American Journal of Cardiology
Volume 106, Issue 6 , Pages 764-769, 15 September 2010

Relation of Elevated Plasma Renin Activity at Baseline to Cardiac Events in Patients With Angiographically Proven Coronary Artery Disease

  • Joseph B. Muhlestein, MD

      Affiliations

    • Intermountain Medical Center, Murray, Utah
    • University of Utah, Salt Lake City, Utah
    • Corresponding Author InformationCorresponding author: Tel: (801) 507-4701; fax: (801) 507-4789
  • ,
  • Heidi T. May, PhD

      Affiliations

    • Intermountain Medical Center, Murray, Utah
  • ,
  • Tami L. Bair, BS

      Affiliations

    • Intermountain Medical Center, Murray, Utah
  • ,
  • Margaret F. Prescott, PhD

      Affiliations

    • Novartis Pharmaceuticals Corporation, East Hanover, New Jersey
  • ,
  • Benjamin D. Horne, PhD

      Affiliations

    • Intermountain Medical Center, Murray, Utah
    • University of Utah, Salt Lake City, Utah
  • ,
  • Richard White, PhD

      Affiliations

    • Research Evaluation Unit, Oxford PharmaGenesis Ltd., Oxford, United Kingdom
  • ,
  • Jeffrey L. Anderson, MD

      Affiliations

    • Intermountain Medical Center, Murray, Utah
    • University of Utah, Salt Lake City, Utah

Received 21 January 2010; received in revised form 23 April 2010 published online 02 August 2010.

Plasma renin activity (PRA) is a measure of renin–angiotensin system activity and is associated with cardiovascular outcomes in patients with heart failure (HF). We conducted a prospective analysis to assess whether elevated baseline PRA is associated with cardiovascular outcomes in 1,165 patients with coronary artery disease (≥70% stenosis on the coronary angiogram) enrolled in the Intermountain Heart Collaborative Study. The exclusion criteria included previous myocardial infarction (MI) or HF, ejection fraction ≤45%, and a discharge diagnosis of MI/β-blocker treatment. Baseline PRA measurements were evaluated as risk categories (≤0.50, 0.51 to 2.30, and >2.30 ng/ml/h) and as tertiles (≤0.40, 0.41 to 1.90, and ≥1.90 ng/ml/h). Predefined cardiovascular outcomes were assessed for a minimum follow-up of 3 years (mean 6.4 ± 3.2, maximum 14.6) using Cox regression analysis to adjust for the baseline characteristics. The mean patient age was 64.4 years; most patients were men (73.1%) and hypertensive (63.2%). Elevated baseline PRA (high vs low category; >2.30 vs ≤0.50 ng/ml/h) was associated with a significantly increased risk of 3-year cardiac morbidity/mortality (hazard ratio 1.96; p = 0.004), MI (hazard ratio 2.41; p = 0.02), HF hospitalization (hazard ratio 4.39; p = 0.03), and all-cause death (hazard ratio 1.80; p = 0.01). Elevated baseline PRA was also associated with longer-term HF hospitalization (hazard ratio 2.12; p = 0.004) and all-cause death (hazard ratio 1.56; p = 0.002). Similar results were observed for the PRA tertiles. The association of PRA with outcomes was observed after correction for hypertension, hyperlipidemia, diabetes, a family history of cardiovascular events, smoking, renal failure, and the use of statins. In conclusion, elevated baseline PRA is associated with cardiac morbidity and mortality in patients with coronary artery disease but normal left ventricular function and no previous MI or HF.

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 This study was supported by Novartis Pharmaceuticals Corporation, East Hanover, New Jersey.

 Dr. Muhlestein has served on speakers' bureaux for Bristol-Myers Squibb, GSK, Merck, Novartis, and Sanofi-Aventis. Dr. Prescott is an employee of Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, and is thus eligible for Novartis stock and stock options. Dr. White is an employee of Oxford PharmaGenesis Ltd., which has received project funding from Novartis Pharmaceuticals Corporation, East Hanover, New Jersey.

PII: S0002-9149(10)01036-2

doi:10.1016/j.amjcard.2010.04.040

American Journal of Cardiology
Volume 106, Issue 6 , Pages 764-769, 15 September 2010