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Jake H
25.4K posts
Jake H
@MarketPicker
Founding member of @DormRoomCap. Market participant (equities/options). Likes/Retweets are not an endorsement.
USA Katılım Ekim 2013
815 Takip Edilen854 Takipçiler
👉 Oral PCSK9 Inhibition: High-Efficacy Lipid Lowering Moves to the Oral Era
📍 Randomized evidence shows substantial LDL-C reduction (~50%) with oral PCSK9 inhibitors vs placebo
📍 Consistent effects across atherogenic parameters:
ApoB ↓ ~40–50%
Non-HDL-C ↓ ~45%
Lp(a) ↓ ~15–25%
📍 Safety profile comparable to placebo, including:
No excess adverse events
No signal for diabetes within available follow-up
1️⃣ MK-0616 (Enlicitide): Phase 3–Level Evidence
👆 LDL-C reduction ~60% at dose-aligned analyses
👆 ApoB reduction ~50%, supporting particle-level impact
👆 Minimal heterogeneity at consistent dosing
👆 Concordant reductions in non-HDL-C and Lp(a)
Pharmacodynamic profile:
👆 Tight coupling between LDL-C and ApoB reduction
👆 Consistent effect across study designs when exposure is standardized
2️⃣ AZD0780 (Laroprovstat): Mechanistic and Clinical Signal
Demonstrates significant LDL-C lowering in randomized trials
👆 LDL-C reduction ~50%
👆 Directionally consistent reductions in ApoB and other lipid parameters
👆 Contributes to reproducibility of oral PCSK9 pathway inhibition
Pharmacological attributes:
👆 Oral delivery with measurable systemic effect
👆 Supports class-level biological validity
📍 Integrated Lipid Effects
LDL-C reduction parallels ApoB lowering, consistent with enhanced clearance of ApoB-containing particles
Non-HDL-C reduction reflects broad impact on atherogenic lipoproteins
Lp(a) lowering is present but quantitatively smaller, aligning with partial LDL receptor–mediated clearance
📍 Conclusion
Oral PCSK9 inhibition achieves high-intensity lipid lowering with consistent effects across atherogenic markers and a favorable short-term safety profile.
👆 Next step: demonstration of cardiovascular outcomes to define its role in risk reduction strategies.
🔓 Open Access
🔗sciencedirect.com/science/articl…
@society_eas
@nationallipid
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Daniel Berglind, PhD@DanielBerglind
Muscles don’t grow from “the pump” alone. The key signal for hypertrophy is likely mechanical tension: muscle fibers producing high force under load. Train hard, controlled, through full ROM, close to failure, and progress over time. Tension builds. pmc.ncbi.nlm.nih.gov/articles/PMC12…
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Daniel Berglind, PhD@DanielBerglind
Want to look good, be strong, jump, sprint & move well? Train like an athlete, not a silo: Build muscle like a bodybuilder. Power like a weightlifter/sprinter. Control & mobility like a gymnast. Carry heavy like a farmer. pmc.ncbi.nlm.nih.gov/articles/PMC93… pmc.ncbi.nlm.nih.gov/articles/PMC79…
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Jake H retweetledi
Vaccines save lives. This is only controversial if you view science as political. thelancet.com/journals/lance…
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Tracking food and counting macros is a total pain in the ass.
But I’ve been doing it for a few months, have found the process to be very valuable in informing my nutrition. I have even made some changes because of it.
Anybody else track (regularly)?
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Worrying about food ingredients? This is the risk perception gap | The risk perception gap: excessive concern about things that pose little risk and insufficient concern about things that pose greater risk news.immunologic.org/p/worrying-abo…
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Are Cancer Rates Skyrocketing—or Are We Better at Detection? news.immunologic.org/p/are-cancer-r…
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Same with cholesterol. It’s all about pushing pharmaceuticals and making billions. End Big Pharma now.
“Sudden And Unexpected”@toobaffled
They changed the numbers… again! 1970: Normal BP = 160/95 1985: 140/90 Now: 110/70 is the “new normal” Every time they lower the goalposts, millions more people suddenly “need” meds. Coincidence? Or just great business? Your blood pressure didn’t change .. the rules did.
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@WSJ I think my only issue with this framing (as a non-expert) is the idea of a younger individual (e.g., 20-45 years old) with elevated LDL-C/apoB (e.g., above 130) who has a CAC of zero thinking or being told they don’t need to worry about their cholesterol. @Drlipid @MohammedAlo
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Measuring cholesterol levels has long been the main way doctors assess the risk of heart disease. Increasingly, people are opting, too, for a simple, relatively affordable test: a coronary artery calcium scan.
Here’s more to know about the scans: 🔗 on.wsj.com/420z0pJ
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Jake H retweetledi
BREAKING: The average price of a gallon of gas in the US surges to $4.43/gallon, now up +61% since December.
Americans will spend ~$90 billion more at the pump in a year than they would with gasoline at $3.00.
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Jake H retweetledi
The USA is the wealthiest country in the world and spends 3-4x more on healthcare than any other high-income country, yet it has a life expectancy that's 3-4 years lower
Many people blame the high rates of obesity and a highly processed diet for this, but the truth is a lot more nuanced than that⬇️⬇️
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Jake H retweetledi
@Jon_8675309 @SamaHoole Who’s getting paid for prescribing generic drugs? 😂
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@SamaHoole It’s not so much the pharma industry, it’s the big group primary care doctors that get extra visits for Rx renewals.
Talk for five minutes, bill for $500.
After patent expiration that is.
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Statin guidelines over 50 years:
1970s: "Total cholesterol over 280 is high." Result: a relatively small market.
1988: "Actually, 240 is high." Result: millions more added overnight.
2001: "Actually, focus on LDL. Get it under 100." Result: tens of millions of new customers.
2013: "Forget the numbers. Use a risk calculator." Result: over 50 million Americans recommended statins.
2018: "Widen the criteria. Include borderline risk." Result: even broader eligibility.
2026: "We should consider statins for children." Result: eventually everyone is a patient.
The goalposts didn't move because the science changed.
They moved because the market needed to grow.
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@SamaHoole The data continued to get better…that’s how science works. It’s not a grand conspiracy.
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Look at the pattern.
Cholesterol. They lowered "normal" LDL from 240 to 70. Statin sales climbed to $25 billion at peak.
Blood pressure. They lowered "normal" from 160 to 130. Drug sales climbed to $29 billion.
Same playbook. Lower the definition. Create millions of new patients. Sell the drug.
In 2017 alone, 31 million Americans went to bed healthy and woke up hypertensive. The American Academy of Family Physicians refused to endorse the new guidelines. They cited conflicts of interest on the panel.
Combined: $46 billion per year in drugs. Revenue from testing the root cause: $0.
Sources: ATP I-III (NCEP), ACC/AHA 2013/2017, WHO/ISH, JNC5/7. Market: IMARC, GMI 2024.
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They told you cholesterol is killing you. Cholesterol is a hero molecule. Every cell in your body needs it. Your brain is made of it. Your hormones are built from it.
They told you salt is killing you. Salt is an essential mineral. Your nerves need it to fire. Your muscles need it to contract. Your heart needs it to beat.
They made these two essential parts of human biology into villains. Then they sold you $46 billion in drugs every year to fight them.
Here is what they never told you.
The lower your cholesterol goes, the more you die. 12.8 million people studied. U-curve confirmed in every age and sex group.
The lower your salt goes, the more you die. 130,000 people studied. 49 countries. U-curve confirmed.
Two scapegoats. Two drugs. One lie.
They never tested the real cause. Insulin resistance. The root of heart disease. The root of diabetes. The root of high blood pressure.
There is no drug for it. There is no billing code for it. So they never looked.
Insulin.
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@MarketPicker @MohammedAlo If you assume the environmental mismatches are immutable, sure, for secondary prevention definitely, for primary prevention less so.
Dr Alo is bought and paid for. Ignore him
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I actually look forward to taking gels on runs.
They taste great. Give you energy. Make you faster.
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