Link to Buck's Results:

https://drive.google.com/file/d/19BJaZNYwBxlPx4nR9695Q2NC3nNpgW6y/view?usp=sharing

https://drive.google.com/file/d/1br1ikAJKmgKev9X3jkS7nUPdXpAqMzYd/view?usp=sharing

Section 1: Overview of Cholesterol Metabolism

• Cholesterol in the Body:
  • Cholesterol is essential for cell membrane integrity, hormone synthesis, and bile acid production.
  • It is produced endogenously in the liver and absorbed exogenously from dietary sources.
• Endogenous Production:
  • Cholesterol is synthesized in the liver through the mevalonate pathway.
  • Key intermediates: Lathosterol and Desmosterol, indicators of cholesterol production rate.
• Exogenous Absorption:
  • Dietary cholesterol is absorbed in the intestines along with plant sterols like Beta-sitosterol and Campesterol.
  • These sterols compete with cholesterol for absorption, reflecting dietary cholesterol absorption levels.

Section 2: Detailed Analysis of the Test Components

• Production Markers:
  • Lathosterol:
    • Precursor in the cholesterol biosynthesis pathway.
    • Elevated levels indicate increased hepatic cholesterol synthesis (overproduction).
    • Example: Lathosterol level of 329 µmol x 100/mmol in my study indicates hyperactive cholesterol production.
  • Desmosterol:
    • Another precursor in the synthesis pathway, contributing to total cholesterol production.
    • High levels reinforce the diagnosis of increased cholesterol production.
    • Example: Desmosterol level of 74 µmol x 100/mmol in my study supports elevated production.
• Absorption Markers:
  • Beta-sitosterol:
    • Plant sterol absorbed in the intestines, competes with cholesterol.
    • High levels suggest increased absorption of dietary cholesterol.
    • Example: Beta-sitosterol level of 120 µmol x 100/mmol indicates borderline absorption.
  • Campesterol:
    • Similar to Beta-sitosterol, reflects cholesterol absorption efficiency.
    • Elevated levels indicate increased absorption.
    • Example: Campesterol level of 113 µmol x 100/mmol within normal limits but suggests absorption could be a factor.
• Cholesterol Balance Score:
  • Ratio of production to absorption markers.
  • A higher score indicates predominant cholesterol production; a lower score indicates absorption as the main issue.
  • Example: Score of 2.4 suggests overproduction is the dominant issue.

Section 3: Clinical Implications and Treatment Strategies

• Frequency of Overproduction vs. Overabsorption:
  • Common to see patients with either overproduction or overabsorption, but less commonly both.
  • Overproducers: Significant portion of hypercholesterolemia patients, especially those with genetic conditions like Familial Hypercholesterolemia.
  • Overabsorbers: Often have high-cholesterol diets or genetic predispositions.
• Treatment Implications:
  • Overproducers: Statins are first-line treatment; they inhibit HMG-CoA reductase in cholesterol synthesis.
  • Overabsorbers: Ezetimibe, which inhibits intestinal cholesterol absorption, can be effective.
  • Combination Therapy: Considered for mixed dyslipidemia cases.
• Case Examples:
  • Example of a patient with high production markers but borderline absorption: Statin therapy may be appropriate, with potential addition of Ezetimibe.
  • Example of a patient who is a high absorber but not a high producer: Dietary changes and Ezetimibe might suffice without statins.

Section 4: Physiological Mechanisms and Genetic Considerations

• Pathophysiology of Cholesterol Production:
  • Overproduction may result from genetic mutations (LDL receptor or PCSK9) or conditions like insulin resistance.
• Pathophysiology of Cholesterol Absorption:
  • Increased absorption could be due to genetic polymorphisms (NPC1L1 gene), leading to higher dietary cholesterol absorption.

Section 5: Practical Application in Clinical Practice

• Incorporating the Test into Clinical Workflow:
  • Integrate the Boston Heart Cholesterol Balance Test for patients with unexplained hypercholesterolemia or non-responders to standard therapy.
  • Tailor treatment based on whether a patient is an overproducer, an over absorber, or both.
• Patient Communication:
  • Explain test results in an understandable way, emphasizing personalized treatment plans.