J-Shaped Relationship between Blood Pressure and Mortality in Hypertensive Patients: New Insights from a Meta-Analysis of Individual-Patient Data

  1. Florent Boutitie, MSc;
  2. François Gueyffier, MD;
  3. Stuart Pocock, PhD;
  4. Robert Fagard, MD;
  5. Jean Pierre Boissel, MD; and
  6. for the INDANA Project Steering Committee
  1. From Claude Bernard University, Lyon, France; London School of Hygiene and Tropical Medicine, London, United Kingdom; and Leuven University, Leuven, Belgium.

    Abstract

    Background: Population-based longitudinal studies of hypertension have usually shown a continuous and positive relationship between blood pressure and mortality. However, several studies in hypertensive patients receiving treatment have described this relationship as J-shaped, with an increased risk for events in patients with low blood pressure.

    Objective: To assess the evidence for a J-shaped relationship between blood pressure and mortality and its relation to treatment.

    Design: Meta-analysis of individual-patient data.

    Setting: Seven randomized clinical trials from the INDANA (INdividual Data ANalysis of Antihypertensive intervention) database.

    Patients: 40 233 persons with hypertension (mean follow-up, 3.9 years).

    Intervention: Primarily β-blockers or thiazide diuretics versus placebo or no treatment.

    Measurements: Diastolic and systolic blood pressure and number of cardiovascular, noncardiovascular, and all-cause deaths in yearly periods of follow-up.

    Results: The analysis included data on 1655 deaths (56% cardiovascular). A J-shaped relationship between diastolic blood pressure and risk for death was observed for total and cardiovascular mortality in treated patients (nadir, 84 and 80 mm Hg, respectively) and untreated patients (nadir, 90 and 85 mm Hg, respectively). For noncardiovascular deaths, the relationship was J-shaped in the treated group (nadir, 84 mm Hg) and negative in the control group. Similar results were observed for systolic blood pressure. The presence of patients with wide pulse pressure did not explain these findings.

    Conclusions: The increased risk for events observed in patients with low blood pressure was not related to antihypertensive treatment and was not specific to blood pressure–related events. Poor health conditions leading to low blood pressure and an increased risk for death probably explain the J-shaped curve.

    Article and Author Information

    • Acknowledgments: The authors thank John Coope, Jeffrey Cuttler, Tord Ekbom, Lawrence Friedman, Mitchell Perry, Ronald Prineas, and Eleanor Schron for contributing data to the INDANA project.

    • Grant Support: By the European Community as part of the BIOMED 2 program (contract BMH4-CT98-3291).

    • Requests for Single Reprints: Florent Boutitie, MSc, EA643 Clinical Pharmacology Unit, Faculte RTH Laennec, BP 8071–69376 Lyon Cedex 08, France; e-mail, flb{at}upcl.univ-lyon1.fr.

    • Current Author Addresses: Mr. Boutitie and Drs. Gueyffier and Boissel: EA643 Clinical Pharmacology Unit, Faculte RTH Laennec, BP 8071–69376 Lyon Cedex 08, France.

    • Dr. Pocock: Medical Statistics Unit, London School of Hygiene and Tropical Medicine, Keppel Street, WC1E 7HT London, United Kingdom.

    • Dr. Fagard: Hypertension and Cardiovascular Rehabilitation Unit, University of Leuven, U.Z. Gasthuisberg, Herestraat 49, B-3000 Leuven, Belgium.

    • Author Contributions: Conception and design: F. Boutitie, F. Gueyffier, S. Pocock.

    • Analysis and interpretation of the data: F. Boutitie, F. Gueyffier, S. Pocock, R. Fagard, J.P. Boissel.

    • Drafting of the article: F. Boutitie, F. Gueyffier, J.P. Boissel.

    • Critical revision of the article for important intellectual content: F. Boutitie, F. Gueyffier, S. Pocock, R. Fagard.

    • Final approval of the article: F. Boutitie, F. Gueyffier, S. Pocock, R. Fagard.

    • Provision of study materials or patients: F. Gueyffier, R. Fagard.

    • Statistical expertise: F. Boutitie, S. Pocock.

    • Obtaining of funding: F. Gueyffier, J.P. Boissel.

    • Administrative, technical, or logistic support: F. Boutitie.

    • Collection and assembly of data: F. Gueyffier, R. Fagard, J.P. Boissel.

    Summary for Patients

    • Summaries for Patients:Relationship between Blood Pressure and Death among Treated Hypertensive Patients at the High and Low Ends of Blood Pressure Control Ann Intern Med March 19, 2002 136:I49
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    1. Ann Intern Med March 19, 2002 vol. 136 no. 6 438-448
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