Gender-differences in Polyvascular disease: implications for lipid-lowering management and cardiovascular outcomes
Authors: Katasako A , Kataoka Y , Murai K , Iwai T , Funabashi S , Takagi K , Otsuka F , Nakao K , Takamisawa I , Nishihira K , Asaumi Y , Nicholls S , Tsujita K , Noguchi T 
Published: October 2024

Abstract

Background
Polyvascular disease (PolyVD) exhibits extensive atherosclerotic disease in multiple vascular beds. Despite lowering LDL-C with a statin, patients with PolyVD still present elevated risks of subsequent atherosclerotic cardiovascular events, suggesting the need to better understand pathophysiology of PolyVD. Female gender has been reported to mitigate severity of atherosclerotic disease and future events’ risks. However, whether this gender-difference exists in patients with PolyVD remains to be fully elucidated yet.

Purpose
To characterize gender-differences in cardiovascular outcomes in patients with and without PolyVD, respectively.

Methods
The on-going multi-center registry enroll patients with CAD receiving intravascular imaging-guided PCI. The current study included 679 patients with CAD. PolyVD was defined as the concomitance of other atherosclerotic cardiovascular disease (stroke and/or LEAD). In patients with PolyVD (n=185) and Non-PolyVD (n=494), clinical characteristics and major cardiovascular outcomes (MACE) were compared between men and women, respectively. MACE was defined as a composite of cardiovascular death, non-fatal MI, ischemic stroke, LEAD and coronary revascularization.

Results
The proportion of women was 21% and 18% in Non-PolyVD and PolyVD subjects, respectively. In patients with non-PolyVD, women were more likely to be older (75 vs. 68 years, p&lt;0.001) and exhibit a lower BMI (22.3 vs. 24.0 kg/m2, p&lt;0.001) with a lower frequency of previous myocardial infarction (13.5 vs. 24.9%, p=0.01). LDL-C levels did not differ between the two groups [102 (76-130) vs. 93 (71-120) mg/dL, p=0.06). However, during the observational period (median=3 years), women were associated with a lower frequency of MACE compared to men (HR=0.31, 95%CI=0.13-0.78, p=0.012, Figure, Table). In patients with PolyVD, BMI, and the frequency of established risk factors and previous myocardial infarction were comparable between men and women. Despite the use of high-intensity statin in over 40% of study subjects (44 vs. 36%, p=0.41), women still exhibited an elevated level of LDL-C [103 (74-122) vs. 82 (64-103) mg/dL, p=0.04]. Furthermore, in contrast to Non-PolyVD patients, similar cardiovascular outcomes were observed in both men and women with PolyVD (Figure). On multivariate analysis adjusting clinical characteristics, women were not a significant factor associated with a reduced risk of MACE (Table).

Conclusion
18% of PolyVD were women who presented a higher LDL-C level. While women with Non-PolyVD exhibited better cardiovascular outcomes compared to men, this gender-difference did not exist in patients with PolyVD. Our findings indicate that female PolyVD did not necessarily show better outcomes but similar cardiovascular event’s risks compared to men. Further intensified anti-atherosclerotic managements are required in both men and women with PolyVD.