Dr.Toba kazemi
Associate Professor of Cardiology
BUMS-BCRC
17 Esfand 1390
‫تعريف ‪:‬‬
‫‪ ‬به اختالل سطح چربیهای سرم که منجر به افزایش ریسک‬
‫بیماریهای قلبی عروقی می شود‪ ،‬گفته می شود که شامل‬
‫هیپرکلسترولمی‪ ،‬هیپرتری گلیسریدمی‪LDL ،‬باال و‬
‫‪HDL‬پایین می باشد‪.‬‬
‫اهميت ديس ليپيدمي‬
‫چربي خون‬
‫تغيير در ميزان چربي‬
‫احتمال بيماري قلبي عروقي‬
‫‪LDL‬‬
‫به ازاي ‪1mg/dl‬افزايش‬
‫افزايش ‪ %1‬احتمال بيماري در زنان ومردان‬
‫‪Non-HDL‬‬
‫به ازاي ‪1mg/dl‬افزايش‬
‫افزايش ‪ %1‬احتمال بيماري در زنان ومردان‬
‫‪TG‬‬
‫به ازاي ‪89 mg/dl‬افزايش‬
‫افزايش ‪ %37‬احتمال بيماري در زنان و‪%14‬‬
‫درمردان‬
‫‪HDL‬‬
‫به ازاي ‪1mg/dl‬افزايش‬
‫كاهش ‪ %3‬در ميزان مرگ ومير بيماري قلبي در‬
‫زنان و‪%2‬درمردان‬
Log-linear Relationship Between LDL-C Levels and
Relative Risk for CHD
3.7
2.9
Relative
Risk
for
Coronary
Heart
Disease
(Log Scale)
2.2
1.7
1.3
1.0
40
70
100
130
160
190
LDL-Cholesterol, mg/dL
This relationship is consistent with a large body of epidemiological data and with data •
available from clinical trials of LDL-lowering therapy
These data suggest that for every 30-mg/dL change in LDL-C, the relative risk for CHD is •
changed in proportion by about 30%. The relative risk is set at 1.0 for LDL-C 40 mg/dL.
Grundy S, et al. Circulation. 2004;110:227-239
Risk of CHD by TG Level
The Framingham Heart Study (30-Year Follow-Up)
N = 5127 patients
with no history of CHD
3
Men
Relative CHD Risk
2.5
Women
2
1.5
1
0.5
0
50
100
150
200
250
300
350
400
TG Level, mg/dL
of data from the Framingham Heart Study, including 5127 patients aged 30
0 years without CHD, to
determine
relationship
between
TGsfrom
and
CHD.
Reprinted
from Castellithe
WP. Am
J Cardiol. 1992;70:3H-9H,
with permission
Elsevier.
‫تقسيم بندي‬
‫پترنهاي افزايش ليپيدها(تقسيم بندي‬
‫فريدريكسون)‬
‫اوليه ‪/‬ثانويه‬
‫هيپركلسترومي‪/‬هيپرتريگليسريدمي‬
‫‪/‬كاهش‪HDL‬‬
‫علل ايجاد‬
‫‪ ‬اوليه(ژنتيك)‬
‫‪ ‬ثانويه (تغييرات شيوه زندگي‪/‬بيماريها و‪).....‬‬
)‫اوليه(ژنتيك‬

Primary causes : single or multiple gene
mutations that result in either overproduction or
defective clearance of TG and LDL cholesterol, or
in underproduction or excessive clearance of HDL
 Primary disorders, the most common cause of
dyslipidemia in children, do not cause a large
percentage of cases in adults.
Secondary causes

Secondary causes contribute to most cases of
dyslipidemia in adults.
 The most important secondary cause in developed
countries is a sedentary lifestyle with excessive
dietary intake of saturated fat, cholesterol, and
trans fats.
 Other :DM, alcohol overuse, chronic kidney
disease, hypothyroidism, primary biliary cirrhosis
and liver diseases
 Drugs: Thiazides, β-blockers, retinoids, highly
active antiretroviral agents, estrogen , progestins,
(FH)‫هيپركلسترولمي فاميليال‬

FH is an AD disorder characterized :
 elevated LDL-C + normal TG , tendon xanthomas, premature
CAD
 FH is caused by a large number (>1000) mutations
in the LDL receptor gene.
 The elevated levels of LDL-C in FH are due to an increase in
the production of LDL from IDL (since a portion of IDL is
normally cleared by LDL receptor-mediated endocytosis) and
a delayed removal of LDL from the blood.
 FH homozygotes: 2 mutated LDL receptor
 FH heterozygotes: 1 mutant allele
 Individuals with FH homozygotes have
higher LDL-C levels than those FH heterozygotes
LDL receptor
A normal LDL receptor
A mutated LDL receptor
Homozygous FH


1 in 1 million persons worldwide.
The disease has >90% penetrance so both parents of FH
homozygotes usually have hypercholesterolemia.

Clinical manifestation:

cutaneous xanthomas on the hands, wrists, elbows, knees, heels, or
buttocks present in childhood
CHOL are usually >500 mg/dL and can be higher than 1000 mgldL.
Important complication of is accelerated atherosclerosis, which can result in
disability and death in childhood.
Atherosclerosis often develops first in the aortic root, where it can cause
aortic valvular or supravalvular stenosis, and typically extends into the
coronary ostia, which become stenotic.



Homozygous FH

Exams and Tests:

A physical examination may reveal xanthomas and corneal arcus.
A strong family history of familial hypercholesterolemia or early heart
attacks
High levels of LDL in either or both parents.
Individuals from families with a strong history of early heart attacks should
have blood tests done to determine lipid levels.



Dysbetalipoproteinemia



Dysbetalipoproteinemia,, is a rare lipid disorder characterized by high levels
of blood cholesterol & TG.
CHOL range from 300-600 mg/dL. TG are usually >400 mg/dL and may
exceed 1000 mg/dL.
Moderately elevated total cholesterol and triglyceride levels accompanied by
the presence of palmar crease xanthomas confirm the diagnosis
dysbetalipoproteinemia
Clinical findings






Patients may have no physical findings or may have skin lesions called
xanthomas, particularly in more severe presentations.
Xanthoma striata palmaris
Tuberoeruptive and tuberous xanthomas
Corneal arcus ,
Xanthelasmas
Obesity or signs of hypothyroidism may be noted.
‫عالیم بالیني‬
‫‪‬‬
‫‪‬‬
‫‪‬‬
‫‪‬‬
‫‪‬‬
‫عالمتي كه مشخصا مربوط به ديس ليپيدمي فندارد‬
‫ممكنست فرد با عاليم مثل بيماري كرونر يا عروق محيطي‬
‫‪High levels of TGs (> 1000 mg/dL) can cause acute‬‬
‫‪pancreatitis.‬‬
‫خطر بيماري كرونر زودرس‬
‫طبيعي شدن ليپيد مانع ايجاد يا پيشرفت‬
‫عوارض(‪.)premature CAD/pancreatitis‬‬
‫يافته هاي باليني‬






High levels of LDL :eyelid xanthelasmas; arcus corneae;
tendinous xanthomas .
familial hypercholesterolemia :the above findings plus planar
or cutaneous xanthomas
severe elevations of TGs can have eruptive xanthomas
Patients with dysbetalipoproteinemia can have palmar and
tuberous xanthomas
Severe hypertriglyceridemia (> 2000 mg/dL) can give retinal
arteries and veins a creamy white appearance (lipemia
retinalis).
Extremely high lipid levels also give a lactescent (milky)
appearance to blood plasma.
Diagnosis


Lipid profile measurement
Testing should be postponed until after resolution of acute
illness, because TGs increase and cholesterol levels
decrease in inflammatory states. Lipid profiles can vary for
about 30 days after an acute MI; however, results
obtained within 24 h after MI are usually reliable enough
to guide initial lipid-lowering therapy.
 TC, TGs, and HDL cholesterol are measured directly.
 LDL cholesterol = TC − [HDL cholesterol + )TGs ÷ 5)]
(Friedewald formula).
 This calculation is valid only when TGs are < 400 mg/dL
and patients are fasting

Screening: A fasting TC, TGs, HDL cholesterol, and
calculated LDL cholesterol should be obtained in all
adults ≥ 20 yr and should be repeated every 5 yr.

screening patients < 20 yr: atherosclerotic risk factors,
such as diabetes, hypertension, cigarette smoking, and
obesity; premature CAD in a parent, grandparent, or
sibling; or a cholesterol level > 240 mg/dL or known
dyslipidemia in a parent.
 12 hours fasting
Other tests

1- Lp(a) measurement :
 Patients with premature atherosclerotic cardiovascular
disease
 cardiovascular disease with normal or near-normal lipid
levels
 high LDL levels refractory to drug
 Patients with an extensive family history of heart disease
 2-C-reactive protein and homocysteine measurement may
be considered in the same populations.
 3-Tests for secondary causes

3-Tests for secondary causes :
 FBS,
 liver enzymes,
 Creatinin
 TSH
 urinary protein
 For who? (newly diagnosed dyslipidemia , when a
component of the lipid profile has changed for the worse.
 A definite age after which no require screening ??
 into their 80s, especially in the presence of
atherosclerotic cardiovascular disease.
US Hypertriglyceridemia (HTG) Prevalence
TG ≥500
mg/dL
~2.5%
5-6 M patients
TG 200-499 mg/dL*
~13%
~28 M patients
US Adult Population
Total = 217 million
HIGH TG
 INDEPENDENT
RISK FACTOR FOR
HEART ATTACK
 INDEPENDENT RISK FACTOR FOR
STROKE
 ASSOCIATED WITH LOW HDL
 ASSOCIATED WITH INCREASED
CLOTTING VIA HIGH PLASMINOGEN
ACTIVATOR INHIBITOR ACTIVITY,
HYPOFIBRINOLYSIS (CAN’T CHOP UP
BLOOD CLOTS EASILY)
 A FUNDAMENTAL PART OF
‫‪‬اغلب ثانويه به عوامل ديگر‬
‫استروژنهاي اگزوژن‪,OCP‬‬
‫الكل زياد‬
‫ديابت خوب كنترل نشده‬
‫مصرف كورتن سيستميك‬
‫نارسايي كليه‬
Familial hypertriglyceridemia







Familial hypertriglyceridemia is a common disorder passed
down through families in which the level of TG are higher than
normal.
The condition is not associated with a significant increase in
cholesterol levels.
An autosomal dominant fashion
Familial hypertriglyceridemia does not usually become
noticeable until puberty or early adulthood.
Obesity, hyperglycemia (high blood glucose levels), and high
levels of insulin are often also present and may cause even
higher triglyceride levels.
about 1 in 500 individuals in the United States.
Risk factors are a family history of hypertriglyceridemia or a
family history of heart disease before the age of 50.
Familial hypertriglyceridemia
Exams and Tests

People with a family history of this condition should have blood tests to
check very low density lipoprotein (VLDL) and triglyceride levels. Blood tests
usually show a mild to moderate increase in triglycerides (about 200 to 500
mg/dL)
‫رويكرد تشخيصي تريگليسريد باال‬
‫‪ ‬رد علل ثانویه‬
‫‪ ‬بررسي میزان تریگلیسرید‬
‫‪ ‬بیش از ‪ 500‬درمان بر اساس تري گلیسرید‬
‫‪ ‬در صورتی که تری گلیسرید خون بین ‪200- 500 mg/dL‬‬
‫باشد ابتدا باید‬
‫‪ Non -HDL–ChOL‬را محاسبه کنیم و سپس تصمیم بگیریم‬
‫‪(Non-HDL chol=Total Chol-HDL(. ‬‬
‫‪( Target Non-HDL =LDL+30) ‬‬
‫‪LOW HDL‬‬
‫علل‪:‬‬
‫‪ ‬اغلب همراه با مقاومت به انسولين است ( تري‬
‫گليسريد باال ‪ ،‬چاقي ‪ .‬اضافه وزن ‪ ،‬فعاليت فيزيكي كم ‪،‬‬
‫ديابت تيپ ‪) 2‬‬
‫‪ ‬سيگار‬
‫‪ ‬رژيم با كربو هيدرات خيلي زياد‬
‫‪ ‬داروها (بتابلوكرها ‪ ،‬استروئيدهاي آنابوليك ‪ ،‬پروژستين‬
‫ها )‬
‫درمان ‪LOW HDL‬‬
‫‪ HDL‬پايين همراه باِ ‪LDL‬‬
‫باال‬
‫‪ HDL‬پايين همراه با تريِ‬
‫گليسريد‬
‫درمان بر اساس ‪ LDL‬انجام شود‬
‫درمان بر اساس تريِ گليسريد باال‬
‫رژيم فعاليت بدني ‪ ،‬كاهش وزن‬
‫‪Isolated LOW HDL‬‬
‫اگر بيمار ‪ CAD‬يا ‪: CAD equivalent‬‬
‫درمان با فيبرات يا نياسين‬
Ddiagnostic approach-summary
1-Measure fasting lipoproteins
2-primary/secondary
3- Identify CAD or CAD equivalents &
CAD risk factors Slide 32
4- If ≥ 2 major risk factors without CAD or CAD
equivalent, assess 10-yr risk of MI or CAD death
using Framingham risk tables
5-refer to NCEP ATP III Guidelines for
Treatment of Hyperlipidemia
‫سطح چربیهای سرمی در افراد بالغ (‪(mg/dl‬‬
‫طبیعی‬
‫باالی طبیعی‬
‫باال‬
‫خیلی باال‬
‫)‪(high‬‬
‫)‪(very-high‬‬
‫توتال کلسترول‬
‫‪<200‬‬
‫‪200-239‬‬
‫‪≤ 240‬‬
‫‪--‬‬
‫‪LDL‬‬
‫‪< 130‬‬
‫‪130-159‬‬
‫‪160-189‬‬
‫‪≤ 190‬‬
‫تری گلیسرید‬
‫‪< 150‬‬
‫‪150-199‬‬
‫‪200-499‬‬
‫‪≤ 500‬‬
‫)‪(normal‬‬
‫‪HDL‬‬
‫‪(high‬‬‫)‪normal‬‬
‫غير طبیعی ‪ < 40 :‬در مردها و ‪ < 50‬در زنها‬
‫‪≤ 60‬حد خيلي خوب وپيشگيري كننده از بيماريهاي قلبي عروقي محسوب ميشود‪.‬‬





Rule out secondary causes(FBS,U/A,CR,TSH,LFT)
Sedentary lifestyle, obesity, and smoking are all associated with
low HDL-C levels, and patients should be counseled about
these issues.
Patients with hyperlipidemia, especially hypertriglyceridemia,
who drink alcohol should be encouraged to decrease their
intake.
Drugs
Attempts should be made to diagnose the primary lipid disorder
 CAD
equivalents:

Peripheral arterial disease
 Abdominal aortic aneurysm
 Symptomatic carotid artery disease
 Diabetes mellitus
 Major





CAD risk factors in dyslipidemia:
Cigarette smoking
Hypertension (BP ≥ 140/90 or on antihypertensive drug)
Low HDL (≤ 40 mg/dL [1.03 mmol/L])
Family history of premature CAD (CAD in a male 1st-degree
relative < 55 or in a female 1st-degree relative < 65)
Age (men ≥ 45, women ≥ 55)
Framingham Ten Year Risk
Men
Women
Framingham Ten Year Risk
0
Framingham Ten Year Risk
0
3
0
Non-Smoker
Framingham Ten Year Risk
0
3
0
1
HDL = 43
Framingham Ten Year Risk
0
3
0
SBP = 119, untreated
1
0
4
Framingham Ten Year Risk
0
3
0
1
0
4
‫سطح ایده ال‪LDL‬و ‪Non HDL‬در افراد مختلف‬
‫‪HDL‬‬
‫‪non‬هدف‬‫(‪) mg/dl‬‬
‫شروع رژیم‬
‫شروع دارو غذایی و فعالیت‬
‫كمتر از ‪100‬‬
‫‪≤ 70‬‬
‫‪≤ 70‬‬
‫‪LDL‬هدف‬
‫)‪(mg/dl‬‬
‫كمتر از‬
‫‪70‬‬
‫ميزان ریسک‬
‫وضعیت بیمار‬
‫‪Very High‬‬
‫بيماري عروق كرونر و ديابت يا چند‬
‫ريسك فاكتور قلبي‬
‫كمتر از ‪130‬‬
‫‪≤ 100‬‬
‫‪≤ 100‬‬
‫كمتر از ‪100‬‬
‫‪High‬‬
‫كمتر از ‪130‬‬
‫‪≤ 130‬‬
‫‪≤ 130‬‬
‫كمتر از ‪100‬‬
‫‪Moderately‬‬
‫‪High‬‬
‫كمتر از ‪160‬‬
‫‪≤ 160‬‬
‫‪≤ 130‬‬
‫كمتر از ‪130‬‬
‫‪Moderate‬‬
‫كمتر از ‪190‬‬
‫‪≤ 190‬‬
‫‪≤ 160‬‬
‫كمتر از ‪160‬‬
‫‪low‬‬
‫بيماري عروق كرونر يا معادالت‬
‫آن‪‬‬
‫≤‪2‬ريسك فاكتور قلبي و احتمال‬
‫بيماري كرونر در ‪10‬سال آینده بين‪-20‬‬
‫‪%10‬‬
‫≤ ‪2‬ريسك فاكتور قلبي و‬
‫احتمال بيماري كرونر در‬
‫‪10‬سال آینده کمتر از ‪%10‬‬
‫يك ريسك فاكتور ويا كمتر‬
TREATMENT
Ddiagnostic approach-summary
1-Measure fasting lipoproteins
2-primary/secondary
3- Identify CAD or CAD equivalents &
CAD risk factors
4- If ≥ 2 major risk factors without CAD or CAD
equivalent, assess 10-yr risk of MI or CAD death
using Framingham risk
5-refer to NCEP ATP III Guidelines for
Treatment of Hyperlipidemia
‫معرفی بیمار شماره ‪:1‬‬
‫‪‬‬
‫‪‬‬
‫‪‬‬
‫خانم ‪ 54‬ساله ای به کلینیک پیشگیری از بیماریهای غیرواگیر جهت بررسی‬
‫وضعیت سالمت خود مراجعه می کند ‪.‬وي هیچگونه عالمتی ندارد و تاکنون‬
‫کامالً سالم بوده است‪ .‬سابقه دیابت‪ ،‬هیپرتانسیون و بیماری قلبی عروقی را‬
‫در خانواده ذکر نمی کند‪ .‬در معاینه نکته غیرطبیعی مشاهده نشد‪.‬‬
‫آزمایشات خون بیمار بعد از ‪ 12‬ساعت ناشتایی به شرح زیر است‪:‬‬
‫‪FBS=85‬‬
‫‪Chol = 220‬‬
‫‪TG= 332‬‬
‫‪HDL=42‬‬
‫‪LDL=111‬‬
‫‪‬‬
‫بیمار خانم ‪ 54‬ساله ای است که به جز سن باال ریسک فاکتور دیگرقلبي عروقي ندارد‪.‬‬
‫فشارخون و قند خون بیمار در حد طبیعی است‪ .‬کلسترول توتال‪ LDL ،‬و ‪ HDL‬تقریبا ً در حد‬
‫قابل قبولي است‪ ،‬اما تری گلیسرید بیمار باالست‬
‫‪‬‬
‫‪Non HDL- ChOL = 220-42=178‬‬
‫باتشكر از همه شركت كنندگان‬
‫‪www.bums.ac.ir/heart‬‬