Dyslipidemia.docx

 Cholesterol is lipid serves as precursor to
steroid hormones , bile acid, and the main
component of cell membrane.
 Cholesterol in blood reflect 40-60% of
endogenous cholesterol.
 Cholesterol , triglyceride and lipid transport
through lipoprotein.
 Saturated ,unsaturated fats and cholesterol
digested, reformulated and packaged into
chylomicrons by cell of intestinal
endothelium.
Source:clinical pharmacy &therapeutic 5th edition

Category Composition
Chylomicrons Triglycerides
exogenousdietary
Very low density lipoproteins (VLDLs) Triglycerides
Intermediate density lipoproteins
(IDL)
Triglycerides &Cholesterol
Low density lipoproteins (LDL) Cholesterol
High density lipoproteins (HDL) Cholesterol

 Chylomicrons enter the lymphatic system and
travel through body until broken down by
lipoprotein lipase in the capillary beds to
chylomicron remnant (smaller , less dense and
contain apolipoprotein B48,E and then
cleared from circulation by LDL receptor in the
liver
 This is replenishing cholesterol pool in the liver
which synthesize cholesterol also by
endogenous pathway and transported by
LDL,VLDL and HDL.
 Triglyceride (TG) synthesis by the liver in the
excess of carbohydrate and secreted as VLDL

 VLDL contain five times more TG than
cholesterol and contain apolipoprotein
C-II,B-100 ,E. Apolipoprotein B-100 and E
link with LDL cell receptor.
 Apo lipoprotein C-II function as cofactor
for lipoprotein lipase.

VLDL
VLDL
remnant
Clearance
by hepatic
receptor
IDL
LDL TG
TG
TG
Free fatty
acid

 LDL is primary atherogenic lipoprotein and
the smaller size of LDL particle of more able
to penetrate into sub endothelial tissue
where it contribute to the development of
atherosclerosis .
 Two type of LDL been associated with CHD:
1 Lipoprotein(a) LP(a) particle is LDL particle
surrounded by plasminogen –like protein
2Atherogenic lipoprotein phenotype B found
in30%population associated with CHD risk.

 The atherosclerotic plaque formation
initiated by entrance of LDL and LP(a)into
sub endothelial space with their oxidative
modified free radicals produced by cells
which activated macrophage yielding lipid
rich foam which continue to progress with
same times of the cell proliferation and
collagen synthesis.
 HDL rich in cholesterol and very small
,However appears in reverse cholesterol
transport resulting in anti atherogenic effect.

source:www.pharmacy times .com

 HDL may prevent or remove cholesterol in
the intimae by :
1competitively inhibit uptake of LDL by
endothelial cells
2 prevent LDL oxidation.
3 inhibit platelet activation by LDL and
aggregation by increase prostacyclin
production.
4promote fibrolysis by stabilizing
prostacyclin.
 LDL serve as marker of metabolism of
chylomicron and VLDL (increase TG,
decrease HDL).

1- Type I (high level of chylomicrons).
2-Type II a (high level of LDL)
3-Type II b (high level of LDL+VLDL)
4-Type III (high level of IDL )
5-Type IV (high level of VLDL)
6-Type V ( high level of VLDL
+chylomicrons)
Source:hand book of pharmacotherapy 8th edition

 Dyslipidaemia defined as elevated of
total cholesterol ,LDL, TG, low HDL or
combination of these abnormalities.
 According to etiology dyslipidaemia
classified to:
1- primary or genetic lipoprotein disorder.
2-secondary dyslipidaemia (drugs
&diseases).

Secondary dyslipidaemia due to:
1. Diseases( liver disease ,chronic renal
failure ,nephrotic syndrome, obesity
,hypothyroidism ,diabetes ,alcohol )
2. Drugs (corticosteroids,thiazide diuretic
,cyclosporine ,oral contraceptive , HIV
protease inhibitors ,B-blockers)
Source:clinicl pharmacology 5th edition

 In type I there are:
1-repeated attack of pancreatitis.
2-abdominal pain.
3-euraptive cutanous xanthomatosis.
4-hepatosplenomegaly beginning in
childhood.
Note: symptoms severity increased with
increased dietary fat intake. accelerated
atherosclerosis not associated with this
disease

 Type III the clinical feature appears after 20
years :
1- xanthoma
2- severe atherosclerosis
 Type IV occur in adult and similar to
secondary dyslipidaemia.
 Type V :
-abdominal pain , pancreatitis ,xanthoma
,peripheral polyneuropathy and renal
insufficient.
Note: atherosclerosis is increased with this
disorder

 Angina.
 Myocardial infraction (MI).
 Arrhythmias.
 Stroke.
 Peripheral arterial disease.
 Abdominal aortic aneurysm.
 Sudden death.

 CVD is the leader amongst the causes of
death worldwide.
 Prevalence of CVD including CHD is
increasing rapidly in Sudan.
 Increasing burden of risk factors like:
› Hypertension
› Smoking
› Obesity
› Diabetes
› Dyslipidemia

Total 58 million death worldwide
CVD 30%
17.4 million
OTHERS
3.3 times than the total
no. of death due to HIV,
Malaria, and
Tuberculosis combined

Cardiovascular disease is the leading cause of death
among adults worldwide
CVD 7.2 million
Cancer 6.3 million
Cerebrovascular Disease 4.6 million
Acute Lower Respiratory Tract Infections 3.9 million
Tuberculosis 3.0 million
COPD (Chronic Obstructive Pulmonary Disease) 2.9 million
Diarrhoea (Including Dysentery) 2.5 million
Malaria 2.1 million
AIDS 1.5 million
Hepatitis B 1.2 million
Source: WHO 2005

Sex and country Total cholesterol
Women ≥200 mg/dl* ≥240 mg/dl**
China, 65–74 yrs 47.8% 18.2%
Spain, ≥65 yrs 77.6% 45.8%
England, ≥65 yrs 91.7% 54.6%
Mexico, ≥60 yrs 44.2% --
South Africa, ≥60 yrs 58.0% --
Thailand, ≥60 yrs -- 10.8%
Turkey, ≥70 yrs 58.5% 23.8%
Men ≥200 mg/dl* ≥240 mg/dl**
China, 65–74 yrs 30.6% 7.5%
Spain, ≥65 yrs 52.5% 23.1%
England, ≥65 yrs 81.9% 40.4%
Mexico, ≥60 yrs 56.9% --
South Africa, ≥60 yrs 78.7% --
Thailand, ≥60 yrs -- 18.4%
Turkey, ≥70 yrs 42.5% 17.0%
 Source:A&D journal pubmed 2013 online .article about cholesterol and cardiovascular
disease

 DM in Africa: Up to 13% or more adults in
urban communities.
 Diabetes is present in 10% of all hospital
admission in Sudan.
 Diabetes is responsible for 10% of
hospital mortality.
Source:Diabetes Int 2000; 10: 18-9.

Diabetic Dyslipidemia in Sudan
Variables Mean (SD) Values P-value
Diabetic patients
N=250
Controls
N=60
Total cholesterol
(mmol/L)
5.69 (0.29) 5.20 (0.15) NS
Triglycerides
(mmol/L)
1.71 (0.27) 1.16 (0.21) <0.05
HDL-C
(mmol/L)
0.93 (0.15) 1.11 (0.18) <0.05
LDL-C
(mmol/L)
Half of the diabetic
population in Sudan suffers
3.68 (0.21) 3.45 (0.14) NS
VLDL-C
(mmol/L)
from dyslipidemia
1.01 (0.26) 0.81 (0.11) NS
TC/HDL-C 6.11 (1.86) 4.69 (0.13) NS
Source:Eastern Mediterranean Health Journal, Vol. 14, No. 2, 2008

 What is being tested?
Cholesterol &Triglyceride in the blood sample.
Total cholesterol is determined from the
amount of cholesterol found in HDL, LDL and
VLDL.
LDL - if triglycerides < 400 then LDL is
calculated using Friewald formula:
((Calculated LDL=chol−HDL−TG/5)).
If triglycerides > 400 then LDL is measured
directly.
Non HDL= Total cholesterol – HDLc.
Source: labtest online.org

 How to ensure quality of the sample?
Fasting for 9-12 hrs before making the test
,only water is permitted.
 When it is ordered ?
Adult:
Healthy adult with no risk factor for heart
disease once every 5 years.

 Children &Adolescent :
AAP(American academy of pediatrics) recommended
one test between 9 -11 yrs &again between 17- 21 yrs
.
 What does test results means?
LDL Cholesterol
Optimal: Less than 100 mg/dL (2.59 mmol/L)
Near/above optimal: 100-129 mg/dL (2.59-3.34
mmol/L)
Borderline high: 130-159 mg/dL (3.37-4.12 mmol/L)
High: 160-189 mg/dL (4.15-4.90 mmol/L)
Very high: Greater than 190 mg/dL (4.90 mmol/L)

 Total Cholesterol
Desirable: Less than 200 mg/dL (5.18 mmol/L)
Borderline high: 200-239 mg/dL (5.18 to 6.18 mmol/L)
High: 240 mg/dL (6.22 mmol/L) or higher
 HDL Cholesterol
Low level, increased risk: Less than 40 mg/dL (1.0
mmol/L) for men and less than 50 mg/dL (1.3 mmol/L)
for women
Average level, average risk: 40-50 mg/dL (1.0-1.3
mmol/L) for men and between 50-59 mg/dl (1.3-1.5
mmol/L) for women
High level, less than average risk: 60 mg/dL (1.55
mmol/L) or higher for both men and women

 Fasting Triglycerides
Desirable: Less than 150 mg/dL (1.70 mmol/L)
Borderline high: 150-199 mg/dL(1.7-2.2 mmol/L)
High: 200-499 mg/dL (2.3-5.6 mmol/L)
 Non-HDL Cholesterol
Optimal: Less than 130 mg/dL (3.37 mmol/L)
Near/above optimal: 130-159 mg/dL (3.37-
4.12mmol/L)
Borderline high: 160-189 mg/dL (4.15-4.90 mmol/L)
High: 190-219 mg/dL (4.9-5.7 mmol/L)

 Result in children and adolescents
Test Acceptable
mg/dl
Borderline
mg/dl
High mg/dl
Total
cholesterol
Less than 170 170 -199 Greater than
or equal 200
Non HDL
cholesterol
Less than 120 120-140 Greater than
or equal 145

 Therapeutic lifestyle change(TLC)should
be the first approach tried in all patient
this includes:
 Dietary restriction of cholesterol and
saturated fatty acid.
 Regular exercise.
 Weight reduction.
Source:pharnacotherapy text book 7th edition

 Inhibit cholesterol synthesis by inhibit
(HMG-Co A), increase LDL receptor and
enhance receptor mediated metabolism
and clearance of LDL from serum.
 Beneficial effect on lipid parameters:
 LDL c ↓ 18%-55%
 HDL c ↑5-15%
 TG ↓7%-30%
 24%-40% reduction in coronary events.
source: medescape.org/ view article/561751

 Potential adverse effects:
Myalgia ,Myopathy and increased liver
enzymes
 Contraindications:
Liver disease.
 Precautions:
CYP3A4 enzyme inducer(phenytoin &
barbiturate)
CYP3A4 enzyme inhibitors(ciclosporin &
ketoconazole)

 Potential pleiotropic effects:
 Improve endothelial function(up regulate
eNOs, scavenge superoxide)
 Antithrombotic effects(improve fibrinolytic
balance ,inhibit platelet aggregation)
 Anti-inflammatory effects(decrease
activation of NF ,decrease macrophage
infiltration)
 Enhance plaque stability
 Attenuate vascular smooth muscle cell
proliferation

Response to statin
Is there a role of ‘GENE’?

 Genetic variation in HMGCR may
contribute to variation in the response
 The CAP study, a 6-week simvastatin (40
mg/d) trial.
 Designed to examine role of gene in
ethnic variability in statin response in
African/African Americans and
Caucasians.
Source :Circulation 2008;117;1537-1544

 People carrying either H-2 or H-7 haplotypes:
 African/African American: 64%
 Caucasians: 11.6%
 12 people carrying both, H-2 and H-7
haplotypes
 11 were African/African American
 1 was Caucasian
 LDL-C reduction in carriers of both, H-2 and H-7
haplotypes vs. non-carriers -28% vs. -41.5%
Source:Circulation 2008;117;1537-1544

 We need high dose of statins:
Increasing prevalence of risk factors
Presence of multiple risk factors is also very
high.
Studies have established that African respond
lesser to statins compared to Caucasians.
Two (H-2 and H-7) SNP haplotypes are commonly
associated with poor response to statins and
these haplotypes are highly prevalent in African
compared to Caucasians.
Statins: benefits are beyond LDL-C and are dose
dependent.
Source :Circulation 2008;117;1537-1544

 Early, intensive lipid-lowering treatment with
statin, initiated during the acute phase of
unstable angina or non–Q-wave MI, reduces
early recurrent ischemic events
 A benefit was observed in a population with
low to normal baseline LDL-C levels.
Source:Schwartz et al JAMA 2001;285:1711-8

 Increase peripheral lipolysis and decrease
hepatic TG production(by binding to
peroxysome proliferators activated receptors
alpha in hepatocytes PPAR alpha)
 Beneficial effects on lipid parameter:
 TG ↓ 25%-50%
 LDLc ↓ or remain the same or↑
 LDL &HDL ↑ 10%-25% in hypertriglyceridemia
 Adverse effects:
GIT up set, cholelithiasis , myositis .
 Contraindication: hepatic or renal dysfunction
,gallbladder diseases.
 Indication: hypertrigylceridemia(type
IV&V)combined hyperlipidemia(type IIb) with
low HDLc.

 Beneficial effect on lipid parameter:
 LDLc ↓ 5%-25%
 TG ↓20%-60%
 HDL ↑15%-39%
 Reduce coronary events
 Adverse effect :
 Flushing ,itching ,headache
 Hepatotoxicity
 Activation of peptic ulcer
 Hyperglycemia/reduced insulin senetivity
 Contraindications:
Active liver disease, peptic ulcer disease
NOTE: Tredaptive(nicotinic acid +laropriprant)2008
Laropriprant(selective antagonist of prostaglandin D2 receptor).

 Binding to bile acid and increase excretion of
cholesterol
 LDL c↓ 15%-30%
 HDL c ↑3%-5%
 TG may increase in patient with elevated TG
 Reduced coronary events
 Adverse effect:
 GIT intolerance ,constipation, bloating
,abdominal pain, flatulence
 Drug interaction:
 Bind negatively to charged drugs, interfere with
absorption of drugs/fat soluble vitamins(other
drugs 1hr before or 4-6 hrs after)

 Reduce cholesterol absorption by
binding to intestinal cholesterol
transporter (inhibit delivery of cholesterol
to liver &increase hepatic LDL receptor)
 LDL c ↓18%-20%(in monotherapy or
“add-on” to statin no change in TG&HDL.

 Fish oil:
It is rich in omega3 fatty acid ,decrease VLDL
synthesis and little change in LDL and HDL
level.
Omega 3 fatty acids protect against CHD
mortality particularly sudden death.
Can be used as alternative to fibrate or in
combination with statins.
 Soluble fibers:
Bind to bile acids in the gut and increase
conversion of cholesterol to bile acids in the
liver.

 CETP:
It transfers cholesterol from HDL to LDL&VLDL ,so it
inhibition will result in increase of HDL level and
reduce cardiovascular events.
 Combination drug therapy:
First monotherapy is used ,then if there is alack of
response combination is used.
In general Statins + bile acid sequestrants .
niacin+ bile acid sequesterant.
Both provide great reduction in total &LDL cholesterol.
To increase HDL level gemifebrozil or niacin is used.

drug Dosage forms Usual daily dose Maximum
daily dose
cholestyramine Bulk powder 4g
packet
8g TID 32g
Colestipol
hydrochlorid
Bulk powder 5g
packet
10g BID 30g
colesevelam 625 mg tablet 1,875mg BID 4,375mg
niacin 50,100,250,500mg
tab
125,250,500mg
cap
1,000-2,000 mg
once daily
6g
Extended release
niacin
500,750,1000mg
tab
1000-2000mg
once daily
2000mg
Fenofibrate 67.134,200mg cap
54,160,40,120mg
tab
54mg or 67mg 201mg
gemfibrizol 300mg cap 600mg BID 1.5g
ezetimibe 10mg tab 10mg 10mg
source:pharmacotherapy text book.7th edition

drug Dosage form Usual daily dose Maximum daily
dose
lovastatin 20,40mg tab 20-4-mg 80mg
pravastatin 10,20,40,80mg
tab
10-20mg 40mg
simvastatin 5,10,20,40,80mg
tab
10-20mg 80mg
atorvastatin 10,20,40,80mg
tab
10mg 80mg
rosuvastatin 5,10,20,40 mg
tab
5mg 40mg
pitavastatin 1,2,4mg 2mg 4mg
source:pharmacotherapy textbook. 7th edition

 According to the NCEP(national cholesterol education
programme &the national institute of health (USA):
 The most important step in management of high cholesterol level
in the blood is assessing person’s risk status. By 3 steps:
 First: detecting fast lipoprotein profile (total cholesterol , LDL c,
HDL c ,TG).
 Second: identifying any risk determinants.
 Third: estimation of 10 years CHD risk according to Framingham
scoring.
 Major risk determinants:
 Cigarette smoking
 Hypertension
 Low HDL ≤ 40mgdl
 Family history of CHD
 Age { men ≥45 yrs women≥55ys}
Note :there are other factors ,but only the major factors modify LDL c
goals
Source: Ntional cholesterol education programme.National heart,lung&blood
institute NIH publication No .01-3670 May 2011

For individual
with
Trial of
dietary
therapy
&counseling
Initiate drug
therapy if LDL
remain
LDL
cholesterol
goal
Risk of CHD
for
10yrs(framing
ham score)
No CHD&>0-
1 risk factor
6 – 12 month ≥ 190 mg/dl
≥4.9 mmol/L
>160 mg /dl
>4.1 mmol/L
> 10 %
No CHD &<2
CHD risk
factor
3 – 6 month ≥ 160 mg/dl
≥4.1 mmol/L
>130 mg/dl
> 3.4 mmol/L
10 -20%
Established
CHD
6 – 12 weeks ≥ 130 mg/dl
≥3.4 mmol/L
≤ 100 mg/dl
≤ 2.6 mmol/L
< 20%
source:www.nhlbi.nih.gov/guidelines/cholesterol/atp3/index.htm

 It constitute due to , life habit risk factors
and emerging factors .
 It characteristic by atherogenic
dyslipideamia, abdominal obesity, insulin
resistance and high blood pressure
(DROP syndrome)

Risk factors Defining level
Men >102 cm (>40 in)
Women >88 cm (>35 in)
≥150 mg/dL
Men <40 mg/dL
Women <50 mg/dL
≥130/85 mmHg
Abdominal Obesity Waist
Circumference
Triglycerides
HDL cholesterol
Blood pressure
Fasting glucose ≥110 mg/dL

 Target of therapy :
1 primary target (LDL cholesterols)
2 secondary target (metabolic syndrome)
 Modalities of therapy:
1Therapeutic lifestyle change(TLC)
2Drug therapy

Nutrient Recommended intake
Saturated fat Less than 7% of total
calories
Polyunsaturated fat Up to 10% of total calories
Monounsaturated fat Up to 20% of total calories
Total fat 25-35% of total calories
Carbohydrate 50-60% of total calories
Fiber 20-30 g/day
Protein Approximately 15% of total calories
Cholesterol Less than 200 mg/day

Visit 1
Begin Lifestyle
Therapies
Visit 2
Evaluate LDL
response
If LDL goal
not
achieved,
intensify
LDL-lowering
therapy
Visit 3
Evaluate LDL
response
If LDL goal not
achieved,
consider
adding drug Tx
Visit N
Monitor
Adherence to
TLC

Initiate
LDL-lowering
drug therapy
If LDL goal not
achieved,
intensify
LDL-lowering
therapy
If LDL goal not
achieved,
intensify
drug therapy
or
refer to a lipid
specialist
Monitor
response and
adherence to
therapy

 the clinical approach calls for TLC for
primary prevention of CHD .
 For higher risk persons , clinical
approach intensifies prevention
strategies . aiming to reduce long tern
risk > 10 years.

 The recent clinical trials demonstrate that
LDL lowering therapy reduce (coronary
mortality, major coronary events,
procedures and strokes)
 For persons with established CHD or CHD
equivalent ,ATPIII specifies an LDL c <
100 mg/dl as the goal of therapy for
secondary prevention.

 pharmacists should always counsel
patients on the disease process, and
reinforce lifestyle modifications, with
added emphasis on the benefits of
intervention and compliance.
 The most important message pharmacists
can relay to patients is that the
management of dyslipidemia is not a
short- term assignment with immediate,
visible outcomes. Rather, it is a long-term
process that should be integrated into
one’s daily life.
Source: pharmacytimes.com

 Implementing clinical pharmacy services in
Jordan has improved the lipid profile of
dyslipidemic patients, majority of pharmacist
recommendation (90.4%) were followed by
physician and the overall lipid lowering agent
use was increased to (91.8%) in intervention
group patient & (86.5%) in control group
compared to (69.9%-78.8%) respectively at
baseline.
 Article: (The role of clinical pharmacist on lipid
control in dyslipidemic patients in Jordan)
Source: Int J clin pharm 2011 Ap;33(2):229-236

 Interdisciplinary medication team that
include clinical pharmacists in lipid
lowering management resulted in
improved treatment success as measured
by reduction in LDL level (5 %-22% per
visit)
 Article: (Assessment of clinical
pharmacist management of lipid lowering
therapy in primary care)
Source: J manage care pharm 2003May;9(3):269-273

Dyslipidemia.docx

More Related Content

What's hot

Similar to Dyslipidemia.docx

Recently uploaded

Dyslipidemia.docx

Editor's Notes