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jeudi 1 décembre 2011

FIFTEEN ESSENTIAL QUESTIONS ABOUT CHOLESTEROL

Fifteen Essential Questions About Cholesterol

Cholestrol is essential for vital cell and body functions and is therefor essential for life. High levels of cholesterol are good marker for cardiovascular diseases like narrowed or blocked arteries(atheroscelrosis) resulting in reduced oxeygenated supplies to vital organs and tissues leading to angina, heart attack, heart failure and other related diseases. We have attempted to cover the topic as answers to 15 frequently asked questions.

Table des matières




LES AUTEURS


Salim Djelouat
Professor Medical Analyses and Medical bacteriology / Scientific Author / knolAuteur
Krishan Maggon
Consultant Pharmaceutical Biotechnology R&D & Advisor, Geneva, Switzerland & New York, USA
Knol Publishing Guild (KPG)
Serving the publishing aspirations of Knol writers, Planet Earth





Cholesterol is a water insoluble lipid or fatty substance and is produced by the liver from fatty foods or fats in foods we eat. Cholesterol was first isolated,  purified from gallstones and described  in the year 1769 by a French chemist Francoise Poulletier de la Salle. The metabolism and biosythesis was extensively studied during the early to mid decades of the last century.  The discovery and development of the first statin Mevacor by Merck scientists led by Roy Vegelos and Ed Scolnick led to the identification of cholesterol as a surrogate marker for cardiovacsular disease (atheroscelrosis or arterioscelrosis) and its spotlight in the media. The market success of statins like Zocor, Lipitor, Crestor has reinforced the cholesterol topic and discussion as part of our daily life.


 
Excess levels of cholesterol along with a variety of trigger factors can built up in our arteries and star blocking free flow of blood which carries oxygen. Statistically speaking, one can say today, that 20 to 30% of the adult population is touched by a cholesterol excess.
In the absence of obvious symptoms and of any feeling of pain, one lets cholesterol settle, from where an absence of assumption of responsibility early which will rock us towards vascular and cardiovascular pathologies, heavy and expensive treatments.

We provide you through a set of frequently asked questions and answers about cholesterol and the part it plays in cardiovascular diseases. After reading the knol you know:  what is cholesterol, to make a difference between the good and bad cholesterol, to control its cholesterol level, to modify its food behaviors and its practices of life, finally to deal with your own health.

Before the development and marketing of lipid lowering drugs of the statin class, only 1 million patients out of 25 % affected US population were treated in the early 1980s. The drugs used were fibrates and chelating agents with poor efficacy, oral suspension and serious adverse reactions. The approval of lovastatin (Mevacor, Merck) by the FDA in 1987, provided the first highly effective and relatively safe drug in easy to take oral pill form. Clever marketing and educational programs by Merck in collaboration with the American Heart Association and the federal government National Cholesterol Educational Program in late 80s and free cholesterol testing with diagnostic companies increased. Once the awareness was there, the solution was to treat it with an effective drug which was Mevacor. Mevacor became the most successful new market launch in 1988 with sales crossing 280 million and it became a blockbuster within 4 years.

So 1987-1988 are the years when cholesterol became a major issue and it increased with the successful introductions of Zocor, Pravachol, Lipitor and Crestor in the 90s and the past decade. Both Zocor and Pravachol had annual sales of over 5 billion dollars before going generic. Lipitor the best selling drug of all times since the past 8 years had peak annual sales of over 13.5 billion 2 years ago is going generic at the end of 2011. Crestor the last new statin brand under patent coverage had sales of over 6 billion in 2010.


1 - What is cholesterol ?

Cholesterol is a fatty substance essential to the life.
It takes part in the manufacture of all the cells and the hormones of the organization.
Cholesterol is the most important lipid of the organization.
As a lipid, cholesterol constitutes the energy reserve of the cell.
By its presence, it gives flexibility and force to the walls of the cells and also ensures their protection vis-a-vis the external aggressions.
It transports the vitamins A, D, E, K It intervenes in the manufacture of the sex hormones, the corticosteroids (like cortisone) natural and of the components of the bile.
Cholesterol thus remains essential to the correct operation of the human body.
In a word, cholesterol is cement of the human body.



Cholesterol-3d.png


 

2 - Source of cholesterol ?

Cholesterol is a grease manufactured by the liver (75%), the intestine and the corticosuprarenal glands (glands located at the top of each kidney) and the third is brought back by the food (especially the eggs, the meat offals, butter, full-cream milk…).
The cholesterol brought by food is not technically speaking a greasy substance, because it does not provide energy.

 

3 - Why cholesterol levels increase  ?

Cholesterol increases because:

    a - our food bad habits, especially by the contribution of saturated fatty acids (butter, cheese, cream-coloured, ox greases, certain oils, etc).

    b
- stress


    c
- Certain genetic predispositions (family antecedents of hypercholesterolemia, diabetes, cardiovascular diseases)


    d
- certain diseases and as private individuals renal diseases and the hypothyroid


    e
- arterial hypertension


    f
- diabetes


    g
- on weight (or obesity, which, when it is present, is often associated an excess of bad cholesterol, a hypertension or a diabetes)


    h
- of our sedentary life (i.e. lack of exercise, at least of 3 times 30 mn of physical exercise per week)


    i
- nicotinism (current or stopped since less than 3 years)


    j
- alcohol


    k
- Drug induced  (especially the HIV tritherapy, birth control pills)

Net Cholesterol Balance in Humans

Image from : 


4 - Risks of  elevated  cholesterol  ? 

The increase in the cholesterol level in blood is at the origin of the coronary disease (angina pectoris, myocardial infarction).
It is one of the principal factors of risk of these diseases with the tobacco, arterial hypertension and the diabetes.
The cholesterol excess will give a sclerotic plaque to the the arteries, especially the coronary arteries.


5 - What it is a Plaque ? 

Cholesterol in excess will settle on the walls of the arteries, in particular the arteries of the heart (coronary arteries).
 A plaque will develop very early and will worsen with the passing of years and will have as a consequence:

        a - to reduce the diameter of the arteries
        b - to block the passage of increasingly blood, from where the cells will be deprived from oxygen and will die
        c - to support the formation of clots of blood (thromboses).

All these symptoms will give the ischaemic accident which according to the blocked artery will involve, either myocardial infarction, or the cerebral vascular accident, or arteritis of the lower limbs.
    Unfortunately the described symptoms appear often only late in the process.
 
Image from NHLBI
 
Atherosclerosis
 



6 - What is generally called "good or bad" fat ?

It should initially be known that there are not the “maid” or “bad greases” is, since in fact the excessive or insufficient quantities introduced can have consequences prejudicial for the organism. 

    “Good greases”, called the unsaturated fatty acids, are especially present in oils, the oilseeds and fish.     Omegas 3, omegas 6 and omegas 9, are today of topicality, because they take part in the correct operation of the cardiovascular system and unfortunately they are not produced by the human body.

    “Bad greases”, called the saturated fatty acids, are found in butter, the margarine, the fatty meats (lamb and ox), the dairy products, the cheese Gruyere, the chips, the chocolate the daily consumption of meat containing of greases saturated double the lipidic contribution, which will involve a clogging of the body.


7 - What is "good or bad" cholesterol ?

To reach the various organs and tissues of the organism, cholesterol will use conveyors or chaperons who allow it to circulate in blood.
Cholesterol circulates in blood via the LDL (Low Density Lipoproteins) which is a conveyor charged to direct cholesterol towards the cells.
The cells will collect the quantity of cholesterol necessary for the correct operation.
The cholesterol surplus is then dealt with by the HDL (High Density Lipoproteins) which goes rebooked towards the liver or it will be recycled and partially eliminated by biliary salts.
If the LDL-cholesterol surplus is very important or if HDL-cholesterol is insufficient, LDL-cholesterol will remain in blood.
LDL-cholesterol in excess and what is called “bad cholesterol” will settle little by little on the arterial walls and will cause a contracting initially and then an obstruction of the blood vessels at the origin of cardiovascular accidents.

On the other hand, more the HDL-cholesterol rate (or “good cholesterol”) is important; more the level of protection against the problems cardiovascular is high.

Reverse Cholesterol transport Image from HDL-Cholesterol by Robert Rosenson, MD

 

National Cholesterol Education Program

NCEP Logo
    The National Heart, Lung, and Blood Institute (NHLBI) launched the National     Cholesterol Education Program (NCEP) in November 1985. The goal of the NCEP     is to contribute to reducing illness and death from coronary heart disease (CHD)     in the United States by reducing the percent of Americans with high blood         cholesterol. Through educational efforts directed at health professionals and the public, the NCEP aims to raise awareness and understanding about high blood cholesterol as a risk factor for CHD and the benefits of lowering cholesterol levels as a means of preventing CHD.



8 - Know you your cholesterol level ?

It rests on each one of us to take the initiative of an analysis of blood, when that is not prescribed by the doctor.
The analysis of blood is the only means to detect a possible hypercholesterolemy.
In general the proportioning of cholesterol is recommended for the first tracking as of the 20 years age, even 16 years for certain family antecedents.

    The blood assessment must relate normally to:

  • The proportioning of total cholesterol
  • HDL-cholesterol
  • the proportioning of triglycerides

    Rate of cholesterol: 
  • Rate of ideal cholesterol: < 2 gram per liter
  • Rate of limit cholesterol: between 2 and 2,50 gram per liter
  • Rate of high cholesterol: > 2,50 gram by liter
Only LDL-cholesterol defines the cardiovascular risk, the therapeutic assumption of responsibility in case will be depended on the presence or not of the other factors of risk.
    Threshold of LDL cholesterol according to the factors of risk:

        1 - Patients without another factor of risk: > 2,20g/l (5,7 mmol/l)
        2 - Patients having another factor of risk: > 1,90g/l (4,9 mmol/l)
        3 - Patients having two other factors of risk:  > 1,60g/l (4,1 mmol/l)
        4 - Patients having more than two other factors of risk:  > 1,30g/l (3,4 mmol/l)
        5 - Patients having a coronary disease:  > 1g/l (2.6 mmol/)

These values must be modulated according to the age, of the sex and the triglyceride and cholesterol levels HDL.

The association or not of other factors of risks which make it possible to evaluate the risk and to define the action to be taken, fall within the competence of the attending practitioner.

 



9 - Which are the methods and the interpretation of the results ?

The patient has had to fast for 12 hours and must avoid smoking before the examination.               Interpretation rests initially and above all on the physiological variations and which are related on the age and the pregnancy at the woman.

The pathological variations are due mainly to:
  • nutritional contributions too rich in fat content
  • hypothyroïdie
  • nephrotic syndrome
  • family hypercholesterolemia
  • Malnutrition, hyperthyroîdie or hepatic insufficiency, are marked by a fall of the cholesterol level.


10 - Does cholesterol excess contributes to the weight gain?

    The ponderal overload which is placed preferably in the high parts of the body (neck, girdles scapular, abdomen) very often accompanies by many anomalies:

  • hypertension,
  • diabetes of the type 2,
  • Increase in triglycerides and hypercholesterolemy.

An even moderate loss of weight improves health of the people whose index of body mass index (BMI) is higher than the normal.
To calculate its BMI, it is necessary to divide its weight by its size. 
BMI  normal is equal to 24
 
 
Mevalonate pathway  :
http://en.wikipedia.org/wiki/Cholesterol_synthesis





11 - Which type of anti-cholesterol diet ?

A good food is the first treatment of a cholesterol excess.
This food can even sometimes make avoid a medicamentous treatment and almost always makes it possible to decrease the cardiovascular risk.
As many good reasons to adopt the good dietetic rules.
To overcome cholesterol, it is initially to supervise its food.

    The principal dietetic priorities are now well defined and it is in particular about:

1 - To reduce the total contribution of greases, which should represent not more than 30 to 35% of the total calories.

2 - To decrease the saturated fatty acids, which are generally responsible for a rise of cholesterol and in particular of the LDL.

3 - to privilege the unsaturated fatty acids, which are beneficial and allow a reduction in total cholesterol and LDL-cholesterol and this whole while preserving HDL-cholesterol (good cholesterol).

4 - to limit the food cholesterol contribution, in particular by the contribution of animal greases (butter, the lipids of the meats, cheeses), meat offals and the egg yolk.

5 - to increase the contribution of protective antioxydants by consuming fresh fruits and vegetables which are rich in vitamins C, E, beta-carotene
 
 
CHD Mortality
by Health Service Area, 1996-98
 



12 - Impact of cholesterol on my daily life : what I have to do ? 

In practice, to follow the 5 principal described priorities, amounts complying with some simple rules and which are (described rules following our daily realities and function of what one to find on our premises):

a - to replace butter by a vegetable margarine rich in fatty acid polyinsaturés and containing antioxydants of vegetable origin.

b - to use a made up vegetable oil (if you managed to find it on the market), if not one uses two (02) different oils: olive oil (or groundnuts) with another oil, is the sunflower oil, in order to obtain an optimal balance in fatty acids.

c - to consume reduced dairy products (skimmed milk or skimmed half, these milks is obtained in their removing either all the cream, or part of the cream), reduced cheeses, type the cow which laughs light.

e - avoid pastry makings E - to eat fish, if possible 2 to 3 times per weeks (the sardine is enough amply)

e - choose lean meats by withdrawing the visible fatty parts and avoid the meats with nets of greases kind chops

g - do not exceed 2 eggs per week, but the egg white can be consumed without limitation.

h - privilege the fruits and fresh preferably of seasons, out of preserve or possibly frozen vegetables.
 

13- Why is it necessary to eat  vegetables and fruits in a

model anti-cholestérol diet?


Due to the low fat content and calories, the fruits and the vegetables satisfy while bringing micro nutrients (vitamins, minerals, trace elements, fibres), essential at the organism.
They contain in particular antioxydants, which prevent the oxidation of cholesterol and avoid the formation of plates in the arteries.
Associated with a reduction in saturated greases, the fruit consumption and vegetables promote good cardiovascular health.



14 - Are anti-cholesterol diets effective ?

Dietetic measurements have a real impact on health.
A well followed model diet fad makes it possible to lower up to 8% the cholesterol-LDL rate.
This type of model is based above all on the reduction in the fatty acids saturated with the food to the profit of the polyinsaturés fatty acids and in addition on an increase in the vegetable fruit consumption, cereals (complete preferably) and physical activity.


15 - It is said that cholesterol varies according to the seasons ?    

Indeed very serious studies showed that the cholesterol level varies with the seasons.
It is higher in autumn and in winter and drops to spring and in summer.
This fluctuation of the cholesterol level inter season, remains partly very mysterious, from where it involves consequences on the assumption of responsibility of the patients.
The seasonal variations of cholesterol are marked among women than at the men.
In summer, the physical activity and the loss of weight can explain the reduction in the rate of cholesterol in blood, contrary to the winter which is much more favourable with sedentariness, therefore to the catch of weight.
With that, Can be added hormonal factors, one knows that the solar exposure can influence the secretion of certain hormones which indirectly, will influence the cholesterol level.
To also underline that the phenomena known as of hémodilution and hemoconcentration were reported, which could also explain the majority of these variations.


Michael S Brown and Joseph Goldstein, USA were awarded Nobel Prize in Medicine in 1985 for their discovery concerning regulation of cholesterol metabolism.

Goldstein, J.L. and Brown, M.S.: History of discovery: The LDL receptor. Arterioscler. Thromb. Vasc. Biol. 29: 431-438, 2009.

Prof M. Brown                  Prof J. Goldstein
Photo of Michael S. Brown        Photo of Dr. Joseph Goldstein


Images From Brown Goldstein Lab


SREBP Pathway

Inflammatory cholesterol-rich atherosclerotic plaques in coronary arteries nourishing heart muscle. 


 
 
  Steroidogenesis, using cholesterol as building material

High Cholesterol
Introduction — Lipids, such as cholesterol and triglycerides, are fats that are an integral part of cells, and that may...
by Robert Rosenson, MD

 
 
Drugs and brands used to control cholesterol levels
 
Crestor - rosuvastatin calcium
 
WelChol
 
lipitor
 
Zetia® (ezetimibe) Add strength with confidence.

 
NIASPAN®, Niacin Extended-Release Tablets
 
 
 
Statin + Welchol vs statin titration1
 


National Cholesterol Education Month

September is National Cholesterol Education Month, a good time to get your blood cholesterol checked and take steps to lower it if it is high. National Cholesterol Education Month is also a good time to learn about lipid profiles and about food and lifestyle choices that help you reach personal cholesterol goals.
High blood cholesterol affects over 65 million Americans. It is a serious condition that increases your risk for heart disease. The higher your cholesterol level, the greater the risk. You can have high cholesterol and not know it. Lowering cholesterol levels that are too high lessens your risk for developing heart disease and reduces the chance of having a heart attack or dying of heart disease.
The National Heart, Lung, and Blood Institute offers helpful resources to use during National Cholesterol Education Month.

For Individuals




Available only in print
Get these public education booklets for yourself and share them with family and friends.


For Persons with High Blood Cholesterol Who Need to Lower It


For Community Group Education Programs

Offer an educational session for groups who may benefit from a better understanding of cholesterol. Use these teaching tools:

Make cholesterol information booklets available at your worksite, health center, community center, or HMO. Have plenty of copies on hand for screening events.


For Clinicians

Refresh your skills in cholesterol assessment and management with:


For Everyone



For Bulletin Board Displays

Use pages from these resources to create an educational display in September:
  • High Blood Cholesterol: What You Need to Know
  • Tables and Text from Your Guide to Lowering Your Cholesterol with Therapeutic Lifestyle Changes (TLC)
    • What's Your Heart Disease Risk? - p. 8
    • What's Your 10-Year Risk for a Heart Attack? - pp. 10-12
    • Drop Your Cholesterol with TLC - p. 16
    • Setting Your LDL Goal - p. 9
    • The TLC Diet: A Heart Healthy Eating Plan - p.19
    • Sample Saturated Fat Intakes - p. 22
    • Fiber Solutions - p. 28
    • Fiber Really Counts - p. 29
    • How to Make Heart Healthy Meals - pp. 39-40
    • Losing Weight and Gaining Heart Health - pp. 49-50
    • How to Lower Your Calories on TLC - p. 50
    • Choose the Foods That Help You Lose - pp. 51-52
    • A Handy Guide to Calories Burned in Common Activities - p. 46
    • Benefits of Regular Physical Activity - p. 42
    • Getting Active - p. 44



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