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. 2019 Mar 1;26(3):272-281.
doi: 10.5551/jat.44735. Epub 2018 Aug 21.

Association of Decreased Docosahexaenoic Acid Level After Statin Therapy and Low Eicosapentaenoic Acid Level with In-Stent Restenosis in Patients with Acute Coronary Syndrome

Shusuke Yagi  1   2 , Daisuke Kondo  3 , Takayuki Ise  1 , Daiju Fukuda  4 , Koji Yamaguchi  1 , Tetsuzo Wakatsuki  1 , Yutaka Kawabata  1 , Hiroyuki Ito  1 , Yoshihito Saijo  1 , Hiromitsu Seno  1 , Kumiko Sutou  1 , Rie Ueno  1 , Takafumi Todoroki  1 , Kenya Kusunose  1 , Tomomi Matsuura  1 , Takeshi Tobiume  1 , Hirotsugu Yamada  1 , Takeshi Soeki  1 , Michio Shimabukuro  4   5 , Ken-Ichi Aihara  6 , Masashi Akaike  7 , Masataka Sata  1
Affiliations

Association of Decreased Docosahexaenoic Acid Level After Statin Therapy and Low Eicosapentaenoic Acid Level with In-Stent Restenosis in Patients with Acute Coronary Syndrome

Shusuke Yagi et al. J Atheroscler Thromb. .

Abstract

Aim: It is speculated that statin therapy modulates the synthesis of polyunsaturated fatty acids (PUFA), including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). However, the data available on the effects of statin therapy on the serum levels of PUFA and the subsequent impact on in-stent restenosis (ISR) in patients with acute coronary syndrome (ACS) are limited.

Methods: A total of 120 ACS patients who received emergent coronary stent implantation, follow-up coronary angiography to evaluate ISR, and new statin therapy were enrolled. We measured the serum levels of the PUFA and lipids at the onset of ACS and at the follow-up coronary angiography.

Results: The follow-up coronary angiography revealed 38 ISR cases. New statin therapy significantly reduced the serum levels of DHA and low-density lipoprotein cholesterol (LDL-C), while it did not affect EPA level. Single regression analysis revealed that a decreased serum level of LDL-C was associated with decreased DHA level. The multiple logistic regression analysis revealed that the decreased DHA level after statin therapy and low serum level of EPA on admission were determinants of prevalence of ISR.

Conclusion: Statin therapy decreased the serum level of DHA with a parallel reduction in LDL-C level in patients with ACS. Decreased DHA level after statin therapy and low EPA level on admission are risk factors for ISR, indicating that in patients with ACS, decreased serum levels of DHA may be a residual target for the prevention of ISR.

Keywords: Docosahexaenoic acid; Eicosapentaenoic acid; In-stent restenosis; Polyunsaturated fatty acids.

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Conflict of interest statement

M. Sata received research funding from Tanabe-Mitsubishi, Takeda, Astellas, Bayer Healthcare, Daiichi-Sankyo, MSD, and Ono, and lecture fees from Astellas, Boehringer Ingelheim, Bayer Healthcare, Mochida, Takeda, Tanabe-Mitsubishi, Novartis, AstraZeneca, MSD, and Shionogi. The Department of Cardio-Diabetes Medicine, Tokushima University Graduate School, is supported in part by unrestricted research grants from Actelion, Boehringer Ingelheim, Kowa, and Tanabe-Mitsubishi. The others declare no conflict of interest.

Figures

Fig. 1.
Fig. 1.
Flowchart of the study
Fig. 2.
Fig. 2.
Change in the levels and ratio of PUFA after statin therapy stratified by statin dosage (*p < 0.05 compared with low dosage) Δ: levels and ratio of PUFA on follow-up–levels and ratio of PUFA on ACS onset
Fig. 3.
Fig. 3.
Change in the levels and ratio of PUFA after statin therapy stratified by statin type Δ: levels of and ratio of PUFA on follow-up–levels of and ratio of PUFA on ACS onset Rosva, rosuvastatin; Pitava, pitavastatin; Atrova, atorvastatin; Prava, pravastatin; Fluva, fluvastatin.
Fig. 4.
Fig. 4.
Correlation between changes in low-density lipoprotein cholesterol and changes in docosahexaenoic acid Changes in the serum levels of DHA (DHA on follow-up–DHA on ACS onset) are correlated with changes in the LDL-C (LDL-C on follow-up–LDL-C on ACS onset).
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