Elevated Lipoprotein(a) as a potential residual risk factor associated with lipid-rich coronary atheroma in patients with type 2 diabetes and coronary artery disease on statin treatment: Insights from the REASSURE-NIRS registry

Hayato Nakamura; Yu Kataoka; Stephen J. Nicholls; Rishi Puri; Satoshi Kitahara; Kota Murai; Kenichiro Sawada; Hideo Matama; Takamasa Iwai; Satoshi Honda; Masashi Fujino; Kensuke Takagi; Shuichi Yoneda; Fumiyuki Otsuka; Kensaku Nishihira; Yasuhide Asaumi; Kenichi Tsujita; Teruo Noguchi

doi:10.1016/j.atherosclerosis.2022.03.033

Elevated Lipoprotein(a) as a potential residual risk factor associated with lipid-rich coronary atheroma in patients with type 2 diabetes and coronary artery disease on statin treatment: Insights from the REASSURE-NIRS registry

Hayato Nakamura, Yu Kataoka, Stephen J. Nicholls, Rishi Puri, Satoshi Kitahara, Kota Murai, Kenichiro Sawada, Hideo Matama, Takamasa Iwai, Satoshi Honda, Masashi Fujino, Kensuke Takagi, Shuichi Yoneda, Fumiyuki Otsuka, Kensaku Nishihira, Yasuhide Asaumi, Kenichi Tsujita, Teruo Noguchi

Medicine Monash Health

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

18 Citations (Scopus)

Abstract

Background and aims: The residual risk of atherosclerotic cardiovascular disease (ASCVD) in patients with diabetes on statin therapy warrants identification of other pro-atherogenic drivers. Lipoprotein(a) [Lp(a)] promotes the formation of necrotic cores within vessel walls. Given that patients with diabetes have an Lp(a)-associated ASCVD risk, Lp(a) might lead to plaque vulnerability in patients with diabetes on statin therapy. Methods: We analyzed target lesions that underwent PCI in 312 patients with coronary artery disease (CAD) on statin treatment from the REASSURE-NIRS registry (NCT04864171). Maximum 4-mm lipid-core-burden index (maxLCBI_4mm) in target lesions was measured with near-infrared spectroscopy (NIRS) imaging. The relationship between Lp(a) levels and maxLCBI_4mm was investigated in patients with and without diabetes. Results: High-intensity statin use (p = 0.49) and on-treatment low-density lipoprotein cholesterol (LDL-C) (p = 0.32) and Lp(a) levels (p = 0.09) were comparable between patients with and without diabetes. Lp(a) levels were significantly associated with maxLCBI_4mm in patients with diabetes (p = 0.01) but not in patients without diabetes (p = 0.96). Multivariate analysis showed that LDL-C levels (p = 0.03) predict maxLCBI_4mm in patients without diabetes, but not Lp(a) levels (p = 0.91). Both LDL-C (p = 0.01) and Lp(a) (p = 0.04) levels were independent predictors of maxLCBI_4mm in patients with diabetes. Even in patients with diabetes achieving LDL-C <1.8 mmol/L (70 mg/dL), Lp(a) levels remained associated with maxLCBI_4mm (p = 0.04). Conclusions: A significant relationship between Lp(a) and maxLCBI_4mm exists in patients with diabetes and CAD on statin treatment, even with LDL-C <1.8 mmol/L (70 mg/dL). Lp(a) might be associated with more vulnerable coronary atheroma in patients with diabetes despite receiving statin therapy.

Original language	English
Pages (from-to)	183-189
Number of pages	7
Journal	Atherosclerosis
Volume	349
DOIs	https://doi.org/10.1016/j.atherosclerosis.2022.03.033
Publication status	Published - May 2022

Keywords

LDL-C
Lipid-rich plaque
Lipoprotein (a)
Near-infrared spectroscopy
Type 2 diabetes mellitus

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.atherosclerosis.2022.03.033

Cite this

Nakamura, H., Kataoka, Y., Nicholls, S. J., Puri, R., Kitahara, S., Murai, K., Sawada, K., Matama, H., Iwai, T., Honda, S., Fujino, M., Takagi, K., Yoneda, S., Otsuka, F., Nishihira, K., Asaumi, Y., Tsujita, K., & Noguchi, T. (2022). Elevated Lipoprotein(a) as a potential residual risk factor associated with lipid-rich coronary atheroma in patients with type 2 diabetes and coronary artery disease on statin treatment: Insights from the REASSURE-NIRS registry. Atherosclerosis, 349, 183-189. https://doi.org/10.1016/j.atherosclerosis.2022.03.033

@article{cfd1f73e4dff41c7b11e200f6a303bc8,

title = "Elevated Lipoprotein(a) as a potential residual risk factor associated with lipid-rich coronary atheroma in patients with type 2 diabetes and coronary artery disease on statin treatment: Insights from the REASSURE-NIRS registry",

abstract = "Background and aims: The residual risk of atherosclerotic cardiovascular disease (ASCVD) in patients with diabetes on statin therapy warrants identification of other pro-atherogenic drivers. Lipoprotein(a) [Lp(a)] promotes the formation of necrotic cores within vessel walls. Given that patients with diabetes have an Lp(a)-associated ASCVD risk, Lp(a) might lead to plaque vulnerability in patients with diabetes on statin therapy. Methods: We analyzed target lesions that underwent PCI in 312 patients with coronary artery disease (CAD) on statin treatment from the REASSURE-NIRS registry (NCT04864171). Maximum 4-mm lipid-core-burden index (maxLCBI4mm) in target lesions was measured with near-infrared spectroscopy (NIRS) imaging. The relationship between Lp(a) levels and maxLCBI4mm was investigated in patients with and without diabetes. Results: High-intensity statin use (p = 0.49) and on-treatment low-density lipoprotein cholesterol (LDL-C) (p = 0.32) and Lp(a) levels (p = 0.09) were comparable between patients with and without diabetes. Lp(a) levels were significantly associated with maxLCBI4mm in patients with diabetes (p = 0.01) but not in patients without diabetes (p = 0.96). Multivariate analysis showed that LDL-C levels (p = 0.03) predict maxLCBI4mm in patients without diabetes, but not Lp(a) levels (p = 0.91). Both LDL-C (p = 0.01) and Lp(a) (p = 0.04) levels were independent predictors of maxLCBI4mm in patients with diabetes. Even in patients with diabetes achieving LDL-C <1.8 mmol/L (70 mg/dL), Lp(a) levels remained associated with maxLCBI4mm (p = 0.04). Conclusions: A significant relationship between Lp(a) and maxLCBI4mm exists in patients with diabetes and CAD on statin treatment, even with LDL-C <1.8 mmol/L (70 mg/dL). Lp(a) might be associated with more vulnerable coronary atheroma in patients with diabetes despite receiving statin therapy.",

keywords = "LDL-C, Lipid-rich plaque, Lipoprotein (a), Near-infrared spectroscopy, Type 2 diabetes mellitus",

author = "Hayato Nakamura and Yu Kataoka and Nicholls, {Stephen J.} and Rishi Puri and Satoshi Kitahara and Kota Murai and Kenichiro Sawada and Hideo Matama and Takamasa Iwai and Satoshi Honda and Masashi Fujino and Kensuke Takagi and Shuichi Yoneda and Fumiyuki Otsuka and Kensaku Nishihira and Yasuhide Asaumi and Kenichi Tsujita and Teruo Noguchi",

note = "Funding Information: This study was partially funded by research grant from Fukuda Memorial Foundation in 2018. Funding Information: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Yu Kataoka has received research support from Nipro and Abbott, and honoraria from Nipro, Abbott, Kowa, Amgen, Sanofi, Astellas, Takeda and Daiichi-Sankyo. Stephen J. Nicholls is a recipient of a Principal Research Fellowship from the National Health and Medical Research Council of Australia and has received research support from AstraZeneca, Amgen, Anthera, CSL Behring, Cerenis, Eli Lilly, Esperion, Resverlogix, Novartis, InfraReDx and Sanofi-Regeneron and is a consultant for Amgen, Akcea, AstraZeneca, Boehringer Ingelheim, CSL Behring, Eli Lilly, Esperion, Kowa, Merck, Takeda, Pfizer, Sanofi-Regeneron and Novo Nordisk. Rishi Puri has received speaker fees from Amgen and Sanofi, served as a consultant for Cerenis, Medtronic, Philips, Boston Scientific, Shockwave and on advisory boards for Centerline Biomedical, Medtronic, Bioventrix and holds minor equity in Centerline Biomedical. Kota Murai has received honoraria from Abbot, Terumo, Amgen and Zeon Medical, and support for attending meetings from OrbusNeich. Other authors have nothing to disclose. Publisher Copyright: {\textcopyright} 2022 Elsevier B.V.",

year = "2022",

month = may,

doi = "10.1016/j.atherosclerosis.2022.03.033",

language = "English",

volume = "349",

pages = "183--189",

journal = "Atherosclerosis",

issn = "0021-9150",

publisher = "Elsevier",

}

Nakamura, H, Kataoka, Y, Nicholls, SJ, Puri, R, Kitahara, S, Murai, K, Sawada, K, Matama, H, Iwai, T, Honda, S, Fujino, M, Takagi, K, Yoneda, S, Otsuka, F, Nishihira, K, Asaumi, Y, Tsujita, K & Noguchi, T 2022, 'Elevated Lipoprotein(a) as a potential residual risk factor associated with lipid-rich coronary atheroma in patients with type 2 diabetes and coronary artery disease on statin treatment: Insights from the REASSURE-NIRS registry', Atherosclerosis, vol. 349, pp. 183-189. https://doi.org/10.1016/j.atherosclerosis.2022.03.033

Elevated Lipoprotein(a) as a potential residual risk factor associated with lipid-rich coronary atheroma in patients with type 2 diabetes and coronary artery disease on statin treatment: Insights from the REASSURE-NIRS registry. / Nakamura, Hayato; Kataoka, Yu; Nicholls, Stephen J. et al.
In: Atherosclerosis, Vol. 349, 05.2022, p. 183-189.

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

TY - JOUR

T1 - Elevated Lipoprotein(a) as a potential residual risk factor associated with lipid-rich coronary atheroma in patients with type 2 diabetes and coronary artery disease on statin treatment

T2 - Insights from the REASSURE-NIRS registry

AU - Nakamura, Hayato

AU - Kataoka, Yu

AU - Nicholls, Stephen J.

AU - Puri, Rishi

AU - Kitahara, Satoshi

AU - Murai, Kota

AU - Sawada, Kenichiro

AU - Matama, Hideo

AU - Iwai, Takamasa

AU - Honda, Satoshi

AU - Fujino, Masashi

AU - Takagi, Kensuke

AU - Yoneda, Shuichi

AU - Otsuka, Fumiyuki

AU - Nishihira, Kensaku

AU - Asaumi, Yasuhide

AU - Tsujita, Kenichi

AU - Noguchi, Teruo

N1 - Funding Information: This study was partially funded by research grant from Fukuda Memorial Foundation in 2018. Funding Information: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Yu Kataoka has received research support from Nipro and Abbott, and honoraria from Nipro, Abbott, Kowa, Amgen, Sanofi, Astellas, Takeda and Daiichi-Sankyo. Stephen J. Nicholls is a recipient of a Principal Research Fellowship from the National Health and Medical Research Council of Australia and has received research support from AstraZeneca, Amgen, Anthera, CSL Behring, Cerenis, Eli Lilly, Esperion, Resverlogix, Novartis, InfraReDx and Sanofi-Regeneron and is a consultant for Amgen, Akcea, AstraZeneca, Boehringer Ingelheim, CSL Behring, Eli Lilly, Esperion, Kowa, Merck, Takeda, Pfizer, Sanofi-Regeneron and Novo Nordisk. Rishi Puri has received speaker fees from Amgen and Sanofi, served as a consultant for Cerenis, Medtronic, Philips, Boston Scientific, Shockwave and on advisory boards for Centerline Biomedical, Medtronic, Bioventrix and holds minor equity in Centerline Biomedical. Kota Murai has received honoraria from Abbot, Terumo, Amgen and Zeon Medical, and support for attending meetings from OrbusNeich. Other authors have nothing to disclose. Publisher Copyright: © 2022 Elsevier B.V.

PY - 2022/5

Y1 - 2022/5

N2 - Background and aims: The residual risk of atherosclerotic cardiovascular disease (ASCVD) in patients with diabetes on statin therapy warrants identification of other pro-atherogenic drivers. Lipoprotein(a) [Lp(a)] promotes the formation of necrotic cores within vessel walls. Given that patients with diabetes have an Lp(a)-associated ASCVD risk, Lp(a) might lead to plaque vulnerability in patients with diabetes on statin therapy. Methods: We analyzed target lesions that underwent PCI in 312 patients with coronary artery disease (CAD) on statin treatment from the REASSURE-NIRS registry (NCT04864171). Maximum 4-mm lipid-core-burden index (maxLCBI4mm) in target lesions was measured with near-infrared spectroscopy (NIRS) imaging. The relationship between Lp(a) levels and maxLCBI4mm was investigated in patients with and without diabetes. Results: High-intensity statin use (p = 0.49) and on-treatment low-density lipoprotein cholesterol (LDL-C) (p = 0.32) and Lp(a) levels (p = 0.09) were comparable between patients with and without diabetes. Lp(a) levels were significantly associated with maxLCBI4mm in patients with diabetes (p = 0.01) but not in patients without diabetes (p = 0.96). Multivariate analysis showed that LDL-C levels (p = 0.03) predict maxLCBI4mm in patients without diabetes, but not Lp(a) levels (p = 0.91). Both LDL-C (p = 0.01) and Lp(a) (p = 0.04) levels were independent predictors of maxLCBI4mm in patients with diabetes. Even in patients with diabetes achieving LDL-C <1.8 mmol/L (70 mg/dL), Lp(a) levels remained associated with maxLCBI4mm (p = 0.04). Conclusions: A significant relationship between Lp(a) and maxLCBI4mm exists in patients with diabetes and CAD on statin treatment, even with LDL-C <1.8 mmol/L (70 mg/dL). Lp(a) might be associated with more vulnerable coronary atheroma in patients with diabetes despite receiving statin therapy.

AB - Background and aims: The residual risk of atherosclerotic cardiovascular disease (ASCVD) in patients with diabetes on statin therapy warrants identification of other pro-atherogenic drivers. Lipoprotein(a) [Lp(a)] promotes the formation of necrotic cores within vessel walls. Given that patients with diabetes have an Lp(a)-associated ASCVD risk, Lp(a) might lead to plaque vulnerability in patients with diabetes on statin therapy. Methods: We analyzed target lesions that underwent PCI in 312 patients with coronary artery disease (CAD) on statin treatment from the REASSURE-NIRS registry (NCT04864171). Maximum 4-mm lipid-core-burden index (maxLCBI4mm) in target lesions was measured with near-infrared spectroscopy (NIRS) imaging. The relationship between Lp(a) levels and maxLCBI4mm was investigated in patients with and without diabetes. Results: High-intensity statin use (p = 0.49) and on-treatment low-density lipoprotein cholesterol (LDL-C) (p = 0.32) and Lp(a) levels (p = 0.09) were comparable between patients with and without diabetes. Lp(a) levels were significantly associated with maxLCBI4mm in patients with diabetes (p = 0.01) but not in patients without diabetes (p = 0.96). Multivariate analysis showed that LDL-C levels (p = 0.03) predict maxLCBI4mm in patients without diabetes, but not Lp(a) levels (p = 0.91). Both LDL-C (p = 0.01) and Lp(a) (p = 0.04) levels were independent predictors of maxLCBI4mm in patients with diabetes. Even in patients with diabetes achieving LDL-C <1.8 mmol/L (70 mg/dL), Lp(a) levels remained associated with maxLCBI4mm (p = 0.04). Conclusions: A significant relationship between Lp(a) and maxLCBI4mm exists in patients with diabetes and CAD on statin treatment, even with LDL-C <1.8 mmol/L (70 mg/dL). Lp(a) might be associated with more vulnerable coronary atheroma in patients with diabetes despite receiving statin therapy.

KW - LDL-C

KW - Lipid-rich plaque

KW - Lipoprotein (a)

KW - Near-infrared spectroscopy

KW - Type 2 diabetes mellitus

UR - http://www.scopus.com/inward/record.url?scp=85128520036&partnerID=8YFLogxK

U2 - 10.1016/j.atherosclerosis.2022.03.033

DO - 10.1016/j.atherosclerosis.2022.03.033

M3 - Article

C2 - 35450750

AN - SCOPUS:85128520036

SN - 0021-9150

VL - 349

SP - 183

EP - 189

JO - Atherosclerosis

JF - Atherosclerosis

ER -

Nakamura H, Kataoka Y, Nicholls SJ, Puri R, Kitahara S, Murai K et al. Elevated Lipoprotein(a) as a potential residual risk factor associated with lipid-rich coronary atheroma in patients with type 2 diabetes and coronary artery disease on statin treatment: Insights from the REASSURE-NIRS registry. Atherosclerosis. 2022 May;349:183-189. doi: 10.1016/j.atherosclerosis.2022.03.033

Elevated Lipoprotein(a) as a potential residual risk factor associated with lipid-rich coronary atheroma in patients with type 2 diabetes and coronary artery disease on statin treatment: Insights from the REASSURE-NIRS registry

Abstract

Keywords

UN SDGs

Access to Document

Other files and links

Cite this