C-reactive protein tests: The right way to use them

The same year that the Great Depression was ramping up, Betty Boop debuted, frozen foods began to be commercially sold, and a couple of pioneers in science discovered C-reactive protein (CRP). This protein is synthesized in the liver and rises in response to inflammation, tissue damage, and infection, specifically by the secretion of interleukins and other cytokines by macrophages and T cells. CRP is a nonspecific marker for disease and can be used to help diagnose bacterial infections and inflammatory disorders. Levels are dependent upon the severity of overall inflammation in the body. Infections including pneumonia and tuberculosis, inflammatory bowel disease, certain cancers, dementia, and rheumatoid arthritis will elicit elevated levels.

There are links between higher levels of CRP and insufficient sleep, smoking, stress, dietary issues such as high saturated fats, vitamin deficiencies, and even altitude.^1-4 Estrogen-based medications may raise levels, as will pregnancy, most often in later stages. Exercise, which of course is part of a healthy lifestyle, is interesting as related to inflammation. In the short term, it produces an inflammatory response, but in the long term, it is anti-inflammatory.⁵

In the presence of acute inflammation, body tissue is destroyed, causing a release of interleukin-1 (IL-1) and interleukin-6 (IL-6) that stimulate the production of CRP and cause the rapid increase. Therefore, CRP is classified as an acute phase reactant. Other examples of acute phase reactants are fibrinogen, ferritin, and haptoglobin. CRP begins to rise within 6 to 12 hours and peaks within 24 to 48 hours. Low levels can be seen in noninfectious metabolic inflammatory states such as cardiac ischemia, uremia, or smoking.

Inflammation: A major link between oral and systemic diseases

The dangers of high fibrinogen levels

To measure CRP, there are two types of tests: standard and high sensitivity (hsCRP). HsCRP is also termed CRP cardiac, which is considered a marker for low-grade vascular inflammation. The conventional CRP test measures a wide range, so it’s often used to check for early inflammation and infection but is less sensitive at low range. The high-sensitivity test can detect proteins at lower concentrations, which is more effective than conventional CRP tests.

Cardiovascular disease

Elevated levels of CRP may predict high-risk patients with cardiovascular and peripheral vascular disease. According to the American Heart Association,⁶ you are at low risk of developing cardiovascular disease if your hsCRP level is lower than 1.0 mg/L (milligram per liter). Average risk is considered between 1.0 mg/L and 3.0 mg/L, and high risk is higher than 3.0 mg/L.

Of course, this is just one marker to consider. Since CRP measures inflammation for a variety of reasons, a patient might have high levels without arterial disease. Bacterial infections are responsible for about 90% of cases of CRP levels higher than 50 mg/l.⁷

Results in a study of almost 30,000 women found that levels of hsCRP were more accurate than cholesterol measurements for predicting risk of cardiovascular events.⁸ In fact, the women with the highest levels were more than four times as likely to suffer a heart attack or stroke. There is also a relationship between vitamin D levels, CRP, and the likelihood of having a cardiovascular event.⁹

Periodontal disease

Periodontal pathogens not only induce local inflammation and tissue destruction but are also involved in systemic increases in inflammatory and immune responses. Many clinical studies have shown elevated CRP in patients with periodontal disease.^10-12

Could we speculate that treating periodontal disease would lower CRP levels? Yes! Research in systemically healthy adults who had periodontitis and had periodontal therapy showed not only a lowered hsCRP but also an increase in high-density lipoprotein (HDL).¹³ A pilot trial of 94 participants found decreased serum CRP of 0.5 mg/L six months after completion of periodontal therapy and a reduction in interleukin-6 (IL-6).¹⁴

How about patients who aren’t systemically healthy? A meta-analysis assessing scaling and root planing patients who have type 2 diabetes found a positive impact on both CRP and HbA1c.¹⁵ The plight of high cholesterol is real, and hearing that nonsurgical therapy showed improved periodontal health and decreased LDL and CRP in hyperlipidemic patients with chronic periodontal disease is intriguing.¹⁶

Endodontics

There are relationships between infected teeth and elevated CRP. High levels of IL-6 have been identified in an inflamed pulp and periapical lesions, and it has been indicated that CRP is expressed in periodontal ligaments. CRP is strongly upregulated in direct association with IL-6 expression levels in resident and infiltrating inflammatory cells.¹⁷

Research released in 2022 comparing single-sitting root canal therapy and multiple-sitting therapy with levels of IL-6, tumor necrosis factor-a (TNF-α), and hsCRP, found serum expression levels lowered after treatment.¹⁸ Additionally, research by Poornima et al. showed a positive effect stemming from root canal treatment and lowering hsCRP levels.¹⁹

CRP has both pro-inflammatory and anti-inflammatory properties and is involved in the identification and clearance of foreign pathogens and impaired cells. CRP has an extremely diverse causality, can be difficult to interpret, and shouldn’t be used as an isolated test. But knowing your numbers is key for all disease prevention, and this is yet another avenue to explore for checking overall wellness.

Working with a health-care provider in a precision medicine approach is essential. If CRP is elevated, lifestyle interventions may help. Increasing aerobic exercise, quitting smoking, losing weight, and following a heart-healthy diet are all beneficial. There is some evidence that taking statins to lower cholesterol can reduce CRP levels.

Keep the faith in the operatory when trying to instill wellness with your patients. In a small way, our treatment of disease is notable. When, for the umpteenth time, you are explaining why your patient needs periodontal therapy and the frustration is mounting, remember that what you are trying to accomplish is nothing short of transformative for your patient.

Explaining the potentially grave outcomes associated with endodontic lesions can also become tiresome, but it’s worth the effort to support our patients to live longer, healthier lives.

Editor's note: This article appeared in the January/February 2023 print edition of RDH magazine. Dental hygienists in North America are eligible for a complimentary print subscription. Sign up here.

References

Meier-Ewert HK, Ridker PM, Rifai N, et al. Effect of sleep loss on C-reactive protein, an inflammatory marker of cardiovascular risk. J Am Coll Cardiol. 2004;43(4):678-683. doi:10.1016/j.jacc.2003.07.050
van Dijk WD, Akkermans R, Heijdra Y, et al. The acute effect of cigarette smoking on the high-sensitivity CRP and fibrinogen biomarkers in chronic obstructive pulmonary disease patients. Biomark Med. 2013;7(2):211-219. doi:10.2217/bmm.12.112
Johnson TV, Abbasi A, Master VA. Systematic review of the evidence of a relationship between chronic psychosocial stress and C-reactive protein. Mol Diagn Ther. 2013;17(3):147-164. doi:10.1007/s40291-013-0026-7
Stöwhas AC, Latshang TD, Lo Cascio CM, et al. Effects of acute exposure to moderate altitude on vascular function, metabolism and systemic inflammation. PLoS One. 2013;8(8):e70081. doi:10.1371/journal.pone.0070081
Kasapis C, Thompson PD. The effects of physical activity on serum C-reactive protein and inflammatory markers: a systematic review. J Am Coll Cardiol. 2005;45(10):1563-1569. doi:10.1016/j.jacc.2004.12.077
Ridker PM. Cardiology Patient Page. C-reactive protein: a simple test to help predict risk of heart attack and stroke. Circulation. 2003;108(12):e81-e85. doi:10.1161/01.CIR.0000093381.57779.67
Nehring SM, Goyal A, Patel BC. C Reactive Protein. StatPearls Publishing. January 2022. Updated July 18, 2022. https://www.ncbi.nlm.nih.gov/books/NBK441843/
Ridker PM, Hennekens CH, Buring JE, Rifai N. C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. N Engl J Med. 2000;342(12):836-843. doi:10.1056/NEJM200003233421202
Li Q, Dai Z, Cao Y, Wang L. Association of C-reactive protein and vitamin D deficiency with cardiovascular disease: a nationwide cross-sectional study from National Health and Nutrition Examination Survey 2007 to 2008. Clin Cardiol. 2019;42(7):663-669. doi:10.1002/clc.23189
Gomes-Filho IS, Freitas Coelho JM, da Cruz SS, et al. Chronic periodontitis and C-reactive protein levels. J Periodontol. 2011;82(7):969-978. doi:10.1902/jop.2010.100511
Bansal T, Pandey A, Deepa D, Asthana AK. C-reactive protein (CRP) and its association with periodontal disease: a brief review. J Clin Diagn Res. 2014;8(7):ZE21-ZE24. doi:10.7860/JCDR/2014/8355.4646
Kumar S, Shah S, Budhiraja S, Desai K, Shah C, Mehta D. The effect of periodontal treatment on C-reactive protein: a clinical study. J Nat Sci Biol Med. 2013;4(2):379-382. doi:10.4103/0976-9668.11699
Leite AC, Carneiro VM, Guimarães Mdo C. Effects of periodontal therapy on C-reactive protein and HDL in serum of subjects with periodontitis. Rev Bras Cir Cardiovasc. 2014;29(1):69-77. doi:10.5935/1678-9741.20140013
D’Aiuto F, Parkar M, Andreaou G, Brett PM, Ready D, Tonetti MS. Periodontitis and atherogenesis: causal association or simple coincidence? J Clin Periodontol. 2004;31:402-411
Baeza M, Morales A, Cisterna C, et al. Effect of periodontal treatment in patients with periodontitis and diabetes: systematic review and meta-analysis. J Appl Oral Sci. 2020;28:e20190248. doi:10.1590/1678-7757-2019-0248
Tawfig A. Effects of non-surgical periodontal therapy on serum lipids and C-reactive protein among hyperlipidemic patients with chronic periodontitis. J Int Soc Prev Community Dent. 2015;5(Suppl 1):S49-S56. doi:10.4103/2231-0762.156524
Garrido M, Dezerega A, Bordagaray MJ, et al. C-reactive protein expression is up-regulated in apical lesions of endodontic origin in association with interleukin-6. J Endod. 2015;41(4):464-469. doi:10.1016/j.joen.2014.12.021
Agrawal R, Bhardwaj M, Doley B, et al. Expression of IL-6, TNF-α, and hs-CRP in the serum of patients undergoing single-sitting and multiple-sitting root canal treatment: a comparative study. J Family Med Prim Care. 2022;11(5):1918-1922. doi:10.4103/jfmpc.jfmpc_846_21
Poornima L, Ravishankar P, Abbott PV, Subbiya A, PradeepKumar AR. Impact of root canal treatment on high-sensitivity C-reactive protein levels in systemically healthy adults with apical periodontitis - a preliminary prospective, longitudinal interventional study. Int Endod J. 2021;54(4):501-508. doi:10.1111/iej.13444