Sex related differences in vascular interventions and outcome of patients with critical limb threatening ischemia in a real-world cohort
Authors: Makowski L , Feld J , Koeppe J , Engelbertz C , Illner J , Kuehnemund L , Fischer A , Lange S A , Droege P , Guenster C , Gerss J , Reinecke H , Freisinger E ,   Gender Vasc
Published: October 2021

Abstract

Background
The prevalence of critical limb threatening ischemia (CLTI) is increasing worldwide and the focus is the reduction of outcome events like death or amputation of the lower limb (LL). Sex related differences in medical supply and outcome are a current matter of debate.

Purpose
In the present study, we included patients with CLTI in an unselected “real-world” cohort and studied sex related differences in their risk profile and vascular interventions, as well as their impact on long-term outcome.

Methods
We analyzed 119,953 unselected patients of the public health insurance in Germany (AOK), which were hospitalized between 2010 and 2017 for a main diagnosis of CLTI (Rutherford stage (RF) 4–6). In our data files, a baseline period of 2 years previous index hospitalization and a follow-up period until 2018 was included.

Results
In our cohort, more than half were male CLTI patients (57% male vs. 43% female), while female CLTI patients were at higher age (median: 73.8 years male vs. 81.4 years female). Male patients had higher ratios of diabetes, dyslipidemia, smoking, cerebrovascular disease and chronic coronary syndrome, whereas female CLTI patients show a higher prevalence of hypertension, atrial fibrillation, chronic heart failure and chronic kidney disease (all p&lt;0.001). During index hospitalisation more than one quarter of all CLTI patients suffered from rest pain (RF 4), and approximately one third for minor (RF 5) and one third for major (RF 6) tissue lost. Female patients were more often diagnosed with RF 5 (32% male vs. 36% female), while the proportion of male patients was slightly higher at RF 4 (29% male vs. 27% female) and RF 6 (39% male vs. 37% female, all p&lt;0.001).
During index hospitalization, almost 70% underwent any diagnostic angiography and in 63% of all patients a revascularization procedure was performed. Both were carried out more often in male patients (both p&lt;0.001).The Kaplan Meier curve showed an increased mortality rate in female patients during follow up (figure 1), while no differences were observed for the combined endpoint amputation of the LL or death. Interestingly after adjustment for age and patients risk'constellation, female gender was associated with increased overall-survival (female HR 0.95; 95%-CI 0.94–0.96, p&lt;0.001) and amputation-free survival which is a combined endpoint of amputation of the LL or death (female HR 0.84; 95%-CI 0.83–0.85, p&lt;0.001).

Conclusion
Female patients with CLTI were older and showed lower rates of diagnostic angiography and revascularization procedures of the LL during index hopsitalization. Nevertheless, male sex was an independent risk factor for all-cause mortality and the combined endpoint amputation of the LL or death during long-term follow-up. These results indicate that further analyses are needed to determine the various individual needs of male and female CLTI patients.

Funding Acknowledgement
Type of funding sources: Public grant(s) – National budget only. Main funding source(s): The project upon which this publication is based was funded by The Federal Joint Committee, Innovation Committee (G-BA, Innovationsfonds, number 01VSF18051).