Dyslipidemia

Presentor: Juhliad Lebenu (FMR-II)

Moderator: Dr. Meseret (MD,FM Specialist)

12/27/2023 1
 Lipoproteins
• Are complexes of lipids and proteins that are
synthesized in small intestine and liver.
• Lipoproteins are essential for transport of
cholesterol, triglycerides (TGs), and fat-soluble
vitamins in the blood.
• It contain a core of hydrophobic lipids
surrounded by a shell of hydrophilic lipids and
proteins (called apolipoproteins)that interact
with body fluids.
12/27/2023 2
 Structure of lipoprotein

12/27/2023 3
 Lipoprotein classification
The plasma lipoproteins are divided into five major
classes based on their relative density.

12/27/2023 4
 Lipoprotein metabolism

12/27/2023 5
 Dyslipidemia
• A disorder of lipoprotein metabolism,
including lipoprotein overproduction or
deficiency.
• It may be manifested by elevation of the total
cholesterol, low-density lipoprotein (LDL)
cholesterol and the triglyceride
concentrations, and a decrease in the high-
density lipoprotein (HDL).

12/27/2023 6
• The majority of patients with dyslipidemia
have some combination of genetic
predisposition (often polygenic) and
environmental contribution.

• Many, but not all, patients with dyslipidemia

are at increased risk for ASCVD,

12/27/2023 7
 Primary causes

 Familial Combined Hyperlipidemia (FCHL)

 Familial Hypertriglyceridemia(FHTG)
 Familial Chylomicronemia Syndrome (FCS)
 Familial Hypercholesterolemia (FH)
 Other rare genetic syndromes

12/27/2023 8
 Familial Combined Hyperlipidemia (FCHL)

 Occurs in ~1 in 100–200 individuals and is an

important contributor to premature coronary
heart disease (CHD);
~20% of patients who develop CHD under age
60 have FCHL.
 Elevations in plasma levels of TGs (VLDL) and
LDL-C (including small dense LDL) and reduced
plasma levels of HDL-C [+ apoB ]

12/27/2023 9
 Affected family members typically have one
of three possible phenotypes:
(1). Elevated plasma levels of LDL-C,
(2). Elevated plasma levels of TGs due to
elevation in VLDL, or
(3). Elevated plasma levels of both LDL-C and TG.

12/27/2023 10
The presence of a mixed dyslipidemia (plasma
TG levels between 200 and 600 mg/dL and
 Total cholesterol levels between 200 and 400
mg/dL, usually with HDL-C levels <40 mg/dL in
men and<50 mg/dL in women) and
 A family history of dyslipidemia and/or
premature CHD suggests the diagnosis.

12/27/2023 11
 Aggressive treatment
- Life style modification
- Most patients require lipid-lowering drug
therapy, starting with statins.

12/27/2023 12
 Familial Hypertriglyceridemia

o Characterized by elevated fasting TGs without

a clear secondary cause, average to below
average LDL-C levels, low HDL-C levels, and a
family history of hypertriglyceridemia.
o In contrast to FCHL,
- apoB levels are not elevated.
- FHTG is not generally associated with a
significantly increased risk of CHD.

12/27/2023 13
o Management is mostly focused on reduction
of TGs to prevent pancreatitis.
o Dietary and lifestyle changes.
o Lipid-lowering drug therapy ( statin)
- Patients who are at high risk for CHD
o Patients with plasma TG levels >500 mg/dL
after a trial of diet and exercise -> fibrate or
fish oil
12/27/2023 14
 Familial Hypercholesterolemia (FH)

 FH is also known as autosomal dominant

hypercholesterolemia (ADH).
 is characterized by elevated plasma levels of
LDL-C in the absence of hypertriglyceridemia.
 caused by mutations (LDLR gene ) that lead to
reduced function of the LDL receptor activity
in the liver -> a reduced rate of clearance of
LDL from the circulation.

12/27/2023 15
 Heterozygous FH prevalence is estimated to
be ~1 in 250 individuals.
 Associated with LDL-C>190 mg/dL
( >160mg/dl in children) in the absence of a
secondary etiology, and a family history of
hypercholesterolemia and/or premature
coronary disease.

12/27/2023 16
 Patients should always be actively treated to
lower plasma levels of LDL-C, preferably
starting in childhood.
 Diet low in saturated and trans fat
 Statin
 Cholesterol absorption inhibitor (ezetimibe), a
PCSK9 inhibitor, or a bile acid sequestrant are
the next-line classes of drugs.

12/27/2023 17
 Homozygous FH prevalence ~ 1 in million
should be suspected in a child or young adult
with LDL >400 mg/dL( >500mg, AACE) without
secondary cause.
 Patients with homozygous FH must be treated
aggressively to delay the onset and
progression of CVD.
 Statins and PCSK9 inhibitors

12/27/2023 18
 A small-molecule inhibitor of the microsomal
TG transfer protein (MTP) and an antisense
oligonucleotide to apoB, are approved in U.S
(in patients who have insufficient response to
statins and PCSK9 inhibitors.)
 LDL apheresis
 Liver transplantation

12/27/2023 19
 Familial Chylomicronemia Syndrome (FCS)

• Genetic deficiency or inactivity of LPL results

in impaired lipolysis and profound elevations
in plasma chylomicrons.
• While chylomicronemia predominates, in fact
these patients often have elevated plasma
levels of VLDL as well.
• Fasting TG levels are almost invariably >1000
mg/dL and fasting cholesterol levels are also
elevated.
12/27/2023 20
• The diagnosis of familial chylomicronemia
syndrome is a clinical diagnosis based on
persistence and severity of
hypertriglyceridemia in the setting of a history
of proven or suspected acute pancreatitis.

12/27/2023 21
 Secondary causes

 Undesirable lifestyle conditions

 Medical conditions

 Medications

12/27/2023 22
12/27/2023 23
12/27/2023 24
 Screening
 Hypercholesterolemia is a cause of premature
CHD that is highly treatable and therefore
persons should be actively screened.

 Plasma lipid levels should be measured,

preferably after a 12-h overnight fast in all
adults.

12/27/2023 25
 According to 2018 AHA/ACC Guideline on the
Management of Blood Cholesterol. Fasting
lipid profile should be done : -
- In adults with a family history of premature
ASCVD or genetic hyperlipidemia.
- In adults in whom an initial non fasting lipid
profile reveals a triglycerides level of 400 mg/dL
or higher (> 4.5 mmol /L),

12/27/2023 26
o The total cholesterol and TGs in the plasma
are measured enzymatically, & then the
cholesterol in the supernatant is measured to
determine the HDL-C.
o The LDL-C is then estimated using the
following equation (the Friedewald formula):
LDL-C = total cholesterol – (TG/5) – HDL-C

12/27/2023 27
 Which screening tests
o Lipid assessment tests should include total
cholesterol, LDL-C, TG.
o The non-HDL-C (total cholesterol minus HDLC)
should be calculated if moderately elevated TG (200
to 500 mg/dL), diabetes, and/or established ASCVD.
o Apo B may be useful to assess residual risk and
guide decision-making in :
- at risk individuals (TG ≥ 150, HDL-C < 40, prior
ASCVD event

12/27/2023 28
- T2DM, and/or the insulin resistance syndrome
[even at target LDL-C levels]
- to assess the success of LDL-C lowering therapy
o hsCRP to stratify ASCVD risk in individuals with
a borderline standard risk assessment, or in
those with an intermediate or higher risk with
an LDL-C < 130 mg/dL.
o CAC - refining risk stratification

12/27/2023 29
12/27/2023 30
 Treatment
 The major goals in the clinical management of
lipoprotein disorders are:
1) prevention of acute pancreatitis in patients
with severe hypertriglyceridemia; and
2) prevention of CVD and related
cardiovascular events.

12/27/2023 31
 Management of Severe Hypertriglyceridemia

• It is generally considered appropriate medical

practice to intervene in patients with TGs >500
mg/dL in order to reduce the risk of
pancreatitis.
• Lifestyle – Diet ( fat and simple CHO), Aerobic
exercise/regular physical activity, weight loss
and bariatric surgery( in extreme cases )

12/27/2023 32
• Pharmacology
- Patients who persist in having fasting TG >500
mg/dL despite active lifestyle management.
 Fibrates:- LPL activity (enhancing TG
hydrolysis), promote β-oxidation of fatty acids,
and may reduce VLDL TG.
- Gemfibrozil - 600 mg bid
- Fenofibrate - 145 mg qd
12/27/2023 33
 Omega-3 fatty acids (fish oils): are present in
high concentration in fish and in flaxseed.
- doses of 3–4 g/d are effective
 In addition, statins can reduce plasma TG
levels and also reduce CVD risk, and should be
used in patients with severe
hypertriglyceridemia who are at increased risk
of CVD.

12/27/2023 34
12/27/2023 35
 Management of Cholesterol
to prevent CVS disease

12/27/2023 36
 Primary ASCVD prevention

 Primary prevention of ASCVD over the life

span requires attention to prevention or
management of ASCVD risk factors beginning
early in life.
 One major ASCVD risk factor is elevated serum
cholesterol usually identified clinically as
measured LDL-C.

12/27/2023 37
 Cardiovascular risk assessment tools

12/27/2023 38
 In children, adolescents (10 to 19 yrs of age),
and young adults (20 to 39 yrs of age), priority
should be given to estimation of lifetime risk
and promotion of lifestyle risk reduction.
 Drug therapy is needed only in selected
patients with LDL-C levels >160 mg/dL or very
high LDL-C levels (190 mg/dL ).

12/27/2023 39
 Three major higher-risk categories are patients
with severe hypercholesterolemia (LDL-C levels
>190 mg/dL), adults with diabetes mellitus, and
adults 40 to 75 years of age.
 Patients with severe hypercholesterolemia and
adults 40 to 75 years of age with DM are
candidates for immediate statin therapy
without further risk assessment.

12/27/2023 40
12/27/2023 41
Risk-Enhancing Factors
 Useful for identifying specific factors that
influence risk. Their presence helps to confirm
a higher risk state and thereby supports a
decision to initiate or intensify statin therapy.
 LDL-C > 160 mg/dL, apoB > 130 mg/dL
(particularly when accompanied by
persistently elevated triglycerides), & elevated
Lp(a) denote high lifetime risk for ASCVD and
favor initiation of statin therapy
12/27/2023 42
 Primary prevention in older Adults

12/27/2023 43
 Primary prevention in young Adults

 Young adults with primary elevations of LDL-C >

190 mg/dl have a long-term ASCVD burden
and statin therapy is recommended.
 However even moderate hypercholesterolemia
can accelerate development of atherosclerosis
and secondary causes should be addressed
appropriately.

12/27/2023 44
 When risk-enhancing factors, such as a family
history of premature ASCVD are present long
term statin therapy is suggested
 Elevations of LDL-C persisting after excluding
secondary causes suggests genetic forms of
hypercholesterolemia.
 In young adults without phenotypically severe
hypercholesterolemia, risk assessment should
begin by estimation of lifetime risk(PCE)
12/27/2023 45
 Primary prevention in children and
adolescents

12/27/2023 46
12/27/2023 47
  Statins may be considered at age 8 years in the presence of concerning family
history, extremely elevated LDL-C level, or elevated Lp(a), in the context of
informed shared decision-making and counseling with the patient and family.

12/27/2023 48
 Issues Specific to Women

12/27/2023 49
 Secondary ASCVD Prevention

 Clinical ASCVD encompasses ACS, those with

history of MI, stable or unstable angina or
coronary or other arterial revascularization,
stroke, TIA or PAD including aortic aneurysm,
all of atherosclerotic origin.
 High-intensity statin therapy is indicated for
clinical ASCVD, but if this cannot be used,
moderate-intensity statin therapy can be
initiated.
12/27/2023 50
12/27/2023 51
12/27/2023 52
 Summary of non-Pharmacologic and
pharmacologic interventions

12/27/2023 53
 Lipid-Lowering Drugs
 HMG-CoA Reductase Inhibitors (Statins)
- Among lipid-lowering drugs, statins are the
cornerstone of therapy, in addition to healthy
lifestyle interventions.
 Cholesterol Absorption Inhibitors.
- Ezetimibe: 10 mg daily
It lowers LDL-C levels by 13% to 20% and has a
low incidence of side effects
12/27/2023 54
 Bile Acid Sequestrants (Resins): primarily
reduce plasma LDL-C levels but can TGs. It is
drug of choice in children and in women and
reduces LDL-C levels by 15% to 30%.
- Cholestyramine: 4 g daily (32 g daily max.)
- Colestipol: 5 g daily (40 g daily max.)
- Colesevelam: 3750 mg daily (4375 mg daily)

12/27/2023 55
 PCSK9 Inhibitors : are antibodies that bind to
circulating PCSK9 and prevent its interaction
with the LDL receptor. highly effective in
lowering LDL-C, with a mean 50–60%
reduction in LDL-C.
- Evolocumab: 140 mg SQ q 2 weeks
- Alirocumab: 75 mg SQ q 2 weeks

12/27/2023 56
Specialized Drugs For Homozygous FH: reduce
VLDL production and LDL-C
-MTP inhibitor Lomitapide :5mg daily,60(max.
-ApoB inhibitor Mipomersen :200 mg SC wkly
LDL Apheresis: Patients who cannot reduce
their LDL-C to acceptable levels despite
optimally tolerated drug therapy

12/27/2023 57
12/27/2023 58
 Adherence to changes in lifestyle and effects
of LDL-C–lowering medication should be
assessed 4 to 12 weeks after statin initiation
or dose adjustment and every 3 to 12 months
thereafter based on need to assess adherence
or safety

12/27/2023 59
 Statin associated side effects
o Dyspepsia, headaches, fatigue, and muscle or
joint pains.
o Severe myopathy, rhabdomyolysis, T2DM –
rare
o Elevation in liver transaminases ALT and AST.
- check enzymes before starting therapy, at 2–3
months, and then annually
- > 3 ULN :-discontinuing the medication
12/27/2023 60
12/27/2023 61
 References
 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/
NLA/PCNA Guideline on the Management of Blood
Cholesterol 2018
 AACE/ACE Management of dyslipidemia and prevention of
cardiovascular disease algorithm 2020
 Harrisons principle of Internal Medicine , Twentieth
edition(Vol 1 and Vol 2) , 2018
 AACE/ACE Management of dyslipidemia and prevention of
cardiovascular disease 2017

12/27/2023 62
 THANK YOU !

12/27/2023 63