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@ARTICLE{AlKassou:267507,
author = {Al-Kassou, Baravan and Al-Kassou, Lara and Mahn, Thorsten
and Lütjohann, Dieter and Shamekhi, Jasmin and Willemsen,
Nicola and Niepmann, Sven Thomas and Baldus, Stephan and
Kelm, Malte and Nickenig, Georg and Latz, Eicke and Zimmer,
Sebastian},
title = {{C}holesterol {C}rystal {D}issolution {R}ate of {S}erum
{P}redicts {O}utcomes in {P}atients {W}ith {A}ortic
{S}tenosis {U}ndergoing {T}ranscatheter {A}ortic {V}alve
{R}eplacement.},
journal = {Journal of the American Heart Association},
volume = {13},
number = {3},
issn = {2047-9980},
address = {New York, NY},
publisher = {Association},
reportid = {DZNE-2024-00153},
pages = {e031997},
year = {2024},
abstract = {Aortic stenosis has pathophysiological similarities with
atherosclerosis, including the deposition of
cholesterol-containing lipoproteins. The resulting
cholesterol crystals activate the NLRP3 (NOD-like receptor
protein 3) inflammasome, leading to inflammation and
cardiovascular diseases. We aimed to investigate the
cholesterol crystal dissolution rate (CCDR) of serum in
patients with aortic stenosis and to assess the prognostic
value of this biomarker.The study included 348 patients with
aortic stenosis undergoing transcatheter aortic valve
replacement. The CCDR was measured using flow cytometry to
enumerate cholesterol crystals that were added to a serum
solution, at baseline and after 2 hours of incubation. Based
on the median CCDR, the cohort was stratified into high and
low cholesterol crystal dissolvers. The incidence of the
primary end point, a composite of 1-year all-cause mortality
and major vascular complication, was significantly lower in
the high CCDR group (7.3 per 100 person-years) compared with
the low CCDR group (17.0 per 100 person-years, P=0.01). This
was mainly driven by a lower 1-year mortality rate in
patients with a high CCDR (7.3 versus 15.1 per 100
person-years, P=0.04). Unplanned endovascular interventions
were significantly less frequent in high cholesterol crystal
dissolvers (12.8 versus 22.6 per 100 person-years, P=0.04).
Although low-density lipoprotein cholesterol levels were
comparable in both groups (101.8±37.3 mg/dL versus
97.9±37.6 mg/dL, P=0.35), only patients with a low CCDR
showed a benefit from statin treatment. In multivariate
analysis, low CCDR (hazard ratio, 2.21 $[95\%$ CI,
0.99-4.92], P=0.04) was significantly associated with 1-year
mortality.The CCDR is a novel biomarker associated with
outcome in patients with aortic stenosis undergoing
transcatheter aortic valve replacement. It may provide new
insights into patients' anti-inflammatory capacity and
additional prognostic information beyond classic risk
assessment.},
keywords = {Humans / Transcatheter Aortic Valve Replacement / Treatment
Outcome / Aortic Valve Stenosis / Risk Assessment /
Biomarkers / Aortic Valve: surgery / Risk Factors / TAVR
(Other) / calcific aortic stenosis (Other) / cholesterol
crystal dissolution rate (Other) / cholesterol crystals
(Other) / Biomarkers (NLM Chemicals)},
cin = {AG Latz ; AG Latz},
ddc = {610},
cid = {I:(DE-2719)1013024},
pnm = {351 - Brain Function (POF4-351)},
pid = {G:(DE-HGF)POF4-351},
typ = {PUB:(DE-HGF)16},
pmc = {pmc:PMC11056150},
pubmed = {pmid:38240198},
doi = {10.1161/JAHA.123.031997},
url = {https://pub.dzne.de/record/267507},
}