Preventive cardiology
Relation of Coronary Atherosclerosis Determined by Electron Beam Computed Tomography and Plasma Levels of N-terminal Pro-Brain Natriuretic Peptide in a Multiethnic Population-Based Sample (The Dallas Heart Study)

https://doi.org/10.1016/j.amjcard.2005.06.073Get rights and content

Elevated plasma levels of B-type natriuretic peptide (BNP) and N-terminal pro-BNP (NT–pro-BNP) are seen in the setting of cardiac ischemia and are associated with adverse outcomes in patients with coronary artery disease. The mechanisms leading to natriuretic peptide elevation in patients with coronary artery disease, including the contribution of coronary atherosclerosis itself, have not been fully elucidated. Measurement of NT–pro-BNP, electron beam computed tomography, and cardiac magnetic resonance imaging were performed in 2,445 subjects from the Dallas Heart Study who were free of heart failure and renal insufficiency. Electron beam computed tomography–determined coronary artery calcium scores were categorized as none (<10), mild (≥10 to <100), moderate (≥100 to <400), and severe (≥400). NT–pro-BNP levels increased significantly across increasing coronary artery calcium score categories (p <0.0001 for trend). In multivariate models adjusted for age, gender, race, body mass index, hypertension, history of myocardial infarction, angina, angiotensin-converting enzyme inhibitor use, β-blocker use, left ventricular (LV) ejection fraction, and LV mass, higher coronary artery calcium scores remained independently associated with higher log NT–pro-BNP levels (p = 0.03). This association persisted in similar models excluding patients with low LV ejection fractions, LV hypertrophy, angina pectoris, and a history of myocardial infarction. In conclusion, these findings support the hypothesis that coronary atherosclerosis may directly influence the activation of the cardiac neurohormonal system.

Section snippets

Study population

The Dallas Heart Study is a population-based, multiethnic, probability sample of subjects in Dallas County. Details of the study design and the characteristics of the enrolled cohort have been previously described.13 All participants provided informed consent to participate in the study, and the Institutional Review Board of the University of Texas Southwestern Medical Center approved the study protocol. The study involved 3 separate visits, with the first consisting of field interviews and

Results

Subjects with older age, female gender, non-black race, lower body mass index, history of hypertension, myocardial infarction, or angina, use of angiotensin-converting enzyme inhibitors or β blockers, reduced LV ejection fraction, and LV hypertrophy had significantly higher plasma levels of NT–pro-BNP than subjects not meeting these criteria (Table 1). In contrast, no association was observed between diabetes mellitus, tobacco use, and hypercholesterolemia and plasma NT–pro-BNP levels.

Discussion

In a large and carefully phenotyped population-based cohort, we have demonstrated for the first time an independent association between the burden of coronary atherosclerosis, as measured by EBCT, and circulating levels of NT–pro-BNP. This association persisted after adjusting for LV structural and functional parameters, a history of myocardial infarction, and symptoms of angina pectoris, suggesting that atherosclerosis itself may stimulate natriuretic peptide synthesis and release. In

Acknowledgment

We thank Ronald Peshock, MD, for his interpretation of the cardiac magnetic resonance imaging results and Teresa Eversole, BS, for her administrative aid and Jody Balko, MMSc, for running the NT–pro-BNP assays. Reagents for NT–pro-BNP were provided by Roche Diagnostics, Indianapolis, Indiana.

References (30)

  • M.S. Sabatine et al.

    Acute changes in circulating natriuretic peptide levels in relation to myocardial ischemia

    J Am Coll Cardiol

    (2004)
  • B. Palumbo et al.

    Usefulness of brain natriuretic peptide levels to discriminate patients with stable angina pectoris without and with electrocardiographic myocardial ischemia and patients with healed myocardial infarction

    Am J Cardiol

    (2004)
  • A. Ruck et al.

    ANP and BNP but not VEGF are regionally overexpressed in ischemic human myocardium

    Biochem Biophys Res Commun

    (2004)
  • J.A. de Lemos et al.

    The prognostic value of B-type natriuretic peptide in patients with acute coronary syndromes

    N Engl J Med

    (2001)
  • T. Omland et al.

    N-terminal pro-B-type natriuretic peptide and long-term mortality in acute coronary syndromes

    Circulation

    (2002)
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    This study was supported by the Donald W. Reynolds Foundation, Dallas, Texas, and Roche Diagnostics, Indianapolis, Indiana, and partially supported by USPHS GCRC grant M01-RR00633 from the National Institutes of Health/NCRR-CR, Bethesda, Maryland. Dr. de Lemos was supported by grants and received consulting fees from Roche Diagnostics, Indianapolis, Indiana.

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