Dyslipidemia

Primary (Genetic) Dyslipidemia

Primary dyslipidemia tends to refer to elevated cholesterol that is the result of a genetic disorder. 

The most common genetic dyslipidemia is familial hypercholesterolemia (FH).  

• FH is autosomal dominant. 
• Children homozygous for FH have very high LDL (generally >400 mg/dL). 
  • HDL-C and TG levels are usually normal or only mildly abnormal. 
• Prevalence of homozygous FH is 1:160,000 to 400,000. (ref)(ref)  

Data from the CASCADE FH Registry show that, among children homozygous for FH  

• Xanthomas are often seen as early as 6 months of age. 
• ~19% have aortic stenosis. 
• ~44% have atherosclerotic cardiovascular disease (ASCVD).
  • Median age of onset is 8.9 years. 

Aggressive management of dyslipidemia in children homozygous for FH is needed to prevent ASCVD. 

Approximately 1 in 250 people are heterozygous for FH. 

• Children heterozygous for FH almost never have signs or symptoms. 
• An LDL-C ≥160 mg/dL suggests heterozygous FH, particularly with a family history of significantly elevated cholesterol or preterm coronary artery disease. 
• High-density lipoprotein cholesterol (HDL-C) and TG levels are usually normal, although some heterozygous for FH have lifestyle-induced dyslipidemia, presenting with low HDL-C and elevated TG in addition to LDL-C elevation. 
• Individuals heterozygous for FH have substantially increased lifetime risk of accelerated atherosclerotic cardiovascular disease.  

Far less common is familial chylomicronemia syndrome (FCS, also called hyperlipoproteinemia type 1 or LPL deficiency).  

• FCS affects about 1 in 1 million people worldwide.
• TG levels exceed 1,000 to 2,000 mg/dL. 
• FCS generally manifests before 10 years of age, with about 25% presenting in the first year after birth. 
  • Children with FCS present with 
    • Abdominal pain attributable to acute pancreatitis 
    • Xanthomas, which are present in about 50% of cases  

Secondary dyslipidemia

The most prevalent form of secondary dyslipidemia is atherogenic dyslipidemia.  

• Commonly seen in individuals with obesity, insulin resistance, or type 2 diabetes. 
• Patients have elevated serum triglycerides and low HDL-C.
• LDL-C levels may be within the reference range, but lipoprotein analysis shows increased concentrations of small, dense LDL particles. 
• The most effective treatment for this lipid disorder is change in diet and physical activity.  

Other causes of secondary dyslipidemia  

• Hypothyroidism, inflammatory or infectious conditions, renal disease, or diabetes. 
• Rarely, liver disease, inborn errors of metabolism, and other conditions can cause dyslipidemia. 
• Many medications can adversely affect lipid levels.  
  • Corticosteroids, isotretinoin, β-blockers, select chemotherapeutic or antiretroviral agents.  

To reduce the risk of heart disease in children: 

• The AAP endorses the recommendations of the National Heart, Lung, and Blood Institute (NHLBI).
• Dietary advice should be provided within the framework of shared decision-making and family-centered care. 
• A clinician should assess willingness to change and identify potential barriers, including food costs and access. 
• Advice should consider the age and development of the child, cultural norms, and personal preferences.