C-Reactive Protein (CRP) and High-Sensitivity C-Reactive Protein (hs-CRP): Diagnostic Significance and Clinical Insights

 Authors: Payal Bhandari, M.D.

Contributors: Tejal, Hailey Chin, Nigella Umali Ruguian, Vivi Chador, Amer Džanković

C-Reactive Protein (CRP) 

C-Reactive Protein (CRP) is a protein made by the liver that is sent into the bloodstream in response to inflammation. Inflammation is the body’s way of protecting tissues if one’s been injured or has an infection.  Abnormally high levels may be an indication of metabolic inflammation, autoimmune issues, serious infection or other disorders.

Typical Adult Range

Ranges and thresholds can vary due to: 

(1) Lab-specific equipment, techniques, and chemicals, and 

(2) Patient demographics, including age, sex, and ethnicity.

 

Cardiac C-Reactive Protein (hs-CRP) 

Cardiac C-Reactive Protein (hs-CRP) is a protein synthesized by the liver in response to inflammation. Inflammation is the body’s way of protecting tissues when injured or dealing with an infection. hs-CRP is used to assess risk of developing cardiovascular disease or ischemic events.

Typical Adult Range

Ranges and thresholds can vary due to: 

(1) Lab-specific equipment, techniques, and chemicals, and 

(2) Patient demographics, including age, sex, and ethnicity.

 

Key Insights

Proteins are important for the body. They help build tissues, transport substances, and support chemical reactions. Blood has two main proteins: albumin and globulins. The body constantly breaks down and makes new proteins using amino acids from food. The C-reactive protein (CRP) test measures inflammation in the blood caused by undigested food or invaders. High CRP levels can thicken the blood, making it harder for red blood cells to deliver oxygen and remove waste. The high-sensitivity C-reactive protein (hs-CRP) test looks for long-term stress that damages organs, blood vessels, and gut health. High hs-CRP levels can signal a higher risk of heart attack or stroke in the next year or two. CRP and hs-CRP levels can change based on exercise, diet, hydration, and medication, making them useful for tracking inflammation-related health issues.

 

What are the C-reactive protein (CRP) and High-Sensitivity C-reactive protein (hs-CRP) Tests? 

The C-reactive protein (CRP) test measures CRP, a protein made by the liver when the body is stressed or injured. CRP helps remove damaged cells, but high levels can mean the body is inflamed. When body temperature rises, it can damage cells, thicken the blood, and raise blood pressure. This makes it harder for red blood cells to deliver oxygen and remove waste, leading to low oxygen levels and more fat storage. Inflammation can also damage blood vessels and the gut, allowing harmful substances to leak into the blood. These substances trigger the immune system to fight infections.

The high-sensitivity CRP (hs-CRP) test checks for chronic inflammation, showing how it affects organs, blood vessels, and the gut. Monitoring CRP and hs-CRP levels can help assess overall health and the risk of serious health problems.

 

CRP and hs-CRP Synthesis

 

The liver makes C-reactive protein (CRP), which is linked to inflammation. CRP production is mainly influenced by how well the body uses energy from food through cellular respiration.

Most cells, except for red blood cells (RBCs), platelets, and white blood cells (WBCs), get their energy from the mitochondria (the cell’s power source). RBCs transport oxygen, which is crucial for energy production. WBCs and platelets help fight infections, clean up tissue damage, prevent excessive bleeding, and aid in wound healing.

Figure 1: Cellular respiration turns food into energy for the body. It mainly happens in the mitochondria and creates energy molecules like ATP. The process uses oxygen, which helps produce ATP. Carbon dioxide (CO2) is a waste product and is exhaled through the lungs.

When energy is low (like during fasting or intense exercise), the body breaks down muscle protein and fat to produce ATP. The brain can’t use fat for energy directly, so fat is turned into glucose through a process called ketogenesis. This creates more ATP from fat (34 ATP from fat vs. 2 ATP from glucose). This helps the brain rely less on carbs and protein and has several benefits:

  • Stabilizes protein metabolism and lowers inflammation

  • Reduces excess fat and harmful hormones

  • Removes toxic waste from cells

  • Balances body temperature

  • Supports healing

Hormones like glucagon, insulin, and somatostatin help make energy through ketogenesis. Stress hormones like cortisol and adrenaline break down glucose and produce reactive oxygen species (ROS), which damage cells and slow down cell repair. Stress also increases blood acidity, reducing insulin and glucose uptake by cells, which limits oxygen and energy for organs. Chronic stress can cause low oxygen levels, reducing energy and harming cells. High levels of inflammatory proteins, like C-reactive protein, show that undigested food in the blood is causing harmful inflammation.

 

                          

Figure 2: Fat cells, liver, and muscles break down fats, proteins, and other substances to make glucose and ketones. Ketones are used for energy during fasting, intense exercise, insulin shortage, or when the brain needs more energy. Ketones provide much more energy (34 ATP) than glucose (2-4 ATP). This process is controlled by circadian rhythm genes.

 

Regulation of CRP and hs-CRP Blood Levels

Unlike fat, most of the protein we eat can’t be stored in the body. More than 90% of it is broken down into amino acids, which are the building blocks of proteins. Each day, the body breaks down and rebuilds about 250 grams of protein. Any extra protein that isn’t used for energy is turned into glycogen (a form of stored glucose) and then stored as fat.

 

Figure 3:  Amino acids derived from food and muscle protein are placed into a “amino acid pool” and used to form new proteins and other nitrogen-containing compounds. 

 

When we chew, bacteria in the mouth turn 40% of nitrates from food into nitric oxide, which helps keep arteries healthy and blood pressure stable. The rest is excreted in urine. The food then moves to the stomach, where acid and enzymes break down proteins into amino acids. This mixture moves to the small intestine, where bacteria like Veillonella, Neisseria, and Lactobacillus:

  • Help break down proteins and produce energy

  • Make nitric oxide

  • Process vitamins for the body to use

  • Turn fiber into useful fatty acids

  • Help neutralize stomach acid and aid digestion.

 

Figure 4: Plant-based proteins turn into nitric oxide (NO) through bacteria in the mouth, small intestine, and skin. This helps blood flow, control blood pressure, and protect tissues. Nitrates and nitrites return to the mouth and skin, where bacteria make NO. NO keeps arteries flexible and reduces inflammation, infections, and cancer growth.

 

                               

Figure 5: When you eat protein, bacteria, stomach acid, and enzymes break it down into smaller parts. These parts go to the liver and other organs. Chemicals from the pancreas and small intestine protect the gut lining from damage. Without them, toxins could leak into the bloodstream, causing leaky gut syndrome.

Stress reduces blood flow to the digestive system, slowing digestion and lowering healthy gut bacteria and stomach acid. This can cause nutrient shortages and allow undigested food particles to damage the gut lining. Harmful substances enter the bloodstream, thickening the blood and making it harder for red blood cells to deliver oxygen. This leads to low oxygen levels, higher blood sugar, and more harmful molecules.

 

Figure 6: A healthy gut microbiota is key to good digestion and metabolism. When healthy bacteria decrease (dysbiosis), it can disrupt metabolism, lower energy, and cause inflammation, raising harmful proteins in the blood.

High temperatures can damage cells, mutate genes, and slow cell growth. Excess fat in the blood sticks to blood vessels, causing white blood cells to release CRP and trigger inflammation. Platelets and muscle cells help remove damaged cells, form scar tissue, and create new blood vessels, leading to atherosclerosis.

 

         

Figure 7: C-reactive protein (CRP) shows the body is repairing damage from atherosclerosis, where fat builds up in blood vessels. This blocks blood flow, raises blood pressure, and affects circulation. The buildup prevents bleeding caused by undigested food, but over time, it can thicken blood vessels with scar tissue and plaque, damaging organs.

Clinical Significance of Monitoring CRP and hs-CRP Blood Levels

Non-alcoholic fatty liver disease (NAFLD) is a major cause of high CRP levels in the blood. It ranges from simple fat buildup in the liver to serious conditions like NASH, which can lead to liver scarring and organ failure. NAFLD is linked to metabolic syndrome and diabetes, where excess fat and inflammation harm the body.

Liver diseases are rising due to lifestyle changes. NAFLD was the 8th leading cause of death in the U.S. in 2016, affecting 25% of people worldwide. Risk factors include ethnicity, lifestyle, and genetics, with Hispanic Americans, especially of Mexican descent, having higher rates.

Obesity is a major health issue, causing diseases like diabetes and heart problems. In 2018, over 68% of U.S. adults were overweight or obese, and abdominal obesity has increased by 10% in recent years.

 

Figure 8:  Chronic liver damage increases proinflammatory proteins (like CRP) and decreases anti-inflammatory proteins (like antioxidants). Nutrients focus on healing and stopping bleeding, which causes more damage to organs, blood vessels, and the microbiota.

 

High CRP and hs-CRP Blood Levels

High CRP and hs-CRP levels are linked to atherosclerosis, where overactive blood cells focus on repairing tissue rather than supporting vital functions. These cells produce proteins like CRP and heat, damaging the gut and healthy cells. As damaged cells and bacteria increase, blood cells help infections, tumors, and organ damage grow. High CRP levels are also linked to liver disease and a weakened immune system. This causes fluid to move out of blood vessels, leading to dehydration and swelling, which can harm cells and cause serious health problems.

Low CRP and hs-CRP Blood Levels 

Low CRP and hs-CRP blood levels usually mean that the body is good at burning fat, controlling blood sugar, and keeping inflammation in check. This helps the body get enough energy for important functions while preventing tissue damage and inflammation.

 

Conclusion 

C-reactive protein (CRP) and high-sensitivity CRP (hs-CRP) are important markers of inflammation and can show the risk of serious health issues. Proteins like albumin help with blood flow, nutrient transport, and blood pressure. When CRP and hs-CRP levels rise, it means cells are damaged, and the body works to repair them. If not managed, this can affect oxygen delivery, raise body temperature, and harm organs. Lifestyle changes like drinking water, eating healthy, exercising, and managing stress can lower inflammation and reduce the risk of heart disease, diabetes, and other health problems. Regularly checking CRP and hs-CRP levels helps doctors diagnose and treat conditions effectively.

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