Reliability of C-reactive Protein as a Biomarker for Cardiovascular and Oral Diseases in Young and Old Subjects.

BACKGROUND: Increased C-reactive protein (CRP) levels are associated with various diseases such as cardiovascular diseases (CVDs), periodontal diseases, and other inflammatory diseases and can be an effective biomarker for predicting future risks of periodontal diseases. AIMS: The present trial was carried out to evaluate if CRP levels are lower in healthy and young individuals as compared to individuals with high body mass index (BMI), gingival index, and CVDs by assessing CRP levels in young and old individuals (more than 45 years).
MATERIALS AND METHODS: A total of 174 participants were recruited for the study and were divided into three following groups: Less than 45 years healthy participants (n = 124), more than 45 years healthy participants, and more 45-year-old participants with CVDs (n = 25). The collected data were subjected to the statistical analysis.
RESULTS: In Group I, females had a CRP level of 8476 ± 6.86 pg, females of Group II had a CRP value of 13,262 ± 3.76, and in females of Group III CRP value was 22,761 ± 6.24 pg. These values, respectively, for males were 8494 ± 7.68, 13,840 ± 4.82, and 13,839 ± 3.8. In smokers, the CRP values for Group I, II, and III were 29,012 ± 14.66, 12,568 ± 4.16, and 16,826 ± 3.42, respectively.
CONCLUSION: CRP levels were higher in males as compared to females. Higher BMI was associated with higher values of CRP. The participants with higher BMI presented higher CRP values irrespective of age. Copyright:

INTRODUCTION

Cardiovascular diseases (CVDs) are emerging as the main cause of death in the world causing approximately 17 million deaths in a year, and the number is expected to increase shortly which accounts for more death than cancers of all types combined.[1] Foam cell formation in CVD leads to elevated C-reactive protein (CRP) levels which in turn can lead to CVDs. Consistently, elevated levels of CRP in CVDs indicate the presence of inflammation in CVDs. CRP is associated with systemic inflammation and low during normal conditions.[2]

Gingivitis and periodontitis are inflammatory diseases of the supporting tissues of teeth caused by plaque, microorganisms, and calculus and can result in systemic diseases such as diabetes and CVDs. Periodontitis being a chronic inflammatory disease also involves acute inflammatory markers of the immune system such as fibrinogen, CRP, and/or plasminogen activator inhibitors.[3] Gingivitis and periodontitis are also related to the CVDs as a higher incidence of CVDs is found in participants of periodontal diseases. Various indices are used to measure periodontal diseases including gingival index and periodontal index.[4]

Obesity is affecting a large population globally and is one of the major causes of morbidity. Obesity is measured by body mass index (BMI), where a BMI of more than 25 kg/m2 in adults shows obesity. Various diseases caused by obesity include musculoskeletal diseases, respiratory diseases, infertility, dermatological diseases, CVDs, gallbladder diseases, diabetes, and cancers of certain types.[5]

CRP associated with various inflammatory diseases is measured using the enzyme-linked immunosorbent assay (ELISA) test, which is an antigen-antibody test. The ELISA test is used in two ways using the immunoassay system. Both the assays showed some difference but high accuracy and reliability in detecting the levels of CRP.[6] Various studies in previous literature have established a link between inflammatory periodontal diseases such as gingivitis and periodontitis with high CRP levels. Very scarce data in the literature are available regarding the relation of high CRP and gingivitis with other diseases including CVD and obesity.[7] Hence, the present trial was carried out to evaluate if CRP levels are lower in healthy and young individuals as compared to individuals with high BMI, gingival index, and CVDs by assessing CRP levels in young (<45 years) and old individuals (more than 45 years).

MATERIALS AND METHODS

The present trial was carried out to evaluate if CRP levels are lower in healthy and young individuals as compared to individuals with high BMI, gingival index, and CVDs by assessing CRP levels in young and old individuals (more than 45 years). The study included three groups as follows: One group with the age <45 years and with no CVDs or other medical diseases, 2nd group having participants higher than 45 years of age with no CVDs or other medical diseases, and 3rd group having participants higher than 45 years with CVD.

The present study collected the plasma specimen from the included participants to assess the CRP levels. The study included both males and females within the age group of 18–78 years with a mean age of 47.6 years. A total of 174 participants were recruited for the study and were divided into three following groups:

Group I: Less than 45 years healthy participants (n = 124)

Group II: More 45 years healthy participants (n = 25)

Group III: More 45 years old participants with CVDs (n = 25)

To be included in the study, the participants had to be of 18 years or more, in a mental and physical sound state, and ready to provide plasma sample. The exclusion criteria for the study were participants with the tumor in the oral cavity, generalized excessive plaque and calculus, caries affecting the large number of teeth, generalized and advanced periodontal disease, mobility and suppuration in gingival areas, and with teeth mobility. Furthermore, participants having systemic diseases other than CVDs, pregnant females, lactating females, and participants with immunosuppression were excluded from the study.

The demographic characteristics of the study participants were recorded followed by an examination of the oral cavity to assess the periodontal status. A thorough examination of the facial symmetry, buccal mucosa, lips, lymph nodes, tongue, palate, floor of the mouth, and teeth was carried out. Following examination, gingival index[8] was evaluated. Finally, the CRP levels were assessed from the plasma obtained from 5 ml of whole blood obtained from participants both at baseline and last visit. After this, BMI of all study participants was also calculated using the standardized formula in kg/m2. The collected data were subjected to the statistical analysis.

RESULTS

The demographic characteristics of the study participants were recorded and are summarized in Table 1. The study included both males and females within the age range of 18 years to 78 years with a mean age of 47.6 years. The study had 83 females (47.70%), and 52.29% males (n = 91). 40.80% study participants were smokers (n = 71) and 59.19% (n = 103) were non-smokers. The mean BMI of the study participants was 29.6 kg/m2.

Table 1

Demographic characteristics of the study participants

Characteristic	Number (n=174), n (%)
Mean age	47.6
Age range	18-78
Sex
Females	83 (47.70)
Males	91 (52.29)
Smoking status
Positive	71 (40.80)
Negative	103 (59.19)
Mean BMI	29.6

BMI: Body mass index

The present study also assessed the CRP levels in smokers and of different sex. The results are listed in Table 2. The results showed that in Group I, <45 years healthy participants (n = 124) females had a CRP level of 8476 ± 6.86 pg, females of Group II had a CRP value of 13,262 ± 3.76, and in females of Group III CRP value was 22,761 ± 6.24 pg. These values, respectively, for males were 8494 ± 7.68, 13,840 ± 4.82, and 13,839 ± 3.8. In smokers, the CRP values for Group I, II, and III were 29,012 ± 14.66, 12,568 ± 4.16, and 16,826 ± 3.42, respectively. For nonsmokers, the CRP values were 30,124 ± 28.14, 16,826 ± 3.42, and 18,748 ± 26.26 for Groups I, II, and III, respectively.

Table 2

Effect of sex and smoking on C-reactive protein in study subjects

Characteristic	Sex		Smoking status
	Females	Males	Positive	Negative
CRP (page) for Group I ?45 years healthy participants (n=124)	8476±6.86	8494±7.68	29012±14.66	30124±28.14
CRP (page) for Group II >45 years healthy participants (n=25)	13262±3.76	13840±4.82	12568±4.16	16826±3.42
CRP (in page) for Group III >45 years old participants with CVDs (n=25)	22761±6.24	13839±3.8	16826±3.42	18748±26.26

CRP: C-reactive protein, CVDs: Cardiovascular diseases

On evaluating the gingival index for the three groups, the results showed that for females the values for the gingival index for the three groups were 0.779 ± 0.72, 2.06 ± 0.88, and 2.29 ± 1.1, respectively. The respective values for males in Group I, II, and III were 0.86 ± 0.66, 2.145 ± 0.74, and 2.16 ± 0.92. The CRP values concerning gingival index in three groups, respectively, were found to be 31,492 ± 8.74, 18,926 ± 6.82, and 42,168 ± 7.92. It was seen that the values increased from Group I to Group III for females, males, and CRP. Concerning BMI, the values in females for Group I, II, and III were 25.07 ± 3.24, 23.07 ± 3.78, and 27.02 ± 2.86, respectively. These values for males in three groups were 25.04 ± 4.12, 23.54 ± 3.26, and 30.025 ± 2.78, respectively. BMI values for both males and females were higher for Group I, and then decreased for Group II, and the highest BMI was seen for Group III. The CRP values concerning BMI in three groups, respectively, were found to be 32,168 ± 9.22, 18,954 ± 8.14, and 43,682 ± 9.68. These values showed statistical variation in agreement with the values for gingival index [Table 3].

Table 3

Effect of gingival index and body mass index on C-reactive protein in study groups

Characteristic	Group I ?45 years healthy subjects (n=124)	Group II ? 45 years healthy subjects (n=25)	Group III ?45 years old subjects with CVDs (n=25)
Gingival index
Females	0.779±0.72	2.06±0.88	2.29±1.1
Males	0.86±0.66	2.145±0.74	2.16±0.92
CRP values	31492±8.74	18926±6.82	42168±7.92
BMI
Females	25.07±3.24	23.07±3.78	27.02±2.86
Males	25.04±4.12	23.54±3.26	30.025±2.78
CRP values	32168±9.22	18954±8.14	43682±9.68

CRP: C-reactive protein, BMI: Body mass index, CVDs: Cardiovascular diseases

DISCUSSION

The study results have shown that on evaluating the gingival index for the three groups, the results showed that CRP values in three groups, respectively, were found to be 31,492 ± 8.74, 18,926 ± 6.82, and 42,168 ± 7.92. It was seen that the values increased from Group I to Group III for females, males, and CRP. Concerning BMI, the values in females for Group I, II, and III were 25.07 ± 3.24, 23.07 ± 3.78, and 27.02 ± 2.86, respectively. These values for males in three groups were 25.04 ± 4.12, 23.54 ± 3.26, and 30.025 ± 2.78, respectively. BMI values for both males and females were higher for Group I, and then decreased for Group II, and the highest BMI was seen for Group III. The CRP values concerning BMI in three groups, respectively, were found to be 32,168 ± 9.22, 18,954 ± 8.14, and 43,682 ± 9.68. These values showed statistical variation in agreement with the values for gingival index. These findings were in agreement with the studies of Perio diseases and BMI[9] conducted in 2003 where authors linked gingival diseases to BMI values. The gingival index values were higher in males than females except for Group III having old subjects with CVDs. These values were consistent with the study of LaMonte MJ et al.[10] in 2017 where the authors reported more CRP in older females reaching menopause.

The study evaluated the correlation of CRP levels in males and females. On evaluating it was seen that higher CRP levels were found in males as compared to females. The results showed that in Group I, <45 years healthy participants (n = 124) females had a CRP level of 8476 ± 6.86 pg, females of Group II had a CRP value of 13,262 ± 3.76, and in females of Group III CRP value was 22,761 ± 6.24 pg. These values, respectively, for males were 8494 ± 7.68, 13,840 ± 4.82, and 13,839 ± 3.8. The values were nonsignificant in Group I having healthy young participants. In the older group, values were higher in females. These findings were similar to the findings by Alzalzalah[11] in 2017 where the authors reported results similar to the present study.

The present study also assessed the CRP levels in smokers and of different sex. The results showed that in Group I, <45 years healthy subjects (n = 124) females had a CRP level of 8476 ± 6.86 pg, females of Group II had a CRP value of 13,262 ± 3.76, and in females of Group III CRP value was 22,761 ± 6.24 pg. These values, respectively, for males were 8494 ± 7.68, 13,840 ± 4.82, and 13,839 ± 3.8. In smokers, the CRP values for Group I, II, and III were 29,012 ± 14.66, 12,568 ± 4.16, and 16,826 ± 3.42, respectively. For nonsmokers, the CRP values were 30,124 ± 28.14, 16,826 ± 3.42, and 18,748 ± 26.26 for Group I, II, and III respectively. Low CRP levels were seen in smokers compared to nonsmokers. Furthermore, lower GI values were seen in smokers owing to less bleeding after vasoconstriction as suggested by Bansal et al.[12] in 2014 regarding the CRP values.

CONCLUSION

The present study concludes that CRP detection can act as an important, reliable, and easy biomarker to predict the risk for future CVD. The results regarding age, sex, BMI, and gingival index showed that CRP levels were higher in males compared to females. Higher BMI was associated with higher values of CRP. The participants with higher BMI presented higher CRP values irrespective of age. Similar results were demonstrated for gingival index values where higher index values were associated with high CRP values. Inconclusive results were seen concerning smoking which can be due to the small sample size.

The study had few shortcomings including the geographical area bias, small sample size, and monitoring period. Future studies should focus on conducting studies in different regions with larger sample sizes and monitoring periods to reach a definitive conclusion.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.