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Demonstrating the pharmacogenetic effects of angiotensin-converting enzyme inhibitors on long-term prognosis of diastolic heart failure

The Pharmacogenomics Journal volume 10, pages 46–53 (2010)Cite this article

Abstract

The objective of this study was to evaluate the effects of angiotensin-converting enzyme (ACE) inhibitors and pharmacogenetic interaction on the survival of the patients with diastolic heart failure (DHF). A total of 285 subjects with DHF confirmed by echocardiography were recruited in the period between 1995 and 2003. Baseline characteristics (age, sex, prior history, medication, and echocardiographic findings) and genetic polymorphisms (ACE gene insertion/deletion (I/D) polymorphism; T174M, M235T, G-6A, A-20C, G-152A, and G-217A polymorphisms of the angiotensinogen (AGT) gene; and A1166C polymorphisms of the angiotensin II type I receptor (AT1R)) were collected and matched (by propensity score) in those who received and those who did not receive ACE inhibitors. The patients were followed up to 10 years. Kaplan–Meier curves and Cox regression models were used to demonstrate the survival trend. The 85 patients who received ACE inhibitors and the other 85 patients who did not were found to have comparable baseline characteristics and polymorphism distribution. Prescription of ACE inhibitors was associated with a significant decrease in overall mortality (hazard ratio (HR), 0.45; 95% confidence interval (CI), 0.24–0.83; P=0.01), and a lower rate of cardiovascular events at 4000 days (HR, 0.53; 95% CI, 0.32–0.90; P=0.02). In addition, ACE I/D gene D allele was associated with higher overall mortality as compared with the I allele (HR, 2.04; P=0.003). This effect was diminished in those who received ACE inhibitors. The use of ACE inhibitor was associated with a significant decrease in long-term mortality and cardiovascular events in the patients with DHF. Genetic variants in the renin-angiotensin system genes were also associated, but their effects could be modified by the use of ACE inhibitors.

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Acknowledgements

We are indebted to the study coordinators who enrolled the patients from National Taiwan University Hospital and its affiliations.

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Author notes

  1. C-K Wu and J-L Luo: These two authors contributed equally to this work.

Authors and Affiliations

  1. Department of Internal Medicine, National Taiwan University Hospital, Yun-Lin Branch, Yun-Lin, Taiwan

    C-K Wu, J-W Lin & J-J Hwang

  2. Division of Cardiology, Department of Internal Medicine, National Taiwan University College of Medicine and Hospital, Taipei, Taiwan

    C-K Wu, C-T Tsai, C-L Cheng, J-K Lee, L-Y Lin, J-J Hwang & F-T Chiang

  3. Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University Hospital, Taipei, Taiwan,

    C-K Wu

  4. Departments of Internal Medicine and Health, Keelung Hospital, Keelung, Taiwan

    J-L Luo

  5. Department of Family Medicine, Mackay Memorial Hospital, Taipei, Taiwan

    Y-T Huang

  6. Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan

    J-K Lee & F-T Chiang

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  1. C-K Wu
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Correspondence to J-W Lin or F-T Chiang.

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Wu, CK., Luo, JL., Tsai, CT. et al. Demonstrating the pharmacogenetic effects of angiotensin-converting enzyme inhibitors on long-term prognosis of diastolic heart failure. Pharmacogenomics J 10, 46–53 (2010). https://doi.org/10.1038/tpj.2009.39

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