https://doi.org/10.1007/s00392-025-02625-4
1Universitätsklinikum Ulm Klinik für Innere Medizin II Ulm, Deutschland; 2Alb-Donau Klinikum Innere Medizin Ehingen (Donau), Deutschland
Introduction:
Gender-specific aspects are becoming increasingly recognized in cardiovascular medicine. Little is known about differences in serum biomarkers between men and women undergoing transcatheter edge-to-edge mitral valve repair (M-TEER) for mitral regurgitation (MR). The goal of this study was to identify sex-specific biomarker expression profiles in MR patients and to elucidate potential implications for outcome prediction after M-TEER.
Gender-specific aspects are becoming increasingly recognized in cardiovascular medicine. Little is known about differences in serum biomarkers between men and women undergoing transcatheter edge-to-edge mitral valve repair (M-TEER) for mitral regurgitation (MR). The goal of this study was to identify sex-specific biomarker expression profiles in MR patients and to elucidate potential implications for outcome prediction after M-TEER.
Methods:
We prospectively examined 242 patients, who received M-TEER at our center between April 2017 and December 2020. Propensity score matching was carried out between genders adjusting for left-ventricular function, coronary artery disease and presence of secondary MR. 103 matched pairs of men and women were further analyzed. A commercial multiplex protein assay (Cardiovascular III, Olink, Uppsala, Sweden) was used to quantify expression levels of 92 defined biomarkers. We then assessed differences in biomarker expression between male and female patients. In addition, we investigated gender-specific predictors of 1-year mortality.
We prospectively examined 242 patients, who received M-TEER at our center between April 2017 and December 2020. Propensity score matching was carried out between genders adjusting for left-ventricular function, coronary artery disease and presence of secondary MR. 103 matched pairs of men and women were further analyzed. A commercial multiplex protein assay (Cardiovascular III, Olink, Uppsala, Sweden) was used to quantify expression levels of 92 defined biomarkers. We then assessed differences in biomarker expression between male and female patients. In addition, we investigated gender-specific predictors of 1-year mortality.
Results:
206 patients were included in the final analysis (50% male, 50% female). Baseline clinical characteristics were largely similar between genders (age 76.3 vs. 77.2 years, p = 0.24; baseline MR grade IV 86.0 vs. 81.7%, p = 0.43). Most significant differences in baseline biomarker expression levels were seen for matrix metalloproteinase 3 (MMP3; expression 0.7-fold in women, p < 0.001), peptidase inhibitor 3 (PI3, 0.7-fold, p = 0.002), insulin-like growth factor binding protein 7 (IBP-7, 0.8-fold, p = 0.034) and fatty acid-binding protein 4 (FABP4, 1.6-fold, p = 0.001). Differential expression of NT-proBNP (0.7-fold, p = 0.07) and suppressor of tumorigenicity 2 (ST2, 0.8-fold, p = 0.09) was borderline significant.
206 patients were included in the final analysis (50% male, 50% female). Baseline clinical characteristics were largely similar between genders (age 76.3 vs. 77.2 years, p = 0.24; baseline MR grade IV 86.0 vs. 81.7%, p = 0.43). Most significant differences in baseline biomarker expression levels were seen for matrix metalloproteinase 3 (MMP3; expression 0.7-fold in women, p < 0.001), peptidase inhibitor 3 (PI3, 0.7-fold, p = 0.002), insulin-like growth factor binding protein 7 (IBP-7, 0.8-fold, p = 0.034) and fatty acid-binding protein 4 (FABP4, 1.6-fold, p = 0.001). Differential expression of NT-proBNP (0.7-fold, p = 0.07) and suppressor of tumorigenicity 2 (ST2, 0.8-fold, p = 0.09) was borderline significant.
Gender-specific impact on 1-year mortality was tested using multivariate Cox regression analysis adjusting for EuroSCORE II and procedural success. Among all 92 biomarkers, ST2, NT-proBNP, MMP3 and paraoxonase 3 (PON3) showed significant interaction with gender regarding the primary endpoint (p for interaction of all four biomarkers < 0.05).
ST2 had an independent impact on mortality in both men and women, however this effect was more pronounced in women (Hazard Ratio (HR) for women 4.462 (95% confidence interval (CI) 2.193 – 9.079), p < 0.001; for men 1.581 (95% CI 1.103 – 2.268), p = 0.013).
The other three markers were independently predictive of 1-year mortality only in women: NT-proBNP was upregulated 4.6-fold in women who reached the endpoint (HR 1.786, 95% CI 1.354 – 2.356, p < 0.001), MMP3 was upregulated 2.1-fold (HR 2.976, 95% CI 1.746 – 5.075, p < 0.001). Strikingly, the most prominent gender-specific effect on outcome was seen for PON3, of which baseline expression was similar in men and women. PON3 was downregulated 0.5-fold in women, who died within one year (HR 0.258, 95% CI 0.129 – 0.515, p < 0.001), no differential effect was seen in men, who reached the endpoint.
Conclusion:
This analysis has revealed differences in pre-procedural biomarker expression between female and male patients undergoing M-TEER. ST2, NT-proBNP, MMP3 and PON3 emerged as independent predictors of 1-year mortality specifically in females. This hypothesis-generating study warrants further gender-specific examination of these promising biomarkers, which might be useful for individually tailored risk prediction.
This analysis has revealed differences in pre-procedural biomarker expression between female and male patients undergoing M-TEER. ST2, NT-proBNP, MMP3 and PON3 emerged as independent predictors of 1-year mortality specifically in females. This hypothesis-generating study warrants further gender-specific examination of these promising biomarkers, which might be useful for individually tailored risk prediction.