Cholesterol update

Medical Q&A [Moderated]
1

Jordan,
You gave me some advice on cholesterol back in May ((https://forum.barbellmedicine.com/forums/nutrition-q-a-with-dr-jordan-feigenbaum/37522-lowering-cholesterol)). I followed it, and now:
I meet the 2018 Activity Guidelines for Americans
I get ~6% of calories from saturated fat
My waist is 35" (from 37")
I lost 11lbs (196 down from 207)
I eat 8-10 servings of fruit & vegetables/day (up from 6) with >50g fiber

However, my blood lipids are now:
Total: 196 (down from 213)
HDL: 47 (basically unchanged from 48)
LDL: 132 (down from 139)
Triglycerides: 80 (down from 136)

Based on the Pooled Cohort Equation risk calculator referenced in your most excellent article on The Science of Red Meat and Health, my 10 year risk* of ASCVD is 0.9% and a statin is not recommended. I’m really happy with such a low risk number, but I can’t shake the thought that I still have “high cholesterol”.

My question is this: am I just supposed to wait until I’m 60 and go on a statin or is there anything else I can do in the mean time? Every non-statin cholesterol treatment I’ve researched (niacin, berberine, n3 fatty acids, plant sterols/stanols, bile acid sequestrants) seems to have no impact on mortality, CVD rates, or anything else meaningful (except maybe PCSK9 inhibitors).

Thanks again,
Rob

  • I’m only 37, so I input age 40 into the calculator to get a result
2

Nice work with the lifestyle changes!

There are no other lifestyle measures we’d recommend at this point. There are many genetic influences that may be at play here that may be beyond the ability of lifestyle interventions to alter.

As far as non-statin therapies, there are several with demonstrated efficacy for lowering CV risk including PCSK9 inhibitors, ezetimibe, bile acid sequestrants (which do in fact lower risk), fibrates (in certain cases), eicosapent ethyl, and a few other less commonly used treatments.

3

[quote=“Austin Baraki, post:2, topic:7621, username:Austin_Baraki”]
Nice work with the lifestyle changes!
[/quote]Thanks!

[quote=“Austin Baraki, post:2, topic:7621, username:Austin_Baraki”]
There are no other lifestyle measures we’d recommend at this point. There are many genetic influences that may be at play here that may be beyond the ability of lifestyle interventions to alter.
[/quote]Again, thank you. I’ll just keep on keepin’ on.

I probably should have been more careful with my wording - I was looking at those therapies for primary prevention as a monotherapy. My go-to resource has been Cochrane reviews, and based mostly on those, my take is:

PCSK9 inhibitors - “Large trials with longer follow-up are needed to evaluate PCSK9 inhibitors versus active treatments as well as placebo”, i.e. the jury’s still out.
Ezetimibe - “there is limited evidence regarding the role of ezetimibe in primary prevention and the effects of ezetimibe monotherapy in the prevention of CVD, and these topics thus requires further investigation”. Not much benefit but it looks like it reduces CV outcomes in people on maximal doses of statins though.
Bile acid sequestrants - reduced lipid values but I couldn’t find anything discussing risk when used as a monotherapy (only in conjunction with statins)
Fibrates - "Moderate-quality evidence suggests that fibrates lower the risk for cardiovascular and coronary events in primary prevention, but the absolute treatment effects in the primary prevention setting are modest (absolute risk reductions < 1%), so minimal practical benefit
Eicosapent ethyl - this looks really promising as an add-on to statin therapy, but I couldn’t find anything for its use as a monotherapy

Does my layman’s understanding generally align with your viewpoint? I truly appreciate the opportunity to discuss this with you and refine my understanding of the topic.

4

We would not agree with your take on PCSK 9 inhibitors, as they have demonstrated efficacy for primary and secondary risk reduction of cardiovascular events. Additionally, some of the other medications listed here have a bit more complicated relationship when used for primary risk reduction of ASCVD. I don’t think I agree with most of the text bytes listed here out of context.

That said, we would not recommend other non statin agents used as monotherapy for someone with an elevated ASCVD risk unless they could not tolerate statins therapy unless someone could not tolerate them, which is relatively rare.

In your case where the risk is 0.9%, there are no interventions that significantly lower your risk in a meaningful way. Maintaining this type of risk profile via diet, exercise, and other lifestyle interventions would be the recommendation.

-Jordan

5

Yeah, unfortunately getting into the details of the data here would take a lot more time than we have available.

But regarding PCSK9 inhibitors for example, I would agree that trials with longer follow up would be great to have, but it is important to point out that the main trials on those drugs demonstrated cardiovascular benefit even over a very short timeframe that was mediated by their reduction in LDL on top of statin therapy, and this is the type of benefit that grows larger over time. In other words, the fact that they were able to show risk reduction over a short period of time, for a disease that occurs very slowly, over the course of decades, isremarkable.

Any therapy that lowers blood levels of apoB-containing lipoprotein particles (including LDL-P) will lower cardiovascular risk.
https://www.nejm.org/doi/full/10.1056/NEJMra1806939

6

[quote=“Jordan Feigenbaum, post:4, topic:7621, username:Jordan_Feigenbaum”]

We would not agree with your take on PCSK 9 inhibitors, as they have demonstrated efficacy for primary and secondary risk reduction of cardiovascular events. Additionally, some of the other medications listed here have a bit more complicated relationship when used for primary risk reduction of ASCVD. I don’t think I agree with most of the text bytes listed here out of context.

[/quote] Interesting; I appreciate the feedback. I’ll keep perusing the literature to learn more.

That seemed to be the resounding consensus from what I saw: use a statin unless it’s not tolerated or the dose required to achieve the desired outcome is exorbitantly high.

[quote=“Jordan Feigenbaum, post:4, topic:7621, username:Jordan_Feigenbaum”]

In your case where the risk is 0.9%, there are no interventions that significantly lower your risk in a meaningful way. Maintaining this type of risk profile via diet, exercise, and other lifestyle interventions would be the recommendation.
[/quote] Crystal clear - got it.

Of course, and I’m grateful for what time you have given to the topic.

[quote=“Austin Baraki, post:5, topic:7621, username:Austin_Baraki”]
But regarding PCSK9 inhibitors for example, I would agree that trials with longer follow up would be great to have, but it is important to point out that the main trials on those drugs demonstrated cardiovascular benefit even over a very short timeframe that was mediated by their reduction in LDL on top of statin therapy, and this is the type of benefit that grows larger over time. In other words, the fact that they were able to show risk reduction over a short period of time, for a disease that occurs very slowly, over the course of decades, is remarkable.
[/quote] Hadn’t thought about the time aspect of it - makes sense.

Thanks for the links.