Impaired Cholesterol‐Uptake Capacity of HDL Might Promote Target‐Lesion Revascularization by Inducing Neoatherosclerosis After Stent Implantation

Abstract

Background We evaluated the importance of high‐density lipoprotein (HDL) functionality for target‐lesion revascularization in patients treated with coronary stents using a rapid cell‐free assay system to evaluate the functional capacity of HDL to accept additional cholesterol (cholesterol‐uptake capacity; CUC). Methods and Results From an optical coherence tomography (OCT) registry of patients treated with coronary stents, 207 patients were enrolled and their HDL was functionally evaluated by measuring the CUC. Follow‐up OCT was performed (median duration, 24.5 months after stenting) to evaluate the presence of neoatherosclerosis. Clinical follow‐up was performed to assess target‐lesion revascularization for a median duration of 42.3 months after stent implantation. Neoatherosclerosis was identified in 37 patients (17.9%). Multivariate logistic regression analysis revealed that a decreased CUC was independently associated with neoatherosclerosis (odds ratio, 0.799; P <0.001). The CUC showed a significant inverse correlation with incidence of target‐lesion revascularization (odds ratio, 0.887; P =0.003) and with lipid accumulation inside stents, suggesting that neoatherosclerosis contributes to the association between CUC and target‐lesion revascularization. Conclusions Impaired HDL functionality, detected as decreased CUC, might lead to future stent failure by provoking atherogenic changes of the neointima within stents. Both quantitative and qualitative assessments of HDL might enable the improved prediction of clinical outcomes after stent implantation.

Serum HDL cholesterol uptake capacity in subjects from the MASHAD cohort study: Its value in determining the risk of cardiovascular endpoints

“…A large and growing body of cohort studies has investigated the cholesterol efflux capacity of HDL using ABCA1 up‐regulated cells 10,11,21 . A single‐cohort study exists in which Nagano et al have described the importance of HDL functionality for targeting coronary lesion revascularization within patients who were treated with coronary stents using a cell‐free assay 15 . Their result demonstrates that CUC at follow‐up optical coherence tomography (OCT) was significantly lower in a group who developed neo‐atherosclerosis (NA+) compared to NA‐ group (Log Rank p < 0.001).…”

“…Measurement of cholesterol uptake capacity (CUC) is a newly developed cell‐free, sensitive, and high‐throughput assay that reflects the functionality of HDL without using radio‐isotope labelling and cells 14 . Toh et al (2019) evaluated HDL function through the cell‐free CUC method in patients treated with coronary stents, mentioned that impaired HDL function might anticipate stent failure 15 . The research has tended to focus on qualitative rather than a quantitative assessment of HDL to improve the prediction of cardiovascular and atherosclerosis clinical outcomes.…”

Impact of High-Density Lipoprotein Function, Rather Than High-Density Lipoprotein Cholesterol Level, on Cardiovascular Disease Among Patients With Familial Hypercholesterolemia

“…In the present study, we found that serum CUC was highly correlated with HDL-C concentrations, indicating that the amount of HDL is a major determinant of CUC. Conversely, although CUC showed a significant inverse association with CAD, no such relationship could be demonstrated for HDL-C. We previously reported similar findings, [16][17][18]20 suggesting that functional assessment of HDL by CUC has more important clinical implications than quantitative HDL measurement.…”

Prevalence and Impact of Neoatherosclerosis on Clinical Outcomes After Percutaneous Treatment of Second-Generation Drug-Eluting Stent Restenosis

“…Current smoking, renal insufficiency, ACE (angiotensin-converting enzyme) inhibitor or angiotensin II receptor blocker use, poor lipid profile, high-sensitivity C-reactive protein, underlying lipid-rich plaque, longer duration from stent implantation, or stent type have been associated with neoatherosclerosis. [3][4][5][6][7][8][9][10][11] The prevalence of neoatherosclerosis in the current study including only restenotic second-generation DES was 28.5% (146/512) with a median time from implantation to ISR of 2.8 (1.1-5.2) years. In autopsy cases studied a median of 2 years from DES implantation, Mori et al 16 showed lower prevalence of neoatherosclerosis (fibroatheroma) in cobalt-chromium everolimus-eluting stents (20%) compared with stainless steel sirolimus-eluting stents (41%).…”