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  • Dennis Lipton, MD

hs-CRP (high sensitivity C-Reactive Protein)

Updated: May 27, 2019

Why do I test hsCRP*? What is it and why should you care?


C-reactive protein (CRP) was first discovered back in 1930 as a protein that reacted with the C-polysaccharide of Streptococcus Pneumonia, in patients with pneumonia. It was soon confirmed to be non-specific marker of immune activation, elevated in most inflammatory or infectious disorders. Specifically, it is produced by the liver in response to IL-6. IL-6 is one of a family of cytokines that spark and maintain inflammatory immune reactions, either to pathogens (bacteria or viruses) or to tissue damage (ie, an injury). This is the body’s way of fighting infection and healing wounds.


CRP is appropriately very elevated with any acute injury or infection. After the acute illness or insult is resolved, the CRP should fall, along with other inflammatory mediators, and your immune system should resume its normal low-grade surveillance activity. Unfortunately, with chronic illness, the inflammation does not resolve. CRP can remain slightly elevated. Chronic gum disease or other dental conditions can raise inflammation and CRP. Gastro-intestinal problems are associated with elevated CRP. Fat cells release IL-6 which raises inflammation and CRP. Stress (or heightened perception of stress), Sleep apnea, or even just a poor night of sleep is inflammatory. There is a list of foods that are considered ‘pro-inflammatory’.


The problem with all this inflammation is that it takes a toll on all the cells in your whole body, notably your brain and blood vessels. The endothelial cells that line your arteries become dysfunctional. If you have high cholesterol, high blood sugar, or high blood pressure, this effect is magnified. LDL particles stick to the inside of your endothelial cell. Macrophages (immune cells that devour pathogens) come to the ‘rescue’ and gobble up the LDL and its associated proteins and cholesterol. This macrophage sounds the alarm, causing activation of the immune system, leading to a vicious cycle that results in a growing cholesterol plaque.

This also pertains to brain health. Inflammation as measured by CRP has been clearly associated with decline in cognitive function with age. Your brain is mainly composed of neurons and glial cells. Neurons are the ones that do the ‘thinking’ through synapse formation and transmission of neural signals. A neuronal cell is like a spoiled CEO with 3-4 ‘assistants’ (glial cells) surrounding it. The glial cells carefully care for the neuron with food, information, safety, and metabolic waste removal. If the brain senses inflammation (danger), the glial cells are the ones to respond. They can’t pamper the neuron while they are away putting out the fires of inflammation. The neuron’s health suffers, leading to a down-regulation of neural networks, synapses, and neurons. (note, this is very simplified!).


Because the human body is so resilient and resourceful, these processes can be completely asymptomatic for many years. Often the first ‘symptom’ is sudden cardiac death, or cognitive impairment. I use the CRP (hs, or ‘high sensitivity’ CRP to be more specific) to detect this low-grade inflammation. If elevated, should prompt more aggressive risk assessment and reduction. It may also prompt a search for an underlying inflammatory condition that can be addressed (ie gingivitis, rheumatoid arthritis, psoriasis, etc), thereby reducing risk. Most often, however, it can be reduced with healthy lifestyle choices. We’ll go over some of these mechanisms in the next post.


*hsCRP vs just CRP. In a typical CRP assay, if the level is below 5, it is simply reported as <5, or 'less than 5'. This assay is useful when following a known infectious or inflammatory condition. The high sensitivity assay, which is more technically difficult and more expensive, gives a discrete value down to 0.2. This is useful when screening or following for smoldering low grade chronic inflammation, which is a disease risk as noted. You want this value as low as possible.


https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4891873/ lower CRP = more successful aging. Higher CRP corresponds with more aging related diseases.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4772636/ Higher CRP correlates with cognitive decline.

https://www.ncbi.nlm.nih.gov/pubmed/29108529 Concentration of CRP is highly correlated with cognitive decline

https://www.alzforum.org/news/research-news/midlife-peripheral-inflammation-may-drive-later-cognitive-decline CRP elevation in mid-life drives late life cognitive decline

https://www.ahajournals.org/doi/pdf/10.1161/ATVBAHA.107.157164 elevated CRP ‘clearly associated’ with future coronary heart disease events.


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