Sex-specific differences and long-term outcome of patients with coronary artery disease and chronic kidney disease: the Coronary Artery Disease and Renal Failure (CAD-REF) Registry

Abstract

Background: Cardiovascular morbidity and mortality are closely linked to chronic kidney disease (CKD). Sex-specific long-term outcome data of patients with coronary artery disease (CAD) and CKD are scarce.

Methods: In the prospective observational multicenter Coronary Artery Disease and REnal Failure (CAD-REF) Registry, 773 (23.1%) women and 2,579 (76.9%) men with angiographically documented CAD and different stages of CKD were consecutively enrolled and followed for up to 8 years. Long-term outcome was evaluated using survival analysis and multivariable Cox-regression models.

Results: At enrollment, women were significantly older than men, and suffered from more comorbidities like CKD, hypertension, diabetes mellitus, and multivessel coronary disease. Regarding long-term mortality, no sex-specific differences were observed (Kaplan-Meier survival estimates: 69% in women vs. 69% in men, plog-rank = 0.7). Survival rates decreased from 89% for patients without CKD at enrollment to 72% for patients with CKD stages 1-2 at enrollment and 49% for patients with CKD stages 3-5 at enrollment (plog-rank < 0.001). Cox-regression analysis revealed that sex or multivessel coronary disease were no independent predictors of long-term mortality, while age, CKD stages 3-5, albumin/creatinine ratio, diabetes, valvular heart disease, peripheral artery disease, and left-ventricular ejection fraction were predictors of long-term mortality.

Conclusions: Sex differences in CAD patients mainly exist in the cardiovascular risk profile and the extent of CAD. Long-term mortality was not depended on sex or multivessel disease. More attention should be given to treatment of comorbidities such as CKD and peripheral artery disease being independent predictors of death. Clinical Trail Registration ClinicalTrials.gov Identifier: NCT00679419.

Keywords: Chronic kidney disease; Coronary artery disease; Long-term mortality; Sex; Treatment.

Conflict of interest statement

CE has received travel support from Bayer Vital outside the submitted work. EF reports grants from Bayer outside the submitted work. HR reports personal fees from Daiichi-Sankyo, DiaPlan, MedUpdate, NeoVasc, NovoNordisk, Pfizer, and Pluristem, all outside the submitted work. He has received research grants from the German Federal Ministry for Education and Research (BMBF), Bard, Biotronik, BMS/Pfizer, and Pluristem, all outside the submitted work, KW has received consulting fees/honoraria from Biotronik, Boston Scientific, Novartis. GB has no direct interest to declare with regard to this specific topic. However, during the course of this register, he had received funds from Sanofi-Aventis as chairman of the German Atrial Fibrillation Network and in his position as Co-PI for running a clinical trial, and he had been on the advisory board of Boehringer-Ingelheim for a topic not related to this registry. EB declares no conflict of interest. She has received research grants from the German Federal Ministry for Education and Research (BMBF). EB was supported by a Heisenberg Professorship from the Deutsche Forschungsgemeinschaft (Br1589/8–2). All other authors declare no conflict of interest.

© 2021. The Author(s).

Figures

Fig. 1

Kaplan–Meier survival analyses. a Kaplan–Meier curve for the cumulative survival of women (red line) and men (blue line) during 8-year follow-up. There was no difference in survival between women and men. b Kaplan–Meier curve for the cumulative survival of patients according to their renal status at enrollment. Cumulative hazard was significantly different between the three groups. (plog-rank < 0.001). Green line displays patients without CKD, blue line displays patients with CKD stages 1–2, and red line displays patients with CKD stages 3–5. c Kaplan–Meier curve for the cumulative survival of women and men according to their renal status at enrollment. There was no difference in the hazards for women and men within the same CKD group. Light green line displays women without CKD, dark green line displays men without CKD, light blue line displays women with CKD stages 1–2, dark blue line displays men with CKD stages 1–2, light red line displays women with CKD stages 3–5, and dark red line displays men with CKD stages 3–5