Ask most physicians to name the most important risk factor for heart disease, and the chances are good they will name LDL cholesterol as the baddest of bad actors. Low-density lipoprotein cholesterol (LDLC) is perceived as the # 1 contributor to clogged arteries and heart attacks. Statins lower LDLC. Case closed. Not so fast! CRP is short for C-reactive protein, which signals the presence of inflammation. High-sensitivity CRP inflammation may be at least as important as LDL cholesterol when it comes to predicting heart disease danger in high-risk patients. That’s the conclusion of an impressive study published in The Lancet (March 6, 2023).
What Is CRP Inflammation?
C-reactive protein (CRP) is a natural compound your body makes in response to inflammation. This protein is made in your liver as a reaction to some inflammatory process. Infection, for example, can trigger the production of CRP.
People who have cancer or an auto-immune condition such as ulcerative colitis, rheumatoid arthritis or lupus can also have elevated hs (high-sensitivity) CRP levels. People with underlying heart disease may also have elevated CRP inflammation.
Normal CRP Levels?
What’s considered a “normal” hs CRP level? First, this is a bit controversial. Remember, CRP inflammation is not specific to the heart. It represents overall inflammation in the body. Different laboratories may establish different levels.
We are providing numbers below as mg/dL. Some labs express these as mg/L. For example, 0.3 mg/dL is equivalent to 3 mg/L.
Roughly speaking, anything less than 0.3 mg/dL is considered “normal.”
People with CRP levels of 0.3 to 1.0 mg/dL have a minor elevation and are also considered normal. (This is also expressed as 3-10 mg/L). Diabetes, an upper respiratory tract infection or gum disease could all produce such levels.
If a high-sensitivity CRP lab test comes in between 1.0 to 10.0 mg/dL the result is considered “moderate.” It could indicate an autoimmune condition such as arthritis or an inflammatory condition like bronchitis.
Anything over 10.0 mg/dL is considered “high.” It could indicate a nasty viral infection or some other serious inflammatory reaction including heart disease.
What If Your CRP Inflammation is High?
Many cardiologists aren’t sure what to make of an elevated CRP score. Consequently, they much prefer to use LDL cholesterol as their go-to risk factor.
However, the Harvard Health Article titled:“C-Reactive Protein test to screen for heart disease: Why do we need another test?” offers this perspective:
“The Blind Spot
“But for all its virtues, cholesterol testing is seriously flawed. Research has shown that only about 50% of the people who have heart attacks have high LDL. If LDL levels are supposed to be an alarm, then it’s not going off for half of those who might benefit from a wake-up call.”“…because cholesterol screening does miss so many incipient heart attacks, it suggests that cholesterol doesn’t adequately explain heart disease.
“Inflammation seems to be that explanation, and C-reactive protein (CRP), a by-product of inflammation, may provide the test.”
The New Study on CRP Inflammation in The Lancet
Dr. Paul Ridker is one of the country’s leading cardiologists. He is the Eugene Braunwald Professor of Medicine at Harvard School of Medicine. He is also the director of the Center for Cardiovascular Disease Prevention at Brigham and Women’s Hospital in Boston.
Dr. Ridker, Dr. Steve Nissen (another heavy hitter in cardiology) and their colleagues analyzed data from three major statin studies (Lancet, March 6, 2023). Over 30,000 high-risk patients were enrolled in trials called PROMINENT, REDUCE-IT or STRENGTH.
Investigators measured both high-sensitivity CRP inflammation as well as LDL cholesterol of patients in these three studies. All patients in the trials were taking statins.
The researchers wanted to determine whether:
“…residual inflammatory risk (as measured by high-sensitivity C-reactive protein) was a stronger predictor of cardiovascular events, cardiovascular death, and all-cause death than residual cholesterol risk (as measured by low-density lipoprotein cholesterol).”
In other words, this was a smack down competition between CRP and LDLC. Which risk factor was more likely to lead to ongoing heart problems in high-risk patients already taking statin-type cholesterol-lowering drugs?
The Envelope Please:
The authors state:
“In patients with—or at high risk of—atherosclerotic disease, who are receiving contemporary statins, vascular inflammation appears to be a stronger driver of residual cardiovascular event risk than cholesterol.”
“In conclusion, in this analysis of 31 245 patients receiving contemporary statins, residual inflammatory risk assessed by high-sensitivity CRP was a stronger predictor of risk for future cardiovascular events and death than residual cholesterol risk assessed by LDLC.”
We have heard from one cardiologist who does not think much of this study. He is a great believer in LDL cholesterol as the key risk factor in heart disease. He believes statins are the unique answer to that risk factor.
But the authors of this new study suggest that:
“…targeting LDLC alone is unlikely to completely reduce atherosclerotic risk and that inflammatory pathways have yet to be fully exploited to reduce fatal and non-fatal cardiovascular event rates.”
How to Combat CRP Inflammation?
Dr. Ridker and his colleagues mention the anti-inflammatory gout medicine colchicine (Colcrys):
“To date, three randomised trials have shown that targeted anti- inflammatory therapy with canakinumab [Ilaris] or colchicine can significantly lower cardiovascular event rates among patients receiving statins in the absence of any reduction in LDLC. For general practice, the most applicable current anti-inflammatory agent for vascular protection is oral colchicine 0·5 mg daily, an inexpensive generic regimen that has shown relative and absolute risk reductions at least as large as those obtained in comparable trials of adjunctive lipid-lowering agents.”
Doctors routinely prescribe colchicine to prevent and treat gout attacks. The FDA has not approved its use to prevent or treat heart attacks. Experts would consider that an off-label use.
By the way, colchicine is a very old drug. In fact it may be one of the oldest medications currently in use. The medicine comes from the Colchicum autumnale plant. You may recognize it as autumn crocus. There are references to the healing properties of this herb in the Ebers Papyrus (1500 BCE Egypt). More information can be found in the British Journal of Dermatology, Jan. 3, 2018.
Data for Colchicine:
Are there any data to support the prescribing of colchicine to prevent heart attacks? Glad you asked!
A study published in the New England Journal of Medicine (Nov. 5, 2020) offered some interesting information:
“A total of 5522 patients underwent randomization; 2762 were assigned to the colchicine group and 2760 to the placebo group. The median duration of follow-up was 28.6 months.
“In a randomized trial involving patients with chronic coronary disease, the risk of cardiovascular events was significantly lower among those who received 0.5 mg of colchicine once daily than among those who received placebo.”
A systematic review and meta-analysis published in the European Heart Journal (July 21, 2021) reported:
“Our meta-analysis indicates that low-dose colchicine reduced the risk of MACE [major adverse cardiovascular events] as well as that of myocardial infarction [heart attack], stroke, and the need for coronary revascularization [stents] in a broad spectrum of patients with coronary disease.”
They added this caveat:
“There was no difference in all-cause mortality and fewer cardiovascular deaths were counterbalanced by more non-cardiovascular deaths.”
Evidence Supporting the Chinese Herb Astragalus Against CRP Inflammation:
Astragalus (Astragalus membranaceus) is a traditional Chinese herb used to help fight off respiratory infections. A new placebo-controlled trial from the UK shows that a component in this herbal medicine can help people recovering from heart attacks (GeroScience, April 22, 2023). The compound, TA-65, reduces inflammation better than existing medications. After a year of treatment with this oral medicine, CRP inflammation was 62 percent lower among those on TA-65 than those on placebo. It also improves immunity and lowers the risk of complications including chest pain. This herbal dietary supplement appears to be safe.
An Anti-Inflammatory Lifestyle:
I am not advocating the use of colchicine or astragalus to prevent heart attacks. I am advocating an anti-inflammatory style of living. It’s not something most cardiologists are recommending, but we think it is a low risk strategy. It should lower CRP inflammation.
What does such an approach look like? For starters, the PREDIMED study involving a Mediterranean diet supplemented with extra olive oil or nuts produced impressive cardiovascular benefits! You can read about this research and other studies at this link.
Cardiologists are often surprised to learn that this approach produces results similar to those of their favorite medications.
Here is the bottom line on the PREDIMED study:
After less than five years, people in the Mediterranean diet groups had suffered approximately 30 percent fewer heart attacks, strokes and deaths due to cardiovascular causes than those in the low-fat diet control group. That compares quite well to the use of statins. These cholesterol-lowering drugs reduce the possibility of such an event by about 25 percent (JAMA Cardiology, June 1, 2016). (This is relative risk in both cases; absolute risk reduction is much lower.)
Learn More:
Here’s more about inflammation:
You may want to listen to our recent interview with gastroenterologist Dr. Robynne Chutkan. She discusses her latest book, The Anti-Viral Gut: Tackling Pathogens from the Inside Out. She designed a dietary approach to calm inflammation in the digestive tract and boost the immune system.
We think it makes sense for the cardiovascular system too. You can listen to our interview by clicking on the white arrow inside the green circle under the representation of germs in the GI tract. An alternate approach would be to scroll to the bottom of the page and click on the “Download the mp3” link to download the free podcast.
You may also find our article titled “How to Reduce CRP and Inflammation” of value. Here is a link.
And here’s additional information on lifestyle approaches:
Finally, you will find lots of tips for following an anti-inflammatory lifestyle in our eGuide to to Cholesterol Control and Heart Health. It is located in our Health eGuides section of the website at this link. You will also learn about a risk factor for heart disease that most physicians do not measure. We think Lp(a), known as lipoprotein (a), is critically important. For some people it may be as bad, or worse, than LDL cholesterol.
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Share your thoughts about CRP inflammation in the comment section below. Have you ever had a high-sensitivity CRP test? What did your doctor recommend if your levels were high?
