Circulating Plasma Proteins in Aortic Stenosis: Associations With Severity, Myocardial Response, and Clinical Outcomes.

Autor:	Tan ESJ; National University Heart Centre Singapore Singapore.; Yong Loo Lin School of Medicine National University of Singapore Singapore Singapore., Choi H; Yong Loo Lin School of Medicine National University of Singapore Singapore Singapore.; Cardiovascular Research Institute, National University Health System Singapore Singapore., DeFilippi CR; Inova Heart and Vascular Institute Falls Church VA., Oon YY; Sarawak Heart Centre Kota Samarahan Sarawak Malaysia., Chan SP; National University Heart Centre Singapore Singapore.; Yong Loo Lin School of Medicine National University of Singapore Singapore Singapore., Gong L; Yong Loo Lin School of Medicine National University of Singapore Singapore Singapore., Lunaria JB; Yong Loo Lin School of Medicine National University of Singapore Singapore Singapore., Liew OW; Yong Loo Lin School of Medicine National University of Singapore Singapore Singapore.; Cardiovascular Research Institute, National University Health System Singapore Singapore., Chong JP; Yong Loo Lin School of Medicine National University of Singapore Singapore Singapore.; Cardiovascular Research Institute, National University Health System Singapore Singapore., Tay EL; National University Heart Centre Singapore Singapore.; Asian Heart and Vascular Centre Singapore Singapore., Soo WM; National University Heart Centre Singapore Singapore., Yip JW; National University Heart Centre Singapore Singapore.; Yong Loo Lin School of Medicine National University of Singapore Singapore Singapore., Yong QW; Tan Tock Seng Hospital Singapore Singapore., Lee EM; Tan Tock Seng Hospital Singapore Singapore., Daniel Yeo PS; Tan Tock Seng Hospital Singapore Singapore.; Apex Heart Clinic Gleneagles Hospital Singapore Singapore., Ding ZP; National Heart Centre Singapore Singapore., Tang HC; National Heart Centre Singapore Singapore., Ewe SH; National Heart Centre Singapore Singapore., Chin CWL; National Heart Centre Singapore Singapore., Chai SC; Changi General Hospital Singapore Singapore., Goh PP; Asian Heart and Vascular Centre Singapore Singapore., Ling LF; Khoo Teck Puat Hospital Singapore Singapore., Ong HY; Khoo Teck Puat Hospital Singapore Singapore., Richards AM; National University Heart Centre Singapore Singapore.; Yong Loo Lin School of Medicine National University of Singapore Singapore Singapore.; Cardiovascular Research Institute, National University Health System Singapore Singapore.; Christchurch Heart Institute, University of Otago Christchurch New Zealand., Ling LH; National University Heart Centre Singapore Singapore.; Yong Loo Lin School of Medicine National University of Singapore Singapore Singapore.; Cardiovascular Research Institute, National University Health System Singapore Singapore.
Jazyk:	angličtina
Zdroj:	Journal of the American Heart Association [J Am Heart Assoc] 2024 Oct; Vol. 13 (19), pp. e035486. Date of Electronic Publication: 2024 Sep 30.
DOI:	10.1161/JAHA.124.035486
Abstrakt:	Background: Echocardiographic indexes of aortic stenosis may not comprehensively reflect disease morbidity. Plasma proteomic profiling may add prognostic value in these patients. Methods and Results: Proximity extension assays (Olink) of 183 circulating cardiovascular and inflammatory proteins were performed in a prospective follow-up study of 122 asymptomatic/minimally symptomatic patients (mean±SD age, 69.1±10.9 years; 61% men) with moderate to severe aortic stenosis and preserved left ventricular ejection fraction. Protein signatures of higher-risk echocardiographic subgroups were determined. Associations of proteins with the primary composite outcome (heart failure hospitalization, progression to New York Heart Association class III-IV, or all-cause mortality) were evaluated using competing risk analyses, with aortic valve replacement being the competing risk. Network analysis unveiled mutually exclusive communities of proteins and echocardiographic parameters, connected only through NT-proBNP (N-terminal pro-B-type natriuretic peptide). Members of the tumor necrosis factor receptor superfamily (TNFRSF1A, TNFRSF1B, and TNFRSF14), and trefoil factor-3 were major hub proteins among the circulating biomarkers. Left ventricular global longitudinal strain >-15% was associated with higher levels of proteins, primarily of inflammation and immune regulation, whereas aortic valve area <1 cm 2 , E/e' >15, and left atrial reservoir strain <20% were associated with higher levels of NT-proBNP. Of 14 proteins associated with the primary end point, phospholipase-C, C-X-C motif chemokine-9, and interleukin-10 receptor subunit β demonstrated the highest hazard ratios after adjusting for clinical factors ( q <0.05). Conclusions: Plasma proteins involved in inflammation and immune regulation were differentially expressed in patients with aortic stenosis with reduced left ventricular global longitudinal strain, and associated with adverse clinical outcomes. Their incorporation into aortic stenosis risk stratification warrants further assessment.
Databáze:	MEDLINE
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