Clinical

Correlation
GROUP 2A

ABELLA
AVENA
BALLESTEROS
BARROGA
BUNGAOEN
CATOLOS
ATHEROSCLEROSIS
 ATHEROSCLEROSIS
● Arteries carry blood from the heart to the rest of the body. They are
lined with a thin layer endothelium that keeps them smooth and
allows blood to flow easily.

● Atherosclerosis is the narrowing of arteries due to plaque build up on

the artery walls.

● It starts when the endothelium becomes damaged, allowing the

harmful type of cholesterol to build up in the artery wall.

● LDL is believed to play a central role in initiating and

promoting plaque formation in the endothelium
 ATHEROSCLEROSIS
● The plaques are deposited in the subendothelial space where it is taken
by various cells including macrophages.

● This alters the gene and protein expression pattern of these cells in the
subendothelium and can promote inflammatory response particularly
when LDL becomes oxidized.

● In some cases, the plaque eventually, breaks open. If this happens,

platelets gather in the affected area and can stick
together, forming blood clots which can block the
artery, leading to life-threatening complications,
such as stroke and heart attack.
 ATHEROSCLEROSIS
● Atherosclerosis can lead to serious problems, including:

● Coronary artery disease. The arteries that supply blood to our heart,
when they are blocked, it can cause angina or a heart attack.

● Carotid artery disease. The arteries that supply blood to our brain,
when they are blocked, it can cause stroke.

● Peripheral arterial disease. The arteries are in our arms,

legs and pelvis, when they are blocked, it can cause
numbness, pain in the limbs.
 Signs and Symptoms
• Symptoms do not show until
Cardiovascular Disease develops

• Numbness or weakness in your arms

or legs

• Severe headache

• High blood pressure

• Arrhythmia

• Angina
Diagnosis
• A diagnosis will be based on medical
history, Blood test (Lipid profile), and a
physical exam

• Ultrasound

• CT Scan to find arteries that are

hardened and narrowed
 Treatment Option
● Medication (ACE inhibitors)

● Angioplasty to open the arteries

● Surgery for severe cases of

arteriosclerosis
Prevention
• Diet modification - avoid saturated
fats, they increase levels of bad
cholesterol.

• Exercise - will improve fitness levels,

lower blood pressure, and help weight
loss.

• Quit Smoking
HYPERLIPOPROTENEMIA
 HYPERLIPOPROTENEMIA
● Disease states associated with abnormal serum lipids caused by
malfunctions in the synthesis, transport or catabolism of lipoproteins
 FAMILIAL HYPERCHOLESTEROLEMIA (FH)
● is an autosomal dominant disorder that causes severe elevations in
total cholesterol and low-density lipoprotein cholesterol (LDLc)
 Signs and Symptoms

Ø Xanthomas are noted commonly on the

Achilles tendons and metacarpal phalangeal
extensor tendons of the hands of patients with
untreated FH.
 Signs and Symptoms
Homozygous FH in children include the following:

• Symptoms consistent with ischemic heart disease,

peripheral vascular disease, cerebrovascular
disease, or aortic stenosis
• Tendonitis or arthralgias
• Unusual skin lesions, such as cutaneous
xanthomas at birth or by early childhood
• Corneal arcus may be present
• Murmur of aortic stenosis may be present
 Signs and Symptoms
Heterozygous FH in adults include the following:

• Long-standing history of severe

hypercholesterolemia dating back to childhood
• If no previous acute coronary event, symptoms
consistent with ischemic heart disease, especially
in the presence of other cardiovascular risk
factors (especially smoking)
• Past or present symptoms of recurrent Achilles
tendonitis or arthritic complaints
• Xanthelasmas
 Pathophysiology
• FH is a disorder of absent or grossly malfunctioning low-density
lipoprotein (LDL) receptors.
• The LDL receptor gene is located on the short arm of chromosome
19, and the protein is composed of 860 amino acids. It is the
primary determinant of hepatic LDL uptake, which normally
processes approximately 70% of circulating LDL.
• ApoE is found on most lipoproteins other than LDL, including very
low-density lipoprotein (VLDL) and chylomicrons and their
remnants, intermediate-density lipoprotein (IDL), and a subclass of
high-density lipoprotein (HDL).
• The LDL receptor binds apoE with higher affinity than apoB-100,
and some mutations in the receptor may spare uptake of LDL by
allowing binding to apoE.
 Treatment Option
• Most patients with homozygous
FH do not survive adulthood
beyond age 30 years unless treated
with unusual methods, such as liver
transplantation, LDL apheresis, or
ileal bypass surgery to dramatically
lower their LDLc levels.
Prevention
• Lifestyle modification, including diet (limited
saturated fats, trans fats, and cholesterol);
weight management; aerobic/toning
exercises

• HMG-CoA reductase inhibitors (statins) (eg,

simvastatin, atorvastatin, or rosuvastatin),
and one or more other LDL lowering
medications

• Estrogen replacement therapy in

postmenopausal women
 FAMILIAL HYPOALPHALIPOPROTEINEMIA
● Is a relatively common genetic condition that causes the body to
produce low levels of HDL or high-density lipoprotein (known as
“good” cholesterol). Low HDL can increase the risk of developing
cardiovascular disease, including an added risk for heart attack and
stroke.
 Signs and Symptoms
• Some patients remain asymptomatic until advanced
adulthood.
• Others may present from adolescence with a
combination of the following symptoms:
• Blurred vision due to corneal opacities or cataract
• Tubero-eruptive, tendinous, palmar and/or planar
xanthomas
• Xanthelasmas
• Premature coronary heart disease (CHD) (e.g.
myocardial infarction, carotid atherosclerosis)
 Pathophysiology
• Mutations in the ABCA1 gene or the APOA1 gene cause familial HDL
deficiency. The proteins produced from these genes work together to
remove cholesterol and phospholipids from cells.

• The ABCA1 gene provides instructions for making a protein that removes
cholesterol and phospholipids from cells by moving them across the cell
membrane. The movement of these substances across the membrane is
enhanced by another protein called apolipoprotein A-I (apoA-I), which is
produced by the APOA1 gene. Once outside the cell, the cholesterol and
phospholipids combine with apoA-I to form HDL. ApoA-I also triggers a
reaction that converts cholesterol to a form that can be fully integrated
into HDL and transported through the bloodstream.
 Diagnosis
• Diagnosis is based on biochemical analysis of
plasma Apo A-I and HDL cholesterol levels
showing extremely low HDL cholesterol levels
and very low to undetectable Apo A-I (inferior
to 5 mg/dL). Low HDL cholesterol levels are
associated with normal VLDL and LDL
cholesterol levels, and normal or decreased
triglyceride levels. Histological examination of
skin lesions reveals numerous foam cells.
Diagnosis is confirmed by genetic testing.
 Diagnosis
• The differential diagnosis includes Tangier
disease, LCAT deficiency (see these terms)
and secondary causes of extremely low HDL
cholesterol levels that include medications
(androgenic steroids, paradoxical response to
fibrates) and malignancies.
 Treatment Option
● To date, there is no curative therapy.
● In case of carotid atherosclerosis or
cardiovascular complications, a low-fat
diet balanced in anti-oxidants (e.g.
Mediterranean type) may be combined
with statins (HMGCoA reductase
inhibitors) that lower LDL cholesterol
levels below 70 mg/dL.
 Treatment Option
● Oral anti-oxidants, or infused synthetic HDL-
mimetics or reconstituted HDL, are being
investigated as potential anti-atherosclerotic
therapies.
● Regular cardiovascular monitoring should be
offered to Apo AI deficient patients with
extremely low HDL cholesterol (<20 mg/dL)
because of the increased risk (Odds Ratio x2-3) of
coronary artery disease. In cases exhibiting signs of
amyloidosis, long-term follow-up of target organ
function should be proposed.
 ABETALIPOPROTEINEMIA
● Is a condition characterized by the inability to fully absorb dietary
fats, cholesterol and fat-soluble vitamins.
 Signs and Symptoms
s/s usually appear in the first few months of life; they can
include:
• Failure to thrive in infancy

• Digestive symptoms such as diarrhea and steatorrhea (foul-

smelling stools)
• Abnormal, star-shaped red blood cells (acanthocytosis)

• Nervous system (neurologic) symptoms beginning in

childhood such as slower intellectual
development; peripheral neuropathy; poor muscle
coordination; ataxia; and intention tremors
• Eye (ophthalmologic) symptoms such as decreased night

and color vision; retinitis pigmentosa in adolescence; and

gradual deterioration of vision, often leading to blindness
in the fourth decade of life
 Pathophysiology
• Caused by changes (mutations) in the MTTP gene.
The MTTP gene gives the body instructions to make
a protein needed for creating beta-lipoproteins.
• These lipoproteins are necessary for the body to absorb fats,
cholesterol, and fat-soluble vitamins (vitamins A, D, E and K),
and for transporting these substances in the blood.
• Mutations in the MTTP result in a lack of beta-lipoproteins,
leading to an inability to absorb and transport these
substances.
• This in turn leads to the nutritional and neurologic
problems in affected people.
 Diagnosis
• The Genetic Testing Registry (GTR) provides
information about the genetic tests available
for abetalipoproteinemia. The intended
audience for the GTR is health care providers
and researchers. Patients and consumers with
specific questions about a genetic test should
contact a health care provider or a genetics
professional.
 Diagnosis
• Prenatal testing may be available for
pregnancies at increased risk if
the mutations in the family have been
identified.
 Treatment Option
● A nutritionist or other qualified medical
professional should be consulted for specific
dietary instruction in people with
abetalipoproteinemia. Treatment involves
very large doses of vitamin E, as well as large
doses of vitamin supplements containing
other fat-soluble vitamins (vitamin A, vitamin
D, and vitamin K). Linoleic acid supplements
are also recommended.
 Treatment Option
● Several diet changes and/or restrictions are
also needed to prevent stomach problems. A
low-fat diet may help with digestive
symptoms; medium chain triglycerides may
be used (under supervision of a specialist) as
a source of fat in the diet.
 Treatment Option
● Management in adults typically focuses on
specific complications associated with the
disorder, and depends on the signs and
symptoms present. Affected people may
need consultations with several other types
of specialists, including a
lipidologist, gastroenterologist, hepatologist,
ophthalmologist, and neurologist.
HYPERTRIGLYCERIDEMIA
 HYPERTRIGLYCERIDEMIA
● Elevated plasma triglyceride concentration
● RISK FACTORS:
○ coronary artery disease
○ diet
○ stress
○ physical inactivity
○ smoking
● Hypertriglyceridemia is usually asymptomatic until

triglycerides are greater than 1000-2000 mg/dL.

○ GI: Pain in the mid-epigastric, chest, or back regions; nausea,

vomiting

○ Respiratory: Dyspnea

○ Dermatologic: Xanthomas

○ Ophthalmologic: Corneal arcus, xanthelasmas

 CLASSIFICATIONS:
1. PRIMARY HYPERTRIGLYCERIDEMIA
● FAMILIAL CHYLOMICRONEMIA (hyperlipoproteinemia type 1) and
PRIMARY MIXED HYPERLIPIDEMIA (type 5)
○ presence of chylomicrons after a 12–14-hour period of fasting.
○ Above 10 mmol/L
○ CLINICAL FEATURES:
■ eruptive xanthomata
■ lipemia retinalis
■ hepatosplenomegaly
■ focal neurologic
■ symptoms
■ recurrent epigastric
■ pain with increased
■ risk of pancreatitis.
● FAMILIAL CHYLOMICRONEMIA
○ CHILDHOOD
○ deficiency of lipoprotein lipase, apo CII activity or homozygous gene mutations

● PRIMARY MIXED HYPERLIPIDEMIA

○ ADULT
○ less severe functional deficiency and infrequent detection of gene mutations
○ presence of secondary factors
○ greater elevation of total cholesterol
● FAMILIAL HYPERTRIGLYCERIDEMIA (type 4)
○ Elevated VLDL
○ Low HDL
○ 3-10 mmol/L

● FAMILIAL COMBINED HYPERLIPOPROTENEMIA (type 2B)

○ increased VLDL
○ Increased LDL
○ depressed HDL
○ heterozygosity for LPL or
○ APOC3 gene mutations
● FAMILIAL HYPERTRIGLYCERIDEMIA (type 4)
○ Elevated VLDL
○ Low HDL
○ 3-10 mmol/L

● FAMILIAL COMBINED HYPERLIPOPROTENEMIA

(type 2B)
○ increased VLDL
○ Increased LDL
○ depressed HDL
○ heterozygosity for LPL or
○ APOC3 gene mutations
● FAMILIAL DYSBETALIPOPROTENEMIA
(type 3)
○ Increased intermediatedensity lipoproteins or β-VLDL
○ decreased LDL
○ tuberous or tuberoeruptive xanthomata on the extensor
surfaces of their extremities
○ planar-or palmar-crease
○ xanthomata
○ increased risk of cardiovascular disease
2. SECONDARY HYPERTRIGLYCERIDEMIA
● Obesity is probably the metabolic stressor most frequently
associated poorly controlled type 2 diabetes
● excessive alcohol consumption
● OBESITY, METABOLIC SYNDROME, DIABETES
○ elevated triglyceride
○ Low HDL-C levels
○ TYPE 2 DIABETES:
■ Impairment of the ability of insulin to stimulate glucose
uptake
■ Inadequate compensation for insulin insensitivity
- Insulin-resistant people without type 2 diabetes:

■ hyperinsulinemia is associated with a cluster of metabolic

abnormalities (METABOLIC SYNDROME)
○ metabolic syndrome and in type 2 diabetes

■ increased plasma concentrations of VLDL, with or without

chylomicronemia

■ 9 deficient lipoprotein lipase

■ Activity increased cholesteryl ester transfer protein activity

■ increased flux of free fatty acids to the liver

● ALCOHOL
○ increased plasma VLDL, with or without chylomicronemia.
○ plasma triglyceride measurements can remain within the
normal range
○ markedly increased plasma triglycerides.
● RENAL DISEASE
○ Nephrotic syndrome
■ increases in apo B–containing lipoproteins, including
VLDL
○ Uremia
● PREGNANCY
○ Chylomicronemia
○ Complicated by pancreatitis

● NAFLD
○ Elevated triglyceride
○ depressed HDL-C levels
 Pathophysiology
• VLDL and chylomicrons become relatively cholesterol-
enriched once the triglyceride core is hydrolyzed at
peripheral tissues.
• remnant triglyceride-rich lipoproteins may be atherogenic.
• cholesterol content of triglyceride-rich lipoproteins may
contribute to plaque development.
• lipolysis of triglyceride-rich lipoproteins produces free fatty
acids, lysolecithin, and other reactive lipids that may have
pro-inflammatory and pro-coagulant effects.
 Pathophysiology
• related to release of excess free fatty acids and lysolecithin
from chylomicrons exceeding the binding capacity of
albumin in pancreatic capillaries.
• The unbound free fatty acids are thought to form micellar
structures with detergent properties, causing injury and
ischemia leading to pancreatitis.
• Risk of pancreatitis markedly increases with triglycerides
levels above 200 mg/dL
 Diagnosis
• The Genetic Testing Registry (GTR) provides
information about the genetic tests available
for abetalipoproteinemia. The intended
audience for the GTR is health care providers
and researchers. Patients and consumers with
specific questions about a genetic test should
contact a health care provider or a genetics
professional.
 Treatment Option
● NON-PHARMACOLOGICAL TREATMENT:
○ weight reduction, dietary modification and exercise
○ Alcohol consumption should be reduced or
eliminated
○ Omega-3 F.A intake

● PHARMACOLOGICALTREATMENT:
○ FIBRATES: reduce the quantity of small, dense LDL
particles and increase HDL-C
○ STATIN: CHD
○ NIACIN: lower plasma triglyceride levels by up to
45%, raise plasma HDL-C by up to 25%, and reduce
plasma LDL-C by up to 20%.
 Prevention
• Lifestyle modification is the foundation
for management of hypertriglyceridemia
and can reduce plasma TG levels by up to
60 percent.
 LIPOPROTEIN A ELEVATION
● consists of a particle similar to LDL and 2 protein molecules known as
ApoB and Apo(a).
● causal link to atherosclerosis, heart attacks, strokes, aortic valve
disease and heart failure.
● 20-30 mg/dl are associated with a two-fold risk of developing
coronary artery disease
 Pathophysiology
• Increase levels can be transient in the presence of
inflammatory processes or tissue damages such as those
occuring with acute phase proteins.
• Followed by episode of AMI
Ø Lp(a) increase in the first 24 hrs
Ø Return to baseline values in approx. 30 days
 Pathophysiology
• Increased in chronic inflammatory disease such as RA, SLE,
AIDS and conditions such as after heart transplant, CRF and
PAH.
• Decreased in liver disease and abusive use of steroids.
• Atherogenesis: direct deposition of lipoprotein on arterial
wall.
Ø Undergo oxidation and taken up by macrophages via
scavenger receptors.
Ø Transformation of macrophages into foam cells,
precursors of atherosclerosis.
 Pathophysiology
• Interfere with fibrinolytic system and competing with
plasminogen for binding sites of endothelial cells, inhibiting
fibrinolysis and promoting intravascular thrombosis.
 Treatment Option
● NO specific therapy to decrease Lp(a) levels
○ Ezetimibe
○ Niacin
○ LDL apheresis
○ Hormone replacement
○ L-carnitine
○ Methotrexate
 Prevention
• Lifestyle modification is the foundation
for management of hypertriglyceridemia
and can reduce plasma TG levels by up to
60 percent.
Thank You
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