Coronary Artery Disease Severity in Patients with Inflammatory Bowel Disease

Abstract

This study investigates whether inflammatory bowel disease (IBD) is associated with greater severity of coronary artery disease (CAD). In this single-centre case–control study, 55 Egyptian patients with IBD were compared with 55 healthy controls using conventional cardiovascular risk factors, inflammatory biomarkers, carotid intima–media thickness (CIMT), and coronary angiography quantified by the SYNTAX score [1]. Patients with IBD demonstrated significantly higher leukocyte counts, high-sensitivity C-reactive protein (hs-CRP), fasting blood glucose, CIMT, SYNTAX scores, and a greater prevalence of carotid atherosclerotic plaques than healthy controls. Multivariable logistic regression identified diabetes mellitus, hypertension, smoking, and IBD as independent predictors of severe CAD. Based on these findings, the authors propose that chronic inflammatory biomarkers should be incorporated into cardiovascular risk assessment for patients with IBD [1]. The study addresses a clinically important and increasingly relevant question. As the global incidence of IBD continues to rise, recognition of its extraintestinal manifestations, particularly cardiovascular complications, has become a major area of investigation. The observed association between systemic inflammation, carotid atherosclerosis, and greater angiographic complexity of CAD is biologically plausible and consistent with current understanding of inflammation-mediated endothelial dysfunction, accelerated atherogenesis, and vascular remodeling [2,3]. Furthermore, the study contributes valuable data from an Egyptian population, where evidence regarding cardiovascular risk among patients with IBD remains relatively limited. Nevertheless, several methodological considerations warrant a cautious interpretation of the findings. First, the case–control design is appropriate for identifying associations but does not permit causal inference. Residual confounding, reverse causation, and selection bias cannot be excluded. Moreover, the relatively modest sample size limits statistical power, increases uncertainty around effect estimates, and reduces the precision of multivariable analyses. These limitations should temper the strength of the authors' conclusions. A particularly important concern relates to the multivariable logistic regression results. The authors report that IBD independently predicts severe CAD with an odds ratio (OR) of 2.77 and a highly significant p value (<0.001). However, the corresponding 95% confidence interval (0.603–12.76) includes the null value of one, indicating that the association is not statistically significant by conventional interpretation. This discrepancy represents a major internal inconsistency within the statistical analysis and requires clarification. Either the confidence interval, odds ratio, or p value appears to have been reported incorrectly. Until this inconsistency is resolved, confidence in the reported independent association between IBD and CAD severity remains limited. Another important limitation is the incomplete adjustment for disease-specific confounders. Although conventional cardiovascular risk factors such as diabetes, hypertension, and smoking were included in the regression model, several clinically relevant IBD-related variables were omitted. These include disease duration, cumulative inflammatory burden, disease activity, corticosteroid exposure, biologic or immunosuppressive therapy, prior intestinal surgery, and nutritional status. Each of these factors has the potential to independently influence cardiovascular risk. Consequently, the observed association may reflect the cumulative effects of chronic systemic inflammation and its treatment rather than IBD itself. The interpretation of the study outcomes also requires greater nuance. The SYNTAX score is a validated tool for assessing the anatomical complexity of coronary lesions and guiding decisions regarding coronary revascularization; however, it was not designed as a direct measure of total coronary atherosclerotic burden [4]. Higher SYNTAX scores primarily reflect lesion complexity, including bifurcation lesions, chronic total occlusions, diffuse disease, tortuosity, and calcification, rather than plaque quantity alone. Likewise, CIMT is an established marker of subclinical vascular disease but demonstrates only a modest correlation with coronary atherosclerosis. More direct assessments of coronary plaque burden, such as coronary computed tomography angiography (CCTA) or coronary artery calcium (CAC) scoring, would provide stronger evidence regarding the extent of coronary atherosclerosis [5]. Therefore, although the reported differences in SYNTAX score and CIMT are statistically significant, their direct clinical implications should be interpreted with caution. The broader literature examining the relationship between IBD and cardiovascular disease remains heterogeneous. Several observational studies and meta-analyses have demonstrated an increased incidence of cardiovascular events among patients with IBD, particularly during periods of active disease and persistent systemic inflammation [6]. However, Mendelian randomization studies—which are inherently less susceptible to residual confounding and reverse causation—have not consistently supported a causal relationship between genetically determined IBD and atherosclerotic cardiovascular disease. These findings suggest that previously observed associations may be mediated by chronic inflammation, medication exposure, lifestyle factors, or healthcare-related confounding rather than a direct biological effect of IBD itself. Consequently, the current evidence base remains insufficient to establish causality. From a clinical perspective, this study reinforces the importance of comprehensive cardiovascular risk assessment in patients with IBD. However, the available evidence does not currently justify modification of existing cardiovascular risk prediction algorithms. There is insufficient prospective evidence to demonstrate that incorporating inflammatory biomarkers into established cardiovascular risk models improves risk discrimination, clinical decision-making, or patient outcomes. Until robust longitudinal studies become available, management should continue to prioritize aggressive modification of traditional cardiovascular risk factors, optimal control of intestinal inflammation, and minimization of prolonged corticosteroid exposure whenever clinically feasible. Overall, the authors provide valuable regional evidence demonstrating greater coronary lesion complexity, increased carotid atherosclerosis, and heightened systemic inflammation among patients with IBD compared with healthy controls. However, several important limitations—including the observational case–control design, modest sample size, statistical inconsistency in the multivariable regression results, incomplete adjustment for disease-specific confounding variables, and the inherent limitations of SYNTAX score and CIMT as surrogate measures of coronary atherosclerosis—preclude firm causal conclusions. Future large-scale, prospective, multicentre studies incorporating cumulative inflammatory exposure, disease activity, treatment history, advanced coronary imaging, and hard cardiovascular endpoints are necessary before inflammation-based cardiovascular risk algorithms can be recommended for routine clinical practice in patients with IBD. 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