We read with great interest the recent article by Urbanowicz et al. [1] evaluating the association between biological sex and long-term survival following off-pump coronary artery bypass (OPCAB) surgery using bilateral internal mammary artery grafting. The authors should be commended for addressing an important and increasingly recognized topic in cardiovascular surgery, particularly in the context of sex-related differences in coronary artery disease presentation and revascularization outcomes.
The observation of improved long-term survival among female patients is intriguing and potentially hypothesis-generating. However, several methodological and interpretive/interpretation considerations warrant further discussion.
First, the markedly unbalanced sex distribution represents an important limitation. Only 32 female patients were included among the 276 analyzed participants, corresponding to approximately 12% of the study cohort. Such a small subgroup substantially limits statistical robustness and may lead to unstable survival estimates, particularly during extended follow-up periods. Although Kaplan-Meier analysis demonstrated a statistically significant difference between sexes, the relatively small number of women raises concerns regarding the precision and reproducibility of the observed effect.
Second, the absence of multivariable time-to-event analysis considerably limits the interpretation of the findings. While unadjusted Kaplan-Meier curves and log-rank testing are appropriate for exploratory analyses, no Cox proportional hazards regression model was performed to account for potential confounding variables. This issue is particularly relevant given the baseline differences reported between groups, including a lower prevalence of dyslipidemia and significantly lower creatinine levels among female patients both well-established determinants of cardiovascular and long-term mortality outcomes [2]. Therefore, the conclusion that female sex constitutes an “independent favorable prognostic factor” appears to extend beyond the analytical framework presented in the study.
Third, the exclusive inclusion of patients undergoing OPCAB with bilateral internal mammary artery grafting introduces a potential selection bias. Previous registry-based studies have demonstrated that women are less frequently treated with multiple arterial grafting strategies and may therefore represent a highly selected subgroup when bilateral mammary artery revascularization is used [3]. Consequently, the external validity and generalizability of the findings to broader coronary artery bypass grafting (CABG) populations remain uncertain. In addition, long-term outcomes after OPCAB are known to be strongly influenced by patient selection, surgical expertise, and completeness of revascularization, as demonstrated in large randomized trials and meta-analyses comparing off-pump and on-pump techniques [4].
Furthermore, although the discussion presents several biologically plausible explanations for the observed findings – including sex-related differences in endothelial function, immune modulation, and hormonal influences these mechanisms remain speculative in the absence of supporting biomarker, inflammatory, or mechanistic data. Prior investigations have emphasized that sex-related differences in cardiovascular outcomes are multifactorial and are often influenced by disparities in comorbidity burden, referral patterns, treatment strategies, socioeconomic factors, and healthcare access rather than intrinsic biological differences alone [5].
Another issue deserving attention relates to statistical reporting and data presentation. Several inconsistencies in the manuscript tables may benefit from clarification or correction. For example, some laboratory parameters and procedural variables appear to contain unit-labeling inaccuracies, including creatinine and triglyceride variables reported with “[years]” units, as well as formatting irregularities in percentage reporting. Although these issues do not necessarily alter the principal findings, clearer data presentation would improve overall methodological transparency and readability.
Importantly, the current findings may be more appropriately interpreted as demonstrating an unadjusted association between female sex and improved long-term survival after OPCAB rather than establishing female sex as an independent prognostic factor. Accordingly, the results should be considered exploratory and hypothesis-generating until validated in larger cohorts with balanced sex representation and comprehensive multivariable adjustment.
In summary, this study contributes valuable data to the growing literature investigating sex-related differences in surgical coronary revascularization. Nevertheless, larger multicenter studies incorporating adequately powered female cohorts, multivariable survival modeling, and mechanistic characterization are necessary to clarify whether female sex independently influences long-term outcomes following OPCAB surgery.
We appreciate the authors’ contribution and look forward to further investigations in this important field.
