You make sound arguments.
I’m not convinced that clinically meaningful atherosclerosis leading to cardiovascular events is inevitable, especially in those with a CA
C of zero, even in very advanced old age. It may be similar to prostate cancer whereby most die with it, rather than because of it.
I’m very sensitive to medication side effects, unless the medication is strictly necessary. Things pop up like this association of ezetimibe with intestinal cancers:
Very fair. I actually agree that if you have CAC of 0 and are >65 y/o, you probably don’t need to worry about dying of atherosclerotic causes in your life. It’s already clear that you are not predisposed to its development, barring starting to smoke a pack per day.
I do think for younger people here who are concerned about suboptimal lipids, however, it does make sense to pay more attention to optimization. Once you start down the CVD path, it begins to compound quickly.
Your last point is interesting. Especially the intestinal cancers finding is certainly non-trivial. I recall reading a paper indicating increased risk of lung cancer (I think adenocarcinoma, I can’t remember) in long-term use of ACE inhibitors. That being said, the increased risk was pretty minor compared to the sequalae of lifelong hypertension.
I think at the end of the day it really comes down to playing the odds. Are you young, with some risk factors for CAD, and willing to prioritize CVD health over any risks associated with lipid therapy? A statin probably makes sense. Cardiovascular disease remains the number 1 killer in the modern world, and mitigating that makes a lot of sense. But for the 65+ y/o person I mentioned previously, it may not be necessary.
Fair enough. Good points. This discussion will continue to evolve I’m sure.
Absolutely! Looking forward to it.
What is the best way to measure your CAC? Sorry if it was mentioned earlier, but I must have missed it. Just trying to broaden my understanding. Thank you in advance.
Lots of private clinics offer the scan in the US, typically a few hundred dollars I think:
Examples and Details below:
Looking at figure 1, rapamycin is associated with dyslipidemia but protective against vascular damage, cardiac hypertrophy, and mitochondrial dysfunction.
Virtually all of the transplant patients I see in dermatology are on tacrolimus rather than sirolimus/rapamycin. Any idea why this is, given all the potential health benefits of sirolimus vs tacrolimus? That figure says it all! It just comes across as irresponsible to be putting all these patients on oral tacrolimus, but there must be a rational reason these providers are choosing it.
I can’t imagine any advantages of tacro over rapamycin or everolimus.
Makes no sense to me.
Maybe their doctors want to use the most recently developed medication? Or maybe the tacrolimus rep has been doing a stellar job? Seems sirolimus is cheaper too…
According to this study however, patients withdrew from the Sirolimus group at a much higher rate than the tacrolimus group even though both drugs were considered to be effective.
Causes of withdrawal were poor wound healing (n = 4), enteric fistula (n = 1), pancreatitis (n = 1), and pneumonitis (n = 1). Subsequent to first amendment, 8 patients underwent TAC or SRL introduction on day 7; SRL was withdrawn in 4 of the 5 because of recurrent mouth ulcers (n = 2), pancreatitis (n = 1), lymphocele (n = 1), and enteric fistula (n = 1), with a median time to withdrawal of 77 days.
So, it appears that sirolimus side-effects at high dosages are worse than tacrolimus.
A similar study with equally bad results for rapamycin.
Wow. By reading this, I would assume tacrolimus is far superior to sirolimus.
No difference in cancer rates? No difference in mortality rates? This really makes me question if sirolimus really does what it is supposed to in humans. 
Well in fairness kidney transplant patients have an entirely different set of concerns. But it does temper my enthusiasm for experimenting with higher than recommended dosages of rapamycin.
My doctor recommended 6MG per week and I am sticking with that.
Exactly. I think 6-9 mg weekly is the sweet spot. They weren’t kidding when they said to stop increasing the dosage when you start to see more side effects!
My girlfriend who sometimes prescribes everolimus as part of cancer treatment says all here patients hate it because of the stomatitis they all get. She was sure I would get stomatitis too but so far going as high as 12mg with grapefruit juice nothing yet maybe because I am a dentist and or on a carnivore diet, so nothing for the bacteria in my mouth to feed on…
This article claims that apoB is a better indicator of cardiovascular risk than LDL-C but non-HDL-C is a better indicator than apoB.
If this is the case you needn’t spend the extra money for an apoB test as non-HDL-C is included in the standard panel most doctors prescribe.
“Assessing whether CAD risk is proportional to non-HDL-C or apoB”
“Many sequence variants have discordant effects on non-HDL-C and apoB. These variants allowed us to show that the causal mechanism underlying the relationship between apolipoprotein B particles and CAD is more associated with non-HDL-C than apoB particle concentration.”
“Thus, the genetic effects on CAD risk are proportional to effects on non-HDL-C, but not to effects on apoB.”
“Conclusion: Our MR analyses demonstrate that the contribution of apoB-containing particles to atherogenesis is better captured by non-HDL-C than apoB particle concentration. We show that apoB and non-HDL-C are not clinically equivalent”
I’m coming to the same conclusion. Non HDL is easier, cheaper, and more prognostic.
ApoB is 78. By some standards, that pretty good since its under 90. But according to my notes, Attia says apoB should be under 30.
Non-HDL-C is 123. My target is to be under 130, so I’m already there.
As someone who’s improved from high CVD risk to low risk, with a history of smoking, high CAC score, probable angina, hyperlipidemia, I like to have targets, even if they are unachievable.
I want to continue trying to reverse the damage brought about during my reckless youth. Any idea what would be a comparable target for optimal non-HDL-C?
It seems that under 130 is a good goal. Under 100 may be ideal and even under 80 if you’re at a high risk.
I have had 4 colonoscopies. The first found polyps. The second found pre-cancerous polyps. 3rd found nothing and the 4th found polyps. I would rather they find and remove polyps instead of finding cancer.