Towards Blood Biomarkers for Detection of Preclinical Atherosclerosis

Early atherosclerosis, meaning the stage at which there are only smaller, still-harmless fatty deposits in artery walls, is present in a sizable fraction of people in their 40s. This can be evaluated with imaging technologies, but suitable imaging approaches are comparatively expensive. Given a reliable, cheaper way to detect this early progression of the condition, adjustments in lifestyle and application of therapies might significantly postpone later mortality. It is always easier to start early in order to slow progression of age-related disease than it is to attempt to fix matters later, once atherosclerotic plaque is more developed and life-threatening.

Established plaque cannot be meaningfully reversed using presently available therapies. In particular, lowering LDL cholesterol in the bloodstream, via statins and the like, has little effect on plaque size. Given approaches under development, it will be possible to reverse plaque and aim for a cure for atherosclerosis in the future, however. Given the development of therapies capable of this goal, only realized in animal studies to date, then a marker of early atherosclerosis could lead to early reversal, periodic clearance of preclinical plaque in order to prevent atherosclerosis from ever developing.

Unbiased plasma proteomics discovery of biomarkers for improved detection of subclinical atherosclerosis

Imaging of subclinical atherosclerosis improves cardiovascular risk prediction on top of traditional risk factors. However, cardiovascular imaging is not universally available. This work aims to identify circulating proteins that could predict subclinical atherosclerosis. Hypothesis-free proteomics was used to analyze plasma from 444 subjects from PESA cohort study (222 with extensive atherosclerosis on imaging, and 222 matched controls) at two timepoints (three years apart) for discovery, and from 350 subjects from AWHS cohort study (175 subjects with extensive atherosclerosis on imaging and 175 matched controls) for external validation. A selected three-protein panel was further validated by immunoturbidimetry in the AWHS population and in 2999 subjects from ILERVAS cohort study.

PIGR, IGHA2, APOA, HPT, and HEP2 were associated with subclinical atherosclerosis independently from traditional risk factors at both timepoints in the discovery and validation cohorts. Multivariate analysis rendered a potential three-protein biomarker panel, including IGHA2, APOA, and HPT. Immunoturbidimetry confirmed the independent associations of these three proteins with subclinical atherosclerosis in AWHS and ILERVAS. A machine-learning model with these three proteins was able to predict subclinical atherosclerosis in ILERVAS, and also in the subpopulation of individuals with low cardiovascular risk.

In conclusion, plasma levels of IGHA2, APOA and HPT are associated with subclinical atherosclerosis independently of traditional risk factors and offers potential to predict this disease. The panel could improve primary prevention strategies in areas where imaging is not available.


48 & so far I'm healthy. But definitely a bit worried about arteriosclerosis. 95 APOB I'm not sure if that is good or bad. LDL between 110 and 120. Remnant (VLDL) under 15.

This sort of tech can't happen soon enough. Whoever figures it out is going to make a boatload of money. I'll be a happily paying customer for sure.

Posted by: Matt at April 8th, 2022 5:36 PM

Roughly how long does it take before an article appears in sci-hub?

Posted by: Matt at April 9th, 2022 12:41 PM

That reminds me of this proposal from JAHA

Essentially the claim is that early lesions - as opposed to mature plaque - are still reversible. The authors argue for a 'hit hard' approach of suppressing plasma apo B through intensive LDL-C lowering to a target of 20-40 mg/dL for a period of three years in those who are still in 'early life'. (which they define as young as 25).

I confess to finding the idea tempting as I'm in that age cohort and don't fit the standard criteria for LDL intervention.

Posted by: Chris at April 9th, 2022 4:16 PM

I've got a feeling we need blood or other failry non invasive measures for each of the 7 categories of SENS damage/hallmarks of aging.

What gets measured gets done.

Imagine if there was a blood test for senescent cell burden. Then someone paying for a few doses of dastinib + quercetin could also perhaps pay a few hundred dollars for someone old down in Costa Rica or Colombia to also recieve the same few doses but they could get assesed by a local doctor with this simple blood test in a small clinical trial that skirts the FDA bureaucratic costs.

I can't imagine this happening with the current skin punch and then analysis tests for senescent cells, which are painful, require a specialist dermatologist, and co-operating lab to do the analysis.

This data could then lead to more people benefiting from D+Q (or not if it does nothing). And then perhaps further small low cost trials studying other endpoints such as knee pain, and then to futther (relatively) low cost trials under the FDA in the US.

Basically these "illegal" small trials could de-risk an intervention enough for a US university team to get a funding grant to do a small trial. But a cheap and simple blood test seems to be essential.

Posted by: jimofoz at April 11th, 2022 12:32 AM
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