Labs in Dyslipedemia

Download as pptx, pdf, or txt
Download as pptx, pdf, or txt
You are on page 1of 38

Lab Testing in Dyslipidemia

INTRODUCTION
 
• Lipids, such as cholesterol and triglyceride, are insoluble in
plasma.

• They are made soluble by attachment to circulating lipoproteins


that transport lipids to various tissues for
– energy utilization,
– lipid deposition,
– steroid hormone production, and
– bile acid formation.
INTRODUCTION

Lipoproteins are spherical macromolecular complexes containing


• a core of relatively insoluble lipids (triglycerides and cholesteryl esters)
surrounded by
• a coat of phospholipids, unesterified cholesterol, and apoproteins
INTRODUCTION

Lipoproteins are classified according to their densities into five major


lipoproteins in blood:

• chylomicrons;
• very low-density lipoprotein (VLDL);
• intermediate-density lipoprotein (IDL);
• low-density lipoprotein (LDL); and
• high-density lipoprotein (HDL).

Each of these classes of lipoproteins carries cholesterol and triglyceride to a


varying degree.
Exogenous pathway of lipid metabolism
• In the intestinal cell, absorbed free fatty acids combine with glycerol to form triglycerides, and, to a lesser
degree, absorbed cholesterol is esterified to form cholesteryl esters. These lipids are assembled as chylomicrons;
the main apolipoprotein (apo) is B-48, but apo C-II and E are acquired as the chylomicrons enter the circulation.
Apo C-II is a cofactor for lipoprotein lipase which makes the chylomicrons progressively smaller in part by
hydrolyzing the core triglycerides and releasing free fatty acids. The chylomicron remnants that are cleared from
the circulation by hepatic chylomicron remnant receptors for which apo E is a high-affinity ligand.
• The endogenous pathway begins with the synthesis in the liver of nascent VLDL particles,
containing apolipoproteins (apo) B-100 and E. Cholesteryl esters and other apolipoproteins,
some of which are derived from HDL catabolism, are added to form the mature VLDL particle.
The lipolytic action of lipoprotein lipase (for which apo C-II is the primary ligand) cleaves VLDL
into smaller VLDL remnants that are enriched in apo B-100 and E. The remnants are either
cleared by the LDL and remnant receptors in the liver or hydrolyzed by hepatic triglyceride
lipase to yield LDL particles containing apo B-100.
DYSLIPIDEMIA

One definition of dyslipidemia is


• total cholesterol, LDL-C, triglyceride, or lipoprotein(a) levels above the
90th percentile
or
• HDL or apo A-1 levels below the 10th percentile for the general
population.

Term used is for lipid values that are associated with disease or increased
risk of disease and for which lipid-altering therapy might be of value.
Disorders of lipoproteins

• Previously classified by numbers (Fredrickson 1-5) which


referred, in general, to the abnormal lipids present;

• Currently they are more often referred to by descriptors


which characterize the lipoprotein abnormalities.
– classified as follows: hypercholesterolemia, low levels of HDL
cholesterol, hypertriglyceridemia, and combined
hyperlipidemia.
Fredrickson classification of lipid disorders
Frederickson
Lipoprotein abnormality Typical lipid levels
phenotype
I Chylomicrons TG >99th percentile
TC >90th percentile; depending upon type, may
IIa LDL
also see apolipoprotein B ≥90th percentile
Depending upon type, TC and/or TG
IIb LDL and VLDL ≥90th percentile and apolipoprotein B
≥90th percentile
III Remnants of VLDL and TC and TG >90th percentile
chylomicrons
TC >90th percentile; depending upon type, may
IV VLDL
also see TG >90th percentile or low HDL
V Chylomicrons and VLDL TG >99th percentile
Causes of Dyslipidemia

Lipoprotein disorders can be primary or secondary

• Primary causes: genetic factors , inherited


Causes of Dyslipidemia

Secondary causes

• Hypothyroidism
• Dysgammaglobulinemia (systemic lupus erythematosus, multiple myeloma)
• Cholostatic diseases of the liver due to abnormal lipoproteins, as in primary biliary cirrhosis
• Chronic renal failure
• T2DM
• Obesity
• Excessive alcohol intake
• Metabolic syndrome
• Antihypertensive medications (thiazide diuretics and b-adrenergic blocking agents)
• Corticosteroid therapy (or severe stress that increases endogenous corticosteroids)
• Orally administered estrogens, oral contraceptives, pregnancy
• Protease inhibitors for treatment of HIV infection
• Sedentary life
Indications for measurement
The lipid profile and its components are some of the most
commonly ordered laboratory tests in clinical practice.

• The most common indication for this test (or its


components) is for aiding the process of determining
cardiovascular disease (CVD) event risk.
Indications for measurement
Other indications for these tests include the following:

• Identifying patients who are at high risk for a lipid abnormality due
to a family history of genetic disorder, such as familial
hypercholesterolemia.
• Identifying the cause of another clinical problem such as
pancreatitis.
• Managing patients with established atherosclerotic CVD.
• Evaluating the efficacy of and/or adherence with lipid-lowering
therapy and lifestyle modification.
WHO SHOULD BE SCREENED —

For young adults who have not been screened as children, we


obtain a baseline lipid profile at the time of initiation of care with
an adult primary care practitioner to screen for familial
hyperlipidemia and to assess cardiovascular disease (CVD) risk.

CVD risk is influenced by :


- age (increases as patients get older), sex (more common in men than women), hypertension, DM,
cigarette smoking, obesity, sedentary lifestyle, and family history of premature coronary heart
disease (CHD; first-degree male relative with CHD before age 55; first-degree female relative with
CHD before age 65).
• For patients at higher cardiovascular risk (hypertension, diabetes
mellitus, cigarette smoking, family history of premature CHD),
lipid screening should be performed in males between the ages of
25 to 30 and in females between the ages of 30 to 35 with yearly
follow up.

• For patients at lower cardiovascular risk (none of the above


factors), we suggest lipid screening be performed in males at age
35 and in females at age 45 with follow up every 5 years.
Measurement of blood lipids and lipoproteins

LIPID PROFILE AND COMPONENTS


 
A standard serum lipid profile measures:
• Concentration of total cholesterol
• HDL cholesterol
• Triglycerides
• Estimated LDL cholesterol
Total cholesterol and HDL cholesterol

• Serum total cholesterol and HDL-C are measured


directly
• They can be obtained in fasting or nonfasting state
• Total cholesterol is determined from the amount of
cholesterol found in HDL, LDL and VLDL
Total cholesterol
• Desirable < 200 mg/dL
• Borderline 200-239
• High ≥ 240

HDL:
• Low (undesirable) < 40 mg/dL
• High (desirable) ≥ 60 mg/dL
Total cholesterol to HDL cholesterol ratio 

• The ratio of total cholesterol or LDLc to HDL cholesterol concentration are


used in epidemiological studies to categorize populations into high- and low-
risk subgroups.

Cholesterol/HDL ratio:
• Optimal < 4
• Borderline 4-5
• High risk > 5
LDL/HDL ratio: risk factor if ≥ 3.33
LDL cholesterol

• LDL cholesterol is generally calculated using the Friedewald formula,


LDLc  =  Total cholesterol -  HDLc  - VLDLc .
where VLDLc ≈ TG/5
LDLc  =  Total cholesterol - (HDLc + TG/5)

• The Friedewald formula is applied to lipid values measured in the


fasted state (8-12 hours of not eating or drinking (except water)).
• In a non-fasting patient, the contribution of post-prandial chylomicrons
to the total lipoprotein pool makes the formula much less accurate.
• The extent of variability with calculated LDL cholesterol
may be greater than with other laboratory tests since
the value is influenced by the method error from each of
the independent lipid measurements (total cholesterol,
triglycerides, and HDL cholesterol).
Direct LDLc measurement 

• Assays are available to directly measure the LDL cholesterol


concentration
• should be considered in patients with a total triglyceride
concentration >400 mg/dL (4.516 mmol/L).

• There are strong associations between total LDL particle


concentration and cardiovascular disease
Direct LDLc measurement 

• LDLc is the primary lipid measure for cardiovascular disease risk


assessment and guide to therapy.

• LDL c should be monitored every 6 weeks after the initiation of


treatment until the LDLc target is achieved.

• Measurement every 6 to 12 months is reasonable in patients adherent


to lifestyle modifications
NON-HDL CHOLESTEROL 

• Non-HDL cholesterol = total cholesterol - HDLc.

• Non-HDLc includes all cholesterol present in lipoprotein particles


that is considered atherogenic, including LDL, lipoprotein(a), IDL, and
VLDL.

• Non-HDLc fraction may be a better tool for risk assessment than LDL
cholesterol.
ASCVD Risk Categories and LDL-C Treatment Goals
Treatment goals
Risk category Risk factors/10-year risk LDL-C Non-HDL-C Apo B
(mg/dL) (mg/dL) (mg/dL)
– Progressive ASCVD including unstable angina in individuals after
achieving an LDL-C <70 mg/dL
– Established clinical cardiovascular disease in individuals with  
Extreme risk DM, stage 3 or 4 CKD, or HeFH <55 <80 <70
– History of premature ASCVD (<55 male, <65 female)  

– Established or recent hospitalization for ACS, coronary, carotid


or peripheral vascular disease, 10-year risk >20%
Very high risk – DM or stage 3 or 4 CKD with 1 or more risk factor(s) <70 <100 <80
– HeFH

– ≥2 risk factors and 10-year risk 10%-20%


High risk – DM or stage 3 or 4 CKD with no other risk factors <100 <130 <90

Moderate risk ≤2 risk factors and 10-year risk <10% <100 <130 <90
Low risk 0 risk factors <130 <160 NR

Abbreviations: ACS, acute coronary syndrome; apo, apolipoprotein; ASCVD, atherosclerotic cardiovascular disease; CKD, chronic kidney disease;
DM, diabetes mellitus; HeFH, heterozygous familial hypercholesterolemia; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density
lipoprotein cholesterol; NR, not recommended.
Triglycerides

• Triglycerides are carried in chylomicron and VLDL


particles.
• Triglyceride levels are influenced by recent food intake
and should be measured in the fasting state when
possible.
Classification of Elevated Triglyceride Levels

TG category TG concentration (mg/dL) TG goal

Normal <150

Borderline high 150-199


<150 mg/dL
High 200-499

Very high ≥500

The most common indications for measuring triglyceride levels, either as a standalone test or as part of a lipid
profile, include:
●Establishing the etiology of acute pancreatitis
●Monitoring treatment of hypertriglyceridemia
●Screening family members for familial hypertriglyceridemia
Lipoprotein (a) or Lp(a)

• Lp(a)- LDL like particle with a molecule of apolipoprotein B-100 linked by a disulfide bridge
to apolipoprotein (a).

• Apo(a) component has homology with plasminogen in terms of structure and competes
with plasminogen for binding sites resulting in reduced fibrinolysis and the formation of
blood clots (thrombosis).

• Lp(a) is also thought to speed up atherosclerosis by binding LDL, Ca and other components
into an atherosclerotic plaque on the blood vessel wall.

• This dual action of Lp(a) explains its role in the promotion of cardiovascular disease.
Nonfasting lipid profiles may be used to calculate "remnant"
cholesterol.

• Remnant cholesterol is either measured directly or calculated


as: non-HDLc – directly measured LDLc.

• Remnant cholesterol can be used as a marker of myocardial


infarction (MI) and as a predictor of initial and recurrent
cardiovascular events
Apolipoproteins

• Each LDL particle contains one molecule of apolipoprotein


B.

• Apo B measurements (reflecting the particle concentration


of LDL and all other atherogenic lipoproteins) may be
useful to assess the success of LDL-C–lowering therapy.
CAUSES OF INACCURATE RESULTS

• The presence of a circulating monoclonal protein


(falsely low values of HDL and/or LDL cholesterol).

• The calculated LDLc may be inaccurate in patients with a triglyceride


levels above 400 mg/dL (4.516 mmol/L).

• Fall in LDLc and HDLc and rise in triglycerides after 24 to 48 hours after
an acute MI (and also surgical trauma or infection) with a maximal
effect at seven days, and these changes persisted for approximately
two months. And 96 hours after a non-ST elevation MI.
Secondary causes of dyslipidemia must be excluded with a:

• thorough medical and dietary history


• laboratory testing for
– glucose and HbA1c
– thyroid,
– liver, and
– renal function levels.
Additional testing in cases of familial dyslipedemias
Thank you

You might also like