Abstract P288: Multiple Versus Single Lesions in Lower-Extremity Peripheral Arterial Disease: 2.5-Year Risk of Recurrent Cardiovascular Events
Authors: van Zitteren Moniek , Denollet Johan , Jones Phil G , Spertus John A , Heyligers Jan M , de Fijter Marnix , Burger Desirée , Nooren Maria M , Vriens Patrick W , Smolderen Kim G 
Published: July 2021

Background:
Lower-extremity peripheral arterial disease (PAD) is associated with an increased risk of mortality and high resource utilization. Therefore, there is a real need to assess PAD patients' risk for an initial cardiovascular event as well as their risk for multiple, serial cardiovascular events over time. Although it is expected, but unexplored, that those with a greater burden of disease (e.g. multiple vs. single lesions) would have an increased risk for events, common modeling strategies only emphasize time to first event. We tested a novel recurrent event model to examine whether more advanced disease is associated with a persistent, increased risk for subsequent cardiovascular events.

Methods:
A prospective cohort of 717 patients with newly diagnosed PAD - enrolled from 2 vascular clinics in The Netherlands - underwent duplex ultrasound testing at enrollment to determine the presence of multiple vs. single lesions. A traditional time-to-first event Cox regression model examined the association between multiple vs. single (reference) lesions and 2.5-year cardiovascular events, adjusting for site, demographics and risk factors (see Table). We then replicated these analyses using an advanced Cox-based model for recurrent events.

Results:
A total of 324 out of 717 (44.5%) patients had multiple lesions. After 2.5 year follow-up, patients with multiple lesions not only had an increased time-to-first cardiovascular event risk (35.2% vs. 32.8%; adjusted HR=1.32; 95%CI 1.07-1.62), but also had an increased risk of recurrent cardiovascular events (60.2% vs.47.7%; adjusted HR=1.24; 95%CI 1.00-1.53) (Table).

Conclusions:
Using a recurrent event model, we were able to demonstrate that patients with PAD who present with multiple lesions are not only at increased risk of having a first cardiovascular event, but also remain at increased risk for subsequent events over 2.5 years of observation; even after their first event and subsequent management of their PAD.

Table-The Association Between Having Multiple vs. Single Lesions and 2.5-Year Cardiovascular Events
*

Model
Unadjusted
Adjusted

HR (95% CI)
P-value
HR (95% CI)
P-value

(1) Time-to-First Event Model

Cox Proportional Hazards Model
1.36 (1.12-1.67)
0.003
1.32 (1.07-1.62)
0.008

(2) Cox-Based Model for Recurrent Events

Conditional-Gap Time
†

1.36 (1.17-1.66)
0.002
1.24 (1.00-1.53)
0.047

The unadjusted and adjusted effects (Hazard Ratio [HR], 95% Confidence Interval [CI]) for (1) a traditional time-to-first event Cox Proportional Hazards model and (2) an advanced Cox-based model for recurrent events are depicted.

Covariates in the adjusted model included: site, age, sex, history of cerebrovascular disease, history of cardiac disease, chronic obstructive pulmonary disease, hypertension, diabetes mellitus, kidney disease, current smoking, and hyperlipidemia.

*

Cardiovascular events constituted of admissions for peripheral, coronary, and carotid revascularizations, bleeding events, abnormal cardiac rhythm, heart failure, non-fatal stroke/transient ischemic attack, non-fatal myocardial infarction, angina, other ischemic events, and fatal myocardial infarction/stroke, and other cardiovascular death;

†

Risk interval is the time elapsed since each prior event.