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Research Article | Volume 30 Issue 7 (July, 2025) | Pages 198 - 202
Correlation Between Subclinical Inflammatory Markers and Early Vascular Changes in Asymptomatic Young Adults with Cardiovascular Risk Factors
 ,
 ,
1
MBBS, GMERS Medical College, Vadnagar, Gujarat, India
2
Junior Resident, Department of Pediatrics, GMERS Medical College, Vadnagar, Gujarat, India
Under a Creative Commons license
Open Access
Received
June 9, 2025
Revised
July 6, 2025
Accepted
July 13, 2025
Published
July 26, 2025
Abstract

Background: Cardiovascular disease (CVD) often has a long asymptomatic phase before clinical manifestations appear. Subclinical inflammation and early vascular alterations such as increased carotid intima-media thickness (CIMT) and arterial stiffness are considered early indicators of atherosclerosis. Identifying these markers in young adults with cardiovascular risk factors (CVRFs) may help in early intervention and prevention strategies. Materials and Methods: A cross-sectional observational study was conducted on 120 asymptomatic young adults aged 20–35 years with at least one CVRF (e.g., family history, obesity, smoking, hypertension, or dyslipidemia). Serum levels of high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), and fibrinogen were measured as inflammatory markers. Vascular changes were assessed using carotid ultrasonography to measure CIMT and pulse wave velocity (PWV) for arterial stiffness. Statistical analyses included Pearson correlation and multiple linear regression to examine associations between inflammatory markers and vascular parameters. Results: The mean hs-CRP level was 2.8 ± 1.2 mg/L, IL-6 was 3.5 ± 1.0 pg/mL, and fibrinogen was 345 ± 50 mg/dL. CIMT averaged 0.63 ± 0.07 mm, and PWV was 7.2 ± 1.1 m/s. Significant positive correlations were observed between hs-CRP and CIMT (r = 0.45, p < 0.01), IL-6 and PWV (r = 0.39, p < 0.01), and fibrinogen and CIMT (r = 0.33, p < 0.05). Regression analysis indicated hs-CRP as an independent predictor of CIMT (p = 0.004).Conclusion: This study highlights a strong association between subclinical inflammatory markers and early vascular changes in young adults with CVRFs. Early identification of these markers may allow timely lifestyle or pharmacological interventions to prevent progression to overt CVD.

Keywords
INTRODUCTION

Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality worldwide, accounting for over 17 million deaths annually, with a significant proportion attributed to atherosclerosis and its complications (1). Traditionally viewed as a disease of middle-aged and older adults, there is increasing evidence that the atherosclerotic process begins early in life, often remaining subclinical for years before manifesting as clinical events such as myocardial infarction or stroke (2,3). Consequently, early detection of vascular changes and underlying pathophysiological mechanisms is critical for effective prevention strategies.

Recent studies suggest that chronic low-grade inflammation plays a pivotal role in the initiation and progression of atherosclerosis, even in asymptomatic individuals (4). Inflammatory biomarkers such as high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), and fibrinogen have been recognized as early indicators of vascular injury and endothelial dysfunction, which are key events in atherogenesis (5,6). These markers are elevated in individuals with traditional cardiovascular risk factors (CVRFs) such as obesity, hypertension, dyslipidemia, smoking, and a positive family history of CVD, even in the absence of overt clinical symptoms (7,8).

Carotid intima-media thickness (CIMT) and pulse wave velocity (PWV) are established non-invasive tools used to assess subclinical atherosclerosis and arterial stiffness, respectively. Both parameters have shown predictive value for future cardiovascular events in young and middle-aged adults (9,10). While numerous studies have explored these markers in older or symptomatic populations, data focusing on their relevance in asymptomatic young adults with CVRFs remain limited.

Therefore, this study aims to evaluate the correlation between subclinical inflammatory markers (hs-CRP, IL-6, and fibrinogen) and early vascular changes (CIMT and PWV) in apparently healthy young adults with identifiable cardiovascular risk factors. Identifying early vascular alterations in this demographic may offer valuable insights into the prevention and early management of cardiovascular diseases.

MATERIALS AND METHODS

Study Design and Participants

A total of 120 asymptomatic young adults aged between 20 and 35 years were enrolled. Participants were included if they had at least one identifiable cardiovascular risk factor such as a positive family history of CVD, current or past smoking, obesity (BMI ≥25 kg/m²), hypertension (systolic BP ≥130 mmHg or diastolic BP ≥85 mmHg), or dyslipidemia. Individuals with a history of cardiovascular, renal, hepatic, or autoimmune disease, recent infection or inflammation, or those on anti-inflammatory or lipid-lowering medication were excluded.

 

Data Collection and Laboratory Analysis

Demographic data and clinical parameters including age, gender, BMI, blood pressure, smoking history, and family history were recorded using a structured questionnaire. Blood samples were collected after an overnight fast to assess inflammatory markers including high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), and plasma fibrinogen levels. hs-CRP was measured using a high-sensitivity immunoturbidimetric assay, IL-6 by enzyme-linked immunosorbent assay (ELISA), and fibrinogen using the Clauss clotting method.

 

Assessment of Vascular Parameters

Carotid intima-media thickness (CIMT) was measured using high-resolution B-mode ultrasonography (7.5 MHz linear transducer). Measurements were taken at the distal common carotid artery, 1 cm proximal to the bifurcation, on both sides. The average of three readings from each side was recorded as the final CIMT value. Arterial stiffness was assessed using pulse wave velocity (PWV), measured between the carotid and femoral arteries using a validated non-invasive oscillometric device.

 

Statistical Analysis

All data were entered into Microsoft Excel and analyzed using SPSS version 25. Continuous variables were expressed as mean ± standard deviation (SD). Pearson’s correlation coefficient was used to determine the association between inflammatory markers and vascular measurements. Multivariate linear regression was performed to assess independent predictors of vascular changes. A p-value <0.05 was considered statistically significant.

RESULTS

A total of 120 asymptomatic young adults (68 males and 52 females) were included in the study. The mean age of the participants was 27.3 ± 4.1 years. Table 1 summarizes the baseline demographic and clinical characteristics of the study population. The most common cardiovascular risk factor was a positive family history (42%), followed by dyslipidemia (36%) and obesity (30%).

 

Table 1. Baseline characteristics of the study participants (n = 120)

Parameter

Value (Mean ± SD) / Frequency (%)

Age (years)

27.3 ± 4.1

Male:Female

68:52

BMI (kg/m²)

26.4 ± 3.2

Systolic BP (mmHg)

128.7 ± 9.5

Diastolic BP (mmHg)

84.1 ± 6.3

Smokers

28 (23.3%)

Positive family history

50 (41.7%)

Dyslipidemia

43 (35.8%)

Obesity (BMI ≥25 kg/m²)

36 (30.0%)

 

Inflammatory marker levels and vascular parameters are presented in Table 2. The mean hs-CRP was 2.8 ± 1.2 mg/L, IL-6 was 3.5 ± 1.0 pg/mL, and fibrinogen was 345 ± 50 mg/dL. CIMT was 0.63 ± 0.07 mm, and PWV measured 7.2 ± 1.1 m/s.

 

Table 2. Inflammatory and vascular parameters

Parameter

Mean ± SD

hs-CRP (mg/L)

2.8 ± 1.2

IL-6 (pg/mL)

3.5 ± 1.0

Fibrinogen (mg/dL)

345 ± 50

CIMT (mm)

0.63 ± 0.07

PWV (m/s)

7.2 ± 1.1

 

Correlation analysis revealed significant positive associations between inflammatory markers and vascular parameters (Table 3). hs-CRP showed a moderate correlation with CIMT (r = 0.45, p < 0.01) and PWV (r = 0.31, p < 0.05). IL-6 was positively correlated with PWV (r = 0.39, p < 0.01), while fibrinogen was significantly associated with CIMT (r = 0.33, p < 0.05).

 

Table 3. Correlation between inflammatory markers and vascular parameters

Correlation Pair

Pearson’s r

p-value

hs-CRP vs CIMT

0.45

<0.01

hs-CRP vs PWV

0.31

<0.05

IL-6 vs PWV

0.39

<0.01

Fibrinogen vs CIMT

0.33

<0.05

 

Multiple linear regression analysis demonstrated that hs-CRP remained an independent predictor of increased CIMT (β = 0.28, p = 0.004) after adjusting for age, BMI, and blood pressure (Table 4).

 

Table 4. Multiple linear regression for predictors of CIMT

Variable

β Coefficient

Standard Error

p-value

hs-CRP

0.28

0.09

0.004

Age

0.12

0.07

0.08

BMI

0.09

0.06

0.14

Systolic BP

0.10

0.08

0.12

These findings suggest that subclinical inflammation, especially elevated hs-CRP, is significantly associated with early vascular changes such as increased CIMT and arterial stiffness in young adults with cardiovascular risk factors (Table 3, Table 4).

DISCUSSION

The present study examined the relationship between subclinical inflammatory markers and early vascular alterations in asymptomatic young adults with cardiovascular risk factors (CVRFs). Our findings revealed that higher levels of hs-CRP, IL-6, and fibrinogen were significantly associated with increased carotid intima-media thickness (CIMT) and arterial stiffness, suggesting that inflammation contributes to early vascular remodeling even in the absence of clinical cardiovascular disease.

Chronic low-grade inflammation is increasingly recognized as a key contributor to the pathogenesis of atherosclerosis and cardiovascular events. hs-CRP, a sensitive acute-phase reactant, has been shown to predict future cardiovascular events independently of traditional risk factors (1). In our study, hs-CRP demonstrated a significant positive correlation with CIMT and pulse wave velocity (PWV), consistent with findings from previous population-based studies (2,3).

Interleukin-6 (IL-6), a pro-inflammatory cytokine involved in hepatic synthesis of acute-phase proteins, also showed a strong association with PWV, reinforcing its role in vascular stiffness and endothelial dysfunction (4). Elevated IL-6 has been reported to influence vascular tone by promoting oxidative stress and reducing nitric oxide bioavailability, thereby contributing to increased arterial stiffness (5,6). Fibrinogen, another systemic inflammatory marker, correlated positively with CIMT in our study, aligning with earlier reports that highlight its role in promoting vascular smooth muscle proliferation and atheroma formation (7,8).

CIMT is a validated surrogate marker of subclinical atherosclerosis, and its progression has been linked to higher risk of myocardial infarction and stroke (9). Our findings of increased CIMT in young adults with elevated inflammatory markers point toward the early onset of atherogenic changes, underscoring the importance of monitoring vascular health even in asymptomatic individuals. Similarly, PWV, an indicator of arterial stiffness, has been independently associated with future cardiovascular morbidity and mortality (10,11).

The relationship between inflammation and vascular alterations observed in this study supports the hypothesis that inflammatory mechanisms are active in the subclinical phase of cardiovascular disease. These associations were observed in a young cohort, indicating that pathophysiological changes may begin much earlier than traditionally assumed. Other studies in young and middle-aged populations have also demonstrated similar trends, emphasizing the cumulative effect of CVRFs and inflammation on early vascular dysfunction (12,13).

Furthermore, the finding that hs-CRP was an independent predictor of CIMT after adjusting for confounding variables highlights its potential utility as a screening biomarker. This is in agreement with data from the Framingham Heart Study and other longitudinal cohorts that demonstrated the predictive value of hs-CRP in vascular remodeling and cardiovascular risk stratification (14,15).

CONCLUSION

In conclusion, this study provides evidence that subclinical inflammation is significantly associated with early vascular changes in young adults with cardiovascular risk factors. hs-CRP, IL-6, and fibrinogen may serve as useful biomarkers in identifying individuals at elevated cardiovascular risk before clinical manifestations arise. Future prospective studies with larger cohorts and long-term follow-up are needed to confirm these findings and guide early prevention strategies.

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  7. Maahs DM, Jalal D, Chonchol M, Johnson RJ, Rewers M, Snell-Bergeon JK. Impaired renal function further increases odds of 6-year coronary artery calcification progression in adults with type 1 diabetes: the CACTI study. Diabetes Care. 2013 Sep;36(9):2607–14. doi:10.2337/dc12-2538.
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