Rethinking Atherosclerosis: A 21st Century Approach - How Low Should LDL Really Go?

I didn’t know any of this, so thanks for posting. I happen to be on colchicine (gout medicine) for CVD prevention, so it might be something to at least research for those on BA.

It seems you are saying that higher uric acids can contribute to tendon ruptures. I think my level is fine, and I also take dapagliflozin, but what do you try to keep yours below? BA does very little for me, but I will take any help I can get.

I can guarantee it does.
“Uric acid and urea nitrogen are both nitrogenous waste products cleared by the kidneys, and though they have different metabolic origins, their levels are closely linked by shared kidney function. Elevated levels of either can indicate kidney dysfunction.”

Though it won’t affect your EGFR, so you’re left wondering, “Why do I have one marker that says I may have a kidney problem and another marker that indicates that my kidney function is okay?”

So still another supplement or med, along with creatine, that you may want to stop for a few days before your bloodwork.

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Dr Attia preaches that ApoB is the parameter to get down. His is around 35, same as 20 yr old, and says you can take Artherosclerosis off the table by getting to these levels of no plaque formation. He takes Repatha, ROSUVASTATINA + EZETIMIBA 10/10 mg to get there. Im 79 and only take ROSUVASTATINA + EZETIMIBA 10/10 mg and Apob is 56. LDL 36. Have to take PCSK9 drugs to get real low. Had CT angiogram 1 yr ago, looking for soft plaque, only found calcified, score of 30. Heart function outstanding. Now I will focus on Metabolism with GLP 3, peptide

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Most statin trials are only 4-6 years. But lifelong lowering of even a little bit produces massive reductions in mortality. From abstract -

Sequence variations in PCSK9, low LDL, and protection against coronary heart disease Sequence variations in PCSK9, low LDL, and protection against coronary heart disease - PubMed

these mutations were associated with a 28 percent reduction in mean LDL cholesterol and an 88 percent reduction in the risk of CHD

Of the 9524 white subjects examined, 3.2 percent had a sequence variation in PCSK9 that was associated with a 15 percent reduction in LDL cholesterol and a 47 percent reduction in the risk of CHD

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Strongly agree. After all, it’s the number 1 killer, by far, and we understand the mechanisms really well. If all of us believe in probability, it just doesn’t make sense to leave your LDL-C at anything above 70mg/dl unless you have a really really good reason.

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Hanging out with this crowd makes me feel like my ApoB of 58 is living life too dangerously. :wink:

Then I talk to my friends in RL who are fine with an LDL of 120 because their doctor said it’s normal.

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After investiging, it appears the pain in my left lower calf region may be an ergonomic issue due to a crappy office chair that I am using. I’m still looking into it though.

Here’s hoping it’s not Achilles Tendinopathy.

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Perhaps of help?

Below is a concise, evidence-based overview of how Achilles tendinopathy is diagnosed and the key clinical features. This is based on current sports-medicine and orthopedic consensus (e.g., Alfredson, Cook & Purdam, Khan et al.), with uncertainty noted.


1. Diagnostic Process (Clinical, Not Lab-Based)

Achilles tendinopathy is a clinical diagnosis. No blood tests are useful; imaging is supportive, not decisive.

A. Patient History (Primary Component)

Clinicians look for:

  • Insidious onset of pain in the Achilles region, often after increased training load or mechanical stress.
  • Stiffness and pain on first steps in the morning, improving after a few minutes of walking.
  • Pain that worsens with tendon loading (running, jumping, heel raises).
  • Temporary improvement with warm-up, then worsening with higher loads.
    These features differentiate tendinopathy from acute tears or inflammatory bursitis.

B. Physical Examination

  1. Palpation

    • Focal tenderness directly over the tendon (mid-portion tendinopathy, 2–6 cm above calcaneus).
    • Thickening of the tendon compared to the other side.
    • Local nodularity in chronic cases.
  2. Functional Loading Tests

    • Pain on single-leg heel raise (especially eccentric lowering).
    • Pain during hopping test (pain reproduced when hopping in place).
    • Reduced plantarflexion strength or endurance compared to the contralateral limb.
  3. Differential Maneuvers

    • Thompson test normal (rules out rupture).
    • Dorsiflexion range of motion and calf muscle tightness contribute as risk factors.

C. Imaging (Optional; used when diagnosis uncertain)

Not required for most cases.

  • Ultrasound
    • Tendon thickening
    • Hypoechogenicity
    • Neovascularization in some, but not all cases
    Note: Findings have poor correlation with symptoms; many asymptomatic athletes show “abnormal” tendons.

  • MRI
    • Reserved for unclear cases, partial tears, surgical planning.
    • Shows fusiform thickening, T1/T2 signal changes.

Imaging helps rule out partial tears, retrocalcaneal bursitis, Haglund deformity, insertional tendinopathy, or other pathologies.


2. Key Symptoms of Achilles Tendinopathy

Core, Highly Characteristic Symptoms

  • Achilles pain during or after loading, especially running, jumping, or stair climbing.
  • Morning stiffness and pain on first steps.
  • Pain decreases after warming up, then returns post-activity.
  • Localized point tenderness in tendon.
  • Tendon thickening (observable or on palpation).
  • Pain on heel raises or hopping.

Full response:

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Yes. Then what I have is different from Achilles Tendinopathy. Time for a new office chair. :slight_smile:

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The problem with many cardiology studies is that they are much more association-based than causation-based. Therefore finding absolute truths in cardiology is allusive. For example, lowering cholesterol levels is associated with reducing heart attacks (particularly in males who have previously had a heart attack); statins reduce arterial inflammation and this isassociated with a reduction in heart attacks (Ridker et al); lowering ApoB is associated with reducing the risk of heart attacks.

Therefore we need to be very careful on this topic not to give absolute statements. The absolute statement from this Substack article about lipid lowering medications not affecting the brain is one such nonsense example:
“Lowering LDL in the blood doesn’t drain cholesterol from the brain any more than closing the highway drains fuel from parked cars.”

We know that statin tablets are divided into lipophylic tablets like simvastatin that CAN cross the BBB and do have higher higher “pleiotrophic” , or brain side effect than hydrophilic statins like rosuvastatin. In turn this does not mean that hydrophilic statins don’t give brain side effects but that they are much less likely to do so. (The Effects of Statins on Neurotransmission and Their Neuroprotective Role in Neurological and Psychiatric Disorders - PMC)

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Sure, there’s association. But so far, I also don’t think there’s any good evidence that statin use, or super low ApoB, is associated with anything bad.

In fact, I’m not even sure that “brain side effects” are well documented. As far as I know, the whole lipophilic vs hydrophilic statin thing is mostly just speculation.

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DeStrider, from personal experience Achilles tendonitis is very, very painful and slow healing. It hampers the ability to walk dramatically. As others noted, a tendon rupture sounds like it could be devastating. Maybe it’s the BA and maybe not, but as you said, “lay off the BA for a while.” I hope it helps, but, of course, tendons and ligaments are very slow healing, from my experience 6 months and more.

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Lifelong reductions in LDL-C by genetic variants in HMGCR reduces heart disease risk by 19% for every 10 mg/dl decrease:

Variants in PCSK9 and HMGCR were associated with nearly identical protective effects on the risk of cardiovascular events per decrease of 10 mg per deciliter (0.26 mmol per liter) in the LDL cholesterol level: odds ratio for cardiovascular events, 0.81 (95% confidence interval [CI], 0.74 to 0.89) for PCSK9 and 0.81 (95% CI, 0.72 to 0.90) for HMGCR.

https://www.nejm.org/doi/10.1056/NEJMoa1604304

Every 39 mg/dl decrease might reduce the risk of dementia by 76%:

Meta-analysis of one-sample Mendelian randomization odds ratios per 1 mmol/L (39 mg/dL) lower non-HDL-C was 0.24 (0.18–0.31) for HMGCR, 0.18 (0.12–0.25) for NPC1L1, 0.97 (0.70–1.35) for PCSK9, 1.66 (0.52–5.36) for ANGPTL4, 1.41 (0.63–3.16) for LPL, and 0.30 (0.26–0.34) for CETP. Cox regression and two-sample Mendelian randomization results were mostly directionally consistent.

https://alz-journals.onlinelibrary.wiley.com/doi/10.1002/alz.70638

And increases the chance of achieving 90th percentile lifespan compared to higher levels:

The effects were strengthened to around 2 years of life lost in multivariable mendelian randomisation and were replicated in conventional two-sample mendelian randomisation (odds ratio [OR] of surviving to the 90th centile of lifespan: 0·38 per 1 SD higher apoB in offspring, 95% CI 0·22–0·65).

https://www.thelancet.com/journals/lanhl/article/PIIS2666-7568(21)00086-6/fulltext

It’s the Rate-Limiter on ASCVD: Apolipoprotein B (ApoB)

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Follow:
Matt Kaeberline
Prevmed Ford Brewer
Peter Attia
Rhonda Patrick
Physionics Nick Verhoven
Dr Brad Stanfield
Gil Carvalho, nutrition simple
Nick Norwitz
Dave Feldman

Low dose Crestor Rosuvastatine:
Pitavastatin even better, helps insulin resistance, no diabetes. No generic,
Got it at USA Marley Drug for $1 pill,
But Medicare pays for Crestor.
Attia: 5mg daily lowers 85% LDL, no reason to take more than 10mg.
30% reduction is preferred by Heart association, even Crestor 2.5mg does.
Crestor Half Life last 2 days, so 5mg every 2 days is good. Pitavastatin think HL is shorter, daily required.
Crestor has multiple pleiotropic benefits in addition to LDL lowering. Gotta find Prevmed video bout it.
Know have severe atherosclerosis.
Decades w LDL 240, LDL-C 300,Triglicerids 400, just 1 years into statins. Will take low dose forever.
Need Cardiac CT angiography, with Ai cuantitative Analisis (Heartflow better than Cleerly, $1,200), modern CT w 4 millisieverts radiation max, fast 320-640 slice dual source, Proton machine, 1 heart beat enough. None available PR.
Measures plaque volume, 250-500-750 ML3, calcified & etherogenous safe, soft pus plaque is the widow maker.
CAC calcium score useless.
CIMT, Carotid intima media thickness, not as good, need certified tech.

Baby aspirin 81mg:
Endoscopy found gastric erosion. Read aspirin stops/nullify platelet for its 10 day life , new platelets restore by 4th day, so take it every 4-5 days. Take other: omega-3, Nato, curcumin, lots of garlic, 2 garlic pills, organic, black aged.

Low dose Cialis 5mg.

Namenda for brain hippocampus.

Attia:
Rapatha, potent, very safe. Soon in pill.
Bempedoic acid, nexletol is pro drug, effect only inside the liver, potent and safe.
Statins whole body, all cells.
Zetia, Ezetimibe, Less potent. 5mg, half of usual 10mg dose, just as good, less renal load.

5mg Crestor & Zetia, for now.

Had 2015-2025 brain MRI.
Radiologist found sinusitis, going to ENT to stop it. Found mastoiditis.
Missed loss of Hipocampus.
Need volumetric Ai Analisis to compare 2015 to 2025, to find if damage was already present in 2015 due to 25 year high alcohol, almost daily blackouts,
Or Hipocampus is cause Alzheimer, 92 yo mother w level 6 Alzheimer.
Father w diabetes, renal failure, died 2015.
Sister w 20 yr lupus, now afib w pacemaker, congestive heart failure,
was 5 2 w 240 pounds, now 200.
Brother w blood cancer.

Terrified of dying, just now doing 68,000 mile checkup.
Taking all drugs available .
Medics are mostly mediocre, incompetent, some w ethical faults.

Radiologist most incompetent, can’t tell if fatty liver regressed, wrong liver Fibroscan said at level 3,but exam parameters said level 1,had to amend the exam,
Terrible at abdominal sonogram, 5 line, spaghetti no coma, no punctuation wathsoever. Vs one who did organ by organ detailed description.

Ophthalmologist left me half blind in both IOL eyes, rude, incompetent, inept, will do iol replacement in 10 years when new acomodaron lenses arrive.

No Dr ever said anything bout my 240 LDL, 400 Triglicerids, 68 renal GFR.
None said anything to sister cause low 40s GFR, for decades.

So I need to be in charge of my health,
and money, many mistakes.

Girlfriend reached 200. Just started Zepbound Lilly Direct. Hope Trump Initiative lowers price, next year Medicare w $50 copay.
Newer retatrutide GLP-1, GIP, Glucagon, may be available next year, right now compounding farmacies deliver it now, cheap.
Bodybuilders into it, too, cutting fase.
GLP-4 bioglutide w GLP-1, GIP, Glucagon, igf-1, if real, pill, no gastric problems, sounds fake.
Desperately want them.
Arterial, Inflamation (hope arthritis, everybody has it by 60s), renal, liver fat, brain.

Went from 180 to 150, 13% fat, 3-2 viceral fat, the hard way, diet, back into weightlifting gym after L4-L5 sciatica, last year. Have free weight olímpicsl gym inside my apartment, comercial gym in the condo, did 4 weekdays 2 year heavy gym stint till 2016 retinal detachment stopped tracks, 2024 sciatica also.

Need 30 more additional great healthspan years, MINIMUM.

have year 2060 plan. 105 yr old, young.
Athletic, lean, muscular.

Imagine 2040s, 2050s, 2080s, 2100 medicine, tech.

Envy 20 year Olds, will reach year 2100.
By then, GLP-80, all lean, all muscular athletic, maybe restarting puberty is the answer, it’s there, Dormant. Let the body build a 20 year young body, again.

Ai w 20 billion Ai robots, each doing what 10 humans did, perfect, connected.
Humans obsolete for labor.
All, even 100s w 20 yr body, face.

Aging, disease, gone.

Scifi movies tv is so mediocre, robots nowhere.

CRISPER Genetic control, GLP, Incretins, peptides, SARM, selective androgens, full anabolic, no androgenic.
MRNA Vaccine tech that makes cell produce any proteins.
Wearables, instead of CGM,
Continuous Blood Monitoring, CBM.
Perfect vision, skin. Hair, teeth.

Moon, Mars, near solar system resources.
Almost free energy, water, resources.
Bots will do agriculture, food, housing. Everything.
Post scarcity, new world order.
Longevity escaped.

By 2060, hope.
By 2100 for sure.

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Welcome to the community! It’s a valiant attempt to fit the whole universe into one post, but we also welcome multiple posts with discrete subject matter🙂! Hope to see you post more.

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If you are having issues with eGFR and kidneys, you may look into an SGLT2I like empagliflozin (Jardiance) - 10 mg.

As for your cholesterol, a low dose statin, ezetemibe and Bempedoic Acid should be your foundation and you may consider a PCSK9I like Repatha. I would use them all in your situation. I have found that Omega-3 with a high EPA really helps bring down my triglycerides.

Good Luck and Good Health!

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Thanks.
I’m not diabetic, So I have been prescribed Farxiga.Had a recent episode where it seems I had an acute kidneys case. Got alarmed, scared. Father went into diálisis and soon, a year, died.
But also were taking creatinine.
So had a flush out month, and repeated the labs, GFR went back to high 60s.
Also did a CISTATIN-C GFR and it came out 80.
Plus all my other markers my nefphrologist told me are OK.

Of course I’m not looking at my health now only, I’m thinking bout my health, my priority, to when I’m 90s, like my mom. Mom GFR is 48.
92 Age, has Alzheimer level 6 of 7.
She was strong an healthy, though Alzheimer level 5, till December last year. But had a pulmonary issue and has deteriorated considerably, mind and body.

Desperate cause my lifelong Colesterol high,
Just 2 years on statins.
haven’t checked w a CT angiogram,
hopefully w Heartflow Ai, that shows mostly calcified plaque. So I’m nervous, little scared.
Till then.

Plus my brain MRI scan 4 months ago got me floored when my neurologist showed me in my MRI images that I have hippocampus loss.
Shocked when he showed me the image. Didn’t expect it. Terrorised.

Just had my colonoscopy. scared cause polips 10 years ago, Peter Attia comments scared the BJesus out me. Found polips, but seems nothing bad, will repeat in a year. Had endoscopy. Prostate exam too. Soft and small. Lifelong PSA 0.6.
Got today Abdominal liver MRI medical order from MD internist. Sonogram and Fibroscan from mediocre radiologist, didn’t convinced me bout previous fatty liver result being overcomed. Have also ENT CT order for chronic sinusitis, Inflamation, brain MRI 2025 still shows sinusitis had in 2015 MRI.

Together w DEXA order, for bones w fat Analisis, but w abdominal MRI and my 152 weight, 13% fat, 2-3 viceral fat score, w 8 electrode scale readings, hope, expect to have less half pound viceral far, no fatty liver, Diagnosed previously, w no liver scaring cause 20 year long alcohol abuse and fatty liver.
I need 25 more healthy years, minimum. Being 90s as good or better than today.
My life up to now, wasted.

Retired and want to move to Europe, move to Rome, not Italy, live in Rome at least a decade.
From this home base visit Athens, Paris, Barcelona, Madrid, London.
Im a history junky, science, tech, space, Christian origins, movies streaming, medicine, longevity, weightlifting w no steroids, and more.
I need 30 more years, minimum.

And imagine w 2040s medicine, 2050s.
Have high hopes, but being soon in my 70s, running scared.

Sorry for my difficult English.

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If, when, get Rapatha, too expensive now, somebody here said LDL can reach 40s, peter attia say 30s literally stops atherosclerosis in its tracks,
Plus Ezetimibe, and low dose Crestor,
And maybe even low dose Bempedoic acid,

And my low carb, low glucose,
Maybe in this respect,
I’m Gotta get outa weed of atherosclerosis.

Will repeat a Kraft test, OGTT w insulin response.
Test a year ago, Insulin/glucose started dropping at the 1 hour mark, kraft level 2.

W my low carb diet, exercise,
hope to reach level 1 Kraft:
30 minute to drop glucose, insulin.

Being fully insulin sensitive, another goal.

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Although I see good things coming for longevity, (Thank you RapamycinNews) I wish I could be as optimistic as you about the future for humanity, but with our abject failure to address climate change, social and income inequality, I’m not sure how much of the consequences I want to observe. My objective is to maintain optimum health while alive, which this forum is helping me to do. I do not fear the Reaper. I have lived a life of quality, honesty and service to others. If there is a God they will welcome me to the afterlife. If there is no God, my consciousness will end or be temporarily interrupted as I work towards my reincarnation as a giant fruit bat (based on my current dietary preferences).

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You really can’t stress yourself out by worrying about the things you can’t control. If we start going down those rabbit holes and really start to believe in a doomed society, it will do us no good.

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