CT Angiograms have fairly high radiation dose so doctors might be reluctant to prescribe it unnecessarily : Have you tried getting a CIMT Ultrasound (lower resolution and cost than CT Angiogram, but no radiation) or MRI Angiogram (higher resolution and cost than CT Angiogram, but also no radiation)? I would try the CIMT Ultrasound first (around $275 without insurance) and if it shows something (in the Carotid Artery), follow up with a MRI Angiogram (around $600 without insurance) to see how bad it is.
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Repatha appears to have refrigeration requirements. I am not sure how to ensure they will be followed to ensure efficacy.
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Thanks. I like your idea of seeking other tests. Hopefully my PCP will agree despite my CAC score of 0.
Ah yes - no guarantees that anything from India has been kept in refrigerated storage. But perhaps given the price differential it may be worth a test - and check cholesterol afterwards to see if it worked or not…
From the repatha website:
Storage of Repatha:If removed from the refrigerator, the Repatha SureClick autoinjector should be kept at room temperature at 68°F to 77°F (20°C to 25°C) in the original carton and must be used within 30 days.
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I, like you, am pro-active for health. Get your LDL to 20 mg/dL.
See: Circulation. 2023;147:1192-1203. Conclusions: Long-term LDL’s 20mg/dL was associated with lower risk of cardiovascular outcomes with no significant safety concerns.
I prevailed with my cardiologist to get Repatha, he was thankfully in agreement after seeing 50% blockage in the ccat scan. First attempt for insurance coverge was denied; however, his office made an appeal and the denial was reversed. Probably a routine occurrence. You could try to get a consult with a cardiologist who is also a lipidologist and would advocate for you.
Anyway, Repatha caused me to have an extremely runny nose 7 days after the first dose; I took an antihistamine and it stopped this side effect and the runny nose issue was gone. Good luck.
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This issue of how low to go on LDL/APOB has been discussed ad nauseam in this thread already: Rapamycin and risk of cardiovascular disease
But yes… going too low doesn’t seem to be much of a risk (though using multiple medications to get there may incur some risk)
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I take only Repatha, no statin. Took the Statin very briefly, just until I could get on Repatha. After about 6 months on Repatha, Lp(a) went from 40 to 29 mg/dl. LDLC went from 124 to 69 and APOB went from 95 to 70. That’s low enough for me, I think. Was reading that very low LDL can increase risk of hemorrhagic stroke. Everything is a tradeoff. Interestingly the Repatha also decreased my very high HDL from 125 to 119 which is good news, though might be noise?
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Do you take Repatha as suggested, every two weeks, 140mg?
Why did you decide for Repatha?
I take Repatha, 140 every two weeks. No adverse reactions and it has gotten my Lp(a) down from 40 to 29 and also reduced LDLC and APOB. I wrote a longer response on a thread I started about high HDL.
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As of Feb 20th, one month on Repatha, , my LDL is 17 which is superb; apoB is 28 also super.
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What were the levels before? Any other Apo a lowering meds?
Any change in Lp(a)?
I’m on-board with trying a PCSK9 inhibitor for my high LDL which I’ve had for years (164 in November, but because of my overall good health i don’t qualify for a statin via insurance). But what am i shooting for? LDL under 70? LDL of 20 permanently? LDL of 20 for a time and then relax?
I recently head an interview with Thomas Dayspring in which he said an LDL measure of zero should not be an issue (i assume this is hyperbole?). So what’s recommended?
PCSK9 inhibitors appear to be very safe, and with fewer side effects than statins if I’m reading the papers correctly.
Statins are dirt cheap, you don’t need insurance for them. 180 doses of 5 mg rosuvastatin is $7.70 if split in half. So $15 a year.
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I’ve been taking Praluent for a few months now with no noticeable side effects. My cholesterol (and apoB specifically) has never been better.
Now I’ve noticed this link in another thread with a Mendelian randomization showing PCSK9 decreases increases risk for Alzheimer’s.
Even if the above is true it seems that another study shows preliminary evidence that APOB increases risk for Alzheimer’s disease.
I plan to keep taking Praluent, but hope that my blood brain barrier provides some protection from Praluent so I can enjoy the many benefits of a low apoB without worrying about unintended consequences of the medication.
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Scientists shut off Pcsk9 in mice, via epigenetic editing:
Discussion
In this study, we show that LNP-mediated delivery of mRNAs encoding ETRs to the liver of mice can lead to durable (nearly one year of follow-up) epigenetic silencing of Pcsk9. Notably, epi-silencing proved to be stable also after partial hepatectomy, further confirming the heritable nature of the epigenetic marks deposited by the ETR technology and indicating that epi-silenced hepatocytes remained competent for liver regeneration. When compared with RNAi, for which multiple administrations are required31, our approach is configured as a one-and-done treatment, a feature shared only with other genome-editing technologies. Unlike the latter approaches, however, the ETR technology does not require the induction of potentially genotoxic DNA breaks to inactivate the desired gene32,33,34. This feature represents a safety advantage, especially when aiming at multiplex epi-silencing, as both gene editing, and to a lesser extent, base editing can cause reciprocal chromosomal translocations33,35,36. Moreover, epi-silencing differs from genome editing in that it can be reverted by either pharmacological intervention or treatment with editors equipped with a transcriptional activator, as previously shown in cell lines15,22. As such, epi-silencing would allow for temporally controlled silencing of the targeted gene and the reversal of treatment-related adverse effects. Here, we also show that the ETR technology can establish substantial levels of epi-silencing in vivo, at values that are already compatible with several experimental and therapeutic applications. In our experimental settings, epi-silencing performed as well as conventional gene editing (up to 75% of Pcsk9 inhibition).
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Update to my January post on taking Repatha. I started in May 2023. I have now paused it. Here’s why:
I got the script because I had moderately high Lp(a) – so refused to take a statin. Also, I have the C;C phenotype on the gene 9p21 which significantly raises risk. CAC score of 0.96. Total Chol about 232 but very high HDL and low Trigs. Normal BP and BMI, good cardio function Depending on what you read/believe, I had low-moderate risk.
Blood glucose increased. This can happen in some patients on statins. Recent H1AC was 5.8 – just barely prediabetic. But insulin down to 2! Studies (mouse studies) shows that PCSK9i’s can cause insulin to drop and also raise glucose. The lowering of PCSK9 occurs in the liver. which leads to more LDL receptors and lower cholesterol. But it also leads to more LDL receptors in the pancreas and that somehow leads to the Beta cells putting out less insulin. Once again: in mice.
I had two minor symptoms that can also be caused by Repatha – an annoying skin sensitivity and mild upper respiratory short of breath sensation. These have both abated. But just another bit of information that makes me think the Repatha was the cause of the low insulin.
My cholesterol levels (including Lp(a) ) had decreased significantly while on Repatha. But I decided to take a break from the Repatha. At about the same time that this was happening I came across a paper that showed a U-shaped phenomenon whereby both lower and higher total cholesterol (total, not LDL) correlated with higher all cause mortality. Before starting Repatha, I was at the sweet spot of 232 of total cholesterol, with very high HDL and low Trigs. I am still concerned about the Lp(a) but my plan is to double down on efforts to reduce inflammation. Have read that if you can keep inflammation very low, the risk from Lp(a) is reduced. My Lp(a) was 40 and went down to 29. My CRP was 2.2 so not ideal.
My glucose is now down from about 100 to 90, HbA1C from 5.8 to 5.5. Insulin from 2 to 3. But I have been calorie restricting, so???
I will re-asses in a few months. Give all the above, my current mindset is to forgo lipid lowering drugs entirely, focus hard on inflammation through diet and exercise. Was already doing that but will amp it up. To be continued . . .
Would appreciate reactions, questions, suggestions.
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@Deborah_Hall : Would def work on getting inflammation levels down, have you measured inflammation in other ways than CRP? What has the CRP trend been over time?
Re a U shaped association of cholesterol and mortality - those studies are just correlations and likely driven by reverse causation. For instance, cancer often drives cholesterol down, and cancer of course drives mortality - in those cases it’s clear that it’s not low cholesterol driving mortality but cancer driving the mortality. Association studies are a very weak for of evidence, while clinical trials and Mendelian Randomization studies are much stronger forms of evidence and generally suggest that lower Apo B/LDL is better. You can read what I and @AnUser have extensively written and provided evidence for on this forum on that.
In general, would mostly care about Apo B and Lp(a) and perhaps LDL and less about total cholesterol numbers.
Lower insulin might actually be a feature and not a bug or side effect in the context of longevity - as long as you find other ways to lower the glucose levels (and spikes). There are many, many ways of accomplishing lower glucose (often with evidence of having other additional longevity benefits - eg dietary optimization, food sequencing, Acarbose, SGLT-inhibitors, adding extra fiber to your diet, etc - all of these are discussed a lot on this forum).
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Hi
I dont know if anyone is interested or if I can do it, but some of you guys know that I work in a pharmacy, we’ve got a Praluent 150mg that is going to the destruction, not cause it is perishable, but because is has been payed by someone but has never come back to take it. We can’t sell it a second time. 120€ is anyone wants it. Retail price in France : +/- 420€
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Maybe not relevant but if you can’t sell it a second time, how can you charge €120 for it? Just curious.
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Novel PCSK9 Inhibitor Reduced LDL by 50%
Lerodalcibep, a novel, third-generation proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, reduced low-density lipoprotein cholesterol (LDL-C) by more than 50% after 1 year in patients with or at a high risk for cardiovascular disease (CVD), new phase 3 results showed.
Newer, more stringent LDL targets in 90% of patients receiving lerodalcibep vs only 16% of those on placebo, despite concurrent treatment with a statin or statin plus ezetimibe.
“This hopefully gives doctors a more practical PCSK9 antagonist that’s small volume, can be administered monthly, and is an alternative to the every 2 week injection of monoclonal antibodies and probably more effective in LDL cholesterol–lowering compared to the small interfering RNA” medicines, study author Eric Klug, MBBCh, MMed, associate professor, Division of Cardiology, University of the Witwatersrand, Johannesburg, South Africa, told theheart.org | Medscape Cardiology.
https://www.medscape.com/viewarticle/novel-pcsk9-inhibitor-reduced-ldl-50-2024a10007hi
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