Cholesterol Efflux Capacity Associates with the Ankle-Brachial Index but Not All-Cause Mortality in Patients with Peripheral Artery Disease.

Robert K Clemens,Wijtske Annema,Andreas Ritsch,Lucia Rohrer,Monika Hunjadi,Beatrice Amann-Vesti,Arnold Von Eckardstein,Thomas O Meier

doi:10.3390/diagnostics11081407

Abstract

Background: Cholesterol efflux is an important mechanism by which high-density lipoproteins (HDLs) protect against cardiovascular disease. As peripheral artery disease (PAD) is associated with high mortality rates, mainly due to cardiovascular causes, we investigated whether cholesterol efflux capacity (CEC) of apolipoprotein B (apoB)-depleted plasma, a widely used surrogate of HDL function, may serve as a predictive marker for mortality in this patient population. Methods: In this prospective single-center study (median follow-up time: 9.3 years), apoB-containing lipoproteins were precipitated from plasma of 95 patients with PAD and incubated with J744-macrophages, which were loaded with radiolabeled cholesterol. CEC was defined as the fractional radiolabel released during 4 h of incubation. Results: Baseline CEC was lower in PAD patients that currently smoked (p = 0.015) and had a history of myocardial infarction (p = 0.011). Moreover, CEC showed a significant correlation with HDL-cholesterol (p = 0.003) and apolipoprotein A-I levels (p = 0.001) as well as the ankle-brachial index (ABI, p = 0.018). However, CEC did not differ between survivors and non-survivors. Neither revealed Kaplan–Meier and Cox regression analyses any significant association of CEC with all-cause mortality rates. Conclusion: Taken together, CEC is associated with ABI but does not predict all-cause mortality in patients with PAD.

Highlights

Peripheral artery disease (PAD) is a very prevalent condition in developed countries.Around one in five people over the age of 65 suffer from PAD [1] and the number of PAD patients is expected to increase facing the growing elderly population
We investigated the predictive value of cholesterol efflux capacity (CEC), an important antiatherosclerotic functionality of high-density lipoproteins (HDLs), for mortality in PAD and determining factors influencing HDL cholesterol efflux potential in this patient population
We previously found that traditional markers of peripheral atherosclerosis, ankle-brachial index (ABI) and carotid intima-media thickness (cIMT), did not predict mortality in the PAD patient population used in this study [20]

Summary

Introduction

Peripheral artery disease (PAD) is a very prevalent condition in developed countries.Around one in five people over the age of 65 suffer from PAD [1] and the number of PAD patients is expected to increase facing the growing elderly population. Peripheral artery disease (PAD) is a very prevalent condition in developed countries. PAD are at high risk for morbidity and mortality, especially caused by cardiovascular events like myocardial infarction, stroke, and critical limb ischemia [2]. According to data from the Reduction of Atherothrombosis for Continued Health (REACH) registry patients with PAD exhibited a cardiovascular event rate (composite of myocardial infarction, stroke, vascular death, and rehospitalization due to vascular events) of 21% after one year of follow-up and increasing to 40% at 3 years [3]. PAD experiencing a future cardiovascular event was even higher as patients with coronary artery disease or cerebrovascular disease [3]. Accurate and early identification of PAD patients at high risk of future cardiovascular morbidity and mortality is essential

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