RISK FACTORS

IRREVERSIBLE•Masculine gender•Increasing age•Genetic traits•Body build

POTENTIALLY REVERSIBLE

•Smoking•Dyslipidaemia•Obesity•Hypertension•Physical in activity•Diabetes

GEOGRAPHICAL•Climate and season

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.

CLASSES1.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. D5. E6. 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 the-

water insoluble lipids water soluble forms water insoluble lipids.

Remember, fat floats on water, because

it is lighter than water

TRIGYLYCERIDES FROM GUT TO ADIPOCYTE- Chylomicrons.

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 ADIPOCYTE-

very low-density lipoprotein. The liver receive fat from a number of

sources-1. From chylomicrons remnants2. From circulating fatty acids3. From uptake of intermediate

lipoproteins4. 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 CELL-

Low 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 LIVER-

High 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 protein-PHOSPHOLIPIDS disk.

The ability of HDL, to function as a cholesterol transporter is dependent on the activity of Cu-dependent enzyme-LECITHIN CHOLESTEROL ACYL TRANSFERASE.

LIPOPROTEIN LIPASE It is an enzyme that hydrolyzes lipids in lipo-

protein, 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 are- 100 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

LIPOPROTEIN

ORIGIN DENSITY RANGE

MAJOR LIPID

MAJOR PROTEIN

FUNCTION

Chylomicrons

Small intestine

<0.94 TG B-48A-I,A-II

Absorption and transportation 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

LIPOPROTEIN

ORIGIN DENSITY RANGE

MAJOR LIPID

MAJOR PROTEIN

FUNCTIONS

LDL Plasma, IDL

1.019-1.063

Cholesterol esters

B-100 Cholesterol ester transport

HDL Liver, small intestine

1.063-1.21 Phospholipids and cholesterol

A-I Removal of cholesterol from extrahepatic tissues

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 GUIDELINES- A 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 optimal100-129 Near optimal/above

optimal130-159 Borderline high160-189 high>190 Very high

Total cholesterol

< 200 desirable200-239 Borderline high>240 High

HDL cholesterol

<40 Low >60 High

STEP 2- Identify 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 10-year (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.

Abdominal obesity*MenWomen

Waist circumference>102 cm (>40 in)>88 cm (>35 in)

Triglycerides >150 mg/dl

HDL cholesterolMenWomen

<40 mg/dl<50 mg/dl

Blood pressure >130/>85 mmHg

Fasting glucose >110 mg/dl

Risk factor defining level

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

<150 Normal150-199 Borderline high

200-499 High

>500 Very high

ATP III Classification of Serum Triglycerides (mg/dL)

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 HyperlipidemiasGene Defect

LipoproteinsElevated

Diagnosis Clinical Findings

Treatment

Familial HypercholesterolemiaHeterozygousLDL-receptor

LDL Serum cholesterol >300 mg/dl, normal TGs, affected first-degree relative

Tendon xathomas, Archus corneae,premature CHD

drug therapy

HomozygousLDL-receptor

LDL Serum cholesterol from 500 mg/dl to 1000 mg/dl, skin biopsy with measure of LDLreceptor activity

XanthomatosisProgresses rapidly, CHD in first decade of life

Remove LDL, liverTransplant

Familial Defectlve apo &1O0

Apo B-100 LDL Elevated serumcholesterol, normal TG

Tendon xanthomas,premature CHD

drug therapy

Gene Defect

LipoproteinsElevated

Diagnosis Clinical Findings

Treatment

Polygenic HypercholesterolemiaUnknown Chylomicro

ns,VLDL remnant

absence of secondary causes of hypercholesterolemia, <10% of first-degreerelatives affected

Absence oftendonxanthomas

drug therapy

Familial Dysbetalipoprotelnemia

Apo E Chylomicrons,VLDLRemnants

Lipoprotein electrophoresis or ratio of VLDL to totalplasma TG

Palmar and tuberoeruptive xanthomas,CHD

Weight reduction,low-fat, low cholesteroldiet,minimize alcoholConsumption,estrogenreplacement inwomen, drugtherapy

Gene Defect

LipoproteinsElevated

Diagnosis Clinical Findings

Treatment

Familial Combined Hyperlipidemia

Unknown TGs, totalcholesterol,HDL

Plasma TGs 200-800mg/dl, cholesterol220-400 mg/dl, HDL<40 mg/dl, familyhistory ofhyperlipidemia/premature CHD,elevated plasma apo B

Often present:visceral adiposity,glucoseintolerance,insulin resistance,hypertension,hyperuricemia,premature CHD

TLC, drug therapy,Weight reduction, increased physical activity,aggressive bloodglucose control

Gene Defect

LipoproteinsElevated

Diagnosis Clinical Findings

Treatment

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-

800-1000 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 TESTSAbdominal obesity Waist circumferenceMen Women

>102 cm(>40 inc )>88 cm (35 inch )

triglycerides >150 mg/dl HDL cholesterolMenWomen

<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 highArterial blood pressure ,the force exerted per unit area on the walls of arteries.

Systolic blood pressure(SBP),the blood pressure duringthe contraction phase of the cardiac cycle, has to be140 mm Hg or higher; or the diastolic blood pressure(DBP), the pressure during the relaxation phase of theCardiac cycle, has to be 90 mm Hg or higher, and they areReported 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 SystolicBP(mm Hg)*

DiastolicBP(mm Hg)*

Normal <120 <80Prehypertension 120-139 80-89Stage 1 hypertension 140-159 90-99Stage 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

Environmental factor

Genetic influences

Defects in renal Na

hemostasis

Defects in vascular smooth muscle

growth and structure

Inadequate Na excretion

Vascular wall thickness

Salt and H2O retention

Plasma and ECF Volume

Cardiac output

Functional vasoconstrict

ion

Vascular reactivity

Total peripheral resistance

Hypertension

Blood pressure Blood flow to kidneys

Juxtaglomerularapparatusin kidneysRenin

Angtiotensinogen Angiotensin I

Angiotensin II

Adernal cortex Vasoonstriction

of arteriolesAldosterone

Salt and waterRetention by kidneys Blood volume Blood

pressure

DO NOT USE 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- 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. Protein- 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- The quantity of fat should be reduced to provide about 20% energy.

Carbohydrate- The rest of the energy i.e about 60-65% should be from carbohydrate foods.

Sodium- Decrease 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