Beyond LDL: Rethinking Women’s Heart Disease Risk

The cholesterolization of heart disease was premature, extreme, and narrow-minded.

We have culturally and medically adopted this theory: high cholesterol means high risk of heart disease.

In particular, we've focused on LDL cholesterol or "bad" cholesterol.

It turns out, there's a lot more to this story that's still being discovered.

What is cholesterol?

Cholesterol is a waxy substance transported around the body in various vehicles, or lipoproteins.

High Density Lipoprotein (HDL) scavenges cholesterol and delivers in back to the liver for processing, while Low Density Lipoprotein (LDL) delivers cholesterol out to the body. This is why HDL has been dubbed "good" and LDL "bad".

What is cholesterol used for in the body?

It's not the demon we've been taught. It's vital to bodily function.

Cell membranes: every cell in our body is surrounded by a membrane of lipids (fats) containing cholesterol.

Hormones: cholesterol is the back bone of the hormones we love so much: estrogen, progesterone, testosterone.

Vitamin D: cholesterol is also a precursor to vitamin D formation.

Eyes: the cell membranes in the lens of the eye are solely made up of cholesterol.

What are the types of cholesterol on a standard lipid panel?

A standard lipid panel will typically check:

• Total cholesterol

• Triglycerides

• LDL (Low Density Lipoprotein)

• HDL (High Density Lipoprotein)

• VLDL (Very Low Density Lipoprotein)

And often ratios of those to each other.

What lipids are on an expanded lipid panel?

• ApoB:

  • A particle carried by all "bad" cholesterol lipoproteins

  • More associated with heart disease risk than LDL

    
    

• ApoAl

  • Protein component of HDL

  • Has anti-inflammatory capacity and is decreased by inflammatory states

    
    

• Lp(a):

  • A type of LDL particle

  • Strong genetic and ethnic component

  • consider checking once

Size Matters

Sorry to the guys, it's official: size matters.

Smaller and more dense particles are associated with higher heart risk. Presumably these smaller particles have an easier time penetrating the blood vessel lining (called the endothelium)

Particle size may also be tested on an expanded lipid panel.

When it comes to our cholesterol particles, bigger is better.

What do we know about women specifically?

We know more now about the lipid profiles and metabolism of women, particularly midlife women, decades after statins have been widely prescribed to women.

With the hormonal changes of menopause, we may see increases in LDL, triglycerides, apoB while seeing decreasing HDL.

Inflammation and arterial stiffness also increase with the menopause transition, signs of vascular dysfunction.

Statins in women

26% of women over 40 are on a statin.

Presumably, this is to prevent a heart attack or death from a heart attack.

It turns out this has not been shown in the data.

Could this be because women are not studied or under studied in statin trials? It could be. Only 21 of 1500 trials studied women. Of those, only nine published the data by sex. That means the others had results lumped together for men and women.

Or could it be because they don't work the same for women as they do for men?

We could start by studying things appropriately in women.

According to the American Heart Association in their 2020 document on the menopause transition and heart health, data supporting statins preventing heart attacks and death are lacking.

Yet, the recommendations for adults to be on statins does not distinguish between men and women.

Other therapies

Like statins, other cholesterol-lowering therapies have not been adequately studied in women.

Therapies aimed to increase HDL ("good cholesterol") have not shown benefit and in fact, one trial (the ILLUMINATE trial) was stopped early due to increased cardiac events and mortality.

What can women do?

• Ask for an expanded lipid panel, as discussed above

  
  

• Decrease inflammation:

  • I mentioned the endothelium (the blood vessel lining) as the point of entry for lipoproteins that cause heart disease

  • Endothelial dysfunction is a core abnormality in metabolic diseases, including during pregnancy.

  • Maintaining healthy endothelium is therefore very important

  • This can be done by: sleeping, eating unprocessed foods, reducing stress, exercising

    
    

• Honor circadian rhythm:

  • See natural light first thing in the morning

  • Avoid artificial light, especially at night

  • Sleep

    
    

• Use HRT if you're an appropriate candidate

  • Hormone Replacement Therapy or our natural hormones help maintain our insulin

  • sensitivity and typical female fat distribution

    
    

• Use transdermal (skin patch) estradiol rather than oral (tablet) estradiol if using HRT

  • Skin patch HRT bypasses liver metabolism which is where cholesterol and clotting factor metabolism takes place

    
    

• Eat fat:

  • Higher fat diets (30% of daily intake) are associated with improved particle sizes of lipoproteins

  • Eggs DO NOT increase the risk of abnormal lipids.

    
    

• Cut carbs:

  • No one wants to be told this, but it's the truth

  • Carbohydrates in excess will be converted into Triglycerides (on your cholesterol panel) and stored as fat

    
    

• Limit total energy intake:

  • Weight loss by a chronic energy deficit is associated with improved lipids

  • Alternate day fasting or "acute energy deficit" is also associated with improved lipids.

    
    

• Do not smoke

  • Smoking is independently associated with heart disease and death

  • This is damaging to the endothelium

    
    

• Build muscle

  • This will maintain insulin sensitivity (rather than resistance)

I'm not anti-medicine.

I'm not anti-prescription (most HRT I prescribe is via prescription).

I am anti-blind trust.

I am anti-blind spots in medicine, while medicine pretends it's all figured out.

I am pro-nuance.

The difference between men and women is too much to ignore.

Resources:

Some of the information contained in this article is the result of my training, medical knowledge, and personal experience without a specific source to be cited.

Disclaimer: This is not medical advice. This is for educational purposes only. Discuss with your doctor.

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Harvard Health Publishing (2014). Should you seek advanced cholesterol testing?. Retrieved from https://www.health.harvard.edu/womens-health/should-you-seek-advanced-cholesterol-testing-

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