Article In Brief
A large US-based study of recurrence of intracerebral hemorrhage (ICH) found that black and Asian patients are at a higher risk of ICH recurrence than whites, and private insurance was associated with significant reduced risk.
Black and Asian patients have a higher risk of recurrent intracerebral hemorrhage (ICH) than do white patients, according to a new longitudinal analysis published online December 12, 2019, in Neurology.
The study was led by a multi-institutional team of researchers from the US and the UK, the largest such study of ICH recurrence in a diverse US-based population.
The study also found that patients with private insurance have a significantly reduced risk of recurrent hemorrhagic stroke compared with patients on Medicaid and Medicare.
“The issue of recurrence in ICH is a relatively new thing within the last decade,” sayd lead study author Kevin N. Sheth, MD, FAAN, professor of neurology and neurosurgery, associate chair for clinical research in the department of neurology, and division chief for neurocritical care and emergency neurology at Yale School of Medicine.
“Hemorrhagic stroke has been the deadliest stroke subtype, but over the years that mortality has declined. Now there are more survivors, and these issues surrounding what happens when you survive becomes more important. One of those issues is, what do we know about the chances of having another one?”
Multiple studies have investigated racial and ethnic disparities in ischemic stroke, as well as in first-ever ICH, which is the most devastating form of stroke, associated with severe disability in most survivors and a 40 percent case-fatality rate at one month. But only one previous study had assessed these disparities in recurrent ICH. It too found that black patients were at higher risk than whites, although it did not find the same increased risk in Asians and did identify an increased risk in Hispanics.
“On a large scale, our findings affirm these previous results suggesting that minority populations really are at higher risk for recurrent ICH compared to white populations,” Dr. Sheth said.
Study Design, Findings
In the new analysis, Dr. Sheth and his colleagues used 2005-2011 administrative claims data from the Healthcare Cost and Utilization Project California State Inpatient Database, which allows the tracking of individuals' hospitalizations over time in a large, racially and ethnically diverse population. All adult patients with a first-time diagnosis of ICH who survived to discharge and were California residents (to reduce bias related to lack of follow-up data) were included, unless they presented with a concurrent trauma diagnosis.
In the study population—comprising 31,355 patients with an ICH diagnosis who survived to discharge—1.4 percent, or 1,330 patients, experienced a recurrent ICH over a median follow-up of 2.9 years.
Compared with those who did not experience recurrence, patients with recurrent ICH were more likely to be black (11 percent vs 9 percent) or Asian (17 percent vs 14 percent, p=0.004). They were also less likely to have private insurance (18 percent vs 23 percent, p=0.001). Even after a sensitivity analysis excluding admissions with a concurrent diagnosis of infection within 30 days, black patients (HR 1.26; 95% CI 1.04-1.53; p=0.017) and Asians (HR 1.28; 95% CI 1.09-1.51; p=0.003) remained at an increased risk compared to whites, and those with private insurance remained at a reduced risk compared to patients with Medicare (HR 0.74; 95% CI 0.63- 0.86; p<0.001).
“The mechanisms underlying these racial/ethnic differences remain unclear but are likely mediated by socioeconomic factors that disproportionately impact minorities,” the study authors wrote.
“Socioeconomic status may influence access to healthcare, early detection of hypertension and compliance with antihypertensive medications, which in turn impact the risk of recurrent ICH. Prior studies have shown that racial and ethnic minorities are less likely to achieve recommended blood pressure goals. Further study of interventions to control blood pressure in ICH survivors at both the individual and population level is warranted.”
The insurance-related findings are consistent with several previous studies that have reported worse health outcomes in stroke patients with Medicaid and Medicare compared to those with private insurance. But the authors noted that it's difficult to tease out the underlying contributing factors. “...[I]t remains unknown whether these disparities represent true differences in the quality of care between insurance providers or if they represent confounding by baseline socioeconomic and health differences between groups,” they wrote.
“We have known for some time that there are various racial and ethnic disparities, as well as regional variation worldwide, in the incidence of ICH,” said Sebastian Koch, MD, professor of clinical neurology and chief of the stroke program at the University of Miami's Miller School of Medicine. “The highest rates of ICH are actually seen in Japan and China, which strongly suggests, perhaps, that there is some underlying biological reason why certain stroke subtypes may occur more frequently in some populations than others. What's particularly interesting about this study is that I think this is the first time that ICH in an Asian-American population was compared to other US racial and ethnic groups.”
“This paper confirms a lot of other data that we have regarding stroke in minority populations,” agreed Mitchell S. Elkind, MD, MS, FAAN, professor of neurology and epidemiology at Columbia University Vagelos College of Physicians and Surgeons in New York City and an attending neurologist on the Stroke Service at the NewYork-Presbyterian Hospital.
“What's unique about it is that it addresses hemorrhage and recurrent stroke, both of which are less common, so we have less data about those [conditions]. It also perhaps indirectly addresses the mechanism by which those disparities occur, because it suggests that patients with private insurance have a lower rate of recurrence than those with public insurance.”
But experts were cautious about placing too much emphasis on the results regarding insurance status. “There are significant confounding factors on this question,” said Matthew L. Flaherty, MD, a neurologist at the University of Cincinnati Neuroscience Institute, a member of the UC Stroke Team, and a professor of neurology at the UC College of Medicine.
“Patients who had recurrent ICH were less sick than patients who did not, suggesting that some of the sicker group died after discharge and were thus not at risk of recurrent hemorrhage. The recurrence group had shorter hospital stays, were less likely to be intubated, less likely to have a DNR order, and more likely to be discharged home. That suggests to me that this is a different population, probably influenced by medical comorbidities, and goals of care for these patients that might well differ in patients with different types of insurance status. This study could not identify patients who died outside the hospital. It's also likely there are unidentified socio-economic factors that differ by insurance status. Administrative databases in general are subject to things like coding errors, which is a limitation.”
Nonetheless, said Dr. Elkind, it is reasonable to suggest that neurologists should be aware of a potentially heightened risk of ICH recurrence in minority populations and those who may have less access to health care resources. “The underlying problem is often access to health care, whether it is doctor's visits or medications, so one may want to be especially attentive to those patients who may not have such access.”
“This paper adds evidence that despite our best attempts to adjust for common risk factors—things like age, blood pressure, smoking, diabetes, and so on—there is a component to stroke recurrence, including ICH, that may be based on the genetics behind race or ethnicity,” said Lee Birnbaum, MD, interim director of stroke at UT Health San Antonio.
“We can't change a person's genetics, but we can certainly focus on known risk factors for first-time and recurrent ICH, and the most significant risk factor across all races and ethnicities is hypertension. Blood pressure is not just a primary care issue: neurologists should always be involved in the treatment of hypertension for stroke prevention, particularly after an ICH.”
He noted that some blood pressure medications can be more or less effective in different populations, so the selection of these medications can be race- or ethnicity-specific. “We also know that the Asian population can have more intracranial atherosclerosis than other populations, and so that may be a group to target more aggressively with cholesterol-lowering medicines,” he said. “However, there is evidence that intense lowering of LDL and cholesterol may possibly increase the risk for recurrent ICH, so the verdict on just how aggressive to be about lowering cholesterol after an ICH is still out.”
At the clinician and practice level, treatment and management must take into consideration each patient's social situation, said Salvador Cruz-Flores, MD, FAAN, a stroke neurologist who is professor and founding chair of the department of neurology at Texas Tech University Health Sciences Center at El Paso.
“Consider the difficulties that this person may have to even get to your office and try to find ways to adapt and allow them access to care. We aren't in a position to give away medications, but sometimes we tend to use the expensive ones as opposed to cheaper ones that may have similar efficacy in controlling blood pressure. We need to have culturally appropriate plans to engage and educate different populations in the importance of adherence to treatment.”
Two secondary prevention trials for ICH survivors will be launching in 2020. ASPIRE is a randomized, double-blinded, phase 3 clinical trial designed to test the efficacy and safety of anticoagulation, compared with aspirin, in patients with a recent ICH. SATURN, a multicenter prospective, randomized, open-label, and blinded end-point assessment (PROBE) trial, aims to determine whether continuation vs. discontinuation of statin drugs after spontaneous lobar ICH is the best strategy.
“This is very exciting; there has never before been a secondary prevention trial in ICH in the United States,” said Dr. Sheth. “Now there are more survivors, and the nihilism in the field is being chipped away.”
Given this environment, Dr. Cruz-Flores suggests that the AAN and other professional societies should push to identify societal-level interventions to help narrow the disparities in access and outcomes identified by the new paper and the larger body of evidence around stroke care. “That's where we can do better and where we are probably failing,” he says. “For example, the AAN could develop evidence-based guidelines to manage stroke recurrence in underserved populations. There must be a way that we as a society can manage these recurring and disproportionate risks for stroke.”
Dr. Sheth agrees. “As we do for other diseases, and for cardiovascular health broadly, we must better understand the details about disparities and access to care in ICH. What are the real drivers and how do we attack them?”
Dr. Sheth, the senior author, receives research grants from the NIH and the American Heart Association. Drs. Koch, Elkind, and Salvador-Cruz had no competing interests.