A total of 164 patients were included in this study, with 82 patients in the AF group and 82 in the NSR group. The mean age of the AF group was significantly higher than that of the NSR group (71.5 ± 8.4 years vs. 61.3 ± 9.1 years; p < 0.001). As age is a well-established risk factor for AF, this difference was addressed in the subsequent analysis by including age as a covariate in multivariate logistic regression models to account for its potential confounding effect.

Table 1

Variables	NSR (n = 82)	AF (n = 82)
Age (years)	61.341	71.548
Male (n)	41	44
Heart rate (bpm)	71.4	78.5
LVH (n)	3	10
RBBB (n)	1	7
LBBB (n)	0	3
LAFB (n)	0	3

AF, atrial fibrillation; LAFB, left anterior fascicular block; LBBB, left bundle branch block; LVH, left ventricular hypertrophy; NSR, normal sinus rhythm; RBBB, right bundle branch block

Patients in the NSR group had an average heart rate of 71.4 beats per minute (bpm), while those in the AF group had a higher average heart rate of 78.5 bpm. A higher proportion of patients in the AF group (n = 10) presented with left ventricular hypertrophy (LVH) than in the NSR group (n = 3). In the NSR group, 1 patient had right bundle branch block (RBBB). The AF group had 7 patients with RBBB, 3 patients with left bundle branch block (LBBB), and 3 with left anterior fascicular block (LAFB). No left-sided conduction abnormality was observed in the NSR group (Table 1).

In the NSR cohort, the clinical diagnoses included 16 individuals with coronary artery disease (CAD), 9 reporting chest discomfort, 3 with a history of myocardial infarction (MI), and 4 diagnosed with aortic stenosis. Additionally, 1 patient had undergone aortic valve replacement, 3 had mitral valve replacement, and 1 had tricuspid valve replacement. Heart failure was present in 6 individuals, cardiomyopathy in 4, and angina pectoris in 15. Tachycardia was noted in 9 patients, Takayasu disease in 1, hypertension in 6, and a history of cancer in 4. In the AF cohort, diagnoses were distributed as follows: 45 patients with AF, 2 with CAD, 7 with chest discomfort, 4 with MI, 5 with aortic stenosis, 8 with mitral valve replacement, 2 with tricuspid valve replacement, 5 with heart failure, 2 with cardiomyopathy, and 2 with angina pectoris (Table 2).

Table 2

Variables	NSR (n = 82)	AF (n = 82)
Atrial fibrillation	0	45
Coronary artery disease	16	2
Chest discomfort	9	7
Myocardial Infarction	3	4
Aortic stenosis	4	5
Aortic valve replacement	1	0
Mitral valve replacement	3	8
Tricuspid valve replacement	1	2
Heart failure	6	5
Cardiomyopathy	4	2
Angina pectoris	15	2
Tachycardia	9	0
Takayasu disease	1	0
Hypertension	6	0
Cancer	4	0
Total	82	82

AF, atrial fibrillation; CRP, C-reactive protein; NSR, normal sinus rhythm

Figure 1

The average CRP level among patients with NSR was 4.92 mg/L, with 68 individuals falling within the normal range (0–8 mg/L) and 14 exceeding it. The mean CRP level was 28.56 ± 6.84 mg/L in the AF group and 4.92 ± 1.73 mg/L in the NSR group. The mean difference in CRP levels between the two groups was 23.64 mg/L, with a 95% confidence interval (CI) of 19.87–27.41 mg/L (p = 0.002) (Figure 1).

Figure 2

The average NLR value in patients with NSR was 2.51, with 66 individuals falling within the normal range (1–3). Furthermore, 6 individuals had NLR values below the lower threshold of normalcy, while 10 surpassed the upper limit of the normal range. The mean NLR was 2.74 ± 1.12 in the AF group and 2.51 ± 0.98 in the NSR group. The mean difference in NLR was 0.23, with a 95% CI of -0.14 to 0.60 (p = 0.3161), suggesting a lack of statistical significance in differentiating between the two groups (Figure 2).

The ROC curve analysis demonstrated an area under the curve (AUC) of 0.658 for CRP, with a corresponding sensitivity (SE) of 0.0431. For NLR, the AUC was 0.577, with an SE of 0.0449. For CRP+NLR, the AUC improved to 0.667, with an SE of 0.0422 (Figure 3 and Table 3).

Figure 3

Table 3

Variable	AUC	SE	95% CI
CRP	0.658	0.0431	0.583 – 0.732
NLR	0.577	0.0449	0.489 – 0.665
CRP+NLR	0.667	0.0422	0.593 – 0.741

AUC, area under the curve; CI, confidence intervals; CRP, C-reactive protein; NLR, neutrophil-to-lymphocyte ratio; NSR, normal sinus rhythm; SE, sensitivity

The significant difference observed in CRP levels between patients with AF and those with NSR underscores the potential role of inflammation in AF pathogenesis. This finding aligns with that of previous studies suggesting an association between elevated CRP levels and the development, progression, and recurrence of AF. Numerous epidemiological and mechanistic investigations have highlighted the multifaceted relationship between inflammation and AF, implicating CRP as a promising biomarker for risk stratification and prognostication in patients with AF.

Existing research has consistently demonstrated elevated CRP levels in patients with AF compared to those in individuals with NSR, implicating systemic inflammation in the pathophysiology of AF. Tanaka et al. 14 found that an elevated CRP level was significantly associated with AF. Hijazi et al. 23 showed that elevated IL-6 levels were related to old age, persistent and permanent AF, and heart failure. The prognostic significance of CRP in AF is further supported by its association with adverse cardiovascular outcomes, including stroke, heart failure, and mortality.

These findings highlight the clinical relevance of CRP as a biomarker for identifying high-risk individuals, guiding therapeutic interventions, and monitoring disease progression in AF. Incorporating CRP measurements into risk prediction models may enhance risk stratification strategies and facilitate personalized management approaches in patients with AF.

Despite the lack of statistically significant differences between patients with AF and NSR, the clinical relevance of NLR in AF management nevertheless merits consideration. While NLR has been implicated in various inflammatory conditions and cardiovascular diseases, its utility as a prognostic or diagnostic marker in AF remains uncertain. However, given the complex pathophysiology of AF, exploring the potential role of NLR as a supplementary biomarker in risk stratification and treatment response assessment could be valuable.

Several factors may contribute to the observed lack of significance in NLR levels between AF and NSR groups. These include the heterogeneous nature of AF, with diverse underlying etiologies and comorbidities that may influence inflammatory marker profiles differently. Additionally, variations in patient characteristics, such as age, sex, and disease duration, could confound the association between NLR and AF. Methodological considerations, including assay techniques and sample handling procedures, may also impact the accuracy and reproducibility of NLR measurements, potentially attenuating the observed differences between groups.

While the nonsignificant finding underscores the limitations of NLR as a standalone biomarker for discriminating between patients with AF and NSR, it highlights the need for a comprehensive multimodal approach to risk assessment and patient management in AF. Integrating clinical, demographic, and biochemical parameters, including NLR, CRP, and other inflammatory markers, may enhance risk stratification models and improve patient outcomes. Future studies employing longitudinal designs and larger sample sizes are warranted to validate these findings and elucidate the clinical implications of inflammatory marker profiling in AF management.

The combined marker, referred to as CRP+NLR, demonstrated the highest AUC and SE compared to CRP and NLR individually. These findings suggest that the integration of CRP and NLR values into a single combined marker can enhance the ability to stratify risk among patients with AF and provide a better indicator of inflammatory status.

It is noteworthy that both CRP and NLR yielded statistically significant SE, indicating that their association with AF was unlikely random. Additional studies involving larger sample sizes and varied patient demographics are needed to confirm these findings and to better understand the mechanisms contributing to the observed associations.

In interpreting the findings of this study, several limitations must be acknowledged. First, the relatively small sample size may have constrained the statistical power, potentially diminishing the ability to detect significant differences in biomarkers between the AF and NSR groups. Furthermore, the cross-sectional nature of the study precludes the establishment of a causal relationship between elevated CRP and NLR levels and AF. Confounding variables such as comorbidities or other inflammatory conditions were not fully controlled. Future research should aim to address these limitations by conducting studies with larger and more diverse patient populations to validate the observed associations and to enhance the generalizability of the findings. Prospective longitudinal studies would be particularly valuable in determining whether changes in biomarkers over time are predictive of AF onset or recurrence, helping in clarifying the causal relationship between CRP and NLR levels and AF. Additionally, exploring the combined use of CRP and NLR in a composite biomarker model across different clinical settings may provide further insights into their utility in AF risk stratification and management.