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Disorders of lipid and lipoprotein metabolism are characterized
by dyslipidemia, which is defined as either elevated or low levels
of one or more of the major lipoprotein classes: chylomicrons, very-low-density
lipoproteins (VLDL), low-density lipoproteins (LDL), and high-density
lipoproteins (HDL). Dyslipidemia can result from the expression
of a mutation in a single gene that plays a paramount role in lipoprotein
metabolism. More often, dyslipidemia reflects the influence of multiple
genes. Environmental influences such as excessive dietary intake
of fat and calories and limited physical activity, particularly
when associated with overweight or obesity, can also contribute
significantly to dyslipidemia. This chapter presents a theoretical
and practical approach to the diagnosis and treatment of dyslipidemia
in infants, children, and adolescents. The major clinical complication
of dyslipidemia is a predilection to atherosclerosis starting early
in life and leading to cardiovascular disease (CVD) in adulthood.
At the extremes of dyslipidemia, where inherited disorders of lipid
and lipoprotein metabolism are more likely to occur, premature CVD
is more frequent and can be accompanied by deposition of lipid in
various tissues. Children with profound hypertriglyceridemia are
at high risk of pancreatitis.
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A number of clinical, epidemiological, metabolic, genetic, and
randomized clinical trials strongly support the tenet that the origins
of atherosclerosis and CVD risk factors begin in childhood and adolescence
and that treatment should begin early in life.1
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Several longitudinal pathological studies from the general population have
found that early atherosclerotic lesions of fatty streaks and fibrous
plaques in children, adolescents, and young adults who died from
accidental causes are significantly related to higher antecedent levels
of total cholesterol (TC) and LDL-C (LDL-C); to lower levels of
HDL-C (HDL-C); and to other CVD risk factors such as obesity, higher
blood pressure, and cigarette smoking.1 These risk
factors’ effects on coronary lesion severity are multiplicative
rather than additive.
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Four major prospective population studies from Muscatine, Bogalusa,
the Coronary Artery Risk Development in Young Adults (CARDIA) and
the Special Turku Coronary Risk Factor Intervention Project (STRIP) showed
that CVD risk factors in children and adolescents, particularly
LDL-C and obesity, predicted clinical manifestations of atherosclerosis
in young adults, as judged by coronary artery calcium, carotid intima
medial thickness (IMT), or brachial flow-mediated dilatation.1 In
regard to CVD events, medical students at Johns Hopkins who had
a TC level >207 mg/dL had five times the risk of developing
CVD 40 years later than students who had a TC level <172. 1
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Studies have also been performed in high-risk youth; these individuals
were selected because one parent had CVD or because
they have inherited a known metabolic disorder of lipoprotein metabolism
that produces premature CVD. Half of the young progeny of men who
had CVD before age 50 had one of seven dyslipidemic profiles: elevated
LDL-C alone (type IIa) or combined with high TG (type IIb); elevated
TG alone (type IV); low HDL-C alone (hypoalpha); and type IIa, ...