Selected Papers from the Editorial BoardIdentifying Sex Dimorphism in Peripheral Artery Disease with Platelet Mapping
Introduction
There is a growing appreciation for the differences in etiology, disease progression, and outcomes of cardiovascular conditions as they relate to sex.1 The prevalence and burden of peripheral artery disease (PAD) is equal, if not higher, in women compared to men.2,3 Clinical outcomes following lower extremity revascularization are worse in women, with higher rates of wound complications, major amputations, and mortality.4 Disease progression is also worse, with women experiencing a faster functional decline and greater loss of mobility over time.5
However, women are notably underrepresented in existing PAD studies, contributing to a significant gap in clinical and physiologic knowledge regarding the etiology and natural history of female-specific disease.6 What is known is paradoxical: traditional cardiometabolic risk factors associated with cardiovascular disease are less prevalent in females and at the same time females are more sensitive than males to the effects of certain risk exposures.7, 8, 9, 10 Importantly, there is an emerging consensus that there may be ineffectively measured, or yet unidentified, key risk factors for PAD in women.1 This highlights the importance of understanding sexual dimorphism in cardiovascular biology, in which sex-biased gene expression results in phenotypic divergence of disease.11
Thromboelastography (TEG), an established viscoelastic method for hemostasis testing, with wide adoption within the cardiac and transplant populations, may provide some insight. Unlike other assays that aim to quantify platelet reactivity, TEG with Platelet Mapping provides clot analysis with and without thrombin, offering the opportunity to not only study platelet function, but also may overcome the confounding effect of direct oral anticoagulant medications on platelet function, which is yet to be established.12
We hypothesize that quantifying platelet variability from eventually be used, in conjunction with other thromboelastographic metrics, to detect dysregulation in clotting parameters and establish cohort-specific antithrombotic management. This prospective observational study aimed to establish differences in platelet reactivity between sexes in those PAD patients undergoing lower extremity revascularization.
Section snippets
Study Population
Patients scheduled for lower extremity revascularization procedures within the Vascular Surgery department at a large tertiary care center were prospectively enrolled between December 2020 and January 2022. Open surgical, endovascular, and hybrid procedures were included. Procedure types included re-establishing in-line flow inflow insufficiency, outflow insufficiency, or combined cases involving both inflow and outflow pathology. Exclusion criteria were inability to provide informed consent,
Demographics, Comorbid Conditions, and Procedure Details
One hundred seven patients were analyzed, of which 70 were male and 37 were female. Age at the time of enrollment, race/ethnicity, body mass index, and tobacco use did not differ significantly between groups. Diabetes was stratified as controlled (HbA1c < 7%) or uncontrolled (HbA1c ≥ 7%). The prevalence of uncontrolled diabetes in male patients was significantly higher compared to female patients (18.6% vs. 2.7%, P = 0.03). Patients with hypertension were stratified as those requiring only 1
Discussion
Women face a disproportionate burden from many types of cardiovascular disability and mortality, including a greater lifetime risk of cerebrovascular events, a greater risk of death following MI, and poorer outcomes after lower extremity revascularization procedures compared to men.8,13, 14, 15 Because PAD affects millions across the United States, and is now recognized as a global pandemic, it is imperative that we work to understand this inequality.2
Given the historic male predominance in
Conclusion
Although female patients with PAD currently experience the same treatment paradigms as male patients, it is known that the natural history, disease progression, and response to intervention are significantly worse. In this cohort of patients undergoing lower extremity revascularization, females had a significantly lower prevalence of traditional cardiometabolic risk factors for PAD. On the other hand, high platelet reactivity in women, with increased platelet aggregation and diminished platelet
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Cited by (3)
The impact of sex on platelet responses to aspirin in patients with peripheral artery disease
2024, American Journal of HematologyPeripheral Artery Disease in Women
2022, Journal of Critical Limb Ischemia
Funding: Grant support for this research was provided by Haemonetics, Boston, MA.
Disclosure: The authors have no conflicts of interest to report.