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

Eur Heart J. 2010 Dec;31(23):2897-908. doi: 10.1093/eurheartj/ehq328. Epub 2010 Sep 16.

Abstract

Aim: In 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 results: We evaluated 10 001 patients with CAD and a low-density lipoprotein (LDL) cholesterol level <130 mg/dL, randomized to atorvastatin 80 vs. 10 mg, enrolled 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.

Conclusion: In patients with CAD, a low BP (<110-120/<60-70 mmHg) portends an increased risk of future cardiovascular events (except stroke).

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antihypertensive Agents / administration & dosage*
  • Atorvastatin
  • Blood Pressure / physiology*
  • Coronary Disease / etiology
  • Coronary Disease / mortality
  • Coronary Disease / physiopathology
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Heart Arrest / etiology
  • Heart Arrest / mortality
  • Heart Arrest / physiopathology
  • Heptanoic Acids / administration & dosage*
  • Humans
  • Hypertension / drug therapy*
  • Hypertension / mortality
  • Hypertension / physiopathology
  • Male
  • Middle Aged
  • Myocardial Infarction / etiology
  • Myocardial Infarction / mortality
  • Myocardial Infarction / physiopathology
  • Pyrroles / administration & dosage*
  • Risk Factors
  • Stroke / etiology
  • Stroke / mortality
  • Stroke / physiopathology
  • Treatment Outcome

Substances

  • Antihypertensive Agents
  • Heptanoic Acids
  • Pyrroles
  • Atorvastatin