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 role in the development of CVD
Relative risk for CHD
LOG-LINEAR RELATIONSHIP BETWEEN
LDL-C LEVELS AND RELATIVE RISK FOR CHD2
LDL-Cholesterol (mg/dl)
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
European Guidelines on cardiovascular disease prevention in clinical practice (version 2012). European Heart Journal 2012; 33: 1635–1701.
Grundy et al Circulation 2004; 110;
Cholesterol Treatment Trialists’ (CTT) Collaborators. Lancet DOI: /S (12)

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 T HE EARLY ADULTHOOD1
Atheroscelosis prevalence (%)
Age
Tuzcu et al. Circulation 2001; 103:
Daniels et al. Pediatrics 2008; 122:
National High Blood Pressure Education Program Working Group on High Blood Pressure in children and adolescents. Pediatrics 2004; 114:
US Preventive Services Task Force. Pediatrics 2010; 125:
Juonala et al. Circulation 2010; 122:

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:
Pletcher et al. Ann Intern Med 2010; 153:
Berry et al. N Engl J Med 2012; 366:
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:

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 doi: /ijo

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:

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 IN 1969–20021
North Karelia
Start of the North Karelia Project
All Finland
Extension of the Project nationally
CHD mortality (per inhabitants)
National Institute for Health and Welfare, Finland.
Vartiainen et al. Int J Epidemiol 2010; 39:
Valsta et al. Public Health Nutr 2010; 13:
North-Karelia Project was a community-based program in Finland to change coronary risk factors:
- smoking
- serum cholesterol
- changing saturated fats to vegetable oils
- blood pressure
Means:
Mass media, workplaces, children primary care, schools, hospitals, local communities
Training programs
Mobilization of public support through local leaders
New social organizations (housewives’ groups)
Involving food industry and grocery stores to change food supplies (e.g. less salt, less fat)

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
Vartiainen et al. Int J Epidemiol 2010 ; 39:
Presentation name / Author
15/04/2017 12

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
mmol/L
Oulu province
Parallel with the positive changes in the diet, less saturated fat and more vegetables, the mean serum cholesterol has declined in the population level
Vartiainen et al. Int J Epidemiol 2010 ; 39:

14. OBSERVED AND PREDICTED SERUM CHOLESTEROL REDUCTION IN FINLAND1
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
mmol/L
Observed serum cholesterol
Valsta et al. Public Health Nutr 2010; 13:

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 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 DOI: /
Magnussen et al. Pediatr Nephrol DOI: /s y
Laitinen et al. Circulation DOI: /CIRCULATIONAHA
Daniels et al. Pediatrics 2008; 122:
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
North-Karelia Project was a community-based program to change coronary risk factors:
- smoking
- serum cholesterol
- changing saturated fats to vegetable oils
- blood pressure
Means:
Mass media, workplaces, children primary care, schools, hospitals, local communities
Training programmes
Mobilization of public support through local leaders
New social organizations (housewives’ groups)
Involving food industry and grocery stores to change food supplies (e.g. less salt, less fat)
Puska P. In: Puska et al (eds.). The North Karelia Project: From North Karelia to national action. Helsinki University Printing House 17

18. Dietary management of LDL cholesterol

19. OBSERVED AND PREDICTED SERUM CHOLESTEROL REDUCTION IN FINLAND1
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:

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 DOI: /S (12)
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 alone
Healthy diet with plant stanol ester
Statin medication
Healthy diet
Reduction in LDL (%)
Plant stanol ester
Statin medication
Modified from:
Hallikainen and Uusitupa. Am J Clin Nutr 1999; 69:
Blair et al. Am J Cardiol 2000; 86:

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

23. LDL LOWERING EFFECT OF SELECTED DIETARY CHOICES
Plant stanol ester is the most effective
dietary option in lowering cholesterol
LDL LOWERING EFFECT OF SELECTED DIETARY CHOICES
The graph:
1. Plant stanols (0,8 g/day), e.g. less than half a bottle of Benecol
2. Plant stanols (2 g/day), e.g. 1 bottle of Benecol
3. Plant stanols (3 g/day), e.g. 1,5 bottles of Benecol
4. Soluble fibre (5-15 g/day), e.g bananas
5. Soy protein (25 g/day), e.g. 1 l of soy milk
6. Replacing saturated fats with mono- & polyunsaturated fats, e.g. switching from 25 g of butter/day to 20 g of vegetable oil/day
7. Beta-glucan (3 g/day), e.g. 3 bowls of oatmeal porridge, 2 dl each
8. Omega-3 from fish oil (2 g/day), e.g. 150 g of salmon 23

24. LDL cholesterol lowering
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:

25. Plant stanol ester as a part of lifestyle intervention
PLANT STANOL ESTER RECOMMENDED AS PART OF THE LIFESTYLE INTERVENTION
LDL-C level
LOW
HIGH
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
Statin medication alone
Healthy diet + plant stanol ester + statin medication
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:
Blair et al. Am J Cardiol 2000; 86:

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
Milk from Chile
Feta cheese from Greece
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.
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).
Eur Heart J 2012; 33:

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
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
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
European Society of Cardiology (ESC): European Guidelines on cardiovascular disease prevention in clinical practice,  
National Heart, Lung, and Blood Institute (NHLBI) & National Institutes of Health (NIH) & American Academy of Pediatrics (AAP): Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents, 2011.
ESC & European Atherosclerosis Society (EAS): ESC/EAS Guidelines for the management of dyslipidemias, 2011.
The Australian Heart Foundation: Position statement on phytosterol/stanol enriched foods, 2009.
AAP: Lipid Screening and Cardiovascular Health in Childhood, 2008.
American Diabetes Association (ADA): Nutrition Recommendations and Interventions for Diabetes, 2008.
ADA & American College of Cardiology (ACC): Lipoprotein Management in Patients With Cardiometabolic Risk, 2008.
American Heart Association (AHA) / ACC: Guidelines for secondary prevention for patients with coronary and other atherosclerotic vascular disease, 2006.
Joint British Societies: JBS 2: Guidelines on prevention of cardiovascular disease in clinical practice, 2005.
International Atherosclerosis Society (IAS): Harmonized Guidelines on Prevention of Atherosclerotic Cardiovascular Diseases, 2005.
Joint WHO/FAO Expert Consultation: Diet, nutrition, and the prevention of chronic diseases, 2003.
International Lipid Information Bureau: Dyslipidemia and Coronary Heart Disease - The ILIB Lipid Handbook for Clinical Practice, 2003.
NCEP & NIH: 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.
In addition to these guidelines mentioned, there are several local national guidelines recommending the use of plant stanols.

40. Thank you!