THE ROLE OF

HYPERLIPEDEMIA
IN ARTERIOSCLEROSIS
BY
PURER VITI
Outline
• Introduction
• Reactions of cholesterol
• Causes of hyperlipidemia
• Risk factors of hyperlipidemia
• Arteriosclerosis
• Pathophysiology
• Complication
• Lab diagnosis
• Treatment options
INTRODUCTION
Definition

• Hyperlipidemia, hypercholesterolemia or dyslipidemia is the

presence of raised or abnormal levels of lipids and / or lipoproteins in
the blood
• Lipids are insoluble in aqueous solution
• Lipids(fatty molecules) are transported in a protein capsule
• Density of the lipids and type of protein determine the fate of the
particles and to its influence on metabolism
 INTRO CONT….
• Lipids and lipoproteins abnormalites are extremely common in the
general population and are regarded as a highly modifiable risk
factors for cardiovascular disease due to the influence of cholesterol

• CHOLESTEROL is the most clinically relevant lipid substance

contributing to artheriosclerosis(LDL-C)
• In addition some forms of lipids and lipoprotein abnormalities may
predidpose to acute pancreatitis
REACTIONS OF CHOLESTEROL
SYNTHESIS
• Acetyl-CoAs are converted to 3-hydroxy-methylglutaryl-CoA
• HMG-CoA is converted to mevalonate. Catalysed by HMG-CoA
reductase(HMGR)
• Mevalonate is converted to the isoprene-based molecule, isopentyl
pyrophosphate(IPP), with the concomitant loss of CO2
• IPP is converted to squalene.
• Squalene is converted to cholesterol
Hypercholesterolemia: Causes
• Cholesterol, a simple lipid found in a cell membrane, is a precursor of steroids, bile acids, and
vitamin D and a major part of atherosclerotic plaques

• Most circulating blood cholesterol is synthesized from the liver acetyl CoA and is excreted as bile
salts

• Only 25% of blood cholesterol is from the diet, but high fat diets increase liver cholesterol
production and blood cholesterol levels

• HMG-CoA formation from HMGCoA reductase, the rate determining step in cholesterol
synthesis, is regulated via feedback inhibition

• When cholesterol uptake is low, the liver and the small intestines increase cholesterol synthesis
Hypercholesterolemia: Causes (cont..)
• The plaque forming ability of cholesterol is related to LDLs, which
promotes plaque formation
• HDLs remove cholesterol from arteries and transport it to the liver
• HDLs remove cholesterol from Plaques and slow artherosclerosis
• Control of cholesterol and LDL levels is a major goal in heart disease
Therapy
Risk Factors of Hyperlipidemia
• High fat intake
• Obesity(BMI>30)
• Type 2 diabetes melitus
• Advanced age
• Hypothyroidism
• Obstructive liver disease
• Genetics
• Drug induced:glucocorticoids, thiazide diuretics, beta blockers,
protease inhibitors, alcohol
 Arteriosclerosis
• Arteriosclerosis is a type of vascular disease where blood vessels carryong oxygen away from the heart(arteries)
become damaged from factors such as high cholesterol, high blood pressure, diabetes and certain genetic
influences

• Atherosclerosis, the most common form is also the most serious coronary artery disease and cerebrovascular
disease

• Artherosclerosis is patchy intimal plaques (artheromas) in medium sized and large arteries

• The plaques contain lipids, inflammatory cells, smooth muscle cells and connective tissue

• Artherosclrosis can affect all large and medium sized arteries, including the coronary, carotid and cerebral arteries
of the extremities and major arteries of the extremeties
• It is the leading cause of mobidity and mortality in the Us and most developed countries
Risk factors for Atherosclerosis
• Dyslipidemia
• Diabetes
• Cigarette smooking
• Family history
• Sedentary life style
• Obesity
• hypertension
Pathophysiology of Artherosclerosis
• When excess cholesterol deposits on cells and on the inside walls of blood vessels it
forms an artherosclerotic plaque
• The first step of artherosclerosis is injury to the endothelium which results in
atherosclerotic lesion formation
• Whwn the plaque ruptures, blood clots form which lead to decreased blood flow,
resulting in cardiovascular events
• Symptoms develop when growth or rupture of the plaque reduces or obstructs
blood flow; symptoms vary by artery affected
• Diagnosis is clinical and confirmed by angiography, ultrasonography, or other
imaging test
• Treatment includes risk factor and dietary modifications, physical activities,
antiplatelets drugs, and antiatherogenic drugs
Complications of Hyperlipidemia
• Unstable angina
• Myocardial infaction(heart attack)
• Ischemic cerebrovascular disease(stroke)
• Coronary Artery Disease (heart disease)
• Retinopathy (loss of vision)
• Nephropathy (kidney disease)
• Neuropathy (loss of sensation in the feets and legs)
 Laboratory diagnosis and classification
• The fasting lipid profile is analysed ( TC, LDL-C, HDL-C, TG)

-LDL-C<100mg/dl…………………..Optimal
-100 -129mg/dl………………near to above optimal
-130-159mg/dl………………borderline high
-160-189mg/dl……………..high
-> or =190mg/dl…………….very high
TG <150mg/dl…………………..optimal
-150 -199mg/dl………………borderline high
-200-249mg/dl……………… high
-> or = 500mg/dl……………..very high
-> or =190mg/dl…………….very high
- Total-C
-<200mg/dl……………………Desirable
200 – 239mg/dl…………….Borederline high

> or = 240mg/dl…………………………….High
HDL-C
<40mg/dl……………………………….Low
> 60 or = 60mg/dl……………………High
Treatment Goals
1. Reduce total cholesterol and LDL (bad) cholesterol and increase HDL
2. Prevent the formation of atherosclerotic plaques and stop the
progression of establidhed plaques
3. Prevent heart disease
4. Prevent morbidity and mortality
THANK YOU