Editing C-reactive protein (section)

== Clinical significance ==

===Diagnostic use===
CRP is used mainly as an inflammation marker. Apart from [[liver failure]], there are few known factors that interfere with CRP production.<ref name=Pepys/> [[Interferon type I#IFN-α|Interferon alpha]] inhibits CRP production from liver cells which may explain the relatively low levels of CRP found during viral infections compared to bacterial infections <ref>{{cite journal | vauthors = Enocsson H, Sjöwall C, Skogh T, Eloranta ML, Rönnblom L, Wetterö J | title = Interferon-alpha mediates suppression of C-reactive protein: explanation for muted C-reactive protein response in lupus flares? | journal = Arthritis and Rheumatism | volume = 60 | issue = 12 | pages = 3755–3760 | date = December 2009 | pmid = 19950271 | doi = 10.1002/art.25042 | doi-access = free }}</ref><ref name="pmid33584722">{{cite journal | vauthors = Enocsson H, Gullstrand B, Eloranta ML, Wetterö J, Leonard D, Rönnblom L, Bengtsson AA, Sjöwall C | title = C-Reactive Protein Levels in Systemic Lupus Erythematosus Are Modulated by the Interferon Gene Signature and CRP Gene Polymorphism rs1205 | journal = Frontiers in Immunology | volume = 11 | issue =  | pages = 622326 | date = 2020 | pmid = 33584722 | pmc = 7876312 | doi = 10.3389/fimmu.2020.622326 | doi-access = free }}</ref>

Measuring and charting CRP values can prove useful in determining disease progress or the effectiveness of treatments. [[ELISA]] and [[radial immunodiffusion]] methods are available for research use, while [[immunoturbidimetry]] is used clinically for CRP and [[nephelometry (medicine)|nephelometry]] is typically used for hsCRP.<ref>{{cite journal | vauthors = Grützmeier S, von Schenck H | title = Four immunochemical methods for measuring C-reactive protein in plasma compared | journal = Clinical Chemistry | volume = 35 | issue = 3 | pages = 461–463 | date = March 1989 | pmid = 2493344 | doi = 10.1093/clinchem/35.3.461 | doi-access = free }}</ref><ref name="pmid12551878" /> Cutoffs for cardiovascular risk assessment have included:
* low: hs-CRP level under 1.0&nbsp;mg/L
* average: between 1.0 and 3.0&nbsp;mg/L
* high: above 3.0&nbsp;mg/L

Normal levels increase with [[aging]].<ref>Thomas, Lothar, ''Labor und Diagnose''. TH-Books, Frankfurt, 2008, p. 1010</ref> Higher levels are found in late [[Pregnancy|pregnant]] women, mild [[inflammation]] and [[viral infection]]s (10–40&nbsp;mg/L), active inflammation, bacterial infection (40–200&nbsp;mg/L), severe [[bacterial infections]] and [[burn]]s (>200&nbsp;mg/L).<ref name="pmid22787338">{{cite journal | vauthors = Chew KS | title = What's new in Emergencies Trauma and Shock? C-reactive protein as a potential clinical biomarker for influenza infection: More questions than answers | journal = Journal of Emergencies, Trauma, and Shock | volume = 5 | issue = 2 | pages = 115–117 | date = April 2012 | pmid = 22787338 | pmc = 3391832 | doi = 10.4103/0974-2700.96477 | doi-access = free }}</ref>

CRP cut-off levels indicating bacterial from non-bacterial illness can vary due to [[co-morbidities]] such as [[malaria]], [[HIV]] and [[malnutrition]] and the stage of disease presentation.<ref>{{cite journal | vauthors = Dittrich S, Tadesse BT, Moussy F, Chua A, Zorzet A, Tängdén T, Dolinger DL, Page AL, Crump JA, D'Acremont V, Bassat Q, Lubell Y, Newton PN, Heinrich N, Rodwell TJ, González IJ | title = Target Product Profile for a Diagnostic Assay to Differentiate between Bacterial and Non-Bacterial Infections and Reduce Antimicrobial Overuse in Resource-Limited Settings: An Expert Consensus | journal = PLOS ONE | volume = 11 | issue = 8 | pages = e0161721 | date = 2016-08-25 | pmid = 27559728 | pmc = 4999186 | doi = 10.1371/journal.pone.0161721 | veditors = Yansouni C | doi-access = free | bibcode = 2016PLoSO..1161721D }}</ref> In patients presenting to the emergency department with suspected sepsis, a CRP/albumin ratio of less than 32 has a negative predictive value of 89% for ruling out sepsis.<ref>{{cite journal | vauthors = Sisto UG, Di Bella S, Porta E, Franzoi G, Cominotto F, Guzzardi E, Artusi N, Giudice CA, Dal Bo E, Collot N, Sirianni F, Russo S, Sanson G | title = Predicting sepsis at emergency department triage: Implementing clinical and laboratory markers within the first nursing assessment to enhance diagnostic accuracy | journal = Journal of Nursing Scholarship | date = June 2024 | volume = 56 | issue = 6 | pages = 757–766 | pmid = 38886920 | doi = 10.1111/jnu.13002 }}</ref>

CRP is a more sensitive and accurate reflection of the acute phase response than the ESR<ref name="pmid23689052"/> ([[erythrocyte sedimentation rate]]). ESR may be normal while CRP is elevated. CRP returns to normal more quickly than ESR in response to therapy.{{citation needed|date=July 2022}}

=== Cardiovascular disease ===

Recent research suggests that patients with elevated basal levels of CRP are at an increased risk of [[diabetes]],<ref name="pmid11466099">{{cite journal | vauthors = Pradhan AD, Manson JE, Rifai N, Buring JE, Ridker PM | title = C-reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus | journal = JAMA | volume = 286 | issue = 3 | pages = 327–334 | date = July 2001 | pmid = 11466099 | doi = 10.1001/jama.286.3.327 | doi-access = free }}</ref><ref name="pmid17327459">{{cite journal | vauthors = Dehghan A, Kardys I, de Maat MP, Uitterlinden AG, Sijbrands EJ, Bootsma AH, Stijnen T, Hofman A, Schram MT, Witteman JC | title = Genetic variation, C-reactive protein levels, and incidence of diabetes | journal = Diabetes | volume = 56 | issue = 3 | pages = 872–878 | date = March 2007 | pmid = 17327459 | doi = 10.2337/db06-0922 | doi-access = free }}</ref> [[hypertension]] and [[cardiovascular disease]]. A study of over 700 nurses showed that those in the highest [[quartile]] of [[trans fat]] consumption had blood levels of CRP that were 73% higher than those in the lowest quartile.<ref name="pmid15735094">{{cite journal | vauthors = Lopez-Garcia E, Schulze MB, Meigs JB, Manson JE, Rifai N, Stampfer MJ, Willett WC, Hu FB | title = Consumption of trans fatty acids is related to plasma biomarkers of inflammation and endothelial dysfunction | journal = The Journal of Nutrition | volume = 135 | issue = 3 | pages = 562–566 | date = March 2005 | pmid = 15735094 | doi = 10.1093/jn/135.3.562 | doi-access = free }}</ref> Although one group of researchers indicated that CRP may be only a moderate risk factor for cardiovascular disease,<ref name="pmid15070788">{{cite journal | vauthors = Danesh J, Wheeler JG, Hirschfield GM, Eda S, Eiriksdottir G, Rumley A, Lowe GD, Pepys MB, Gudnason V | title = C-reactive protein and other circulating markers of inflammation in the prediction of coronary heart disease | journal = The New England Journal of Medicine | volume = 350 | issue = 14 | pages = 1387–1397 | date = April 2004 | pmid = 15070788 | doi = 10.1056/NEJMoa032804 | doi-access = free }}</ref> this study (known as the Reykjavik Study) was found to have some problems for this type of analysis related to the characteristics of the population studied, and there was an extremely long follow-up time, which may have attenuated the association between CRP and future outcomes.<ref>Koenig, Wolfgang (2006). [https://archive.today/20120723185617/http://www.crphealth.com/conf/hcp/5,59/doctor.wolfgang.koenig.c-reactive.protein.%96.a.critical.cardiovascular.risk.html "C-reactive protein - a critical cardiovascular risk marker"]. CRPhealth.com.</ref> Others have shown that CRP can exacerbate [[ischemic]] [[necrosis]] in a [[complement (biology)|complement]]-dependent fashion and that CRP inhibition can be a safe and effective therapy for [[Myocardial infarction|myocardial]] and [[Cerebral infarction|cerebral]] [[infarct]]s; this has been demonstrated in animal models and humans.<ref name="pmid16642000">{{cite journal | vauthors = Pepys MB, Hirschfield GM, Tennent GA, Gallimore JR, Kahan MC, Bellotti V, Hawkins PN, Myers RM, Smith MD, Polara A, Cobb AJ, Ley SV, Aquilina JA, Robinson CV, Sharif I, Gray GA, Sabin CA, Jenvey MC, Kolstoe SE, Thompson D, Wood SP | title = Targeting C-reactive protein for the treatment of cardiovascular disease | journal = Nature | volume = 440 | issue = 7088 | pages = 1217–1221 | date = April 2006 | pmid = 16642000 | doi = 10.1038/nature04672 | s2cid = 4324584 | bibcode = 2006Natur.440.1217P | url = https://ro.uow.edu.au/cgi/viewcontent.cgi?article=6831&context=scipapers }}</ref><ref name="pmid37893085">{{cite journal | vauthors = Ding Z, Wei Y, Peng J, Wang S, Chen G, Sun J | title = The Potential Role of C-Reactive Protein in Metabolic-Dysfunction-Associated Fatty Liver Disease and Aging | journal = Biomedicines | volume = 11 | issue = 10 | date = October 2023 | page = 2711 | pmid = 37893085 | pmc = 10603830 | doi = 10.3390/biomedicines11102711 | doi-access = free | url = }}</ref><ref name="pmid35407379">{{cite journal | vauthors = Torzewski J, Brunner P, Ries W, Garlichs CD, Kayser S, Heigl F, Sheriff A | title = Targeting C-Reactive Protein by Selective Apheresis in Humans: Pros and Cons | journal = Journal of Clinical Medicine | volume = 11 | issue = 7 | date = March 2022 | page = 1771 | pmid = 35407379 | pmc = 8999816 | doi = 10.3390/jcm11071771 | doi-access = free | url = }}</ref>

It has been hypothesized that patients with high CRP levels might benefit from use of [[statins]]. This is based on the [[JUPITER trial]] that found that elevated CRP levels without hyperlipidemia benefited. Statins were selected because they have been proven to reduce levels of CRP.<ref name=Pepys/><ref name="pmid18997196">{{cite journal | vauthors = Ridker PM, Danielson E, Fonseca FA, Genest J, Gotto AM, Kastelein JJ, Koenig W, Libby P, Lorenzatti AJ, MacFadyen JG, Nordestgaard BG, Shepherd J, Willerson JT, Glynn RJ | title = Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein | journal = The New England Journal of Medicine | volume = 359 | issue = 21 | pages = 2195–2207 | date = November 2008 | pmid = 18997196 | doi = 10.1056/NEJMoa0807646 | doi-access = free }}</ref> Studies comparing effect of various statins in hs-CRP revealed similar effects of different statins.<ref name="pmid22025854">{{cite journal | vauthors = Sindhu S, Singh HK, Salman MT, Fatima J, Verma VK | title = Effects of atorvastatin and rosuvastatin on high-sensitivity C-reactive protein and lipid profile in obese type 2 diabetes mellitus patients | journal = Journal of Pharmacology & Pharmacotherapeutics | volume = 2 | issue = 4 | pages = 261–265 | date = October 2011 | pmid = 22025854 | pmc = 3198521 | doi = 10.4103/0976-500X.85954 | doi-access = free }}</ref><ref name="pmid11306519">{{cite journal | vauthors = Jialal I, Stein D, Balis D, Grundy SM, Adams-Huet B, Devaraj S | title = Effect of hydroxymethyl glutaryl coenzyme a reductase inhibitor therapy on high sensitive C-reactive protein levels | journal = Circulation | volume = 103 | issue = 15 | pages = 1933–1935 | date = April 2001 | pmid = 11306519 | doi = 10.1161/01.CIR.103.15.1933 | doi-access = free }}</ref> A subsequent trial however failed to find that CRP was useful for determining statin benefit.<ref name="pmid21277016">{{cite journal | title = C-reactive protein concentration and the vascular benefits of statin therapy: an analysis of 20,536 patients in the Heart Protection Study | journal = Lancet | volume = 377 | issue = 9764 | pages = 469–476 | date = February 2011 | pmid = 21277016 | pmc = 3042687 | doi = 10.1016/S0140-6736(10)62174-5 | collaboration = Heart Protection Study Collaborative Group | vauthors = Jonathan E, Derrick B, Emma L, Sarah P, John D, Jane A, Rory C }}</ref>

In a [[meta-analysis]] of 20 studies involving 1,466 patients with [[coronary artery disease]], CRP levels were found to be reduced after exercise interventions. Among those studies, higher CRP concentrations or poorer lipid profiles before beginning exercise were associated with greater reductions in CRP.<ref name="pmid22520533">{{cite journal | vauthors = Swardfager W, Herrmann N, Cornish S, Mazereeuw G, Marzolini S, Sham L, Lanctôt KL | title = Exercise intervention and inflammatory markers in coronary artery disease: a meta-analysis | journal = American Heart Journal | volume = 163 | issue = 4 | pages = 666–76.e1–3 | date = April 2012 | pmid = 22520533 | doi = 10.1016/j.ahj.2011.12.017 }}</ref>

To clarify whether CRP is a bystander or active participant in [[atherogenesis]], a 2008 study compared people with various genetic CRP variants. Those with a high CRP due to genetic variation had no increased risk of cardiovascular disease compared to those with a normal or low CRP.<ref name="pmid18971492">{{cite journal | vauthors = Zacho J, Tybjaerg-Hansen A, Jensen JS, Grande P, Sillesen H, Nordestgaard BG | title = Genetically elevated C-reactive protein and ischemic vascular disease | journal = The New England Journal of Medicine | volume = 359 | issue = 18 | pages = 1897–1908 | date = October 2008 | pmid = 18971492 | doi = 10.1056/NEJMoa0707402 | doi-access = free }}</ref> A study published in 2011 shows that CRP is associated with lipid responses to low-fat and high-polyunsaturated fat diets.<ref name="pmid19297430">{{cite journal | vauthors = St-Onge MP, Zhang S, Darnell B, Allison DB | title = Baseline serum C-reactive protein is associated with lipid responses to low-fat and high-polyunsaturated fat diets | journal = The Journal of Nutrition | volume = 139 | issue = 4 | pages = 680–683 | date = April 2009 | pmid = 19297430 | pmc = 2666362 | doi = 10.3945/jn.108.098251 }}</ref>

=== Coronary heart disease risk ===

Arterial damage results from [[macrophage|white blood cell]] invasion and [[inflammation]] within the wall. CRP is a general marker for inflammation and infection, so it can be used as a very rough proxy for heart disease risk. Since many things can cause elevated CRP, this is not a very [[Sensitivity and specificity|specific]] prognostic indicator.<ref name="Lloyd-Jones">{{cite journal | vauthors = Lloyd-Jones DM, Liu K, Tian L, Greenland P | title = Narrative review: Assessment of C-reactive protein in risk prediction for cardiovascular disease | journal = Annals of Internal Medicine | volume = 145 | issue = 1 | pages = 35–42 | date = July 2006 | pmid = 16818927 | doi = 10.7326/0003-4819-145-1-200607040-00129 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Bower JK, Lazo M, Juraschek SP, Selvin E | title = Within-person variability in high-sensitivity C-reactive protein | journal = Archives of Internal Medicine | volume = 172 | issue = 19 | pages = 1519–1521 | date = October 2012 | pmid = 22945505 | pmc = 3613132 | doi = 10.1001/archinternmed.2012.3712 }}</ref> Nevertheless, a level above 2.4&nbsp;mg/L has been associated with a doubled risk of a coronary event compared to levels below 1&nbsp;mg/L;<ref name=Pepys/> however, the study group in this case consisted of patients who had been diagnosed with unstable angina pectoris; whether elevated CRP has any predictive value of acute coronary events in the general population of all age ranges remains unclear. Currently, C-reactive protein is not recommended as a cardiovascular disease screening test for average-risk adults without symptoms.<ref name=Cecil>{{cite book | vauthors = Goldman L |title=Goldman's Cecil Medicine |url=https://archive.org/details/goldmanscecilmed00mdle |url-access=limited |publisher=Elsevier Saunders |location=Philadelphia |isbn=978-1437727883 |year=2011 |pages=[https://archive.org/details/goldmanscecilmed00mdle/page/n317 54] |edition=24th }}</ref>

The [[American Heart Association]] and U.S. [[Centers for Disease Control and Prevention]] have defined risk groups as follows:<ref>{{cite web |url=http://labtestsonline.org/understanding/analytes/hscrp/tab/test |title=hs-CRP |access-date=June 3, 2013}}</ref><ref name="pmid12551878" />
* Low Risk: less than 1.0&nbsp;mg/L
* Average risk: 1.0 to 3.0&nbsp;mg/L
* High risk: above 3.0&nbsp;mg/L
But hs-CRP is not to be used alone and should be combined with elevated levels of [[cholesterol]], [[LDL-C]], [[triglycerides]], and glucose level. [[Smoking]], hypertension and diabetes also increase the risk level of cardiovascular disease.

=== Fibrosis and inflammation ===

[[Scleroderma]], [[polymyositis]], and [[dermatomyositis]] elicit little or no CRP response.{{citation needed|date=June 2022}} CRP levels also tend to remain low despite inflammatory activity in [[systemic lupus erythematosus]] (SLE) unless [[serositis]] or [[synovitis]] is present. This may be explained by increased levels of type I IFN in SLE, since type I IFN (i.e IFN alpha) inhibits hepatic CRP production.<ref>{{cite journal | vauthors = Enocsson H, Karlsson J, Li HY, Wu Y, Kushner I, Wetterö J, Sjöwall C | title = The Complex Role of C-Reactive Protein in Systemic Lupus Erythematosus | journal = Journal of Clinical Medicine | volume = 10 | issue = 24 | pages = 5837 | date = December 2021 | pmid = 34945133 | pmc = 8708507 | doi = 10.3390/jcm10245837 | doi-access = free }}</ref> A polymorphisms of the CRP gene which cause lower CRP levels is also more frequent in SLE patients compared with controls.<ref>{{cite journal | vauthors = Enocsson H, Gullstrand B, Eloranta ML, Wetterö J, Leonard D, Rönnblom L, Bengtsson AA, Sjöwall C | title = C-Reactive Protein Levels in Systemic Lupus Erythematosus Are Modulated by the Interferon Gene Signature and CRP Gene Polymorphism rs1205 | journal = Frontiers in Immunology | volume = 11 | pages = 622326 | date = 2021-01-28 | pmid = 33584722 | pmc = 7876312 | doi = 10.3389/fimmu.2020.622326 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Enocsson H, Sjöwall C, Kastbom A, Skogh T, Eloranta ML, Rönnblom L, Wetterö J | title = Association of serum C-reactive protein levels with lupus disease activity in the absence of measurable interferon-α and a C-reactive protein gene variant | journal = Arthritis & Rheumatology | volume = 66 | issue = 6 | pages = 1568–1573 | date = June 2014 | pmid = 24574329 | doi = 10.1002/art.38408 }}</ref> Elevations of CRP in the absence of clinically significant inflammation can occur in [[kidney failure]]. CRP level is an independent risk factor for atherosclerotic disease. Patients with high CRP concentrations are more likely to develop [[stroke]], [[myocardial infarction]], and severe [[Peripheral artery disease|peripheral vascular disease]].<ref name="Risk">{{cite journal | vauthors = Clearfield MB | title = C-reactive protein: a new risk assessment tool for cardiovascular disease | journal = The Journal of the American Osteopathic Association | volume = 105 | issue = 9 | pages = 409–416 | date = September 2005 | pmid = 16239491 | url = http://www.jaoa.org/content/105/9/409.full | access-date = 2013-02-10 | url-status = dead | archive-url = https://web.archive.org/web/20120110071000/http://www.jaoa.org/content/105/9/409.full | archive-date = 2012-01-10 }}</ref> Elevated level of CRP can also be observed in [[inflammatory bowel disease]] (IBD), including [[Crohn's disease]] and [[ulcerative colitis]].<ref name="pmid23689052">{{cite journal | vauthors = Liu S, Ren J, Xia Q, Wu X, Han G, Ren H, Yan D, Wang G, Gu G, Li J | title = Preliminary case-control study to evaluate diagnostic values of C-reactive protein and erythrocyte sedimentation rate in differentiating active Crohn's disease from intestinal lymphoma, intestinal tuberculosis and Behcet's syndrome | journal = The American Journal of the Medical Sciences | volume = 346 | issue = 6 | pages = 467–472 | date = December 2013 | pmid = 23689052 | doi = 10.1097/MAJ.0b013e3182959a18 | s2cid = 5173681 }}</ref><ref name="Vermeire 661–665">{{cite journal | vauthors = Vermeire S, Van Assche G, Rutgeerts P | title = C-reactive protein as a marker for inflammatory bowel disease | journal = Inflammatory Bowel Diseases | volume = 10 | issue = 5 | pages = 661–665 | date = September 2004 | pmid = 15472532 | doi = 10.1097/00054725-200409000-00026 | s2cid = 11984165 }}</ref>

High levels of CRP has been associated to point mutation Cys130Arg in the ''APOE'' gene, coding for [[apolipoprotein E]], establishing a link between [[lipid]] values and inflammatory markers modulation.<ref>{{cite journal | vauthors = Sidore C, Busonero F, Maschio A, Porcu E, Naitza S, Zoledziewska M, Mulas A, Pistis G, Steri M, Danjou F, Kwong A, Ortega Del Vecchyo VD, Chiang CW, Bragg-Gresham J, Pitzalis M, Nagaraja R, Tarrier B, Brennan C, Uzzau S, Fuchsberger C, Atzeni R, Reinier F, Berutti R, Huang J, Timpson NJ, Toniolo D, Gasparini P, Malerba G, Dedoussis G, Zeggini E, Soranzo N, Jones C, Lyons R, Angius A, Kang HM, Novembre J, Sanna S, Schlessinger D, Cucca F, Abecasis GR | title = Genome sequencing elucidates Sardinian genetic architecture and augments association analyses for lipid and blood inflammatory markers | journal = Nature Genetics | volume = 47 | issue = 11 | pages = 1272–1281 | date = November 2015 | pmid = 26366554 | pmc = 4627508 | doi = 10.1038/ng.3368 }}</ref>{{MEDRS|date=November 2019}}<ref name="Vermeire 661–665"/>

=== Cancer ===

The role of inflammation in cancer is not well understood. Some organs of the body show greater risk of cancer when they are chronically inflamed.<ref>{{cite journal | vauthors = Lu H, Ouyang W, Huang C | title = Inflammation, a key event in cancer development | journal = Molecular Cancer Research | volume = 4 | issue = 4 | pages = 221–233 | date = April 2006 | pmid = 16603636 | doi = 10.1158/1541-7786.MCR-05-0261 | doi-access = free }}</ref>  While there is an association between increased levels of C-reactive protein and risk of developing cancer, there is no association between genetic polymorphisms influencing circulating levels of CRP and cancer risk.<ref name="pmid22035340">{{cite journal | vauthors = Allin KH, Nordestgaard BG | title = Elevated C-reactive protein in the diagnosis, prognosis, and cause of cancer | journal = Critical Reviews in Clinical Laboratory Sciences | volume = 48 | issue = 4 | pages = 155–170 | year = 2011 | pmid = 22035340 | doi = 10.3109/10408363.2011.599831 | s2cid = 40322991 }}</ref>

In a 2004 [[prospective cohort study]] on colon cancer risk associated with CRP levels, people with [[colon cancer]] had higher average CRP concentrations than people without colon cancer.<ref name="pmid14762037">{{cite journal | vauthors = Erlinger TP, Platz EA, Rifai N, Helzlsouer KJ | title = C-reactive protein and the risk of incident colorectal cancer | journal = JAMA | volume = 291 | issue = 5 | pages = 585–590 | date = February 2004 | pmid = 14762037 | doi = 10.1001/jama.291.5.585 | doi-access = free }}</ref> It can be noted that the average CRP levels in both groups were well within the range of CRP levels usually found in healthy people. However, these findings may suggest that low inflammation level can be associated with a lower risk of colon cancer, concurring with previous studies that indicate [[Non-steroidal anti-inflammatory drug|anti-inflammatory drugs]] could lower colon cancer risk.<ref name="pmid12621133">{{cite journal | vauthors = Baron JA, Cole BF, Sandler RS, Haile RW, Ahnen D, Bresalier R, McKeown-Eyssen G, Summers RW, Rothstein R, Burke CA, Snover DC, Church TR, Allen JI, Beach M, Beck GJ, Bond JH, Byers T, Greenberg ER, Mandel JS, Marcon N, Mott LA, Pearson L, Saibil F, van Stolk RU | title = A randomized trial of aspirin to prevent colorectal adenomas | journal = The New England Journal of Medicine | volume = 348 | issue = 10 | pages = 891–899 | date = March 2003 | pmid = 12621133 | doi = 10.1056/NEJMoa021735 | doi-access = free }}</ref>

=== Obstructive sleep apnea ===

C-reactive protein (CRP), a marker of systemic inflammation, is also increased in [[obstructive sleep apnea]] (OSA).  CRP and interleukin-6 (IL-6) levels were significantly higher in patients with OSA compared to obese control subjects.<ref name="pmid23533751">{{cite journal | vauthors = Latina JM, Estes NA, Garlitski AC | title = The Relationship between Obstructive Sleep Apnea and Atrial Fibrillation: A Complex Interplay | journal = Pulmonary Medicine | volume = 2013 | pages = 621736 | year = 2013 | pmid = 23533751 | pmc = 3600315 | doi = 10.1155/2013/621736 | doi-access = free }}</ref> Patients with OSA have higher plasma CRP concentrations that increased corresponding to the severity of their [[apnea-hypopnea index]] score.  Treatment of OSA with CPAP ([[continuous positive airway pressure]]) significantly alleviated the effect of OSA on CRP and IL-6 levels.<ref name="pmid23533751"/>

=== Rheumatoid arthritis ===

In the context of [[rheumatoid arthritis]] (RA), CRP is one of the acute phase reactants, whose assessment is defined as part of the joint 2010 ACR/[[European Alliance of Associations for Rheumatology|EULAR]] classification criteria for RA with abnormal levels accounting for a single point within the criteria. <ref>Kay J, Upchurch KS. ACR/EULAR 2010 rheumatoid arthritis classification criteria. Rheumatology (Oxford). 2012 Dec;51 Suppl 6:vi5-9. doi: 10.1093/rheumatology/kes279. PMID 23221588.</ref> Higher levels of CRP are associated with more severe disease and a higher likelihood of radiographic progression. Rheumatoid arthritis associated antibodies together with 14-3-3η [[YWHAH]] have been reported to complement CRP in predicting clinical and radiographic outcomes in patients with recent onset inflammatory polyarthritis.<ref name="PMC4736641">{{cite journal | vauthors = Carrier N, Marotta A, de Brum-Fernandes AJ, Liang P, Masetto A, Ménard HA, Maksymowych WP, Boire G | title = Serum levels of 14-3-3η protein supplement C-reactive protein and rheumatoid arthritis-associated antibodies to predict clinical and radiographic outcomes in a prospective cohort of patients with recent-onset inflammatory polyarthritis | journal = Arthritis Research & Therapy | volume = 18 | issue = 37 | pages = 37 | date = February 2016 | pmid = 26832367 | pmc = 4736641 | doi = 10.1186/s13075-016-0935-z | doi-broken-date = 1 November 2024 | s2cid = 1926353 | doi-access = free }}</ref> Elevated levels of CRP appear to be associated with common comorbidities including cardiovascular disease, [[metabolic syndrome]], diabetes and interstitial lung (pulmonary) disease. Mechanistically, CRP also appears to influence [[osteoclast]] activity leading to [[bone resorption]] and also stimulates [[RANKL]] expression in peripheral blood [[monocyte]]s.<ref name="PMID 33385862">{{cite journal | vauthors = Pope JE, Choy EH | title = C-reactive protein and implications in rheumatoid arthritis and associated comorbidities | journal = Seminars in Arthritis and Rheumatism | volume = 51 | issue = 1 | pages = 219–229 | date = February 2021 | pmid = 33385862 | doi = 10.1016/j.semarthrit.2020.11.005 | s2cid = 230108148 | doi-access = free }}</ref>

It has previously been speculated that [[single-nucleotide polymorphism]]s in the CRP gene may affect clinical decision-making based on CRP in rheumatoid arthritis, e.g. DAS28 (Disease Activity Score 28 joints). A recent study showed that CRP [[genotype]] and [[haplotype]] were only marginally associated with serum CRP levels and without any association to the DAS28 score.<ref name="pmid25359432">{{cite journal | vauthors = Ammitzbøll CG, Steffensen R, Bøgsted M, Hørslev-Petersen K, Hetland ML, Junker P, Johansen JS, Pødenphant J, Østergaard M, Ellingsen T, Stengaard-Pedersen K | title = CRP genotype and haplotype associations with serum C-reactive protein level and DAS28 in untreated early rheumatoid arthritis patients | journal = Arthritis Research & Therapy | volume = 16 | issue = 5 | pages = 475 | date = October 2014 | pmid = 25359432 | pmc = 4247621 | doi = 10.1186/s13075-014-0475-3 | doi-access = free }}</ref> Thus, that DAS28, which is the core parameter for inflammatory activity in RA, can be used for clinical decision-making without adjustment for CRP gene variants.{{citation needed|date=November 2021}}

=== Viral infections ===

Increased blood CRP levels were higher in people with [[avian flu]] [[H7N9]] compared to those with [[H1N1]] (more common) influenza,<ref name="pmid26809124">{{cite journal | vauthors = Wu W, Shi D, Fang D, Guo F, Guo J, Huang F, Chen Y, Lv L, Li L | title = A new perspective on C-reactive protein in H7N9 infections | journal = International Journal of Infectious Diseases | volume = 44 | pages = 31–36 | date = March 2016 | pmid = 26809124 | doi = 10.1016/j.ijid.2016.01.009 | doi-access = free }}</ref> with a review reporting that severe H1N1 influenza had elevated CRP.<ref name="pmid30288556">{{cite journal | vauthors = Vasileva D, Badawi A | title = C-reactive protein as a biomarker of severe H1N1 influenza | journal = Inflammation Research | volume = 68 | issue = 1 | pages = 39–46 | date = January 2019 | pmid = 30288556 | pmc = 6314979 | doi = 10.1007/s00011-018-1188-x }}</ref> In 2020, people infected with [[COVID-19]] in [[Wuhan, China]], had elevated CRP.<ref name="pmid32031570">{{cite journal | vauthors = Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, Wang B, Xiang H, Cheng Z, Xiong Y, Zhao Y, Li Y, Wang X, Peng Z | title = Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China | journal = JAMA | volume = 323 | issue = 11 | pages = 1061–1069 | date = March 2020 | pmid = 32031570 | pmc = 7042881 | doi = 10.1001/jama.2020.1585 | doi-access = free }}</ref><ref name="pmid32007143">{{cite journal | vauthors = Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, Qiu Y, Wang J, Liu Y, Wei Y, Xia J, Yu T, Zhang X, Zhang L | title = Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study | journal = Lancet | volume = 395 | issue = 10223 | pages = 507–513 | date = February 2020 | pmid = 32007143 | pmc = 7135076 | doi = 10.1016/S0140-6736(20)30211-7 | doi-access = free }}</ref><ref name="pmid32061335">{{cite journal | vauthors = Zhang J, Zhou L, Yang Y, Peng W, Wang W, Chen X | title = Therapeutic and triage strategies for 2019 novel coronavirus disease in fever clinics | journal = The Lancet. Respiratory Medicine | volume = 8 | issue = 3 | pages = e11–e12 | date = March 2020 | pmid = 32061335 | pmc = 7159020 | doi = 10.1016/S2213-2600(20)30071-0 | doi-access = free }}</ref>