Lp(a) is cleared primarily by LDL receptors, but apo(a) physically camouflages the apoB receptor-binding domain — so statins that upregulate LDL receptors barely move Lp(a), while PCSK9 inhibitors achieve a modest, variable reduction. The only definitive fix is blocking apo(a) synthesis, which an antisense oligonucleotide drug (ISIS/Akcea) is targeting in Phase III.
2
After statin therapy reduces the standard LDL-P load, LP-PLA2 and oxidized-phospholipid biomarkers become relevant for stratifying residual inflammatory risk — but Dayspring argues F2-isoprostanes (urine) and oxLDL are more mechanistically defensible than LP-PLA2 activity, whose two large inhibitor trials showed zero event reduction.
3
ADMA and SDMA are the most biologically coherent blood tests for endothelial dysfunction: both impair nitric oxide synthesis via arginine, SDMA also captures early renal impairment, and the combination explains why elevated homocysteine predicts vascular disease through a clear mechanistic pathway.
4
ApoC3 on LDL particles blocks LDL receptor clearance and predicts statin non-response — the CARE trial post-hoc showed pravastatin failed to reduce events in patients whose LDL carried apoC3 — and an antisense drug targeting apoC3 is in development as a longevity-relevant genetic target.
Protocols
Concrete recipes — what, when, how much, and why
7 items
Screen Lp(a) with particle count (LP(a)-P), not mass — then add OxPL-apoB follow-up if elevated
WhatOrder LP(a)-P (apoB-based electrophoretic count) as the primary Lp(a) metric, not LP(a) mass. If LP(a)-P is elevated, order oxidized phospholipids on apoB (OxPL-apoB) to identify which patients carry the highest-risk, oxidized-lipid-laden LP(a) particles.
WhenAt cardiovascular risk baseline evaluation; in patients with less-than-expected statin response where unrecognized LP(a)-P may account for persistent LDL-P elevation.
DoseSingle measurement is adequate for LP(a)-P (genetically determined, stable across life). OxPL-apoB adds stratification without repeat testing.
For whomAll patients at cardiovascular risk; critical in patients with persistent LDL-P elevation despite adequate statin therapy.
WhyLP(a) mass is unreliable due to variable apo(a) molecular weight. A patient with LDL-P 1600 and LP(a)-P 600 has only 1000 statin-targetable particles. Without knowing the split, clinicians misinterpret inadequate statin response.
CaveatsLP(a)-P requires specialized electrophoretic labs (True Health Diagnostics); NMR total LDL-P includes LP(a) particles without separating them.
Dayspring's clinical example illustrates the gap: 600 LP(a)-P particles out of 1600 total LDL-P means a 40% statin response leaves total LDL-P around 960 — dominated by untouched LP(a) particles. Sam Tsimikas' research shows OxPL-apoB identifies the subset of high-LP(a) patients whose particles carry oxidized phospholipid cargo and are most prone to atherothrombotic events.
Mechanism
Apo(a) carries lysine-rich kringle domains that scavenge oxidized lipid moieties. LP-PLA2 on the LP(a) particle activates inside the arterial wall when exposed to reactive oxygen species, generating pro-atherogenic lysophosphatidylcholine.
Excess LP little a — whatever — let me now do this follow-up test, and if that's also up, let's discuss everything we can possibly do until that miracle drug hopefully comes along.
PCSK9 inhibitor for high Lp(a): variable adjunct benefit, not a cure
WhatFor patients with very high LP(a)-P already indicated for PCSK9 inhibition based on LDL-P, note that a modest, variable reduction in LP(a)-P will occur as a secondary benefit. Do not use PCSK9i solely for LP(a) lowering given cost and lack of LP(a)-specific indication.
WhenHigh-cardiovascular-risk secondary prevention patients who have maximized statin and ezetimibe and still carry elevated LP(a)-P.
For whomHigh-risk secondary prevention patients with elevated LP(a)-P who cannot access the investigational antisense drug.
WhyPCSK9 inhibitors extend LDL receptor longevity, allowing more time to eventually clear even LP(a) particles whose apoB domain is partially camouflaged by apo(a). Effect is variable because the degree of masking varies with apo(a) isoform size.
CaveatsThird-party payers will not cover PCSK9i specifically for LP(a) lowering. Without a dedicated LP(a)-lowering trial, it remains impossible to prove event reduction attributable to LP(a) reduction vs LDL-P reduction.
The only way you can do that now is see maybe try niacin which is a weak lowering of 20%, or a PCSK9 inhibitor which would be an individual response range.
Maximize apoB reduction before adding anti-inflammatory drugs
WhatBefore prescribing IL-1 antagonists, colchicine, or low-dose methotrexate for elevated inflammatory markers, maximize apoB/LDL-P reduction (statin + ezetimibe ± PCSK9i). Re-measure hsCRP/fibrinogen after reaching LDL-P goal.
WhenIn any patient with elevated inflammation markers AND elevated LDL-P — address both simultaneously but treat LDL-P as the primary lever.
For whomAll patients with co-elevated LDL-P and inflammation markers. Anti-inflammatory drug therapy is additive, not primary, except in secondary prevention with LDL-P already at goal.
WhyApoB particles entering the arterial wall and oxidizing are the upstream driver of arterial inflammation. Removing the upstream driver reduces inflammation more reliably than blocking downstream inflammatory mediators.
CaveatsIL-1 antagonist (canakinumab) data showed event reduction but also increased fatal infections and costs $30,000/year. Colchicine and methotrexate trials were ongoing at time of recording.
If I lower apoB I reduce inflammation — so that's one, perhaps, that's your first therapeutic initiative: lowering apoB by nutrition or if the risk category is high enough, a drug.
Order ADMA + SDMA + arginine as the endothelial function panel
WhatA single blood assay returns ADMA, SDMA, and arginine. Elevations in ADMA and SDMA signal impaired nitric oxide synthesis; elevated SDMA in isolation may primarily indicate renal impairment. Use the combined panel in primary prevention patients with borderline apoB.
WhenPrimary prevention workup in patients where a positive result would shift the decision threshold toward earlier pharmacologic intervention; also in patients with elevated homocysteine as mechanistic clarification.
DoseSingle measurement. Repeat after 3–6 months of targeted intervention (homocysteine reduction, blood pressure control, insulin resistance treatment).
For whomPrimary prevention patients aged 40–55 with borderline apoB; athletes with unreliable creatinine who need renal function assessment; patients with elevated homocysteine needing mechanistic context.
WhyNo other available biomarker reports directly on endothelial function. Elevated ADMA/SDMA converts ambiguous borderline-apoB cases to clear arguments for intervention.
Mechanism
ADMA directly inhibits endothelial NOS. SDMA depletes arginine via catabolism. Homocysteine impairs ADMA clearance. Together they provide a linked pathway from methylation defects to nitric oxide deficiency to endothelial dysfunction.
If I measured ADMA, SDMA — if they're high, you might presume hey, maybe that's a blood test that actually tells us something about endothelial function. I don't think we have another that has anything close to it.
Also said
“Homocysteine really inhibits the clearance of ADMA, and that's very clear — when you correct it, that would therefore screw up nitric oxide production.”— Closing the mechanistic loop: MTHFR → homocysteine → ADMA → NOS inhibition → endothelial dysfunction.
Add F2-isoprostanes (spot urine) as a pro-oxidative state marker
WhatOrder a spot urine F2-isoprostane assay to detect systemic fatty acid peroxidation. Elevations redirect clinical focus to anti-oxidative nutritional interventions and strengthen the case for pharmacologic intervention when apoB is borderline.
WhenIn primary prevention patients resistant to lifestyle advice who need concrete biomarker evidence; in high-LP(a) patients to assess whether systemic oxidative stress is activating LP(a)-carried LP-PLA2.
DoseSpot urine sample (not 24-hour collection). Re-check at 3–6 months after dietary change.
For whomPatients with borderline lipid panels and lifestyle patterns (high processed-food intake, low vegetable intake, smoking, metabolic syndrome) likely to produce a pro-oxidative environment.
WhyF2-isoprostanes reflect fatty acid peroxidation — the upstream oxidative process that eventually produces arterial wall lipid oxidation. Preferred over plasma oxLDL, which detects minimally-oxidized apoB aldehyde adducts rather than true phospholipid oxidation.
The best of all is as fatty acids get oxidized, derivatives form — they're called isoprostanes — and you can easily assay something called F2-isoprostanes, which have clearly been linked to pro-oxidative states. It's a urine test, not a serum test.
Address VLDL remnants through insulin resistance treatment, then fibrate if pharmacologic
WhatWhen elevated VLDL cholesterol signals remnant accumulation (triglycerides ÷ 5 or non-HDL minus LDL-C is disproportionately elevated), treat the underlying insulin resistance first: carbohydrate restriction, time-restricted eating, metformin. If pharmacologic, add a fibrate to statin/ezetimibe for the VLDL/remnant compartment.
WhenAfter LDL-P is partially controlled but non-HDL remains elevated; in patients with triglycerides above 150 with insulin resistance markers.
For whomPatients with metabolic syndrome, T2D, or insulin-resistant dyslipidemia with residual TG burden after statin therapy.
WhyApoC3-laden VLDL particles resist lipoprotein lipase clearance and accumulate. Fibrates lower apoC3 and VLDL in TG-rich lipoprotein states; carbohydrate restriction reduces hepatic VLDL production at the source.
CaveatsLarge VLDL-P on NMR is an insulin resistance marker, not a therapeutic target in itself. Fibrate-statin myopathy risk is lower with fenofibrate than gemfibrozil.
If I think you have remnants, the nutritional therapy is going to be I'm gonna address insulin resistance in you — and so I'm being an advocate of some degree of carbohydrate restriction and certainly a clear advocate for fasting as part of your dining.
Measure red blood cell omega-3 index (not plasma) before and after omega-3 supplementation
WhatOrder RBC omega-3 index (phospholipid EPA + DHA as percentage of total fatty acids) before starting omega-3 supplementation to confirm deficiency, and at 3–4 months after to verify response.
WhenBefore any omega-3 therapeutic decision; specifically when considering prescription EPA (Vascepa/icosapentaenoic acid) or DHA-containing products for apoC3 reduction.
DoseRBC omega-3 index has a 60–90 day half-life. Target range: 8–12%. Deficiency threshold: below 4%.
For whomAll patients being considered for omega-3 supplementation; patients with apoC3-enriched LDL who may specifically benefit from DHA.
WhyPlasma free fatty acid levels reflect recent meals. RBC index integrates intake over months, like glycated hemoglobin for glucose, and confirms true tissue omega-3 status. Negative omega-3 trials used non-deficient populations at sub-pharmacologic doses — measuring deficiency first resolves this problem.
I would encourage you to measure red blood cell omega-3s — they are like a glycohemoglobin, have a 13 or 60–90 day half-life — rather than a plasma free fatty acid, which might be what did you eat for lunch.
What's new
Personal practice updates, fresh positions, predictions
8 items
Lp(a) particle count, not mass, is the right metric — and NMR cannot provide it
~10 min
LP little-a mass weighs the entire particle including all lipids and proteins, making it unreliable because apo(a) molecular weight varies enormously between individuals. LP little-a particle count (LP(a)-apoB by electrophoresis + immunostaining) is the gold standard, but is only available through specific labs like True Health Diagnostics, not NMR.
Why this matters: Most labs report mass; most clinicians treat it as equivalent to particle count. They are not interchangeable, and misclassification can dramatically under- or over-estimate cardiovascular risk.
Background
NMR essays lipid content of particles, not protein content, so NMR cannot separate LP(a) particles from other LDL particles in the same density range.
Dayspring explains: electrophoresis separates all lipoproteins on a gel, and LP(a) migrates to a distinctive position due to its surface charge. The LP(a) band is then immunostained with an anti-apoB antibody to count particles directly. That number is technically 'LP(a)-apoB' but is abbreviated LP(a)-P. The key clinical implication: a patient with an LDL-P of 1600 nmol/L and an LP(a)-P of 600 nmol/L has only 1000 non-LP(a) LDL particles that a statin can actually target. Even a 40% statin response will leave total LDL-P elevated because the 600 LP(a) particles are untouched.
If LP little a particles are dangerous wouldn't you like to have an excellent accurate concentration in them? Well the only way you can do that nowadays... is I have to separate all lipoproteins electrophoretically.
Also said
“The molecular weight of apo B is known because it's pretty much the same whereas the molecular weight of apo little a is very very variable so that's another reason LP little a mass becomes a useless metric.”— Quantifies why mass is unreliable — the variable component dominates the measurement.
Statins cannot lower Lp(a) because apo(a) masks the apoB LDL-receptor binding domain
~18 min
LDL receptors bind apoB at the receptor-binding domain. On LP(a) particles, the attached apo(a) protein physically camouflages that domain, reducing LDL receptor affinity. Statins upregulate receptors that then preferentially clear standard LDL particles first; LP(a) particles remain elevated regardless of receptor upregulation.
Why this matters: Explains a clinical puzzle: statins dramatically lower LDL-C yet LP(a) is largely statin-resistant, leaving high-LP(a) patients with substantial residual risk after first-line treatment.
Dayspring's mechanistic model: apo(a) is camouflaging the LDL receptor binding domain on apoB, and therefore LP(a) particles don't bind as rapidly or as vividly to an LDL receptor. By contrast, PCSK9 inhibitors extend receptor longevity on the hepatocyte surface — giving more receptor time to eventually clear even the partially-camouflaged LP(a) particles, producing a modest, individual-response-range lowering effect. The primary determinant of LP(a) concentration is apo(a) production in the liver, not clearance, which is why production-targeted approaches (antisense) will be the definitive solution.
My guess is apo(a) is affecting totally efficacious binding to an LP little a particle — it's camouflaging the LDL receptor binding domain on apo B and therefore I better learn how to inhibit synthesis of it.
LP-PLA2 inhibitor trials: two mega-trials, zero event reduction — the test has severe limitations
~35 min
Two large pharmaceutical trials gave LP-PLA2 inhibitors to high-risk patients, drastically reduced LP-PLA2 activity and mass, and found zero reduction in cardiovascular events. FDA indication is for primary prevention screening only — explicitly NOT for secondary prevention or patients already on lipid therapy, because Mendelian randomization shows LP-PLA2 levels are not causally linked to outcomes.
Why this matters: LP-PLA2 is still widely ordered and sometimes used to guide therapy. Dayspring argues this is scientifically unjustified — the enzyme is a marker of what LP(a) carries into the arterial wall, not an independent causal driver.
Background
LP-PLA2 is produced by macrophages, sits on LDL (especially small dense LDL and LP(a) particles), and catalyzes oxidation of phospholipids inside the arterial wall, producing lysophosphatidylcholine — a pro-atherogenic molecule.
The only defensible clinical use Dayspring acknowledges: in primary prevention, a patient with borderline apoB who has elevated LP(a) AND elevated LP-PLA2 may represent higher risk — the dual marker suggesting the LP(a) particles are carrying more LP-PLA2 into the artery wall where it will activate in an oxidative environment. He stopped measuring MPO (myeloperoxidase) two years ago for similar reasons — the mechanistic story is interesting but the clinical evidence for actionability is weak.
The data is pretty poor — most people don't even know the only thing the FDA has given that approval for is as a screening test in primary prevention — never ever for anybody on a lipid modulating drug or who has known coronary atherosclerosis.
Also said
“There have been two mega trials where pharmaceutical industry has developed LP PLA-2 inhibitors, gave them to patients, shut down LP PLA-2 activity, drastically reduced LP PLA-2 mass levels, plummeted — no outcome reduction whatsoever.”— The trial evidence, not just the Mendelian data, kills LP-PLA2 as a therapeutic target.
ADMA and SDMA as endothelial function biomarkers — the homocysteine connection explained
~55 min
ADMA (asymmetric dimethylarginine) directly inhibits nitric oxide synthase; SDMA (symmetric dimethylarginine) enhances catabolism of arginine. Both deplete the arginine pool needed to make nitric oxide. SDMA is renally cleared, so elevated SDMA also captures early renal impairment. Homocysteine's association with vascular disease now has a mechanistic explanation: homocysteine impairs ADMA clearance, leading to nitric oxide deficiency.
Why this matters: Gives the first mechanistically coherent blood test for endothelial dysfunction — the one gap in the standard lipid-panel workup. Also explains the homocysteine–cardiovascular association through a clear biochemical pathway.
Dayspring advocates measuring ADMA, SDMA, and arginine together (all three come from the same assay), with SDMA additionally acting as a renal function marker superior to creatinine in athletes whose elevated muscle mass inflates creatinine. His primary use case: a primary prevention patient with borderline apoB — if ADMA/SDMA are elevated, that is evidence of active endothelial dysfunction, which converts a lifestyle-first plan into a stronger argument for earlier intervention.
Perhaps the best use of ADMA/SDMA is in the primary prevention setting where you got a little borderline apoB level — if those markers are up, that tells me whatever is going on in you, you have endothelial dysfunction, so you're down the road towards vascular pathology.
Also said
“Homocysteine really inhibits the clearance of ADMA, and that's very clear — when you correct it, that would therefore screw up nitric oxide production... it brings even oxidation into the process.”— The mechanistic link that finally explains why elevated homocysteine predicts cardiovascular disease.
ApoC3 on LDL: the CARE trial showed statins fail in apoC3-enriched LDL — and an antisense drug is coming
~1 h 30 min
Frank Sachs' post-hoc analysis of the CARE trial found pravastatin failed to reduce cardiovascular events in patients whose LDL particles carried apoC3 — even though it still lowered apoB. ApoC3 delays clearance of all triglyceride-rich lipoproteins, increases CETP-mediated cholesterol enrichment, and makes LDL residual risk statin-resistant.
Why this matters: Identifies a subgroup where statin therapy is essentially futile from an events-reduction standpoint, who require apoC3-targeted therapy — and establishes apoC3 as a longevity gene candidate.
Background
ApoC3 is a pro-inflammatory protein that retards lipoprotein lipase activity, blocks VLDL and chylomicron clearance, and extends the half-life of all TG-rich lipoproteins.
Dayspring: 'I don't believe and I could stand corrected... that there is a longevity gene on cardiovascular disease that is a stronger predictor of longevity than hypo-functioning apoC3.' The antisense drug being developed would suppress hepatic apoC3 production. A new trial comparing DHA versus EPA showed DHA specifically lowers apoC3 whereas EPA does not.
Those who had high triglycerides — pravastatin was a useless drug — it didn't reduce any events... the only people that got event reduction where pravastatin lowered triglycerides was those who had apoC3-enriched LDL particles.
Also said
“I don't believe... there is a longevity gene on cardiovascular disease that is a stronger predictor of longevity than hypo-functioning apoC3.”— Elevates apoC3 loss-of-function to the top longevity target in cardiovascular medicine.
REDUCE-IT imminent: high-dose prescription EPA as statin adjunct
~1 h 45 min
The REDUCE-IT trial (statin ± prescription-strength EPA in high-risk patients) was complete at time of recording, results expected at American Heart Association. Dayspring and Attia anticipate a positive result. High-dose EPA lowers apoB by an additional 8–10% beyond statin monotherapy.
Why this matters: Would be the first outcome evidence validating prescription omega-3 as a cardiovascular event-reduction drug on top of statins — at a time when mainstream medicine had largely dismissed all omega-3 therapy as useless.
Dayspring's key methodological critique of negative omega-3 trials: they use sub-pharmacologic doses and do not measure who is deficient. He recommends measuring red blood cell EPA+DHA (not plasma free fatty acids) because RBC omega-3 index reflects true tissue status over 60–90 days.
Now clearly high dose prescription-strength EPA can be a helpful adjunct of therapy to lower apoB and whether it's clearing remnants or whatever it's doing it's lowering apoB an additional 8–10%. Great — and it's a pretty innocuous therapy.
F2-isoprostanes as the most defensible pro-oxidative state biomarker
~43 min
As fatty acids are oxidized they generate F2-isoprostanes, measurable in spot urine. Dayspring rates F2-isoprostanes above oxLDL and MPO for detecting a systemic pro-oxidative state because they arise directly from fatty acid peroxidation — the upstream event that leads to arterial wall lipid oxidation.
Why this matters: Clinicians widely order oxLDL but Dayspring explains that in plasma, true LDL oxidation does not occur — antioxidants are too abundant. OxLDL assays capture minimally-oxidized apoB with aldehyde adducts, an imperfect proxy. F2-isoprostanes directly measure the fatty acid oxidation process.
The best of all is as fatty acids get oxidized, derivatives form — they're called isoprostanes — and you can easily assay something called F2-isoprostanes, which have clearly been linked to pro-oxidative states. Now it's a urine test, not a serum test.
DHA lowers apoC3; EPA does not — upends the conventional EPA-first framing
~1 h 33 min
A trial comparing DHA versus EPA head-to-head found DHA is the fraction that lowers apoC3, while EPA does not. This matters because apoC3 is causally linked to cardiovascular outcomes and longevity. Dayspring updated his view from 'more of an EPA guy' based on this data.
Why this matters: Challenges the EPA-centric narrative (driven by REDUCE-IT) by showing DHA has its own mechanistically important target that EPA lacks.
DHA is the one that lowers apoC3 — not EPA. So all of these mega advocates of EPA, I don't know if apoC3 trees are involved there.
Recommendations
Products, supplements, and tools mentioned in the episode
2 items
High-dose prescription EPA (icosapentaenoic acid / Vascepa) as statin adjunct
Supplement
Prescription-strength EPA as an adjunct to statin therapy in high-cardiovascular-risk patients. Lowers apoB an additional 8–10% and anticipated to show cardiovascular event reduction in REDUCE-IT.
Dayspring distinguishes prescription-grade EPA from OTC supplements: 'They're using some miniscule, not a pharmacologic dose of these things.' He also cautions about conversion capacity: some patients cannot efficiently convert EPA to DHA, which matters given the new apoC3-lowering data showing DHA (not EPA) is the fraction that targets apoC3.
vs alternatives
Low-dose OTC omega-3 dismissed as inadequate dosing. Fibrates preferred for TG-rich/remnant compartment; EPA addresses apoB broadly and potentially apoC3 via DHA conversion.
Clearly high-dose prescription-strength EPA can be a helpful adjunct of therapy to lower apoB and whether it's clearing remnants or whatever it's doing, it's lowering apoB an additional 8–10%.
Carlson's or Nordic Naturals as OTC fish oil quality benchmarks
Supplement
When prescription EPA is not accessible, Attia names Carlson's and Nordic Naturals as the two OTC brands he will recommend based on purity and quality testing.
Attia acknowledges he does not know the esterification vehicle (triglyceride vs ethyl ester) for these brands, which matters for bioavailability. Dayspring adds: most OTC supplements are mono- or di-glycerides, not triglycerides — meaning only one of the three fatty acid positions carries omega-3, requiring larger doses to achieve pharmacologic omega-3 levels.
There are only two supplements over the counter that I fancy — one is Carlson's, the other is Nordic Naturals — just based on some of the toxicology stuff.
True Health Diagnostics — LP(a)-P (electrophoretic particle count) assay
Service Sponsored · disclosed
The only lab Dayspring identifies as offering LP(a) particle count via electrophoresis + anti-apoB immunostaining, as opposed to the widely-available but unreliable LP(a) mass assay.
DisclosureDayspring explicitly discloses he works for True Health Diagnostics, which holds proprietary rights to the LP(a)-apoB assay.
Dayspring: 'We've already announced I do work for True Health Diagnostics — the lab that actually did the development of the LP little a apoB assay which True Health absorbed and got proprietary rights to.' Despite the commercial disclosure, the scientific superiority of particle count over mass is Dayspring's primary argument.
If you want LP little a particle count, you need the electrophoretic separation — and that's available through True Health Diagnostics.
Textbook of Molecular and Clinical Biochemistry (lipids and apolipoproteins chapter) — Dayspring and Molly co-authored
Book Sponsored · disclosed
Dayspring references a 70-page chapter he co-authored with NHLBI director Alan Remaley covering lipids and apolipoproteins for clinicians wanting the most rigorous technical reference on the subject matter covered in the five-part series.
DisclosureDayspring is a co-author of the 70-page lipid chapter in this textbook.
Dayspring: 'It would take another 15 minutes to list all the lipid gods who have been available to me... I don't go on the internet and read stuff or make things up — I try and ask experts.' He frames the chapter as the post-series deep-reference for serious clinicians, not a general-public resource.
It's an expensive book. I don't expect you if you're not a lipid ologist or somebody seriously into this clinician to go out and buy it — but there is a lot of information out there.
Lines worth pulling out — contrarian, specific, or perfectly phrased
6 items
Earl got buried in his mid-50s with a sudden acute myocardial infarction sitting at home watching TV... there are many young age needless deaths occurring with a very preventable, treatable disease that's being ignored totally because they don't go and get a check or they're getting bad advice based on the wrong metrics.
The emotional center of the five-part Dayspring series — Tom's fireman friend Earl who refused medical care and died of preventable MI in his 50s. Transforms the technical lecture into a mission statement.
My guess is apo(a) is affecting totally efficacious binding to an LP little a particle — it's camouflaging the LDL receptor binding domain on apo B — and therefore I better learn how to inhibit synthesis of it.
The clearest mechanistic explanation for the most-asked clinical question in lipidology: why statins do not lower Lp(a).
I don't believe... there is a longevity gene on cardiovascular disease that is a stronger predictor of longevity than hypo-functioning apoC3.
Places apoC3 loss-of-function above PCSK9, ApoE, and all other known variants as the most powerful cardiovascular-longevity genetic factor Dayspring is aware of.
There have been two mega trials where pharmaceutical industry has developed LP PLA-2 inhibitors, gave them to patients, shut down LP PLA-2 activity, drastically reduced LP PLA-2 mass levels, plummeted — no outcome reduction whatsoever.
The definitive clinical evidence that LP-PLA2 is a marker, not a causal driver — despite being widely ordered as an actionable test.
The best of all is as fatty acids get oxidized, derivatives form — they're called isoprostanes — and you can easily assay something called F2-isoprostanes, which have clearly been linked to pro-oxidative states.
Dayspring's preferred pro-oxidative biomarker — mechanistically upstream of the arterial wall events that cause atherosclerosis, and available from a simple spot urine.
LP little a mass becomes a useless metric... the molecular weight of apo little a is very very variable.
The single clearest explanation for why standard LP(a) mass testing gives clinicians a false sense of precision.
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