The J-curve in Patients Randomly Assigned to Different Systolic Blood Pressure Targets - an Experimental Approach to an Observational Paradigm
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 two large randomized trials that randomly allocated hypertensive patients at high-risk for cardiovascular disease to intensive (SBP<120 mmHg) or conventional treatment (SBP<140 mmHg) were pooled and harmonized for outcomes and follow-up duration. Using natural cubic splines, the hazard ratio for all-cause mortality and cardiovascular events was plotted against the mean on-treatment systolic blood pressure per treatment group.
Results—The pooled data consisted of 194,875 on-treatment SBP measurements in 13,946 (98.9%) patients. 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 BMI, smoked more often and had a higher frequency of diabetes 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 only be established via randomized clinical trials.
- hypertension, high blood pressure
- hypertension, low blood pressure
- cardiovascular research
- cardiovascular outcomes
- antihypertensive agent
- Received July 3, 2017.
- Revision received August 4, 2017.
- Accepted September 7, 2017.