The association between dental caries and serum crp in the us adult population: evidence from NHANES 2015–2018

Abstract

Background

Dental caries remains one of the most prevalent diseases worldwide, affecting 29.4% of the global population. Despite numerous efforts to diagnose, predict, and prevent dental caries, the incidence continues to rise. Salivary biomarkers provide a non-invasive means for early detection of various oral conditions. C-reactive protein (CRP) is a key marker, elevated in both oral and general inflammatory conditions such as diabetes, periodontitis and oral squamous cell carcinoma. Considering the emerging connection between oral and systemic health, it is worth exploring the various factors associated with this widespread disease. This study investigates the association between CRP levels and dental caries in the United States population, utilizing data from the National Health and Nutrition Examination Survey (NHANES).

Methods

The study analyzed data from the 2015–2018 NHANES cycles, focusing on a nationally representative sample of individuals aged 30 years and above. Weighted multivariable negative binomial and logistic regression analyses were employed to explore the relationship between dental caries and CRP levels, adjusting for age, gender, race, education level, diabetes status, and gum disease.

Results

The results of the negative binomial regression analysis demonstrated a positive association between higher CRP levels and an increased mean number of dental caries (Adjusted Mean Ratio [AMR] = 1.7; 95% CI: 1.3 – 2; P: < 0.001). The logistic regression analysis showed that individuals with higher CRP levels have a 50% increase in the odds of developing dental caries (AOR: 1.5, CI: 1.2 – 1.9; P: < 0.01).

Conclusion

The results of this cross-sectional study of the U.S. population highlight the positive association between high CRP levels and increased dental caries. These findings contribute to the growing body of evidence supporting the integration of oral and systemic health care. Further research is necessary to deepen our understanding of the mechanistic relationship between CRP levels and dental caries.

Introduction

The World Health Organization (WHO) has continually highlighted the significant impact of poor oral health on overall health and quality of life [1], emphasizing that concerns extend beyond dental caries. Dental caries is a noncommunicable, multifactorial disease influenced by various biological, microbial, behavioral, psychosocial, and environmental factors [2]. The disease process involves an imbalance between protective factors and pathological factors, leading to a net loss of minerals from the tooth surface and the formation of carious lesions [3]. It is recognized as the most prevalent human infectious disease [1], affects approximately 2.3 billion individuals (29.4% of the global population) in their permanent teeth and 532 million individuals (7.8% of the global population) in their primary teeth [4]. Despite various preventive measures, such as sugar reduction, regular brushing, and fluoride usage [5], the incidence of dental caries continues to escalate worldwide [6]. This underscores the urgency of developing innovative tools for the prediction and diagnosis of dental caries to enhance our understanding and prevention strategies.

The oral cavity is a complex environment, home to a diverse array of bacteria, proteins, enzymes, metabolites, cytokines, and other biomarkers present in saliva [7]. Biomarkers in saliva are essential for providing insights into physiological states, facilitating risk assessment, diagnosis, prognosis, and disease monitoring [8].

Salivary biomarkers offer a non-invasive approach for the early detection of various oral inflammatory conditions. For example, it was found that cytokines such as interleukin-1β (IL-1β) and metalloproteinase-8 (MMP-8)are elevated in the saliva of patients with periodontal disease [9–12] and salivary interleukin-8(IL-8) was elevated in patients with oral squamous cell carcinoma (OSCC) [13, 14,12]. Additionally, salivary Interleukin-6 (IL-6) demonstrate high sensitivity and specificity for detecting oral inflammatory conditions [12]. As a result, advanced platforms such as the Oral Fluid NanoSensor Test (OFNASET) offer salivary diagnostic tools, making saliva a valuable tool for monitoring both oral health conditions [15].

Recently, salivary C-Reactive Protein (CRP) has garnered significant attention as a potential biomarker for a variety of oral inflammatory and immune conditions [16, 17], including periodontitis [18], oral cancer [19], and oral lichen planus [20]. Moreover, CRP levels in saliva have been found to strongly correlate with elevated blood CRP levels in systemic inflammatory diseases such as Crohn’s disease [21], diabetes [22], and cardiovascular disease [23]. The advent of new technology enabling the detection of CRP in saliva underscores its diagnostic and monitoring potential for these conditions, given to the non-invasive nature and ease of saliva collection [23].

Emerging studies have explored the role of salivary biomarkers for diagnosing dental caries such as alpha-amylase, acidic proline-rich protein-1, histatin-5, lactoperoxidase, and statherin [7]. However, there exists a noticeable gap in the research concerning the relationship between salivary biomarkers and dental caries.

Given the bidirectional relationship between oral and systemic conditions such as periodontal disease, diabetes, and dental caries (Mishra, Iqbal et al.), the interplay between these conditions often involves immune or inflammatory responses [24]. Elevated CRP levels in the oral cavity can indicate local inflammation and a compromised oral immune system, as CRP is secreted by immune cells [25]. This inflammation and immune reaction can disrupt the balance of the oral microbiome [26], target specific bacteria, and potentially contribute to the development of dental caries.

The association between elevated salivary CRP levels and dental caries has been the subject of a few studies. However, these studies are marked by several limitations, including small sample sizes of 12 subjects [27], unadjusted confounding factors such as gum and periodontal disease [28], and a lack of generalizability due to being conducted at only one clinic site in Saudi Arabia [29]. This study aims to overcome these limitations by employing a larger-scale approach, thereby narrowing the knowledge gap and validating previous findings.

While other inflammatory biomarkers such as IL-6 and Tumor Necrosis Factor (TNF) in the oral cavity might correlate with oral inflammatory conditions [30], there is no evidence that IL-6 and TNF levels in blood correlate with those in saliva. In this analysis, we used the NHANES dataset, which includes biomarkers from blood but not from saliva.

On the other hand, well-established evidence shows a strong correlation between CRP levels in blood and saliva [22, 31], indicating that salivary CRP can serve as a reliable proxy for serum CRP as an indicator of oral inflammation [31]. Hence, in this secondary analysis of NHANES, we are exploring the association between CRP in blood and dental caries in a representative sample of the adult US population. This approach builds on existing evidence of the correlation between blood and salivary CRP, potentially paving the way for novel insights and strategies for the detection and monitoring of this pervasive health issue.

Methods

Study population

Data were sourced from the National Health and Nutrition Examination Survey (NHANES), a cross-sectional study designed to assess the health and nutritional status of the U.S. population. This analysis utilized data from the 2015 and 2018 NHANES cycles, obtained from the publicly accessible NHANES database NHANES Questionnaires, Datasets, and Related Documentation. The NHANES program received approval from the National Center for Health Statistics (NCHS) Ethics Review Board, with all participants providing informed consent. Our study focused on individuals aged 30 years or older who had participated in the Oral Health Examination. The dataset included information on the prevalence of dental caries across all coronal surfaces, as well as laboratory data for CRP, encompassing a total of 12,862 participants.

Outcome variable: dental caries

Dental examinations were conducted in a Mobile Examination Center (MEC) by dentists trained and licensed in at least one U.S. state. Each tooth, excluding wisdom teeth, was assessed for coronal caries using the NHANES variable “0HX05CTC.” The category for “untreated dental caries” included the codes J and Z. The examination process involved drying the teeth with air and inspecting them with a surface-reflecting mirror and a No. 23 explorer to identify any untreated dental caries. The criteria for conducting a comprehensive dental examination are detailed in the NHANES Oral Health Examiners Manual [32]. Subsequently, the dental caries outcome variable was recoded in two formats: as a count variable, indicating the number of decayed teeth per individual, and as a binary variable, signifying the presence or absence of dental caries in each assessed tooth.

Exposure variable: C-reactive protein (CRP)

The blood samples were collected from participants at the mobile examination center using standardized protocol. Blood was drawn via venipuncture using standard phlebotomy techniques. The blood is collected in tubes designed to separate the serum, which is used for CRP analysis. Specimens were brought to room temperature before analysis, and laboratory staff maintained a quality assurance log to ensure accuracy. C-Reactive Protein reagent is based on the highly sensitive Near Infrared Particle Immunoassay rate methodology. An anti-CRP antibody-coated particle binds to CRP in the patient sample resulting in the formation of insoluble aggregates causing turbidity then it was measured on the Beckman Coulter UniCel DxC 600 Synchron and the Beckman Coulter UniCel DxC 660i Synchron Access chemistry analyzers [33]. The NHANES code “LBXHSCRP” was used to identify CRP levels. The categorization of CRP levels into high level (≥ 3 mg/L) and normal level (< 3 mg/L) established a binary variable for analysis [34].

Coronary heart disease

The data for this variable was collected by asking participants if they had ever been told they had coronary heart disease. The responses were classified into two categories: “Yes” or “No,”.

Diabetes status

The categorization of participants into diabetic or non-diabetic groups was based on responses to a specific question in a questionnaire: “Other than during pregnancy, have you ever been told by a doctor or other health professional that you have diabetes or sugar diabetes?” This approach utilized self-reported information to gauge participants’ awareness of their diabetic status.

Gum conditions

The evaluation of gum disease was conducted by asking participants, “Do you think you might have gum disease?” This was accompanied by a brief description of potential symptoms of gum disease, including swollen, receding, sore or infected gums, or loose teeth. Participants were prompted to respond with: 1 = Yes, 2 = No, or 9 = I don’t know, creating a categorical variable.

Additional covariates

Participants over the age of 30 were categorized into age groups: “30–34 years,” “35–44 years,” “45–64 years,” and “65 + years.” Gender was classified as either “Male” or “Female.” Race/ethnicity was broken down into “Non-Hispanic White,” “Non-Hispanic Black,” “Hispanic,” “Non-Hispanic Asian,” and “Other race, including multiracial.” Educational attainment was categorized as “ < High school,” “High school/GED,” or “Some college or more.” Body mass index (BMI) was classified into “Underweight,” “Normal,” “Overweight,” and “Obese.” Smoking status was simplified into two categories: “No” or “Yes, currently smoking (every day or some days).”

Statistical analysis

Chi-square test was utilized for comparing groups with categorical variables, with results presented as counts and percentages. To explore the association between dental caries prevalence and elevated levels of CRP, weighted multivariate negative binomial and logistic regression analyses were performed, adjusting for several covariates: Age, Gender, Race/ethnicity, Education level, Body Mass Index (BMI), Smoking status, Diabetes, Coronary Heart Disease, and Gum Disease. The presence of multicollinearity among independent variables was evaluated using Variance Inflation Factors (VIF), with a threshold of 5. A VIF below 5 was considered indicative of negligible multicollinearity, while values above 5 suggested significant multicollinearities. Due to a VIF exceeding 5, BMI was excluded from the regression analyses to ensure model validity. All statistical analyses were conducted using STATA software, version 18.0.

Results

Our sample included 50.85% females and 49.15% males. Among the samples, 17.10% were White, 11.07% were African American, 22.08% were Asian, 32.33% were Hispanic, and 17.42% were of other races.

Our findings showed that 23.15% of participants (2978 out of 12,862) had at least one tooth affected by dental caries. Within this subgroup, 40.40% (1203 out of 2978) exhibited elevated CRP levels. (Table 1).

Table 1.

Descriptive and demographics of individuals stratified by untreated dental caries for individuals aged 30 years or above in the National Health and Nutrition and Examination Survey, 2015-2018 cycles

Independent Variable		Total(n)	No Dental caries(n)	%	At least one tooth with dental caries(n)	%	P Value
CRP	average	9077	7302	72.28	1775	60.45	<0.001
	elevated	3785	2582	27.72	1203	39.55
Age	30-34	853	585	11.34	268	13.02	<0.10
	35-49	2358	1633	31.44	725	34.32
	45-64	2579	1789	32.74	790	33.61
	65+	2076	1496	24.48	580	19.05
Gender	Males	6959	5264	47.50	1695	53.44	<0.001
	Females	7328	5799	52.50	1529	46.56
Race/ethnicity	non-hispanic     white	4473	3549	62.38	924	53.92	<0.001
	non-hispanic black	3219	2231	10.09	988	18.25
	Hispanic	4064	3142	17.02	922	19.26
	non-hispanic asian	1747	1502	6.02	245	3.93
	other races	784	639	4.50	145	4.65
Education level	High school	1929	1137	9.09	792	19.91	<0.001
	High school/GED	2117	1312	20.01	805	33.67
	some college or more	5464	4231	70.89	1233	46.42
Diabetes	No	12916	10157	92.70	2758	87.36	<0.001
	Yes	1364	899	7.30	465	12.64
Body mass index	Underweight	1877	1736	9.95	141	3.28	<0.001
	Normal	4267	3444	30.15	823	26.50
	Overweight	3648	2751	27.72	897	27.20
	Obese	4352	3029	32.17	1323	43.03
Smoking	No	2143	1535	66.28	608	43.08	<0.001
	Every or some day	1718	898	33.72	820	56.92
Coronary heart disease	No	9142	6429	96.8	2713	96.16	<0.61
	Yes	349	241	3.20	108	3.84
Gum disease	Yes	1580	937	16.38	643	30.21	<0.001
	No	6160	4502	82.87	1658	67.34
	I don't know	125	63	0.75	62	2.46

Table 1 also showed that individuals aged 45–64 years had the highest prevalence of dental caries at 33.43% (790 out of 2363). Racial demographics indicated that non-Hispanic Black participants had the highest incidence of dental caries at 30.65% (988 out of 3224), with males more likely to have dental caries than females (52.57% or 1695 out of 3224). Interestingly, females exhibited higher CRP levels (58.89% or 2576 out of 4374) compared to males. Among body mass index (BMI) categories, the obese group showed the highest percentage of dental caries at 41.55% (1323 out of 3184). Smokers were found to have a higher percentage of dental caries (57.42% or 820 out of 1428) compared to non-smokers.

Table 2 shows the analysis of CRP levels across different demographics and highlighted that the age group of 45–64 years had the highest CRP levels at 34.81% (1129 out of 3243). Non-Hispanic White participants recorded the highest CRP levels at 32.33% (1414 out of 4374). Moreover, a significant majority of non-diabetic individuals (92.2% or 9910 out of 10,739) had normal CRP levels, suggesting a relationship between diabetes and elevated CRP levels.

Table 2.

Descriptive and demographics of individuals stratified by C-reactive protein levels for individuals aged 30 years or above in the National Health and Nutrition and Examination Survey, 2015-2018 cycles

Independent Variable		Total	normal CRP(n)	%	abnormal CRP(n)	%	P Value
Dental caries	No	9884	7302	81.52	2582	72.11	<0.001
	Yes	2978	1775	18.48	1203	27.89
Age	30-34	830	556	11.75	274	10.15	<0.001
	35-49	2370	1445	30.60	925	31.41
	45-64	2750	1621	31.68	1129	35.38
	65+	2513	1598	25.98	915	23.07
Gender	Male	7390	5592	52.41	1798	40.66	<0.001
	Female	7727	5151	47.59	2576	59.34
Race/ethnicity	Non-Hispanic white	4886	3472	61.21	1414	59.92	<0.001
	Non-Hispanic black	3273	2198	10.52	1075	12.87
	Hispanic	4359	3010	17.51	1349	18.49
	Non-Hispanic Asian	1739	1446	6.37	293	3.27
	Other races	860	617	4.38	243	5.44
Education level	High school	2186	1335	12.11	851	14.01	<0.001
	High school/GED	2278	1357	22.28	921	27.07
	Some college or more	5565	3618	65.60	1947	58.92
Diabetes	No	13527	9910	93.22	3617	85.40	<0.001
	Yes	1582	829	6.78	753	14.60
Body mass index	Underweight	2233	2050	12.68	183	2.39	<0.001
	Normal	4183	3631	34.33	552	13.23
	Overweight	3752	2718	29.45	1034	23.67
	Obese	4518	2021	23.53	2497	60.71
Smoking	No	2399	1484	59.25	915	56.85	<0.028
	Every or some day	1874	1097	40.75	777	43.15
Coronary heart disease	No	9563	6028	96.53	3535	95.48	<0.149
	Yes	441	263	3.47	178	4.52
Gum disease	yes	1650	964	17.69	686	22.12	0.005
	No	6681	4179	81.28	2502	76.55
	I don't know	130	75	1.03	55	1.33

The results of the negative binomial regression analysis demonstrated a positive association between higher CRP levels and an increased mean number of dental caries (Adjusted Mean Ratio [AMR] = 1.7; 95% Confidence Interval: 1.3 – 2; P < 0.001) (Table 3). Furthermore, the analysis showed statistically significant associations with demographic and health-related factors. Gender was a significant factor, with females having a lower mean number of dental caries compared to males (AMR = 0.7; P = 0.03). Racial differences were observed, with Hispanics and non-Hispanic Asians exhibiting significantly lower mean number of dental caries compared to non-Hispanic Whites (AMR: 0.9 and 0.7, respectively; P-values: 0.04 and 0.14, respectively). Smoking status showed a significant association with dental caries (AMR = 2.2; P < 0.01), indicating that smokers are at a higher risk.

Table 3.

Weighted multivariate negative binomial regression analysis of the association between dental caries and C-reactive protein for individuals aged 30 years and above. Data were extracted from 2015–2018 NHANES cycles

Independent variables	Adjusted Mean ratio “AMR”	P value	95% Conf. Interval
C-Reactive protein	1.7	< 0.01	1.3—2.1
Age: Reference: 30–34
35–49	0.9	0.75	0.6—1.3
45–64	0.9	0.21	0.5—1.1
65 +	0.7	0.02	0.4—0.9
Sex: reference: males	0.7	0.03	0.6—1
Race: reference: Non-Hispanic white
Non-Hispanic black	1.4	< 0.01	1.1—1.8
Hispanic	0.9	0.44	0.6—1.2
Non-Hispanic Asian	0.7	0.14	0.4—1.1
Other races	1.4	0.04	1—2.2
Educational level: Reference: < high school
High school/GED	0.8	0.25	0.6—1.1
Some college or more	0.4	< 0.01	0.3—0.5
Diabetes Mellitus	1.1	0.21	0.9—1.6
Smoking	2.2	< 0.01	1.7—2.8
Coronary heart disease	0.8	0.5	0.5—1.3
Gum disease	0.4	< 0.01	0.4—0.5

C reactive protein (CRP) High and low levels of CRP are defined as =  > 3 mg/L and < 3.0 mg/L respectively. Smoking The status of smoking was relying on whether the participant is now smoking cigarettes or not. Diabetes if the Doctor informed you have diabetes before, Gum disease Do you think you might have gum disease?

The logistic regression analysis aligned with the negative binomial regression findings, showing that higher CRP levels were associated with increased odds of dental caries incidence (Adjusted Odds Ratio [AOR] = 1.5; 95% Confidence Interval: 1.2 – 1.9; P < 0.01) (Table 4). Individuals with ‘some college or more’ education had significantly lower odds of developing dental caries compared to those with less than a high school education (AOR = 0.4; P < 0.01), highlighting the influence of education on dental health.

Table 4.

Weighted multivariate Logistic regression analysis of the association between dental caries and C-reactive protein for individuals aged 30 years and above. Data were extracted from 2015–2018 NHANES cycles

Independent variables	Adjusted Odds ratio “AOR”	P value	95% Conf. Interval
C-Reactive protein	1.5	< 0.01	1.2 – 1.9
Age: Reference: 30–34
35–49	0.9	0.76	0.6—1.4
45–64	0.8	0.54	0.5—1.4
65 +	0.7	0.18	0.4 – 1.2
Sex: reference: males	0.7	0.05	0.6—1
Race: reference: Non-Hispanic white
Non-Hispanic black	1.7	< 0.01	1.3—2.3
Hispanic	0.8	0.42	0.6—1.2
Non-Hispanic Asian	0.6	0.05	0.4—1
Other races	1.3	0.28	0.7—2.3
Educational level: Reference: < high school
High school/GED	0.8	0.23	0.6 – 1.1
Some college or more	0.4	< 0.01	0.3—0.5
Diabetes Mellitus	1.2	0.21	0.8—1.7
Smoking	2.4	< 0.01	1.9 – 3.2
Coronary heart disease	0.9	0.87	0.5 – 1.7
Gum disease	0.9	0.4	0.8—1

C reactive protein (CRP) High and low levels of CRP are defined as =  > 3 mg/L and < 3.0 mg/L respectively. Smoking The status of smoking was relying on whether the participant is now smoking cigarettes or not. Diabetes if the Doctor informed you have diabetes before, Gum disease Do you think you might have gum disease?

Discussion

This secondary analysis of representative data from the adult U.S. population investigated the relationship between serum CRP levels and dental caries. Our findings revealed a positive association between elevated serum CRP levels and a higher prevalence of dental caries.

CRP, known for its role in both acute and chronic inflammatory responses, is produced by the liver and serves as a well-established marker of systemic inflammation when present in the bloodstream [35].

In our study, we used serum CRP as a proxy for salivary CRP to assess the relationship with dental caries. This approach is grounded in well-established evidence showing a strong correlation between salivary and blood CRP levels, suggesting that elevated salivary CRP may reflect inflammatory conditions within the oral cavity [31]. Furthermore, a systematic review of 130 studies confirmed this strong correlation [31]. The robust relationship between salivary and blood CRP levels supports the use of salivary CRP as a reliable surrogate marker for systemic inflammation [22, 31].

Dental caries is a noncommunicable disease influenced by various biological, behavioral, psychosocial, and environmental factors, which interact with various local factors within the oral environment, including proteins, immune cells, metabolites, and other biomarkers [36]. These interactions are a fundamental aspect of oral microbiome dynamics [37], suggesting a plausible link between heightened oral inflammation—manifested by increased CRP levels—and the bacteria responsible for dental caries [36, 37].

This correlation underpins the theory that oral bacteria, especially those implicated in the development of dental caries, may potentially contribute to systemic inflammatory responses, as evidenced by increased CRP levels [38].

This backdrop supports the hypothesis that a rise in oral inflammation, as indicated by elevated CRP levels, could be associated with the presence of cariogenic bacteria. This theory is grounded in the notion that the oral immune response to oral bacterial infections could precipitate a rise in CRP levels, signaling an inflammatory state both within the oral cavity and systemically [39].

The analogy of associating CRP levels with dental caries mirrors the established connection between CRP and periodontal diseases [40, 41]. Periodontal diseases, which involve inflammation of the teeth’s supporting structures such as the bone and gums, are consistently associated with elevated levels of inflammatory biomarkers, particularly CRP in the oral cavity [42]. Consequently, an increase in oral inflammation, indicated by elevated oral CRP levels, could exacerbate the proliferation of cariogenic bacteria.

This link highlights that oral infections—whether from cariogenic bacteria responsible for dental caries or periodontopathic bacteria causing periodontal diseases—can affect systemic inflammation markers like CRP [43]. This observation is pertinent to the recognized bidirectional link between oral and systemic inflammation [44].

Both dental caries and periodontal diseases originate from unique bacterial communities within the oral biofilm [45], with distinct inflammatory pathways [45]. The immune system’s response to cariogenic bacteria in dental caries and periodontopathic bacteria in periodontal diseases may lead to the production of inflammatory mediators, including CRP [40]. Therefore, elevated CRP levels act as indicators of inflammation, which could be reflective of oral diseases such as periodontal diseases and potentially dental caries. This inflammatory response underscores the significant effect of oral infections on systemic health [43, 46].

Given the potential link between periodontal disease, dental caries, and oral inflammation, it was crucial to adjust for periodontal disease in the analysis. However, in the 2017–2018 cycle, no periodontal exam was performed on the participants. Instead, we used the survey question, “Do you think you might have gum disease?’ accompanied by a brief description of potential gum disease symptoms, including swollen, receding, sore or infected gums, or loose teeth, as a proxy for oral inflammation”. This adjustment was incorporated into the model. The lack of direct clinical assessments of periodontal health represents a limitation in the study.

Furthermore, saliva plays a crucial role in preventing dental caries [47]. Systemic and local inflammation can cause structural changes in salivary glands through the action of lymphocytes and inflammatory cytokines, such as CRP, leading to decreased saliva production—a known risk factor for dental caries [48]. Additionally, inflammation can alter the concentration of antimicrobial peptides, affecting the production and function of protective saliva proteins [49]. These changes could potentially increase susceptibility to dental caries, emphasizing the complex interplay between oral health, systemic inflammation, and overall well-being.

Limitations and future direction

This study, being cross-sectional in nature, faces inherent limitations in assessing temporality and causality. It remains unclear whether increased CRP causes dental caries or if dental caries leads to elevated CRP levels. Another limitation stems from the reliance on serum CRP measurements, as salivary CRP samples, which could offer more direct evidence of oral inflammation, were not collected in the NHANES dataset. Additionally, an objective assessment of periodontal status was not available within these NHANES cycles, restricting our ability to fully understand the role of periodontal health in the context of systemic inflammation and dental caries. However, we used the survey question, “Do you think you might have gum disease?” as a proxy for confounding due to oral inflammation.

Despite these limitations, the study has several strengths that bolster its findings. These include the large sample size and its representation of the adult US population, which minimizes selection bias. Furthermore, the study controlled for known confounding factors such as gum inflammation, systemic disease, smoking, and other demographic variables. This analysis provides a novel opportunity to understand the relationship between dental caries and CRP, guiding future research directions.

Future studies should aim to include salivary CRP measurements to directly assess the impact of oral inflammation on the development of dental caries. Moreover, collecting oral microbiome samples will add another layer of understanding regarding the interaction between immune response and host response in the development of dental caries. Longitudinal designs are needed to establish causality and temporal dynamics between elevated CRP levels, dental caries, and periodontal and systemic diseases. Investigating these relationships in greater depth could unveil potential pathways through which oral bacteria and inflammatory biomarkers contribute to dental caries. This line of inquiry is crucial for developing diagnostic and monitoring tools as well as targeted interventions that improve oral health and potentially mitigate systemic inflammatory conditions.

Conclusion

Our study demonstrated a positive association between elevated serum CRP levels and an increased prevalence of dental caries in the adult U.S. population. These findings offer valuable insights into the interplay between systemic and oral inflammation and their impact on oral health. Our findings underscore the importance of incorporating inflammatory biomarkers into dental health assessments, paving the way for more comprehensive diagnostic and monitoring strategies.

Abbreviations

NHANES

National Health and Nutrition Examination Survey

US

United States

CRP

C-reactive Protein

IL-1β

Interleukin-1β

IL-8

Interleukin-8

IL-6

Interleukin-6

MMP-8

Matrix metalloproteinase-8

TNF

Tumor Necrosis Factor

MEC

Mobile Examination Center

BMI

Body mass index

VIF

Variance Inflation Factors

AMR

Adjusted Mean Ratio

AOR

Adjusted Odds Ratio

Authors’ contributions

Abdullah A.: Drafting the initial manuscript, managing the project, literature review, data analysis and interpretation. Hend A.: Study concept, methodology and critical revisions to the manuscript. Hesham A. and Muath A.: Data coding and critical manuscript revisions. Abdulaziz A., Saleh A., Woroud A. Sara A. and Dalal A.: Assistance in manuscript writing, editing, data interpretation, literature review and critical revisions to the manuscript. All authors gave final approval and agreed to be accountable for all aspects of the work.

Funding

This study did not receive any external funding.

Availability of data and materials

The datasets generated and/or analyzed during the current study are available in the National Health and Nutrition Examination Surveys (NHANES) repository, [NHANES Questionnaires, Datasets, and Related Documentation (cdc.gov)] Accessed January 30, 2024.

Declarations

Ethics approval and consent to participate

All participants were provided written informed consent, and all study procedures were approved by the National Center for Health Statistics Research Ethics Review Board. This study was carried out in accordance with the appropriate research guidelines and regulations.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.