Impact of Atorvastatin Treatment in First-Degree Relatives of Patients With Premature Coronary Artery Disease With Endothelial Dysfunction: A Double-Blind, Randomized, Placebo-Controlled Crossover Trial

Authors

  • Sung-Jin Hong MD,

    1. Division of Cardiology, Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
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  • Hyuk-Jae Chang MD, PhD,

    1. Division of Cardiology, Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
    2. Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Republic of Korea
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  • Sungha Park MD, PhD,

    1. Division of Cardiology, Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
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  • Dae Ryong Kang PhD,

    1. Division of Clinical Research Affairs, Yonsei University College of Medicine, Seoul, Republic of Korea
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  • Sanghoon Shin MD,

    1. Division of Cardiology, Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
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  • In-Jeong Cho MD,

    1. Division of Cardiology, Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
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  • Chi Young Shim MD, PhD,

    1. Division of Cardiology, Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
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  • Geu-Ru Hong MD, PhD,

    1. Division of Cardiology, Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
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  • Jong-Won Ha MD, PhD,

    1. Division of Cardiology, Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
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  • Namsik Chung MD, PhD

    1. Division of Cardiology, Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
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  • This work was supported by the National Research Foundation of Korea grant funded by the Korea government (MEST; no. 2012027176) and by the Chong Kun Dang Pharmaceutical Corp., Seoul, Korea. ClinicalTrials.gov: NCT00917527. The authors have no other funding, financial relationships, or conflicts of interest to disclose.

Address for correspondence:

Hyuk-Jae Chang,

MD Division of Cardiology

Severance Cardiovascular Hospital

Yonsei University Health System

250 Seongsanno, Seodaemun-gu Seoul 120-752, Korea

hjchang@yuhs.ac

Abstract

Background

A family history of premature coronary artery disease (CAD) is a well-known risk factor for cardiovascular events.

Hypothesis

Atorvastatin may improve endothelial dysfunction (ED) in the first-degree relatives (FDRs) of patients with premature CAD with ED.

Methods

Thirty-five FDRs (median age, 52 years [interquartile range (IQR), 46–57 years], 21 male) of patients with premature CAD with ED were recruited in a prospective trial with a crossover double-blind design: 6 weeks of treatment with atorvastatin 40 mg/day followed by placebo, or vice versa. After each treatment, the digital pulse wave amplitude was determined by EndoPAT to obtain the reactive hyperemia index (RHI), a measure for endothelial function. The primary outcome was the difference of RHI between atorvastatin and placebo treatment.

Results

Low-density lipoprotein cholesterol was lower after atorvastatin compared with placebo treatment (124 [102–145] mg/dL vs 67 [50–73] mg/dL, P < 0.001). However, RHI was not different after atorvastatin compared with placebo treatment (1.9 [1.5–2.4] vs 1.9 [1.6–2.2], P = 0.902). Also, the augmentation index was similar after each treatment. These results were observed both in subjects who had indications for statin treatment (31%) and those who did not (69%) according to National Cholesterol Education Program Adult Treatment Panel III guidelines.

Conclusions

Despite improvement in the lipid profile, atorvastatin failed to improve ED in the FDRs of patients with premature CAD with ED. Although we identified those with ED in FDRs of patients with premature CAD as a high-risk group for future cardiovascular events, atorvastatin treatment may not be a beneficial primary prevention strategy for this population.

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