intensive LDL lowering3 LOG-LINEAR RELATIONSHIP BETWEEN LDL-C LEVELS AND RELATIVE RISK FOR CHD2 Relative risk for CHD LDL-Cholesterol (mg/dl) European Guidelines on cardiovascular disease prevention in clinical practice (version 2012). European Heart Journal 2012; 33: 1635–1701. Grundy et al Circulation 2004; 110; 227-239 Cholesterol Treatment Trialists’ (CTT) Collaborators. Lancet 2012. DOI:10.1016/S0140-6736(12)60367-5.

  5. Lowering LDL cholesterol:The earlier the better (1) • It is acknowledged that atherosclerosis begins in childhood1 • Guidelines recommend the assessment and management of cardiovascular risk factors already in youth2-4 • The optimal age for pediatric risk factor screening starts at 9 years of age but the prevention of cardiovascular disease should begin at even younger age5 ATHEROSCLEROSIS DEVELOPS FROM THE EARLY ADULTHOOD1 Atheroscelosis prevalence (%) Age Tuzcu et al. Circulation 2001; 103: 2705-2710. Daniels et al. Pediatrics 2008; 122: 198-208. National High Blood Pressure Education Program Working Group on High Blood Pressure in children and adolescents. Pediatrics 2004; 114: 555-576. US Preventive Services Task Force. Pediatrics 2010; 125: 361-367. Juonala et al. Circulation 2010; 122: 2514-2520.

  6. Lowering LDL cholesterol:The earlier the better (2) • High levels of CVD risk factors in young schoolchildren are highly predictive for higher carotid IMT as an adult1 • Dyslipidemia in young adulthood is associated with coronary atherosclerosis 2 decades later2 • Optimal CVD risk factor profile in midlife substantially lowers the lifetime risk of fatal CVD3 • Latest research shows that exposure to low LDL-C levels from early life is substantially more effective than the current practice of lowering LDL-C only later in life4 Juonala et al. Circulation 2010; 122: 2514-2520. Pletcher et al. Ann Intern Med 2010; 153: 137-146. Berry et al. N Engl J Med 2012; 366: 321-329. Ference et al. Paper presented at the ACC Congress in March, 2012. 6

  7. LDL cholesterol:The lower the better • LDL-C levels between 1.3 and 1.8 mmol/l are considered as physiological • Every 1.0 mmol/l reduction in LDL-C results in 20-25% reduction in fatal and nonfatal vascular events1 • LDL-C below 1.8 mmol/l is associated with the lowest risk of recurrent CVD events2 European Guidelines on cardiovascular disease prevention in clinical practice (version 2012). European Heart Journal 2012; 33: 1635–1701. Baigent et al. BMJ 2009; 376: 1670-1681.

  8. Low cholesterol associated with better quality of life • Low serum cholesterol level in midlife predicts not only better survival but also better physical function and quality of life at old age1 • On the contrary, high CVD risk in midlife is associated with frailty at old age2 Strandberg et al. J Am Coll Cardiol 2004; 44: 1002– 1008. Strandberg et al. Int J Obes 2012. doi: 10.1038/ijo.2012.83.

  9. Diet as a tool for effective cholesterol lowering

  10. Diet is effective in LDL cholesterol reduction and CVD prevention • Lowering LDL cholesterol is the primary target in dyslipidemia management and cardiovascular disease prevention1 • Healthy lifestyle, including a healthy diet, always forms the basis for the management1,2 • Lowering LDL cholesterol by diet is as beneficial as lowering LDL cholesterol by medication3 European Guidelines on cardiovascular disease risk prevention in clinical practice (version 2012). European Heart Journal 2012; 33: 1635–1701. Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Final Report. National Cholesterol Education Program, National Heart, Lung, and Blood Institute, National Institutes of Health 2002. La Rosa. Am J Cardiol 2007; 100: 240-242.

  11. Dietary changes - a key success factor in preventing CHD mortality in Finland • Age-standardized CHD mortality has dramatically declined in working-age men in North Karelia and in all Finland1 • Reductions in serum cholesterol explain most of this decline2 • Dietary changes explain most of the decrease in serum cholesterol3 • Foods with plant stanol ester may have contributed to the beneficial effect of the diet3 AGE-STANDARDIZED CHD MORTALITY IN FINLAND IN MEN AGED 35-64 IN 1969–20021 North Karelia Start of the North Karelia Project All Finland Extension of the Project nationally CHD mortality (per 100 000 inhabitants) National Institute for Health and Welfare, Finland. Vartiainen et al. Int J Epidemiol 2010; 39: 504-518. Valsta et al. Public Health Nutr 2010; 13: 932-938.

  12. What explains the decline in CHD mortality? Reductions in serum cholesterol explain most of the observed and predicted decline in CHD mortality in Finland OBSERVED AND PREDICTED DECLINE IN CHD MORTALITY IN MEN1 Smoking Diastolic BP Cholesterol Percentage (%) All risk factors Observed 12 Presentation name / Author Vartiainen et al. Int J Epidemiol 2010 ; 39: 504-518.

  13. Significant decline in serum cholesterol in Finland MEAN SERUM CHOLESTEROL IN MEN IN FINLAND1 North Karelia county Northern Savo county Southwestern Finland Helsinki and Vantaa cities Oulu province mmol/L Vartiainen et al. Int J Epidemiol 2010 ; 39: 504-518.

  14. Dietary changes explain most of the serum cholesterol reduction in Finland OBSERVED AND PREDICTED SERUM CHOLESTEROL REDUCTION IN FINLAND1 Medication effect Dietary effect Medication + dietary effect Observed serum cholesterol mmol/L Valsta et al. Public Health Nutr 2010; 13: 932-938.

  15. Positive dietary changes are achievable In Finland, heart-healthy changes in diet have been achieved at population level EXAMPLES OF DIETARY CHANGES IN FINLAND1 Skimmed milk Vegetables daily Butter on bread Prevalence of dietary habits in men (%) Health Behaviour and Health among the Finnish Adult Population, Spring 2011. Publications of the National Institute for Health and Welfare (THL). Report 45/2012.

  16. Every bite has an effect on health • All foods have an effect on our health; therefore it is important to adopt healthy dietary habits as early as possible • Unhealthy diet in childhood is linked in adults to1 • CVD risk factors • Early unbeneficial vascular changes • Recent guidelines as well as the latest research strongly encourage individuals at all ages to follow a heart-healthy diet1-6 Kaikkonen et al. Ann Med 2012. DOI:10.3109/07853890.2012.671537. Magnussen et al. Pediatr Nephrol 2011. DOI:10.1007/s00467-011-1990-y Laitinen et al. Circulation 2012. DOI: 10.1161/CIRCULATIONAHA.111.073585. Daniels et al. Pediatrics 2008; 122: 198-208. European Guidelines on cardiovascular disease prevention in clinical practice (version 2012). European Heart Journal 2012; 33: 1635–1701. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (ATP III). Final Report. National Cholesterol Education Program (NCEP) 2002.

  17. Key learnings of the Finnish North Karelia project1 • Prevention of cardiovascular diseases is possible and pays off • Population based CVD prevention is the most cost effective and sustainable approach • Influencing lifestyles such as dietary habits of the population is of key importance Puska P. In: Puska et al (eds.). The North Karelia Project: From North Karelia to national action. Helsinki University Printing House 2009. http://www.thl.fi/thl-client/pdfs/731beafd-b544-42b2-b853-baa87db6a046 17

  18. Dietary management of LDL cholesterol

  19. Diet - a key factor in cholesterol reduction1 • Dietary changes, especially changes in fat quality, explained 60 to 65% of the observed decrease in serum cholesterol levels in Finland • The effect of lipid-lowering medication was less significant, only 7 to 16% • Plant stanol and sterol-containing margarines may have had an additional beneficial effect on the observed cholesterol levels since the 1990’s OBSERVED AND PREDICTED SERUM CHOLESTEROL REDUCTION IN FINLAND1 Medication effect Dietary effect Medication + dietary effect mmol/L Observed serum cholesterol Valsta et al. Public Health Nutr 2010; 13: 932-938

  20. Especially low risk patients benefit from dietary prevention • Lowering LDL-C reduces the risk of major vascular events also in the people of low CVD risk (<10%)1 • In those cases lifestyle changes should be the primary treatment2 • Patients may also be reluctant to use medication for cholesterol management • Healthy diet including foods with added plant stanols may result in as good LDL-C reduction as achieved with medication Cholesterol Treatment Trialists’ (CTT) Collaborators. Lancet 2012. DOI:10.1016/S0140-6736(12)60367-5. ESC/EAS Guidelines for the management of dyslipidemias. Atherosclerosis 2011; 217S1: S1-S44.

  21. Plant stanol ester boosts the LDL lowering effect of diet Healthy diet including foods with added plant stanol ester is almost as effective as medication and offers an effective cholesterol lowering option especially for low risk patients. LDL CHOLESTEROL LOWERING EFFICACY OF DIET AND MEDICATION Healthy diet Healthy diet with plant stanol ester Healthy diet alone Statin medication Reduction in LDL (%) Plant stanol ester Statin medication Modified from: Hallikainen and Uusitupa. Am J Clin Nutr 1999; 69: 403-410. Blair et al. Am J Cardiol 2000; 86: 46-52.

  22. Plant stanol ester –effective and recommended dietary option for LDL management

  23. Plant stanol ester is the most effective dietary option in lowering cholesterol LDL LOWERING EFFECT OF SELECTED DIETARY CHOICES 23

  24. The recommended way in LDL cholesterol lowering Therapeutic Lifestyle Changes If LDL goal not reached with TLC in 6 weeks, add Plant stanol ester If LDL goal not reached in 6 weeks, add Pharmaceuticals Monitor adherence to TLC diet after 4-6 months Modified from Model of steps in TLC (US NCEP): JAMA 2001; 285: 2486-2497.

  25. Plant stanol ester as a part of lifestyle intervention PLANT STANOL ESTER RECOMMENDED AS PART OF THE LIFESTYLE INTERVENTION LDL-C level HIGH LOW No intervention Lifestyle intervention including plant stanol ester CVD risk Lifestyle intervention (incl. plant stanol ester) and medication HIGH ESC/EAS Guidelines for the management of dyslipidemias. Atherosclerosis 2011; 217S1: S1-S44 European Guidelines on cardiovascular disease prevention in clinical practice (version 2012). European Heart Journal 2012; 33: 1635–1701. Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Final Report. National Cholesterol Education Program, National Heart, Lung, and Blood Institute, National Institutes of Health. 2002

  26. Plant stanol ester complements statin treatment INCREMENTAL REDUCTION IN LDL CHOLESTEROL WITH PLANT STANOL ESTER Healthy diet + plant stanol ester + statin medication Statin medication alone Statin medication + plant stanol ester Statin medication Reduction in LDL cholesterol (%) Plant stanol ester Healthy diet Modified from: Hallikainen and Uusitupa. Am J Clin Nutr 1999; 69: 403-410. Blair et al. Am J Cardiol 2000; 86: 46-52.

  27. Combining more effective than doubling Adding plant stanol ester to statin treatment results in more effective LDL-C lowering than the doubling of the statin dose 10% ADDITIONAL LDL REDUCTION WITH PLANT STANOL ESTER Statin starting dose Statin starting dose x 2 Statin starting dose x 4 Statin only Statin + plant stanol ester Statins and plant stanol ester

  28. Plant stanol ester only in Benecol foods

  29. Benecol foods contain Plant stanol ester • Benecol foods are available globally in 30 countries • Plant stanol ester can be added to almost any food format, but the most common are yogurt drinks, margarines and yogurts Margarine from Ireland Yogurt from UK Bread from Romania Cereal drink from Thailand Feta cheese from Greece Milk from Chile Yogurt drink from Finland Yogurt drink from Spain Smoothie from Indonesia

  30. Role of healthcare professionals in dietary behavior • Benecol market research shows that patients frequently seek for healthcare professionals’ (HCPs’) opinion and approval regarding the use of cholesterol lowering functional foods • Recommendation by HCPs results in regular use of cholesterol lowering functional foods • Consumption of foods with added plant stanols encourages patients also to make other positive dietary changes, so >20% decrease in LDL-C can be accomplished

  31. Conclusions

  32. Conclusions • Lowering LDL-cholesterol is one of the key actions when targeting cardiovascular health • CVD prevention should start already in childhood, and beneficial dietary choices are always the cornerstone of it • Plant stanol ester is widely recommended as part of the cholesterol-lowering diet • It reduces LDL-C by approximately 10% as part of any type of diet • Combined with statins it brings off an additional 10% LDL-C reduction • HCPs are in a key role in encouraging patients to follow a heart-healthy diet

  33. Plant stanol ester in the treatment and prevention guidelines

  34. ESC/EAS Guidelines for the management of dyslipidemias, 2011 • The magnitude of the effect of functional foods enriched with phytosterols is graded highest possible and the level of evidence is of class ’A’ • ’Based on the available evidence, foods enriched with phytosterols (1-2 g/day) may be considered for individuals with elevated TC and LDL-C values in whom the total CV risk assessment does not justify the use of cholesterol-lowering drugs.’ • ’Functional food containing phytosterols additionally reduce LDL-C levels by up to 5-10% in patients taking stable dose of a statin, and this combination is also well tolerated and safe.’ The Task Force for the management of dyslipidemias of the European Society of cardiology (ESC) and the European Atherosclerosis Society (EAS). ESC/EAS Guidelines for the management of dyslipidemias. Atherosclerosis 2011; 217S1: S1-S44. 34

  35. European Guidelines on cardiovascular disease prevention in clinical practice (version 2012) • Functional foods containing phytosterols (plant sterols and stanols) are effective in lowering LDL cholesterol levels by on average 10%, when consumed in amounts of 2 g/day. • The cholesterol-lowering effect is additional to that obtained with a low-fat diet or use of statins. • Some recent research indicates that, especially for stanols, further cholesterol reduction can be obtained with higher doses. The Fifth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice. European Guidelines on cardiovascular disease prevention in clinical practice (version 2012).

  36. US NCEP ATPIII shows that it is possible to reach even 20-30% reduction in LDL-C with dietary changes and by including foods with added plant stanols into the diet. APPROXIMATE AND CUMULATIVE LDL CHOLESTEROL REDUCTION ACHIEVABLE BY DIETARY MODIFICATION National Cholesterol Education Program & National Institute of Health , Third report of the National Cholesterol Education Program (NCEP) Expert Panel on detection, Evaluation and Treatment of High Blood Cholesterol in Adults Adult Treatment Panel III, 2002

  37. US NHLBI Expert Panel Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents • Plant stanol ester can safely enhance LDL-C lowering effects in children with FH • Especially children with primary elevations of LDL-C who do not achieve LDL-C goals with dietary treatment alone may benefit from plant stanol ester. Such an approach may lower LDL-C sufficiently to avoid the necessity of drug treatment. • Plant stanols (up to 2 g/d) can be used after age 2 years in children with familial hypercholesterolemia. • Short-term studies show no harmful effects in healthy children. National Heart, Lung, and Blood Institute & National Institutes of Health & American Academy of Pediatrics, 2011.

  38. Nutrition Recommendations and Interventions for Diabetes • Plant stanols and sterol are considered as an additional therapeutic option for LDL cholesterol lowering complementing the standard recommendations of limiting saturated and trans fats and dietary cholesterol and increasing soluble fiber consumption. • ’in individuals with type 2 diabetes, intake of 2 g/day plant sterols and stanols has been shown to lower plasma total and LDL cholesterol’ American Diabetes Association, 2008 American Diabetes Association & American College of Cardiology, 2008

  39. Expert bodies recommending the use of plant stanols for lowering LDL cholesterol European Society of Cardiology, 2012 National Heart, Lung, and Blood Institute & National Institutes of Health & American Academy of Pediatrics, 2011 European Society of Cardiology & European Atherosclerosis Society, 2011 The Australian Heart Foundation, 2009 American Academy of Pediatrics, 2008 American Diabetes Association, 2008 American Diabetes Association & American College of Cardiology, 2008 American Heart Association & American College of Cardiology, 2006 Joint British Societies, 2005 International Atherosclerosis Society, 2005 Joint WHO/FAO Expert Consultation, 2003 International Lipid Information Bureau, 2003 National Cholesterol Education Program & National Institute of Health, 2002

  40. Thank you!

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