J Curve in Patients Randomly Assigned to Different Systolic Blood Pressure Targets: An Experimental Approach to an Observational Paradigm

Circulation. 2017 Dec 5;136(23):2220-2229. doi: 10.1161/CIRCULATIONAHA.117.030342. Epub 2017 Sep 22.


Background: Low systolic blood pressure (SBP) values are associated with an increased risk of cardiovascular events, giving rise to the so-called J-curve phenomenon. We assessed the association between on-treatment SBP levels, cardiovascular events, and all-cause mortality in patients randomized to different SBP targets.

Methods: Data from 2 large randomized trials that randomly allocated hypertensive patients at high risk for cardiovascular disease to intensive (SBP<120 mm Hg) or conventional (SBP<140 mm Hg) treatment were pooled and harmonized for outcomes and follow-up duration. Using natural cubic splines, we plotted the hazard ratio for all-cause mortality and cardiovascular events against the mean on-treatment SBP per treatment group.

Results: The pooled data consisted of 194 875 on-treatment SBP measurements in 13 946 patients (98.9%). During a median follow-up of 3.3 years, cardiovascular events occurred in 1014 patients (7.3%), and 502 patients died (3.7%). For both blood pressure targets, an identical shape of the J curve was present, with a nadir for cardiovascular events and all-cause mortality just below the SBP target. Patients in the lowest SBP stratum were older, had a higher body mass index, smoked more often, and had a higher frequency of diabetes mellitus and cardiovascular events.

Conclusions: Low on-treatment SBP levels are associated with increased cardiovascular events and all-cause mortality. This association is independent of the attained blood pressure level because the J curve aligns with the SBP target. Our results suggest that the benefit or risk associated with intensive blood pressure-lowering treatment can be established only via randomized clinical trials.

Clinical trial registration: URL: https://www.clinicaltrials.gov. Unique identifiers: NCT01206062 and NCT00000620.

Keywords: blood pressure; cardiovascular system; diabetes mellitus; hypertension.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Antihypertensive Agents / adverse effects
  • Antihypertensive Agents / therapeutic use*
  • Blood Pressure / drug effects*
  • Cause of Death
  • Female
  • Humans
  • Hypertension / diagnosis
  • Hypertension / drug therapy*
  • Hypertension / mortality
  • Hypertension / physiopathology
  • Male
  • Middle Aged
  • Risk Assessment
  • Risk Factors
  • Systole
  • Time Factors
  • Treatment Outcome


  • Antihypertensive Agents

Associated data

  • ClinicalTrials.gov/NCT01206062
  • ClinicalTrials.gov/NCT00000620