SPRINT (Systolic Blood Pressure Intervention Trial) is a landmark trial conducted by the National Institutes of Health (NIH), which provided critical insights into the effect a lower blood pressure target (i.e. <120mmHg) had on reducing heart disease risk.1 Regardless of the study’s clear findings of better overall outcomes with intensive treatment, an aggressive blood pressure lowering could also be associated with risks, one of which includes an increased risk of stroke through cerebral hypoperfusion.2 Nonetheless, in the 142nd Annual Meeting of the American Neurological Association (ANA), the post-hoc analysis of SPRINT, as presented by Prof. Jack Tsao, the Department of Neurology, the University of Tennessee Health Science Center, has reassured physicians that an aggressive systolic blood pressure (SBP) control was not linked to an increased stroke risk.2
SPRINT-based blood pressure targets
As covered by another article named “2017 ACC/AHA Guidelines: Hypertension Starts at 130/80” in this issue of OmniHealth Practice, the new blood pressure guidelines now define hypertension as 130/80mmHg, while putting a yellow light (i.e. elevated BP) for people with SBP 120-129mmHg and DBP (diastolic BP) <80mmHg.3 This proposition of a tighter blood pressure control relative to the prior standard (140/90mmHg) represents partial acceptance of the SPRINT trial data that was first published in the New England Journal of Medicine in 2015.1
The main findings showed that among 9,361 patients enrolled in SPRINT (aged >50 years, with SBP>130mmHg, who were at high risk for cardiovascular events), those treated to a SBP target of <120mmHg had a significantly lower rate of the primary composite outcome of myocardial infarction, other acute coronary syndromes, stroke, heart failure, or death from cardiovascular causes, than those treated to a SBP target of <140mmHg (1.65% vs 2.19% per year; HR for intensive treatment=0.75; 95% CI: 0.64-0.89; p<0.001; Figure 1A).1 In addition, the intensive-treatment group had a significantly lower all-cause mortality (HR=0.73; 95% CI: 0.60-0.90; p=0.003; Figure 1B).1
While the SPRINT trial had made a strong argument that a SBP target of <120mmHg should be attained, the results were received with some controversies in the medical community, including safety concerns of possible harms due to hypotension. 2,4 Indeed, a higher rate of hypotension was reported in the intensive treatment group, which could have resulted in decreased cerebral perfusion pressure and increased stroke risk. 2 This may particularly be an issue since the automated measurement systems used in the study consistently resulted in readings lower than what patients typically see in a physician’s office (routine manual measurements), meaning that a standard of 120mmHg would be an overshoot. 4
Intensive blood pressure lowering and the risk of stroke
To better assess this safety concern, Dr. Tsao and his team further evaluated the data on 8,844 participants enrolled in SPRINT, and the changes in mean arterial pressure (MAP) and pulse pressure (PP) on stroke and syncope were investigated.2
Dr. Tsao explained that the patients’ lowest MAP and PP were used for the analysis. During a median follow-up of 3.26 years, there were 132 stroke cases (1.49%) and 187 syncope cases (2.1%).2 The mean minimal MAP was 78.21mmHg and mean minimal PP was 45.1mmHg. While there was an increased risk for hypotension and syncope with lower MAP and PP, neither increased the stroke risk.2
In line with the main findings of SPRINT, this analysis also reaffirmed that an increase in blood pressure is associated with poor outcomes: the stroke risk increased ~30% with every 5mmHg increase in MAP or PP (adjusted HR=1.31, 95% CI: 1.18–1.45 [for MAP]; HR=1.30, 95% CI: 1.19–1.42 [for PP]). 2 In addition, there was a 39% (HR=1.39, 95% CI: 1.27–1.51) and 14% (HR=1.14; 95% CI: 1.06–1.23) increase in syncope risk with every 5mmHg increase in MAP and PP, respectively.2
“We thought we would see an increased stroke risk with low MAP, so we were actually very happy to find that our primary hypothesis — that there would be an increased stroke risk — was not confirmed,” Dr. Tsao said. 5
“[Our findings suggest that] aggressive treatment to get systolic blood pressure under 120mmHg is a good thing… clinicians can safely lower systolic blood pressure when treating patients with hypertension without worrying that they will inadvertently cause a stroke through cerebral hypoperfusion by lowering blood pressure too much,” concluded Dr. Tsao. 5
SPRINT: A major impact on hypertension management?
With regard to the heated debate on the validity of blood pressure measurements in the SPRINT trial, Dr. Tsao has expressed confidence in the quality of data collected. “We’ve talked with the company that made the monitors for the SPRINT study and found that the measurement of SBP was an actual value while DBP was derived,” Dr. Tsao said. 5
Dr. Tsao further elaborated, “we also found out that there was a good correlation between manual measurements of both systolic and diastolic blood pressure and the automated system, so that systolic and diastolic blood pressure measurements of the system used were within 1 to 3mmHg.” 5 Thus, Dr. Tsao believed that their approach is valid, “automated blood pressure is the approach used by most medical centers and any therapy uses these measurements to adjust therapy in practice.”5
Collectively, this study demonstrated that aggressive blood pressure lowering did not result in a higher stroke rate, even from a theoretical hypoperfusion perspective, which is surely reassuring to physicians in implementing a stringent blood pressure control in daily practice.
1. Wright JT, Jr., Williamson JD, Whelton PK, et al. A Randomized Trial of Intensive versus Standard Blood-Pressure Control. N Engl J Med 2015;373:2103-16.
2. Tsao JW, Gibney KD, Wang J, et al. Lowering Systolic Blood Pressure Does Not Increase Stroke Risk: An Analysis of the Systolic Blood Pressure Intervention Trial (SPRINT) Data. American Neurological Association; 2017; San Diego, California. Abstract#M150.
3. Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol 2017. [Epub ahead of print]
4. Bakris G. Response by Bakris to Letter Regarding Article, “The Implications of Blood Pressure Measurement Methods on Treatment Targets for Blood Pressure”. Circulation 2017;135:e47.
5. No Increased Stroke Risk With Intensive Systolic BP Lowering. Medscape, 2017. (Accessed December 18, 2017, at https://www.medscape.com/viewarticle/887446_print.)