hs-CRP blood test: what your CRP level says about inflammation

CRP and hs-CRP: the same protein, two methods

C-reactive protein (CRP) is made in the liver when the body reacts to infection, inflammation or tissue damage. The level rises within 4–6 hours, peaks after 3–4 days and falls again quickly, because its half-life is only 18 hours. sundhed.dk – Patienthåndbogen sundhed.dk – Lægehåndbogen

The standard CRP test, which Danish GPs often run in the surgery from a finger prick, is designed to detect infections. Most Danish laboratories use an upper limit of 5, 8 or 10 mg/L. In healthy people CRP is usually below 1 mg/L, and the standard method cannot distinguish differences in the low range. sundhed.dk – Patienthåndbogen sundhed.dk – Lægehåndbogen

hs-CRP stands for high-sensitivity CRP. It is the same protein, measured with a more sensitive method, so you can tell the difference between, say, 0.5 and 3 mg/L. Some laboratories report in nmol/L: 10 mg/L equals about 100 nmol/L. sundhed.dk – Patienthåndbogen sundhed.dk – Lægehåndbogen

Normal ranges: what does your CRP level mean?

The cardiovascular risk cut-offs come from a joint statement by the US Centers for Disease Control and Prevention (CDC) and the American Heart Association (AHA). The values for infection and disease come from the Danish medical handbook on sundhed.dk. The figures are a guide, and laboratories may measure slightly differently. sundhed.dk – Lægehåndbogen PMID 12551878

How to get a reliable result

hs-CRP fluctuates more from day to day than, for example, cholesterol. A single number can therefore be misleading. The AHA and CDC recommend using the average of two measurements taken about two weeks apart, and repeating the test if it is above 10 mg/L. sundhed.dk – Lægehåndbogen PMID 12551878

The test only makes sense if the result can change something. If you already have known heart disease, diabetes with organ damage or an LDL above 5 mmol/L, you are already in a group where your doctor will recommend treatment. In that case hs-CRP rarely changes the decision. sundhed.dk – Lægehåndbogen PMID 12551878

• Be well: wait at least two weeks after a cold, flu, dental work, a sprain or surgery.
• Avoid very hard exercise or a marathon in the days before the test.
• You do not need to fast.
• Tell your doctor if you take the pill or oestrogen tablets, which can raise CRP.
• Use the same laboratory when you want to track changes.

hs-CRP and the heart: a marker, not a cause

A large pooled analysis of 54 studies with 160,309 people showed that a three-fold higher CRP was linked to a 37% higher risk of heart disease after adjusting for blood pressure, cholesterol, smoking and diabetes. When the researchers also adjusted for fibrinogen, another inflammatory protein, the figure fell to 23%. PMID 34458905 PMID 20031199 PMID 18971492

Danish researchers have shown that CRP itself is unlikely to damage blood vessels. In a Copenhagen study, people with gene variants that raise CRP by up to 64% did not have more heart attacks or strokes. High CRP, on the other hand, was associated with a 1.6-fold higher risk of heart disease. The conclusion is that CRP is the smoke signal of inflammation, not the fire itself. PMID 34458905 PMID 20031199 PMID 18971492

That is why European prevention guidelines do not recommend routine hs-CRP testing for everyone. The test can be used as an add-on when your doctor is unsure whether you should start preventive treatment. PMID 34458905 PMID 20031199 PMID 18971492

Inflammation as a treatment target: JUPITER, CANTOS and colchicine

The JUPITER trial gave 17,802 healthy people with LDL below 3.4 mmol/L and hs-CRP of at least 2 mg/L either a statin or placebo. The statin lowered LDL by 50% and hs-CRP by 37%, and the combined endpoint of heart attack, stroke, cardiovascular death, revascularisation and hospitalisation for unstable angina fell by 44%. PMID 18997196 PMID 28845751 PMID 32865380

The CANTOS trial tested canakinumab, an antibody against the inflammatory messenger interleukin-1β, in 10,061 people who had had a heart attack. The best dose gave 15% fewer new cardiac events without changing cholesterol, but more fatal infections. The drug is not approved for heart disease. PMID 18997196 PMID 28845751 PMID 32865380

Low-dose colchicine (0.5 mg daily), an old gout drug, gave 31% fewer cardiac events in 5,522 people with known coronary artery disease. There were, however, slightly more deaths from other causes. Colchicine for the heart is only relevant in agreement with a cardiologist. PMID 18997196 PMID 28845751 PMID 32865380

What the trials have in common is that participants were already at high risk. No trials show that healthy people with a mildly raised hs-CRP live longer from anti-inflammatory drugs or supplements. PMID 18997196 PMID 28845751 PMID 32865380

What raises hs-CRP – and what can you do?

Low-grade inflammation usually has an explanation. Smokers and people with overweight have higher CRP than non-smokers and people of normal weight. Find the likely source before you buy supplements. How diet can dampen inflammation is covered in our article on the anti-inflammatory diet. sundhed.dk – Lægehåndbogen PMID 34458905

A 12-week plan if your hs-CRP is above 3 mg/L

An hs-CRP above 3 mg/L is not a diagnosis. It is a signal to look at your overall risk and at the habits driving the inflammation. This plan is based on European prevention advice. PMID 34458905 PMID 12551878

• Week 0: Repeat the test after two weeks of good health, and have your blood pressure, cholesterol and HbA1c measured at the same time.
• Week 1: Review your overall risk with your doctor – hs-CRP alone does not decide whether you need medication.
• Weeks 1–12: Stop smoking, and move for at least 30 minutes on most days, ideally with strength training twice a week.
• Weeks 1–12: Aim for 5–10% weight loss if you are overweight, and keep alcohol below 10 standard drinks a week.
• Week 4: Book a dental check-up, and talk to your doctor if you snore or wake up unrefreshed.
• Week 12: A new hs-CRP test under the same conditions as the first.

When should you see a doctor?

The Danish medical handbook states that a mildly raised CRP without an obvious explanation should lead to further investigation. Contact your GP if CRP is above 10 mg/L in two tests, or if you have fever, weight loss, night sweats, swollen or tender joints, persistent abdominal pain with diarrhoea, or a new headache with tenderness at the temples after the age of 50. sundhed.dk – Patienthåndbogen sundhed.dk – Lægehåndbogen

In older people, a persistently mildly raised CRP can also be an early sign of disease that does not yet cause clear symptoms, such as a chronic infection or cancer. Low-range values between 0.5 and 5 mg/L are associated with the risk of both cardiovascular disease and cancer. That is why an unexplained finding should be followed up rather than simply put down to lifestyle. sundhed.dk – Patienthåndbogen sundhed.dk – Lægehåndbogen

Call 112 (the European emergency number) for high fever with feeling very unwell, shortness of breath or chest pressure. Outside surgery hours, call your local out-of-hours service – 1813 in the Capital Region of Denmark. sundhed.dk – Patienthåndbogen sundhed.dk – Lægehåndbogen