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Randomized Controlled Trial
. 2019 May 1;26(5):432-441.
doi: 10.5551/jat.45989. Epub 2018 Oct 15.

Cumulative Effects of LDL Cholesterol and CRP Levels on Recurrent Stroke and TIA

Kazuo Kitagawa  1 , Naohisa Hosomi  2 , Yoji Nagai  3 , Tatsuo Kagimura  4 , Toshiho Ohtsuki  5 , Hirofumi Maruyama  2 , Hideki Origasa  6 , Kazuo Minematsu  7 , Shinichiro Uchiyama  8 , Masakazu Nakamura  7 , Masayasu Matsumoto  2   9 ; J-STARS collaborators
Affiliations
Randomized Controlled Trial

Cumulative Effects of LDL Cholesterol and CRP Levels on Recurrent Stroke and TIA

Kazuo Kitagawa et al. J Atheroscler Thromb. .

Abstract

Aims: To investigate the relative contribution of on-treatment low-density lipoprotein (LDL) cholesterol and C-reactive protein (CRP) to the risk of recurrent stroke and transient ischemic attack (TIA) in patients with history of ischemic stroke.

Methods: A total of 1095 patients with non-cardioembolic ischemic stroke were randomized into two groups: control and patients receiving 10 mg of pravastatin per day. After excluding 18 patients who did not have baseline CRP data, the effects of LDL cholesterol and CRP on recurrent stroke and TIA were prospectively assessed in 1077 patients.

Results: During the follow-up of 4.9±1.4 years, there were 131 recurrent stroke or TIA cases. Patients with ontreatment LDL cholesterol ＜120 mg/dL showed 29% reduction in recurrent stroke and TIA than those with LDL cholesterol ≥ 120 mg/dL (event rate 2.20 vs. 3.11 per 100 person-years, hazard ratio [HR] 0.71, 95% confidence interval (CI) 0.50-0.99, p＝0.048). Patients with CRP ＜1 mg/L had 32% reduction compared with that of patients with CRP ≥ 1 mg/L (event rate 2.26 vs. 3.40 per 100 person-years; HR 0.68, 95% CI 0.48-0.96, p＝0.031). Although LDL cholesterol and CRP levels were not correlated in individual patients, those who achieved both LDL cholesterol ＜120 mg/dL and CRP ＜1 mg/L showed 51% reduction compared with that of patients with LDL cholesterol ≥ 120 mg/dL and CRP ≥ 1 mg/L (event rate 2.02 vs. 4.19 per 100 person-years; HR 0.49, 95% CI 0.31-0.79).

Conclusions: The control of both LDL cholesterol and CRP levels appears to be effective for preventing recurrent stroke and TIA in patients with non-cardiogenic ischemic stroke.

Keywords: Cholesterol; Crp; Inflammation; Statin; Stroke prevention.

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Conflict of interest statement

KK serves on the speakers' bureau of Takeda Pharmaceutical Company Limited, Nippon Boehringer Ingelheim Co., Ltd., Daiichi Sankyo Company, Limited, MSD K.K., Mitsubishi Tanabe Pharma Corporation, Shionogi & Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., Astellas Pharma Inc., Kyowa Hakko Kirin Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Sanofi K.K., Shionogi Inc., Pfizer Inc., Bristol-Myers Squibb Company, Bayer Yakuhin, Ltd., received research grant from Grants-in-Aid for Scientific Research (15H04844), Takeda Pharmaceutical Company Limited, Nippon Boehringer Ingelheim Co., Ltd., Daiichi Sankyo Company, Limited, MSD K.K., Sumitomo Dainippon Pharma Co., Ltd., Astellas Pharma Inc., AstraZeneca K.K., Kyowa Hakko Kirin Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Sanofi K.K., Eisai Co., Ltd, Pfizer Inc., and Bayer Yakuhin, Ltd. NH serves on the speakers' bureau of Mochida Phamaceutical Co., Ltd. HM received research grant from Daiichi Sankyo Company, Eisai Co., Ltd, Pfizer Inc., Takeda Pharmaceutical Company Limited, Otsuka Inc., Nihon Pharmaceutical, Shionogi, Teijin Pharma, Fuji Film, Nippon Boehringer Ingelheim Co., Ltd., Limited, Nihon Medi-Physics, Bayer Yakuhin, Ltd., MSD K.K., Kyowa Hakko Kirin Co., Ltd., Novartis, Mitsubishi Tanabe Pharma. KM serves on the speakers' bureau of Otsuka Pharmaceutical Co., Ltd., Bayer Yakuhin,. SU serves on the speakers' bureau of Boehringer Ingelheim, Bristol-Myers Squibb, and Bayer Yakuhin MM serves on the speakers' bureau of Takeda Pharmaceutical Company Limited, Nippon Boehringer Ingelheim Co., Ltd., Daiichi Sankyo Company, Limited, MSD K.K., Sumitomo Dainippon Pharma Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Sanofi K.K., Bristol-Myers Squibb Company, Bayer Yakuhin, Ltd., Novartis Pharma K.K., received research grant from Daiichi Sankyo Company, Eisai Co., Ltd, Pfizer Inc., Takeda Pharmaceutical Company Limited, Otsuka Inc., Nihon Pharmaceutical, Nippon Boehringer Ingelheim Co., Ltd., Limited, Nihon Medi-Physics, Bayer Yakuhin, Ltd., MSD K.K., Mitsubishi-Tanabe Pharma, Shionogi IncOther authors had no conflicts of interest.

Figures

Fig. 1.
Fig. 1.
Trial profile
Fig. 2.
Fig. 2.
Relationship between LDL cholesterol and CRP levels at baseline and on treatment, and relationship between changes in the CRP and LDL cholesterol levels after treatment in the statin group
Fig. 3.
Fig. 3.
(A) The cumulative incidence of recurrent stroke and TIA according to on-treatment LDL cholesterol levels (above or below 100 mg/dL). (B) The cumulative incidence of recurrent stroke and TIA according to on-treatment LDL cholesterol levels (above or below 120 mg/dL). (C) The cumulative incidence of recurrent stroke and TIA according to on-treatment CRP levels (above or below 1 mg/L).
Fig. 4.
Fig. 4.
(A, C) Patients enrolled within 6 months after index stroke (early cohort): (B, D) Patients enrolled after 6 months since index stroke (late cohort). (A, B) The cumulative incidence of recurrent stroke and TIA according to on-treatment CRP levels (above or below 1 mg/L). (C, D) The cumulative incidence of recurrent stroke and TIA according to on-treatment LDL cholesterol levels (above or below 120 mg/dL).
Fig. 5.
Fig. 5.
Annual event rate in four groups according to on-treatment levels of LDL cholesterol (above or below 120 mg/dL) and CRP (above or below 1 mg/L).
See this image and copyright information in PMC

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