AnUser
#1029
See, no reason to get up in their face and be angry at them for their sign.
OK guys - back on topic please
1 Like
ng0rge
#1031
Gee Dad, it was all @desertshores fault…I was just quietly playing tiddlywinks…
OK, my turn to stir the pot:
Higher levels of a certain gut microbiome may lead to a higher risk of heart failure, independent of other risk factors, a new study from the Cleveland Clinic and Tufts University suggests.
Researchers focused on the gut microbiome trimethylamine N-oxide pathway, TMAO. Findings were recently published in the journal Circulation: Heart Failure.
3 Likes
adssx
#1033
High cholesterol absorption: A risk factor of atherosclerotic cardiovascular diseases? 2023
High cholesterol absorption is relatively frequent in humans. In a general population, about one third were found to be high cholesterol absorbers (>60% cholesterol absorption). According to the results of genetic, metabolic, and population-based studies and lipid-lowering interventions, it seems evident that statin monotherapy neither reduces ASCVD events nor improves plaque regression in individuals with high cholesterol absorption efficiency. Thus, these results confirm the original findings in the 4S trial. Statin monotherapy is also inferior to the combination of statin-ezetimibe therapy in high cholesterol absorbers.
Both treatment regimens can be combined with statins to achieve an additive reduction in LDL-C concentrations. This is important because statins inhibit the ezetimibe- and phytostanol–induced activation of cholesterol synthesis, and on the other hand ezetimibe and phytostanol ester inhibit the statin-induced increase in cholesterol absorption. Since there is noteworthy prevalence of high cholesterol absorption in the general population, it is important to identify high-absorbers. Optimal treatment therapy for them includes both reduction of cholesterol absorption and cholesterol synthesis in order to effectively reduce the risk of ASCVDs.
If this paper (shared by DrLipid) is correct, shouldn’t hyperabsorbers only use ezetimibe and hypoabsorbers only use statins? Could this explain why ezetimibe + statins isn’t significantly better in RCTs vs statins alone as they look at the overall population without distinguishing the absorption efficiency?
I would be great to have a trial where they first test people and depending on their absorption efficiency give them ezetimibe, statin or the combination.
Good to know: x.com
[EDIT: I might be wrong, the boss says “Even cholesterol hyperabsorbers will have some response to statins & likewise cholesterol hypersynthesizers still get lipid-lowering benefit from ezetimibe.”]
3 Likes
adssx
#1034
This chart only shows the average. When you display the min, max, median, and first and third quartile, it’s a different story (source):
There’s a huge variability and only the higher doses are effective (LDL reduction > 0%) in most (>75%) people.
1 Like
mccoy
#1035
I would read the graph a little differently, please check if I’m right or wrong. Outliers are not usually considered in such a discussion since they probably reflect some rare anomaly in lipids metabolism
-With the higher dose (10 mg) LDL reduction > 0% in ALL the sample (100%).
-With lower doses, 1 to 5 mg, LDL reduction > 0% in ALL or nearly aLL the sample (about 99-100%).
But, ruling out the distribution extremes, it is striking again to see how the median difference in reduction between 1 and 5 mg is almost nihil.
2 Likes
mccoy
#1036
I think you are right, I’ll have to read the paper but do I remember well Dr Lipid saying that using statins in hyperabsorbers would cause an even greater absorption, by hyperactivation of the Nieman-pick receptors?
When we start a medical intervention without an idea of our position in the absorbers’ distribution, we are apparently making a bet. The combo statins+ezetimibe conceptually might be seen as hedging the bet.
Another strategy, excluding the specific sophisticated analyses on absorption markers, would be to start with a single drug only and watching the results, this will make clear if we lean towards the hyper or the hypo absorbers.
2 Likes
adssx
#1037
You’re right, I edited my comment, thanks for correcting my mistake!
1 Like
mccoy
#1038
NP, that’s a very eloquent graph and conceptually reminds us that the response is not a single number but rather a random variable, without prior knowledge we may sit anywhere along that distribution.
Also, it reminds us that, when we see a claim: “It lowered LDL-C up to 38%”, that it refers to the 100th percentile, which represents only the most optimistic case.
2 Likes
adssx
#1039
Exactly. The paper I shared above concludes: “In the absence of effective and practical solutions to diagnose high cholesterol absorbers, combination lipid-lowering therapy (statin + ezetimibe) should be the first-line strategy, not only in very high-risk patients but in all subjects prescribed cholesterol–lowering drug treatment.”
mccoy
#1040
I also found a sentence which is related to Dr. Lipid’s words about this interesting mechanism of conservation of cholesterol concentration, where a reduction in cholesterol synthesis brings about an increase in cholesterol absorption and the other way around.
…
This is important because statins inhibit the ezetimibe- and phytostanol–induced activation of cholesterol synthesis, and on the other hand ezetimibe and phytostanol ester inhibit the statin-induced increase in cholesterol absorption.
Re: synthesis, let’s not sleep on bempedoic acid. That is going to be my approach. Right now I’m on 10mg atorvastatin, and while it did lower my LDL somewhat, it is still well above 100. So I’m going to add bempedoic acid 180mg + ezetimibe 10mg, courtesy of Indian pharmacies. I’ll see what this does for my lipids.
3 Likes
The sweet spot for atorvastatin is somewhere between 20mg and 40mg for LDL-C reduction, safety and support in studies.
Atorvastatin 5 mg lowered my ApoB from 67 to 48, so even a low dose is quite powerful.
6 Likes
RapAdmin, can I just say, you are a stellar contributor who finds just the best stuff! As happens, the very high HDL score and CAC of zero at age 66, is highly relevant to me, because those are my numbers. So a sincere thank you for this and all that you do 
3 Likes
mccoy
#1047
The article looks extremely interesting and carries a practical individualizable procedure that can be of use to anyone of us interested into keeping CV risk below an acceptable threshold. I wonder if we should open a separate topic for this, the discussion may take some time. I intend to use this procedure for personalized intervention.
OK, for all those specifically interested, I opened a specific thread.
4 Likes
adssx
#1048
From what I remember the article doesn’t give any quantitative threshold so is fairly useless, no?
1 Like
