Sex difference in outcomes after coronary artery bypass grafting: follow-up data of the Netherlands Heart Registration

This study included data from the national database of the Netherlands Heart Registration (Nederlandse Hart Registratie, NHR). This prospective database comprises data of all patients undergoing cardiac surgery in the Netherlands. The process and rationale behind data collection was reported elsewhere [8]. In addition to demographic characteristics and type of intervention, the database also includes parameters concerning postoperative morbidity and mortality and all risk factors that are required for calculation of the most frequently used risk scores. Although this database was initiated for quality evaluation of cardiovascular interventions, its completeness in registering pre- and postoperative variables enables anonymised long-term follow-up of patients undergoing cardiac surgical interventions. For this study, isolated CABG or off-pump coronary artery bypass grafting (OPCAB) cases were included for analysis. The Appendix lists all hospitals that participate in the registry.

The study was a retrospective multi-centre cohort study of prospectively collected data from 16 cardiothoracic centres in the Netherlands. Data were collected for patients undergoing CABG between 2013 and 2019. The Medical Research Ethics Committee (MEC-U) approved the study and waived the need for informed consent (W19.269).

The NHR database was searched for all preoperative data and baseline characteristics required for calculation of the EuroSCORE I [4]. EuroSCORE II was not calculated, as some values required to calculate this version of the EuroSCORE were not available [4]. Short-term outcomes included early mortality (30-day mortality), postoperative complications [stroke, myocardial infarction (MI), pneumonia, reintubation, prolonged ventilation, readmission to the intensive care unit, renal failure, gastrointestinal complications, re-exploration for bleeding and arrhythmia] and length of hospital stay. Definitions of postoperative complications are provided in Tab. S1 (Electronic Supplementary Material).

During mid-term follow-up, all-cause mortality was derived from the municipal administration records and was completed for all patients. We defined reintervention as unplanned coronary intervention of the target coronary vessel, including percutaneous coronary intervention (PCI) or CABG, after initial treatment. If patients underwent both PCI and CABG postoperatively, the first event that occurred counted. Reinterventions did not include planned PCI as a part of hybrid coronary revascularisation following primary CABG.

The NHR database has an exceptionally high data completeness for baseline characteristics. Two non-mandatory variables had a relatively high proportion of missing data: extracorporeal circulation time (ECC time) (18.2%) and cross-clamp time (18.1%). Given the higher levels (> 10%) of missing data for these variables, it was inappropriate to apply a multiple imputation method. Furthermore, 118 patients (0.2%) were lost to follow-up and therefore were not included in survival analysis.

Continuous variables are presented as mean ± SD, in case of skewedness as median with interquartile range. Categorical data are expressed as frequencies and percentages and were compared using the χ² test. If the minimum expected cell-size assumption did not apply, data were analysed with Fisher’s exact test. Continuous variables were compared using a t-test or, in the case of non-normal distribution, with the Mann-Whitney U test. Mid-term survival was demonstrated with Kaplan-Meier survival curves. Subgroup analysis was performed for patients aged < 70 years and ≥ 70 years, based on the recommendation of the current guidelines for conduit selection [8]. Differences between survival curves were assessed using the log-rank test. Variables that were associated with mid-term mortality were identified using Cox regression. Independent variables with a significance level p < 0.05 in the univariate model were entered in the multivariate model. Proportional hazard assumption was checked graphically using log minus log survival plots. Hazard ratios (HR) are reported with associated 95% confidence intervals (CI). All reported p-values were two-sided and were considered statistically significant if p < 0.05. Statistical analyses were performed using SPSS software (V26, IBM, Armonk, NY, USA) and R statistics (R Foundation, Vienna, Austria).

In total, 51,753 patients underwent CABG in the Netherlands between 2013 and 2019. The majority of patients were male (80.6%); the mean age of the study population was 66.4 ± 9.5 years. Comorbidities, including diabetes mellitus (DM), chronic lung disease and peripheral vascular disease (PVD), were more common in women than in men. Furthermore, unstable angina pectoris was more frequently observed in women, and consequently, emergency surgery was performed more often in women than in men. These differences resulted in a higher median logistic EuroSCORE for women [4.30 (2.47–7.58)] compared to men [2.53 (1.51–4.66)] (p < 0.001). Further demographic and baseline characteristics are shown in Table 1, and Table S2 (Electronic Supplementary Material) shows the baseline characteristics of the age subgroups (< 70 and ≥ 70 years).

OPCAB was performed more frequently in women than in men (17.4% vs 16.4%, p = 0.02). The number of distal anastomoses was higher among men than among women [median 3.0 (3.0–4.0) vs 3.0 (2.0–4.0), p < 0.001]. More men than women received ≥ 2 arterial grafts (23.2% vs 15.9%, p < 0.001). Additional operative details are shown in Tab. 2.

In the overall cohort (n = 51,753), 30-day mortality was 1.2% (n = 611), and perioperative MI occurred in 5.8% of patients. A higher 30-day mortality rate was observed in women than in men (1.9% vs 1.0%, p < 0.001). The incidence of perioperative MI, stroke, prolonged intubation, urinary tract infection (UWI) and deep sternal wound infection was higher in women than in men (all p < 0.001) (Tab. 2).

Median follow-up for the total cohort was 3.6 (1.8–4.8) years [men 3.5 (1.8–4.8) years, women 3.6 (1.7–4.8)]. In the total cohort, mid-term survival rate was 92.7% (93.1% in male patients, 91.3% in female patients (p < 0.001)) (Fig. 2). For patients aged ≥ 70 years, no significant difference in mid-term survival was observed between men and women (p = 0.71) (Fig. 3). In the subgroup analysis for patients aged < 70 years, a statistically significant worse mid-term survival was found in women compared to men (p < 0.001) (Fig. 3).

Multivariate Cox regression analysis (Table S3, Electronic Supplementary Material; Tab. 3) revealed that female sex itself was not significantly associated with mid-term mortality (Table S3, Electronic Supplementary Material). In patients aged < 70 years (Tab. 3), worse mid-term survival was associated with female sex, age, chronic lung disease, PVD, DM, serum creatinine > 200 µm/l, recent MI, decreased left ventricular ejection fraction (LVEF) and emergency surgery. Both OPCAB and the use of ≥ 2 arterial grafts were associated with lower mid-term mortality. In the subgroup ≥ 70 years (Tab. 3), no statistically significant association was found between mid-term mortality and female sex (Tab. 3).

Reintervention rate in the total population of the study is 3.5% (n = 1792). A higher non-adjusted reintervention rate was found in women than in men (4.5% vs 3.2%, p < 0.001), which is mainly driven by a higher number of unplanned postoperative PCIs.

The current study has some limitations mostly due to the retrospective nature of the study. Additionally, some variables, such as ECC and cross-clamp time, were missing in a relatively large proportion of our study population. The primary endpoint of the study is all-cause mortality. The registry does not include the cause of death, which could be relevant for the interpretation of mortality rates.