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Blood measurements of hs-CRP are often performed to assess the risk of future heart disease. It has also been suggested that hs-CRP can be used to target therapy and tailor risk modification to prevent cardiovascular disease (CVD).
Therefore it is important to understand when and why these measurements should be done, and how they should be interpreted.
It has been known for ages that inflammation plays a major role in the development of heart disease. Although the idea initially emerged in the late 1800’s, it was sidelined for decades in favor of the so-called cholesterol hypothesis.
However, recently the “inflammation hypothesis” has resurfaced and many scientists believe inflammation is a primary causative factor in many chronic diseases of today, such as diabetes, heart disease, cancer and degenerative brain disease.
A standard lipid profile is commonly used to assess the risk of heart disease. Blood levels of LDL-cholesterol (LDL-C) are traditionally used for risk assessment. LDL-C is often used as a therapeutic target as well and dietary recommendations and drug therapy often primarily aim at lowering LDL-C.
CRP and hsCRP
C-reactive protein (CRP) is produced by the liver. This protein was discovered in 1930 by William Tillett and Thomas Francis, investigators at the Rockefeller University. They found it could be isolated from the blood of patients with a particular type of pneumonia. Later it was discovered that elevated CRP-levels could be measured in blood in response to inflammation.
The difference between CRP and hs-CRP is contained in the “hs” abbreviation; “high sensitivity.”
CRP is traditionally measured down to concentrations of 3-5 mg/L, whereas hs-CRP measures down to levels around 0.3 mg/L. This improved sensitivity allows hs-CRP to be used to detect low-grade inflammation.
The Predictive Value of hs-CRP
In 1943 Gunnar Lofstrom, a Swedish scientist described elevated blood levels of CRP in patients with heart attack (acute myocardial infarction).
Studies in the 1990’s further confirmed the association between CRP and atherosclerotic coronary artery disease and acute cardiovascular events such as heart attacks and stroke.
However, although CRP-levels were found to be raised in patients with these disorders, the question remained whether CRP levels among healthy individuals could predict future cardiovascular events.
With the publication of the Physician’s Health Study (PHS) in 1997, there was a paradigm change in the use of hs-CRP as a marker of cardiovascular risk.
The study was a prospective evaluation of 22.000 initially healthy men. Baseline levels of hs-CRP were significantly higher among those who subsequently went on to have a heart attack or stroke compared to those who did not. The results indicated that the predictive value of hs-CRP was independent of other risk factors such as blood cholesterol and smoking. The results also suggested that hs-CRP was a better predictor of cardiovascular events than several other inflammatory biomarkers.
In the WHS (Women’s Health Study), LDL-C was compared with hs-CRP in almost 28.000 healthy women who were followed for eight years. After correction for other risk factors, hs-CRP was found to be a stronger predictor of cardiovascular events than LDL-C. Women in the high hs-CRP and low LDL-C group were at greater absolute risk than the subgroup with low hs-CRP and high LDL-C levels. However, screening for both biological markers provided a better predictive value than either test alone.
What Is the Ideal Level of hs-CRP?
Large scale clinical trials have used a hs-CRP cut point of 2 mg/ml for defining an increased risk of CVD.
This would imply that those who have hs-CRP above 2 mg/ml are at increased risk.
However, a desirable value is probably less than 1 mg/ml. An hs-CRP level higher than 3 mg/ml is associated with increased risk in most studies.
- Low risk: less than 1.0 mg/L
- Average risk: 1.0 to 3.0 mg/L
- High risk: above 3.0 mg/L
- Above 10 mg/mL usually indicates acute inflammation
Can hs-CRP Be Used to Target Therapy?
It has been suggested that hs-CRP may be used to select patients who may benefit from treatment with statin drugs or to tailor the intensity of risk modification in general.
The JUPITER trial randomized 17.800 middle-aged to elderly individuals at intermediate or low-risk to treatment with rosuvastatin (a cholesterol lowering drug) or placebo. Patients selected for the study had to have hs-CRP > 2mg/l, and LDL-C < 130 mg/dl (3.37 mmol/l). Rosuvastatin significantly lowered both hs-CRP and LDL-C. There were significantly fewer cardiovascular events on rosuvastatin compared with placebo (44% relative risk reduction).
The results of the JUPITER trial may indicate that hs-CRP levels can be helpful for selecting individuals who may benefit from statin therapy.
The Limitations of Measuring hs-CRP
It is important to remember that both CRP and hs-CRP become elevated in a wide range of acute and chronic inflammatory conditions such as infections, rheumatic arthritis, many other inflammatory diseases, and many cancers. These conditions cause release of interleukin-6 and other cytokines that trigger the synthesis of CRP by the liver.
Because there are many disparate conditions that can increase CRP and hs-CRP, an elevated CRP level does not indicate a specific disease.
Due to its poor sensitivity and low negative predictive value, measurements of hsCRP can not be used to rule out disease.
Most clinical guidelines have emphasized that data from experimental research, epidemiological studies, and large clinical trials do not provide conclusive evidence for the routine use of hsCRP measurements for risk prediction.
At this time, there is insufficient evidence to recommend widespread use of hs-CRP in clinical practice.
22 thoughts on “hs-CRP”
Not certain of my facts, just a memory of reading that one of the lead authors who came out in favour of using hsCRP as predictive of heart disease, also owns the patent on the test… do hope I am not maligning someone here……
Methods section: “All participants were followed for the occurrence of first cardiovascular events, including nonfatal myocardial infarction, nonfatal ischemic stroke, coronary revascularization procedures, and death from cardiovascular causes” —> from the study you linked [Comparison of C-Reactive Protein and Low-Density Lipoprotein Cholesterol Levels in the Prediction of First Cardiovascular Events]
I’m unable to access the complete study.
Were all-cause mortality events included in the analysis.
If so, does the effectiveness of this particular statin change?
Also, what are the relative & absolute risk statistics?
Here is the link to the free access full paper. Notice that this was not a statin trial. The study compared the predictive value of using hs-CRP vs. LDL-C to assess the risk for future cardiovascular events.
LDL-C is quite a weak predictor of overall mortality & since you cannot have atherosclerosis without inflammation, but you can have it with high & low cholesterol values…HS-CRP & CRP seem much more indicative of underlying issues causing chronic or acute inflammation, respectively.
[For the general population] I don’t see why it matters that a marker gives a risk measure for a SPECIFIC event…isn’t it more important that we know something is wrong, reliably first, & then to dig deeper with other markers?
Statins seem like such old school medicine honestly – I fail to see its use in 99% of cases…
Actually, LDL-C is at the very least a decent indicator of CVD risk whereas inflammation markers have limited clinical use – at least according to the evidence so far.
And as far as statins being “old school medicine” is concerned, I take it that you mean they’re effective among CVD patients and those belonging to a group of people at high risk of developing CVD? You know, instead of being a panacea – which, consequently, is something that low carbers/paleo hacks/CAM practicioners etc. etc. all believe they’ve found … 🙂
LDL-C relating to CVD risk is based on a weak chain of causality: the Dietary Fat hypothesis —> working via the Lipid Hypothesis, which then supposedly accounts for CVD events: nope, sorry, this has been constantly shown to break down right from the Dietary Fat hypothesis.
See Chris Masterjohn’s important distinctions here https://blog.cholesterol-and-health.com/2011/02/proper-use-of-term-lipid-hypothesis.html & here https://blog.cholesterol-and-health.com/2011/02/origin-of-lipid-hypothesis-and-proposal.html .
I agree, LC/Paleo isn’t a panacea. Not because the principles underlying them are incorrect, simply because their names don’t tell us enough about health & nutrition to make them “catch all terms”.
What is much more easy to show is that statins are incredibly ineffective, block a fundamental process within the body, are mired in corruption & big pharma, hidden research, extreme range & magnitude of side effects, promotes the “band-aid” approach to health and the list goes on…
“LDL-C relating to CVD risk is based on a weak chain of causality: the Dietary Fat hypothesis —> working via the Lipid Hypothesis, which then supposedly accounts for CVD events: nope, sorry, this has been constantly shown to break down right from the Dietary Fat hypothesis.”
You do realize that the sc. lipid hypothesis (relevance of blood lipid levels in CVD) and dietary fat hypothesis (relevance of dietary fat in CVD) are two separate things? There is absolutely NO doubt about the roles of LDL, HDL etc. in the development in CVD. To imply otherwise is to utter a religious statements, nothing whatsoever to do with science.
And as far as LDL-C is concerned, it’s clearly a risk factor. Which, of course, means that not everyone who has high LDL-C is in danger or that not everyone who has low LDL-C is safe. That should go without saying.
“What is much more easy to show is that …”
… your claims are conspiracy theory BS. Plain and simple. Statins have been clearly shown to be effective in clinical studies (for people with established CVD and/or people who have high risk of contracting CVD). Statin therapy lowers LDL-C, but not up to a point where any of the important cellular processes involving cholesterol would be disturbed (since the amount of cholesterol required is but a fraction of what circulates in the blood of an average Westerner). And the “band-aid” BS is simply another case of people who have been cured “wrongly”.
In other words, what you’re saying is nothing new. Just like many other forms of denialism (Holocaust, HIV etc. etc.), it just refuses to die out.
Ad hominem attacks, utter dismissal and missing the point (intentionally or not). I’m done. Have a good life.
God I love people who shoot the same ol’ crapload of denialist clichés and then act all hurt & teary-eyed when someone points this out.
FYI, none of what I stated above constitutes an ad hominem. No part was directed against your person: I simply commented on your CLAIMS.
Your statement that LDL-C IS a risk factor is interesting in that it does not predict 70+% of adverse cardiovascular events. The clinical trials that have clearly established the role of LDL are mostly absent. I am glad you have some. The ones I have seen, show, in the words of Pfizer regarding their trial, that the absolute risk reduction is 1% for people with KNOWN risk factor: and one thing is certain, Pfizer is going to provide the BEST number that they can come up with, Not very impressive given the NNT is 99 to 1.
You also believe yoghurt diminishes the incidence of Type 2 diabetes. I have stripped my serratus off my ribs from LMAO on that one.
You know Robin, if you actually bothered to give references to back up your silly claims, I might reply in length.
But since I know that you won’t (because you can’t), this seems to be the end of this escapade.
You do realize that the sc. lipid hypothesis (relevance of blood lipid levels in CVD) and dietary fat hypothesis (relevance of dietary fat in CVD) are two separate things?
What….two separate things? These two concepts are highly entwined for humans and non-human primates alike, something that is acknowledged by pretty much every single institution working with public health. Saturated fats are the most potent LDL -elevating fatty acids. As concluded by the Glueck (member of McGovern panel) in response to skeptics:
Animal studies, particularly in subhuman primates, reveal an unequivocal causal relation between dietary cholesterol or saturated fat, plasma cholesterol levels and development or regression of atherosclerosis
Working from the Darwinian foundation (the backbone of Western biomedical science), chronic elevation of LDL should induce CHD independent of mechanism used in every single mammalian specimen.
Doc, the inflammation story is pretty much sorted out:
“Taken together, all of these findings suggest that the inflammation associated with atherogenesis is not sufficient in itself to cause further lesion progression or even to maintain lesions at a steady state once the hypercholesterolemia has been fully corrected. In other words, many (or even most) of the inflammatory processes in the advancing lesion are downstream responses ultimately traceable to hyperlipidemia and its consequences. Consequently, early and aggressive correction of hypercholesterolemia may be sufficient”.
Yes, treating dyslipidemias through statin medications has brought us [in the words of wise Borat] GREAT SUCCESS!!
Oh, wait…it hasn’t actually – has it?
It’s 2014. You have a computer that can access the internetubez (I think that’s what they’re called?). Use it – maybe for something else than regurgitating “committee science”.
Compared to the treament options BEFORE statins: yes, it has.
Check this out: Studer et al (2005), “Effect of different antilipidemic agents and diets on mortality: a systematic review” when talking about mortality, overall and cardiovascular. Statin therapy is clearly superior and clearly the only option that’s unequivoically efficient …
(… because the role of n3-fatty acids is based on a SINGLE study that has not been replicated since -whereas the potency of statins in people with established CVD and/or in high risk population has been shown numerous times)
“What….two separate things?”
Yes. The influence of food on lipid levels is a different case than the role of lipid levels in the etiology of atherosclerosis.
Now this, of course, doesn’t mean that foods can’t/don’t pay a role in the etiology of atherosclerosis. That too should go without saying.
I found the discussion so far of interest but I doubt if it has changed significantly my clinical approaches to risk reduction. My comment is this, I “believe” that when it comes to effectively predicting or preventing CV disease in a given patient and not a study population with specific inclusion and exclusion criteria, we are dealing inevitably with multi-variable analyses and significant contextual variables. Factors associated with lipids, inflammation, stress, blood pressure, genetics, platelet aggregation, diet, sleep, affect, pain scores, substance abuse, etc. etc…..are all part of the clinical picture.
Bottom line, as it stands in terms of laboratory data I feel reassured if the intervention is relatively safe and the risks of CV events are relatively high, that seeing hsCRP come down, HDL-C go up, and LDL-C go down are good signs to see.
I also believe that our relative “fixation” on these specific lab variables are in part a product of how interventions in our culture are incentivized including the process by which substances are allowed to be produced and marketed.
There are significant financial interests that are at stake when there are products which can be eventually widely marketed. Thank you all for your contributions.
Great information. Thank you for sharing this to us.
MY WIFE PRAFULLA ADESHRA
LATEST REPORTS SHOWS THAT
HIGH SENSITIVE C – REACTIVE PROTINE [HSCRP] VALUE >10.5 MG/L
TOTAL CHOLESTEROL 219
TC/HDL CHOLESTEROL RATIO 3.5
LDL/HDL RATIO 3.5
Stop eating so many carbs
Hi How is your wife’s health now.? What is her HS-CRP value. I recently got 3.67 MG/L. Iam bit worried about it. Can U advice me?. My reports show that
TOTAL CHOLESTEROL PHOTOMETRY 182 mg/dl 125-200
HDL CHOLESTEROL – DIRECT PHOTOMETRY 44 mg/dl 35-80
LDL CHOLESTEROL – DIRECT PHOTOMETRY 110 mg/dl 85-130
TRIGLYCERIDES PHOTOMETRY 122 mg/dl 25-200
TC/ HDL CHOLESTEROL RATIO CALCULATED 4.1 Ratio 3 – 5
LDL / HDL RATIO CALCULATED 2.5 Ratio 1.5-3.5
VLDL CHOLESTEROL CALCULATED 24.4 mg/dl 5 – 40
NON-HDL CHOLESTEROL CALCULATED 137.8 mg/dl < 160
HOMOCYSTEINE C.L.I.A 35.2 µmol/L
HIGH SENSITIVITY C-REACTIVE PROTEIN (hs-CRP) NEPHELOMETRY 3.62 mg/L.
Please share your views on this
My hs-crp level- 8. mg/L
ldl- 2.70 mmol/l
chol/hdl ratio 2.88
non-hdl colestrol 3.31 mmol/l
Can anyone suggest what does the test results shows?
My hs-C REACTIVE PROTEIN IS 3.87 mg/l please consult problem
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