Non-Alcoholic Fatty Liver Disease (NAFLD) is an emerging and increasingly prevalent chronic liver disorder characterized by excessive fat accumulation within hepatocytes in individuals without significant alcohol consumption (1). Globally, NAFLD affects approximately 25% of the adult population and is now recognized as the most common chronic liver disease worldwide (2). It represents the hepatic manifestation of metabolic syndrome and is strongly associated with obesity, insulin resistance, type 2 diabetes mellitus, hypertension, and dyslipidemia (3,4).

Although initially considered a liver-specific disorder, NAFLD is now widely acknowledged as a multisystem disease with significant cardiovascular implications. Cardiovascular disease (CVD) remains the leading cause of mortality among patients with NAFLD, exceeding liver-related complications such as cirrhosis and hepatocellular carcinoma (5). The shared pathophysiological mechanisms between NAFLD and CVD—including chronic inflammation, oxidative stress, endothelial dysfunction, and atherogenic dyslipidemia— contribute to accelerated atherosclerosis in these patients (3,6).

Carotid intima-media thickness (CIMT), measured by B-mode ultrasonography, is a wellestablished, non-invasive marker of subclinical atherosclerosis (7). Increased CIMT independently predicts future cardiovascular events such as myocardial infarction and ischemic stroke in asymptomatic individuals (8). Several studies have demonstrated that patients with NAFLD exhibit elevated CIMT values compared to healthy individuals, even after adjustment for conventional cardiovascular risk factors, suggesting that NAFLD may independently contribute to vascular damage (9,10).

The prevalence of NAFLD continues to rise globally, including in Asian populations and developing countries such as Pakistan (2,11). Regional variations in metabolic risk factors, dietary patterns, and obesity trends may influence disease progression and associated cardiovascular risk. However, limited local data exist regarding the relationship between NAFLD severity and subclinical atherosclerosis assessed through CIMT. Given the growing burden of NAFLD and its cardiovascular consequences, early detection of vascular involvement is essential. Sonographic measurement of CIMT provides a safe, accessible, and cost-effective method for identifying individuals at increased cardiovascular risk before the onset of clinical events (7). Therefore, this study was conducted to evaluate carotid intima-media thickness in patients with NAFLD and to compare these findings with healthy individuals, aiming to determine whether NAFLD is associated with increased CIMT and to assess its potential role as a non-invasive tool for early cardiovascular risk stratification.

This case-control study was conducted at the University Ultrasound Clinic, Green Town Lahore, over nine months. A total of 84 participants were included, comprising 42 patients with sonographically diagnosed NAFLD and 42 healthy controls. The sample size was calculated at a 99% confidence level and 95% power based on previously reported mean CIMT values. Convenient sampling was used. Participants aged 18–75 years were included. Individuals with alcohol consumption >20 g/day or acute/chronic liver disease were excluded. Liver assessment was performed using a 5 MHz convex probe to grade fatty liver based on hepatic echogenicity. Carotid intima-media thickness (CIMT) was measured bilaterally using a 5–13 MHz linear probe as the distance between the lumen-intima and media-adventitia interfaces of the common carotid artery. Ethical approval was obtained from the University of Lahore, and written informed consent was taken from all participants. Data were analyzed using SPSS version 25. Mean ± SD was calculated for quantitative variables, and ANOVA and t-tests were applied. A p-value <0.05 was considered statistically significant.

The findings of a study investigating CIMT in patients with NAFLD using sonography are presented in this chapter. This section presents the statistical findings of CIMT measurements in patients with NAFLD compared with healthy controls and a group that does not have hepatic asbestosis. The collected data were statistically tested to find out if there were meaningful differences between the groups and look for links between CIMT and BMI, lipid profile, liver enzyme levels and different metabolic parameters. Descriptive statistics, comparative studies and correlation findings are used to organize the results, ensuring a complete view of distinctive vascular changes in the NAFLD population is presented.

DESCRIPTIVE STATISTICS

Table 1 descriptive statistics

Eighty-four participants were divided into control (n=41), mild (n=24), moderate (n=12), and severe  (n=7) NAFLD groups. Mean CIMT values increased progressively with NAFLD severity on both  sides. For the right carotid artery, mean CIMT was 0.45 mm in controls and increased to 0.5333 mm, 0.5667 mm, and 0.5500 mm in mild, moderate, and severe groups, respectively. For the left carotid artery, mean CIMT rose from 0.4573 mm in controls to 0.5208 mm, 0.5875 mm, and 0.6071 mm across increasing NAFLD grades. Overall, patients with more severe NAFLD demonstrated thicker carotid artery walls, indicating a positive association between NAFLD severity and subclinical atherosclerosis.  

ANALYSIS OF VARIENCE (ANOVA)

Table 2:ANOVA

Analysis of variance (ANOVA) demonstrated significant differences in carotid intima-media thickness (CIMT) across NAFLD severity groups. For the right carotid artery, a significant association was observed (F(3,80) = 4.351, p = 0.007), indicating that CIMT increased with NAFLD severity. Similarly, left carotid CIMT showed a stronger significant difference among groups (F(3,80) = 7.688, p < 0.001). These findings suggest that increasing liver fat severity is associated with progressive thickening of the carotid artery walls, reflecting subclinical atherosclerosis. The stronger association on the left side highlights the potential value of CIMT as a non-invasive biomarker for early vascular changes in NAFLD patients.  

LINE GRAPH FOR RIGHT CAROTID INTIMA-MEDIA THICKNESS (Right Carotid CIMT)

Figure 2: Mean Right Carotid Intima-Media Thickness Across NAFLD Severity Groups

The graphical analysis demonstrates a progressive increase in right carotid CIMT across NAFLD severity groups. Mean CIMT increased from 0.45 mm in controls to 0.533 mm in mild and 0.567 mm in moderate NAFLD. Although a slight reduction was observed in the severe group (0.55 mm), values remained higher than controls. Overall, the trend indicates a positive association between NAFLD severity and right-sided CIMT, supporting its role as a marker of early subclinical atherosclerosis. The minor decrease in the severe group may be attributable to the small sample size. 

THE LINE GRAPH FOR LEFT CAROTID INTIMA-MEDIA THICKNESS

Figure 3: Left Carotid CIMT

The line graph shows a consistent increase in left carotid CIMT across NAFLD severity groups. Mean CIMT rose from 0.457 mm in controls to 0.521 mm in mild, 0.588 mm in moderate, and 0.607 mm in severe NAFLD. Unlike the right side, no decline was observed in the severe group, indicating a steady progression with disease severity. These findings support a strong association between NAFLD and early subclinical atherosclerosis, particularly reflected by left-sided CIMT measurements.

AGE DISTRIBUTION AMONG STUDY GROUPS

Table 4: distribution

Table shows the average age among people grouped by the severity level of NAFLD. The pattern found is that the mean age increases from group 0 (control) at 24.41 years to group i (mild NAFLD) at 34.42, through group ii (moderate NAFLD) at 41.08 and finally to group iii (severe NAFLD) at 44.71 years. Further, the age range widens slightly with more severe diseases, suggesting that there may be a connection between growing significantly older and more serious cases of NAFLD. 

GENDER DISTRIBUTION AMONG STUDY GROUPS

Table 5. Gender Distribution

The data reveals how the gender of individuals is divided in the sample group. In short, this argument boils down to… Out of the sample, 54 participants (64.3%) are female. • Of all participants in the study, 30 (35.7%) are male. The total sample size is 84 which means the study looked at all males and females in the group. All in all, the proportion of females in the sample is  greater (64.3%) than males (35.7%). 

This study investigated the association between Non-Alcoholic Fatty Liver Disease (NAFLD) and subclinical atherosclerosis assessed by carotid intima-media thickness (CIMT). The findings demonstrated a clear and progressive increase in CIMT values with increasing severity of NAFLD. Both right and left carotid arteries showed significant thickening compared to controls, with stronger statistical significance observed on the left side (p < 0.001). These results suggest that vascular changes begin early in the course of NAFLD and worsen as hepatic steatosis progresses. Mean CIMT values were lowest in the control group and increased across mild, moderate, and severe NAFLD groups. Even patients with mild NAFLD showed significantly elevated CIMT compared to healthy individuals, indicating that early stages of liver fat accumulation are associated with measurable vascular changes. Although a slight reduction in right-sided CIMT was observed in the severe group, this may be attributed to the small sample size in that category rather than a true biological reversal. In contrast, left CIMT showed a consistent rise across all grades, suggesting that it may be a more sensitive indicator of early vascular involvement. Age was positively associated with NAFLD severity, as older participants tended to have more advanced disease. While aging is an independent risk factor for arterial thickening, the consistent increase in CIMT across all NAFLD groups compared to controls indicates that NAFLD contributes to vascular changes beyond the effect of age alone. However, future studies should include multivariate analysis to adjust for confounding factors such as body mass index, smoking status, blood pressure, and metabolic variables. Several pathophysiological mechanisms may explain the observed relationship between NAFLD and increased CIMT. NAFLD is widely regarded as the hepatic manifestation of metabolic syndrome and is strongly associated with insulin resistance, dyslipidemia, oxidative stress, and chronic lowgrade inflammation. Excess hepatic lipid accumulation promotes the release of proinflammatory cytokines such as TNF-α and IL-6, which contribute to endothelial dysfunction and vascular inflammation. Insulin resistance may further stimulate smooth muscle proliferation and lipid deposition within arterial walls, leading to increased intima-media thickness. Additionally, oxidative stress reduces nitric oxide bioavailability, impairing vascular relaxation and promoting arterial stiffness. Together, these mechanisms accelerate atherosclerotic changes reflected by increased CIMT. Clinically, these findings are important because CIMT is a validated, non-invasive marker of early atherosclerosis and an independent predictor of future cardiovascular events. The results support the concept that NAFLD should not be considered solely a liver disorder but rather a systemic metabolic condition with cardiovascular implications. Early identification of vascular changes in NAFLD patients may allow timely lifestyle modification, pharmacological intervention, and cardiovascular risk reduction before the development of overt heart disease. Despite its strengths, including standardized ultrasound assessment and grading of NAFLD severity, this study has limitations. Its crosssectional design prevents determination of causality, and the relatively small sample size, particularly in the severe NAFLD group, may have limited subgroup comparisons. Additionally, metabolic and inflammatory markers were not comprehensively evaluated, which could further clarify the biological relationship between NAFLD and vascular changes. Overall, the findings reinforce the growing evidence that NAFLD is associated with early subclinical atherosclerosis and highlight the potential value of incorporating CIMT measurement into routine evaluation of patients with fatty liver disease

This study demonstrated that patients with NAFLD had significantly increased CIMT compared to healthy controls, with thicker CIMT values observed as NAFLD severity increased, suggesting a link between liver fat and early atherosclerosis. Even in mild stages of liver steatosis, patients showed progressive vascular changes that may raise the risk of cardiovascular disease. These findings support the view that NAFLD is not limited to the liver but is associated with systemic vascular involvement and an increased risk of heart disease. The use of carotid ultrasound allowed safe and effective detection of early atherosclerosis. Overall, the results indicate that worsening liver disease is linked to metabolic and vascular changes that increase arterial thickening and cardiovascular risk, emphasizing the need to include vascular assessment in routine NAFLD evaluation and to manage both liver and cardiovascular risks early. 

Routine carotid ultrasound for CIMT measurement should be considered in NAFLD patients to enable early detection of subclinical atherosclerosis. Management should focus on lifestyle modification, cardiovascular risk reduction, and appropriate pharmacological therapy when needed. A multidisciplinary approach is recommended for comprehensive care. Future longitudinal studies incorporating metabolic and inflammatory markers, along with advanced imaging techniques, are necessary to better understand the relationship between NAFLD progression and vascular changes. 

The cross-sectional design prevents determination of causality between NAFLD and increased CIMT. The small sample size, particularly in severe NAFLD, and single-center setting may limit generalizability. Important metabolic and demographic variables were not fully evaluated, and NAFLD diagnosis relied on operator-dependent ultrasound. Future research with larger, diverse populations and comprehensive metabolic profiling is required. 

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