#3040

This seems to be the best approach indeed: Efficacy of combination therapy with ezetimibe and statins versus a double dose of statin monotherapy in participants with hypercholesterolemia: a meta-analysis of literature | Lipids in Health and Disease

The addition of ezetimibe to statin appears to be more effective on reducing LDL-C and TC concentrations than doubling the statin dose.

See Fig. 2 here for rosuvastatin specifically: https://www.sciencedirect.com/science/article/pii/S0149291818300079

I wonder if there are trials looking at rosuvastatin 10 mg vs 5 mg + ezetimibe in terms of insulin resistance (HOMA-IR), new onset of diabetes, and fasting glucose. [Edit: I quickly searched and could only find a few small trials run for just a few weeks that showed either no significant difference between the two options or some benefits for adding ezetimibe. So TBC over longer periods of time.]

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What's the best statin to take?
#3041

I will try that, 5 mg rosuvastatin and 10 mg ezetimibe. I think based on all available information this seems like the best approach. Ezetimibe could be argued to be decreased to 5 mg as well but it doesn’t matter so much. It’s a very good stack to decrease risk of ASCVD and one I will test now.

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#3042

I believe Ezetimibe has no adverse effect on glucose metabolism and no statistically significant effect on NOD when combined with statins (IMPROVE-IT trial), but I remember in mouse studies some markers of glucose metabolism were improved with Ezetimibe.

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#3043

Yes, ezetimibe seems to improve glycemic control, endothelial function, and mitochondrial health in animal and cell models:

In humans, I could only find one not-so-recent meta-review: Effect of ezetimibe on glycemic control: a systematic review and meta-analysis of randomized controlled trials 2018

Compared with high-dose statin therapy, ezetimibe with low-dose statin for more than 3 months may have a beneficial tendency of effects on glycemic control.

But again, most studies are super short. This recent one, short as well (12w) found that “However, in our study, both HOMA-IR and HOMA-β were decreased only in the rosuvastatin/ezetimibe combination therapy group in which LDL-C was reduced by more than 50% from baseline. After adjusting for DM duration and hypertension, there was not a statistically significant difference in HOMA-IR change between the two groups. These results suggest that ezetimibe effects on insulin sensitivity might be influenced by several factors such as baseline insulin resistance and insulin secretory capacity.” (Comparative Efficacy of Rosuvastatin Monotherapy and Rosuvastatin/Ezetimibe Combination Therapy on Insulin Sensitivity and Vascular Inflammatory Response in Patients with Type 2 Diabetes Mellitus 2024)

On another note, I didn’t know that bempedoic acid led to a small weight loss (vs a small weight gain for statins): https://twitter.com/CMichaelGibson/status/1695452860815921635

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#3044

There are actually four ongoing trials looking at this question over longer periods of time:

For whatever reason, they’re ALL run in Korea, and in Korea only, by four different institutions.

(I guess if I had to start a lipid-lowering therapy, I’d start ezetimibe alone first, then, if needed, add bempedoic acid. Then wait and see and reassess the decision whenever more data is available…)

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#3045

Actually there’s this large recent trial (in Korea again!): Effect of moderate-intensity statin with ezetimibe combination vs. high-intensity statin therapy according to sex in patients with atherosclerosis 2023

3780 patients over 3 years, rosuvastatin 10 mg + ezetimibe vs rosuvastatin 20 mg. Conclusion:

LDL cholesterol levels of < 70 mg/dL at 1, 2, and 3 years were more frequently achieved in the ezetimibe combination group than in the high-intensity statin monotherapy group (all P < 0.001) in both sexes.

They write that “The effect of ezetimibe combination therapy for the 3-year composite outcomes was not different in both men and women. The benefits of ezetimibe combination therapy on LDL cholesterol lowering and drug tolerance were similarly observed regardless of sex.” However, ezetimibe might be more beneficial among men over the long run based on the trend below:

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It’s interesting because this MR indicated a potential pro-longevity effect of ezetimibe among men only as well: Ora Biomedical launches crowdfunding of Million Molecule Challenge - #69 by adssx

The improved treatment adherence in the statin+eze arm is also massive (especially among men):

The rate of discontinuation or dose reduction of study drugs due to intolerance was lower in the ezetimibe combination group than in the high-intensity statin monotherapy group in both women (4.5% vs. 8.6%, P = 0.014) and men (4.8% vs. 8.0%, P < 0.001).

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#3046

Given both sources (Carlson and Calley Means).

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#3047

A glass of wine will definitely not help you sleep better: it will sedate you, but that’s not naturalistic sleep. Put on an Oura ring or another good-quality sleep tracker with HRV and watch alcohol wreck your HRV and REM sleep and distort your overnight sleep resting heart rate “hammock” pattern.

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#3048

Who cares? --------===

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#3049

Well, anyone who wants their brains cleared of beta-amyloid, or their experiences encoded in memory, or their emotional regulation to be intact, or their executive function to operate, or to get any of the other benefits of naturalistic sleep.

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#3050

This seems to me to be a reasonable question. You’re used to having a glass of wine with dinner and you really enjoy it. You sleep fine - no trouble - 8 hours - and wake up feeling well rested. You’re healthy, get plenty of exercise, feel energetic - never tired. But then you start hearing about sleep quality and sleep monitors. So you get an Oura ring or whatever and you discover that yes that glass of wine is causing (previously unknown to you) your sleep quality score on your app to be poor. Is that something you should lose sleep over?

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#3051

I don’t think we should overly worry about Oura or other sleep tracker metrics at this point in time.

But there seems to be a lot of clinical data from sleep labs that show how alcohol materially worsens sleep architecture?

Differences in sleep quality over the years and decades seems to be something very significant - perhaps as impactful as the other main pillars that we can influence.

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#3052

I’m not questioning the science behind it. I’m sure that there is something there. But we all have to prioritize and make decisions. For example, it’s probably true that air pollution is worse in the cities. Should we all move to the country or up in the mountains. The science seems to increasingly be saying that any alcohol is bad, but if that glass of wine with dinner is one of your pleasures in life, what are the tradeoffs?

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#3053

Ok, I think I understand you now.

Each person will likely have a different decision on how to weigh the tradeoff. (Just thought it important that we all understand that it likely is a tradeoff).

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#3054

ISWYDT :wink:

You are 40 years old, going about your business, and feel absolutely fine. But you grow concerned about cardiovascular disease. So you go see your doctor, and she hooks you up to some devices. They say you have elevated blood pressure and apoB. Perhaps your sodium, saturated fat, or purine intake is too high and are causing (previously unknown to you) elevations in your BP and apoB. But you feel fine, and you will likely continue to feel fine for decades: at no point will you ‘sense’ that your BP and apoB are too high. Is that something you should lose sleep over?

You’ve just listed them.

Of course, you could look for alternative pleasures, including the new wave of increasingly-credible nonalcoholic wines.

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#3056

I think this is more what I’m getting at, and how the glass of wine ties into the rest of the thread. When someone is overall very fit and healthy and has what would be very good measures (ApoB or otherwise), when do the tradeoffs with your personal comfort level - whether it’s discomfort with taking statins or discomfort with giving up your glass of wine become worth it to achieve that last little percentile of health (like taking your ApoB from 58 to 30 or lower). There’s no (or little) disagreement on the science, perfect is better, but when you are already very good and it’s a small statistical improvement, you have to weigh that against your comfort level.
Not trying to derail this thread but from this article about a recent meta-analysis that said any alcohol is bad for your health, I quote:
" Stockwell says deciding whether and how much to drink is a personal choice. Based on his research, Stockwell estimates that someone who drinks one alcoholic beverage per day shaves about five minutes off their lifespan with each drink, and the losses compound at higher levels of consumption. Whether that’s an acceptable tradeoff, Stockwell says, is up to the drinker."
https://time.com/6267540/alcohol-premature-death-risks/
So one glass of wine per day would decrease your lifespan by 30 hours in a year. I’m 70 now, so by the time I’m a hundred, I would have decreased my lifespan by 38 days. Is that worth losing sleep over? For me…no.

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#3057

And here you have it…a scientific study: Moderate Red Wine Consumption Increases the Expression of Longevity-Associated Genes in Controlled Human Populations and Extends Lifespan in Drosophila melanogaster - PMC

" Our aim was to study the effect of red wine consumption on longevity-related genes in controlled human populations, such as cloistered nuns.The major shortcoming for nutritional intervention studies, especially those on nutrients like wine, is lifestyle. It is likely that individuals with moderate wine consumption also engage in other healthy habits, including stress control. Probably, the only populations that can be strictly controlled are monks and nuns who live in the same environment, with the same routines, and with controlled diets.It is important to underpin that the catholic nuns enrolled in this study had not drunk red wine in the previous two years. We did not use dealcoholized red wine in human studies because of the very low palatability. Our nuns refused to take the non-alcoholic red wine."

Conclusions

The major conclusions of our study are that moderate wine consumption increases the expression of key longevity-associated genes like p53, sirtuin1, catalase, and superoxide dismutase in humans. It also significantly increases longevity-associated gene expression and longevity itself in flies, thus showing that the effects are maintained across the animal kingdom. No serious unwanted side effects were observed.

#3058

… with a short-term, unvalidated surrogate outcome in blood cells :wink:

#3059

But You missed the main point - “We did not use dealcoholized red wine in human studies because of the very low palatability. Our nuns refused to take the non-alcoholic red wine.” Who said the penguins don’t have good taste?

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#3060

Looking at this study again (by US NIH + Oxford researchers in the JACC, so most likely high quality), I’ve just noticed the figure: although it didn’t reach statistical significance it seems that statins may be good for amyloid but bad for Lewy body dementia. (while PCSK9i are neutral for both) Do I understand things correctly? So it might explain the contradictory results in studies around statins and cognition. Could it be that for instance statins reduce the risk of vascular dementia and AD but increase the risk of PD and PDD/DPB/LBD? (pure guess) So they would be overall neutral on “dementia” but with different outcomes by subtype, and because it’s so hard to diagnose the subtypes (and people often have mixed dementia with all pathologies present) it could blur the results in studies. Please correct me if I’m wrong.

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