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

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12 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)183-189
Number of pages7
Publication statusPublished - May 2022


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

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