SAN DIEGO—New data suggest that blood pressure variability is not associated with the risk of recurrent stroke, according to an analysis presented at the 2014 International Stroke Conference. Study results also do not indicate an association between blood pressure variability and ischemic events, hemorrhagic events, or a composite of vascular events.
The investigators did find, however, an association between blood pressure variability and an increased risk of all-cause mortality, said Thalia Field, MD, of the University of Calgary in Canada. Each additional mm Hg of blood pressure variability was associated with a 5% increased risk of all-cause mortality. But, given that the directionality of this relationship is uncertain, blood pressure variability “isn’t necessarily the complete driver for the increase in mortality associated with variability,” said Dr. Field.
Thalia Field, MD
An Analysis of Patients Enrolled in SPS3
To characterize overall visit-to-visit blood pressure variability and to investigate its association with vascular outcomes, Dr. Field and her colleagues analyzed data for patients enrolled in the Secondary Prevention of Small Subcortical Strokes (SPS3) trial. In SPS3, a secondary prevention study, researchers randomized patients with symptomatic lacunar infarcts within 180 days of their event. Patients were randomized in two-by-two factorial design to single versus dual antiplatelet therapy, as well as to higher versus lower blood pressure targets. The study’s primary outcome was recurrent stroke, and secondary outcomes included major vascular events, cognitive decline, and mortality.
Blood pressure was measured according to a well-characterized and previously validated protocol. The investigators examined blood pressure parameters such as systolic and diastolic blood pressure, mean arterial pressure, pulse pressure, and heart rate. Dr. Field and colleagues defined variability in accordance with several criteria, including SD, coefficient of variability, average real variability (ie, the absolute difference in blood pressure from one visit to another), and variability independent of mean (which is derived from curve-fitting SD as a function of mean). The researchers also examined the role of maximum blood pressure.
More than 2,600 patients and more than 36,000 blood pressure measurements were included in the analysis. Patients’ mean age was 63, and nearly two-thirds of patients were male. The average participant had more than 13 follow-up visits over a mean of 3.7 years included in the analysis.
Maximum Systolic Pressure Was Not Associated With Recurrent Stroke
Patients’ mean blood pressure was 131 mm Hg over 72 mm Hg. Average real systolic variability from visit to visit was approximately 12 mm Hg, and average real diastolic variability was 7 mm Hg. Maximum variability between groups was 151 mm Hg over 83 mm Hg. The variability measures were all highly correlated with one another, but only weakly correlated with mean blood pressure.
Dr. Field and colleagues found no association between blood pressure variability and risk of recurrent stroke. The results of the analysis did not change when the investigators grouped patients according to their blood pressure targets.
Previous studies have suggested that maximal systolic blood pressure is more predictive of vascular risk than blood pressure variability. In the SPS3 cohort, however, maximum systolic blood pressure was associated with an increased risk of all-cause mortality, but not with risk of recurrent stroke or major vascular events.
“One of the strengths of our cohort is that this is a large, well-characterized population with a stroke mechanism that is more or less homogeneous,” said Dr. Field. “The blood pressure protocol in SPS3 was also quite well-defined. Furthermore, because patients in SPS3 were medically optimized in accordance with a blood pressure target, as opposed to simply being treated with a particular antihypertensive, we have more of a perspective with regard to the role of variability in an actively treated stroke population.”
Because patients in SPS3 were medically optimized during the trial, their blood pressure variability has multiple causes besides physiologic or pathophysiologic mechanisms. For example, variability in compliance may have contributed to changes in patients’ blood pressure from visit to visit. “The nature of blood pressure control in SPS3, which was both dynamic and intensive, may have precluded us from detecting the association that has been seen in previous stroke prevention cohorts,” Dr. Field concluded.
—Erik Greb