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
• Plant stanol ester – a dietary tool for effective LDL-C
lowering
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
3
Hypercholesterolemia in key role
in the development of CVD
1.
2.
3.
LOG-LINEAR RELATIONSHIP BETWEEN
LDL-C LEVELS AND RELATIVE RISK FOR CHD2
Relative risk for CHD
• 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
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.
4
Lowering LDL cholesterol:
The earlier the better (1)
• It is acknowledged that atherosclerosis
begins in childhood1
• 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
1.
2.
3.
4.
5.
Atheroscelosis prevalence (%)
• Guidelines recommend the assessment and
management of cardiovascular risk factors
already in youth2-4
ATHEROSCLEROSIS DEVELOPS FROM T
HE EARLY ADULTHOOD1
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.
5
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
1.
2.
3.
4.
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
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
1.
2.
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.
7
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
1.
2.
Strandberg et al. J Am Coll Cardiol 2004; 44: 1002– 1008.
Strandberg et al. Int J Obes 2012. doi: 10.1038/ijo.2012.83.
8
Diet as a tool for effective
cholesterol lowering
9
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
1.
2.
3.
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.
10
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
• 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
1.
2.
3.
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.
Start of the North Karelia Project
CHD mortality (per 100 000 inhabitants)
• Reductions in serum cholesterol explain
most of this decline2
AGE-STANDARDIZED CHD MORTALITY IN
FINLAND IN MEN AGED 35-64 IN 1969–20021
North Karelia
All Finland
Extension of the Project nationally
11
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
All risk factors
Percentage (%)
Observed
1.
Vartiainen et al. Int J Epidemiol 2010 ; 39: 504-518.
Presentation name / Author
12
13/04/2015 12
Significant decline in serum
cholesterol in Finland
MEAN SERUM CHOLESTEROL IN MEN IN FINLAND1
North Karelia county
Northern Savo county
Southwestern Finland
mmol/L
Helsinki and Vantaa cities
1.
Oulu province
Vartiainen et al. Int J Epidemiol 2010 ; 39: 504-518.
13
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
1.
Valsta et al. Public Health Nutr 2010; 13: 932-938.
14
Positive dietary changes are achievable
In Finland, heart-healthy changes in diet have been achieved at population level
EXAMPLES OF DIETARY CHANGES IN FINLAND1
Prevalence of dietary habits in men (%)
Skimmed milk
1.
Vegetables daily
Butter on bread
Health Behaviour and Health among the Finnish Adult Population, Spring 2011. Publications of
the National Institute for Health and Welfare (THL). Report 45/2012.
15
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
1.
2.
3.
4.
5.
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.
16
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
1.
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
Dietary management of LDL cholesterol
18
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
OBSERVED AND PREDICTED SERUM CHOLESTEROL
REDUCTION IN FINLAND
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
1.
Valsta et al. Public Health Nutr 2010; 13: 932-938
mmol/L
1
Medication effect
Dietary effect
Medication +
dietary effect
Observed serum
cholesterol
19
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
1.
2.
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.
20
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 with
plant stanol ester
Statin
medication
Reduction in LDL (%)
Healthy diet
alone
Modified from:
1.Hallikainen and Uusitupa. Am J Clin Nutr 1999; 69: 403-410.
2.Blair et al. Am J Cardiol 2000; 86: 46-52.
Healthy diet
Plant stanol ester
Statin medication
21
Plant stanol ester –
effective and recommended
dietary option for LDL management
22
Plant stanol ester is the most effective
dietary option in lowering cholesterol
LDL LOWERING EFFECT OF SELECTED DIETARY CHOICES
23
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
1.
Modified from Model of steps in TLC (US NCEP): JAMA 2001; 285: 2486-2497.
24
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
CVD risk
Lifestyle
intervention
including plant
stanol ester
Lifestyle intervention
(incl. plant stanol ester)
and medication
HIGH
1.
2.
3.
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
25
Plant stanol ester complements
statin treatment
INCREMENTAL REDUCTION IN LDL CHOLESTEROL
WITH PLANT STANOL ESTER
Healthy diet
Statin medication + plant stanol ester
+ plant stanol ester + statin medication
Reduction in LDL cholesterol (%)
Statin
medication
alone
Modified from:
1.Hallikainen and Uusitupa. Am J Clin Nutr 1999; 69: 403-410.
2.Blair et al. Am J Cardiol 2000; 86: 46-52.
Statin medication
Plant stanol ester
Healthy diet
26
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 only
Statin starting dose x 4
Statin + plant stanol ester
Statins and
plant stanol
ester
27
Plant stanol ester only in
Benecol foods
28
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
Yogurt drink
from Finland
Feta cheese
from Greece
Yogurt drink
from Spain
Smoothie from
Indonesia
29
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
30
Conclusions
31
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 hearthealthy diet
32
Plant stanol ester in the
treatment and prevention
guidelines
33
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
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 lowfat 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).
35
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
36
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.
37
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
38
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
39
Thank you!