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

Atherosclerosis. 2022 May:349:183-189. doi: 10.1016/j.atherosclerosis.2022.03.033. Epub 2022 Apr 10.

Authors

Hayato Nakamura¹, Yu Kataoka², Stephen J Nicholls³, Rishi Puri⁴, Satoshi Kitahara⁵, Kota Murai⁵, Kenichiro Sawada⁶, Hideo Matama⁵, Takamasa Iwai⁶, Satoshi Honda⁶, Masashi Fujino⁶, Kensuke Takagi⁶, Shuichi Yoneda⁶, Fumiyuki Otsuka⁶, Kensaku Nishihira⁷, Yasuhide Asaumi⁶, Kenichi Tsujita⁸, Teruo Noguchi⁵

Affiliations

¹ Department of Cardiovascular Medicine, National Cerebral & Cardiovascular Center, 6-1, Kishibe-shinmachi, Suita, Osaka, 564-8565, Japan; Department of Cardiovascular Medicine, Yaeyama Hospital, 584-1, Maesato, Ishigaki, Okinawa, 907-0002, Japan; Department of Advanced Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, 1-1-1, Honjo, Chuo-ku, Kumamoto, 860-0811, Japan.
² Department of Cardiovascular Medicine, National Cerebral & Cardiovascular Center, 6-1, Kishibe-shinmachi, Suita, Osaka, 564-8565, Japan; Department of Advanced Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, 1-1-1, Honjo, Chuo-ku, Kumamoto, 860-0811, Japan. Electronic address: yu.kataoka@ncvc.go.jp.
³ Monash Heart, Monash University, 246 Clayton Rd, Clayton VIC, 3168, Australia.
⁴ Department of Cardiovascular Medicine, Cleveland Clinic, 9500, Euclid Avenue, Cleveland, OH, United States.
⁵ Department of Cardiovascular Medicine, National Cerebral & Cardiovascular Center, 6-1, Kishibe-shinmachi, Suita, Osaka, 564-8565, Japan; Department of Advanced Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, 1-1-1, Honjo, Chuo-ku, Kumamoto, 860-0811, Japan.
⁶ Department of Cardiovascular Medicine, National Cerebral & Cardiovascular Center, 6-1, Kishibe-shinmachi, Suita, Osaka, 564-8565, Japan.
⁷ Department of Cardiology, Miyazaki Medical Association Hospital, 1173, Arita, Miyazaki, Miyazaki, 880-2102, Japan.
⁸ Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, 1-1-1, Honjo, Chuo-ku, Kumamoto, 860-0811, Japan.

PMID: 35450750
DOI: 10.1016/j.atherosclerosis.2022.03.033

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.

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

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Atherosclerosis*
Cholesterol, LDL
Coronary Artery Disease* / diagnostic imaging
Coronary Artery Disease* / drug therapy
Diabetes Mellitus, Type 2* / complications
Diabetes Mellitus, Type 2* / diagnosis
Diabetes Mellitus, Type 2* / drug therapy
Disease Progression
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors* / therapeutic use
Lipoprotein(a)
Percutaneous Coronary Intervention*
Plaque, Atherosclerotic*
Registries
Risk Factors

Substances

Cholesterol, LDL
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Lipoprotein(a)

Associated data

ClinicalTrials.gov/NCT04864171