CRP is a protein that helps you fight infections. However, it is also a marker of low-grade inflammation and a predictor of your heart disease risk. It links stress, emotional, and socioeconomic cues to physiological ones. Keep reading to find out about the symptoms and causes of high CRP.

Why is High C Reactive Protein (CRP) Bad?

Signals Chronic Inflammation and Stress

Apart from acute infection or injury, CRP points to chronic or systemic inflammation. Its levels rise in response to chronic stress [1].

Many chronic conditions are marked by high CRP levels, including high blood sugar, insulin resistance, high blood pressure, obesity, diabetes, gum disease, and heart disease [1, 2, 3, 4, 5].

CRP is not only a marker of inflammation, but it also worsens any underlying inflammation. In the lining of blood vessels, CRP lowers nitric oxide and prostacyclin release, which improve blood flow, while increasing the inflammatory compounds (monocyte chemoattractant protein-1 (MCP-1), interleukin-8 (IL-8), and plasminogen activator inhibitor-1 (PAI-1)) [2].

In monocyte-macrophages, CRP increases reactive oxygen species and proinflammatory cytokines, worsening oxidative stress in the body [2].

High CRP levels increase the risk of diabetes, heart disease, and other chronic diseases. CRP can also create inflammation on its own, damaging blood vessels and increasing oxidative stress in the body.

Symptoms & Health Risks of High C Reactive Protein (CRP)

High CRP levels do not cause symptoms directly. You will only show symptoms related to the cause of your high CRP levels, such as infections or chronic inflammation.

Thus, you may have symptoms of any of the diseases CRP increases your risk for.

1) Cardiovascular Disease

CRP increases inflammation in blood vessels and hardens the arteries, which can eventually lead to heart disease. Plus, it can activate cells that line the interior of blood vessels and can cause their dysfunction [6, 7, 8].

Additionally, CRP reduces nitric oxide release from arteries and veins, depriving tissues of adequate blood flow [8]. Nitric oxide is good for the cardiovascular system because it relaxes blood vessels, increasing oxygen and blood flow throughout the body [8].

To make matters worse, plaques in arteries can also release CRP into the bloodstream, perpetuating the cycle in people who already suffer from heart disease or who are at high risk [6].

When should you be concerned? CRP levels <1 mg/L are considered low-risk, 1 to 3 mg/L as average risk, and >3 mg/L as high risk for cardiovascular disease [8].

High LDL and High CRP: A Deadly Combination

Increased levels of LDL cholesterol in at-risk patients cause blood vessels to increase CRP, which may, in turn, makes more LDL enter blood vessel cells [7].

In healthy people, CRP can predict the risk of dying from a heart attack, blood vessel disease, heart failure, and arrhythmias [6, 8].

Similarly, CRP was additive to LDL cholesterol (and the Framingham 10-year risk score) in predicting future cardiovascular disease in healthy American women in the Women’s Health Study [8].

The American Heart Association and Centers for Disease Control and Prevention recommended using CRP as a risk marker for cardiovascular diseases in people with a Framingham risk score between 10% and 20%. This subgroup of patients may benefit from high-sensitivity (hs)-CRP testing, mainly because physicians are often undecided about the treatment for a patient who is considered at intermediate risk [6].

A controversial trial named JUPITER, healthy people with high-normal CRP levels (> 2 mg/L) given statins experienced a 44% reduction in their risk of heart attacks, stroke, hospital admissions for unstable angina, or death from heart disease [4]. This study has, however, received a lot of critiques and should be taken with a grain of salt [9].

High Blood Pressure

CRP may turn on a pro-inflammatory switch in blood vessels, making them narrow and stiff–resulting in high blood pressure (hypertension) [8].

Elevated CRP preceded new-onset hypertension at an early stage in an elderly healthy population. People with the highest CRP levels had a twofold greater risk of high blood pressure compared to those with the lowest CRP levels [8].

2) Metabolic Syndrome

People with metabolic syndrome have high inflammation and CRP levels. The more features of metabolic syndrome a person has, the more their CRP levels increase (linearly so). It additionally increases the risk of heart complications in people with the syndrome [8].

High CRP is linked with lower HDL cholesterol and greater BMI, belly fat, blood pressure, triglycerides, cholesterol, LDL cholesterol, blood glucose, fasting insulin, and insulin resistance [8].

3) Obesity

Elevated CRP is associated with obesity and abnormal fat metabolism in both adults and children. It is closely linked with high BMI and total calorie intake [10, 11].

Higher CRP correlates with lower adiponectin, a protein that enhances insulin sensitivity and prevents hardening of the arteries [10].

School children who were overweight/obese had higher levels of CRP and IL-6, whereas children with more belly fat and total body fat only had higher levels of CRP. CRP levels can even predict BMI changes during childhood [12, 13].

4) Stroke

High CRP levels are associated with a great risk of strokes, stroke complications, and death. Levels over 3 mg/ml were linked with a 40% increased risk, compared with CRP<1 mg/l over a 15-year follow-up period, especially in men with high blood pressure [14].

5) Obstructive Sleep Apnea

CRP is also increased in obstructive sleep apnea (OSA), which is when people stop breathing during sleep. Patients with more severe sleep apnea have even higher CRP levels [15, 16, 17].

Sleep apnea treatment with CPAP (continuous positive airway pressure) reduced the effect of the disease on CRP levels [16].

Additionally, low magnesium is associated with chronic inflammatory stress and higher CRP concentration in people with sleep apnea [15].

6) Systemic Lupus Erythematosus (SLE)

Low CRP levels may contribute to the development of systemic lupus erythematosus (SLE). This is because CRP may protect against autoimmunity by binding to cellular waste and autoantigens, which helps clear dying cells [18, 19, 20].

If damaged and dying cells aren’t cleared away by macrophages, their waste products build up in various tissues. Animals that can’t clear these dying cells develop autoimmunity. In fact, CRP injections can delay the onset of lupus and the resulting kidney inflammation in mice [20].

People with systemic lupus have don’t produce enough CRP when the body acutely needs it, possibly due to genetic reasons. A mutation in the CRP gene that lowers CRP blood levels has been detected in patients with systemic lupus [20].

Low CRP could also be caused by IgG antibodies, which are found in up to 78% of patients with systemic lupus. IgGbinds CRP, lowering its levels in the blood [20].

The link between CRP and SLE is not that straightforward because people with higher CRP had greater lupus disease activity in a number of other studies [21].

Vitamin D deficiency has also been linked to high CRP in people with lupus [22].

7) Rheumatoid Arthritis

CRP is found in the joint cavity fluid of rheumatoid arthritis (RA) patients and can bind to white blood cells and other inflammatory cells [23].

Inflammation in RA is closely related to the production of CRP and pro-inflammatory cytokines. In patients with rheumatoid arthritis, high CRP is directly linked with worse symptoms [24].

Levels of CRP correlate with changes in inflammation, disease activity, tissue damage, and disability. High CRP is also linked with hardening of the arteries and osteoporosis in people with rheumatoid arthritis [24, 20].

CRP is one of the best predictive markers of joint destruction and disease progression in early rheumatoid arthritis and is a strong predictor of fractures [20].

Additionally, CRP changes within the first 2 weeks of therapy with an anti-TNF agent can determine treatment success [25].

8) Gum Disease

CRP levels are higher in people with gum disease [3].

CRP tends to increase with gum destruction [3]. Patients with aggressive periodontitis had significantly higher CRP compared to the localized aggressive periodontitis and healthy people [3].

Treatment of gum infections, whether by intensive mechanical therapy, drug therapy or extraction, can significantly lower CRP. 6 months of gum therapy lowered CRP levels by about 0.5 mg/l [3].

9) Inflammatory Bowel Disease (IBD)

People with inflammatory bowel disease (IBD) may have high CRP, but this is not always the case. CRP levels of ≤0.5 can exclude IBD in patients with IBS symptoms [26].

In one study, higher CRP before diagnosis was associated with a greater risk of Crohn’s disease and ulcerative colitis [27].

In another study, CRP levels at diagnosis were related to disease severity in patients with ulcerative colitis but had not in patients with Crohn’s disease [28].

One study failed to find a link between CRP and colonic inflammation [29].

10) Fatigue

Low-grade inflammation can lead to fatigue. Higher CRP was linked with fatigue – both in healthy people and in disease-free survivors of breast cancer [30, 31, 32].

11) Depression

Low-grade inflammation is linked to depression. Several studies found a significant association between increased CRP and depressive symptoms. High levels were more frequent in patients with recurrent depression, especially in people who are overweight and have low HDL [33, 34, 35, 36].

CRP levels were linked with a history of suicide attempts in depressed patients. The risk of suicide attempts increased with higher levels of CRP [37, 38].

Hostility was also associated with increased levels of CRP [39].

12) Vision Loss from Age-related Macular Degeneration

Macular degeneration is a medical condition that may result in blurred vision or vision loss.

Several studies suggest a close association between CRP and eye blood vessel disorders. People with higher CRP levels are more likely to get age-related macular degeneration, especially if their CRP levels are over 3 mg/L [40].

High CRP levels (> 3 mg/L) are associated with a two-fold increased risk of late-onset macular degeneration, compared to low levels (< 1 mg/L). Women with levels exceeding 5 mg/L may be at a threefold increased risk [40].

13) Dementia

In the oldest-old, high CRP levels are associated with increased odds of all-cause dementia (memory decline), particularly in women [41].

14) Cancer

Cancer is more likely to develop in chronically-inflamed organs [42]. Unsurprisingly, high CRP levels are linked with an increased risk of developing cancer [43].

Even in apparently healthy people, high levels are associated with an increased risk of colorectal cancer, lung cancer, and cancer in general–excluding breast and prostate cancer [43, 44].

Scientists think the link between high CRP and cancer could be due to three reasons. First of all, high CRP may directly cause cancer. If so, it could be extremely useful in prevention [44].

Secondly, it’s possible that cancer increases CRP, even in the early stages. If this is true, CRP may be used as an early cancer marker, even when a person has no symptoms. And lastly, high CRP may point to another underlying cause of cancer, such as inflammation, high stress, and chronic disease [44].

Higher CRP levels have also been associated with the progression of skin, ovarian, and lung cancer. For this reason, CRP is used to detect cancer recurrence after surgery [43].

Persistently high CRP has also has been reported in colorectal cancer, while preoperative CRP >10 mg/L predicted reduced survival in colorectal cancer patients with liver metastases [42, 43]

What Now?

This post is the second in a four-part series about CRP. Read the other parts to learn about:

Irregular CRP Levels?

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About the Author

Biljana Novkovic - PHD (ECOLOGICAL GENETICS) - Writer at Selfhacked

Dr. Biljana Novkovic, PhD

PhD (Ecological Genetics)

Biljana received her PhD from Hokkaido University.

Before joining SelfHacked, she was a research scientist with extensive field and laboratory experience. She spent 4 years reviewing the scientific literature on supplements, lab tests and other areas of health sciences. She is passionate about releasing the most accurate science & health information available on topics, and she's meticulous when writing and reviewing articles to make sure the science is sound. She believes that SelfHacked has the best science that is also layperson-friendly on the web.

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