Exactly my point, haha. If it’s >70 then you’d be wanting to take medication no matter what.
Fair point, but I think ezetimibe monotherapy is pretty uncommon, so I would assume anybody taking Ezetimibe would already be on a statin.
(And besides, I reckon most doctors are still just ordering total and LDL-C. We can barely convince GPs and other “normal” doctors to order ApoB or Lp(a), let alone thinking about particle sizes haha!)
Most doctors still don’t prescribe Ezetemibe. That’s a head scratcher there. If there is a prescription for a statin, it should always be paired with Ezetemibe IMHO. There’s just no reason not to.
Yes, I had to almost bully my mother’s GP into prescribing it for her. He was saying it’s an old drug, not very good etc. I said “humour me”, and lo-and-behold her LDL-C dropped another 30% from 10mg/d just as I said it would.
Don’t even get me started!!! My sister and brother each have a ‘good’ cardiologists. I had to get them get them to test their apob and lp(a) AND to get ezetimibe.
I also just found out that no one has been testing my much older brother’s A1C, vit d, or b12… (many other thing could be added to the list, but those are less common)… AND no A1C test even though his fasting glucose is high… criminal.
Exactly. That is my thought for many tests that I do not take.
For decades, the standard medical model has obsessively focused on low-density lipoprotein cholesterol (LDL-C) and blood pressure as the primary arbiters of cardiovascular risk. However, this clinical paradigm often fails to account for the substantial residual risk observed in seemingly healthy individuals. A new paradigm is aggressively taking hold: chronic, low-grade systemic inflammation is a causal driver of atherosclerotic cardiovascular disease (ASCVD), and high-sensitivity C-reactive protein (hsCRP) is a highly reliable proxy for this risk.
This population-based study evaluated 448,653 adults from the UK Biobank who had no prior history of ASCVD. The researchers set out to determine if a single baseline measurement of hsCRP could accurately predict major adverse cardiovascular events (MACE), cardiovascular death, and all-cause mortality over a median follow-up of 13.7 years. The findings are unequivocal. Participants with hsCRP levels greater than 3 mg/L faced a 34% higher relative risk of MACE, a 61% increased risk of cardiovascular death, and a 54% higher risk of all-cause mortality compared to those with levels under 1 mg/L. Even at the tighter threshold of 2 mg/L, individuals at or above this mark had a 22% increased risk of MACE.
Crucially, when pitted head-to-head in variable importance analyses, hsCRP ranked above several traditional risk factors—including LDL-C and systolic blood pressure—for predicting cardiovascular outcomes. Furthermore, adding hsCRP to the European standard SCORE2 risk algorithm yielded a total net reclassification improvement of 14.1%, meaning it significantly corrected the risk estimation for a large swath of the population. Serial measurements taken 4.4 years apart in a subset of nearly 16,000 participants proved that hsCRP levels are biologically stable over time, silencing critics who argue the biomarker is too volatile for routine screening.
The overarching message is clear: the absence of standard modifiable risk factors does not guarantee cardiovascular health if systemic inflammation goes unchecked. Routine hsCRP screening is a practical, low-cost tool that provides profound predictive value for primary prevention.
Context: This research was led by investigators at University Hospital Aachen, RWTH Aachen University, in Germany, and published in the European Heart Journal (2025).
Impact Evaluation: The impact score of this journal is 35.7, therefore this is an Elite impact journal.
Open access paper: C-reactive protein and cardiovascular risk in the general population (Dec. 2025)
To me, this is the significant quote worth interrogating. The fact that systemic inflammation, or dry inflammation is a key health driver, has been known for a while now. That hsCRP is a reliable proxy for systemic inflammation is what’s interesting, because there’s always been the worry over hsCRP being reactive to momentary inflammation and so not a reliable long term marker. That was one reason IL-6 is measured too when trying to assess systemic inflammation.
But what’s super interesting is that apparently hsCRP is a long term biomarker that persists for any given individual across years. This immediately raises a whole bunch of questions: is it like genetically determined Lp(a), that’s hard to budge without drugs, is it less hardwired but still set like LDL/HDL levels, super subject to diet/exercise/lifestyle, does lowering it directly through drugs just lower the biomarker number without affecting the underlying inflammation etc. I think there are also likely bounderies beyond which it doesn’t matter much, and is hard to measure, like below 0.25. FWIW, my hsCRP has been pretty stable for decades bouncing around between 0.25 (possibly lab limited sensitivity) and 0.6, but spending most of the time around 0.3.
There is also a bunch of interesting papers in one of the earlier cardiovascular threads showing that high Lp(a) has a negative CVD impact only with elevated hsCRP (and IL-6), around 2+.
I don’t think HSCRP is genetic. My parents both have very low HSCRP results, below 0.5, while mine is about 1.8. Why mine is higher I haven’t a clue.
My working theory is that I don’t get enough sleep (5-6 hours average, sometimes more sometimes less)
Here is what Gemini Pro suggests are the environmental contributors to higher hs-CRP levels (and yes, it seems sleep is likely an issue if its under 7 hours/night).
Long-term exposure to airborne pollutants is consistently linked to elevated hs-CRP. Fine particulate matter penetrates the pulmonary capillary bed, activating alveolar macrophages and the NLRP3 inflammasome, which initiates a systemic cytokine cascade.
The nutritional environment dictates gut microbiome composition and metabolic stress, directly influencing hepatic CRP output.
The psychosocial environment translates to biological wear-and-tear, conceptualized as allostatic load.
Fantastic question! From what I know, CRP is both a biomarker and an active player in inflammation. That makes it a very cool thing to measure because it’s a player and not just a bystander.
However, we also have to consider that this is a large, observational, population-level study. Presumably this population was not actively trying to be healthier. It doesn’t mean that hsCRP is not modifiable in you or me by improving our lifestyle, diet, sleep etc.
I can give a small anecdote to support this. I learned aged 38 that I have sky high Lp(a) at more than 80mg/dl. And I had already learned, aged 31, that I have heterozygous familial hypercholesterolemia, with an LDL-C of around 200mg/dl. However, my inflammation is super low, with hsCRP being essentially undetectable (and all other non-specific inflammation markers being low). I had a CTCA last year which confirmed no detectable soft plaque, and a zero calcium score. However, my colleague, the same age as me, and with better lipids than me, is the skinny-fat insulin resistant type of build, and high (~2.0) hsCRP, and found he had a calcium score of 300. So my little n = 1 does at least support an idea that inflammation is a driver, and that absence of inflammation is protective. I reckon if my inflammatory baseline was higher, my horrible lipids should have resulted in plenty of plaque buildup already.
There is a recent position paper about this which suggests targeting CRP > 3 and using anti-inflammatory drugs to lower it to lower CVD risk: https://www.jacc.org/doi/epdf/10.1016/j.jacc.2025.08.047
CRP is made because of the presence of IL-6 which is caused both by infection and SASP. Hence the background level of CRP is an indicator of the burden of senescent cells.
I did get my CRP (high sensitivity (hs) is only the test not the molecule) below 0.15mg/L, but it has now crept up to 0.36. I think I know why and I intend knocking it back down again later.
It is an acute-phase protein of hepatic origin that increases following interleukin-6 secretion by macrophages and T cells. Its physiological role is to bind to lysophosphatidylcholine expressed on the surface of dead or dying cells (and some types of bacteria) in order to activate the complement system via C1q.[5]
Which are the most recommended drugs/supplements to try?
The paper recommends lifestyle first: quitting smoking, cutting junk food, exercise, healthy weight etc. I know you have that covered 
After that, colchicine, which I believe you already take!
And if hsCRP is still persistently high, it recommends to take more aggressive lipid-lowering actions than you would have otherwise
A+ for your excellent memory!!
I’m happy to report my crp is .5!!!
My husband is the one with 3.5… and this is low for him!!!
He has lifestyle covered too… well, aside from tortilla chips!!
Looks like I should be spiking his salsa with colchicine!
I didn’t know lowering lipids would help his crp, so this is great info to present to him… thx!
I take organic grape seed extract (Pure Synergy) twice daily for general anti-inflammatory benefits. It’s also proven to lower hs-CRP specifically:
Sorry Beth, just to clarify, lowering lipids will not directly help lower CRP.
The overall purpose is to reduce cardiovascular risk. That risk is made up from a bunch of factors, including lipids and inflammation. So the paper is saying that if you can’t control the inflammation (i.e. CRP won’t go down), you can be more aggressive with the lipids to reduce the overall risk.
These numbers are made up, but for example; maybe CRP of 3.5 and LDL-C of 30mg/dl is equal to CRP of 0.5 and LDL-C of 80mg/dl in terms of overall cardiac risk.
Beth - check out this new study… they are talking about SS-31 as a possible solution: Redefining "Inflammageing": Cardiovascular Inflammation is a Symptom of Unresolved Molecular Entropy, Not the Root Cause
I cannot tolerate statins repatha inclisiran bempedoic. severe glute pain. Cannot walk or sleep. CAC 166 and LDL 5.5 / Anyone have this problem and have had relief with a medication/supplement? Someone suggested to try tadalafil, then try rapa, then try ss31. Any strategies?
Thank you for this!!! Good ol’ SS-31 strikes again!!
Btw… you asked if it was giving me extra energy and I was non committal.
After skipping a couple doses, today I gave myself a double dose (aprox 9mg) …coincidence or not, I had more energy and motivation today than I’ve had in forever. My husband even said what has gotten into you. Too soon to be sure it’s related, but days like today pretty much don’t happen.
@Satchel so sorry to hear this and hope someone has some good ideas for you!
Just to be clear - you’ve tried all those medications and they all have the same side effect on you - severe glute pain?
You may want to look at Ezetimibe (Zetia) - another cholesterol-lowering medication.
You mentioned your LDL is 5.5. , Is that a typo, or your actual LDL-C measure in mmol/L? If its real - you must be outside the USA, which is fine, I just wanted to make sure.
I have read that: According to the 2019 European Society of Cardiology (ESC) guidelines, optimal, lower-risk ranges are <3.0 mmol/L, while for very-high-risk patients, the target is reduced to <1.4 mmol/L ( <55 mg/dL)