How can a 19-year-old with a body mass index (BMI) of 16.4 have an elevated lipid profile, specifically hyperlipidemia?

Causes of Elevated Lipid Profile in a 19-Year-Old with Low BMI

Several medical conditions can cause hyperlipidemia in a 19-year-old with a BMI of 16.4, including familial hypercholesterolemia, hypothyroidism, or other genetic lipid disorders.

Primary Causes to Consider

Genetic Disorders

• Familial Hypercholesterolemia (FH): This inherited disorder causes severely elevated LDL cholesterol levels from birth 1

  • Affects approximately 1 in 311 people worldwide
  • Characterized by LDL cholesterol typically 2-3 times higher than normal levels
  • May present with physical signs like tendon xanthomas
  • Strong family history of premature cardiovascular disease

• Familial Combined Hyperlipidemia (FCHL):

  • Can mimic familial hypercholesterolemia phenotypically 2
  • Often presents with elevated total cholesterol and triglycerides
  • May not be associated with obesity

• Elevated Lipoprotein(a):

  • Can present as hyperlipidemia independent of BMI 2
  • Associated with increased cardiovascular risk
  • Found in approximately 44.7% of patients with phenotypic FH without mutations

Secondary Causes

• Endocrine Disorders:

  • Hypothyroidism: Reduces LDL receptor activity and clearance of LDL particles 1
  • Diabetes Mellitus: Can affect lipoprotein metabolism even in lean individuals 1

• Medications:

  • Progestins, anabolic steroids, and some immunosuppressants can elevate LDL cholesterol 1

• Dietary Factors:

  • High intake of saturated fats and trans fats despite low BMI
  • Excessive dietary cholesterol intake

Evaluation Approach

Initial Assessment

1. Detailed Family History:

   • Family history of premature cardiovascular disease (before age 55 in men, 65 in women) 3
   • Family history of hypercholesterolemia

2. Complete Lipid Panel:

   • Total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides
   • Non-HDL cholesterol calculation (Total cholesterol - HDL cholesterol) 3
   • For 17-19 year olds, concerning values include:
     • LDL cholesterol ≥ 130 mg/dL
     • Non-HDL cholesterol ≥ 145 mg/dL
     • HDL cholesterol < 40 mg/dL
     • Triglycerides ≥ 130 mg/dL 3

3. Additional Laboratory Tests:

   • Thyroid function tests (TSH, free T4)
   • Fasting glucose and HbA1c
   • Liver function tests
   • Lipoprotein(a) measurement

Genetic Testing

• Consider genetic testing for FH if LDL cholesterol ≥ 190 mg/dL or ≥ 160 mg/dL with family history of premature CVD 1

Management Considerations

Lifestyle Modifications

• Despite low BMI, dietary modifications are still important:
  • Limit saturated fat intake to <7% of total calories 1
  • Limit trans fat consumption to <1% of energy 1
  • Limit dietary cholesterol to <300 mg per day 1
  • Regular physical activity appropriate for underweight status

Pharmacological Therapy

• For confirmed FH:
  • Statins are first-line therapy
  • Ezetimibe may be added when LDL goals are not achieved with statins alone
  • PCSK9 inhibitors for patients not reaching targets with maximum tolerated statin plus ezetimibe 1

Important Caveats

1. Weight Status Consideration:

   • While hyperlipidemia is typically associated with higher BMI 4, genetic disorders can cause hyperlipidemia independent of weight
   • The low BMI (16.4) suggests malnutrition or another underlying condition that should be addressed concurrently

2. Age-Specific Screening:

   • Universal lipid screening is recommended for individuals 17-21 years of age 3
   • Repeat measurements are needed to confirm diagnosis (average of at least two measurements) 3

3. Risk Assessment:

   • Even at a young age, elevated lipids increase long-term cardiovascular risk
   • Early identification and treatment can prevent premature cardiovascular disease

4. Cascade Screening:

   • If genetic disorders are identified, family members should be screened 1

The combination of low BMI and hyperlipidemia strongly suggests a genetic or secondary cause rather than lifestyle-related dyslipidemia, making thorough evaluation essential for proper diagnosis and management.