Sex related differences in therapy and outcome of patients with low-stage LEAD in a real-world cohort
Authors: Makowski L.-M , Feld J , Koeppe J , Illner J , Kuehnemund L , Wiederhold A , Gerss J , Reinecke H , Freisinger E 
Published: November 2020

Abstract

Background
During the last decades, the prevalence of lower extremity artery disease (LEAD) strongly increased worldwide in both, males and females. Sex-related differences relating to therapy and outcome events are a current matter of debate.

Purpose
Aim of our study was to examine patients with low-stage LEAD in an unselected “real-world” cohort with regard to risk profiles, therapeutic approach and its impact on the progression to chronic limb threatening ischemia (CLTI) and death.

Methods
We analyzed 42,197 unselected patients of the AOK (Allgemeine Ortskrankenkasse) health insurance that were hospitalized between 01.01.2014–31.12.2015 for a main diagnosis of LEAD at Rutherford stage 1–3. Data files included a baseline period of 2 years previous index hospitalization and a follow-up period of up to 5 years.

Results
In our dataset, one third of the LEAD patients were female (32.4% female vs. 67.6% male), being 6 years older (median age: 72.6 years female vs. 66.4 years male). Male patients had higher ratio of diabetes mellitus (40.1% female vs. 42.4% male), nicotine abuse (40.8% female vs. 50.7% male) and chronic coronary syndrome (40.6% female vs. 48.2 male). On the other hand, hypertension (90.3% female vs. 86.9% male), obesity (26.7% female vs. 24.9% male) and chronic kidney disease (29.2% female vs. 26.1% male; all p&lt;0.001) was more often co-prevalent in females. Previous vascular procedures of the lower limbs (LL) (10.2% female vs. 11.8% male) and the receipt of guideline-recommended medication (statins: 45.9% female vs. 50.3% male; blood thinner: 37.1% female vs. 42.7% male; all p&lt;0.001) at baseline was higher in male patients. During index hospitalization, revascularization was performed in 82.8% of all patients, while carried out more often in male patients (81.8% female vs. 83.3% male, p&lt;0.001). After adjustment for risk profiles, female sex was associated with decreased adjusted long-term mortality (HR 0.76; 95%-CI 0.72–0.80). Moreover, male gender was linked with an increased risk of the combined endpoint of CLTI (Rutherford stage 4–6 or amputation of the LL or death; HR 0.89; 95%-CI 0.86–0.93). Interestingly, the prescription of guideline-recommended medication (statins: 63.8% female vs. 65.8% male; blood thinner: 60.2% female vs. 63.5% male; all p&lt;0.001) and performed vascular procedures (33.1% female vs. 36.4% male; p&lt;0.001) was increased in male patients during follow-up.

Conclusion
Female patients with low stage LEAD are older and show less rate of revascularization procedures of the LL and prescription of guideline-recommended medication at baseline and during follow-up. Nevertheless, male gender was an independent risk factor for all-cause mortality and the combined endpoint CLTI during 5 years of long-term follow-up. Further analyses with focus on sex-related differences on health-services supply and outcome quality are needed to correspond to the individual needs of male and female LEAD patients.
Kaplan Meier analysis of the endpoints

Funding Acknowledgement
Type of funding source: Public grant(s) – National budget only. Main funding source(s): National grant