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table 1
lipoprotein classification
Lipoprotein Apolipoprotein Lipid
low density lipoprotein (ldl-C) apob-100 Cholesterol
High density lipoprotein (Hdl-C) apoa-i; apoa-ii Cholesterol
Chylomicron apob-46 triglyceride
Very low density lipoprotein (Vldl) triglyceride
monogenic disorders, such as lipoprotein
lipase deficiency, result in marked TG elevation
(fasting TG>5 mmol/L) and/or chylomicronemia,
and they may be associated
with pancreatitis in childhood.
Familial Obesity
The classic dyslipidemia associated with
obesity includes elevated fasting TG levels
and suppressed HDL-C levels. Therapy
includes diet, lifestyle changes, and implementation
of a heart-healthy lifestyle to
assist the individual and the family. This
type of dyslipidemia is often clustered with
other CVD risk factors such as hypertension
and dysglycemia. This cluster of factors,
also called the metabolic syndrome, is
associated with a 14-fold increased risk of
clinical CVD by 50 years of age, highlighting
the importance of early recognition and
treatment of this disorder (9).
Secondary Causes of Dyslipidemia
In addition to obesity and the primary disorders
resulting in dyslipidemia, numerous
other clinical conditions are recognized
causes of dyslipidemia in children. Important
secondary causes include diabetes, hypothyroidism,
chronic renal insufficiency
or renal failure, and liver disease. Medications
that adversely influence the lipid profile
include retinoids used for the treatment
of acne in youth, glucocorticoids, estrogen,
progestins, and ß-blockers.
Lipid Measurements
Laboratory measurements of lipids should
follow good quality control procedures.
The National Cholesterol Education Program
(NCEP) has developed criteria for
the analytical performance of cholesterol
assays. In addition, the CDC’s Cholesterol
Reference Method Laboratory Network
(CRMLN) certifies clinical diagnostic
products that measure TC, HDL-C, and
LDL-C. The FDA has recognized the value
of the CRMLN’s certification program and
encourages manufacturers to certify their
products through the CRMLN. Today, TC
measurements on most analyzers meet the
NCEP’s 1992 criteria of 3% bias versus the
reference method and imprecision. CDC’s
Division of Laboratory Sciences also maintains
lists of the clinical diagnostic products
that have been certified by the CRMLN that
can be found at www.cdc.gov/labstandards/
crmln.htm.
Various methods are available to determine
HDL-C, but the direct method is
the most widely used. This method typically
involves the selective measurement
of HDL-C after shielding cholesterol in
the non-HDL fractions. While direct homogeneous
methods for assessing LDL-C
are available on many automated analyzers,
most laboratories continue to calculate
LDL-C by the Friedewald equation,
which is based on routinely measured TC,
HDL-C, and TG. The NCEP recommends
that LDL-C be calculated using one of the
following equations:
LDL-C (mg/dL) = TC – HDL-C – TG/5
or
LDL-C (mmol/L) = TC – HDL-C – TG/2.2
Labs can use these equations to calculate
LDL-C levels except when the TGs are very
high or when the sample is obtained under
non-fasting conditions. At very high concentrations
(400 mg/dL or 4.52 mmol/L),
TG/5 or TG/2.2, which is an estimate of
VLDL, will not be valid due to the presence
of chylomicrons. The Friedewald equation
is also not valid for patients with Type
III hyperlipoproteinemia. The enzymatic
measurement of TG is standardized to the
methylene chloride-salicylic acid chromotropic
reference method of the CDC.
Screening for Dyslipidemia in Youth
Population-wide screening for dyslipidemia
in children is not currently recommended.
However, the AHA recommends screening
children who are most likely to have dyslipidemia
or who are at increased risk of CVD
(8). The two primary target groups are
children with genetic dyslipidemias, often
identified by a family history of hyperlipidemia
and/or premature coronary artery
disease (CVD onset at < 55 years of age in
male relatives, < 65 years of age in female
relatives), and children who are obese.
table 3
classification of cvd risk
in children
Total Cholesterol LDL-Cholesterol
mg/dL mmol/L mg/dL mmol/L
acceptable < 170 4.40 < 110 2.85
borderline 170–199 4.4–5.15 110–129 2.85–3.34
High > 200 5.15 > 130 3.34
Source: References 10 and 11.
table 2
recommended interventions
for children with heterozygous
familial hypercholesterolemia
Intervention Type Parameter Target
Dietary < 30% calories from fat
< 7% calories from saturated fat
no trans fat
Physical Activity Active play > 1 h/d
Screen time < 2 h/d
Other CV Risk Factors Assess and counsel:
blood pressure
cigarette smoking
glycemic status
Pharmacotherapy Consider statin therapy if :
male patient is at least 10 years old,
female patient has undergone menarche,
LDL-C persists at ≥4.9 mmol/L or ≥4.2 mmol/L
with other CV risk factor(s) or family history
of PCAD
Source: Reference 8.
In addition, the 2006 scientific statement
from AHA recommends lipid screening
profiles for children with a number of
pediatric disorders that increase their risk
of CVD in young adulthood (8). Diabetes
type 1 and 2, Kawasaki disease with coronary
aneurysms, and chronic and end-stage
renal disease may predispose children to
very early coronary events. Hyperglycemia
in type 1 diabetes is a primary mediator
of atherosclerosis, while in type 2 diabetes,
both hyperglycemia and insulin resistances
are implicated in endothelial dysfunction.
In children with chronic kidney disease,
morbidity and mortality is related not only
to the kidney disease but also to CVD. The
recommendations and goals for intervention
have been tailored to risk (2).
Target Values
Elevated LDL-C is the most clinically significant
marker of dyslipidemia in children
and is used as the basis for treatment.
Table 3 summarizes the NCEP (10) and
< 200 mg/dL
total cholesterol
< 3.35 mmol/L or
130mg/dL LDL-C
American Academy of Pediatrics (AAP)
(11) classification categories based on TC
and LDL-C levels. A major concern among
pediatric care givers has been that a single
cutoff value does not reflect the changes
associated with sex, growth, and maturation.
The Lipid Research Clinics (LRC) Prevalence
study also defined target values for
TC. This 1972–1976 study, sponsored by
the National Heart, Lung, and Blood Institute,
used fasting samples from a cross-
sectional survey of various North American
populations. More age-specific and
sex-specific data from the LRC prevalence
data are shown in Table 4. Levels above the
95th percentile are considered abnormal.
More recently, researchers developed
age- and sex-specific lipoprotein threshold
concentrations for adolescents 12–20 years
of age based on data from the National
Health and Nutrition Examination Surveys
(NHANES) (13). They linked the cut points
to the adult health-based thresholds for
table 4
lipid prevalence data by age
Total cholesterol
Age
(years)
Males Females
75 th 95 th 75 th 95 th
mg/dL mmol/L mg/dL mmol/L mg/dL mmol/L mg/dL mmol/L
5–9 168 4.34 189 4.89 176 4.55 197 5.09
10–14 173 4.47 202 5.22 171 4.42 205 5.30
15–19 168 4.34 191 4.94 176 4.55 207 5.35
ldl-cholesterol
Age
(years)
Males Females
75 th 95 th 75 th 95 th
mg/dL mmol/L mg/dL mmol/L mg/dL mmol/L mg/dL mmol/L
5–9 103 2.66 129 3.34 115 2.97 140 3.62
10–14 109 2.82 132 3.41 110 2.84 135 3.52
15–19 109 2.82 130 3.36 111 2.87 137 3.54
Source: Reference 12.
CliniCal laboratory news JuLy 2008 11