ARTICLE IN BRIEF
Investigators reported that blood pressure even at the prehypertension level increases the risk of recurrent intracerebral hemorrhage.
WASHINGTON—Guidelines for blood pressure control after intracerebral hemorrhage (ICH) may need to be revised, based on results from the largest post-ICH follow-up study to date, researchers said here in a presentation of their findings at the AAN Annual Meeting.
The new analysis showed that even blood pressure at the prehypertension level increases the risk of recurrent ICH.
“Prior studies suggest that blood pressure reduction reduces the risk of recurrent ICH, but the problem is the optimal degree of reduction is poorly understood,” said the senior study author, Christopher Anderson, MD, an assistant professor of neurology at Massachusetts General Hospital and Harvard Medical School in Boston.
To better understand how blood pressure reduction affects that risk, Dr. Anderson, along with first author Alessandro Biffi, MD, and colleagues conducted a single-center observational study of consecutive ICH patients who were enrolled from 2004 to 2011 and followed until the end of 2013.
Ambulatory blood pressure was determined at three, six, nine, and 12 months, and then every six months thereafter. Patients who suffered another hemorrhage within three months of the index event were excluded, Dr. Anderson said, “because in our experience there is a lot of dirty data in there,” with expansion of the initial hemorrhage too often misinterpreted as a recurrent hemorrhage. Cerebellar hemorrhage patients were also excluded.
In all, there were 1,145 patients enrolled, including 505 with lobar hemorrhage and 640 with non-lobar hemorrhage. Recurrences occurred in 102 lobar patients and 42 non-lobar patients. In almost all cases, an index lobar ICH was followed by a recurrent lobar ICH, and an index non-lobar ICH by a recurrent non-lobar ICH.
The risk of recurrence was greater for both hemorrhage types in patients with non-European ancestry, fewer than 10 years of education, and a history of hemorrhage prior to the index event. In the non-lobar patients, a history of ischemic heart disease was also associated with increased risk of recurrence.
For the purposes of the study, blood pressure was considered in three different ways: adequate versus inadequate control, based on published guidelines for prevention of ICH recurrence; JNC-7 hypertension stage; and continuous systolic and diastolic blood pressure recording.
The guidelines, from the American Heart Association and American Stroke Association (AHA/ASA), establish a blood pressure goal of less than 140/90 mm Hg if the patient is nondiabetic, and 130/80 mm Hg if diabetes is present. JNC-7, from the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure, defines normotension as less than 120/80 mm Hg, prehypertension as greater than that but less than 140/90 mm Hg, stage 1 hypertension as greater than that but less than 160/100 mm Hg, and stage 2 hypertension as at or above 160/100 mm Hg.
“For both lobar and non-lobar patients, inadequate blood pressure control above the AHA/ASA guidelines was strongly predictive of hemorrhage recurrence,” Dr. Anderson said, with a hazard ratio of 3.53 for lobar patients and 4.23 for non-lobar patients.
There was a clear “dose-response” effect, with an increase in risk with each increase in JNC-7 stage compared with normotension. “Even prehypertension is strongly predictive, and the risk goes up from there,” he said. The hazard ratio for lobar ICH patients with prehypertension was 2.76, rising to 2.90 and 5.91 for stages 1 and 2, respectively. For non-lobar patients, the ratios were 3.06, 3.88, and 6.23.
For the continuous measurement of blood pressure, risk increased with each 10 mm Hg increase in systolic pressure for both groups of patients. An increase in diastolic pressure was associated with increased risk in non-lobar, but not lobar, patients.
“Elevated blood pressure post-ICH is associated with an increased risk of recurrent ICH for both lobar and non-lobar patients,” Dr. Anderson said, “and there is evidence for a dose-dependent relationship that includes all hypertension stages, including prehypertension. If we can confirm these findings with further studies, the current recommendations for blood pressure control after ICH may be inadequate for preventing recurrence.”
The challenge, he noted, is that reducing blood pressure may come at a cost of increasing the risk for ischemic stroke, ischemic heart failure, renal failure, syncope, and falls.
“We certainly don't want to be preventing ICH while driving people toward these other adverse outcomes,” he said. “Clinical trials will be required to determine the optimal level of blood pressure reduction.”
Regarding the patient group as a whole, Dr. Anderson said, “One supposition would be that recurrent ICH may be an overt clinical manifestation of cerebral small vessel disease, which these patients clearly have.” Control of blood pressure may also help “prevent other manifestations of cerebral small vessel disease in this highly exposed population of ICH survivors, such as cognitive impairment, depression, and gait disorder.”
He also noted that, “even in the pretty medicalized environment of Boston, it is striking how many patients in each category are faced with pretty poor blood pressure control. This is kind of an eye opener for us.”
Kevin Sheth, MD, an associate professor of neurology and neurosurgery at Yale School of Medicine in New Haven, CT, where he is also division chief of neurocritical care and emergency neurology, praised the study. He said the trial was noteworthy for its size — far larger than others looking at similar outcomes — and for its focus on long-term outcomes, rather than the much more common 30 to 90-day survival studies.
“Acute interventions have been the focus of most treatment efforts, including preventing expansion of the hematoma, surgical evacuation, and neuroprotection,” said Dr. Sheth, who serves on the Neurology Today editorial advisory board.
That focus on short-term survival is not surprising, given that the one-year survival for both lobar and non-lobar ICH is less than 50 percent. But addressing recurrent ICH “may facilitate a new treatment approach to a clinically meaningful problem for ICH survivors,” Dr. Sheth said.
But like most good studies, this one raises as many questions as it answers. Among them, he said, is whether apolipoprotein E genotype plays a role in recurrence risk, as it does in risk for ischemic stroke. Perhaps more important, he said, is the question of “the impact of recurrent ICH on long-term functional outcome, rather than mortality. This is very much an open question.”
In addition, Dr. Sheth said, another question remains to be answered: What are the risks from aggressively lowering blood pressure in these patients, especially over the long term? Aggressive control is safe, he said, but is there a downside when looking at it longitudinally?
Dr. Sheth added that if recurrent ICH does have an impact on outcome, and if blood pressure is important to the risk for ICH, then it may be valuable to explore the use of more innovative methods to improve blood pressure control, including novel strategies such as renal denervation.
Finally, Dr. Sheth noted, a patient population such as this will also have a high incidence of ischemic stroke and transient ischemic attack, and it is challenging to determine the separate impacts of cerebral ischemia versus ICH on overall survival, cognition, and functional outcome. “But in order to effectively target intervention, it will be important to understand what the outcome is attributable to,” he said.