Chapter 166

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.

### Background

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

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.

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

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, type IIb, ...

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