The Hidden Complexities of Statins and Cardiovascular Disease (CVD)

This is Dr. Barbara Roberts. She’s a cardiologist and the Director of the Women’s Cardiac Center at one of the Brown University Medical School teaching hospitals. She’s an Associate Clinical Professor of Medicine and takes care of patients, teaches medical students, and does clinical research. She specializes in gender-specific aspects of heart disease, and in heart disease prevention.

We previously reviewed Dr. Barbara Roberts’ excellent book “The Truth About Statins: Risks and Alternatives to Cholesterol-Lowering Drugs”. It prompted some requests to do a main feature about Statins, so we’re doing it today. It’s under the auspices of “Expert Insights” as we’ll be drawing almost entirely from Dr. Roberts’ work.

So, what are the risks of statins?

According to Dr. Roberts, one of the biggest risks is not just drug side-effects or anything like that, but rather, what they simply won’t treat. This is because statins will lower LDL (bad) cholesterol levels, without necessarily treating the underlying cause.

Imagine you got Covid, and it’s one of the earlier strains that’s more likely deadly than “merely” debilitating.

You’re coughing and your throat feels like you gargled glass.

Your doctor gives you a miracle cough medicine that stops your coughing and makes your throat feel much better.

(Then a few weeks later, you die, because this did absolutely nothing for the underlying problem)

You see the problem?

Are there problematic side-effects too, though?

There can be. But of course, all drugs can have side effects! So that’s not necessarily news, but what’s relevant here is the kind of track these side-effects can lead one down.

For example, Dr. Roberts cites a case in which a woman’s LDL levels were high and she was prescribed simvastatin (Zocor), 20mg/day. Here’s what happened, in sequence:

1. She started getting panic attacks. So, her doctor prescribed her sertraline (Zoloft) (a very common SSRI antidepressant) and when that didn’t fix it, paroxetine (Paxil). This didn’t work either… because the problem was not actually her mental health. The panic attacks got worse…
2. Then, while exercising, she started noticing progressive arm and leg weakness. Her doctor finally took her off the simvastatin, and temporarily switched to ezetimibe (Zetia), a less powerful nonstatin drug that blocks cholesterol absorption, which change eased her arm and leg problem.
3. As the Zetia was a stopgap measure, the doctor put her on atorvastatin (Lipitor). Now she got episodes of severe chest pressure, and a skyrocketing heart rate. She also got tremors and lost her body temperature regulation.
4. So the doctor stopped the atorvastatin and tried rosovastatin (Crestor), on which she now suffered exhaustion (we’re not surprised, by this point) and muscle pains in her arms and chest.
5. So the doctor stopped the rosovastatin and tried lovastatin (Mevacor), and now she had the same symptoms as before, plus light-headedness.
6. So the doctor stopped the lovastatin and tried fluvastatin (Lescol). Same thing happened.
7. So he stopped the fluvastatin and tried pravastatin (Pravachol), without improvement.
8. So finally he took her off all these statins because the high LDL was less deleterious to her life than all these things.
9. She did her own research, and went back to the doctor to ask for cholestyramine (Questran), which is a bile acid sequestrent and nothing to do with statins. She also asked for a long-acting niacin. In high doses, niacin (one of the B-vitamins) raises HDL (good) cholesterol, lowers LDL, and lowers tryglycerides.
10. Her own non-statin self-prescription (with her doctor’s signature) worked, and she went back to her life, her work, and took up running.

Quite a treatment journey! Want to know more about the option that actually worked?

Read: Bile Acid Resins or Sequestrants

What are the gender differences you/she mentioned?

A lot of this is still pending more research—basically it’s a similar problem in heart disease to one we’ve previously talked about with regard to diabetes. Diabetes disproportionately affects black people, while diabetes research disproportionately focuses on white people.

In this case, most heart disease research has focused on men, with women often not merely going unresearched, but also often undiagnosed and untreated until it’s too late. And the treatments, if prescribed? Assumed to be the same as for men.

Dr. Roberts tells of how medicine is taught:

❝When I was in medical school, my professors took the “bikini approach” to women’s health: women’s health meant breasts and reproductive organs. Otherwise the prototypical patient was presented as a man.❞

There has been some research done with statins and women, though! Just, still not a lot. But we do know for example that some statins can be especially useful for treating women’s atherosclerosis—with a 50% success rate, rather than 31% for men.

For lowering LDL, it can work but is generally not so hot in women.

Fun fact:

In men:

• High total cholesterol
• High non-HDL cholesterol
• High LDL cholesterol
• Low HDL cholesterol

…are all significantly associated with an increased risk of death from CVD.

In women:

…levels of LDL cholesterol even more than 190 were associated with only a small, statistically insignificant increased risk of dying from CVD.

So…

The fact that women derive less benefit from a medicine that mainly lowers LDL cholesterol, may be because elevated LDL cholesterol is less harmful to women than it is to men.

And also: Treatment and Response to Statins: Gender-related Differences

And for that matter: Women Versus Men: Is There Equal Benefit and Safety from Statins?*

Definitely a case where Betteridge’s Law of Headlines applies!

What should women do to avoid dying of CVD, then?

First, quick reminder of our general disclaimer: we can’t give medical advice and nothing here comprises such. However… One particularly relevant thing we found illuminating in Dr. Roberts’ work was this observation:

The metabolic syndrome is diagnosed if you have three (or more) out of five of the following:

1. Abdominal obesity (waist >35″ if a woman or >40″ if a man)
2. Fasting blood sugars of 100mg/dl or more
3. Fasting triglycerides of 150mg/dl or more
4. Blood pressure of 130/85 or higher
5. HDL <50 if a woman or <40 if a man

And yet… because these things can be addressed with exercise and a healthy diet, which neither pharmaceutical companies nor insurance companies have a particular stake in, there’s a lot of focus instead on LDL levels (since there are a flock of statins that can be sold be lower them)… Which, Dr. Roberts says, is not nearly as critical for women.

So women end up getting prescribed statins that cause panic attacks and all those things we mentioned earlier… To lower our LDL, which isn’t nearly as big a factor as the other things.

In summary:

Statins do have their place, especially for men. They can, however, mask underlying problems that need treatment—which becomes counterproductive.

When it comes to women, statins are—in broad terms—statistically not as good. They are a little more likely to be helpful specifically in cases of atherosclerosis, whereby they have a 50/50 chance of helping.

For women in particular, it may be worthwhile looking into alternative non-statin drugs, and, for everyone: diet and exercise.

Further reading: How Can I Safely Come Off Statins?

Wholesome Health

This is Dr. Sara Gottfried, who some decades ago got her MD from Harvard and specialized as an OB/GYN at MIT. She’s since then spent the more recent part of her career educating people (mostly: women) about hormonal health, precision, functional, & integrative medicine, and the importance of lifestyle medicine in general.

What does she want us to know?

Beyond “bikini zone health”

Dr. Gottfried urges us to pay attention to our whole health, in context.

“Women’s health” is often thought of as what lies beneath a bikini, and if it’s not in those places, then we can basically treat a woman like a man.

And that’s often not actually true—because hormones affect every living cell in our body, and as a result, while prepubescent girls and postmenopausal women (specifically, those who are not on HRT) may share a few more similarities with boys and men of similar respective ages, for most people at most ages, men and women are by default quite different metabolically—which is what counts for a lot of diseases! And note, that difference is not just “faster” or “slower””, but is often very different in manner also.

That’s why, even in cases where incidence of disease is approximately similar in men and women when other factors are controlled for (age, lifestyle, medical history, etc), the disease course and response to treatment may vary considerable. For a strong example of this, see for example:

• The well-known: Heart Attack: His & Hers ← most people know these differences exist, but it’s always good to brush up on what they actually are
• The less-known: Statins: His & Hers ← most people don’t know these differences exist, and it pays to know, especially if you are a woman or care about one

Nor are brains exempt from his…

The female brain (kinda)

While the notion of an anatomically different brain for men and women has long since been thrown out as unscientific phrenology, and the idea of a genetically different brain is… Well, it’s an unreliable indicator, because technically the cells will have DNA and that DNA will usually (but not always; there are other options) have XX or XY chromosomes, which will usually (but again, not always) match apparent sex (in about 1/2000 cases there’s a mismatch, which is more common than, say, red hair; sometimes people find out about a chromosomal mismatch only later in life when getting a DNA test for some unrelated reason), and in any case, even for most of us, the chromosomal differences don’t count for much outside of antenatal development (telling the default genital materials which genitals to develop into, though this too can get diverted, per many intersex possibilities, which is also a lot more common than people think) or chromosome-specific conditions like colorblindness…

The notion of a hormonally different brain is, in contrast to all of the above, a reliable and easily verifiable thing.

See for example:

Alzheimer’s Sex Differences May Not Be What They Appear

Dr. Gottfried urges us to take the above seriously!

Because, if women get Alzheimer’s much more commonly than men, and the disease progresses much more quickly in women than men, but that’s based on postmenopausal women not on HRT, then that’s saying “Women, without women’s usual hormones, don’t do so well as men with men’s usual hormones”.

She does, by the way, advocate for bioidentical HRT for menopausal women, unless contraindicated for some important reason that your doctor/endocrinologist knows about. See also:

Menopausal HRT: A Tale Of Two Approaches (Bioidentical vs Animal)

The other very relevant hormone

…that Dr. Gottfried wants us to pay attention to is insulin.

Or rather, its scrubbing enzyme, the prosaically-named “insulin-degrading enzyme”, but it doesn’t only scrub insulin. It also scrubs amyloid beta—yes, the same that produces the amyloid beta plaques in the brain associated with Alzheimer’s. And, there’s only so much insulin-degrading enzyme to go around, and if it’s all busy breaking down excess insulin, there’s not enough left to do the other job too, and thus can’t break down amyloid beta.

In other words: to fight neurodegeneration, keep your blood sugars healthy.

This may actually work by multiple mechanisms besides the amyloid hypothesis, by the way:

The Surprising Link Between Type 2 Diabetes & Alzheimer’s

Want more from Dr. Gottfried?

You might like this interview with Dr. Gottfried by Dr. Benson at the IMCJ:

Integrative Medicine: A Clinician’s Journal | Conversations with Sara Gottfried, MD

…in which she discusses some of the things we talked about today, and also about her shift from a pharmaceutical-heavy approach to a predominantly lifestyle medicine approach.

Enjoy!