Statins

My view on statins

Having had bypass surgery, I’m a prime candidate for statins - high risk for an event. My heart doctor called me a couple times after my surgery. I told him I was not taking the statin - and he could not understand why.

The biggest thing for me was statins are marketed using relative risk - versus the absolute risk. “You are 50% less likely to have an event if you take the statin”. Even though the absolute risk is miniscule. I felt I was being misled.

Then I discovered doctors, mostly from the UK (socialist medicine where the data is more transparent than in the US - where data is siloed - or hidden) who did not believe in them either - that you could do the same thing with lifestyle changes.

Studies, reviews, double blind - where’s your sources! Studies that showed that cholesterol is good and statins may do more harm than good (dementia) were/are hidden. ¹

And then there is the not insignificant fact that cholesterol is needed by our bodies.

So, that is a hill that I may die on.  😛

The rise of statins

The rise of statins and the controversy surrounding LDL (low-density lipoprotein) cholesterol is an interesting topic in modern medicine. Here is a concise overview of the key points:

1. Statins were first approved in 1987 ² and quickly became one of the most profitable classes of drugs worldwide.
2. They work by inhibiting an enzyme involved in cholesterol production, effectively lowering LDL cholesterol levels.
3. Statins have been shown to reduce the risk of cardiovascular events in many large clinical trials.

Absolute vs Relative risk

1. Relative risk reduction often exaggerates the benefits of statins compared to absolute risk reduction:

• The JUPITER trial reported a 54% relative risk reduction for myocardial infarction mortality with rosuvastatin. However, the absolute risk reduction was only 0.41 percentage points (from 0.76% to 0.35%)³.

• A study on long-term statin treatment reported a 28% relative risk reduction in coronary heart disease deaths, but the absolute risk reduction was only 2.3% (from 9% to 6.7%)⁴.

2. Presenting only relative risk without absolute risk is considered misleading:

• Gigerenzer et al. called this practice “incomplete and misleading risk information”.
• It can lead to overestimation of treatment benefits by both patients and physicians.

3. The absolute risk reduction with statins is often quite small:

• In the JUPITER trial example, the absolute risk reduction was 0.41%. ⁵
• In the 20-year follow-up study, the absolute risk reduction in coronary deaths was 2.3%.

4. Number Needed to Treat (NNT) helps put absolute risk reduction in perspective:

• For all-cause mortality prevention, one study found an NNT of 167 over 4.1 years.
• For preventing one major coronary event, the NNT was 77.

5. Proper risk communication is crucial:

• Presenting both relative and absolute risk allows for more informed decision-making.
• Framing risk information differently can significantly impact patient and physician perceptions.

6. Media often reports relative risk without context:

• Headlines like “X TRIPLES your risk for cancer” can be misleading without absolute risk information.

7. Consideration of potential harms is also important:

• When absolute benefits are small, potential side effects of statins become more relevant in decision-making.

In conclusion, while statins do provide benefits in cardiovascular risk reduction, the absolute risk reduction is often much smaller than the relative risk reduction suggests. Proper communication of both measures is essential for informed decision-making by patients and healthcare providers.⁶

LDL Controversy:

1. LDL has long been dubbed “bad cholesterol” due to its association with heart disease.
2. The “lipid hypothesis” suggests that lowering LDL cholesterol reduces cardiovascular risk.
3. However, some researchers argue that the relationship between LDL and heart disease is more complex than initially thought.

Key points of controversy:

1. Over-prescription: Some argue statins are prescribed too liberally, especially for primary prevention in low-risk individuals.
2. Side effects: While generally well-tolerated, statins can cause muscle pain and, rarely, more serious side effects.
3. Absolute vs. relative risk reduction: Critics argue that the benefits of statins are often overstated in terms of relative risk reduction rather than absolute risk reduction.
4. Role of inflammation: Some researchers suggest that inflammation, rather than LDL itself, may be the primary driver of heart disease.
5. Questioning the lipid hypothesis: A minority of researchers challenge the causal relationship between LDL and heart disease.

Lean Mass Hyper-Responders

”Lean Mass Hyper-Responders” (LMHR) is an interesting and relatively recent development in the field of lipidology and cardiovascular health. Let me break this down:

LMHRs are individuals who exhibit a significant increase in LDL cholesterol levels, often while following a low-carbohydrate or ketogenic diet. They typically have these characteristics:

1. LDL cholesterol ≥ 200 mg/dL
2. HDL cholesterol ≥ 80 mg/dL
3. Triglycerides ≤ 70 mg/dL
4. Low body fat percentage and high muscle mass

Key points about LMHRs:

1. Diet correlation: This phenotype is often observed in individuals following low-carb, high-fat diets.

2. Metabolic health: Despite high LDL levels, these individuals often display other markers of good metabolic health (low triglycerides, high HDL, good insulin sensitivity).

3. Cardiovascular risk uncertainty: The long-term cardiovascular risk for this group is not well understood, as they don’t fit the traditional risk profile.

4. Lipid energy model: Some researchers propose that in LMHRs, high LDL levels might be a result of increased lipid trafficking for energy, rather than a sign of metabolic dysfunction.

5. Genetic factors: There may be genetic predispositions that contribute to this response.

6. Research gaps: This phenotype is not yet well-studied, and more research is needed to understand its implications fully.

7. Clinical dilemma: The high LDL levels in these otherwise healthy individuals present a challenge for clinicians in terms of risk assessment and treatment decisions.

8. Controversy: The existence of healthy individuals with very high LDL levels challenges some aspects of the traditional lipid hypothesis.

Cholesterol is vitally necessary for human health

1. Cell membrane structure: Cholesterol is a key component of cell membranes, providing stability and fluidity.

2. Hormone production: It’s a precursor for steroid hormones, including:

   • Sex hormones (testosterone, estrogen, progesterone)
   • Adrenal hormones (cortisol, aldosterone)

3. Vitamin D synthesis: Cholesterol is converted to vitamin D when skin is exposed to sunlight.

4. Bile acid production: Cholesterol is used to produce bile acids, which are essential for fat digestion.

5. Brain function: The brain contains about 25% of the body’s cholesterol, crucial for neurotransmitter release and synapse formation.

6. Myelin sheath: Cholesterol is a major component of myelin, which insulates nerve fibers.

7. Cellular signaling: It plays a role in intracellular communication and signal transduction.

8. Antioxidant functions: Cholesterol can act as an antioxidant, protecting against free radical damage.

9. Immune system: It’s involved in the function of immune cells and the inflammatory response.

10. Fetal development: Cholesterol is critical for proper fetal development, especially of the brain and nervous system.

The body tightly regulates cholesterol levels, with most being produced endogenously rather than obtained from diet. The liver typically adjusts its production based on dietary intake. ⁷

While high levels of certain cholesterol fractions (particularly oxidized LDL) are associated with cardiovascular risk, it’s important to recognize cholesterol’s vital physiological roles. The debate in medical science isn’t about whether cholesterol⁸ is necessary (it absolutely is), but rather about what constitutes optimal levels and how to balance cardiovascular risk with the body’s need for this essential molecule.

💡 Tip: Instead of seeing if your LDL is high (and getting a statin) look at your Triglyceride / HDL level. If it is 2 or less (100/50) - you are golden.