Transcript Low density lipoprotein

RISK FACTORS
IRREVERSIBLE
•Masculine
gender
•Increasing age
•Genetic traits
•Body build
GEOGRAPHICAL
•Climate and
season
POTENTIALLY
REVERSIBLE
•Smoking
•Dyslipidaemia
•Obesity
•Hypertension
•Physical in
activity
•Diabetes
PSYCHOLOGICAL
•Low socioeconomic
class
•Stressful situation
•Coronary prone
behavior pattern
LIPOPROTEINS AND LIPID
METABOLISM
LIPOPROTEINS
Blood lipids and lipoproteins
Lipoproteins are molecular complex that consist
of lipids and proteins(conjugated proteins)
 They functions as transport vehicles for lipids in
blood plasma.
 Lipoproteins deliver the lipid components to
various tissues for utilization.

STRUCTURE OF LIPOPROTEINS
 A lipoprotein basically consist of neutral lipid
core surrounded by a coat shell or
phospholipids, apoprotein and cholesterol.

Lipoprotein is soluble in aqueous solution.
APOLIPOPROTEINS(APOPROTEINS)
The protein components lipoprotein are known
as apolipiproteins.
 THEY PERFORM THE FOLLOWING FUNCTIONS
 Act as structural components of lipoprotein.
 Recognize the cell membrane surface receptor.

CLASSES
1.Apolipoproteins B form low-density lipoprotein particles. These
proteins have mostly beta-sheet structure .
2.Other apolipoproteins form high-density lipoprotein particles.
These proteins consist of alpha-helices.
There are six classes of apolipoproteins and several
sub-classes:
1. A (apo A-I, apo A-II, apo A-IV, and apo A-V)
2. B (apo B48 and apo B100)
3. C (apo C-I, apo C-II, apo C-III, and apo C-IV)
4. D
5. E
6. H
CHOLESTEROL
 60-70% is carried on LDL, 20%-30% on HDL,
and 10-15% on VLDL
 Population that consume diets high in
saturated fatty acids have increased blood
cholesterol levels.
Functions Major constitute of all cell membranes
 Precursor of bile acid
 Precursor of adrenal and reproductive steroids.
 Essential component of plasma lipoprotein.
 Precursor of vitamin D synthesis.
FACTORS- age, diet high in fat, saturated fat and
cholesterol, genetics, endogenous sex
hormones, body weight, presence of other
diseases.
Total Triglyceride
 The triglyceride-rich lipoproteins include
chylomicrons, LDLs, and any remnants or
intermediary products formed in metabolism.
 All contain the apo B lipoprotein
 Fasting triglyceride Levels are classified as
normal (<150 mg/dl), borderline high (150 to
199 mg/dl), high (200 to 499 mg/dl), and very
high (>500 mg/dl)
METABOLISM
Lipid transport can be understood as thewater insoluble lipids
water soluble forms
water insoluble lipids.
Remember, fat floats on water, because it is
lighter than water
TRIGYLYCERIDES FROM GUT TO ADIPOCYTEChylomicrons.
 Monoglycerides and fatty acids are re-esterified
triglycerides within the mucosal cell.
 The lipid rich particles leave the mucosal cell
and travel through lymphatic channels to the
thoracic duct that empties into the right side of
the heart.
 Chylomicrons leaves the heart through the aorta
and are transported to the adipocyte.

Lipoprotein lipase(LPL), an enzyme bind
chylomicrons (c)and cleave triglycerides
monoglycerides +fatty acids re-esterified
into triglycerides
hydrophobic storage
TRIGLYCERIDES FROM LIVER TO ADIPOCYTEvery low-density lipoprotein.
 The liver receive fat from a number of sources1. From chylomicrons remnants
2. From circulating fatty acids
3. From uptake of intermediate lipoproteins
4. From endogenous body synthesis.
The liver re-esterifie from all sources and wraps
in a heavier coat of protein and phospholipids
to form VLDL.
 This lipoprotein is richer in cholesterol than
chylomicrons.
 In the fed state, large no of VLDL are formed
and then sported to adipocyte.
 Insulin-facilates large storage

CHOLESTEROL FROM DIET AND LIVER TO ALL
CELLLow density lipoprotein
 After LPL has cleaved additional triglyceride
from VLDL, the remnant remaining is called an
intermediate density lipoprotein.
 The endocyte vesicles containing LDL receptors
is fused with lysosome, there by breaking it
down
 The protein is recycles to the cellular amino
acids pool and cholesterol is released for use
by the cell.

CHOLESTEROL FROM CELL TO THE LIVERHigh density lipoproteins
 The HDL facilitates cholesterol turnover by
removing free cholesterol from cell membrane
and scavenging cholesterol from other
lipoproteins.
 HDL particles are formed in the liver as proteinPHOSPHOLIPIDS disk.


The ability of HDL, to function as a cholesterol
transporter is dependent on the activity of Cudependent enzyme-LECITHIN CHOLESTEROL
ACYL TRANSFERASE.
LIPOPROTEIN LIPASE

It is an enzyme that hydrolyzes lipids in lipoprotein, such as those found in chylomicrons,
VLDL, into two FFA and one monoacylglycerol.





LPL is specifically found in endothelial cell linning.
LPL functions as homodimer, and had dual
function of
Triglyceride hydrolyses
Bridging factor for receptor.
Insulin is known to reduce LPL synthesis in
adipocyte
LIPOPROTEIN PROFILE
Include measurement of total cholesterol, LDL
cholesterol, and total triglyceride levels and
thus should be measured after a person has
fasted for 8-12 hours.
 The friedewald formula is.
LDL-C = (TC) – (HDL-C) – (TG/5)

LOW DENSITY LIPOPROTEIN
 A decrease in 1 mg/dl in LDL cholesterol results
in about a 1% to 2% decrease in relative risk for
CHD.
 LDL cholesterol levels for children and adult are100 mg/dl and 123mg/dl
FACTORS THAT INCREASE LDL CHOLESTEROL
 Aging
 Genetics
 Diet
 Reduced estrogen levels
 Diabetes
 obesity
TRIGLYCERIDE LEVELS

During the acute phase response, serum
triglyceride are increased, and HDL cholesterol
is decreased in an effort to move nutrients to
the cell that need them in host defense.
FACTORS THAT INCREASE TRIGLYCERIDE LEVELS
ARE
Diet(excessively low-fat, high refined
carbohydrates)
 Estrogens
 Alcohol
 Obesity
 Untreated diabetes
 Chronic renal failure
 And liver diseases

HIGH DENSITY LIPOPROTEIN CHOLESTEROL

HDL as good cholesterol
A HDL cholesterol levels (> 60 mg/dl)
considered a negative risk factor for CHD.
FACTORS THAT INCREASE HDL CHOLESTEROL
LEVELS
Exogenous estrogen
 Intensive exercise
 Loss of excess body fat
 Moderate consumption of alcohol

The consumption of alcoholic beverages, in
particular red wine, results in reduction in
cardiovascular risk factor and decrease mortality.
PROPERTIES AND FUNCTIONS OF MAJOR
PLASMA LIPOPROTEIN
LIPOPROTEI
N
ORIGIN
DENSITY
RANGE
MAJOR
LIPID
MAJOR
PROTEIN
FUNCTION
Chylomicron
s
Small
intestine
<0.94
TG
B-48
A-I,A-II
Absorption
and
transportatio
n of dietary
fat
VLDL
Liver
0.94-1.006
TG
B-100,
C-I,C-II,C-III
Transport of
TG from liver
to other
tissues.
IDL
Plasma,
VLDL
1.006-1.019 TG and
cholesterol
esters
B-100
Cholesterol
transport,
precursor of
LDL
LIPOPROTEI
N
ORIGIN
DENSITY
RANGE
MAJOR LIPID MAJOR
PROTEIN
LDL
Plasma, IDL
1.019-1.063 Cholesterol
esters
B-100
Cholesterol
ester
transport
HDL
Liver, small
intestine
1.063-1.21
A-I
Removal of
cholesterol
from
extrahepatic
tissues
Phospholipi
ds and
cholesterol
FUNCTIONS
ATP III GUIDLINES
Since 1988,the National Cholesterol Education
Program(NCEP) has issued guidelines
identifying LDL cholesterol as the primary
target of cholesterol therapy.
 ATP III guidelines issued in May 2001,
emphasizes the role of diet and exercise in
decreasing for developing CHD.

KEY FEATURES OF ATP III GUIDELINESA change in minimum accepted level of HDL.
 A new set of therapeutic lifestyle changes.
 Identifying diabetes as CHD risk equivalent .
 Increase attention to the treatment of high TG
levels..
 A sharper focus on cluster of heart disease risk
factor known as the metabolic syndrome.

STEP 1
Determine lipoprotein levels–obtain complete
lipoprotein profile after 9 to 12 hour fast.
ATP III Classification of LDL, Total, and HDL Cholesterol
(mg/dl)Identify
LDL Cholesterol – Primary Target of Therapy
< 100
optimal
100-129
Near optimal/above optimal
130-159
Borderline high
160-189
high
>190
Very high
Total cholesterol
< 200
desirable
200-239
Borderline high
>240
High
HDL cholesterol
<40
Low
>60
High
STEP 2Identify presence of clinical atherosclerotic
disease that confers high risk for coronary heart
disease-
Clinical CHD
 Symptomatic carotid artery disease.
 Peripheral arterial disease.
 Abdominal aortic aneurysm.

STEP 3
Determine presence of major risk factors (other than LDL).
Major Risk Factors (Exclusive of LDL Cholesterol) That Modify
LDL
Goals
 Cigarette smoking
 Hypertension (BP >140/90 mmHg or on antihypertensive
medication)
 Low HDL cholesterol (<40 mg/dl)
 Family history of premature CHD (CHD in male first degree
relative <55 years;
CHD in female first degree relative <65 years)
 Age (men >45 years; women >55 years)
STEP 4
If 2+ risk factors (other than LDL) are present
without CHD or CHD risk equivalent, assess 10year (short-term) CHD risk



Three levels of 10-year risk:
>20% — CHD risk equivalent
n 10-20%
n <10%
STEP 5
Determine risk category:
 Establish LDL goal of therapy.
 Determine need for therapeutic lifestyle
changes (TLC)
 Determine level for drug consideration.
STEP 6
Initiate therapeutic lifestyle changes (TLC) if LDL is above
goal.
TLC Features
 TLC Diet:
 Saturated fat <7% of calories, cholesterol <200 mg/day
 Consider increased viscous (soluble) fiber (10-25 g/day)
and plant stanols/sterols (2g/day) as therapeutic
options to enhance LDL lowering
 Weight management
 Increased physical activity.
STEP 7
Consider adding drug therapy if LDL exceeds
levels.
 Consider drug simultaneously with TLC for
CHD and CHD equivalents
 Consider adding drug to TLC after 3 months for
other risk categories.
STEP - 8
Identify metabolic syndrome and treat, if present, after 3 months of TLC.
Risk factor
defining level
Abdominal obesity*
Men
Women
Waist circumference
>102 cm (>40 in)
>88 cm (>35 in)
Triglycerides
>150 mg/dl
HDL cholesterol
Men
Women
<40 mg/dl
<50 mg/dl
Blood pressure
>130/>85 mmHg
Fasting glucose
>110 mg/dl
Treatment of the metabolic syndrome
Treat underlying causes (overweight/obesity
and physical inactivity):
 Intensify weight management
 Increase physical activity.
Treat lipid and non-lipid risk factors if they
persist despite these lifestyle therapies:
 Treat hypertension
 Use aspirin for CHD patients to reduce
prothrombotic state
 Treat elevated triglycerides and/or low HDL
STEP 9
ATP III Classification of Serum
Triglycerides (mg/dL)
<150
Normal
150-199
Borderline high
200-499
High
>500
Very high
Treat elevated triglycerides.
Treatment of elevated triglycerides (>150 mg/dl)
 Primary aim of therapy is to reach LDL goal
 Intensify weight management
 Increase physical activity
 If triglycerides are >200 mg/dl after LDL goal is
reached, set secondary goal for non-HDL
cholesterol.
GENETIC
HYPERLIPIDEMIAS
Selected Genetic Hyperlipidemias
Gene Defect
Lipoproteins
Elevated
Familial Hypercholesterolemia
Diagnosis
Clinical
Findings
Treatment
Heterozygous
LDL-receptor
LDL
Serum
cholesterol
>300 mg/dl,
normal TGs,
affected firstdegree relative
Tendon
xathomas,
Archus
corneae,
premature CHD
drug therapy
Homozygous
LDL-receptor
LDL
Serum
cholesterol
from
500 mg/dl to
1000 mg/dl,
skin biopsy with
measure of LDL
receptor activity
Xanthomatosis
Progresses
rapidly, CHD in
first decade of
life
Remove LDL,
liver
Transplant
Familial Defectlve apo &1O0
Gene Defect
Lipoproteins
Elevated
Diagnosis
Clinical
Findings
Treatment
Apo B-100
LDL
Elevated serum
cholesterol,
normal TG
Tendon
xanthomas,
premature CHD
drug therapy
Polygenic Hypercholesterolemia
Unknown
Chylomicrons,
VLDL remnant
absence of
Absence of
secondary
tendon
causes of
xanthomas
hypercholestero
lemia, <10% of
first-degree
relatives
affected
drug therapy
Familial Dysbetalipoprotelnemia
Gene Defect
Apo E
Lipoproteins
Elevated
Chylomicrons,
VLDL
Remnants
Diagnosis
Clinical
Findings
Lipoprotein
Palmar and
electrophoresis tuberoeruptive
or ratio of VLDL xanthomas,
to total
CHD
plasma TG
Treatment
Weight
reduction,
low-fat, low
cholesterol
diet,
minimize
alcohol
Consumption,
estrogen
replacement in
women, drug
therapy
Familial Combined Hyperlipidemia
Gene Defect
Unknown
Lipoproteins
Elevated
TGs, total
cholesterol,
HDL
Diagnosis
Plasma TGs
200-800
mg/dl,
cholesterol
220-400
mg/dl, HDL
<40 mg/dl,
family
history of
hyperlipidemia
/premature
CHD,
elevated
plasma apo B
Clinical
Findings
Often present:
visceral
adiposity,
glucose
intolerance,
insulin
resistance,
hypertension,
hyperuricemia,
premature CHD
Treatment
TLC, drug
therapy,
Weight
reduction,
increased
physical
activity,
aggressive
blood
glucose control
DIETARY GUIDELINES
 The total fat should be less than 30 % of the
total energy intake
 MUFA should be between 10% to 15%, PUFA
less than 10%
 Carbohydrate should contribute 55% and
Protein- 15% of daily energy requirement.
 Cholesterol intake must be less than 200mg
per day.
DIETARY MANAGMENT
CALORIES BALANCE AND BODY WEIGHT- 8001000 kcal/day
 PROTEIN- 15% of total calories
 FAT- 10% of daily calorie requirement through fat
intake. Fat should be controlled in quality and
quantity by substituting PUFA for the part of
saturated fat.
 CABOHYDRATE-complex carbohydrates and
resistant starch advised.
Dietary fiber has shown a beneficial effect on the
blood lipid profile (20-30g/day )

Niacin has been known to be effective
treatment of dyslipidemia.
 Niacin increase HDL cholesterol levels.
 non dietary factors such as smoking, tobacco
and drinking alcohol have harmful effects in the
etiology of heart diseases

Consume a diet rich in vegetables and fruits
 Choose whole grain, high fiber foods.
 Consume fish.
 Selecting fat free, 1% fat and low fat dairy
products.
 Minimize your beverages and foods with added
sugars.
 Choose and prepare foods with little or no salt.

METABOLIC SYNDROME

The combination of insulin resistance, reactive
hyperinsulinemia, increased serum triglyceride
concentration, decreased HDL cholesterol and
hypertension are designated as METABOLIC
SYNDROME.
FACTORS
Weight
 Genetics
 Endocrine
 Insulin resistance
 Aging,
 and sedentary lifestyle,

SIGNS AND TESTS
Abdominal obesity
Waist circumference
Men
Women
>102 cm(>40 inc )
>88 cm (35 inch )
triglycerides
>150 mg/dl
HDL cholesterol
Men
Women
<40 mg/dl
<50 mg/dl
Blood pressure
>130mm Hg systolic blood pressure or
>85 mm Hg diasystolic blood pressure
Fasting glucose
>100 mg/dl
TREATMENT
The goal of treatment is to reduce your risk of
heart disease and diabetes.
 Lose weight
 Physical activity

HYPERTENSION
it is often called a "silent killer" because
people with hypertension can be
asymptomatic for years and then have a fatal
stroke or heart attack.
Hypertension is persistently high
Arterial blood pressure ,the force exerted per unit area
on the walls of arteries.

Systolic
blood pressure(SBP),the blood pressure during
the contraction phase of the cardiac cycle, has to be
140 mm Hg or higher; or the diastolic blood pressure
(DBP), the pressure during the relaxation phase of the
Cardiac cycle, has to be 90 mm Hg or higher, and they
are
Reported as 140/90m m Hg.
From the National High Blood Pressure Education Program
Coordinating Committee: The Seventh Report of the Joint
National Committee on Prevention, Detection, Evaluation, and
Treatment of High Blood Pressure, hypertension is classified in
stages based on the risk of developing C VD
STAGES
Systolic
BP
(mm Hg)*
Diastolic
BP
(mm Hg)*
Normal
<120
<80
Prehypertension
120-139
80-89
Stage 1 hypertension
140-159
90-99
Stage 2 hypertension
>160
>100
ETIOLOGY


More than 90 per cent of people with hypertension have no
identifiable cause of elevated blood pressure are said to have
‘primary ‘ ,’ essential’ or ‘idiopathic’ hypertension.
Cause is multifactorial, including
a combination of environmental and generic factors.
Rest of the people with hypertension do have an identifiable
cause and are said to have ‘secondary’ hypertension.



Secondary hypertension may be due to
Renal disease
Use of oral contraceptives in women.
Endocrine diseases.
RISK FACTORS
Pathogenesis of Hypertension
Genetic influences
Defects in renal
Na hemostasis
Environmental factor
Functional
vasoconstrictio
n
Defects in vascular
smooth muscle growth
and structure
Inadequate Na
excretion
Salt and H2O
retention
Plasma and ECF
Volume
Vascular
reactivity
Vascular wall
thickness
Total peripheral
resistance
Cardiac output
Hypertension
Blood pressure
Blood flow to kidneys
Juxtaglomerular
apparatus
in kidneys
Renin
Angtiotensinogen
Angiotensin I
Angiotensin II
Adernal
cortex
Vasoonstriction
of arterioles
Aldosterone
Salt and water
Retention by
kidneys
Blood volume
Blood pressure
DO NOT USE
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

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
Salt in cooking or at the table.
Monosodium glutamate (Ajinomoto).
Baking powder, sodium bicarbonate and sodium benzoate.
Salt preserved foods- pickles, canned foods.
Highly salted foods such as potato chips.
Spices and condiments such as ketchup and sauce.
Cheese, peanut butter, salted butter.
Frozen peas.
Shell fish and dry fish.
Prepared mixes.
Biscuits, cakes, breads, pastries.
Life style modification to manage hypertension
Modification
Recommendation
•Weight reduction
Maintain normal body weight (BMI –
18.5-24.9)
•Adopt dietary Approaches to stop
hypertension, DASH, eating plan
Consume a diet rich in fruits,
vegetables and low-fat dairy products
with a reduced content of saturated
and total fat
•Dietary sodium reduction
Reduces dietary sodium intake to no
more than 6 g sodium chloride
•Physical activity
Engage in regular aerobic physical
activity such as brisk walking (at least
30 minute per day )
•Alcohol consumption
Limit to no more than 2 drinks per day
PRINCIPLES OF DIET
Low calorie
 Low fat
 Low sodium
 With normal protein intake

DIETARY MANAGEMENT
Specifically ,the Dietary Approach to Stop Hypertension
(DASH) Diet Study shows that this low-fat dietary
pattern (including lean meats and nuts while emphasizing
fruits, vegetables, and non fat dairy products)decreased SBP
an average of 6 to 11 mm Hg and DBP by 3 to 6 mm Hg

Energy-

Protein-
An obese patient must be reduced to normal body
weight with low calorie diet.
About 25 kcal/kg of body weight are prescribed.
Alcohol consumption should be reduced.
A diet of 60 g protein is necessary to maintain
proper nutrition.
therefore protein should contribute about 15% to 20% energy.
excess amount of animal protein should be avoided.

Fat-

Carbohydrate- The rest of the energy i.e about 60-65%
The quantity of fat should be reduced to provide about
20% energy.
should be from carbohydrate foods.

SodiumDecrease in the sodium/potassium ratio in the diet is
preferred. sodium restriction 2-3 g/day reduces diastolic
pressure.
Recent studies have shown that sodium restriction
accompanied by weight reduction can effectively control mild
and moderate arterial blood pressure.

Potassium and calcium- An adequate potassium
and calcium intake is an essential part of the
treatment.
 Magnesium-Magnesium is a potent inhibitor of
vascular smooth-muscle contraction and may play a role
in blood pressure regulation as a vasodilator.
The DASH dietary pattern emphasizes foods rich in
magnesium.
 Alcohol Consumption- Alcohol may effect terminal
arterioles or venules and also increase their sensitivity
to circulating vasopressor agents.
For preventing high blood pressure, alcohol intake
should be less than two drinks per day) in men.
In women, no more than one drink a day is
recommended.
SODIUM AND SALT MEASSUREMENT
EQUIVALENT
 Sodium chloride is approximately 40% sodium
and 60% chloride.
 To convert a specified weight of sodium
chloride to its sodium equivalent multiply the
weight by 0.393.
 To convert milligram of sodium to mEq, devide
by the atomic weight of 23
Example 1 tsp of salt = approx 6g of NaCl = 6096 mg
NaCl
 6096 mg NaCl * 0.393 = 2396 mg Na
 2396 mg / 23 = 104 mEq Na
 1g Na= 1000 mg/23 = 43 mEq or mol