Reduced Apolipoprotein M and Adverse Outcomes Across the Spectrum of Human Heart Failure

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Reduced Apolipoprotein M and Adverse Outcomes Across the Spectrum of Human Heart Failure. / Chirinos, Julio A; Zhao, Lei; Jia, Yi; Frej, Cecilia; Adamo, Luigi; Mann, Douglas; Shewale, Swapnil V; Millar, John S; Rader, Daniel J; French, Benjamin; Brandimarto, Jeff; Margulies, Kenneth B; Parks, John S; Wang, Zhaoqing; Sieffert, Dietmar A; Fang, James; Sweitzer, Nancy; Christoffersen, Christina; Dahlbäck, Björn; Car, Bruce D; Gordon, David A; Cappola, Thomas P; Javaheri, Ali.

I: Circulation, Bind 141, Nr. 18, 2020, s. 1463–1476.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Harvard

Chirinos, JA, Zhao, L, Jia, Y, Frej, C, Adamo, L, Mann, D, Shewale, SV, Millar, JS, Rader, DJ, French, B, Brandimarto, J, Margulies, KB, Parks, JS, Wang, Z, Sieffert, DA, Fang, J, Sweitzer, N, Christoffersen, C, Dahlbäck, B, Car, BD, Gordon, DA, Cappola, TP & Javaheri, A 2020, 'Reduced Apolipoprotein M and Adverse Outcomes Across the Spectrum of Human Heart Failure', Circulation, bind 141, nr. 18, s. 1463–1476. https://doi.org/10.1161/CIRCULATIONAHA.119.045323

APA

Chirinos, J. A., Zhao, L., Jia, Y., Frej, C., Adamo, L., Mann, D., ... Javaheri, A. (2020). Reduced Apolipoprotein M and Adverse Outcomes Across the Spectrum of Human Heart Failure. Circulation, 141(18), 1463–1476. https://doi.org/10.1161/CIRCULATIONAHA.119.045323

Vancouver

Chirinos JA, Zhao L, Jia Y, Frej C, Adamo L, Mann D o.a. Reduced Apolipoprotein M and Adverse Outcomes Across the Spectrum of Human Heart Failure. Circulation. 2020;141(18):1463–1476. https://doi.org/10.1161/CIRCULATIONAHA.119.045323

Author

Chirinos, Julio A ; Zhao, Lei ; Jia, Yi ; Frej, Cecilia ; Adamo, Luigi ; Mann, Douglas ; Shewale, Swapnil V ; Millar, John S ; Rader, Daniel J ; French, Benjamin ; Brandimarto, Jeff ; Margulies, Kenneth B ; Parks, John S ; Wang, Zhaoqing ; Sieffert, Dietmar A ; Fang, James ; Sweitzer, Nancy ; Christoffersen, Christina ; Dahlbäck, Björn ; Car, Bruce D ; Gordon, David A ; Cappola, Thomas P ; Javaheri, Ali. / Reduced Apolipoprotein M and Adverse Outcomes Across the Spectrum of Human Heart Failure. I: Circulation. 2020 ; Bind 141, Nr. 18. s. 1463–1476.

Bibtex

@article{00982bfbe132480199fc44aa7b4ee87c,
title = "Reduced Apolipoprotein M and Adverse Outcomes Across the Spectrum of Human Heart Failure",
abstract = "Background: Apolipoprotein M (APOM) mediates the physical interaction between high-density lipoprotein (HDL) particles and sphingosine-1-phosphate (S1P). APOM exerts anti-inflammatory and cardio-protective effects in animal models. Methods: In a subset of Penn-HF study (PHFS) participants (n=297), we measured APOM by ELISA. We also measured total S1P by liquid chromatography-mass spectrometry and isolated HDL particles to test the association between APOM and HDL-associated S1P. We confirmed the relationship between APOM and outcomes using modified aptamer-based APOM measurements, among 2,170 adults in the PHFS and 2 independent cohorts: the Washington University HF registry (n=173) and a subset of the TOPCAT trial (n=218). Finally, we examined the relationship between APOM and ~5000 other proteins (SomaScan assay) to identify biological pathways associated with APOM in HF. Results: In the PHFS, APOM was inversely associated with the risk of death (Standardized Hazard Ratio=0.56; 95{\%}CI=0.51-0.61; P<0.0001) and the composite of death/ventricular assist device or heart transplant (Standardized HR=0.62; 95{\%}CI=0.58-0.67; P<0.0001). This relationship was independent of HDL-C or APOA-I levels. APOM remained associated with death (HR=0.78; 0.69-0.88; P<0.0001) and the composite of death/ventricular assist device/heart transplant (HR=0.85; 95{\%}CI=0.76-0.94; P=0.001) in models that adjusted for multiple confounders. This association was present in both HF with reduced (HFrEF) and preserved (HFpEF) ejection fraction, and was replicated in the Washington University cohort and a HFpEF-only cohort (TOPCAT). The S1P and APOM content of isolated HDL particles strongly correlated (R=0.81; P<0.0001). The top canonical pathways associated with APOM were inflammation (negative association), the coagulation system (negative association) and LXR/RXR activation (positive association). The relationship with inflammation was validated with multiple inflammatory markers measured with independent assays. Conclusions: Reduced circulating APOM is independently associated with adverse outcomes across the spectrum of human HF. Further research is needed to assess whether the APOM/S1P axis is a suitable therapeutic target in HF.",
author = "Chirinos, {Julio A} and Lei Zhao and Yi Jia and Cecilia Frej and Luigi Adamo and Douglas Mann and Shewale, {Swapnil V} and Millar, {John S} and Rader, {Daniel J} and Benjamin French and Jeff Brandimarto and Margulies, {Kenneth B} and Parks, {John S} and Zhaoqing Wang and Sieffert, {Dietmar A} and James Fang and Nancy Sweitzer and Christina Christoffersen and Bj{\"o}rn Dahlb{\"a}ck and Car, {Bruce D} and Gordon, {David A} and Cappola, {Thomas P} and Ali Javaheri",
year = "2020",
doi = "10.1161/CIRCULATIONAHA.119.045323",
language = "English",
volume = "141",
pages = "1463–1476",
journal = "Circulation. Supplement",
issn = "0009-7322",
publisher = "Lippincott Williams & Wilkins",
number = "18",

}

RIS

TY - JOUR

T1 - Reduced Apolipoprotein M and Adverse Outcomes Across the Spectrum of Human Heart Failure

AU - Chirinos, Julio A

AU - Zhao, Lei

AU - Jia, Yi

AU - Frej, Cecilia

AU - Adamo, Luigi

AU - Mann, Douglas

AU - Shewale, Swapnil V

AU - Millar, John S

AU - Rader, Daniel J

AU - French, Benjamin

AU - Brandimarto, Jeff

AU - Margulies, Kenneth B

AU - Parks, John S

AU - Wang, Zhaoqing

AU - Sieffert, Dietmar A

AU - Fang, James

AU - Sweitzer, Nancy

AU - Christoffersen, Christina

AU - Dahlbäck, Björn

AU - Car, Bruce D

AU - Gordon, David A

AU - Cappola, Thomas P

AU - Javaheri, Ali

PY - 2020

Y1 - 2020

N2 - Background: Apolipoprotein M (APOM) mediates the physical interaction between high-density lipoprotein (HDL) particles and sphingosine-1-phosphate (S1P). APOM exerts anti-inflammatory and cardio-protective effects in animal models. Methods: In a subset of Penn-HF study (PHFS) participants (n=297), we measured APOM by ELISA. We also measured total S1P by liquid chromatography-mass spectrometry and isolated HDL particles to test the association between APOM and HDL-associated S1P. We confirmed the relationship between APOM and outcomes using modified aptamer-based APOM measurements, among 2,170 adults in the PHFS and 2 independent cohorts: the Washington University HF registry (n=173) and a subset of the TOPCAT trial (n=218). Finally, we examined the relationship between APOM and ~5000 other proteins (SomaScan assay) to identify biological pathways associated with APOM in HF. Results: In the PHFS, APOM was inversely associated with the risk of death (Standardized Hazard Ratio=0.56; 95%CI=0.51-0.61; P<0.0001) and the composite of death/ventricular assist device or heart transplant (Standardized HR=0.62; 95%CI=0.58-0.67; P<0.0001). This relationship was independent of HDL-C or APOA-I levels. APOM remained associated with death (HR=0.78; 0.69-0.88; P<0.0001) and the composite of death/ventricular assist device/heart transplant (HR=0.85; 95%CI=0.76-0.94; P=0.001) in models that adjusted for multiple confounders. This association was present in both HF with reduced (HFrEF) and preserved (HFpEF) ejection fraction, and was replicated in the Washington University cohort and a HFpEF-only cohort (TOPCAT). The S1P and APOM content of isolated HDL particles strongly correlated (R=0.81; P<0.0001). The top canonical pathways associated with APOM were inflammation (negative association), the coagulation system (negative association) and LXR/RXR activation (positive association). The relationship with inflammation was validated with multiple inflammatory markers measured with independent assays. Conclusions: Reduced circulating APOM is independently associated with adverse outcomes across the spectrum of human HF. Further research is needed to assess whether the APOM/S1P axis is a suitable therapeutic target in HF.

AB - Background: Apolipoprotein M (APOM) mediates the physical interaction between high-density lipoprotein (HDL) particles and sphingosine-1-phosphate (S1P). APOM exerts anti-inflammatory and cardio-protective effects in animal models. Methods: In a subset of Penn-HF study (PHFS) participants (n=297), we measured APOM by ELISA. We also measured total S1P by liquid chromatography-mass spectrometry and isolated HDL particles to test the association between APOM and HDL-associated S1P. We confirmed the relationship between APOM and outcomes using modified aptamer-based APOM measurements, among 2,170 adults in the PHFS and 2 independent cohorts: the Washington University HF registry (n=173) and a subset of the TOPCAT trial (n=218). Finally, we examined the relationship between APOM and ~5000 other proteins (SomaScan assay) to identify biological pathways associated with APOM in HF. Results: In the PHFS, APOM was inversely associated with the risk of death (Standardized Hazard Ratio=0.56; 95%CI=0.51-0.61; P<0.0001) and the composite of death/ventricular assist device or heart transplant (Standardized HR=0.62; 95%CI=0.58-0.67; P<0.0001). This relationship was independent of HDL-C or APOA-I levels. APOM remained associated with death (HR=0.78; 0.69-0.88; P<0.0001) and the composite of death/ventricular assist device/heart transplant (HR=0.85; 95%CI=0.76-0.94; P=0.001) in models that adjusted for multiple confounders. This association was present in both HF with reduced (HFrEF) and preserved (HFpEF) ejection fraction, and was replicated in the Washington University cohort and a HFpEF-only cohort (TOPCAT). The S1P and APOM content of isolated HDL particles strongly correlated (R=0.81; P<0.0001). The top canonical pathways associated with APOM were inflammation (negative association), the coagulation system (negative association) and LXR/RXR activation (positive association). The relationship with inflammation was validated with multiple inflammatory markers measured with independent assays. Conclusions: Reduced circulating APOM is independently associated with adverse outcomes across the spectrum of human HF. Further research is needed to assess whether the APOM/S1P axis is a suitable therapeutic target in HF.

U2 - 10.1161/CIRCULATIONAHA.119.045323

DO - 10.1161/CIRCULATIONAHA.119.045323

M3 - Journal article

C2 - 32237898

VL - 141

SP - 1463

EP - 1476

JO - Circulation. Supplement

JF - Circulation. Supplement

SN - 0009-7322

IS - 18

ER -

ID: 239256455