Jay
#148
LaraPo, This is a paragraph from the Cologuard website:
“False positives and false negatives do occur. In a clinical study, 13% of patients without colorectal cancer or advanced adenomas received a positive result (false positive) and 8% of patients with cancer received a negative result (false negative). The clinical validation study was conducted in patients 50 years of age and older. Cologuard performance in patients ages 45 to 49 years was estimated by sub-group analysis of near-age groups.”
Frequently Asked Questions | Cologuard® For HCPs.
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One way you can reduce your overall chances of false results is to take the test multiple times. If the results from multiple tests are the same, you have less of a chance of an error. If the tests contradict each other, then you can investigate further.
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Thanks for the info. I’ll add 0.5mg colchicine daily with my statin.
AnUser
#151
FYI colchicine is highly toxic, even a 7 mg dose will kill you. So make sure you get it from a reputable source that doesn’t dose it wrongly and keep it away from children etc.
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Thanks for the warning. I’m not sure I trust my source that much 
. Guess I’ll just keep it on my consideration list for now.
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zazim
#153
And God forbid don’t eat a grapefruit or drink grapefruit juice!
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According to @ConquerAging , An LDL between 65 and 120 has the lowest All Cause Mortality when adjusted for all comorbidities. Very Interesting.
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AnUser
#156
Really, so it is a mendelian randomization study or clinical trial?
@ConquerAging does a much better job explaining it than I can. You may just want to watch the video from an expert
@DeStrider Amazing. Thanks for this. I have recently let my LDL increase in an experiment to see if I can improve my mitochondrial function (evaluated by athletic performance and afternoon brain fog) by reducing my statin dosing (5mg EOD vs 10mg EOD). My LDL increased from 40s to 70s. I think I’ll hold here while I watch @ConquerAging experiment.
I’ll add that the experiment was successful although I cannot tell how much the effect was from adding GG supplement and MB.
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AnUser
#159
I don’t understand why you think there is a U-shaped curve when you have seen the Mendelian randomization evidence showing no such curve.
Same with all of the statin, PCSK9 studies where it has shown lower is better.
What is not registering?
“Doublethink means the power of holding two contradictory beliefs in one’s mind simultaneously, and accepting both of them.” George Orwell, 1984.
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AnUser
#160
I have seen it before commenting, obviously, but if you really do not want to think about this at all, you should refer to an expert lipidologist like Allan Sniderman, Thomas Dayspring, or Eugene Braunwald as linked above “How to live to 100…”
It’s interesting to see that people really cannot think clearly about this topic. It’s a pattern that repeats over and over. Despite the fact they have seen superior evidence.
You are also using up the patience of the people who care enough to comment. It’ll end up only Yes men who are agreeing with you.
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Every time there is new evidence, I need to take it into consideration. My current LDL is 120 due to Rapamycin which is up from 89 before. After adding BA and Ezetemibe, I hope to get my LDL to the 60-70 range. This feels like a good range to be in. Even if I wanted it lower than that, I would have to take extreme measures which I am unwilling to do for marginal benefit.
It’s just not possible for most people to keep their LDL below 60, so I am unsure why you are asking people to do the impossible or unreasonable.
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AnUser
#162
It’s not “new evidence” if it’s using a methodology that is inferior. That’s like having a DNA proof on a murderer’s weapon and CCTV camera evidence, and then randomly coming to the discussion exclaiming “A witness just remarked that they think this random person is guilty!” These observational, association studies are dog shit compared to mendelian randomization and clinical trials when they are available, that is also why it is so annoying for us who know.
If there is anything you should think about it is causality. Only focus on causality and if your study methodology can answer it.
Just because you can’t get a LDL level lower doesn’t mean you should find worse evidence to make you satisfied with the level you can reach. That’s called bias.
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You can try for a 0 LDL or ApoB. Whatever floats your boat. From a practical perspective, I’ll do what I can. I am biased towards practical information that I personally can use (along with 95% of the other people here).
I can muse about how Rapamycin can reduce the age of ovaries and pull people out of menopause, but since I’m not a woman, I don’t dig too deep into it. I feel the same about lowering my LDL below 60. It’s never really going to be practical for me so it’s not really worth more than a few musings from me.
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AnUser
#164
I have no clue what you are talking about, you are talking about below 60 mg/dl is not practical now. Your claim was that 120 mg/dl LDL is fine.
If that is not your claim, I don’t see a reason for you to post it.
If it’s because LDL below 65 does not have an additional decrease, you must answer why the study falsely said 120 is okay, but below 65 isn’t and what makes you think you believe the study results at all because of the clearly false results it is reporting. The methodology is clearly flawed, unless you sprinkle some bias on it and selectively use what you want to.
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AnUser
#165
Anyway, other people have commented on that video with similar concerns:
"The U or J-curves in this study are obvious artifacts of the used models and reverse causation issues typical for such an epidemiology study. You can’t account for everything in such dirty data, you need a different methodology. Mendelian randomization studies point out that LDL is causal for atherosclerosis, and the dose-effect curve is a straight line. For example:
- “Effect of Long-Term Exposure to Lower Low-Density Lipoprotein Cholesterol Beginning Early in Life on the Risk of Coronary Heart Disease: A Mendelian Randomization Analysis” doi:10.1016/j.jacc.2012.09.017
- “Low-density lipoproteins cause atherosclerotic cardiovascular disease. 1. Evidence from genetic, epidemiologic, and clinical studies. A consensus statement from the European Atherosclerosis Society Consensus Panel” doi: 10.1093/eurheartj/ehx144"
" @conqueragingordietrying1797 We can’t know all the conditions that can introduce reverse causality, you can get rid of the most significant one, but you can’t account for every imaginable option. That’s why epidemiologists couldn’t untangle alcohol’s effect on CVD from other factors despite trying really hard. Eventually, mendelian randomization studies debunked all these related to alcohol consumption U-curves."
This thread is so long that I don’t know if this study has been previously posted, but it is a very large study with a fairly long time span.
“We conducted a prospective cohort study of 4 467 942 veterans aged >18 years, with baseline outpatient visits from 2002 to 2007 and follow‐up to December 30, 2018”
Confounding factors were taken into account.
“We sought to examine whether the U‐shaped relationship is true and to assess the impact of age on this association.”
“Our results support the lipid hypothesis that lower blood cholesterol is associated with reduced CHD. Furthermore, the hypothesis remained true when TC was low due to use of statins or other lipid‐lowering medication.”
After looking at the hazard ratios it seems to me that cholesterol levels are not such a big deal as we once thought. (or a fairly wide range is acceptable)
https://www.ahajournals.org/doi/10.1161/JAHA.123.030496
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L_H
#167
That’s really interesting. The idea that cohort studies bad, MR and RCTs good is very simplistic. In this area all the different types of study have severe limitations.
If the RCTs are in a different population (e.g. people with prexisting cvd) then they may not tell us much about healthy people. Short RCTs may not tell us much about the long term. And RCTs which are underpowered for All Cause Mortality may not tell us much about ACM. Mist if the RCTs also don’t reduce ldl to very low levels.
With cohort studies the obvious problem is the confounding variables. You would need to know the full detail before being convinced that they’ve factored out everything, so the underlying detail of this study will be interesting. For example was there any undiagnosed cancer in the population which was contributing to both mortality and very low ldl?
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