The issue is that the variables differ by individual, so such global averages must be seen in that light. For some, a given level of ApoB/LDL exposure over time might result in less/more plaque accumulation. So I’m not going to excitedly calculate my exposure according to these graphs. My CAC score at 65 is zero - are these formulas relevant to me?
Given such individual variability, doesn’t it make sense to have regular CAC score tests? As your age increases, the value of the test goes up. But for some unlucky folks who have more accumulation of plaque at lower lipid levels at a shorter time frame, a CAC score test at 35 might catch a problem earlier. So it seems advisable for everyone to get a CAC test early, like 30’s, to catch aggressive plaque development - a kind of screening tool.
But as a precautionary measure you obviously want to lower your ApoB levels as early as possible, at least to below LDL of 70 or so.
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mccoy
#1140
The model presented reflects the average risk of a whole population, or cohort, subjected to a determined cumulative exposure to LDL-C . Sometimes these models may report the variability in response, with percentiles, quartiles and so on. An individual like you with a zero CAC at 65 may perhaps consider him/herself in the lower percentiles of risk, a low responder to LDL-C, as it were.
This inference is not possible in the Ference et al. model.
Of course the above assuming that CAC score at determined ages really reflects the state of responder or not responder to LDL-C
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Neo
#1141
@JeffW @forceofnature which lab are these with
I’m always below the threshold with Quest, but that threshold is higher
Anyone is US know how to measure even more sensitive than <0.15?
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Jonas
#1143
Average person don’t have access to IL-6 blockers, how about a low does intermittent prednisone which is used in conditions characterized by inflammation or immune system overactivity.
https://www.nature.com/articles/s41586-024-07282-7
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adssx
#1144
Cardiovascular benefits of statin plus ezetimibe combination therapy versus statin monotherapy in acute coronary syndrome: a meta-analysis of randomized controlled trials 2024
Six RCTs comprising 20 574 patients with ACS were included, of whom 10 259 (49.9%) were prescribed ezetimibe plus statin. The patient population had an average age of 63.8 years, and 75.1% were male. Compared with statin monotherapy, ezetimibe plus statin significantly reduced major adverse cardiovascular events (MACE) (risk ratio 0.93; 95% CI 0.90–0.97; P < 0.01) and nonfatal myocardial infarction (risk ratio 0.88; 95% CI 0.81–0.95; P < 0.01). There was no significant difference between groups for revascularization (risk ratio 0.94; 95% CI 0.90–1.00; P = 0.03), all-cause mortality (risk ratio 0.87; 95% CI 0.63–1.21; P = 0.42), or unstable angina (risk ratio 1.05; 95% CI 0.86–1.27; P = 0.64).
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Bempedoic acid is a relatively newish entrant into the ApoB/LDL lowering space. No question that BA lowers LDL. It also appears to lower MACE rates in statin intolerant subjects. Well, statin intolerant might be physiologically different from statin tolerant, so the question becomes does BA work equally well in statin tolerant to lower MACE rates.
More saliently, is BA equally effective as statins in lowering CV events per unit of lowered LDL.
It appears that perhaps yes:
Good authors and institutions, but suboptimal conflicts of interest.
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adssx
#1146
BA seems good, but its safety profile is not as good as ezetimibe. And it doesn’t lower LDL much. If obicetrapib is approved, I can imagine BA disappearing from the picture. If not, I assume BA+EZE will be used way more often among statin-intolerant people.
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Good find. Slightly underwhelming results for the addition of ezetimibe, no? Or am I missing something?
adssx
#1148
I don’t know. What’s the MACE reduction for statin therapy in people with ACS? What about other therapies?
It’s also possible that there is one-third of high-respondents (hyperabsorbers) who benefit a lot from ezetimibe while the other two-thirds benefit less. (e.g. -15% MACE for some and -5% for the others giving an average of about -7%).
As to BA safety, compared to eze, debatable. But at least compared to statins doesn’t seem to raise diabetes risk:
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Yes, that’s the big issue with eze, in that the big benefit is only seen in hyperabsorbers, pretty limited group.
adssx
#1151
Not so much:
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).
High cholesterol absorption: A risk factor of atherosclerotic cardiovascular diseases? 2023
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Right, a minority. Of course 30% is better than 5%, but eze is still a much narrower applicability drug compared to statins which work for all except the small minority who are intolerant.
I can attest that the triple therapy of Atorvastatin 5 mg + Bempedoic Acid + Ezetemibe lowered my father’s ApoB from 130 to 34. It lowered mine from 120 to 48. That’s a 74% reduction for my father and a 60% reduction for myself. We now both have the cholesterol levels of little children.
I literally feel young at heart. 
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Bempedoic acid seems to have a reasonable safety profile, at least in the short term (new drug), but gout is a problem:
So maybe SGLT2i to the rescue:
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Congrats, DeStrider, to both you and your father! Because I’m getting ready to hop on the BA+eze train (I’m already on 10mg/day of atorvastatin), I want to know whether the lowering of LDL achieved by BA results in lowering of CV events, hence my questions and PubMed research. Because it’s all well and good to lower LDL, but that by itself doesn’t guarantee benefits - see niacin.
We need to know that BA is at least as safe, and at least as effective per LDL unit lowered as statins. So far, at least according to the studies I cited above, BA seems safe and effective - short term, because as a newish drug, it doesn’t have the clinical track record. Early evidence is cautiously encouraging, although perhaps it’s not as powerful as some statins. I continue to be intrigued by pitavastatin.
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I believe that Bempedoic Acid and Ezetemibe will be just as effective as statins with fewer side effects. Of course we need time to prove it, but I have enough evidence to convince me to continue taking them.
Here is a rather interesting Nick Norwitz yt video, wherein he reports on the results of his consuming an epic amount of eggs (two cartons a day!). Obviously a giant amount of cholesterol taken in. He explains how the body blocks the endogenous production of cholesterol (through cholesin) when in the presence of dietary (exogenous) cholesterol to maintain a balance.
He claims his LDL levels declined by 2%, and when he added 60g a day of fruit (banana, blueberries, cherries etc.), his LDL levels plunged consistent with the LMHR model hypothesis.
All, very interesting, but I wonder how does a drug like ezetimibe fit into this?
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ng0rge
#1160
Short Biography
Nicholas G. Norwitz, PhD, MHP. Dr. Norwitz is pursuing his MD at Harvard Medical School. He received his bachelor’s degree in cellular biology from Dartmouth College in 2018, from where he graduated Valedictorian. He received the Goldwater Scholarship in 2016 as well as the Keasbey Memorial Scholarship in 2018, a merit scholarship that provided funding for his DPhil (PhD) at Oxford University in the UK. He completed his PhD in 2020 on the topic of ketogenics and neurodegenerative disease. He is also a certified metabolic health practitioner (MHP) with the Society of Metabolic Health practitioners. He is published on the topics of Alzheimer’s disease, Parkinson’s disease, ketogenic diets, diabetes, lipidology, inflammatory bowel diseases, osteology, exercise sciences, nutrition sciences, and metabolic health. His primary clinical and research interest is in using lifestyle interventions to prevent or improve chronic metabolic diseases.
And your credentials are? Or maybe you’d rather just post your facial expression.
He explains in the video what’s necessary to get the public’s attention.
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