J-curve revisited: An analysis of blood pressure and cardiovascular events in the Treating to New Targets (TNT) Trial

Sripal Bangalore, Franz H. Messerli, Chuan Chuan Wun, Andrea L. Zuckerman, David Demicco, John B. Kostis, John C. Larosa

Research output: Contribution to journalArticlepeer-review

266 Scopus citations


AimIn patients with coronary artery disease (CAD), a J-curve relationship has been reported between blood pressure (BP) and future cardiovascular events. However, this is controversial. The purpose of the study was to determine the relationship between on-treatment BP and cardiovascular outcomes in patients with CAD. Methods and resultsWe evaluated 10 001 patients with CAD and a low-density lipoprotein (LDL) cholesterol level <130 mg/dL, randomized to atorvastatin 80 vs. 10 mg, enroled in the TNT trial. The post-baseline, time-dependent BPs [systolic blood pressure (SBP) and diastolic blood pressure (DBP)] were categorized into 10 mmHg increments. The primary outcome was a composite of death from coronary disease, non-fatal myocardial infarction (MI), resuscitated cardiac arrest, and fatal or non-fatal stroke. Among the 10 001 patients, 982 (9.82) experienced a primary outcome at 4.9 years (median) of follow-up. The relationship between SBP or DBP and primary outcome followed a J-curve with increased event rates above and below the reference BP range, both unadjusted and adjusted (for baseline covariates, treatment effect, and LDL levels). A time-dependent, non-linear, multivariate Cox proportional hazard model identified a nadir of 146.3/81.4 mmHg where the event rate was lowest. A similar non-linear relationship with a higher risk of events at lower pressures was found for most of the secondary outcomes of all-cause mortality, cardiovascular mortality, non-fatal MI, or angina. However, for the outcome of stroke, lower was better for SBP. ConclusionIn patients with CAD, a low BP (<110-120/<60-70 mmHg) portends an increased risk of future cardiovascular events (except stroke).

Original languageEnglish (US)
Pages (from-to)2897-2908
Number of pages12
JournalEuropean Heart Journal
Issue number23
StatePublished - Dec 2010

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


  • Blood pressure
  • J-Curve
  • TNT trial


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