Association of Lipoprotein(a) With Atherosclerotic Plaque Progression

Yannick  Kaiser; Marwa Daghem; Evangelos Tzolos; Mohammed N Meah; Mhairi Doris; Alastair J  Moss; Jacek Kwiecinski; Jeffrey  Kroon; Nick S.  Nurmohamed; Pim van der Harst; Philip D Adamson; Michelle C Williams; Damini Dey; David E Newby; Erik S.g. Stroes; Kang H Zheng; Marc R Dweck

doi:10.1016/j.jacc.2021.10.044.

Association of Lipoprotein(a) With Atherosclerotic Plaque Progression

Yannick Kaiser, Marwa Daghem, Evangelos Tzolos, Mohammed N Meah, Mhairi Doris, Alastair J Moss, Jacek Kwiecinski, Jeffrey Kroon, Nick S. Nurmohamed, Pim van der Harst, Philip D Adamson, Michelle C Williams, Damini Dey, David E Newby, Erik S.g. Stroes, Kang H Zheng, Marc R Dweck

Research output: Contribution to journal › Article › peer-review

Abstract

Background: Lipoprotein(a) [Lp(a)] is associated with increased risk of myocardial infarction, although the mechanism for this observation remains uncertain.
Objectives: To investigate whether Lp(a) is associated with adverse plaque progression.
Methods: Lp(a) was measured in patients with advanced stable coronary artery disease undergoing coronary CT angiography (CCTA) at baseline and 12 months to assess progression of total, calcific, non-calcific and in particular low-attenuation plaque (necrotic core). High Lp(a) was defined as Lp(a) ≥70 mg/dL. The relationship of Lp(a) with plaque progression was assessed using linear regression analysis, adjusting for body mass index, segment involvement score, and ASSIGN score.
Results: 191 patients (65.9±8.3 years, 152 (80%) men) were included in the analysis, with median Lp(a) values of 100 [82-115] and 10 [5-24] mg/dL in the high and low Lp(a) groups respectively. At baseline, there was no difference in coronary artery disease severity or plaque burden. Patients with high Lp(a) showed accelerated progression of low-attenuation plaque compared with low Lp(a) patients (26.2±88.4 mm3 vs -0.7±50.1 mm3, p=0.020). Multivariable linear regression analysis confirmed the relation between Lp(a) and low-attenuation plaque volume progression (β=10.5% increase for each 50 mg/dL Lp(a), 95% confidence interval 0.7-20.3%). There was no difference in total, calcific, and non-calcific plaque volume progression.
Conclusion: Among patients with advanced stable coronary artery disease, Lp(a) is associated with accelerated progression of coronary low-attenuation plaque (necrotic core). This may explain the association between Lp(a) and the high residual risk of myocardial infarction, providing support for Lp(a) as a treatment target in atherosclerosis.

Original language	English
Journal	Journal of the American College of Cardiology
DOIs	https://doi.org/10.1016/j.jacc.2021.10.044.
Publication status	Published - 25 Jan 2022

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20211010_Lp(a) is associated with adverse plaque progression_cleanAccepted author manuscript, 105 KB
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An Intermediate Clinical Research Fellowship in Cardiovascular Non- Invasive Molecular Imaging
Dweck, M.
UK-based charities
1/12/14 → 30/11/21
Project: Research

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Kaiser, Y., Daghem, M., Tzolos, E., Meah, M. N., Doris, M., Moss, A. J., Kwiecinski, J., Kroon, J., Nurmohamed, N. S., van der Harst, P., Adamson, P. D., Williams, M. C., Dey, D., Newby, D. E., Stroes, E. S. G., Zheng, K. H., & Dweck, M. R. (2022). Association of Lipoprotein(a) With Atherosclerotic Plaque Progression. Journal of the American College of Cardiology. https://doi.org/10.1016/j.jacc.2021.10.044.

@article{f9decdab380545a7a770960764292e41,

title = "Association of Lipoprotein(a) With Atherosclerotic Plaque Progression",

abstract = "Background: Lipoprotein(a) [Lp(a)] is associated with increased risk of myocardial infarction, although the mechanism for this observation remains uncertain. Objectives: To investigate whether Lp(a) is associated with adverse plaque progression.Methods: Lp(a) was measured in patients with advanced stable coronary artery disease undergoing coronary CT angiography (CCTA) at baseline and 12 months to assess progression of total, calcific, non-calcific and in particular low-attenuation plaque (necrotic core). High Lp(a) was defined as Lp(a) ≥70 mg/dL. The relationship of Lp(a) with plaque progression was assessed using linear regression analysis, adjusting for body mass index, segment involvement score, and ASSIGN score.Results: 191 patients (65.9±8.3 years, 152 (80%) men) were included in the analysis, with median Lp(a) values of 100 [82-115] and 10 [5-24] mg/dL in the high and low Lp(a) groups respectively. At baseline, there was no difference in coronary artery disease severity or plaque burden. Patients with high Lp(a) showed accelerated progression of low-attenuation plaque compared with low Lp(a) patients (26.2±88.4 mm3 vs -0.7±50.1 mm3, p=0.020). Multivariable linear regression analysis confirmed the relation between Lp(a) and low-attenuation plaque volume progression (β=10.5% increase for each 50 mg/dL Lp(a), 95% confidence interval 0.7-20.3%). There was no difference in total, calcific, and non-calcific plaque volume progression.Conclusion: Among patients with advanced stable coronary artery disease, Lp(a) is associated with accelerated progression of coronary low-attenuation plaque (necrotic core). This may explain the association between Lp(a) and the high residual risk of myocardial infarction, providing support for Lp(a) as a treatment target in atherosclerosis. ",

author = "Yannick Kaiser and Marwa Daghem and Evangelos Tzolos and Meah, {Mohammed N} and Mhairi Doris and Moss, {Alastair J} and Jacek Kwiecinski and Jeffrey Kroon and Nurmohamed, {Nick S.} and {van der Harst}, Pim and Adamson, {Philip D} and Williams, {Michelle C} and Damini Dey and Newby, {David E} and Stroes, {Erik S.g.} and Zheng, {Kang H} and Dweck, {Marc R}",

note = "Funding Information: Drs Kaiser and Stroes were supported by the Netherlands Heart Foundation CVON 2017-20: generating the best evidence-based pharmaceutical targets for atherosclerosis [GENIUS II]). Dr Dey is supported by the National Institute of Health/National Heart, Lung, and Blood Institute grants (1R01HL148787-01A1 and 1R01HL151266). Dr Dweek is supported by the British Heart Foundation (FS/14/78/31020) and is the recipient of the Sir Jules Thorn Award for Biomedical Research 2015 (15/JTA); has received speaker fees from Pfizer and Novartis; and has received consultancy fees from Novartis, Jupiter Bioventures, and Silence therapeutics. Dr Stroes has received research grants/support to his institution from Amgen, Sanofi, Resverlogix, and Athera; and has served as a consultant for Amgen, Sanofi, Esperion, Novartis, and Ionis Pharmaceuticals. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Publisher Copyright: {\textcopyright} 2022 The Authors",

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doi = "10.1016/j.jacc.2021.10.044.",

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journal = "Journal of the American College of Cardiology",

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Kaiser, Y, Daghem, M, Tzolos, E, Meah, MN, Doris, M, Moss, AJ, Kwiecinski, J, Kroon, J, Nurmohamed, NS, van der Harst, P, Adamson, PD , Williams, MC, Dey, D, Newby, DE, Stroes, ESG, Zheng, KH & Dweck, MR 2022, 'Association of Lipoprotein(a) With Atherosclerotic Plaque Progression', Journal of the American College of Cardiology. https://doi.org/10.1016/j.jacc.2021.10.044.

TY - JOUR

T1 - Association of Lipoprotein(a) With Atherosclerotic Plaque Progression

AU - Kaiser, Yannick

AU - Daghem, Marwa

AU - Tzolos, Evangelos

AU - Meah, Mohammed N

AU - Doris, Mhairi

AU - Moss, Alastair J

AU - Kwiecinski, Jacek

AU - Kroon, Jeffrey

AU - Nurmohamed, Nick S.

AU - van der Harst, Pim

AU - Adamson, Philip D

AU - Williams, Michelle C

AU - Dey, Damini

AU - Newby, David E

AU - Stroes, Erik S.g.

AU - Zheng, Kang H

AU - Dweck, Marc R

N1 - Funding Information: Drs Kaiser and Stroes were supported by the Netherlands Heart Foundation CVON 2017-20: generating the best evidence-based pharmaceutical targets for atherosclerosis [GENIUS II]). Dr Dey is supported by the National Institute of Health/National Heart, Lung, and Blood Institute grants (1R01HL148787-01A1 and 1R01HL151266). Dr Dweek is supported by the British Heart Foundation (FS/14/78/31020) and is the recipient of the Sir Jules Thorn Award for Biomedical Research 2015 (15/JTA); has received speaker fees from Pfizer and Novartis; and has received consultancy fees from Novartis, Jupiter Bioventures, and Silence therapeutics. Dr Stroes has received research grants/support to his institution from Amgen, Sanofi, Resverlogix, and Athera; and has served as a consultant for Amgen, Sanofi, Esperion, Novartis, and Ionis Pharmaceuticals. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Publisher Copyright: © 2022 The Authors

PY - 2022/1/25

Y1 - 2022/1/25

N2 - Background: Lipoprotein(a) [Lp(a)] is associated with increased risk of myocardial infarction, although the mechanism for this observation remains uncertain. Objectives: To investigate whether Lp(a) is associated with adverse plaque progression.Methods: Lp(a) was measured in patients with advanced stable coronary artery disease undergoing coronary CT angiography (CCTA) at baseline and 12 months to assess progression of total, calcific, non-calcific and in particular low-attenuation plaque (necrotic core). High Lp(a) was defined as Lp(a) ≥70 mg/dL. The relationship of Lp(a) with plaque progression was assessed using linear regression analysis, adjusting for body mass index, segment involvement score, and ASSIGN score.Results: 191 patients (65.9±8.3 years, 152 (80%) men) were included in the analysis, with median Lp(a) values of 100 [82-115] and 10 [5-24] mg/dL in the high and low Lp(a) groups respectively. At baseline, there was no difference in coronary artery disease severity or plaque burden. Patients with high Lp(a) showed accelerated progression of low-attenuation plaque compared with low Lp(a) patients (26.2±88.4 mm3 vs -0.7±50.1 mm3, p=0.020). Multivariable linear regression analysis confirmed the relation between Lp(a) and low-attenuation plaque volume progression (β=10.5% increase for each 50 mg/dL Lp(a), 95% confidence interval 0.7-20.3%). There was no difference in total, calcific, and non-calcific plaque volume progression.Conclusion: Among patients with advanced stable coronary artery disease, Lp(a) is associated with accelerated progression of coronary low-attenuation plaque (necrotic core). This may explain the association between Lp(a) and the high residual risk of myocardial infarction, providing support for Lp(a) as a treatment target in atherosclerosis.

AB - Background: Lipoprotein(a) [Lp(a)] is associated with increased risk of myocardial infarction, although the mechanism for this observation remains uncertain. Objectives: To investigate whether Lp(a) is associated with adverse plaque progression.Methods: Lp(a) was measured in patients with advanced stable coronary artery disease undergoing coronary CT angiography (CCTA) at baseline and 12 months to assess progression of total, calcific, non-calcific and in particular low-attenuation plaque (necrotic core). High Lp(a) was defined as Lp(a) ≥70 mg/dL. The relationship of Lp(a) with plaque progression was assessed using linear regression analysis, adjusting for body mass index, segment involvement score, and ASSIGN score.Results: 191 patients (65.9±8.3 years, 152 (80%) men) were included in the analysis, with median Lp(a) values of 100 [82-115] and 10 [5-24] mg/dL in the high and low Lp(a) groups respectively. At baseline, there was no difference in coronary artery disease severity or plaque burden. Patients with high Lp(a) showed accelerated progression of low-attenuation plaque compared with low Lp(a) patients (26.2±88.4 mm3 vs -0.7±50.1 mm3, p=0.020). Multivariable linear regression analysis confirmed the relation between Lp(a) and low-attenuation plaque volume progression (β=10.5% increase for each 50 mg/dL Lp(a), 95% confidence interval 0.7-20.3%). There was no difference in total, calcific, and non-calcific plaque volume progression.Conclusion: Among patients with advanced stable coronary artery disease, Lp(a) is associated with accelerated progression of coronary low-attenuation plaque (necrotic core). This may explain the association between Lp(a) and the high residual risk of myocardial infarction, providing support for Lp(a) as a treatment target in atherosclerosis.

U2 - 10.1016/j.jacc.2021.10.044.

DO - 10.1016/j.jacc.2021.10.044.

M3 - Article

JO - Journal of the American College of Cardiology

JF - Journal of the American College of Cardiology

SN - 0735-1097

ER -

Association of Lipoprotein(a) With Atherosclerotic Plaque Progression

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An Intermediate Clinical Research Fellowship in Cardiovascular Non- Invasive Molecular Imaging

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